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Life, Volume 13, Issue 4 (April 2023) – 213 articles

Cover Story (view full-size image): Despite the improvements in the timely revascularization of acute myocardial infarction, many patients still develop adverse ventricular remodeling and progress to heart failure. In recent years, new pharmacological therapies have emerged for the treatment of HF, including revolutionary drugs such as sodium-glucose cotransporter-2 inhibitors and angiotensin receptor-neprilysin inhibitors, which promote reverse remodeling. Cardiac resynchronization therapy, cardiac contractility modulation, or baroreflex activation therapy are interventional strategies that might provide additional therapeutic benefits. Furthermore, cardiac regenerative therapies such as stem cell transplantation could become a new therapeutic resource in the management of heart failure due to ischemic heart disease. View this paper
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16 pages, 5646 KiB  
Article
Celecoxib, a Non-Steroidal Anti-Inflammatory Drug, Exerts a Toxic Effect on Human Melanoma Cells Grown as 2D and 3D Cell Cultures
by Alessandro Venuta, Rosarita Nasso, Armando Gisonna, Roberta Iuliano, Sara Montesarchio, Vittoria Acampora, Leandra Sepe, Angelica Avagliano, Rosaria Arcone, Alessandro Arcucci and Maria Rosaria Ruocco
Life 2023, 13(4), 1067; https://doi.org/10.3390/life13041067 - 21 Apr 2023
Cited by 1 | Viewed by 2091
Abstract
Cutaneous melanoma (CM) remains one of the leading causes of tumor mortality due to its high metastatic spread. CM growth is influenced by inflammation regulated by prostaglandins (PGs) whose synthesis is catalyzed by cyclooxygenases (COXs). COX inhibitors, including non-steroidal anti-inflammatory drugs (NSAIDs), can [...] Read more.
Cutaneous melanoma (CM) remains one of the leading causes of tumor mortality due to its high metastatic spread. CM growth is influenced by inflammation regulated by prostaglandins (PGs) whose synthesis is catalyzed by cyclooxygenases (COXs). COX inhibitors, including non-steroidal anti-inflammatory drugs (NSAIDs), can inhibit tumor development and growth. In particular, in vitro experiments have shown that celecoxib, a NSAID, inhibits the growth of some tumor cell lines. However, two-dimensional (2D) cell cultures, used in traditional in vitro anticancer assays, often show poor efficacy due to a lack of an in vivo like cellular environment. Three-dimensional (3D) cell cultures, such as spheroids, are better models because they can mimic the common features displayed by human solid tumors. Hence, in this study, we evaluated the anti-neoplastic potential of celecoxib, in both 2D and 3D cell cultures of A2058 and SAN melanoma cell lines. In particular, celecoxib reduced the cell viability and migratory capability and triggered the apoptosis of melanoma cells grown as 2D cultures. When celecoxib was tested on 3D melanoma cell cultures, the drug exerted an inhibitory effect on cell outgrowth from spheroids and reduced the invasiveness of melanoma cell spheroids into the hydrogel matrix. This work suggests that celecoxib could represent a new potential therapeutic approach in melanoma therapy. Full article
(This article belongs to the Special Issue Therapeutic Prevention and Early Detection of Melanoma)
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15 pages, 2733 KiB  
Article
Afamelanotide Is Associated with Dose-Dependent Protective Effect from Liver Damage Related to Erythropoietic Protoporphyria
by Anna-Elisabeth Minder, Xiaoye Schneider-Yin, Henryk Zulewski, Christoph E. Minder and Elisabeth I. Minder
Life 2023, 13(4), 1066; https://doi.org/10.3390/life13041066 - 21 Apr 2023
Cited by 1 | Viewed by 1836
Abstract
In animal models, melanocyte-stimulating hormones (MSHs) protect the liver from various injuries. Erythropoietic protoporphyria (EPP), a metabolic disorder, leads to the accumulation of protoporphyrin (PPIX). In addition to the most prominent symptom of incapacitating phototoxic skin reactions, 20% of EPP patients exhibit disturbed [...] Read more.
In animal models, melanocyte-stimulating hormones (MSHs) protect the liver from various injuries. Erythropoietic protoporphyria (EPP), a metabolic disorder, leads to the accumulation of protoporphyrin (PPIX). In addition to the most prominent symptom of incapacitating phototoxic skin reactions, 20% of EPP patients exhibit disturbed liver functioning and 4% experience terminal liver failure caused by the hepatobiliary elimination of excess PPIX. Skin symptoms are mitigated through the application of the controlled-release implant afamelanotide, an α-MSH analog, every sixty days. Recently, we showed that liver function tests (LFTs) improved during afamelanotide treatment when compared to before treatment. The present study investigated whether this effect is dose-dependent, as the evidence of dose dependency would support a beneficial influence of afamelanotide. Methods: In this retrospective observational study, we included 2933 liver-function tests, 1186 PPIX concentrations and 1659 afamelanotide implant applications in 70 EPP patients. We investigated whether the number of days since the preceding afamelanotide dose or the number of doses during the preceding 365 days had an effect on LFTs and PPIX levels. In addition, we assessed the effect of global radiation. Results: Inter-patient differences exerted the most prominent effect on PPIX and LFTs. In addition, PPIX increased significantly with an increase in the number of days since the last afamelanotide implant (p < 0.0001). ALAT and bilirubin decreased significantly with an increasing number of afamelanotide doses in the preceding 365 days (p = 0.012, p = 0.0299, respectively). Global radiation only influenced PPIX (p = 0.0113). Conclusions: These findings suggest that afamelanotide ameliorates both PPIX concentrations and LFTs in EPP in a dose-dependent manner. Full article
(This article belongs to the Special Issue Heme Metabolism and Porphyria)
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20 pages, 1775 KiB  
Review
Left Ventricular Assist Device as a Destination Therapy: Current Situation and the Importance of Patient Selection
by María Melendo-Viu, David Dobarro, Sergio Raposeiras Roubin, Carmen Llamas Pernas, Candela Moliz Cordón, Miriam Vazquez Lamas, Miguel Piñón Esteban, Maria Ángela Varela Martínez, Emad Abu Assi, Rafael Pita Romero, Juan José Legarra Calderón and Andrés Íñiguez Romo
Life 2023, 13(4), 1065; https://doi.org/10.3390/life13041065 - 21 Apr 2023
Cited by 3 | Viewed by 5518
Abstract
Advanced heart failure is a growing problem for which the best treatment is cardiac transplantation. However, the shortage of donors’ hearts made left ventricular assist devices as destination therapy (DT-LVAD) a highly recommended alternative: they improved mid-term prognosis as well as patients’ quality [...] Read more.
Advanced heart failure is a growing problem for which the best treatment is cardiac transplantation. However, the shortage of donors’ hearts made left ventricular assist devices as destination therapy (DT-LVAD) a highly recommended alternative: they improved mid-term prognosis as well as patients’ quality of life. Current intracorporeal pumps with a centrifugal continuous flow evolved in the last few years. Since 2003, when first LVAD was approved for long-term support, smaller device sizes with better survival and hemocompatibility profile were reached. The most important difficulty lies in the moment of the implant. Recent indications range from INTERMACS class 2 to 4, with close monitoring in intermediate cases. Moreover, a large multiparametric study is needed for considering the candidacy: basal situation, with a special interest in frailty, comorbidities, including renal and hepatic dysfunction, and medical background, considering every prior cardiac condition, must be evaluated. In addition, some clinical risk scores can be helpful to measure the possibility of right heart failure or morbi-mortality. With this review, we sought to summarize all the device improvements, with their updated clinical results, as well as to focus on all the patient selection criteria. Full article
(This article belongs to the Special Issue Advanced Heart Failure Therapy and Mechanical Circulatory Support)
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11 pages, 414 KiB  
Article
Comparing the Impact of COVID-19 on Vaccinated and Unvaccinated Patients Affected by Myasthenia Gravis
by Elena Scarsi, Sara Massucco, Pilar M. Ferraro, Arianna Cella, Stefano G. Grisanti, Andrea Assini, Alessandro Beronio, Fabio Della Cava, Chiara Gemelli, Fabio Bandini, Carlo Serrati, Massimo Del Sette, Angelo Schenone, Luana Benedetti, Valeria Prada and Marina Grandis
Life 2023, 13(4), 1064; https://doi.org/10.3390/life13041064 - 21 Apr 2023
Viewed by 1335
Abstract
We evaluated 13 patients affected by myasthenia gravis (MG) who had coronavirus disease 2019 (COVID-19) before vaccination and 14 myasthenic patients who contracted severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection after vaccination to evaluate factors related to different COVID-19 outcomes. We compared the two [...] Read more.
We evaluated 13 patients affected by myasthenia gravis (MG) who had coronavirus disease 2019 (COVID-19) before vaccination and 14 myasthenic patients who contracted severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection after vaccination to evaluate factors related to different COVID-19 outcomes. We compared the two groups’ previous stability of MG and the severity of SARS-CoV-2 infection. Vaccinated and non-vaccinated patients were comparable in terms of severity of the previous MG course (mean maximum myasthenia gravis Foundation of America–MGFA–Class III) and during SARS-CoV-2 infection (mean MGFA Class II). In non-vaccinated patients, the hospitalization and severe course percentages were 61.5%, while the mortality reached 30.8%. The hospitalization, severe course, and mortality percentages in vaccinated patients were 7.1%. In deceased, non-vaccinated patients, greater myasthenia severity in the past clinical history, but not at the time of infection, was observed. Similarly, older age at MG onset and at the time of infection correlated with a more severe COVID-19 course in non-vaccinated patients (p = 0.03 and p = 0.04), but not in the group of vaccinated patients. In summary, our data support a protective role of vaccination in myasthenic patients, even if anti-CD20 therapy might be associated with a poor immune response to vaccines. Full article
(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)
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18 pages, 3284 KiB  
Article
Increased Trypanosoma cruzi Growth during Infection of Macrophages Cultured on Collagen I Matrix
by Jorgete Logullo, Israel Diniz-Lima, Juliana Dutra B. Rocha, Suzana Cortê-Real, Elias Barbosa da Silva-Júnior, Joyce Cristina Guimarães-de-Oliveira, Alexandre Morrot, Leonardo Marques da Fonseca, Leonardo Freire-de-Lima, Debora Decote-Ricardo and Celio Geraldo Freire-de-Lima
Life 2023, 13(4), 1063; https://doi.org/10.3390/life13041063 - 21 Apr 2023
Viewed by 1443
Abstract
The interactions between cell and cellular matrix confers plasticity to each body tissue, influencing the cellular migratory capacity. Macrophages rely on motility to promote their physiological function. These phagocytes are determinant for the control of invasive infections, and their immunological role largely depends [...] Read more.
The interactions between cell and cellular matrix confers plasticity to each body tissue, influencing the cellular migratory capacity. Macrophages rely on motility to promote their physiological function. These phagocytes are determinant for the control of invasive infections, and their immunological role largely depends on their ability to migrate and adhere to tissue. Therefore, they interact with the components of the extracellular matrix through their adhesion receptors, conferring morphological modifications that change their shape during migration. Nevertheless, the need to use in vitro cell growth models with the conditioning of three-dimensional synthetic matrices to mimic the dynamics of cell-matrix interaction has been increasingly studied. This becomes more important to effectively understand the changes occurring in phagocyte morphology in the context of infection progression, such as in Chagas disease. This disease is caused by the intracellular pathogen Trypanosoma cruzi, capable of infecting macrophages, determinant cells in the anti-trypanosomatid immunity. In the present study, we sought to understand how an in vitro extracellular matrix model interferes with T. cruzi infection in macrophages. Using different time intervals and parasite ratios, we evaluated the cell morphology and parasite replication rate in the presence of 3D collagen I matrix. Nevertheless, microscopy techniques such as scanning electron microscopy were crucial to trace macrophage-matrix interactions. In the present work, we demonstrated for the first time that the macrophage-matrix interaction favors T. cruzi in vitro replication and the release of anti-inflammatory cytokines during macrophage infection, in addition to drastically altering the morphology of the macrophages and promoting the formation of migratory macrophages. Full article
(This article belongs to the Special Issue Interactions between Microorganisms, Their Environment and Host)
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13 pages, 634 KiB  
Article
The Revived Interest in Ageusia Research during the COVID-19 Pandemic: A Bibliometric Analysis
by Andy Wai Kan Yeung
Life 2023, 13(4), 1062; https://doi.org/10.3390/life13041062 - 21 Apr 2023
Cited by 3 | Viewed by 1551
Abstract
The evolution of ageusia research literature has yet to be investigated. This bibliometric study analyzed the entire ageusia research literature indexed in Web of Science, to reveal its growth and the most productive entities in terms of authors, institutions, countries, journals, and journal [...] Read more.
The evolution of ageusia research literature has yet to be investigated. This bibliometric study analyzed the entire ageusia research literature indexed in Web of Science, to reveal its growth and the most productive entities in terms of authors, institutions, countries, journals, and journal categories. In addition, this study aimed to identify medical conditions (and their treatments) that were frequently associated with ageusia. On 7 March 2022, the Web of Science Core Collection database was accessed with the following search query: TS = (ageusia OR “taste loss” OR “loss of taste” OR “loss of gustat*” OR “gustatory loss”). The search identified publications mentioning these terms in their title, abstract, or keywords. No additional filters were placed on publication year, language, etc. The basic publication and citation counts were extracted from the in-built functions of the database. The complete record of the publications was exported into VOSviewer, a bibliometric software for visualizations. The search yielded 1170 publications. The cumulative publication and citation counts of the ageusia research sharply increased in 2020. The most productive author was Professor Thomas Hummel from Technische Universität Dresden. Ageusia research had heavy contributions from the United States, Italy, the United Kingdom, Germany, and India. The top 5 most productive journals mainly belonged to the otorhinolaryngology and medicine categories. The medical conditions frequently investigated in ageusia research included COVID-19, cancers (head and neck, and advanced basal cell), Guillain-Barré syndrome, neurodegenerative diseases, diabetes, and Sjogren’s syndrome. This study could act as a begvinner’s guide for (1) clinicians who are not familiar with ageusia so that they might better understand which scenarios they need to be more aware of since ageusia could be a co-morbidity of a patient’s underlying disease, and (2) for those who wish to search for relevant authors and journals for suitable publications related to the topic. Full article
(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)
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13 pages, 1272 KiB  
Article
Impact of Baseline Clinical Variables on SGLT2i’s Antiproteinuric Effect in Diabetic Kidney Disease
by Irene Capelli, Danilo Ribichini, Michele Provenzano, Daniele Vetrano, Valeria Aiello, Giuseppe Cianciolo, Valentina Vicennati, Alessandro Tomassetti, Ginevra Moschione, Sabrina Berti, Uberto Pagotto and Gaetano La Manna
Life 2023, 13(4), 1061; https://doi.org/10.3390/life13041061 - 21 Apr 2023
Cited by 2 | Viewed by 1480
Abstract
Introduction: Proteinuria is a major risk factor for the progression of chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) demonstrated a nephroprotective and antiproteinuric effect in people with type 2 diabetes (T2DM) and proteinuric CKD. We conducted a retrospective study to evaluate [...] Read more.
Introduction: Proteinuria is a major risk factor for the progression of chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) demonstrated a nephroprotective and antiproteinuric effect in people with type 2 diabetes (T2DM) and proteinuric CKD. We conducted a retrospective study to evaluate clinical and laboratory variables that can help predict proteinuria reduction with SGLT2i therapy. Materials and methods: Patients affected by T2DM and CKD who started any SGLT2i were included in the study. Patients were stratified into two subgroups, Responder (R) and non-Responder (nR), based upon the response to the therapy with SGLT2i, namely the reduction in a 24 h urine proteins test (uProt) of ≥30% from baseline levels. The aim of the study is to analyse differences in baseline characteristics between the two groups and to investigate the relationship between them and the proteinuria reduction. A Kruskal–Wallis test, unpaired t-test and Chi2 test were used to test the difference in means and the percentage (%) between the two groups. Linear and logistic regressions were utilized to analyse the relationship between proteinuria reduction and basal characteristics. Results: A total of 58 patients were enrolled in the study: 32 patients (55.1%) were in the R group and 26 patients (44.9%) in the nR group. R’s patients had a significant higher uProt at baseline (1393 vs. 449 mg/24 h, p = 0.010). There was a significant correlation between baseline uProt and proteinuria reduction with SGLT2i in both univariate (β = −0.43, CI −0.55 to −031; p < 0.001) and multivariate analyses (β = −0.46, CI −0.57 to −0.35, p < 0.001). In the multivariate analysis, there was a significant positive correlation between the estimated glomerular filtration rate (eGFR) and proteinuria reduction (β = −17, CI −31 to −3.3, p = 0.016) and a significant negative correlation with body mass index (BMI) (β = 81, CI 13 to 50, p = 0.021). The multivariate logistic regressions show a positive correlation of being in the R group with diabetic retinopathy at baseline (Odds Ratio (OR) 3.65, CI 0.97 to 13.58, p = 0.054), while the presence of cardiovascular disease (CVD) at baseline is associated with being in the nR group (OR 0.34, CI 0.09 to 1.22, p = 0.1), even if these statements did not reach statistical significance. Conclusions: In this real-life experience, following the administration of SGLT2i, a reduction of more than 30% in proteinuria was observed in more than half of the patients, and these patients had a significantly higher baseline proteinuria value. Variables such as eGFR and BMI are variables that, considered in conjunction with proteinuria, can help predict treatment response before therapy initiation. Different phenotypes of diabetic kidney disease may have an impact on the antiproteinuric response. Full article
(This article belongs to the Section Physiology and Pathology)
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14 pages, 2569 KiB  
Article
Correlation between Maspin Levels in Different Biological Samples and Pathologic Features in Colorectal Adenocarcinomas
by Alexandru Adrian Bratei and Raluca-Ioana Stefan-van Staden
Life 2023, 13(4), 1060; https://doi.org/10.3390/life13041060 - 20 Apr 2023
Cited by 1 | Viewed by 1228
Abstract
Maspin is an important biomarker which was proven to be correlated to many pathological features that can help the oncologists, the surgeons and also the pathologists for choosing the personalized treatment of the patients. Maspin expression correlates with the budding of colorectal adenocarcinomas [...] Read more.
Maspin is an important biomarker which was proven to be correlated to many pathological features that can help the oncologists, the surgeons and also the pathologists for choosing the personalized treatment of the patients. Maspin expression correlates with the budding of colorectal adenocarcinomas that is usually used mostly in immunohistochemistry. In this preliminary study, a small number of patients with clinical and pathological features were selected. Four kinds of samples (tumoral tissues, blood, saliva and urine) were analyzed using a stochastic method using stochastic microsensors. Whole blood maspin concentration values were related to budding, molecular subtype and location. Tissular maspin concentrations were related to location, maxi-mum diameter and pN value from TNM staging system. Salivary maspin concentrations were related to budding, mucinous compound and macroscopic features. Urinary maspin concentrations were related to pT value from TNM staging system, budding and molecular subtype. The correlations made in this paper may be used for fast diagnostic of colorectal adenocarcinomas, after which, it will be tested on a significant number of patients confirmed with colon cancer, in different stages of evolution. Full article
(This article belongs to the Section Medical Research)
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11 pages, 677 KiB  
Article
Effects of Motor Rehabilitation on Balance and Functional Activities in Elderly Patients with Peripheral Neuropathy and Recurrent Falls
by Bernardo Gialanella, Laura Comini, Paola Prometti, Fabio Vanoglio and Raffaele Santoro
Life 2023, 13(4), 1059; https://doi.org/10.3390/life13041059 - 20 Apr 2023
Viewed by 1402
Abstract
To date, little is known about the effects of motor rehabilitation in peripheral neuropathy (PN) patients with a history of recurrent falls (RFH). This study aimed to assess balance and the activities of daily living (ADLs) in elderly lower limb PN patients with [...] Read more.
To date, little is known about the effects of motor rehabilitation in peripheral neuropathy (PN) patients with a history of recurrent falls (RFH). This study aimed to assess balance and the activities of daily living (ADLs) in elderly lower limb PN patients with and without RFH and to verify the effects of motor rehabilitation on balance and ADLs in these patients. We collected data from 64 lower limb PN patients, who underwent a conventional motor rehabilitation program: 35 patients had a history of recurrent falls, and 29 did not. The Berg Balance Scale (BBS) and motor FIM, before and after rehabilitation, were the outcome measures. After rehabilitation, lower limb PN patients with RFH had significantly higher scores in BBS and motor FIM (p < 0.001, for both) than at entry. The final BBS score and effectiveness in the BBS score of lower limb PN patients with RFH were lower than those of patients without RFH (p < 0.05 and p = 0.009, respectively). The study shows that conventional motor rehabilitation improves both balance and ADLs in patients, but balance improvement is lower in those with RFH. Thus, motor rehabilitation can be a therapeutic option for the management of these patients. Full article
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13 pages, 2314 KiB  
Review
The Universally Conserved Unconventional G Protein YchF Is Critical for Growth and Stress Response
by Zhaoheng Lin, Rongfang Li, Zhiwei Han, Yi Liu, Liyang Gao, Suchang Huang, Ying Miao and Rui Miao
Life 2023, 13(4), 1058; https://doi.org/10.3390/life13041058 - 20 Apr 2023
Viewed by 1715
Abstract
The ancient guanine nucleotide-binding (G) proteins are a group of critical regulatory and signal transduction proteins, widely involved in diverse cellular processes of all kingdoms of life. YchF is a kind of universally conserved novel unconventional G protein that appears to be crucial [...] Read more.
The ancient guanine nucleotide-binding (G) proteins are a group of critical regulatory and signal transduction proteins, widely involved in diverse cellular processes of all kingdoms of life. YchF is a kind of universally conserved novel unconventional G protein that appears to be crucial for growth and stress response in eukaryotes and bacteria. YchF is able to bind and hydrolyze both adenine nucleoside triphosphate (ATP) and guanosine nucleoside triphosphate (GTP), unlike other members of the P-loop GTPases. Hence, it can transduce signals and mediate multiple biological functions by using either ATP or GTP. YchF is not only a nucleotide-dependent translational factor associated with the ribosomal particles and proteasomal subunits, potentially bridging protein biosynthesis and degradation, but also sensitive to reactive oxygen species (ROS), probably recruiting many partner proteins in response to environmental stress. In this review, we summarize the latest insights into how YchF is associated with protein translation and ubiquitin-dependent protein degradation to regulate growth and maintain proteostasis under stress conditions. Full article
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13 pages, 1828 KiB  
Article
Cationic Nano-Lipidic Carrier Mediated Ocular Delivery of Triamcinolone Acetonide: A Preclinical Investigation in the Management of Uveitis
by Pradip Nirbhavane, Laxmi Moksha, Gajanand Sharma, Thirumurthy Velpandian, Bhupinder Singh and O. P. Katare
Life 2023, 13(4), 1057; https://doi.org/10.3390/life13041057 - 20 Apr 2023
Cited by 2 | Viewed by 1590
Abstract
The current study was undertaken to evaluate the efficacy of a novel nano-lipoidal eye drop formulation of triamcinolone acetonide (TA) for the topical treatment of uveitis. The triamcinolone acetonide-loaded nanostructured lipid carriers (cTA-NLC) were developed by employing ‘hot microemulsion method’ using biocompatible lipids, [...] Read more.
The current study was undertaken to evaluate the efficacy of a novel nano-lipoidal eye drop formulation of triamcinolone acetonide (TA) for the topical treatment of uveitis. The triamcinolone acetonide-loaded nanostructured lipid carriers (cTA-NLC) were developed by employing ‘hot microemulsion method’ using biocompatible lipids, which exhibited a sustained release nature and enhanced efficacy when evaluated in vitro. The in vivo efficacy of this developed formulation was tested on Wistar rats, and a single-dose pharmacokinetic study was conducted in rabbits. The eyes of animals were examined for any signs of inflammation using the ‘Slit-lamp microscopic’ method. The aqueous humor collected from the sacrificed rats was tested for total protein count and cell count. The total protein count was determined using BSA assay method, while the total cell count was determined by Neubaur’s hemocytometer method. The results showed that the cTA-NLC formulation had negligible signs of inflammation, with a clinical score of uveitis 0.82 ± 0.166, which is much less than control/untreated (3.80 ± 0.3) and free drug suspension (2.66 ± 0.405). The total cell count was also found to be significantly low for cTA-NLC (8.73 ± 1.79 × 105) as compared to control (52.4 ± 7.71 × 105) and free drug suspension (30.13 ± 3.021 × 105). Conclusively, the animal studies conducted showed that our developed formulation holds the potential for effective management of uveitis. Full article
(This article belongs to the Section Pharmaceutical Science)
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35 pages, 1701 KiB  
Review
Pathophysiological Effects of Contemporary Lifestyle on Evolutionary-Conserved Survival Mechanisms in Polycystic Ovary Syndrome
by Jim Parker
Life 2023, 13(4), 1056; https://doi.org/10.3390/life13041056 - 20 Apr 2023
Cited by 4 | Viewed by 3200
Abstract
Polycystic ovary syndrome (PCOS) is increasingly being characterized as an evolutionary mismatch disorder that presents with a complex mixture of metabolic and endocrine symptoms. The Evolutionary Model proposes that PCOS arises from a collection of inherited polymorphisms that have been consistently demonstrated in [...] Read more.
Polycystic ovary syndrome (PCOS) is increasingly being characterized as an evolutionary mismatch disorder that presents with a complex mixture of metabolic and endocrine symptoms. The Evolutionary Model proposes that PCOS arises from a collection of inherited polymorphisms that have been consistently demonstrated in a variety of ethnic groups and races. In utero developmental programming of susceptible genomic variants are thought to predispose the offspring to develop PCOS. Postnatal exposure to lifestyle and environmental risk factors results in epigenetic activation of developmentally programmed genes and disturbance of the hallmarks of health. The resulting pathophysiological changes represent the consequences of poor-quality diet, sedentary behaviour, endocrine disrupting chemicals, stress, circadian disruption, and other lifestyle factors. Emerging evidence suggests that lifestyle-induced gastrointestinal dysbiosis plays a central role in the pathogenesis of PCOS. Lifestyle and environmental exposures initiate changes that result in disturbance of the gastrointestinal microbiome (dysbiosis), immune dysregulation (chronic inflammation), altered metabolism (insulin resistance), endocrine and reproductive imbalance (hyperandrogenism), and central nervous system dysfunction (neuroendocrine and autonomic nervous system). PCOS can be a progressive metabolic condition that leads to obesity, gestational diabetes, type two diabetes, metabolic-associated fatty liver disease, metabolic syndrome, cardiovascular disease, and cancer. This review explores the mechanisms that underpin the evolutionary mismatch between ancient survival pathways and contemporary lifestyle factors involved in the pathogenesis and pathophysiology of PCOS. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome: Current Knowledge and Future Perspectives)
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14 pages, 759 KiB  
Article
Thrombolysis Outcomes in Acute Ischaemic Stroke Patients with Pre-Existing Cognitive Impairment
by Isabela V. P. Ramnarine, Omar W. Rasheed, Peter J. Laud, Arshad Majid, Kirsty A. Harkness and Simon M. Bell
Life 2023, 13(4), 1055; https://doi.org/10.3390/life13041055 - 20 Apr 2023
Cited by 1 | Viewed by 1405
Abstract
Background: Thrombolysis treatment for ischaemic stroke in patients with pre-existing disabilities, including cognitive impairment, remains controversial. Previous studies have suggested functional outcomes post-thrombolysis are worse in patients with cognitive impairment. This study aimed to compare and explore factors contributing to thrombolysis outcomes, including [...] Read more.
Background: Thrombolysis treatment for ischaemic stroke in patients with pre-existing disabilities, including cognitive impairment, remains controversial. Previous studies have suggested functional outcomes post-thrombolysis are worse in patients with cognitive impairment. This study aimed to compare and explore factors contributing to thrombolysis outcomes, including haemorrhagic complications, in cognitively and non-cognitively impaired patients with ischaemic stroke. Materials and Methods: A retrospective analysis of 428 ischaemic stroke patients who were thrombolysed between January 2016 and February 2021 was performed. Cognitive impairment was defined as a diagnosis of dementia, mild cognitive impairment, or clinical evidence of the condition. The outcome measures included morbidity (using NIHSS and mRS), haemorrhagic complications, and mortality, and were analysed using multivariable logistic regression models. Results: The analysis of the cohort revealed that 62 patients were cognitively impaired. When compared to those without cognitive impairment, this group showed worse functional status at discharge (mRS 4 vs. 3, p < 0.001) and a higher probability of dying within 90 days (OR 3.34, 95% CI 1.85–6.01, p < 0.001). A higher risk of a fatal ICH post-thrombolysis was observed in the cognitively impaired patients, and, after controlling for covariates, cognitive impairment remained a significant predictor of a fatal haemorrhage (OR 4.79, 95% CI 1.24–18.45, p = 0.023). Conclusions: Cognitively impaired ischaemic stroke patients experience increased morbidity, mortality, and haemorrhagic complications following thrombolytic therapy. However cognitive status is not independently predictive of most outcome measures. Further work is required to elucidate contributing factors to the poor outcomes observed in these patients and help guide thrombolysis decision-making in clinical practice. Full article
(This article belongs to the Special Issue Feature Papers in Medical Research)
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11 pages, 452 KiB  
Article
Long-Term Follow-Up of Patients Needing Extracorporeal Membrane Oxygenation Following a Critical Course of COVID-19
by Samuel Genzor, Pavol Pobeha, Martin Šimek, Petr Jakubec, Jan Mizera, Martin Vykopal, Milan Sova, Jakub Vaněk and Jan Praško
Life 2023, 13(4), 1054; https://doi.org/10.3390/life13041054 - 20 Apr 2023
Viewed by 1529
Abstract
Introduction: Severe respiratory failure is one of the most serious complications of coronavirus disease 2019 (COVID-19). In a small proportion of patients, mechanical ventilation fails to provide adequate oxygenation and extracorporeal membrane oxygenation (ECMO) is needed. The surviving individuals need long-term follow-up as [...] Read more.
Introduction: Severe respiratory failure is one of the most serious complications of coronavirus disease 2019 (COVID-19). In a small proportion of patients, mechanical ventilation fails to provide adequate oxygenation and extracorporeal membrane oxygenation (ECMO) is needed. The surviving individuals need long-term follow-up as it is not clear what their prognosis is. Aim: To provide a complex clinical picture of patients during follow-up exceeding one year after the ECMO therapy due to severe COVID-19. Methods: All subjects involved in the study required ECMO in the acute stage of COVID-19. The survivors were followed-up for over one year at a specialized respiratory medical center. Results: Of the 41 patients indicated for ECMO, 17 patients (64.7% males) survived. The average age of survivors was 47.8 years, and the average BMI was 34.7 kg·m−2. The duration of ECMO support was 9.4 days. A mild decrease in vital capacity (VC) and transfer factor (DLCO) was observed on the initial follow-up visit (82.1% and 60%, respectively). VC improved by 6.2% and by an additional 7.5% after 6 months and 1 year, respectively. DLCO improved by 21.1% after 6 months and remained stable after 1 year. Post-intensive care consequences included psychological problems and neurological impairment in 29% of patients; 64.7% of the survivors got vaccinated against SARS-CoV-2 within 12 months of hospitalization and 17.6% experienced reinfection with a mild course. Conclusion: The COVID-19 pandemic has significantly increased the need for ECMO. Patients’ quality of life after ECMO is temporarily significantly reduced but most patients do not experience permanent disability. Full article
(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)
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11 pages, 8218 KiB  
Article
Brain Region-Specific Differences in Amyloid-β Plaque Composition in 5XFAD Mice
by Angelika Sabine Bader, Marius-Uwe Gnädig, Merle Fricke, Luca Büschgens, Lena Josefine Berger, Hans-Wolfgang Klafki, Thomas Meyer, Olaf Jahn, Sascha Weggen and Oliver Wirths
Life 2023, 13(4), 1053; https://doi.org/10.3390/life13041053 - 20 Apr 2023
Cited by 2 | Viewed by 1543
Abstract
Senile plaques consisting of amyloid-beta (Aβ) peptides are a major pathological hallmark of Alzheimer’s disease (AD). Aβ peptides are heterogeneous regarding the exact length of their amino- and carboxy-termini. Aβ1-40 and Aβ1-42 are often considered to represent canonical “full-length” Aβ species. Using immunohistochemistry, [...] Read more.
Senile plaques consisting of amyloid-beta (Aβ) peptides are a major pathological hallmark of Alzheimer’s disease (AD). Aβ peptides are heterogeneous regarding the exact length of their amino- and carboxy-termini. Aβ1-40 and Aβ1-42 are often considered to represent canonical “full-length” Aβ species. Using immunohistochemistry, we analyzed the distribution of Aβ1-x, Aβx-42 and Aβ4-x species in amyloid deposits in the subiculum, hippocampus and cortex in 5XFAD mice during aging. Overall plaque load increased in all three brain regions, with the subiculum being the area with the strongest relative plaque coverage. In the subiculum, but not in the other brain regions, the Aβ1-x load peaked at an age of five months and decreased thereafter. In contrast, the density of plaques positive for N-terminally truncated Aβ4-x species increased continuously over time. We hypothesize that ongoing plaque remodeling takes place, leading to a conversion of deposited Aβ1-x peptides into Aβ4-x peptides in brain regions with a high Aβ plaque burden. Full article
(This article belongs to the Special Issue N-Terminal Protein Modifications and Human Diseases)
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6 pages, 187 KiB  
Perspective
Unbalanced Growth, the DNA Replication Cycle and Discovery of Repair Replication
by Philip C. Hanawalt
Life 2023, 13(4), 1052; https://doi.org/10.3390/life13041052 - 20 Apr 2023
Viewed by 1767
Abstract
This article recounts my graduate research at Yale University (1954–1958) on unbalanced growth in Eschericia coli during thymine deprivation or following ultraviolet (UV) irradiation, with early evidence for the repair of UV-induced DNA damage. Follow-up studies in Copenhagen (1958–1960) in the laboratory of [...] Read more.
This article recounts my graduate research at Yale University (1954–1958) on unbalanced growth in Eschericia coli during thymine deprivation or following ultraviolet (UV) irradiation, with early evidence for the repair of UV-induced DNA damage. Follow-up studies in Copenhagen (1958–1960) in the laboratory of Ole Maaløe led to my discovery that the DNA replication cycle can be synchronized by inhibiting protein and RNA syntheses and that an RNA synthesis step is essential for initiation of the cycle, but not for its completion. This work set the stage for my subsequent research at Stanford University, where the repair replication of damaged DNA was documented, to provide compelling evidence for an excision-repair pathway. That universal pathway validates the requirement for the redundant information in the complementary strands of duplex DNA to ensure genomic stability. Full article
15 pages, 2104 KiB  
Article
Assessment of the Association between Entropy in PET/CT and Response to Anti-PD-1/PD-L1 Monotherapy in Stage III or IV NSCLC
by Julie Malet, Julien Ancel, Abdenasser Moubtakir, Dimitri Papathanassiou, Gaëtan Deslée and Maxime Dewolf
Life 2023, 13(4), 1051; https://doi.org/10.3390/life13041051 - 20 Apr 2023
Cited by 1 | Viewed by 1423
Abstract
Anti-PD-1/PD-L1 therapy indications are broadened in non-small cell lung cancer (NSCLC) although immune checkpoint inhibitors (ICI) do not provide benefits for the entire population. Texture features based on positron emission tomography/computed tomography (PET/CT), especially entropy (based on a gray-level co-occurrence matrix (GLCM)), could [...] Read more.
Anti-PD-1/PD-L1 therapy indications are broadened in non-small cell lung cancer (NSCLC) although immune checkpoint inhibitors (ICI) do not provide benefits for the entire population. Texture features based on positron emission tomography/computed tomography (PET/CT), especially entropy (based on a gray-level co-occurrence matrix (GLCM)), could be interesting as predictors in NSCLC. The aim of our retrospective study was to evaluate the association between GLCM-entropy and response to anti-PD-1/PD-L1 monotherapy at the first evaluation in stage III or IV NSCLC, comparing patients with progressive disease (PD) and non-progressive disease (non-PD). In total, 47 patients were included. Response Evaluation Criteria in Solid Tumors (RECIST 1.1) were used to evaluate the response to ICI treatment (nivolumab, pembrolizumab, or atezolizumab). At the first evaluation, 25 patients were PD and 22 were non-PD. GLCM-entropy was not predictive of response at the first evaluation. Furthermore, GLCM-entropy was not associated with progression-free survival (PFS) (p = 0.393) or overall survival (OS) (p = 0.220). Finally, GLCM-entropy measured in PET/CT performed before ICI initiation in stage III or IV NSCLC was not predictive of response at the first evaluation. However, this study demonstrates the feasibility of using texture parameters in routine clinical practice. The interest of measuring PET/CT texture parameters in NSCLC remains to be evaluated in larger prospective studies. Full article
(This article belongs to the Special Issue Thoracic Malignancies: From Prevention and Diagnosis to Late Stages)
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21 pages, 589 KiB  
Review
TIGIT in Lung Cancer: Potential Theranostic Implications
by Carlo Pescia, Giuditta Pini, Edoardo Olmeda, Stefano Ferrero and Gianluca Lopez
Life 2023, 13(4), 1050; https://doi.org/10.3390/life13041050 - 19 Apr 2023
Cited by 2 | Viewed by 2061
Abstract
TIGIT (T cell immunoreceptor with Ig and ITIM domains) is a co-inhibitory receptor expressed on various immune cells, including T cells, NK cells, and dendritic cells. TIGIT interacts with different ligands, such as CD155 and CD112, which are highly expressed on cancer cells, [...] Read more.
TIGIT (T cell immunoreceptor with Ig and ITIM domains) is a co-inhibitory receptor expressed on various immune cells, including T cells, NK cells, and dendritic cells. TIGIT interacts with different ligands, such as CD155 and CD112, which are highly expressed on cancer cells, leading to the suppression of immune responses. Recent studies have highlighted the importance of TIGIT in regulating immune cell function in the tumor microenvironment and its role as a potential therapeutic target, especially in the field of lung cancer. However, the role of TIGIT in cancer development and progression remains controversial, particularly regarding the relevance of its expression both in the tumor microenvironment and on tumor cells, with prognostic and predictive implications that remain to date essentially undisclosed. Here, we provide a review of the recent advances in TIGIT-blockade in lung cancer, and also insights on TIGIT relevance as an immunohistochemical biomarker and its possible theranostic implications. Full article
(This article belongs to the Special Issue Immunotherapy in Lung Cancer and Biomarkers of Response)
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13 pages, 1019 KiB  
Article
Programmatic Implications for Schistosomiasis Elimination Based on Community-Based Survey in the Blue Nile, North Kordofan, and Sennar States, Sudan
by Hassan Ahmed Hassan Ahmed Ismail, Seungman Cha, Yan Jin and Sung-Tae Hong
Life 2023, 13(4), 1049; https://doi.org/10.3390/life13041049 - 19 Apr 2023
Viewed by 1139
Abstract
Schistosomiasis prevalence has remained high in some areas due to reinfection despite repeated mass drug administration interventions. We aimed to explore its risk factors in order to help to design adequate interventions in such high-transmission areas. A total of 6225 individuals residing in [...] Read more.
Schistosomiasis prevalence has remained high in some areas due to reinfection despite repeated mass drug administration interventions. We aimed to explore its risk factors in order to help to design adequate interventions in such high-transmission areas. A total of 6225 individuals residing in 60 villages in 8 districts of North Kordofan, Blue Nile, or Sennar States, Sudan participated in the community-based survey in March 2018. First, we investigated Schistosoma haematobium and Schistosoma mansoni prevalences among school-aged children and adults. Second, the associations between risk factors and schistosomiasis were explored. Those without any type of latrine in their households had higher odds of being infected with schistosomiasis than those with a latrine (odds ratio (OR) = 1.53; 95% confidence interval (CI) 1.20–1.94; p = 0.001), and the odds of being positive for schistosomiasis among people living in a household without an improved latrine were higher than for their counterparts with an improved latrine (OR = 1.63; CI 1.05–2.55; p = 0.03). Furthermore, people with households or outside compounds found to contain human faeces had higher odds of being infected with schistosomiasis than their counterparts (OR = 1.36, 95% CI 1.01–1.83, p = 0.04). Installing an improved latrine and eliminating open defecation should be highlighted in schistosomiasis elimination projects in high-transmission areas. Full article
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12 pages, 291 KiB  
Article
Low–Normal Thyroid Function Is Not Associated with Either Non-Alcoholic Fatty Liver Disease or with Metabolic Dysfunction-Associated Fatty Liver Disease
by Julia Zuarth-Vázquez, Lidia Moreno-Castañeda, Juan Pablo Soriano-Márquez, Alain Velázquez-Alemán, Martha Helena Ramos-Ostos, Misael Uribe, Iván López-Méndez and Eva Juárez-Hernández
Life 2023, 13(4), 1048; https://doi.org/10.3390/life13041048 - 19 Apr 2023
Viewed by 1150
Abstract
Background: The association of low–normal thyroid function (LNTF) with non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated fatty liver disease (MAFLD) is controversial; thus, the aim of this study is to determine this association. Methods: NAFLD was evaluated by controlled attenuation parameter of [...] Read more.
Background: The association of low–normal thyroid function (LNTF) with non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated fatty liver disease (MAFLD) is controversial; thus, the aim of this study is to determine this association. Methods: NAFLD was evaluated by controlled attenuation parameter of transient elastography. Patients were classified by MAFLD criteria. LNTF was defined as TSH levels of 2.5 to 4.5 mIU/L and were divided into three different cut-off points (>4.5 to 5.0, >3.1, and >2.5 mIU/L). Associations between LNTF, NAFLD, and MAFLD were evaluated by univariate and multivariate logistic regression analyses. Results: A total of 3697 patients were included; 59% (n = 2179) were male, and median age and body mass index were 48 (43–55) years and 25.9 (23.6–28.5) kg/m2, respectively, and 44% (n = 1632) were diagnosed with NAFLD. THS levels of 2.5 and 3.1 showed significant associations with the presence of NAFLD and MAFLD; however, LNTF did not show an independent association with the presence of NAFLD or MAFLD in multivariate analysis. According to different cut-off points, patients with LNTF presented similar risks for NAFLD as the general population. Conclusion: LNTF is not associated with NAFLD or MAFLD. Patients with high LNTF are equally at risk for NAFLD as the general population. Full article
17 pages, 692 KiB  
Review
Sarcoidosis and Autoimmune Inflammatory Syndrome Induced by Adjuvants
by Anna Starshinova, Yulia Zinchenko, Anna Malkova, Dmitriy Kudlay, Igor Kudryavtsev and Piotr Yablonskiy
Life 2023, 13(4), 1047; https://doi.org/10.3390/life13041047 - 19 Apr 2023
Cited by 4 | Viewed by 2537
Abstract
Currently, sarcoidosis remains one of the diseases with unknown etiology, which significantly complicates its diagnosis and treatment. Various causes of sarcoidosis have been studied for many years. Both organic and inorganic trigger factors, provoking the development of granulomatous inflammation are considered. However, the [...] Read more.
Currently, sarcoidosis remains one of the diseases with unknown etiology, which significantly complicates its diagnosis and treatment. Various causes of sarcoidosis have been studied for many years. Both organic and inorganic trigger factors, provoking the development of granulomatous inflammation are considered. However, the most promising and evidence-based hypothesis is the development of sarcoidosis as an autoimmune disease, provoked by various adjuvants in genetic predisposed individuals. This concept fits into the structure of the autoimmune/inflammatory syndrome, induced by adjuvants (ASIA) that was proposed in 2011 by Professor Shoenfeld Y. In this paper, the authors reveal the presence of major and minor ASIA criteria for sarcoidosis, propose a new concept of the course of sarcoidosis within the framework of ASIA, and point out the difficulties in creating a model of the disease and the selection of therapy. It is obvious that the data obtained not only bring us closer to understanding the nature of sarcoidosis, but also potentiate new studies confirming this hypothesis by obtaining a model of the disease. Full article
(This article belongs to the Special Issue Clinical Manifestations and Treatment of Autoimmune Diseases)
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14 pages, 2380 KiB  
Review
Critical Assessment of the Anti-Inflammatory Potential of Usnic Acid and Its Derivatives—A Review
by Wojciech Paździora, Irma Podolak, Marta Grudzińska, Paweł Paśko, Karolina Grabowska and Agnieszka Galanty
Life 2023, 13(4), 1046; https://doi.org/10.3390/life13041046 - 19 Apr 2023
Cited by 2 | Viewed by 1418
Abstract
Inflammation is a response of the organism to an external factor that disrupts its natural homeostasis, and it helps to eliminate the cause of tissue injury. However, sometimes the body’s response is highly inadequate and the inflammation may become chronic. Thus, the search [...] Read more.
Inflammation is a response of the organism to an external factor that disrupts its natural homeostasis, and it helps to eliminate the cause of tissue injury. However, sometimes the body’s response is highly inadequate and the inflammation may become chronic. Thus, the search for novel anti-inflammatory agents is still needed. One of the groups of natural compounds that attract interest in this context is lichen metabolites, with usnic acid (UA) as the most promising candidate. The compound reveals a broad spectrum of pharmacological properties, among which anti-inflammatory properties have been studied both in vitro and in vivo. The aim of this review was to gather and critically evaluate the results of the so-far published data on the anti-inflammatory properties of UA. Despite some limitations and shortcomings of the studies included in this review, it can be concluded that UA has interesting anti-inflammatory potential. Further research should be directed at the (i) elucidation of the molecular mechanism of UA; (ii) verification of its safety; (iii) comparison of the efficacy and toxicity of UA enantiomers; (iv) design of UA derivatives with improved physicochemical properties and pharmacological activity; and (v) use of certain forms or delivery carriers of UA, especially in its topical application. Full article
(This article belongs to the Special Issue Inflammation and Natural Products)
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26 pages, 4086 KiB  
Article
Regulation of Cell Proliferation and Nrf2-Mediated Antioxidant Defense: Conservation of Keap1 Cysteines and Nrf2 Binding Site in the Context of the Evolution of KLHL Family
by Gregory A. Shilovsky and Daria V. Dibrova
Life 2023, 13(4), 1045; https://doi.org/10.3390/life13041045 - 19 Apr 2023
Cited by 6 | Viewed by 1755
Abstract
Keap1 (Kelch-like ECH-associated protein 1) is one of the major negative regulators of the transcription factor Nrf2 (nuclear factor erythroid-2-related factor 2), which induces the expression of numerous proteins defending the cell against different stress conditions. Keap1 is generally negatively regulated by post-translational [...] Read more.
Keap1 (Kelch-like ECH-associated protein 1) is one of the major negative regulators of the transcription factor Nrf2 (nuclear factor erythroid-2-related factor 2), which induces the expression of numerous proteins defending the cell against different stress conditions. Keap1 is generally negatively regulated by post-translational modification (mostly via its cysteine residues) and interaction with other proteins that compete with Nrf2 for binding. Cysteine residues in Keap1 have different effects on protein regulation, as basic residues (Lys, Arg, and His) in close proximity to them increase cysteine modification potential. In this paper, we present an evolutionary analysis of residues involved in both mechanisms of Keap1 regulation in the broader context of the KLHL protein family in vertebrates. We identified the typical domain structure of the KLHL protein family in several proteins outside of this family (namely in KBTBD proteins 2, 3, 4, 6, 7, 8, 12 and 14). We found several cysteines that are flanked by basic residues (namely, C14, C38, C151, C226, C241, C273, C288, C297, C319, and C613) and, therefore, may be considered more susceptible to regulatory modification. The Nrf2 binding site is completely conserved in Keap1 in vertebrates but is absent or located in nonaligned DA and BC loops of the Kelch domain within the KLHL family. The development of specific substrate binding regions could be an evolutionary factor of diversification in the KLHL protein family. Full article
(This article belongs to the Special Issue Feature Papers in Protein and Proteomics)
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19 pages, 1049 KiB  
Review
Fermented Vegetables and Legumes vs. Lifestyle Diseases: Microbiota and More
by Eliza Knez, Kornelia Kadac-Czapska and Małgorzata Grembecka
Life 2023, 13(4), 1044; https://doi.org/10.3390/life13041044 - 19 Apr 2023
Cited by 5 | Viewed by 2411
Abstract
Silages may be preventive against lifestyle diseases, including obesity, diabetes mellitus, or metabolic syndrome. Fermented vegetables and legumes are characterized by pleiotropic health effects, such as probiotic or antioxidant potential. That is mainly due to the fermentation process. Despite the low viability of [...] Read more.
Silages may be preventive against lifestyle diseases, including obesity, diabetes mellitus, or metabolic syndrome. Fermented vegetables and legumes are characterized by pleiotropic health effects, such as probiotic or antioxidant potential. That is mainly due to the fermentation process. Despite the low viability of microorganisms in the gastrointestinal tract, their probiotic potential was confirmed. The modification of microbiota diversity caused by these food products has numerous implications. Most of them are connected to changes in the production of metabolites by bacteria, such as butyrate. Moreover, intake of fermented vegetables and legumes influences epigenetic changes, which lead to inhibition of lipogenesis and decreased appetite. Lifestyle diseases’ feature is increased inflammation; thus, foods with high antioxidant potential are recommended. Silages are characterized by having a higher bioavailable antioxidants content than fresh samples. That is due to fermentative microorganisms that produce the enzyme β-glucosidase, which releases these compounds from conjugated bonds with antinutrients. However, fermented vegetables and legumes are rich in salt or salt substitutes, such as potassium chloride. However, until today, silages intake has not been connected to the prevalence of hypertension or kidney failure. Full article
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15 pages, 1389 KiB  
Systematic Review
Pramipexole Augmentation for Treatment-Resistant Unipolar and Bipolar Depression in the Real World: A Systematic Review and Meta-Analysis
by Antonio Tundo, Sophia Betro’, Rocco de Filippis, Fulvia Marchetti, Daniele Nacca, Roberta Necci and Marica Iommi
Life 2023, 13(4), 1043; https://doi.org/10.3390/life13041043 - 19 Apr 2023
Cited by 3 | Viewed by 3853
Abstract
Background: Pramipexole is a dopamine full agonist approved for the treatment of Parkinson’s disease and restless legs syndrome. Its high affinity for the D3 receptor and neuroprotective, antioxidant, and anti-inflammatory activity provides a rationale for the treatment of depression. In this paper, we [...] Read more.
Background: Pramipexole is a dopamine full agonist approved for the treatment of Parkinson’s disease and restless legs syndrome. Its high affinity for the D3 receptor and neuroprotective, antioxidant, and anti-inflammatory activity provides a rationale for the treatment of depression. In this paper, we review studies on the effectiveness and safety of antidepressant pramipexole augmentation in treatment-resistant depression. Methods: This comprehensive systematic review and meta-analysis of observational studies on pramipexole–antidepressant augmentation included patients with resistant unipolar and bipolar depression. The primary outcome measure was the treatment response, measured at the study endpoint. Results: We identified 8 studies including 281 patients overall, 57% women and 39.5% with bipolar disorder and 60.5% with major depressive disorder. The mean follow-up duration was 27.3 weeks (range 8–69). The pooled estimate of treatment response was 62.5%, without significant differences between unipolar and bipolar depression. Safety was good, with nausea and somnolence the most frequent side effects. Conclusions: The findings of this systematic review, needing further confirmation, show that off-label use of pramipexole as augmentation of antidepressant treatment could be a useful and safe strategy for unipolar and bipolar treatment-resistant depression. Full article
(This article belongs to the Special Issue What Is New in Psychiatry and Psychopharmacology?)
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20 pages, 2737 KiB  
Article
Impact of Light and Dark Treatment on Phenylpropanoid Pathway Genes, Primary and Secondary Metabolites in Agastache rugosa Transgenic Hairy Root Cultures by Overexpressing Arabidopsis Transcription Factor AtMYB12
by Thi Minh Hanh Do, Minsol Choi, Jae Kwang Kim, Ye Jin Kim, Chanung Park, Chang Ha Park, Nam Il Park, Changsoo Kim, Ramaraj Sathasivam and Sang Un Park
Life 2023, 13(4), 1042; https://doi.org/10.3390/life13041042 - 19 Apr 2023
Cited by 2 | Viewed by 1904
Abstract
Agastache rugosa, otherwise called Korean mint, has a wide range of medicinal benefits. In addition, it is a rich source of several medicinally valuable compounds such as acacetin, tilianin, and some phenolic compounds. The present study aimed to investigate how the Tartary [...] Read more.
Agastache rugosa, otherwise called Korean mint, has a wide range of medicinal benefits. In addition, it is a rich source of several medicinally valuable compounds such as acacetin, tilianin, and some phenolic compounds. The present study aimed to investigate how the Tartary buckwheat transcription factor AtMYB12 increased the primary and secondary metabolites in Korean mint hairy roots cultured under light and dark conditions. A total of 50 metabolites were detected by using high-performance liquid chromatography (HPLC) and gas chromatography–time-of-flight mass spectrometry (GC-TOFMS). The result showed that the AtMYB12 transcription factor upregulated the phenylpropanoid biosynthesis pathway genes, which leads to the highest accumulation of primary and secondary metabolites in the AtMYB12-overexpressing hairy root lines (transgenic) than that of the GUS-overexpressing hairy root line (control) when grown under the light and dark conditions. However, when the transgenic hairy root lines were grown under dark conditions, the phenolic and flavone content was not significantly different from that of the control hairy root lines. Similarly, the heat map and hierarchical clustering analysis (HCA) result showed that most of the metabolites were significantly abundant in the transgenic hairy root cultures grown under light conditions. Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) showed that the identified metabolites were separated far based on the primary and secondary metabolite contents present in the control and transgenic hairy root lines grown under light and dark conditions. Metabolic pathway analysis of the detected metabolites showed 54 pathways were identified, among these 30 were found to be affected. From these results, the AtMYB12 transcription factor activity might be light-responsive in the transgenic hairy root cultures, triggering the activation of the primary and secondary metabolic pathways in Korean mint. Full article
(This article belongs to the Special Issue Development of Genetic Engineering Technologies for Crops)
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22 pages, 6903 KiB  
Article
Bryorutstroemia (Rutstroemiaceae, Helotiales), a New Genus to Accommodate the Neglected Sclerotiniaceous Bryoparasitic Discomycete Helotium fulvum
by Hans-Otto Baral, Zuzana Sochorová and Michal Sochor
Life 2023, 13(4), 1041; https://doi.org/10.3390/life13041041 - 18 Apr 2023
Cited by 1 | Viewed by 1581
Abstract
The new genus Bryorutstroemia is established for the red-brown, stipitate, bryoparasitic discomycete Helotium fulvum Boud. Combined phylogenetic analysis of ITS and LSU rDNA and EF1α revealed that Bryorutstroemia fulva belongs to the sclerotiniaceous clade, which comprises the paraphyletic families Rutstroemiaceae and Sclerotiniaceae. Bryorutstroemia [...] Read more.
The new genus Bryorutstroemia is established for the red-brown, stipitate, bryoparasitic discomycete Helotium fulvum Boud. Combined phylogenetic analysis of ITS and LSU rDNA and EF1α revealed that Bryorutstroemia fulva belongs to the sclerotiniaceous clade, which comprises the paraphyletic families Rutstroemiaceae and Sclerotiniaceae. Bryorutstroemia formed with Clarireedia a supported clade (Rutstroemiaceae s.l.), though with high distance. Bryorutstroemia closely resembles other Rutstroemiaceae in having uninucleate ascospores with high lipid content and an ectal excipulum of textura porrecta, but is unique because of its bryophilous lifestyle and is extraordinary with its thick-walled inamyloid ascus apex. Although B. fulva was described in 1897, very few records came to our notice. The present study summarizes the known distribution of the species, including 25 personal collections from the years 2001–2022. Bryorutstroemia fulva was most often encountered on Dicranella heteromalla, and rarely on other members of Dicranales or Grimmiales, while inducing necrobiosis of the leaves. A detailed description based on mainly fresh apothecia is provided together with a rich photographic documentation. Six new combinations are proposed based on our phylogenetic results and unpublished personal morphological studies: Clarireedia asphodeli, C. calopus, C. gladioli, C. henningsiana, C. maritima, and C. narcissi. Full article
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13 pages, 2895 KiB  
Article
Bi-DCNet: Bilateral Network with Dilated Convolutions for Left Ventricle Segmentation
by Zi Ye, Yogan Jaya Kumar, Fengyan Song, Guanxi Li and Suyu Zhang
Life 2023, 13(4), 1040; https://doi.org/10.3390/life13041040 - 18 Apr 2023
Viewed by 1035
Abstract
Left ventricular segmentation is a vital and necessary procedure for assessing cardiac systolic and diastolic function, while echocardiography is an indispensable diagnostic technique that enables cardiac functionality assessment. However, manually labeling the left ventricular region on echocardiography images is time consuming and leads [...] Read more.
Left ventricular segmentation is a vital and necessary procedure for assessing cardiac systolic and diastolic function, while echocardiography is an indispensable diagnostic technique that enables cardiac functionality assessment. However, manually labeling the left ventricular region on echocardiography images is time consuming and leads to observer bias. Recent research has demonstrated that deep learning has the capability to employ the segmentation process automatically. However, on the downside, it still ignores the contribution of all semantic information through the segmentation process. This study proposes a deep neural network architecture based on BiSeNet, named Bi-DCNet. This model comprises a spatial path and a context path, with the former responsible for spatial feature (low-level) acquisition and the latter responsible for contextual semantic feature (high-level) exploitation. Moreover, it incorporates feature extraction through the integration of dilated convolutions to achieve a larger receptive field to capture multi-scale information. The EchoNet-Dynamic dataset was utilized to assess the proposed model, and this is the first bilateral-structured network implemented on this large clinical video dataset for accomplishing the segmentation of the left ventricle. As demonstrated by the experimental outcomes, our method obtained 0.9228 and 0.8576 in DSC and IoU, respectively, proving the structure’s effectiveness. Full article
(This article belongs to the Special Issue Artificial Intelligence Applications in Medical Imaging)
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13 pages, 1701 KiB  
Article
Molecular Investigation of Eimeria Species in Broiler Farms in the Province of Vojvodina, Serbia
by Marko Pajić, Dalibor Todorović, Slobodan Knežević, Bojana Prunić, Maja Velhner, Dušica Ostojić Andrić and Zoran Stanimirovic
Life 2023, 13(4), 1039; https://doi.org/10.3390/life13041039 - 18 Apr 2023
Cited by 3 | Viewed by 1532
Abstract
Coccidiosis is a significant poultry disease caused by the Eimeria species. This study aims to determine the prevalence of Eimeria spp. on broiler farms in Vojvodina, along with the identification of parasite species, and assess the implemented biosecurity measures. The study was conducted [...] Read more.
Coccidiosis is a significant poultry disease caused by the Eimeria species. This study aims to determine the prevalence of Eimeria spp. on broiler farms in Vojvodina, along with the identification of parasite species, and assess the implemented biosecurity measures. The study was conducted on 100 broiler chicken farms (28 small-sized; 34 medium-sized; 38 large-sized farms) from June 2018 to December 2021. One pooled sample of faeces was collected from three to six-week-old chickens from each farm, and assessment of biosecurity measures was carried out using a questionnaire. Using the PCR method, DNA of Eimeria was found in 59 samples (59%), while 41 samples (41%) were negative. Four species of Eimeria were identified, and their prevalence was the following: E. acervulina (37%), E. maxima (17%), E. mitis (25%) and E. tenella (48%). A significant difference (p < 0.05) was established in the number of oocysts in flocks from small-sized farms compared to medium-sized farms. It was found that regular implementation of disinfection, disinsection and deratisation measures, as well as all the biosecurity measures, can significantly reduce the occurrence of coccidiosis. These results will help to develop better strategies for the control and prevention of coccidiosis on farms. Full article
(This article belongs to the Special Issue Eimeria and the Future of Coccidiosis Control)
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12 pages, 303 KiB  
Article
Influence of CYP2B6 Genotype on Methadone Dosage in Patients from the Methadone Maintenance Treatment (MMT) Program in Pereira, Colombia
by Carlos Isaza, Oscar Mauricio Castaño-Ramírez, Juan Pablo Vélez, Julieta Henao, Leonardo Beltrán-Angarita and Juan Carlos Sepúlveda-Arias
Life 2023, 13(4), 1038; https://doi.org/10.3390/life13041038 - 18 Apr 2023
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Abstract
Methadone treatment reduces the use of heroin and withdrawal symptoms; however, methadone is an expensive medication with a narrow safety margin. We compared the retention rates, persistence of heroin use, and quality of life of a group of patients undergoing conventional Methadone Maintenance [...] Read more.
Methadone treatment reduces the use of heroin and withdrawal symptoms; however, methadone is an expensive medication with a narrow safety margin. We compared the retention rates, persistence of heroin use, and quality of life of a group of patients undergoing conventional Methadone Maintenance Treatment (MMT) with a group for whom the CYP2B6 516G>T polymorphism was used in addition to the MMT to calculate the required methadone dose. Over 12 weeks, the retention rate, heroin usage, and quality of life of patients under conventional treatment (n = 34) were compared with those of patients for whom we used genetic markers to calculate methadone dosage (n = 38). At the end of the study, 26.4% of patients abandoned the program, and neither demographic nor clinical variables were associated with treatment adherence. Of the remaining patients, 16% of the control group and 8% of patients in the pharmacogenetic group reported heroin use, while both groups showed a 64% reduction in the use of cocaine/crack (no significant differences between the groups were found). Starting in the second week, the methadone dosage was lower among the patients for whom methadone was prescribed based on genotype. Although there were six individuals in the control group and three in the pharmacogenetic group with QTc intervals > 450 ms (a threshold that is considered dangerous), we did not find a relationship between the QTc interval and methadone dosage. There were no differences in the perception of quality of life between the two groups. The results of this pilot study suggest that concerning methadone therapy, the CYP2B6 genotype contributes to reduced effective doses and treatment costs. Full article
(This article belongs to the Section Medical Research)
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