Life | Editor’s choice

11 pages, 419 KiB

Open AccessEditor’s ChoiceArticle

Sexually Transmitted Infections Prevalence and Cascade of Care among Undocumented Sex Workers: A Twenty-Year-Long Experience

by Alessandra Donisi, Agnese Colpani, Beatrice Zauli, Andrea De Vito, Vito Fiore, Sergio Babudieri and Giordano Madeddu

Life 2023, 13(3), 606; https://doi.org/10.3390/life13030606 - 22 Feb 2023

Cited by 3 | Viewed by 1285

Abstract

Undocumented migrant sex-workers (SW) are vulnerable to Sexually Transmitted Infections (STIs). However, data regarding prevalence and linkage-to-care are lacking. Defining epidemiology is crucial to implement preventive measures. We report data from SW attending a facility for migrants in Piacenza, Italy. We collected medical [...] Read more.

Undocumented migrant sex-workers (SW) are vulnerable to Sexually Transmitted Infections (STIs). However, data regarding prevalence and linkage-to-care are lacking. Defining epidemiology is crucial to implement preventive measures. We report data from SW attending a facility for migrants in Piacenza, Italy. We collected medical records from 1999 until 2021. Quantitative variables were summarized as mean and standard deviation (SD), and qualitative ones by absolute and relative frequencies. Logistic regression analysis was performed to assess the relationship between sociodemographic, clinical variables, positive testing, and loss to follow-up (LFU). Overall, 1035 STI episodes were collected, 917 in cisgender-females (CF), and 118 in transgender-females (TF). Overall, 474 diagnoses were made. Three-hundred-ninety-two/474 (82.7%) started therapy, and 264/474 (55.7%) complied with a follow-up. Only 51.5% of HBV and 30.8% of HIV were linked to care. Having symptoms (OR 1.70 (95% CI 1.06–2.73), p = 0.028) and previous STIs (OR 1.36 (95% CI 1.04–1.77), p = 0.022) were associated with a higher chance of STIs, while at-risk intercourse to lower risk (OR 0.19 (95% CI 0.07–0.49), p = 0.001). TF had higher odds of bloodborne infections and syphilis (OR 2.61 (95% CI 1.17–5.80), p = 0.019). Regarding follow-up, the older the patient, the higher the LFU (OR 1.05 (95% CI 1.01–1.10), p = 0.021). Our data showed a high prevalence of STIs and LFU among undocumented SW. TF are even more vulnerable. Further efforts should be put into targeted interventions. Full article

(This article belongs to the Special Issue Exploration of the Unmet Needs of Aging People Living with HIV)

► Show Figures

Figure 1

16 pages, 732 KiB

Open AccessEditor’s ChoiceReview

Exploring the Protective Effect of Food Drugs against Viral Diseases: Interaction of Functional Food Ingredients and SARS-CoV-2, Influenza Virus, and HSV

by Andrea Ricci and Giovanni N. Roviello

Life 2023, 13(2), 402; https://doi.org/10.3390/life13020402 - 01 Feb 2023

Cited by 9 | Viewed by 3694

Abstract

A complex network of processes inside the human immune system provides resistance against a wide range of pathologies. These defenses form an innate and adaptive immunity, in which certain immune components work together to counteract infections. In addition to inherited variables, the susceptibility [...] Read more.

A complex network of processes inside the human immune system provides resistance against a wide range of pathologies. These defenses form an innate and adaptive immunity, in which certain immune components work together to counteract infections. In addition to inherited variables, the susceptibility to diseases may be influenced by factors such as lifestyle choices and aging, as well as environmental determinants. It has been shown that certain dietary chemical components regulate signal transduction and cell morphologies which, in turn, have consequences on pathophysiology. The consumption of some functional foods may increase immune cell activity, defending us against a number of diseases, including those caused by viruses. Here, we investigate a range of functional foods, often marketed as immune system boosters, in an attempt to find indications of their potential protective role against diseases caused by viruses, such as the influenza viruses (A and B), herpes simplex virus (HSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in some cases mediated by gut microbiota. We also discuss the molecular mechanisms that govern the protective effects of some functional foods and their molecular constituents. The main message of this review is that discovering foods that are able to strengthen the immune system can be a winning weapon against viral diseases. In addition, understanding how the dietary components function can aid in the development of novel strategies for maintaining human bodily health and keeping our immune systems strong. Full article

(This article belongs to the Special Issue Nutrition and Dietary Pattern Associated with Diseases)

► Show Figures

Figure 1

14 pages, 3224 KiB

Open AccessEditor’s ChoiceArticle

Antiobesity and Antioxidative Effect of Fermented Brown Rice Using In Vitro with In Vivo Caenorhabditis elegans Model

by Kaliyan Barathikannan, Akanksha Tyagi, Lingyue Shan, Nam-Hyeon Kim, Deuk-Sik Lee, Jong-Soon Park, Ramachandran Chelliah and Deog-Hwan Oh

Life 2023, 13(2), 374; https://doi.org/10.3390/life13020374 - 29 Jan 2023

Cited by 4 | Viewed by 2315

Abstract

Naturally occurring phytochemicals from plants or grains are crucial in reducing various metabolic disorders. Bioactive phytonutrients are abundant in the Asian dietary staple, brown rice. This research evaluated the impact of lactic acid bacteria (LABs) bioconversion and fermentation on antioxidant and antiobesity activities [...] Read more.

Naturally occurring phytochemicals from plants or grains are crucial in reducing various metabolic disorders. Bioactive phytonutrients are abundant in the Asian dietary staple, brown rice. This research evaluated the impact of lactic acid bacteria (LABs) bioconversion and fermentation on antioxidant and antiobesity activities and ferulic acid content in brown rice. The combination of bioconversion with Pediococcus acidilactici MNL5 among all LABs used showed a synergistic impact with 24 h of solid-state brown rice fermentation. The 24-h MNL5 fermented brown rice (FBR) demonstrated the most potent pancreatic lipase inhibitory activity (85.5 ± 1.25%) compared to raw brown rice (RBR) (54.4 ± 0.86%). The antioxidant potential of MNL5-FBR was also found to be highest in the DPPH assay (124.40 ± 2.40 mg Trolox Equiv./100 g, DW), ABTS assay (130.52 ± 2.32 mg Trolox Equiv./100 g, DW), and FRAP assay (116.16 ± 2.42 mg Trolox Equiv./100 g, DW). Based on higher antioxidant and antiobesity activities, samples were quantified for ferulic acid content using the HPLC-MS/MS approach. Furthermore, C. elegans supplementation with FBR showed enhanced life span and lipid reduction in fluorescence microscope analysis compared to the control. Our results indicate that the expression study using the C. elegans model (N2 and Daf-2 models) fat gene was conducted, showing a lowering of obesity ability in FBR-fed worms. Our study indicates that FBR has improved antioxidant and antiobesity actions, especially in MNL5-FBR, and can be employed to develop functional foods that combat obesity. Full article

(This article belongs to the Special Issue The Discovery and Application of Phytochemicals and Bio Actives)

► Show Figures

Figure 1

14 pages, 1182 KiB

Open AccessEditor’s ChoiceReview

Robotic Bronchoscopy: Review of Three Systems

by Maxwell J. Diddams and Hans J. Lee

Life 2023, 13(2), 354; https://doi.org/10.3390/life13020354 - 28 Jan 2023

Cited by 7 | Viewed by 5835

Abstract

Robotic bronchoscopy (RB) has been shown to improve access to smaller and more peripheral lung lesions, while simultaneously staging the mediastinum. Pre-clinical studies demonstrated extremely high diagnostic yields, but real-world RB yields have yet to fully matched up in prospective studies. Despite this, [...] Read more.

Robotic bronchoscopy (RB) has been shown to improve access to smaller and more peripheral lung lesions, while simultaneously staging the mediastinum. Pre-clinical studies demonstrated extremely high diagnostic yields, but real-world RB yields have yet to fully matched up in prospective studies. Despite this, RB technology has rapidly evolved and has great potential for lung-cancer diagnosis and even treatment. In this article, we review the historical and present challenges with RB in order to compare three RB systems. Full article

(This article belongs to the Special Issue Interventional Pulmonology – Review and Updates)

► Show Figures

Figure 1

17 pages, 3317 KiB

Open AccessEditor’s ChoiceArticle

Addition of Arbuscular Mycorrhizal Fungi Enhances Terpene Synthase Expression in Salvia rosmarinus Cultivars

by Emily Leggatt, Alistair Griffiths, Simon Budge, Anthony D. Stead, Alan C. Gange and Paul F. Devlin

Life 2023, 13(2), 315; https://doi.org/10.3390/life13020315 - 23 Jan 2023

Cited by 2 | Viewed by 1942

Abstract

Culinary herbs are commercially cultivated for their wide range of volatile compounds that give characteristic aromas and tastes. Rosemary (Salvia rosmarinus Spenn.) is an excellent model for assessment of methods improvement of volatile production as cultivars offer a wide variety of aromatic [...] Read more.

Culinary herbs are commercially cultivated for their wide range of volatile compounds that give characteristic aromas and tastes. Rosemary (Salvia rosmarinus Spenn.) is an excellent model for assessment of methods improvement of volatile production as cultivars offer a wide variety of aromatic profiles due to the large family of terpene synthase genes. Arbuscular mycorrhizal fungi (AMF) associations have been shown to improve essential oil production in aromatic plants and offer one approach to enhance aroma in commercial herb production. Changes in the expression of seven different terpene synthases were compared in six rosemary cultivars in response to addition of AMF to a peat substrate. Addition of AMF profoundly influenced terpene synthase expression in all cultivars and did so without impacting the optimised plant size and uniformity achieved in these conditions. In addition, two methods for AMF application, developed with the horticultural industry in mind, were tested in this study. Uniform incorporation of AMF mixed into the growing substrate prior to planting of a root plug produced the most consistent root colonisation. Overall, our findings demonstrate the potential for the use of AMF in the improvement of aroma in culinary herbs within a commercial setting but show that outcomes are likely to greatly vary depending on variety. Full article

(This article belongs to the Special Issue Plants as a Promising Biofactory for Bioactive Compounds)

► Show Figures

Figure 1

12 pages, 644 KiB

Open AccessEditor’s ChoiceArticle

Inflammation as Prognostic Hallmark of Clinical Outcome in Patients with SARS-CoV-2 Infection

by Diana Fuzio, Angelo Michele Inchingolo, Vitalba Ruggieri, Massimo Fasano, Maria Federico, Manuela Mandorino, Lavinia Dirienzo, Salvatore Scacco, Alessandro Rizzello, Maurizio Delvecchio, Massimiliano Parise, Roberto Rana, Nicola Faccilongo, Biagio Rapone, Francesco Inchingolo, Antonio Mancini, Maria Celeste Fatone, Antonio Gnoni, Gianna Dipalma and Giovanni Dirienzo

Life 2023, 13(2), 322; https://doi.org/10.3390/life13020322 - 23 Jan 2023

Cited by 4 | Viewed by 1718

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often characterized by a life-threatening interstitial pneumonia requiring hospitalization. The aim of this retrospective cohort study is to identify hallmarks of in-hospital mortality in patients affected by Coronavirus Disease 19 (COVID-19). A total of 150 [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often characterized by a life-threatening interstitial pneumonia requiring hospitalization. The aim of this retrospective cohort study is to identify hallmarks of in-hospital mortality in patients affected by Coronavirus Disease 19 (COVID-19). A total of 150 patients admitted for COVID-19 from March to June 2021 to “F. Perinei” Murgia Hospital in Altamura, Italy, were divided into survivors (n = 100) and non-survivors groups (n = 50). Blood counts, inflammation-related biomarkers and lymphocyte subsets were analyzed into two groups in the first 24 h after admission and compared by Student’s t-test. A multivariable logistic analysis was performed to identify independent risk factors associated with in-hospital mortality. Total lymphocyte count and CD3⁺ and CD4⁺ CD8⁺ T lymphocyte subsets were significantly lower in non-survivors. Serum levels of interleukin-6 (IL-6), lactate dehydrogenase (LDH), C-reactive protein (CRP) and procalcitonin (PCT) were significantly higher in non-survivors. Age > 65 years and presence of comorbidities were identified as independent risk factors associated with in-hospital mortality, while IL-6 and LDH showed a borderline significance. According to our results, markers of inflammation and lymphocytopenia predict in-hospital mortality in COVID-19. Full article

(This article belongs to the Special Issue COVID-19 Prevention and Treatment)

► Show Figures

Figure 1

22 pages, 601 KiB

Open AccessEditor’s ChoiceSystematic Review

A Critical Review of the Psychomotor Agitation Treatment in Youth

by Beniamino Tripodi, Irene Matarese and Manuel Glauco Carbone

Life 2023, 13(2), 293; https://doi.org/10.3390/life13020293 - 20 Jan 2023

Cited by 1 | Viewed by 2396

Abstract

(1) Background: To systematically review evidence on the safety and efficacy of psychopharmacological treatments available for psychomotor agitation (PA) in children and adolescents. (2) Methods: Studies assessing the safety and efficacy of psychopharmacological treatments for acute PA in children and adolescents that were [...] Read more.

(1) Background: To systematically review evidence on the safety and efficacy of psychopharmacological treatments available for psychomotor agitation (PA) in children and adolescents. (2) Methods: Studies assessing the safety and efficacy of psychopharmacological treatments for acute PA in children and adolescents that were published between January 1984 and June 2022 on PubMed were systematically reviewed. We included: (i) papers that presented a combination of the search terms specified in the “Search strategy” sub-paragraph; (ii) manuscripts in English; (iii) original papers; (iv) prospective or retrospective/observational studies and experimental or quasi-experimental reports. The exclusion criteria were: (i) review papers; (ii) non-original studies including editorials and book reviews; (iii) studies not specifically designed and focused on the selected topic. (3) Results: We selected 42 papers: 11 case series (11/42, 26.19%), 8 chart reviews (8/42, 19.05%), 8 case reports (8/42, 19.05%), 6 double-blind placebo-controlled randomized studies (6/42, 14.29%), 4 double-blind controlled randomized studies (4/42, 9.52%), 4 open-label trials (4/42, 9.52%) and 1 case control (1/42, 2.38%). (4) Conclusions: The drugs most frequently used to treat agitation in children and adolescents were ziprasidone, risperidone, aripiprazole, olanzapine and valproic acid. Further studies are needed to evaluate the efficacy/safety ratio, considering the limited number of observations in this field. Full article

(This article belongs to the Special Issue What Is New in Psychiatry and Psychopharmacology?)

► Show Figures

Figure 1

30 pages, 2406 KiB

Open AccessEditor’s ChoiceReview

Biofilm Lifestyle in Recurrent Urinary Tract Infections

by Amr S. Abu Lila, Azza A. H. Rajab, Marwa H. Abdallah, Syed Mohd Danish Rizvi, Afrasim Moin, El-Sayed Khafagy, Shams Tabrez and Wael A. H. Hegazy

Life 2023, 13(1), 148; https://doi.org/10.3390/life13010148 - 04 Jan 2023

Cited by 26 | Viewed by 4460

Abstract

Urinary tract infections (UTIs) represent one of the most common infections that are frequently encountered in health care facilities. One of the main mechanisms used by bacteria that allows them to survive hostile environments is biofilm formation. Biofilms are closed bacterial communities that [...] Read more.

Urinary tract infections (UTIs) represent one of the most common infections that are frequently encountered in health care facilities. One of the main mechanisms used by bacteria that allows them to survive hostile environments is biofilm formation. Biofilms are closed bacterial communities that offer protection and safe hiding, allowing bacteria to evade host defenses and hide from the reach of antibiotics. Inside biofilm communities, bacteria show an increased rate of horizontal gene transfer and exchange of resistance and virulence genes. Additionally, bacterial communication within the biofilm allows them to orchestrate the expression of virulence genes, which further cements the infestation and increases the invasiveness of the infection. These facts stress the necessity of continuously updating our information and understanding of the etiology, pathogenesis, and eradication methods of this growing public health concern. This review seeks to understand the role of biofilm formation in recurrent urinary tact infections by outlining the mechanisms underlying biofilm formation in different uropathogens, in addition to shedding light on some biofilm eradication strategies. Full article

(This article belongs to the Special Issue Urinary Microbiome and Genitourinary System Disorders)

► Show Figures

Figure 1

14 pages, 4212 KiB

Open AccessEditor’s ChoiceReview

Gut Microbiome Composition in Patients with Chronic Urticaria: A Review of Current Evidence and Data

by Mirela Krišto, Liborija Lugović-Mihić, Melba Muñoz, Maja Rupnik, Aleksander Mahnic, Petar Ozretić, Morana Jaganjac, Diana Ćesić and Matea Kuna

Life 2023, 13(1), 152; https://doi.org/10.3390/life13010152 - 04 Jan 2023

Cited by 7 | Viewed by 3828

Abstract

Recent studies have linked gut microorganism composition and chronic urticaria (CU); however, the underlying mechanisms responsible for this connection are unknown. Since the human immune system is in homeostasis with microbiota, and the composition of the microbiome regulates the development and function of [...] Read more.

Recent studies have linked gut microorganism composition and chronic urticaria (CU); however, the underlying mechanisms responsible for this connection are unknown. Since the human immune system is in homeostasis with microbiota, and the composition of the microbiome regulates the development and function of the immune system, it is likely that an alteration of microbiota components (a dysbiosis) could influence the course of chronic spontaneous urticaria (CSU), including disease severity, patient quality of life and treatment outcome. To date, several studies have identified changes in the gut microbiota composition of patients with CSU, though only a few have exhibited metabolic abnormalities associated with gut dysbiosis. The studies on CSU patients predominantly showed that the relative abundance of beneficial bacteria was decreased (Firmicutes and Bacteroides), while that of opportunistic bacteria was increased (Enterobacteria and Proteobacteria). In addition, serum metabolome analysis revealed that gut microbiota-associated alterations in unsaturated fatty acids and the butanoate metabolism pathway may play a role in CSU. These findings are potentially associated with inflammation mediated by the imbalance of Th1/Th2/Th17 cytokines, which might contribute to CSU pathogenesis. Further research in this field could improve clinical, diagnostic, and therapeutic approaches to patients with CSU. By applying new knowledge on gut microbial communities and metabolomics, future CSU therapies could modify the microbiota composition using agents such as probiotics or other similar agents, which, in combination with current standard therapies, could hopefully lead to a reduction in symptoms and an improved quality of life for CSU patients. Full article

(This article belongs to the Section Microbiology)

► Show Figures

Figure 1

26 pages, 1834 KiB

Open AccessEditor’s ChoiceReview

Clinical Guideline on Perioperative Management of Patients with Advanced Chronic Liver Disease

by Lidia Canillas, Amalia Pelegrina, Juan Álvarez, Elena Colominas-González, Antonio Salar, Lluís Aguilera, Fernando Burdio, Antonio Montes, Santiago Grau, Luis Grande and José A. Carrión

Life 2023, 13(1), 132; https://doi.org/10.3390/life13010132 - 03 Jan 2023

Cited by 5 | Viewed by 5736

Abstract

(1) Background: Patients with advanced chronic liver disease (ACLD) are living longer with more comorbidities because of improved medical and surgical management. However, patients with ACLD are at increased risk of perioperative morbidity and mortality; (2) Methods: We conducted a comprehensive review of [...] Read more.

(1) Background: Patients with advanced chronic liver disease (ACLD) are living longer with more comorbidities because of improved medical and surgical management. However, patients with ACLD are at increased risk of perioperative morbidity and mortality; (2) Methods: We conducted a comprehensive review of the literature to support a narrative clinical guideline about the assessment of mortality risk and management of perioperative morbidity in patients with ACLD undergoing surgical procedures; (3) Results: Slight data exist to guide the perioperative management of patients with ACLD, and most recommendations are based on case series and expert opinion. The severity of liver dysfunction, portal hypertension, cardiopulmonary and renal comorbidities, and complexity of surgery and type (elective versus emergent) are predictors of perioperative morbidity and mortality. Expert multidisciplinary teams are necessary to evaluate and manage ACLD before, during, and after surgical procedures; (4) Conclusions: This clinical practice document updates the available data and recommendations to optimize the management of patients with advanced chronic liver disease who undergo surgical procedures. Full article

(This article belongs to the Special Issue Clinical Guidelines in the Health Area)

► Show Figures

Figure 1

10 pages, 250 KiB

Open AccessEditor’s ChoiceArticle

Cytogenetic Effects in Patients after Computed Tomography Examination

by Elizaveta Neronova and Sergei Aleksanin

Life 2022, 12(12), 1983; https://doi.org/10.3390/life12121983 - 27 Nov 2022

Viewed by 1472

Abstract

Millions of people around the world are exposed to low doses of ionizing radiation from diagnostic computed tomography (CT) scans. Currently available data on the potential cancer risk after CT scans are contradictory and therefore demand further investigations. The aim of the current [...] Read more.

Millions of people around the world are exposed to low doses of ionizing radiation from diagnostic computed tomography (CT) scans. Currently available data on the potential cancer risk after CT scans are contradictory and therefore demand further investigations. The aim of the current study was to obtain estimations of genome damage after CT scans in 42 non-cancer patients and to conduct a comparison of the results with 22 control subjects. The frequency of dicentric ring chromosomes and chromosome breaks was significantly increased in irradiated patients compared to the controls. The distribution of dicentrics among the cells demonstrated non-Poisson distribution that reflected non-uniform and partial-body radiation exposure. A fraction of patients followed Poisson distribution, which is typical for uniform whole-body exposures. Some patients demonstrated a level of dicentrics similar to the control subjects. The individual variations in the frequency and dicentric distribution suggested complex mechanisms of chromosome aberration induction and elimination that could be associated with individual radiosensitivity, as well as previous diagnostics that used ionizing radiation or the redistribution of small fractions of irradiated lymphocytes within the circulatory pull. In conclusion, CT scans may cause genome damage and possible increases in cancer risk. The introduction of a specific follow-up of such patients, especially in the case of repeated CT scans, is suggested. Full article

(This article belongs to the Special Issue State-of-the-Art in Biomedicine in Russia Federation)

14 pages, 1341 KiB

Open AccessEditor’s ChoiceReview

Fine-Needle Aspiration Cytology for Parotid Tumors

by Masataka Taniuchi, Tetsuya Terada and Ryo Kawata

Life 2022, 12(11), 1897; https://doi.org/10.3390/life12111897 - 15 Nov 2022

Cited by 2 | Viewed by 2667

Abstract

Fine-needle aspiration (FNA) cytology is widely used in clinical practice as a simple and minimally invasive test for parotid tumors that allows for preoperative estimation of benignancy and malignancy, histological type, and malignancy grade and can be performed on an outpatient basis. In [...] Read more.

Fine-needle aspiration (FNA) cytology is widely used in clinical practice as a simple and minimally invasive test for parotid tumors that allows for preoperative estimation of benignancy and malignancy, histological type, and malignancy grade and can be performed on an outpatient basis. In recent years, cell blocks prepared with core needle biopsy (CNB) and liquid-based cytology (LBC) have increased the reliability of immunostaining and molecular biological testing, leading to improved diagnostic accuracy. In 2018, the Milan System for Reporting Salivary Gland Cytology was introduced, but it does not include malignancy grade or histological type, so we proposed the Osaka Medical College classification as a more clinically based cell classification that includes both types of information, and we have reported on its usefulness. This review gives an overview of the history and use of FNA and describes CNB and LBC and the two classification systems. Full article

(This article belongs to the Special Issue New Insights into Diagnosis and Pitfalls in the Treatment of Parotid Tumors)

19 pages, 996 KiB

Open AccessEditor’s ChoiceReview

Acute Respiratory Distress Syndrome and the Use of Inhaled Pulmonary Vasodilators in the COVID-19 Era: A Narrative Review

by Adeel Nasrullah, Shiza Virk, Aaisha Shah, Max Jacobs, Amina Hamza, Abu Baker Sheikh, Anam Javed, Muhammad Ali Butt and Swathi Sangli

Life 2022, 12(11), 1766; https://doi.org/10.3390/life12111766 - 02 Nov 2022

Cited by 5 | Viewed by 2965

Abstract

The Coronavirus disease (COVID-19) pandemic of 2019 has resulted in significant morbidity and mortality, especially from severe acute respiratory distress syndrome (ARDS). As of September 2022, more than 6.5 million patients have died globally, and up to 5% required intensive care unit treatment. [...] Read more.

The Coronavirus disease (COVID-19) pandemic of 2019 has resulted in significant morbidity and mortality, especially from severe acute respiratory distress syndrome (ARDS). As of September 2022, more than 6.5 million patients have died globally, and up to 5% required intensive care unit treatment. COVID-19-associated ARDS (CARDS) differs from the typical ARDS due to distinct pathology involving the pulmonary vasculature endothelium, resulting in diffuse thrombi in the pulmonary circulation and impaired gas exchange. The National Institute of Health and the Society of Critical Care Medicine recommend lung-protective ventilation, prone ventilation, and neuromuscular blockade as needed. Further, a trial of pulmonary vasodilators is suggested for those who develop refractory hypoxemia. A review of the prior literature on inhaled pulmonary vasodilators in ARDS suggests only a transient improvement in oxygenation, with no mortality benefit. This narrative review aims to highlight the fundamental principles in ARDS management, delineate the fundamental differences between CARDS and ARDS, and describe the comprehensive use of inhaled pulmonary vasodilators. In addition, with the differing pathophysiology of CARDS from the typical ARDS, we sought to evaluate the current evidence regarding the use of inhaled pulmonary vasodilators in CARDS. Full article

(This article belongs to the Special Issue Challenges in Stroke Care)

► Show Figures

Figure 1

19 pages, 729 KiB

Open AccessEditor’s ChoiceReview

The Overview of Perspectives of Clinical Application of Liquid Biopsy in Non-Small-Cell Lung Cancer

by Aleksandra Bożyk and Marcin Nicoś

Life 2022, 12(10), 1640; https://doi.org/10.3390/life12101640 - 19 Oct 2022

Cited by 4 | Viewed by 2194

Abstract

The standard diagnostics procedure for non-small-cell lung cancer (NSCLC) requires a pathological evaluation of tissue samples obtained by surgery or biopsy, which are considered invasive sampling procedures. Due to this fact, re-sampling of the primary tumor at the moment of progression is limited [...] Read more.

The standard diagnostics procedure for non-small-cell lung cancer (NSCLC) requires a pathological evaluation of tissue samples obtained by surgery or biopsy, which are considered invasive sampling procedures. Due to this fact, re-sampling of the primary tumor at the moment of progression is limited and depends on the patient’s condition, even if it could reveal a mechanism of resistance to applied therapy. Recently, many studies have indicated that liquid biopsy could be provided for the noninvasive management of NSCLC patients who receive molecularly targeted therapies or immunotherapy. The liquid biopsy of neoplastic patients harbors small fragments of circulating-free DNA (cfDNA) and cell-free RNA (cfRNA) secreted to the circulation from normal cells, as well as a subset of tumor-derived circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA). In NSCLC patients, a longitudinal assessment of genetic alterations in “druggable” genes in liquid biopsy might improve the follow-up of treatment efficacy and allow for the detection of an early progression before it is detectable in computed tomography or a clinical image. However, a liquid biopsy may be used to determine a variety of relevant molecular or genetic information for understanding tumor biology and its evolutionary trajectories. Thus, liquid biopsy is currently associated with greater hope for common diagnostic and clinical applications. In this review, we would like to highlight diagnostic challenges in the application of liquid biopsy into the clinical routine and indicate its implications on the metastatic spread of NSCLC or monitoring of personalized treatment regimens. Full article

(This article belongs to the Special Issue Thoracic Malignancies: From Prevention and Diagnosis to Late Stages)

► Show Figures

Figure 1

16 pages, 621 KiB

Open AccessEditor’s ChoiceReview

The Interplay between Anti-Angiogenics and Immunotherapy in Colorectal Cancer

by Brigida Anna Maiorano, Alessandro Parisi, Evaristo Maiello and Davide Ciardiello

Life 2022, 12(10), 1552; https://doi.org/10.3390/life12101552 - 06 Oct 2022

Cited by 3 | Viewed by 2095

Abstract

Angiogenesis, a hallmark of cancer, plays a fundamental role in colorectal cancer (CRC). Anti-angiogenic drugs and chemotherapy represent a standard of care for treating metastatic disease. Immune checkpoint inhibitors (ICIs) have changed the therapeutic algorithm of many solid tumors. However, the efficacy of [...] Read more.

Angiogenesis, a hallmark of cancer, plays a fundamental role in colorectal cancer (CRC). Anti-angiogenic drugs and chemotherapy represent a standard of care for treating metastatic disease. Immune checkpoint inhibitors (ICIs) have changed the therapeutic algorithm of many solid tumors. However, the efficacy of ICIs is limited to mCRC patients carrying microsatellite instability (MSI-H), which represent approximately 3–5% of mCRC. Emerging evidence suggests that anti-angiogenic drugs could exhibit immunomodulatory properties. Thus, there is a strong rationale for combining anti-angiogenics and ICIs to improve efficacy in the metastatic setting. Our review summarizes the pre-clinical and clinical evidence regarding the combination of anti-angiogenics and ICIs in mCRC to deepen the possible application in daily clinical practice. Full article

(This article belongs to the Special Issue New Insights into the Treatment of Colorectal Cancer in the Era of Precision Medicine)

► Show Figures

Figure 1

12 pages, 993 KiB

Open AccessEditor’s ChoiceArticle

Identification of Universally Applicable and Species-Specific Marker Peptides for Bacillus anthracis

by Natalie Witt, Domenico Galante, Sandro Andreotti, Mostafa Abdel Glil, Antonio Fasanella, David Meierhofer and Herbert Tomaso

Life 2022, 12(10), 1549; https://doi.org/10.3390/life12101549 - 06 Oct 2022

Viewed by 2078

Abstract

Anthrax is a zoonotic infection caused by the bacterium Bacillus anthracis (BA). Specific identification of this pathogen often relies on targeting genes located on two extrachromosomal plasmids, which represent the major pathogenicity factors of BA. However, more recent findings show that these plasmids [...] Read more.

Anthrax is a zoonotic infection caused by the bacterium Bacillus anthracis (BA). Specific identification of this pathogen often relies on targeting genes located on two extrachromosomal plasmids, which represent the major pathogenicity factors of BA. However, more recent findings show that these plasmids have also been found in other closely related Bacillus species. In this study, we investigated the possibility of identifying species-specific and universally applicable marker peptides for BA. For this purpose, we applied a high-resolution mass spectrometry-based approach for 42 BA isolates. Along with the genomic sequencing data and by developing a bioinformatics data evaluation pipeline, which uses a database containing most of the publicly available protein sequences worldwide (UniParc), we were able to identify eleven universal marker peptides unique to BA. These markers are located on the chromosome and therefore, might overcome known problems, such as observable loss of plasmids in environmental species, plasmid loss during cultivation in the lab, and the fact that the virulence plasmids are not necessarily a unique feature of BA. The identified chromosomally encoded markers in this study could extend the small panel of already existing chromosomal targets and along with targets for the virulence plasmids, may pave the way to an even more reliable identification of BA using genomics- as well as proteomics-based techniques. Full article

(This article belongs to the Special Issue Emerging Themes in Anthrax)

► Show Figures

Figure 1

13 pages, 738 KiB

Open AccessEditor’s ChoiceReview

Microbiome in Chronic Kidney Disease

by Theodoros Tourountzis, Georgios Lioulios, Asimina Fylaktou, Eleni Moysidou, Aikaterini Papagianni and Maria Stangou

Life 2022, 12(10), 1513; https://doi.org/10.3390/life12101513 - 28 Sep 2022

Cited by 5 | Viewed by 3177

Abstract

The gut microbiome is a complex collection of microorganisms with discrete characteristics and activities. Its important role is not restricted to food digestion and metabolism, but extends to the evolution, activation and function of the immune system. Several factors, such as mode of [...] Read more.

The gut microbiome is a complex collection of microorganisms with discrete characteristics and activities. Its important role is not restricted to food digestion and metabolism, but extends to the evolution, activation and function of the immune system. Several factors, such as mode of birth, diet, medication, ageing and chronic inflammation, can modify the intestinal microbiota. Chronic kidney disease (CKD) seems to have a direct and unique effect, as increased urea levels result in alteration of the gut microbiome, leading to overproduction of its metabolites. Therefore, potentially noxious microbial uremic toxins, which have predominantly renal clearance, including p-cresyl sulfate, indoxyl sulfate and N-oxide of trimethylamine [Trimethylamine-N-Oxide (TMAO)], accumulate in human’s body, and are responsible not only for the clinical implications of CKD, but also for the progression of renal failure itself. Certain changes in gut microbiome are observed in patients with end stage renal disease (ESRD), either when undergoing hemodialysis or after kidney transplantation. The purpose of this review is to summarize the changes of gut microbiome and the protein bound uremic toxins which are observed in CKD and in different kidney replacement strategies. In addition, we attempt to review the connection between microbiome, clinical implications and immune response in CKD. Full article

(This article belongs to the Section Medical Research)

► Show Figures

Figure 1

15 pages, 2725 KiB

Open AccessEditor’s ChoiceArticle

Differential Expression of Anti-Inflammatory RNA Binding Proteins in Lupus Nephritis

by Raouia Fakhfakh, Emna Bouallegui, Hana Houssaini, Nesrine Elloumi, Fatma Dhafouli, Olfa Abida, Hend Hachicha, Sameh Marzouk, Zouhir Bahloul, Khawla Kammoun, Tahia Boudawara and Hatem Masmoudi

Life 2022, 12(10), 1474; https://doi.org/10.3390/life12101474 - 23 Sep 2022

Cited by 2 | Viewed by 1905

Abstract

Lupus nephritis (LN) is a type of immunological complex glomerulonephritis characterized by chronic renal inflammation which is exacerbated by infiltrating leukocytes and fueled by a variety of pro-inflammatory cytokines. A profound understanding of the pathogenesis of LN is necessary to identify the optimal [...] Read more.

Lupus nephritis (LN) is a type of immunological complex glomerulonephritis characterized by chronic renal inflammation which is exacerbated by infiltrating leukocytes and fueled by a variety of pro-inflammatory cytokines. A profound understanding of the pathogenesis of LN is necessary to identify the optimal molecular targets. The role of RNA-binding proteins (RBPs) in post-transcriptional gene regulation in the immune system is being explored in greater depth to better understand how this regulation is implicated in inflammatory and autoimmune diseases. Tristetraprolin (TTP), Roquin-1/2, and Regnase-1 are 3 RBPs that play a critical role in the regulation of pro-inflammatory mediators by gating the degradation and/or translational silencing of target mRNAs. In this study, we proposed to focus on the differential expression of these RBPs in immune cells and renal biopsies from LN patients, as well as their regulatory impact on a specific target. Herein, we highlight a novel target of anti-inflammatory treatment by revealing the mechanisms underlying RBP expression and the interaction between RBPs and their target RNAs. Full article

(This article belongs to the Special Issue The Interplay between Immune System and the Kidneys: Games without Frontiers?)

► Show Figures

Figure 1

9 pages, 23712 KiB

Open AccessEditor’s ChoiceArticle

Protective Effects of L-2-Oxothiazolidine-4-Carboxylate during Isoproterenol-Induced Myocardial Infarction in Rats: In Vivo Study

by Marija Angelovski, Nikola Hadzi-Petrushev, Dino Atanasov, Aleksandar Nikodinovski, Vadim Mitrokhin, Dimiter B. Avtanski and Mitko Mladenov

Life 2022, 12(10), 1466; https://doi.org/10.3390/life12101466 - 21 Sep 2022

Cited by 2 | Viewed by 1533

Abstract

This study aimed to evaluate the cardioprotective effects of L-2-oxothiazolidine-4-carboxylate (OTC) against isoproterenol (ISO)-induced acute myocardial infarction (MI) in rats. Results demonstrated that OTC treatments inhibited ISO-induced oxidative damage, suppressed lipid peroxidation, and increased superoxide dismutase and catalase activity in the hearts of [...] Read more.

This study aimed to evaluate the cardioprotective effects of L-2-oxothiazolidine-4-carboxylate (OTC) against isoproterenol (ISO)-induced acute myocardial infarction (MI) in rats. Results demonstrated that OTC treatments inhibited ISO-induced oxidative damage, suppressed lipid peroxidation, and increased superoxide dismutase and catalase activity in the hearts of the treated rats compared to those of the untreated controls. The ISO-related NF-κB activation was reduced due to the OTC treatment, and lower degrees of inflammatory cell infiltration and necrosis in the hearts were observed. In summary, OTC treatments exerted cardioprotective effects against MI in vivo, mainly due to enhancing cardiac antioxidant activity. Full article

► Show Figures

Figure 1

19 pages, 1249 KiB

Open AccessEditor’s ChoiceReview

Exosomes and Biomaterials: In Search of a New Therapeutic Strategy for Multiple Sclerosis

by Doddy Denise Ojeda-Hernández, Mercedes A. Hernández-Sapiéns, Edwin E. Reza-Zaldívar, Alejandro Canales-Aguirre, Jordi A. Matías-Guiu, Jorge Matías-Guiu, Juan Carlos Mateos-Díaz, Ulises Gómez-Pinedo and Francisco Sancho-Bielsa

Life 2022, 12(9), 1417; https://doi.org/10.3390/life12091417 - 11 Sep 2022

Cited by 6 | Viewed by 3440

Abstract

Current efforts to find novel treatments that counteract multiple sclerosis (MS) have pointed toward immunomodulation and remyelination. Currently, cell therapy has shown promising potential to achieve this purpose. However, disadvantages such as poor survival, differentiation, and integration into the target tissue have limited [...] Read more.

Current efforts to find novel treatments that counteract multiple sclerosis (MS) have pointed toward immunomodulation and remyelination. Currently, cell therapy has shown promising potential to achieve this purpose. However, disadvantages such as poor survival, differentiation, and integration into the target tissue have limited its application. A series of recent studies have focused on the cell secretome, showing it to provide the most benefits of cell therapy. Exosomes are a key component of the cell secretome, participating in the transfer of bioactive molecules. These nano-sized vesicles offer many therapeutical advantages, such as the capacity to cross the blood-brain barrier, an enrichable cargo, and a customizable membrane. Moreover, integrating of biomaterials into exosome therapy could lead to new tissue-specific therapeutic strategies. In this work, the use of exosomes and their integration with biomaterials is presented as a novel strategy in the treatment of MS. Full article

(This article belongs to the Special Issue Multiple Sclerosis: Research in Remyelination, the Next Step)

► Show Figures

Graphical abstract

13 pages, 1295 KiB

Open AccessEditor’s ChoiceReview

HER2 in Metastatic Colorectal Cancer: Pathology, Somatic Alterations, and Perspectives for Novel Therapeutic Schemes

by Mariia Ivanova, Konstantinos Venetis, Elena Guerini-Rocco, Luca Bottiglieri, Mauro Giuseppe Mastropasqua, Ornella Garrone, Nicola Fusco and Michele Ghidini

Life 2022, 12(9), 1403; https://doi.org/10.3390/life12091403 - 09 Sep 2022

Cited by 9 | Viewed by 2499

Abstract

HER2 is an emerging biomarker in colorectal cancer (CRC). This oncogene plays an essential role in regulating cell proliferation, differentiation, migration, and, more in general, tumorigenesis and tumor progression. The most frequent types of HER2 alterations in CRC include gene amplification and missense [...] Read more.

HER2 is an emerging biomarker in colorectal cancer (CRC). This oncogene plays an essential role in regulating cell proliferation, differentiation, migration, and, more in general, tumorigenesis and tumor progression. The most frequent types of HER2 alterations in CRC include gene amplification and missense mutations in 7–8% of CRC, often being mirrored by HER2 protein overexpression, representing founder events in solid tumors, including CRC. There are currently no approved HER2-targeted therapy guidelines for CRC; however, several studies have shown that HER2 can be effectively targeted in meta-static CRC settings. In this review, we discuss the current knowledge of HER2 testing in CRC and the immediate future perspectives for HER2 targeting in the metastatic setting. Full article

(This article belongs to the Special Issue New Insights into the Treatment of Colorectal Cancer in the Era of Precision Medicine)

► Show Figures

Figure 1

9 pages, 875 KiB

Open AccessEditor’s ChoiceArticle

Urinary Collectrin (TMEM27) as Novel Marker for Acute Kidney Injury

by Sahra Pajenda, Ludwig Wagner, Daniela Gerges, Harald Herkner, Tamar Tevdoradze, Karl Mechtler, Alice Schmidt and Wolfgang Winnicki

Life 2022, 12(9), 1391; https://doi.org/10.3390/life12091391 - 06 Sep 2022

Cited by 4 | Viewed by 1464

Abstract

Acute kidney injury (AKI) is a leading complication in hospitalized patients of different disciplines due to various aetiologies and is associated with the risk of chronic kidney disease, the need for dialysis and death. Since nephrons are not supplied with pain signals, kidney [...] Read more.

Acute kidney injury (AKI) is a leading complication in hospitalized patients of different disciplines due to various aetiologies and is associated with the risk of chronic kidney disease, the need for dialysis and death. Since nephrons are not supplied with pain signals, kidney injury is mostly diagnosed by serum creatinine with a time delay. Recent work has shown that certain urinary biomarkers are available for early detection of AKI. In total, 155 subjects, including 102 patients with AKI at various stages and 53 subjects without AKI, were enrolled, and their course and laboratory data were recorded. Urinary collectrin (TMEM27) was measured by a commercially available ELISA assay. Changes in serum creatinine were used to determine AKI stage. Patients with AKI presented with significantly lower levels of urinary collectrin compared to patients without AKI (1597 ± 1827 pg/mL vs. 2855 ± 2073; p = 0.001). Collectrin was found to inversely correlate with serum creatinine and stages of AKI. Collectrin levels were lowest in AKI stage III (1576 ± 1686 pg/mL; p = 0.001) and also significantly lower in stage II (1616 ± 2148 pg/mL; p = 0.021) and stage I (1630 ± 1956 pg/mL; p = 0.019) compared to subjects without AKI. An optimal minimum collectrin cut-off value of 1606 [95% CI 1258 to 1954] pg/mL was determined to detect AKI. In conclusion, urinary collectrin represents an indicator of AKI that, unlike all other established AKI biomarkers, decreases with stage of AKI and thus may be associated with a novel pathogenic pathway. Full article

(This article belongs to the Special Issue Innovative Biomarker and Precision Medicine)

► Show Figures

Figure 1

8 pages, 244 KiB

Open AccessEditor’s ChoiceArticle

Multiglandular Parathyroid Disease

by Grzegorz Kowalski, Grzegorz Buła, Adam Bednarczyk, Agata Gawrychowska and Jacek Gawrychowski

Life 2022, 12(8), 1286; https://doi.org/10.3390/life12081286 - 22 Aug 2022

Cited by 5 | Viewed by 1460

Abstract

Introduction: Multiglandular parathyroid disease (MGD) is an uncommon cause of primary hyperparathyroidism (pHPT) and has been reported in the literature in 8–33% of patients with pHPT. The aim of our study was to review the clinical characteristics and management of MGD and evaluation [...] Read more.

Introduction: Multiglandular parathyroid disease (MGD) is an uncommon cause of primary hyperparathyroidism (pHPT) and has been reported in the literature in 8–33% of patients with pHPT. The aim of our study was to review the clinical characteristics and management of MGD and evaluation of surgical treatment failures. Methods: We performed a retrospective study of 163 patients with pHPT undergoing parathyroidectomy (PTX) at the Department of General and Endocrine Surgery between 1983 and 2018. All these patients were diagnosed with MGD. This group of patients was compared with a group of 856 patients with solitary disease operated for pHPT in the same period. Results: Among 163 patients—127 (79%) of them had two lesions, 28 (16%) had three, and 8 (5%) four. They were prevalently women over the age of 50. The diagnosis was based on PTH and ionized calcium studies and used sestamibi technetium-99m scintigraphy (MIBI) as well for us. Treatment was surgical. Conclusions: Parathyroidectomy (PTX) for multiglandular parathyroid disease (MGD) is associated with a higher operative risk of failure compared to solitary disease. Preoperative diagnosis and localization of the parathyroid glands is an extremely important element of treatment. Diagnosis is based on PTH and calcium levels. Ultrasonography (USG), MRI, and scintigraphy are very helpful in diagnosis. Mediastinal multiglandular parathyroid disease (MGD) is associated with increased surgical treatment failures. The treatment is surgical and consists of the removal of the masses or complete parathyroidectomy. Based on this study, we support the existence of multiple adenomas and advocate the removal of only macroscopically enlarged parathyroid glands in patients with primary hyperparathyroidism. Full article

(This article belongs to the Special Issue Multiple Endocrine Neoplasia: Basic and Clinical Findings)

18 pages, 1577 KiB

Open AccessEditor’s ChoiceArticle

Studies on Biological and Molecular Effects of Small-Molecule Kinase Inhibitors on Human Glioblastoma Cells and Organotypic Brain Slices

by Julia Hörnschemeyer, Timo Kirschstein, Gesine Reichart, Christin Sasse, Jakob Venus, Anne Einsle, Katrin Porath, Michael Linnebacher, Rüdiger Köhling and Falko Lange

Life 2022, 12(8), 1258; https://doi.org/10.3390/life12081258 - 17 Aug 2022

Cited by 3 | Viewed by 1878

Abstract

Glioblastoma is the most common and aggressive primary brain tumor. Multiple genetic and epigenetic alterations in several major signaling pathways—including the phosphoinositide 3-kinases (PI3K)/AKT/mTOR and the Raf/MEK/ERK pathway—could be found. We therefore aimed to investigate the biological and molecular effects of small-molecule kinase [...] Read more.

Glioblastoma is the most common and aggressive primary brain tumor. Multiple genetic and epigenetic alterations in several major signaling pathways—including the phosphoinositide 3-kinases (PI3K)/AKT/mTOR and the Raf/MEK/ERK pathway—could be found. We therefore aimed to investigate the biological and molecular effects of small-molecule kinase inhibitors that may interfere with those pathways. For this purpose, patient-derived glioblastoma cells were challenged with dactolisib, ipatasertib, MK-2206, regorafenib, or trametinib. To determine the effects of the small-molecule kinase inhibitors, assays of cell proliferation and apoptosis and immunoblot analyses were performed. To further investigate the effects of ipatasertib on organotypic brain slices harboring glioblastoma cells, the tumor growth was estimated. In addition, the network activity in brain slices was assessed by electrophysiological field potential recordings. Multi-kinase inhibitor regorafenib and both MK-2206 and dactolisib were very effective in all preclinical tumor models, while with respect to trametinib, two cell lines were found to be highly resistant. Only in HROG05 cells, ipatasertib showed anti-tumoral effects in vitro and in organotypic brain slices. Additionally, ipatasertib diminished synchronous network activity in organotypic brain slices. Overall, our data suggest that ipatasertib was only effective in selected tumor models, while especially regorafenib and MK-2206 presented a uniform response pattern. Full article

(This article belongs to the Special Issue Future Directions in Diagnosis and Treatment of Glioblastoma)

► Show Figures

Figure 1

13 pages, 1606 KiB

Open AccessEditor’s ChoiceArticle

The Role of the Precuneus in Human Spatial Updating in a Real Environment Setting—A cTBS Study

by Milos Dordevic, Sonja Hoelzer, Augusta Russo, José C. García Alanis and Notger G. Müller

Life 2022, 12(8), 1239; https://doi.org/10.3390/life12081239 - 15 Aug 2022

Cited by 4 | Viewed by 1466

Abstract

As we move through an environment, we update positions of our body relative to other objects, even when some objects temporarily or permanently leave our field of view—this ability is termed egocentric spatial updating and plays an important role in everyday life. Still, [...] Read more.

As we move through an environment, we update positions of our body relative to other objects, even when some objects temporarily or permanently leave our field of view—this ability is termed egocentric spatial updating and plays an important role in everyday life. Still, our knowledge about its representation in the brain is still scarce, with previous studies using virtual movements in virtual environments or patients with brain lesions suggesting that the precuneus might play an important role. However, whether this assumption is also true when healthy humans move in real environments where full body-based cues are available in addition to the visual cues typically used in many VR studies is unclear. Therefore, in this study we investigated the role of the precuneus in egocentric spatial updating in a real environment setting in 20 healthy young participants who underwent two conditions in a cross-over design: (a) stimulation, achieved through applying continuous theta-burst stimulation (cTBS) to inhibit the precuneus and (b) sham condition (activated coil turned upside down). In both conditions, participants had to walk back with blindfolded eyes to objects they had previously memorized while walking with open eyes. Simplified trials (without spatial updating) were used as control condition, to make sure the participants were not affected by factors such as walking blindfolded, vestibular or working memory deficits. A significant interaction was found, with participants performing better in the sham condition compared to real stimulation, showing smaller errors both in distance and angle. The results of our study reveal evidence of an important role of the precuneus in a real-environment egocentric spatial updating; studies on larger samples are necessary to confirm and further investigate this finding. Full article

(This article belongs to the Section Physiology and Pathology)

► Show Figures

Figure 1

17 pages, 535 KiB

Open AccessEditor’s ChoiceReview

Up-Date on Diabetic Nephropathy

by Maria Chiara Pelle, Michele Provenzano, Marco Busutti, Clara Valentina Porcu, Isabella Zaffina, Lucia Stanga and Franco Arturi

Life 2022, 12(8), 1202; https://doi.org/10.3390/life12081202 - 08 Aug 2022

Cited by 35 | Viewed by 5153

Abstract

Diabetes is one of the leading causes of kidney disease. Diabetic kidney disease (DKD) is a major cause of end-stage kidney disease (ESKD) worldwide, and it is linked to an increase in cardiovascular (CV) risk. Diabetic nephropathy (DN) increases morbidity and mortality among [...] Read more.

Diabetes is one of the leading causes of kidney disease. Diabetic kidney disease (DKD) is a major cause of end-stage kidney disease (ESKD) worldwide, and it is linked to an increase in cardiovascular (CV) risk. Diabetic nephropathy (DN) increases morbidity and mortality among people living with diabetes. Risk factors for DN are chronic hyperglycemia and high blood pressure; the renin-angiotensin-aldosterone system blockade improves glomerular function and CV risk in these patients. Recently, new antidiabetic drugs, including sodium–glucose transport protein 2 inhibitors and glucagon-like peptide-1 agonists, have demonstrated additional contribution in delaying the progression of kidney disease and enhancing CV outcomes. The therapeutic goal is regression of albuminuria, but an atypical form of non-proteinuric diabetic nephropathy (NP-DN) is also described. In this review, we provide a state-of-the-art evaluation of current treatment strategies and promising emerging treatments. Full article

(This article belongs to the Special Issue Hyperglycemia: From Pathophysiology to Therapeutics)

► Show Figures

Figure 1

14 pages, 5983 KiB

Open AccessEditor’s ChoiceArticle

Modularity of the Human Musculoskeletal System: The Correlation between Functional Structures by Computer Tools Analysis

by Daniele Della Posta, Jacopo Junio Valerio Branca, Giulia Guarnieri, Cristiana Veltro, Alessandra Pacini and Ferdinando Paternostro

Life 2022, 12(8), 1186; https://doi.org/10.3390/life12081186 - 03 Aug 2022

Cited by 2 | Viewed by 1634

Abstract

Introduction: For many years, anatomical studies have been conducted with a shattered view of the body. Although the study of the different apparatuses provides a systemic view of the human body, the reconstruction of the complex network of anatomical structures is crucial for [...] Read more.

Introduction: For many years, anatomical studies have been conducted with a shattered view of the body. Although the study of the different apparatuses provides a systemic view of the human body, the reconstruction of the complex network of anatomical structures is crucial for the understanding of structural and functional integration. Aim: We used network analysis to investigate the connection between the whole-body osteo-myofascial structures of the human musculoskeletal system. Materials and Methods: The musculoskeletal network was performed using the aNETomy^® anatomical network with the implementation of the open-source software Cytoscape for data entry. Results: The initial graph was applied with a network consisting of 2298 body parts (nodes) and 7294 links, representing the musculoskeletal system. Considering the same weighted and unweighted osteo-myofascial network, a different distribution was obtained, suggesting both a topological organization and functional behavior of the network structure. Conclusions: Overall, we provide a deeply detailed anatomical network map of the whole-body musculoskeletal system that can be a useful tool for the comprehensive understanding of every single structure within the complex morphological organization, which could be of particular interest in the study of rehabilitation of movement dysfunctions. Full article

(This article belongs to the Section Physiology and Pathology)

► Show Figures

Figure 1

5 pages, 758 KiB

Open AccessEditor’s ChoiceCase Report

Symptomatic Vascular Compression of Brainstem May Be Managed Conservatively

by Malik Ghannam, Meaghen Berns, Apameh Salari, Lisa Moore and Kevin Brown

Life 2022, 12(8), 1179; https://doi.org/10.3390/life12081179 - 02 Aug 2022

Viewed by 2452

Abstract

Medulla compression from vertebral artery abnormality is a very rare occurrence with few cases present in the literature. It has been documented to present with a very wide spectrum of clinical symptomatology ranging from asymptomatic to full hemiplegia. There is currently no treatment [...] Read more.

Medulla compression from vertebral artery abnormality is a very rare occurrence with few cases present in the literature. It has been documented to present with a very wide spectrum of clinical symptomatology ranging from asymptomatic to full hemiplegia. There is currently no treatment algorithm in place to guide clinicians encountering such patients but treatments have historically involved major posterior compartment surgical interventions. This case outlined a patient evaluated for dizziness without any other neurological symptoms or signs, found to have abnormal dilatation, elongation, and tortuosity of the vertebral artery with resultant compression of the medulla oblongata. The patient was managed conservatively after discussion of surgical options. This report outlined an important consideration for management of medullar compression by vertebral artery based on symptom severity with the possibility of postponing surgical or endovascular interventions and opting for conservative management with an anti-platelet regimen, particularly in the short term. Full article

(This article belongs to the Special Issue Neurophysiologic Disease Processes and New Methods of Study)

► Show Figures

Figure 1

23 pages, 1338 KiB

Open AccessEditor’s ChoiceReview

Left Ventricular Remodeling after Myocardial Infarction: From Physiopathology to Treatment

by Sabina Andreea Leancă, Daniela Crișu, Antoniu Octavian Petriș, Irina Afrăsânie, Antonia Genes, Alexandru Dan Costache, Dan Nicolae Tesloianu and Irina Iuliana Costache

Life 2022, 12(8), 1111; https://doi.org/10.3390/life12081111 - 24 Jul 2022

Cited by 26 | Viewed by 8207

Abstract

Myocardial infarction (MI) is the leading cause of death and morbidity worldwide, with an incidence relatively high in developed countries and rapidly growing in developing countries. The most common cause of MI is the rupture of an atherosclerotic plaque with subsequent thrombotic occlusion [...] Read more.

Myocardial infarction (MI) is the leading cause of death and morbidity worldwide, with an incidence relatively high in developed countries and rapidly growing in developing countries. The most common cause of MI is the rupture of an atherosclerotic plaque with subsequent thrombotic occlusion in the coronary circulation. This causes cardiomyocyte death and myocardial necrosis, with subsequent inflammation and fibrosis. Current therapies aim to restore coronary flow by thrombus dissolution with pharmaceutical treatment and/or intravascular stent implantation and to counteract neurohormonal activation. Despite these therapies, the injury caused by myocardial ischemia leads to left ventricular remodeling; this process involves changes in cardiac geometry, dimension and function and eventually progression to heart failure (HF). This review describes the pathophysiological mechanism that leads to cardiac remodeling and the therapeutic strategies with a role in slowing the progression of remodeling and improving cardiac structure and function. Full article

(This article belongs to the Special Issue Ischemic Heart Disease in the Context of Different Comorbidities)

► Show Figures

Figure 1

12 pages, 321 KiB

Open AccessEditor’s ChoiceArticle

Alzheimer’s Disease Risk Variant rs3865444 in the CD33 Gene: A Possible Role in Susceptibility to Multiple Sclerosis

by Juraj Javor, Mária Bucová, Vladimíra Ďurmanová, Dominika Radošinská, Zuzana Párnická, Daniel Čierny, Egon Kurča, Daniela Čopíková-Cudráková, Karin Gmitterová and Ivana Shawkatová

Life 2022, 12(7), 1094; https://doi.org/10.3390/life12071094 - 21 Jul 2022

Cited by 1 | Viewed by 1689

Abstract

Polymorphisms in genes encoding receptors that modulate the activity of microglia and macrophages are attractive candidates for participation in genetic susceptibility to multiple sclerosis (MS). The aims of the study were to (1) investigate the association between Alzheimer’s disease-linked variant rs3865444:C>A in the [...] Read more.

Polymorphisms in genes encoding receptors that modulate the activity of microglia and macrophages are attractive candidates for participation in genetic susceptibility to multiple sclerosis (MS). The aims of the study were to (1) investigate the association between Alzheimer’s disease-linked variant rs3865444:C>A in the CD33 gene and MS risk, (2) assess the effect of the strongest MS risk allele HLA-DRB1*15:01 on this association, and (3) analyze the correlation of rs3865444 with selected clinical phenotypes, i.e., age of onset and disease severity. CD33 rs3865444 was genotyped in a cohort of 579 patients and 1145 controls and its association with MS risk and clinical phenotypes was analyzed by logistic and linear regression analysis, respectively. Statistical evaluation revealed that rs3865444 reduces the risk of MS in the HLA-DRB1*15:01-positive subpopulation but not in the cohort negative for HLA-DRB1*15:01. A significant antagonistic epistasis between rs3865444 A and HLA-DRB1*15:01 alleles in the context of MS risk was detected by the interaction synergy factor analysis. Comparison of allele and genotype distribution between relapsing-remitting MS, secondary progressive MS, and control groups revealed that rs3865444 C to A substitution may also be associated with a decreased risk of transition of MS to its secondary progressive form, irrespective of the HLA-DRB1*15:01 carrier status. On the other hand, no correlation could be found between rs3865444 and the age of disease onset or MS severity score. Future studies are required to shed more light on the role of CD33 in MS pathogenesis. Full article

(This article belongs to the Special Issue Neurological Diseases: From Molecular Mechanisms to Therapy)

16 pages, 4808 KiB

Open AccessEditor’s ChoiceReview

Pathogenesis of Distal Symmetrical Polyneuropathy in Diabetes

by Sasha Smith, Pasha Normahani, Tristan Lane, David Hohenschurz-Schmidt, Nick Oliver and Alun Huw Davies

Life 2022, 12(7), 1074; https://doi.org/10.3390/life12071074 - 19 Jul 2022

Cited by 11 | Viewed by 3672

Abstract

Distal symmetrical polyneuropathy (DSPN) is a serious complication of diabetes associated with significant disability and mortality. Although more than 50% of people with diabetes develop DSPN, its pathogenesis is still relatively unknown. This lack of understanding has limited the development of novel disease-modifying [...] Read more.

Distal symmetrical polyneuropathy (DSPN) is a serious complication of diabetes associated with significant disability and mortality. Although more than 50% of people with diabetes develop DSPN, its pathogenesis is still relatively unknown. This lack of understanding has limited the development of novel disease-modifying therapies and left the reasons for failed therapies uncertain, which is critical given that current management strategies often fail to achieve long-term efficacy. In this article, the pathogenesis of DSPN is reviewed, covering pathogenic changes in the peripheral nervous system, microvasculature and central nervous system (CNS). Furthermore, the successes and limitations of current therapies are discussed, and potential therapeutic targets are proposed. Recent findings on its pathogenesis have called the definition of DSPN into question and transformed the disease model, paving the way for new research prospects. Full article

(This article belongs to the Special Issue Peripheral Diabetic Neuropathy: Symptoms, Causes and Treatment)

► Show Figures

Figure 1

11 pages, 1201 KiB

Open AccessEditor’s ChoiceArticle

Finding Emergent Gait Patterns May Reduce Progression of Knee Osteoarthritis in a Clinically Relevant Time Frame

by Dhruv Gupta, Cyril John Donnelly and Jeffrey A. Reinbolt

Life 2022, 12(7), 1050; https://doi.org/10.3390/life12071050 - 14 Jul 2022

Cited by 3 | Viewed by 1873

Abstract

A high contact force between the medial femoral condyle and the tibial plateau is the primary cause of medial compartment knee osteoarthritis (OA). A high medial contact force (MCF) during gait has been shown to be correlated to both the knee adduction moment [...] Read more.

A high contact force between the medial femoral condyle and the tibial plateau is the primary cause of medial compartment knee osteoarthritis (OA). A high medial contact force (MCF) during gait has been shown to be correlated to both the knee adduction moment (KAM) and knee flexion/extension moment (KFM). In this study, we used OpenSim Moco to find gait kinematics that reduced the peaks of the KAM, without increasing the peaks of the KFM, which could potentially reduce the MCF and, hence, the progression of knee OA. We used gait data from four knee OA participants. Our simulations decreased both peaks of the KAM without increasing either peak of the KFM. We found that increasing the step width was the primary mechanism, followed by simulations of all participants to reduce the frontal plane lever arm of the ground reaction force vector about the knee, in turn reducing the KAM. Importantly, each participant simulation followed different patterns of kinematic changes to achieve this reduction, which highlighted the need for participant-specific gait modifications. Moreover, we were able to simulate emerging gait patterns within 15 min, enhancing the relevance and potential for the application of developed methods in clinical settings. Full article

(This article belongs to the Special Issue The Biomechanics of Injury and Rehabilitation)

► Show Figures

Figure 1

14 pages, 1543 KiB

Open AccessEditor’s ChoiceArticle

Combination of Two Manipulative Techniques for the Treatment of Cervicogenic Dizziness: A Randomized Controlled Trial

by Andoni Carrasco-Uribarren, Pilar Pardos-Aguilella, Silvia Pérez-Guillén, Carlos López-de-Celis, Jacobo Rodríguez-Sanz and Sara Cabanillas-Barea

Life 2022, 12(7), 1023; https://doi.org/10.3390/life12071023 - 09 Jul 2022

Cited by 2 | Viewed by 2418

Abstract

Cervicogenic dizziness is clinically associated with upper cervical spine dysfunctions. It seems that manual therapy decreases the intensity of dizziness in these subjects, but what happens to pain measured by pressure pain threshold (PPT) has not been studied. Purpose: analyze the short-term effects [...] Read more.

Cervicogenic dizziness is clinically associated with upper cervical spine dysfunctions. It seems that manual therapy decreases the intensity of dizziness in these subjects, but what happens to pain measured by pressure pain threshold (PPT) has not been studied. Purpose: analyze the short-term effects of combination two manipulation techniques protocol in worst dizziness intensity (wVAS), dizziness and cervical disability, upper cervical spine mobility and mechanosensivity of cervical tissue. Methods: Assessor-blinded randomized controlled trial was developed. A total of 40 patients with cervicogenic dizziness were randomly divided into two groups. The experimental group received three treatments consisting of a functional massage and a manipulation technique, and compared with a control group. The wVAS, dizziness handicap inventory (DHI), neck disability index (NDI), UCS mobility, and PPTs were measured. Measurements were made at the baseline, first follow-up 48 h after intervention and second follow-up 1 month after the intervention. Results: at second follow-up wVAS (p < 0.001), NDI (p < 0.001), DHI (p < 0.001), and upper right trapezius (p < 0.022) and right suboccipital (p < 0.043) PPTs showed a difference between groups in favor of the experimental group. Conclusions: apparently, the proposed intervention protocol decreases the intensity of dizziness and the mechanosensitivity of the cervical tissue and improves the feeling of disability due to neck pain and dizziness. Full article

(This article belongs to the Special Issue The Biomechanics of Injury and Rehabilitation)

► Show Figures

Figure 1

13 pages, 1218 KiB

Open AccessEditor’s ChoiceReview

Cardio-Oncology Rehabilitation—Present and Future Perspectives

by Boaz Elad, Manhal Habib and Oren Caspi

Life 2022, 12(7), 1006; https://doi.org/10.3390/life12071006 - 07 Jul 2022

Cited by 5 | Viewed by 3078

Abstract

Recent advances in cancer therapy have led to increased survival rates for cancer patients, but also allowed cardiovascular complications to become increasingly evident, with more than 40% of cancer deaths now being attributed to cardiovascular diseases. Cardiotoxicity is the most concerning cardiovascular complication, [...] Read more.

Recent advances in cancer therapy have led to increased survival rates for cancer patients, but also allowed cardiovascular complications to become increasingly evident, with more than 40% of cancer deaths now being attributed to cardiovascular diseases. Cardiotoxicity is the most concerning cardiovascular complication, one caused mainly due to anti-cancer drugs. Among the harmful mechanisms of these drugs are DNA damage, endothelial dysfunction, and oxidative stress. Cancer patients can suffer reduced cardiorespiratory fitness as a secondary effect of anti-cancer therapies, tumor burden, and deconditioning. In the general population, regular exercise can reduce the risk of cardiovascular morbidity, mortality, and cancer. Exercise-induced modifications of gene expression result in improvements of cardiovascular parameters and an increased general fitness, influencing telomere shortening, oxidative stress, vascular function, and DNA repair mechanisms. In cancer patients, exercise training is generally safe and well-tolerated; it is associated with a 10–15% improvement in cardiorespiratory fitness and can potentially counteract the adverse effects of anti-cancer therapy. It is well known that exercise programs can benefit patients with heart disease and cancer, but little research has been conducted with cardio-oncology patients. To date, there are a limited number of effective protective treatments for preventing or reversing cardiotoxicity caused by cancer therapy. Cardiac rehabilitation has the potential to mitigate cardiotoxicity based on the benefits already proven in populations suffering from either cancer or heart diseases. Additionally, the fact that cardiotoxic harm mechanisms coincide with similar mechanisms positively affected by cardiac rehabilitation makes cardiac rehabilitation an even more plausible option for cardio-oncology patients. Due to unstable functional capacity and fluctuating immunocompetence, these patients require specially tailored exercise programs designed collaboratively by cardiologists and oncologists. As the digital era is here, with the digital world and the medical world continuously intertwining, a remote, home-based cardio-oncology rehabilitation program may be a solution for this population. Full article

(This article belongs to the Special Issue Cardio-oncology: From Basic Mechanisms and research to Clinical Practice)

► Show Figures

Figure 1

8 pages, 255 KiB

Open AccessEditor’s ChoiceArticle

Fever Correlation with Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) Concentrations in Patients with Isolated Polymyalgia Rheumatica (PMR): A Retrospective Comparison Study between Hospital and Out-of-Hospital Local Registries

by Ciro Manzo, Marcin Milchert, Carlo Venditti, Alberto Castagna, Arvind Nune, Maria Natale and Marek Brzosko

Life 2022, 12(7), 985; https://doi.org/10.3390/life12070985 - 30 Jun 2022

Cited by 1 | Viewed by 2046

Abstract

Background: Polymyalgia rheumatica (PMR) is the most common systemic inflammatory rheumatic disease affecting the elderly. Giant cell arteritis (GCA) is a granulomatous vasculitis affecting the aorta and its branches associated with PMR in up to 20% of cases. In recent studies based on [...] Read more.

Background: Polymyalgia rheumatica (PMR) is the most common systemic inflammatory rheumatic disease affecting the elderly. Giant cell arteritis (GCA) is a granulomatous vasculitis affecting the aorta and its branches associated with PMR in up to 20% of cases. In recent studies based on university hospital registries, fever correlated with the erythrocyte sedimentation rate (ESR) but not with C-reactive protein (CRP) concentrations at the time of diagnosis in patients with isolated PMR. A long delay to a PMR diagnosis was suggested to explain this discrepancy, possibly caused by laboratory alterations (for instance, anemia of chronic disease type) that can influence only ESR. We performed a retrospective comparison study between the university hospital and two out-of-hospital public ambulatory databases, searching for any differences in fever/low-grade fever correlation with ESR and CRP. Methods: We identified all patients with newly diagnosed PMR between 2013 and 2020, only including patients who had a body temperature (BT) measurement at the time of diagnosis and a follow-up of at least two years. We considered BT as normal at <37.2 °C. Routine diagnostic tests for differential diagnostics were performed at the time of diagnosis and during follow-ups, indicating the need for more in-depth investigations if required. The GCA was excluded based on the presence of suggestive signs or symptoms and routine ultrasound examination of temporal, axillary, subclavian, and carotid arteries by experienced ultrasonographers. Patients with malignancies, chronic renal disease, bacterial infections, and body mass index (BMI) > 30 kg/m² were excluded, as these conditions can increase CRP and/or ESR. Finally, we used the Cumulative Illness Rating Scale (CIRS) for quantifying the burden of comorbidities and excluded patients with a CIRS index > 4 as an additional interfering factor. Results: We evaluated data from 169 (73 from hospital and 96 from territorial registries) patients with newly diagnosed isolated PMR. Among these, 77.7% were female, and 61.5% of patients had normal BT at the time of diagnosis. We divided the 169 patients into two cohorts (hospital and territorial) according to the first diagnostic referral. Age at diagnosis, ESR, CRP, median hemoglobin (HB), and diagnostic delay (days from first manifestations to final diagnosis) were statistically significantly different between the two cohorts. However, when we assessed these data according to BT in the territorial cohort, we found a statistical difference only between ESR and BT (46.39 ± 19.31 vs. 57.50 ± 28.16; p = 0.026). Conclusions: ESR but not CRP correlates with fever/low-grade fever at the time of diagnosis in PMR patients with a short diagnosis delay regardless of HB levels. ESR was the only variable having a statistically significant correlation with BT in a multilevel regression analysis adjusted for cohorts (β = 0.312; p = 0.014). Full article

(This article belongs to the Special Issue Innovative Biomarker and Precision Medicine)

22 pages, 1052 KiB

Open AccessEditor’s ChoiceReview

Cancer Cachexia and Antitumor Immunity: Common Mediators and Potential Targets for New Therapies

by Konstantinos Rounis, Dimitrios Makrakis, Ioannis Gioulbasanis, Simon Ekman, Luigi De Petris, Dimitris Mavroudis and Sofia Agelaki

Life 2022, 12(6), 880; https://doi.org/10.3390/life12060880 - 12 Jun 2022

Cited by 1 | Viewed by 2449

Abstract

Cancer cachexia syndrome (CCS) is a multifactorial metabolic syndrome affecting a significant proportion of patients. CCS is characterized by progressive weight loss, alterations of body composition and a systemic inflammatory status, which exerts a major impact on the host’s innate and adaptive immunity. [...] Read more.

Cancer cachexia syndrome (CCS) is a multifactorial metabolic syndrome affecting a significant proportion of patients. CCS is characterized by progressive weight loss, alterations of body composition and a systemic inflammatory status, which exerts a major impact on the host’s innate and adaptive immunity. Over the last few years, the development of immune checkpoint inhibitors (ICIs) transformed the treatment landscape for a wide spectrum of malignancies, creating an unprecedented opportunity for long term remissions in a significant subset of patients. Early clinical data indicate that CCS adversely impairs treatment outcomes of patients receiving ICIs. We herein reviewed existing evidence on the potential links between the mechanisms that promote the catabolic state in CCS and those that impair the antitumor immune response. We show that the biological mediators and processes leading to the development of CCS may also participate in the modulation and the sustainment of an immune suppressive tumor microenvironment and impaired anti-tumor immunity. Moreover, we demonstrate that the deregulation of the host’s metabolic homeostasis in cancer cachexia is associated with resistance to ICIs. Further research on the interrelation between cancer cachexia and anti-tumor immunity is required for the effective management of resistance to immunotherapy in this specific but large subgroup of ICI treated individuals. Full article

(This article belongs to the Collection Tumor Progression, Microenvironments, and Therapeutics)

► Show Figures

Figure 1

12 pages, 1215 KiB

Open AccessEditor’s ChoiceArticle

How Is CYP17A1 Activity Altered in Autism? A Pilot Study to Identify Potential Pharmacological Targets

by Benedikt Andreas Gasser, Johann Kurz, Bernhard Dick and Markus Georg Mohaupt

Life 2022, 12(6), 867; https://doi.org/10.3390/life12060867 - 10 Jun 2022

Cited by 1 | Viewed by 1744

Abstract

Background: Increasing evidence exists that higher levels of androgens can be found in individuals with autism. Evidence yields to a susceptible role of Cytochrome P450 17A1 (CYP17A1) with its catalyzation of the two distinct types of substrate oxidation by a hydroxylase activity (17-alpha [...] Read more.

Background: Increasing evidence exists that higher levels of androgens can be found in individuals with autism. Evidence yields to a susceptible role of Cytochrome P450 17A1 (CYP17A1) with its catalyzation of the two distinct types of substrate oxidation by a hydroxylase activity (17-alpha hydroxylase) and C17/20 lyase activity. However, to what extent steps are altered in affected children with autism versus healthy controls remains to be elucidated. Methods: Urine samples from 48 boys with autism (BMI 19.1 ± 0.6 kg/m², age 14.2 ± 0.5 years) and a matched cohort of 48 healthy boys (BMI 18.6 ± 0.3 kg/m², 14.3 ± 0.5 years) as well as 16 girls with autism (BMI 17.5 ± 0.7 kg/m², age 13.8 ± 1.0 years) and a matched cohort of 16 healthy girls (BMI 17.2 ± 0.8 kg/m², age 13.2 ± 0.8 years) were analyzed for steroid hormone metabolites by gas chromatography-mass spectrometry. Results: The activity of 17-alpha Hydroxylase increased by almost 50%, whereas activity of 17/20 Lyase activity increased by around 150% in affected children with autism. Furthermore, the concentration of Cortisol was higher as compared to the average increase of the three metabolites TH-Corticosterone, 5α-TH-Corticosterone and TH-11β-DH-Corticosterone, indicating, in addition, a stimulation by the CRH-ACTH system despite a higher enzymatic activity. Discussion: As it was shown that oxidative stress increases the 17/20-lyase activity via p38α, a link between higher steroid hormone levels and oxidative stress can be established. However, as glucocorticoid as well as androgen metabolites showed higher values in subjects affected with autism as compared to healthy controls, the data indicate, despite higher CYP17A1 activity, the presence of increased substrate availability in line with the Cholesterol theory of autism. Full article

(This article belongs to the Section Physiology and Pathology)

► Show Figures

Figure 1

12 pages, 4381 KiB

Open AccessEditor’s ChoiceArticle

A Seed-Borne Bacterium of Rice, Pantoea dispersa BB1, Protects Rice from the Seedling Rot Caused by the Bacterial Pathogen Burkholderia glumae

by Yusuke Kouzai and Chiharu Akimoto-Tomiyama

Life 2022, 12(6), 791; https://doi.org/10.3390/life12060791 - 26 May 2022

Cited by 7 | Viewed by 2716

Abstract

Seedling rot, caused by the bacterial pathogen Burkholderia glumae, is a major disease of rice. It originates from pathogen-contaminated seeds and is thus mainly controlled by pesticide treatments of seeds. We previously demonstrated that the seed-borne bacteria of rice may be a [...] Read more.

Seedling rot, caused by the bacterial pathogen Burkholderia glumae, is a major disease of rice. It originates from pathogen-contaminated seeds and is thus mainly controlled by pesticide treatments of seeds. We previously demonstrated that the seed-borne bacteria of rice may be a useful and sustainable alternative to pesticides to manage seedling rot, but they are limited in terms of variety. Here, we report that another seed-borne bacterium, Pantoea dispersa BB1, protects rice from B. glumae. We screened 72 bacterial isolates from rice seeds of three genetically different cultivars inoculated or non-inoculated with B. glumae. 16S rRNA gene sequencing revealed that pathogen inoculation affected the composition of culturable seed-borne bacterial communities and increased the presence of Pantoea and Paenibacillus species. Among three Pantoea and Paenibacillus isolates that exhibit tolerance to toxoflavin, a virulence factor of B. glumae, P. dispersa BB1 significantly mitigated the symptoms of rice seedling rot. The culture filtrate of BB1 inhibited the growth of B. glumae in vitro, suggesting that this isolate secretes antibacterial compounds. Seed treatment with BB1 suppressed pathogen propagation in plants, although seed treatment with the culture filtrate did not. Because BB1 did not show pathogenicity in rice, our findings demonstrate that BB1 is a promising biocontrol agent against seedling rot. Full article

(This article belongs to the Collection State of the Art in Plant Science)

► Show Figures

Figure 1

17 pages, 760 KiB

Open AccessEditor’s ChoiceReview

Acute and Long-Term Consequences of COVID-19 on Arterial Stiffness—A Narrative Review

by Ioana Mădălina Zota, Cristian Stătescu, Radu Andy Sascău, Mihai Roca, Larisa Anghel, Alexandra Maștaleru, Maria Magdalena Leon-Constantin, Cristina Mihaela Ghiciuc, Sebastian Romica Cozma, Lucia Corina Dima-Cozma, Irina Mihaela Esanu and Florin Mitu

Life 2022, 12(6), 781; https://doi.org/10.3390/life12060781 - 25 May 2022

Cited by 9 | Viewed by 3422

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global coronavirus (COVID-19) pandemic. Although initially viewed as an acute respiratory illness, COVID-19 is clearly a complex multisystemic disease with extensive cardiovascular involvement. Emerging evidence shows that the endothelium plays [...] Read more.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global coronavirus (COVID-19) pandemic. Although initially viewed as an acute respiratory illness, COVID-19 is clearly a complex multisystemic disease with extensive cardiovascular involvement. Emerging evidence shows that the endothelium plays multiple roles in COVID-19 physiopathology, as both a target organ that can be directly infected by SARS-CoV-2 and a mediator in the subsequent inflammatory and thrombotic cascades. Arterial stiffness is an established marker of cardiovascular disease. The scope of this review is to summarize available data on the acute and long-term consequences of COVID-19 on vascular function. COVID-19 causes early vascular aging and arterial stiffness. Fast, noninvasive bedside assessment of arterial stiffness could optimize risk stratification in acute COVID-19, allowing for early escalation of treatment. Vascular physiology remains impaired at least 12 months after infection with SARS-CoV-2, even in otherwise healthy adults. This raises concerns regarding the extent of arterial remodeling in patients with preexisting vascular disease and the potential development of a persistent, chronic COVID-19 vasculopathy. Long-term follow up on larger cohorts is required to investigate the reversibility of COVID-19-induced vascular changes and their associated prognostic implications. Full article

(This article belongs to the Section Medical Research)

► Show Figures

Figure 1

15 pages, 3321 KiB

Open AccessEditor’s ChoiceArticle

Role of SaPCR2 in Zn Uptake in the Root Elongation Zone of the Zn/Cd Hyperaccumulator Sedum alfredii

by Jun Ge, Jiayu Lin, Zhiying Wu, Kuan Xu, Jingyu Tao, Haizhong Lin, Shengke Tian and Lingli Lu

Life 2022, 12(5), 768; https://doi.org/10.3390/life12050768 - 23 May 2022

Viewed by 1563

Abstract

Zn pollution is a potential toxicant for agriculture and the environment. Sedum alfredii is a Zn/Cd hyperaccumulator found in China and has been proven as a useful resource for the phytoremediation of Zn-contaminated sites. However, the molecular mechanism of Zn uptake in S. [...] Read more.

Zn pollution is a potential toxicant for agriculture and the environment. Sedum alfredii is a Zn/Cd hyperaccumulator found in China and has been proven as a useful resource for the phytoremediation of Zn-contaminated sites. However, the molecular mechanism of Zn uptake in S. alfredii is limited. In this study, the function of SaPCR2 on Zn uptake in S. alfredii was identified by gene expression analysis, yeast function assays, Zn accumulation and root morphology analysis in transgenic lines to further elucidate the mechanisms of uptake and translocation of Zn in S. alfredii. The results showed that SaPCR2 was highly expressed in the root elongation zone of the hyperaccumulating ecotype (HE) S. alfredii, and high Zn exposure downregulated the expression of SaPCR2 in the HE S. alfredii root. The heterologous expression of SaPCR2 in yeast suggested that SaPCR2 was responsible for Zn influx. The overexpression of SaPCR2 in the non-hyperaccumulating ecotype (NHE) S. alfredii significantly increased the root uptake of Zn, but did not influence Mn, Cu or Fe. SR-μ-XRF technology showed that more Zn was distributed in the vascular buddle tissues, as well as in the cortex and epidermis in the transgenic lines. Root morphology was also altered after SaPCR2 overexpression, and a severe inhibition was observed. In the transgenic lines, the meristematic and elongation zones of the root were lower compared to the WT, and Zn accumulation in meristem cells was also reduced. These results indicate that SaPCR2 is responsible for Zn uptake, and mainly functions in the root elongation zone. This research on SaPCR2 could provide a theoretical basis for the use of genetic engineering technology in the modification of crops for their safe production and biological enhancement. Full article

(This article belongs to the Special Issue Uptake, Translocation, and Metabolism of Trace Metals in Plants)

► Show Figures

Figure 1

14 pages, 703 KiB

Open AccessEditor’s ChoiceReview

Regulatory Effects of Statins on SIRT1 and Other Sirtuins in Cardiovascular Diseases

by Danial Khayatan, Seyed Mehrad Razavi, Zahra Najafi Arab, Maryam Khanahmadi, Saeideh Momtaz, Alexandra E. Butler, Fabrizio Montecucco, Yuliya V. Markina, Amir Hossein Abdolghaffari and Amirhossein Sahebkar

Life 2022, 12(5), 760; https://doi.org/10.3390/life12050760 - 20 May 2022

Cited by 6 | Viewed by 5277

Abstract

Adverse cardiovascular disease (CVD) outcomes, such as sudden cardiac death, acute myocardial infarction, and stroke, are often catastrophic. Statins are frequently used to attenuate the risk of CVD-associated morbidity and mortality through their impact on lipids and they may also have anti-inflammatory and [...] Read more.

Adverse cardiovascular disease (CVD) outcomes, such as sudden cardiac death, acute myocardial infarction, and stroke, are often catastrophic. Statins are frequently used to attenuate the risk of CVD-associated morbidity and mortality through their impact on lipids and they may also have anti-inflammatory and other plaque-stabilization effects via different signaling pathways. Different statins, including atorvastatin, rosuvastatin, pravastatin, pitavastatin, and simvastatin, are administered to manage circulatory lipid levels. In addition, statins are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase via modulating sirtuins (SIRTs). During the last two decades, SIRTs have been investigated in mammals and categorized as a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases (HDACs) with significant oxidative stress regulatory function in cells—a key factor in extending cell lifespan. Recent work has demonstrated that statins upregulate SIRT1 and SIRT2 and downregulate SIRT6 in both in vitro and in vivo experiments and clinical trials. As statins show modulatory properties, especially in CVDs, future investigations are needed to delineate the role of SIRT family members in disease and to expand knowledge about the effects of statins on SIRTs. Here, we review what is currently known about the impact of statins on SIRTs and how these changes correlate with disease, particularly CVDs. Full article

(This article belongs to the Section Pharmaceutical Science)

► Show Figures

Figure 1

17 pages, 1398 KiB

Open AccessEditor’s ChoiceArticle

SIRT1: Genetic Variants and Serum Levels in Age-Related Macular Degeneration

by Kriste Kaikaryte, Greta Gedvilaite, Alvita Vilkeviciute, Loresa Kriauciuniene, Ruta Mockute, Dzastina Cebatoriene, Reda Zemaitiene, Vilma Jurate Balciuniene and Rasa Liutkeviciene

Life 2022, 12(5), 753; https://doi.org/10.3390/life12050753 - 19 May 2022

Viewed by 1775

Abstract

Background: The aim of this paper was to determine the frequency of SIRT1 rs3818292, rs3758391, rs7895833 single nucleotide polymorphism genotypes and SIRT1 serum levels associated with age-related macular degeneration (AMD) in the Lithuanian population. Methods: Genotyping of SIRT1 rs3818292, rs3758391 and rs7895833 was [...] Read more.

Background: The aim of this paper was to determine the frequency of SIRT1 rs3818292, rs3758391, rs7895833 single nucleotide polymorphism genotypes and SIRT1 serum levels associated with age-related macular degeneration (AMD) in the Lithuanian population. Methods: Genotyping of SIRT1 rs3818292, rs3758391 and rs7895833 was performed using RT-PCR. SIRT1 serum level was determined using the ELISA method. Results: We found that rs3818292 and rs7895833 were associated with an increased risk of developing exudative AMD. Additional sex-differentiated analysis revealed only rs7895833 was associated with an increased risk of developing exudative AMD in women after strict Bonferroni correction. The analysis also revealed that individuals carrying rs3818292, rs3758391 and rs7895833 haplotype G-T-G are associated with increased odds of exudative AMD. Still, the rare haplotypes were associated with the decreased odds of exudative AMD. After performing an analysis of serum SIRT1 levels and SIRT1 genetic variant, we found that carriers of the SIRT1 rs3818292 minor allele G had higher serum SIRT1 levels than the AA genotype. In addition, individuals carrying at least one SIRT1 rs3758391 T allele also had elevated serum SIRT1 levels compared with individuals with the wild-type CC genotype. Conclusions: Our study showed that the SIRT1 polymorphisms rs3818292 and rs7895833 and rs3818292-rs3758391-rs7895833 haplotype G-T-G could be associated with the development of exudative AMD. Also, two SNPs (rs3818292 and rs3758391) are associated with elevated SIRT1 levels. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration: From Mechanisms to Therapy)

► Show Figures

Figure 1

13 pages, 6581 KiB

Open AccessEditor’s ChoiceArticle

Diffusion Tensor Imaging of a Median Nerve by Magnetic Resonance: A Pilot Study

by Kanza Awais, Žiga Snoj, Erika Cvetko and Igor Serša

Life 2022, 12(5), 748; https://doi.org/10.3390/life12050748 - 18 May 2022

Cited by 2 | Viewed by 1865

Abstract

The magnetic resonance Diffusion Tensor Imaging (DTI) is a powerful extension of Diffusion Weighted Imaging (DWI) utilizing multiple bipolar gradients, allowing for the evaluation of the microstructural environment of the highly anisotropic tissues. DTI was predominantly used for the assessment of the central [...] Read more.

The magnetic resonance Diffusion Tensor Imaging (DTI) is a powerful extension of Diffusion Weighted Imaging (DWI) utilizing multiple bipolar gradients, allowing for the evaluation of the microstructural environment of the highly anisotropic tissues. DTI was predominantly used for the assessment of the central nervous system (CNS), but with the advancement in magnetic resonance (MR) hardware and software, it has now become possible to image the peripheral nerves which were difficult to evaluate previously because of their small caliber. This study focuses on the assessment of the human median peripheral nerve ex vivo by DTI microscopy at 9.4 T magnetic field which allowed the evaluation of diffusion eigenvalues, the mean diffusivity and the fractional anisotropy at 35 μm in-plane resolution. The resolution was sufficient for clear depiction of all nerve anatomical structures and therefore further image analysis allowed the obtaining of average values for DT parameters in nerve fascicles (intrafascicular region and perineurium) as well as in the surrounding epineurium. The results confirmed the highest fractional anisotropy of 0.33 and principal diffusion eigenvalue of 1.0 × 10⁻⁹ m²/s in the intrafascicular region, somewhat lower values of 0.27 and 0.95 × 10⁻⁹ m²/s in the perineurium region and close to isotropic with very slow diffusion (0.15 and 0.05 × 10⁻⁹ m²/s) in the epineurium region. Full article

(This article belongs to the Special Issue Imaging in Neurosurgery: State of the Art)

► Show Figures

Figure 1

12 pages, 5462 KiB

Open AccessEditor’s ChoiceArticle

Variations in Strain Distribution at Distal Radius under Different Loading Conditions

by Jonas A. Pramudita, Wataru Hiroki, Takuya Yoda and Yuji Tanabe

Life 2022, 12(5), 740; https://doi.org/10.3390/life12050740 - 16 May 2022

Cited by 1 | Viewed by 3302

Abstract

Distal radial fractures exhibit various fracture patterns. By assuming that the strain distribution at the distal radius affects the diversification of the fracture pattern, a parameter study using the finite element model of a wrist developed from computed tomography (CT) images was performed [...] Read more.

Distal radial fractures exhibit various fracture patterns. By assuming that the strain distribution at the distal radius affects the diversification of the fracture pattern, a parameter study using the finite element model of a wrist developed from computed tomography (CT) images was performed under different loading conditions. The finite element model of the wrist consisted of the radius, ulna, scaphoid, lunate, triquetrum, and major carpal ligaments. The material properties of the bone models were assigned on the basis of the Hounsfield Unit (HU) values of the CT images. An impact load was applied to the scaphoid, lunate, and triquetrum to simulate boundary conditions during fall accidents. This study considered nine different loading conditions that combine three different loading directions and three different load distribution ratios. According to the analysis results, the strain distribution at the distal radius changed with respect to the change in the loading condition. High strain concentration occurred in regions where distal radius fractures are commonly developed. The direction and distribution of the load acting on the radius were considered to be factors that may cause variations in the fracture pattern of distal radius fractures. Full article

(This article belongs to the Special Issue The Biomechanics of Injury and Rehabilitation)

► Show Figures

Figure 1

17 pages, 1115 KiB

Open AccessEditor’s ChoiceArticle

Antimicrobial Properties of Compounds Isolated from Syzygium malaccense (L.) Merr. and L.M. Perry and Medicinal Plants Used in French Polynesia

by Camille Quenon, Thierry Hennebelle, Jean-François Butaud, Raimana Ho, Jennifer Samaillie, Christel Neut, Tamatoa Lehartel, Céline Rivière, Ali Siah, Natacha Bonneau, Sevser Sahpaz, Sébastien Anthérieu, Nicolas Lebegue, Phila Raharivelomanana and Vincent Roumy

Life 2022, 12(5), 733; https://doi.org/10.3390/life12050733 - 14 May 2022

Cited by 7 | Viewed by 2847

Abstract

A preliminary ethnopharmacological survey, achieved in French Polynesia, led to the collection of the most cited plants among 63 species used to treat “infectious” diseases, with a description of their medicinal uses. Bibliographical investigations and antimicrobial screening permitted the selection of the botanical [...] Read more.

A preliminary ethnopharmacological survey, achieved in French Polynesia, led to the collection of the most cited plants among 63 species used to treat “infectious” diseases, with a description of their medicinal uses. Bibliographical investigations and antimicrobial screening permitted the selection of the botanical species Syzygium malaccense (Myrtaceae) for phytochemical analysis. Leaves of Syzygium malaccense were usually used in mixture with rhizomes of Curcuma longa to treat infectious diseases such as cystitis. The methanolic plant extracts were tested in vitro with an agar microdilution method on 33 bacteria strains and 1 yeast to obtain their Minimal Inhibitory Concentration (MIC), and cytotoxicity against HepG2 cells were evaluated. Antimicrobial synergistic effects of methanolic plant extracts from leaves of Syzygium malaccense and rhizomes from Curcuma longa were also evaluated. The bio-guided isolation of leaf extract from Syzygium malaccense led to the identification of seven alkyl-salicylic acids (anacardic acids or ginkgolic acids C15:0, C15:1, C17:0, C17:1, C17:2, C17:3 and C19:1) described for the first time in this species. All compounds were tested against Staphylococcus aureus (18.75 < MIC < 75.0 µg/mL), Streptococcus pyogenes (2.34 < MIC < 18.75 µg/mL) and Pseudomonas aeruginosa (MIC = 150 µg/mL), and their structure–activity relationships were discussed. The methanolic extract and salicylic derivatives from S. malaccense showed an interesting antimicrobial activity against Gram+ bacteria, without toxicity on hepG2 cells at 400 μg/mL. Moreover, these antibacterial compounds have already been studied for their anti-inflammatory activity, which supports the therapeutic interest of S. malaccense against infectious diseases. Full article

(This article belongs to the Section Plant Science)

► Show Figures

Figure 1

15 pages, 2842 KiB

Open AccessEditor’s ChoiceArticle

Data Mining Identifies CCN2 and THBS1 as Biomarker Candidates for Cardiac Hypertrophy

by Markus Johansson, Benyapa Tangruksa, Sepideh Heydarkhan-Hagvall, Anders Jeppsson, Peter Sartipy and Jane Synnergren

Life 2022, 12(5), 726; https://doi.org/10.3390/life12050726 - 12 May 2022

Cited by 3 | Viewed by 2871

Abstract

Cardiac hypertrophy is a condition that may contribute to the development of heart failure. In this study, we compare the gene-expression patterns of our in vitro stem-cell-based cardiac hypertrophy model with the gene expression of biopsies collected from hypertrophic human hearts. Twenty-five differentially [...] Read more.

Cardiac hypertrophy is a condition that may contribute to the development of heart failure. In this study, we compare the gene-expression patterns of our in vitro stem-cell-based cardiac hypertrophy model with the gene expression of biopsies collected from hypertrophic human hearts. Twenty-five differentially expressed genes (DEGs) from both groups were identified and the expression of selected corresponding secreted proteins were validated using ELISA and Western blot. Several biomarkers, including CCN2, THBS1, NPPA, and NPPB, were identified, which showed significant overexpressions in the hypertrophic samples in both the cardiac biopsies and in the endothelin-1-treated cells, both at gene and protein levels. The protein-interaction network analysis revealed CCN2 as a central node among the 25 overlapping DEGs, suggesting that this gene might play an important role in the development of cardiac hypertrophy. GO-enrichment analysis of the 25 DEGs revealed many biological processes associated with cardiac function and the development of cardiac hypertrophy. In conclusion, we identified important similarities between ET-1-stimulated human-stem-cell-derived cardiomyocytes and human hypertrophic cardiac tissue. Novel putative cardiac hypertrophy biomarkers were identified and validated on the protein level, lending support for further investigations to assess their potential for future clinical applications. Full article

(This article belongs to the Special Issue The Molecular Mechanism of Cardiovascular Disease)

► Show Figures

Figure 1

16 pages, 6005 KiB

Open AccessEditor’s ChoiceArticle

Biogas Production Potential of Thermophilic Anaerobic Biodegradation of Organic Waste by a Microbial Consortium Identified with Metagenomics

by Lyudmila Kabaivanova, Penka Petrova, Venelin Hubenov and Ivan Simeonov

Life 2022, 12(5), 702; https://doi.org/10.3390/life12050702 - 08 May 2022

Cited by 11 | Viewed by 2290

Abstract

Anaerobic digestion (AD) is a widespread biological process treating organic waste for green energy production. In this study, wheat straw and corn stalks without any harsh preliminary treatment were collected as a renewable source to be employed in a laboratory-scale digester to produce [...] Read more.

Anaerobic digestion (AD) is a widespread biological process treating organic waste for green energy production. In this study, wheat straw and corn stalks without any harsh preliminary treatment were collected as a renewable source to be employed in a laboratory-scale digester to produce biogas/biomethane. Processes parameters of temperature, pH, total solids, volatile solid, concentration of volatile fatty acids (VFA), and cellulose concentration, were followed. The volume of biogas produced was measured. The impact of organic loading was stated, showing that the process at 55 °C tolerated a higher substrate load, up to 45 g/L. Further substrate increase did not lead to biogas accumulation increase, probably due to inhibition or mass transfer limitations. After a 12-day anaerobic digestion process, cumulative volumes of biogas yields were 4.78 L for 1 L of the bioreactor working volume with substrate loading 30 g/L of wheat straw, 7.39 L for 40 g/L and 8.22 L for 45 g/L. The degree of biodegradation was calculated to be 68.9%, 74% and 72%, respectively. A fast, effective process for biogas production was developed from native wheat straw, with the highest quantity of daily biogas production occurring between day 2 and day 5. Biomethane concentration in the biogas was 60%. An analysis of bacterial diversity by metagenomics revealed that more than one third of bacteria belonged to class Clostridia (32.9%), followed by Bacteroidia (21.5%), Betaproteobacteria (11.2%), Gammaproteobacteria (6.1%), and Alphaproteobacteria (5%). The most prominent genera among them were Proteiniphilum, Proteiniborus, and Pseudomonas. Archaeal share was 1.37% of the microflora in the thermophilic bioreactor, as the genera Methanocorpusculum, Methanobacterium, Methanomassiliicoccus, Methanoculleus, and Methanosarcina were the most abundant. A knowledge of the microbiome residing in the anaerobic digester can be further used for the development of more effective processes in conjunction with theidentified consortium. Full article

(This article belongs to the Special Issue The Role of Renewable Resources for Ecology and Human Health)

► Show Figures

Figure 1

12 pages, 2527 KiB

Open AccessEditor’s ChoiceArticle

Type 2 Diabetes Mellitus Facilitates Shift of Adipose-Derived Stem Cells Ex Vivo Differentiation toward Osteogenesis among Patients with Obesity

by Margarita Agareva, Iurii Stafeev, Svetlana Michurina, Igor Sklyanik, Ekaterina Shestakova, Elizaveta Ratner, Xiang Hu, Mikhail Menshikov, Marina Shestakova and Yelena Parfyonova

Life 2022, 12(5), 688; https://doi.org/10.3390/life12050688 - 06 May 2022

Cited by 5 | Viewed by 2411

Abstract

Objective: Sedentary behavior with overnutrition provokes the development of obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). The main progenitor cells of adipose tissue are adipose-derived stem cells (ADSCs) which can change differentiation, metabolic, and secretory phenotypes under obesity conditions. The purpose [...] Read more.

Objective: Sedentary behavior with overnutrition provokes the development of obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). The main progenitor cells of adipose tissue are adipose-derived stem cells (ADSCs) which can change differentiation, metabolic, and secretory phenotypes under obesity conditions. The purpose of this study was to evaluate ADSC osteogenesis activity among patients with obesity in normal glucose tolerance (NGT) and T2DM conditions. Methods: In the study, ADSCs from donors with obesity were used. After clinical characterization, all patients underwent bariatric surgery and ADSCs were isolated from subcutaneous fat biopsies. ADSCs were subjected to osteogenic differentiation, stained with Alizarin Red S, and harvested for real-time PCR and Western blotting. Cell senescence was evaluated with a β-galactosidase-activity-based assay. Results: Our results demonstrated the significantly increased calcification of ADSC on day 28 of osteogenesis in the T2DM group. These data were confirmed by the statistically significant enhancement of RUNX2 gene expression, which is a master regulator of osteogenesis. Protein expression analysis showed the increased expression of syndecan 1 and collagen I before and during osteogenesis, respectively. Moreover, T2DM ADSCs demonstrated an increased level of cellular senescence. Conclusion: We suggest that T2DM-associated cellular senescence can cause ADSC differentiation to shift toward osteogenesis, the impaired formation of new fat depots in adipose tissue, and the development of insulin resistance. The balance between ADSC adipo- and osteogenesis commitment is crucial for the determination of the metabolic fate of patients and their adipose tissue. Full article

(This article belongs to the Special Issue Diabetes Metabolism: Molecular and Integrative Approaches)

► Show Figures

Figure 1

24 pages, 6365 KiB

Open AccessEditor’s ChoiceArticle

The Antileukemic and Anti-Prostatic Effect of Aeroplysinin-1 Is Mediated through ROS-Induced Apoptosis via NOX Activation and Inhibition of HIF-1a Activity

by Shou-Ping Shih, Mei-Chin Lu, Mohamed El-Shazly, Yu-Hsuan Lin, Chun-Lin Chen, Steve Sheng-Fa Yu and Yi-Chang Liu

Life 2022, 12(5), 687; https://doi.org/10.3390/life12050687 - 05 May 2022

Cited by 12 | Viewed by 2582

Abstract

Aeroplysinin-1 is a brominated isoxazoline alkaloid that has exhibited a potent antitumor cell effect in previous reports. We evaluated the cytotoxicity of aeroplysinin-1 against leukemia and prostate cancer cells in vitro. This marine alkaloid inhibited the cell proliferation of leukemia Molt-4, K562 cells, [...] Read more.

Aeroplysinin-1 is a brominated isoxazoline alkaloid that has exhibited a potent antitumor cell effect in previous reports. We evaluated the cytotoxicity of aeroplysinin-1 against leukemia and prostate cancer cells in vitro. This marine alkaloid inhibited the cell proliferation of leukemia Molt-4, K562 cells, and prostate cancer cells Du145 and PC-3 with IC₅₀ values of 0.12 ± 0.002, 0.54 ± 0.085, 0.58 ± 0.109 and 0.33 ± 0.042 µM, respectively, as shown by the MTT assay. Furthermore, in the non-malignant cells, CCD966SK and NR8383, its IC₅₀ values were 1.54 ± 0.138 and 6.77 ± 0.190 μM, respectively. In a cell-free system, the thermal shift assay and Western blot assay verified the binding affinity of aeroplysinin-1 to Hsp90 and Topo IIα, which inhibited their activity. Flow cytometry analysis showed that the cytotoxic effect of aeroplysinin-1 is mediated through mitochondria-dependent apoptosis induced by reactive oxygen species (ROS). ROS interrupted the cellular oxidative balance by activating NOX and inhibiting HIF-1α and HO-1 expression. Pretreatment with N-acetylcysteine (NAC) reduced Apl-1-induced mitochondria-dependent apoptosis and preserved the expression of NOX, HO-1, and HIF-1a. Our findings indicated that aeroplysinin-1 targeted leukemia and prostate cancer cells through multiple pathways, suggesting its potential application as an anti-leukemia and prostate cancer drug lead. Full article

(This article belongs to the Section Pharmaceutical Science)

► Show Figures

Figure 1

10 pages, 1246 KiB

Open AccessEditor’s ChoiceArticle

N-Methyl-D-Aspartate (NMDA) Receptors in the Prelimbic Cortex Are Required for Short- and Long-Term Memory Formation in Trace Fear Conditioning

by Eui-Ho Park, Nam-Soo Kim, Yeon-Kyung Lee and June-Seek Choi

Life 2022, 12(5), 672; https://doi.org/10.3390/life12050672 - 01 May 2022

Cited by 2 | Viewed by 2556

Abstract

Accumulating evidence suggests that the medial prefrontal cortex (mPFC) has been implicated in the acquisition of fear memory during trace fear conditioning in which a conditional stimulus (CS) is paired with an aversive unconditional stimulus (UCS) separated by a temporal gap (trace interval, [...] Read more.

Accumulating evidence suggests that the medial prefrontal cortex (mPFC) has been implicated in the acquisition of fear memory during trace fear conditioning in which a conditional stimulus (CS) is paired with an aversive unconditional stimulus (UCS) separated by a temporal gap (trace interval, TI). However, little is known about the role of the prefrontal cortex for short- and long-term trace fear memory formation. Thus, we investigated how the prelimbic (PL) subregion within mPFC in rats contributes to short- and long-term trace fear memory formation using electrolytic lesions and d,l,-2-amino-5-phosphonovaleric acid (APV), an N-methyl-D-aspartate receptor (NMDAR) antagonist infusions into PL. In experiment 1, pre-conditioning lesions of PL impaired freezing to the CS as well as TI during the acquisition and retrieval sessions, indicating that PL is critically involved in trace fear memory formation. In experiment 2, temporary blockade of NMDA receptors in PL impaired the acquisition, but not the expression of short- and long-term trace fear memory. In addition, the inactivation of NMDAR in PL had little effect on locomotor activity, pre-pulse inhibition (PPI), or shock sensitivity. Taken together, these results suggest that NMDA receptor-mediated neurotransmission in PL is required for the acquisition of trace fear memory. Full article

(This article belongs to the Special Issue Glutamate Receptors)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI