Biomedicines

9 pages, 1948 KiB

Open AccessArticle

First Live-Experience Session with PET/CT Specimen Imager: A Pilot Analysis in Prostate Cancer and Neuroendocrine Tumor

by Lorenzo Muraglia, Francesco Mattana, Laura Lavinia Travaini, Gennaro Musi, Emilio Bertani, Giuseppe Renne, Eleonora Pisa, Mahila Esmeralda Ferrari, Uberto Fumagalli Romario, Ottavio De Cobelli, Nicola Fusco and Francesco Ceci

Biomedicines 2023, 11(2), 645; https://doi.org/10.3390/biomedicines11020645 - 20 Feb 2023

Cited by 5 | Viewed by 1864

Abstract

Objective: to evaluate the feasibility of the intra-operative application of a specimen PET/CT imager in a clinical setting. Materials and methods: this is a pilot analysis performed in three patients who received an intra-operative administration of ⁶⁸Ga-PSMA-11 (n = 2) and ⁶⁸ [...] Read more.

Objective: to evaluate the feasibility of the intra-operative application of a specimen PET/CT imager in a clinical setting. Materials and methods: this is a pilot analysis performed in three patients who received an intra-operative administration of ⁶⁸Ga-PSMA-11 (n = 2) and ⁶⁸Ga-DOTA-TOC (n = 1), respectively. Patients were administrated with PET radiopharmaceuticals to perform radio-guided surgery with a beta-probe detector during radical prostatectomy for prostate cancer (PCa) and salvage lymphadenectomy for recurrent neuroendocrine tumor (NET) of the ileum, respectively. All procedures have been performed within two ongoing clinical trials in our Institute (NCT05596851 and NCT05448157). Pathologic assessment with immunohistochemistry (PSMA-staining and SSA immunoreactivity) was considered as standard of truth. Specimen images were compared with baseline PET/CT images and histopathological analysis. Results: Patients received 1 MBq/Kg of ⁶⁸Ga-PSMA-11 (PCa) or 1.2 MBq/Kg of ⁶⁸Ga-DOTA-TOC (NET) prior to surgery. Specimens were collected, positioned in the dedicated specimen container, and scanned to obtain high-resolution PET/CT images. In all cases, a perfect match was observed between the findings detected by the specimen imager and histopathology. Overall, the PET spatial resolution was sensibly higher for the specimen images compared to the baseline whole-body PET/CT images. Furthermore, the use of the PET/CT specimen imager did not significantly interfere with any procedures, and the overall length of the surgery was not affected using the PET/CT specimen imager. Finally, the radiation exposure of the operating theater staff was lower than 40 µSv per procedure (range 26–40 μSv). Conclusions: the image acquisition of specimens obtained by patients who received intra-surgery injections of ⁶⁸Ga-PSMA-11 and ⁶⁸Ga-DOTA-TOC was feasible and reliable also in a live-experience session and has been easily adapted to surgery daily practice. The high sensitivity, together with the evaluation of intra-lesion tumor heterogeneity, were the most relevant results since the data derived from specimen PET/CT imaging matched perfectly with the histopathological analysis. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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19 pages, 1328 KiB

Open AccessReview

Novel Adipokines and Their Role in Bone Metabolism: A Narrative Review

by Fnu Deepika, Siresha Bathina and Reina Armamento-Villareal

Biomedicines 2023, 11(2), 644; https://doi.org/10.3390/biomedicines11020644 - 20 Feb 2023

Cited by 6 | Viewed by 2645

Abstract

The growing burden of obesity and osteoporosis is a major public health concern. Emerging evidence of the role of adipokines on bone metabolism has led to the discovery of novel adipokines over the last decade. Obesity is recognized as a state of adipose [...] Read more.

The growing burden of obesity and osteoporosis is a major public health concern. Emerging evidence of the role of adipokines on bone metabolism has led to the discovery of novel adipokines over the last decade. Obesity is recognized as a state of adipose tissue inflammation that adversely affects bone health. Adipokines secreted from white adipose tissue (WAT) and bone marrow adipose tissue (BMAT) exerts endocrine and paracrine effects on the survival and function of osteoblasts and osteoclasts. An increase in marrow fat is implicated in osteoporosis and, hence, it is crucial to understand the complex interplay between adipocytes and bone. The objective of this review is to summarize recent advances in our understanding of the role of different adipokines on bone metabolism. Methods: This is a comprehensive review of the literature available in PubMED and Cochrane databases, with an emphasis on the last five years using the keywords. Results: Leptin has shown some positive effects on bone metabolism; in contrast, both adiponectin and chemerin have consistently shown a negative association with BMD. No significant association was found between resistin and BMD. Novel adipokines such as visfatin, LCN-2, Nesfatin-1, RBP-4, apelin, and vaspin have shown bone-protective and osteoanabolic properties that could be translated into therapeutic targets. Conclusion: New evidence suggests the potential role of novel adipokines as biomarkers to predict osteoporosis risk, and as therapeutic targets for the treatment of osteoporosis. Full article

(This article belongs to the Special Issue Feature Reviews in Adipokines)

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23 pages, 3077 KiB

Open AccessArticle

Molecular Screening of Bioactive Compounds of Garlic for Therapeutic Effects against COVID-19

by Huma Ashraf, Erum Dilshad, Tayyaba Afsar, Ali Almajwal, Huma Shafique and Suhail Razak

Biomedicines 2023, 11(2), 643; https://doi.org/10.3390/biomedicines11020643 - 20 Feb 2023

Cited by 1 | Viewed by 1640

Abstract

An outbreak of pneumonia occurred on December 2019 in Wuhan, China, which caused a serious public health emergency by spreading around the globe. Globally, natural products are being focused on more than synthetic ones. So, keeping that in view, the current study was [...] Read more.

An outbreak of pneumonia occurred on December 2019 in Wuhan, China, which caused a serious public health emergency by spreading around the globe. Globally, natural products are being focused on more than synthetic ones. So, keeping that in view, the current study was conducted to discover potential antiviral compounds from Allium sativum. Twenty-five phytocompounds of this plant were selected from the literature and databases including 3-(Allylsulphinyl)-L-alanine, Allicin, Diallyl sulfide, Diallyl disulfide, Diallyl trisulfide, Glutathione, L-Cysteine, S-allyl-mercapto-glutathione, Quercetin, Myricetin, Thiocysteine, Gamma-glutamyl-Lcysteine, Gamma-glutamylallyl-cysteine, Fructan, Lauricacid, Linoleicacid, Allixin, Ajoene, Diazinon Kaempferol, Levamisole, Caffeicacid, Ethyl linoleate, Scutellarein, and S-allylcysteine methyl-ester. Virtual screening of these selected ligands was carried out against drug target 3CL protease by CB-dock. Pharmacokinetic and pharmacodynamic properties defined the final destiny of compounds as drug or non-drug molecules. The best five compounds screened were Allicin, Diallyl Sulfide, Diallyl Disulfide, Diallyl Trisulfide, Ajoene, and Levamisole, which showed themselves as hit compounds. Further refining by screening filters represented Levamisole as a lead compound. All the interaction visualization analysis studies were performed using the PyMol molecular visualization tool and LigPlot+. Conclusively, Levamisole was screened as a likely antiviral compound which might be a drug candidate to treat SARS-CoV-2 in the future. Nevertheless, further research needs to be carried out to study their potential medicinal use. Full article

(This article belongs to the Section Immunology and Immunotherapy)

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19 pages, 2896 KiB

Open AccessReview

Immune Recognition versus Immune Evasion Systems in Zika Virus Infection

by Yee Teng Chan, Yi Ying Cheok, Heng Choon Cheong, Ting Fang Tang, Sofiah Sulaiman, Jamiyah Hassan, Chung Yeng Looi, Kim-Kee Tan, Sazaly AbuBakar and Won Fen Wong

Biomedicines 2023, 11(2), 642; https://doi.org/10.3390/biomedicines11020642 - 20 Feb 2023

Cited by 2 | Viewed by 3456

Abstract

The reemergence of the Zika virus (ZIKV) infection in recent years has posed a serious threat to global health. Despite being asymptomatic or mildly symptomatic in a majority of infected individuals, ZIKV infection can result in severe manifestations including neurological complications in adults [...] Read more.

The reemergence of the Zika virus (ZIKV) infection in recent years has posed a serious threat to global health. Despite being asymptomatic or mildly symptomatic in a majority of infected individuals, ZIKV infection can result in severe manifestations including neurological complications in adults and congenital abnormalities in newborns. In a human host, ZIKV is primarily recognized by RIG-like receptors and Toll-like receptors that elicit anti-viral immunity through the secretion of type I interferon (IFN) to limit viral survival, replication, and pathogenesis. Intriguingly, ZIKV evades its host immune system through various immune evasion strategies, including suppressing the innate immune receptors and signaling pathways, mutation of viral structural and non-structural proteins, RNA modulation, or alteration of cellular pathways. Here, we present an overview of ZIKV recognition by the host immune system and the evasion strategies employed by ZIKV. Characterization of the host–viral interaction and viral disease mechanism provide a platform for the rational design of novel prophylactic and therapeutic strategies against ZIKV infection. Full article

(This article belongs to the Special Issue Immune Response to Viruses and Bacteria)

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16 pages, 1925 KiB

Open AccessReview

Targeted Therapy Development in Acute Myeloid Leukemia

by Tulasigeri M. Totiger, Anirban Ghoshal, Jenna Zabroski, Anya Sondhi, Saanvi Bucha, Jacob Jahn, Yangbo Feng and Justin Taylor

Biomedicines 2023, 11(2), 641; https://doi.org/10.3390/biomedicines11020641 - 20 Feb 2023

Cited by 10 | Viewed by 4264

Abstract

Therapeutic developments targeting acute myeloid leukemia (AML) have been in the pipeline for five decades and have recently resulted in the approval of multiple targeted therapies. However, there remains an unmet need for molecular treatments that can deliver long-term remissions and cure for [...] Read more.

Therapeutic developments targeting acute myeloid leukemia (AML) have been in the pipeline for five decades and have recently resulted in the approval of multiple targeted therapies. However, there remains an unmet need for molecular treatments that can deliver long-term remissions and cure for this heterogeneous disease. Previously, a wide range of small molecule drugs were developed to target sub-types of AML, mainly in the relapsed and refractory setting; however, drug resistance has derailed the long-term efficacy of these as monotherapies. Recently, the small molecule venetoclax was introduced in combination with azacitidine, which has improved the response rates and the overall survival in older adults with AML compared to those of chemotherapy. However, this regimen is still limited by cytotoxicity and is not curative. Therefore, there is high demand for therapies that target specific abnormalities in AML while sparing normal cells and eliminating leukemia-initiating cells. Despite this, the urgent need to develop these therapies has been hampered by the complexities of this heterogeneous disease, spurring the development of innovative therapies that target different mechanisms of leukemogenesis. This review comprehensively addresses the development of novel targeted therapies and the translational perspective for acute myeloid leukemia, including the development of selective and non-selective drugs. Full article

(This article belongs to the Special Issue Development of Small Molecules for Acute Myeloid Leukemia Therapy)

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21 pages, 7321 KiB

Open AccessArticle

The Effects of Probiotics on Small Intestinal Microbiota Composition, Inflammatory Cytokines and Intestinal Permeability in Patients with Non-Alcoholic Fatty Liver Disease

by Nurainina Ayob, Khairul Najmi Muhammad Nawawi, Mohamad Hizami Mohamad Nor, Raja Affendi Raja Ali, Hajar Fauzan Ahmad, Seok Fang Oon and Norfilza Mohd Mokhtar

Biomedicines 2023, 11(2), 640; https://doi.org/10.3390/biomedicines11020640 - 20 Feb 2023

Cited by 18 | Viewed by 3612

Abstract

The prevalence of non-alcoholic fatty liver disease (NAFLD) has soared globally. As our understanding of the disease grows, the role of the gut-liver axis (GLA) in NAFLD pathophysiology becomes more apparent. Hence, we focused mainly on the small intestinal area to explore the [...] Read more.

The prevalence of non-alcoholic fatty liver disease (NAFLD) has soared globally. As our understanding of the disease grows, the role of the gut-liver axis (GLA) in NAFLD pathophysiology becomes more apparent. Hence, we focused mainly on the small intestinal area to explore the role of GLA. We looked at how multi-strain probiotics (MCP^® BCMC^® strains) containing six different Lactobacillus and Bifidobacterium species affected the small intestinal gut microbiota, inflammatory cytokines, and permeability in NAFLD patients. After six months of supplementation, biochemical blood analysis did not show any discernible alterations in either group. Five predominant phyla known as Actinobacteria, Proteobacteria, Firmicutes, Bacteroidota and Fusobacteria were found in NAFLD patients. The probiotics group demonstrated a significant cluster formation of microbiota composition through beta-diversity analysis (p < 0.05). This group significantly reduced three unclassifiable species: unclassified_Proteobacteria, unclassified_Streptococcus, and unclassified_Stenotrophomonas. In contrast, the placebo group showed a significant increase in Prevotella_melaninogenica and Rothia_mucilaginosa, which were classified as pathogens. Real-time quantitative PCR analysis of small intestinal mucosal inflammatory cytokines revealed a significant decrease in IFN-γ (−7.9 ± 0.44, p < 0.0001) and TNF-α (−0.96 ± 0.25, p < 0.0033) in the probiotics group but an increase in IL-6 (12.79 ± 2.24, p < 0.0001). In terms of small intestinal permeability analysis, the probiotics group, unfortunately, did not show any positive changes through ELISA analysis. Both probiotics and placebo groups exhibited a significant increase in the level of circulating zonulin (probiotics: 107.6 ng/mL ± 124.7, p = 0.005 vs. placebo: 106.9 ng/mL ± 101.3, p = 0.0002) and a significant decrease in circulating zonula occluden-1 (ZO-1) (probiotics: −34.51 ng/mL ± 18.38, p < 0.0001 vs. placebo: −33.34 ng/mL ± 16.62, p = 0.0001). The consumption of Lactobacillus and Bifidobacterium suggested the presence of a well-balanced gut microbiota composition. Probiotic supplementation improves dysbiosis in NAFLD patients. This eventually stabilised the expression of inflammatory cytokines and mucosal immune function. To summarise, more research on probiotic supplementation as a supplement to a healthy diet and lifestyle is required to address NAFLD and its underlying causes. Full article

(This article belongs to the Special Issue Metabolic and Genetic Associated Fatty Liver Diseases)

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13 pages, 1812 KiB

Open AccessArticle

The Iron Content of Human Serum Albumin Modulates the Susceptibility of Acinetobacter baumannii to Cefiderocol

by Jenny Escalante, Brent Nishimura, Marisel R. Tuttobene, Tomás Subils, Vyanka Mezcord, Luis A. Actis, Marcelo E. Tolmasky, Robert A. Bonomo and María Soledad Ramirez

Biomedicines 2023, 11(2), 639; https://doi.org/10.3390/biomedicines11020639 - 20 Feb 2023

Cited by 5 | Viewed by 1618

Abstract

The mortality rates of patients infected with Acinetobacter baumannii who were treated with cefiderocol (CFDC) were not as favorable as those receiving the best available treatment for pulmonary and bloodstream infections. Previous studies showed that the presence of human serum albumin (HSA) or [...] Read more.

The mortality rates of patients infected with Acinetobacter baumannii who were treated with cefiderocol (CFDC) were not as favorable as those receiving the best available treatment for pulmonary and bloodstream infections. Previous studies showed that the presence of human serum albumin (HSA) or HSA-containing fluids, such as human serum (HS) or human pleural fluid (HPF), in the growth medium is correlated with a decrease in the expression of genes associated with high-affinity siderophore-mediated iron uptake systems. These observations may explain the complexities of the observed clinical performance of CFDC in pulmonary and bloodstream infections, because ferric siderophore transporters enhance the penetration of CFDC into the bacterial cell. The removal of HSA from HS or HPF resulted in a reduction in the minimal inhibitory concentration (MIC) of CFDC. Concomitant with these results, an enhancement in the expression of TonB-dependent transporters known to play a crucial role in transporting iron was observed. In addition to inducing modifications in iron-uptake gene expression, the removal of HSA also decreased the expression of β-lactamases genes. Taken together, these observations suggest that environmental HSA has a role in the expression levels of select A. baumannii genes. Furthermore, the removal of iron from HSA had the same effect as the removal of HSA upon the expression of genes associated with iron uptake systems, also suggesting that at least one of the mechanisms by which HSA regulates the expression of certain genes is through acting as an iron source. Full article

(This article belongs to the Section Microbiology in Human Health and Disease)

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22 pages, 3443 KiB

Open AccessArticle

Phenotypic Characterization of Male Tafazzin-Knockout Mice at 3, 6, and 12 Months of Age

by Michelle V. Tomczewski, John Z. Chan, Zurie E. Campbell, Douglas Strathdee and Robin E. Duncan

Biomedicines 2023, 11(2), 638; https://doi.org/10.3390/biomedicines11020638 - 20 Feb 2023

Cited by 2 | Viewed by 2225

Abstract

Barth syndrome (BTHS) is an X-linked mitochondrial disease caused by mutations in the gene encoding for tafazzin (TAZ), a key enzyme in the remodeling of cardiolipin. Mice with a germline deficiency in Taz have been generated (Taz-KO) but not [...] Read more.

Barth syndrome (BTHS) is an X-linked mitochondrial disease caused by mutations in the gene encoding for tafazzin (TAZ), a key enzyme in the remodeling of cardiolipin. Mice with a germline deficiency in Taz have been generated (Taz-KO) but not yet fully characterized. We performed physiological assessments of 3-, 6-, and 12-month-old male Taz-KO mice, including measures of perinatal survival, growth, lifespan, gross anatomy, whole-body energy and substrate metabolism, glucose homeostasis, and exercise capacity. Taz-KO mice displayed reduced viability, with lower-than-expected numbers of mice recorded at 4 weeks of age, and a shortened lifespan due to disease progression. At all ages, Taz-KO mice had lower body weights compared with wild-type (Wt) littermates despite similar absolute food intakes. This finding was attributed to reduced adiposity and diminutive organs and tissues, including heart and skeletal muscles. Although there were no differences in basal levels of locomotion between age-matched genotypes, indirect calorimetry studies showed higher energy expenditure measures and respiratory exchange ratios in Taz-KO mice. At the youngest age, Taz-KO mice had comparable glucose tolerance and insulin action to Wt mice, but while these measures indicated metabolic impairments in Wt mice with advancing age that were likely associated with increasing adiposity, Taz-KO mice were protected. Comparisons across the three age-cohorts revealed a significant and more severe deterioration of exercise capacity in Taz-KO mice than in their Wt littermate controls. The Taz-KO mouse model faithfully recapitulates important aspects of BTHS, and thus provides an important new tool to investigate pathophysiological mechanisms and potential therapies. Full article

(This article belongs to the Special Issue Mitochondrial Function in Biomedicines)

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9 pages, 499 KiB

Open AccessArticle

Risk of Severe Alphaherpesvirus Infection after Solid Organ Transplantation: A Nationwide Population-Based Cohort Study

by Ya-Wen Chuang, Shih-Ting Huang, I-Kuan Wang, Ying-Chih Lo, Chiz-Tzung Chang, Cheng-Li Lin, Tung-Min Yu and Chi-Yuan Li

Biomedicines 2023, 11(2), 637; https://doi.org/10.3390/biomedicines11020637 - 20 Feb 2023

Cited by 1 | Viewed by 1466

Abstract

Patients after solid organ transplantation (SOT) are more susceptible to various viral infections, including alphaherpesviruses. Therefore, the aim of our study was to investigate the risk of alphaherpesvirus infections, including herpes simplex and herpes zoster, after solid organ transplantation. Inpatient records from the [...] Read more.

Patients after solid organ transplantation (SOT) are more susceptible to various viral infections, including alphaherpesviruses. Therefore, the aim of our study was to investigate the risk of alphaherpesvirus infections, including herpes simplex and herpes zoster, after solid organ transplantation. Inpatient records from the Taiwan National Health Insurance Research Database (NHIRD) defined solid organ recipients, including heart, liver, lung, and kidney, hospitalized for alphaherpesvirus infections as a severe case group of transplants and matched them with a nontransplant cohort. We enrolled 18,064 individuals, of whom 9032 were in each group. A higher risk of severe alphaherpesvirus infection was noted in solid organ recipients (aHR = 9.19; p < 0.001) than in the general population. In addition, solid organ transplant recipients had the highest risk of alphaherpesvirus infection within 1 year after transplantation (aHR = 25.18). The comparison found a higher risk of herpes zoster and herpes simplex infections in recipients of kidney (aHR = 9.13; aHR = 12.13), heart (aHR = 14.34; aHR = 18.54), and liver (aHR = 5.90; aHR = 8.28) transplants. Patients who underwent solid organ transplantation had a significantly higher risk of alphaherpesvirus infection than the general population. Full article

(This article belongs to the Section Immunology and Immunotherapy)

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20 pages, 381 KiB

Open AccessReview

Multilineage-Differentiating Stress-Enduring Cells (Muse Cells): The Future of Human and Veterinary Regenerative Medicine

by María Gemma Velasco, Katy Satué, Deborah Chicharro, Emma Martins, Marta Torres-Torrillas, Pau Peláez, Laura Miguel-Pastor, Ayla Del Romero, Elena Damiá, Belén Cuervo, José María Carrillo, Ramón Cugat, Joaquín Jesús Sopena and Mónica Rubio

Biomedicines 2023, 11(2), 636; https://doi.org/10.3390/biomedicines11020636 - 20 Feb 2023

Cited by 1 | Viewed by 2390

Abstract

In recent years, several studies have been conducted on Muse cells mainly due to their pluripotency, high tolerance to stress, self-renewal capacity, ability to repair DNA damage and not being tumoral. Additionally, since these stem cells can be isolated from different tissues in [...] Read more.

In recent years, several studies have been conducted on Muse cells mainly due to their pluripotency, high tolerance to stress, self-renewal capacity, ability to repair DNA damage and not being tumoral. Additionally, since these stem cells can be isolated from different tissues in the adult organism, obtaining them is not considered an ethical problem, providing an advantage over embryonic stem cells. Regarding their therapeutic potential, few studies have reported clinical applications in the treatment of different diseases, such as aortic aneurysm and chondral injuries in the mouse or acute myocardial infarction in the swine, rabbit, sheep and in humans. This review aims to describe the characterization of Muse cells, show their biological characteristics, explain the differences between Muse cells and mesenchymal stem cells, and present their contribution to the treatment of some diseases. Full article

(This article belongs to the Special Issue Mesenchymal Stromal (Stem) Cells)

13 pages, 2105 KiB

Open AccessArticle

Influence of FOSL1 Inhibition on Vascular Calcification and ROS Generation through Ferroptosis via P53-SLC7A11 Axis

by Sisi Shao, Yaoxin Liu, Wanzi Hong, Yuanxi Mo, Fen Shu, Lei Jiang and Ning Tan

Biomedicines 2023, 11(2), 635; https://doi.org/10.3390/biomedicines11020635 - 20 Feb 2023

Cited by 2 | Viewed by 2255

Abstract

Background: Vascular calcification during aging is highly prevalent in patients with cardiovascular disease; however, there is still no improvement in clarifying the development of vascular calcification. FOSL1 is a transcription regulator belonging to the AP-1 family, which has a unique function in vascular [...] Read more.

Background: Vascular calcification during aging is highly prevalent in patients with cardiovascular disease; however, there is still no improvement in clarifying the development of vascular calcification. FOSL1 is a transcription regulator belonging to the AP-1 family, which has a unique function in vascular senescence, but its role in vascular calcification needs to be further explored. Methods: Primary mouse vascular smooth muscle cells were isolated and used to construct a calcification model in vitro. Seven-week-old male C57BL/6 mice were used to build the vitD3-induced calcification model in vivo. qRT-PCR and western blot were used to verify the expression of FOSL1 and other genes expressed in vascular smooth muscle cells and aortas. The level of calcification was determined by Alizarin Red S (ARS) staining and the calcium content assay. The level of cellular GSH was detected by the GSH assay kit. Results: Here, we report that FOSL1 was up-regulated after high-calcium/phosphate treatment in both the in vivo and in vitro vascular calcification models. Functional studies have shown that the reduction of FOSL1 attenuates ferroptosis and calcification in vascular smooth muscle cells, as indicated by ARS staining, calcium content assay, and western blot. The inhibition of FOSL1 downregulated the expression of bone-related molecules including Msh Homeobox 2 (MSX2) and tumor necrosis factor receptor superfamily, member 11b/osteoprotegerin (OPG), suggesting that FOSL1 promoted osteogenic differentiation of vascular smooth muscle cells. Furthermore, we found that the ferroptosis-inducing drug erastin can significantly accelerate calcification in the aortic ring while Ferrostatin-1 (fer-1), a drug to protect cells from ferroptosis, can alleviate calcification. Further experiments have shown that inhibiting FOSL1 can promote the expression of ferroptosis-related genes and attenuate calcification. Functionally, cellular GSH levels were increased after the reduction of FOSL1. Conclusions: In this study, we observed a significant protective effect when we reduced the expression of FOSL1 during vascular calcification, and this effect might regulate ferroptosis to a great extent. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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13 pages, 39863 KiB

Open AccessCase Report

Primary Cutaneous Multifocal Indolent CD8+ T-Cell Lymphoma: A Novel Primary Cutaneous CD8+ T-Cell Lymphoma

by Tina Petrogiannis-Haliotis, Kevin Pehr, David Roberge, Ryan N. Rys, Yury Monczak, Gizelle Popradi, Lissa Ajjamada, Naciba Benlimame, Christiane Querfeld, Nathalie Johnson and Hans Knecht

Biomedicines 2023, 11(2), 634; https://doi.org/10.3390/biomedicines11020634 - 20 Feb 2023

Cited by 1 | Viewed by 3173

Abstract

We report the case of a patient who was referred to our institution with a diagnosis of CD4+ small/medium-sized pleomorphic lymphoma. At the time, the patient showed a plethora of lesions mainly localizing to the legs; thus, we undertook studies to investigate the [...] Read more.

We report the case of a patient who was referred to our institution with a diagnosis of CD4+ small/medium-sized pleomorphic lymphoma. At the time, the patient showed a plethora of lesions mainly localizing to the legs; thus, we undertook studies to investigate the lineage and immunophenotype of the neoplastic clone. Immunohistochemistry (IHC) showed marked CD4 and CD8 positivity. Flow cytometry (FCM) showed two distinct T-cell populations, CD4+ and CD8+ (+/− PD1), with no CD4/CD8 co-expression and no loss of panT-cell markers in either T-cell subset. FCM, accompanied by cell-sorting (CS), permitted the physical separation of four populations, as follows: CD4+/PD1−, CD4+/PD1+, CD8+/PD1− and CD8+/PD1+. TCR gene rearrangement studies on each of the four populations (by next generation sequencing, NGS) showed that the neoplastic population was of T-cytotoxic cell lineage. IHC showed the CD8+ population to be TIA-1+, but perforin- and granzyme-negative. Moreover, histiocytic markers did not render the peculiar staining pattern, which is characteristic of acral CD8+ T-cell lymphoma (PCACD8). Compared to the entities described in the 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas, we found that the indolent lymphoma described herein differed from all of them. We submit that this case represents a hitherto-undescribed type of CTCL. Full article

(This article belongs to the Special Issue Translational Discoveries in T-cell Lymphomas)

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18 pages, 1527 KiB

Open AccessReview

Oncogenic Long Noncoding RNAs in Prostate Cancer, Osteosarcoma, and Metastasis

by Aishah Al-Shehri and Sherin Bakhashab

Biomedicines 2023, 11(2), 633; https://doi.org/10.3390/biomedicines11020633 - 20 Feb 2023

Cited by 1 | Viewed by 1850

Abstract

Prostate cancer (PC) is a common malignancy and is one of the leading causes of cancer-related death in men worldwide. Osteosarcoma (OS) is the most common bone cancer, representing 20–40% of all bone malignancy cases. Cancer metastasis is a process by which malignant [...] Read more.

Prostate cancer (PC) is a common malignancy and is one of the leading causes of cancer-related death in men worldwide. Osteosarcoma (OS) is the most common bone cancer, representing 20–40% of all bone malignancy cases. Cancer metastasis is a process by which malignant tumor cells detach from the primary tumor site via a cascade of processes and migrate to secondary sites through the blood circulation or lymphatic system to colonize and form secondary tumors. PC has a specific affinity to the bone based on the “seed and soil” theory; once PC reach the bone, it becomes incurable. Several studies have identified long noncoding RNAs (lncRNAs) as potential targets for cancer therapy or as diagnostic and prognostic biomarkers. The dysregulation of various lncRNAs has been found in various cancer types, including PC, OS, and metastasis. However, the mechanisms underlying lncRNA oncogenic activity in tumor progression and metastasis are extremely complex and remain incompletely understood. Therefore, understanding oncogenic lncRNAs and their role in OS, PC, and metastasis and the underlying mechanism may help better manage and treat this malignancy. The aim of this review is to summarize current knowledge of oncogenic lncRNAs and their involvement in PC, OS, and bone metastasis. Full article

(This article belongs to the Special Issue Women’s Special Issue Series: Biomedicines)

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8 pages, 688 KiB

Open AccessArticle

Acute Acalculous Cholecystitis Associated with Abscesses—An Unknown Dual Pathology

by Cristina Gluhovschi, Florica Gadalean, Silvia Velciov, Ligia Petrica, Ciprian Duta, Mircea Botoca and Daniela Cipu

Biomedicines 2023, 11(2), 632; https://doi.org/10.3390/biomedicines11020632 - 20 Feb 2023

Cited by 1 | Viewed by 1406

Abstract

(1) Introduction and Aims: Little is known about the relationship between renal pathology and gallbladder pathology, although the two organs (the gallbladder and the right kidney) are in close proximity to one another. If a renal abscess disseminates, the gallbladder would be one [...] Read more.

(1) Introduction and Aims: Little is known about the relationship between renal pathology and gallbladder pathology, although the two organs (the gallbladder and the right kidney) are in close proximity to one another. If a renal abscess disseminates, the gallbladder would be one of the secondary organs involved. As the bile provides a favorable environment for the development of pathogenic germs, it allows for the development of acute cholecystitis, even if calculi are absent, thus resulting in the development of acute acalculous cholecystitis. The aim of our study was to analyze the association between acute acalculous cholecystitis (AAC) and renal abscesses. (2) Methods: A department-wide retrospective cohort observational study including 67 patients with renal abscesses, with a mean age of 34.5+/−16.21 years and with five males and 62 females, was conducted. All of the patients were examined by an abdominal ultrasound. The lab tests included CBC with differential liver enzymes and serum bilirubin (in order to assess alterations in the liver function which can be associated with AAC) and serum creatinine (in order to assess the renal function). Blood culture and urine culture tests were also performed. (3) Results: Of the 67 patients with renal abscesses, eight (11.94%) were associated with acute cholecystitis: four cases (5.97%) of acalculous cholecystitis and four cases (5.97%) of calculous cholecystitis, two of which presented biliary sludge (acute micro-calculous cholecystitis). All four cases of acute acalculous cholecystitis presented with sepsis, and there was one case of septic shock at onset. We did not observe an impairment in renal function in the patients presenting with acute acalculous cholecystitis, and hepatic impairment was inconstant and moderate. All of the cases had a favorable outcome after a prompt initiation of intensive antibiotic therapy; both the renal abscess and the acute acalculous cholecystitis receded without further complications. (4) Conclusions: The association of acute acalculous cholecystitis with renal abscesses could be related to the possibility of germ dissemination from the infectious focus. In the case of a renal abscess, careful clinical, lab, and imaging exams of the gallbladder are recommended in order to ensure early therapeutic intervention in the event of an association with acute acalculous cholecystitis. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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13 pages, 2274 KiB

Open AccessArticle

A Preliminary Study on Microbiota Characteristics of Bronchoalveolar Lavage Fluid in Patients with Pulmonary Nodules Based on Metagenomic Next-Generation Sequencing

by Qian Yuan, Xiaojin Wang, Zhanglin Li, Wenzhuo Guo, Hua Cheng and Qingdong Cao

Biomedicines 2023, 11(2), 631; https://doi.org/10.3390/biomedicines11020631 - 20 Feb 2023

Cited by 2 | Viewed by 1504

Abstract

Background: The characteristics and roles of microbes in the occurrence and development of pulmonary nodules are still unclear. Methods: We retrospectively analyzed the microbial mNGS results of BALF from 229 patients with pulmonary nodules before surgery, and performed a comparative analysis of lung [...] Read more.

Background: The characteristics and roles of microbes in the occurrence and development of pulmonary nodules are still unclear. Methods: We retrospectively analyzed the microbial mNGS results of BALF from 229 patients with pulmonary nodules before surgery, and performed a comparative analysis of lung flora between lung cancer and benign nodules according to postoperative pathology. The analysis also focused on investigating the characteristics of lung microbiota in lung adenocarcinomas with varying histopathology. Results: There were differences in lung microbiota between lung cancer and benign lung nodules. Bacterial diversity was lower in lung cancer than in benign lung nodules. Four species (Porphyromonas somerae, Corynebacterium accolens, Burkholderia cenocepacia and Streptococcus mitis) were enriched in lung cancer compared with the benign lung nodules. The areas under the ROC curves of these four species were all greater than 0.6, and the AUC of Streptococcus mitis was 0.702, which had the highest diagnostic value for differentiating lung cancer from benign lung diseases. The significantly enriched microbiota varied with the different pathological subtypes of lung adenocarcinoma. Streptococcus mitis, Burkholderia oklahomensis and Burkholderia latens displayed a trend of increasing from the benign lung disease group to the AIS group, MIA group and IAC group, whereas Lactobacillus plantarum showed a downward trend. Conclusion: Changes in the abundance of lung microbiota are closely related to the development of infiltrating adenocarcinoma. Our findings provide new insights into the relationship between the changes in lung microbiota and the development of lung cancer. Full article

(This article belongs to the Special Issue Microbial Ecology in Health and Disease 2.0)

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17 pages, 2131 KiB

Open AccessArticle

Online Left-Hemispheric In-Phase Frontoparietal Theta tACS Modulates Theta-Band EEG Source-Based Large-Scale Functional Network Connectivity in Patients with Schizophrenia: A Randomized, Double-Blind, Sham-Controlled Clinical Trial

by Ta-Chuan Yeh, Cathy Chia-Yu Huang, Yong-An Chung, Sonya Youngju Park, Jooyeon Jamie Im, Yen-Yue Lin, Chin-Chao Ma, Nian-Sheng Tzeng and Hsin-An Chang

Biomedicines 2023, 11(2), 630; https://doi.org/10.3390/biomedicines11020630 - 20 Feb 2023

Cited by 2 | Viewed by 2006

Abstract

EEG studies indicated that schizophrenia patients had increased resting-state theta-band functional connectivity, which was associated with negative symptoms. We recently published the first study showing that theta (6 Hz) transcranial alternating current stimulation (tACS) over left prefrontal and parietal cortices during a working [...] Read more.

EEG studies indicated that schizophrenia patients had increased resting-state theta-band functional connectivity, which was associated with negative symptoms. We recently published the first study showing that theta (6 Hz) transcranial alternating current stimulation (tACS) over left prefrontal and parietal cortices during a working memory task for accentuating frontoparietal theta-band synchronization (in-phase theta-tACS) reduced negative symptoms in schizophrenia patients. Here, we hypothesized that in-phase theta-tACS can modulate theta-band large-scale networks connectivity in schizophrenia patients. In this randomized, double-blind, sham-controlled trial, patients received twice-daily, 2 mA, 20-min sessions of in-phase theta-tACS for 5 consecutive weekdays (n = 18) or a sham stimulation (n = 18). Resting-state electroencephalography data were collected at baseline, end of stimulation, and at one-week follow-up. Exact low resolution electromagnetic tomography (eLORETA) was used to compute intra-cortical activity. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity across 84 cortical regions at theta frequency (5–7 Hz). EEG data from 35 patients were analyzed. We found that in-phase theta-tACS significantly reduced the LPS between the posterior cingulate (PC) and the parahippocampal gyrus (PHG) in the right hemisphere only at the end of stimulation relative to sham (p = 0.0009, corrected). The reduction in right hemispheric PC-PHG LPS was significantly correlated with negative symptom improvement at the end of the stimulation (r = 0.503, p = 0.039). Our findings suggest that in-phase theta-tACS can modulate theta-band large-scale functional connectivity pertaining to negative symptoms. Considering the failure of right hemispheric PC-PHG functional connectivity to predict improvement in negative symptoms at one-week follow-up, future studies should investigate whether it can serve as a surrogate of treatment response to theta-tACS. Full article

(This article belongs to the Special Issue Neuromodulation: From Theories to Therapies)

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10 pages, 1483 KiB

Open AccessArticle

Uveitis in Children: The Role of Biological Agents in Its Management

by Jamel Corredores, Brice Vofo and Radgonde Amer

Biomedicines 2023, 11(2), 629; https://doi.org/10.3390/biomedicines11020629 - 20 Feb 2023

Cited by 3 | Viewed by 1593

Abstract

We aimed to determine medium and long-term effects of TNF-α inhibitors in patients with pediatric uveitis. This was a retrospective review of medical charts. Included were 50 patients (84 eyes). Mean age at diagnosis was 7.22 ± 4.04 years. At baseline (time of [...] Read more.

We aimed to determine medium and long-term effects of TNF-α inhibitors in patients with pediatric uveitis. This was a retrospective review of medical charts. Included were 50 patients (84 eyes). Mean age at diagnosis was 7.22 ± 4.04 years. At baseline (time of initiation of biologic therapy), all patients had active uveitis. Complete control of uveitis was achieved in 84.52% (n = 71) of eyes, after a median of 3 months (IQR 2 months). Mean LogMAR BCVA at baseline was 0.23 ± 0.44; it remained stable at 12 and 24 months. At baseline, 64% of patients were treated with oral corticosteroids, this decreased to 29.5% at 12 months (p = 0.001) and to 21.9% at 24 months (p < 0.001). Mean time to prednisone dose of ≤0.2 mg/kg/day was 8.1 ± 2.02 months after baseline. A total of 40.5% of eyes were treated with topical steroids at baseline and this significantly decreased to 5.8% at 12 months. Multiple linear regression model was calculated to predict moderate and severe visual loss; only presenting visual acuity accounted for a unique variance in the model. In conclusion, TNF-α inhibitors achieved rapid disease control while enabling a remarkable steroid-sparing effect in children suffering from chronic uveitis. Presenting visual acuity was the sole predictor of moderate to severe visual loss. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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11 pages, 1411 KiB

Open AccessArticle

Simultaneous Quantification of Ivacaftor, Tezacaftor, and Elexacaftor in Cystic Fibrosis Patients’ Plasma by a Novel LC–MS/MS Method

by Federica Pigliasco, Alessia Cafaro, Manuela Stella, Giammarco Baiardi, Sebastiano Barco, Nicoletta Pedemonte, Claudia D’Orsi, Federico Cresta, Rosaria Casciaro, Carlo Castellani, Maria Grazia Calevo, Francesca Mattioli and Giuliana Cangemi

Biomedicines 2023, 11(2), 628; https://doi.org/10.3390/biomedicines11020628 - 20 Feb 2023

Cited by 4 | Viewed by 2053

Abstract

The new breakthrough cystic fibrosis (CF) drug combination of ivacaftor (IVA), tezacaftor (TEZ), and elexacaftor (ELX), namely “caftor” drugs, directly modulates the activity and trafficking of the defective CF transmembrane conductance regulator protein (CFTR) underlying the CF disease. The role of therapeutic drug [...] Read more.

The new breakthrough cystic fibrosis (CF) drug combination of ivacaftor (IVA), tezacaftor (TEZ), and elexacaftor (ELX), namely “caftor” drugs, directly modulates the activity and trafficking of the defective CF transmembrane conductance regulator protein (CFTR) underlying the CF disease. The role of therapeutic drug monitoring (TDM) of caftor drugs in clinical settings has recently been established. The availability of reliable and robust analytical methods for the quantification of IVA, TEZ, and ELX is essential to support dose–concentration–effect studies. We have developed and validated a new liquid chromatography–tandem mass spectrometry (LC–MS/MS) for the rapid and simultaneous quantification of IVA, TEZ, and ELX from the plasma of CF patients. The method was based on a rapid extraction protocol from 50 μL human plasma and separation on a reversed-phase C-18 HPLC column after the addition of deuterated internal standards. Accurate analyte quantification using multiple reaction monitoring (MRM) detection was then obtained using a Thermofisher Quantiva triple-quadrupole MS coupled to an Ultimate 3000 UHPLC. The method has been validated following international (EMA) guidelines for bioanalytical method validation and has been tested on plasma samples from 62 CF patients treated with the three-drug combination IVA/TEZ/ELX, marketed as Kaftrio^® or Trikafta^®, in steady-state condition. The assay was linear over wide concentration ranges (0.008–12 mg/L) in plasma for IVA, TEZ, and ELX, suitable for a broad range of plasma concentrations, and accurate and reproducible in the absence of matrix effects. The stability of analytes for at least 30 days at room temperature could allow for cost-effective shipment and storage. On the same day of sample collection, a sweat test was evaluated for 26 associated patients’ samples, FEV1 (%) for 58, and BMI was calculated for 62. However, Spearman correlation showed no correlation between C_through plasma concentrations of analytes (IVA, TEZ, ELX) and sweat test, FEV1 (%), or BMI. Our method proved to be suitable for TDM and could be helpful in assessing dose–concentration–response correlations in larger studies. Full article

(This article belongs to the Special Issue Advances in Therapeutic Drug Monitoring)

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3 pages, 172 KiB

Open AccessEditorial

Recent Prospective in CAR T-Based Therapy for Solid and Hematological Malignancies

by Hany E. Marei and Carlo Cenciarelli

Biomedicines 2023, 11(2), 627; https://doi.org/10.3390/biomedicines11020627 - 20 Feb 2023

Viewed by 1304

Abstract

Given that CAR-T cell therapy is effective in CD19-positive blood malignancies, it offers great hope for a variety of aggressive tumors that have thus far shown very little response to available therapies [...] Full article

(This article belongs to the Special Issue Recent Prospectives in CAR T-based Therapy for Solid and Hematological Malignancies)

22 pages, 7294 KiB

Open AccessArticle

Evaluation of CAR-T Cells’ Cytotoxicity against Modified Solid Tumor Cell Lines

by Aigul Kh. Valiullina, Ekaterina A. Zmievskaya, Irina A. Ganeeva, Margarita N. Zhuravleva, Ekaterina E. Garanina, Albert A. Rizvanov, Alexey V. Petukhov and Emil R. Bulatov

Biomedicines 2023, 11(2), 626; https://doi.org/10.3390/biomedicines11020626 - 19 Feb 2023

Cited by 22 | Viewed by 2504

Abstract

In recent years, adoptive cell therapy has gained a new perspective of application due to the development of technologies and the successful clinical use of CAR-T cells for the treatment of patients with malignant B-cell neoplasms. However, the efficacy of CAR-T therapy against [...] Read more.

In recent years, adoptive cell therapy has gained a new perspective of application due to the development of technologies and the successful clinical use of CAR-T cells for the treatment of patients with malignant B-cell neoplasms. However, the efficacy of CAR-T therapy against solid tumor remains a major scientific and clinical challenge. In this work, we evaluated the cytotoxicity of 2nd generation CAR-T cells against modified solid tumors cell lines—lung adenocarcinoma cell line H522, prostate carcinoma PC-3M, breast carcinoma MDA-MB-231, and epidermoid carcinoma A431 cell lines transduced with lentiviruses encoding red fluorescent protein Katushka2S and the CD19 antigen. A correlation was demonstrated between an increase in the secretion of proinflammatory cytokines and a decrease in the confluence of tumor cells’ monolayer. The proposed approach can potentially be applied to preliminarily assess CAR-T cell efficacy for the treatment of solid tumors and estimate the risks of developing cytokine release syndrome. Full article

(This article belongs to the Special Issue Roles of T Cells in Immunotherapy)

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10 pages, 1046 KiB

Open AccessBrief Report

Blood Markers of Biological Age Evaluates Clinic Complex Medical Spa Programs

by Fedor I. Isaev, Arsenii R. Sadykov and Alexey Moskalev

Biomedicines 2023, 11(2), 625; https://doi.org/10.3390/biomedicines11020625 - 19 Feb 2023

Viewed by 2338

Abstract

Background: Kivach Clinic has developed a special medical spa program to prevent aging-related conditions in metabolic, cardio-vascular, and neurological states. Spa programs modify diet, physical activity, and lymphatic drainage, as it deteriorates with aging. We investigated its influence on the blood markers of [...] Read more.

Background: Kivach Clinic has developed a special medical spa program to prevent aging-related conditions in metabolic, cardio-vascular, and neurological states. Spa programs modify diet, physical activity, and lymphatic drainage, as it deteriorates with aging. We investigated its influence on the blood markers of biological age of patients during their stay to objectify the potential of spa treatment for influencing the risk of age-related events. Methods: The artificial deep learning model Aging.ai 3.0 was based on blood parameters. The change in the biological age of 43 patients was assessed after their 14-day spa treatment at Kivach Clinic. Results: Biological age decreased in 29 patients (median decrease: 8 years, mean: 8.83 years), increased in 10 patients (median increase: 3 years, mean: 5.33 years) and remained unchanged in 4 patients. Overall mean values for the entire patient group were as follows: median value was −3 years, and mean was −4.79 ± 1.2 years (p-value = 0.00025, t-test). Conclusions: The capability of specially selected medical spa treatment to reduce human biological age (assessed by Aging.AI 3.0) has been established. Full article

(This article belongs to the Topic New Insights on Chronic Illness: Pathogenesis, Prevalence, Prevention, and Systemic Therapies)

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13 pages, 914 KiB

Open AccessArticle

Ocular Behçet Disease—Clinical Manifestations, Treatments and Outcomes According to Age at Disease Onset

by Michael Ostrovsky, Amir Rosenblatt, Salam Iriqat, Abdallah Shteiwi, Yael Sharon, Michal Kramer, Vicktoria Vishnevskia-Dai, Shaul Sar, Yosif Boulos, Oren Tomkins-Netzer, Natalie Lavee, Yael Ben-Arie-Weintrob, Hadas Pizem, Tamar Hareuveni-Blum, Marina Schneck, Raz Gepstein, Dua Masarwa, Nakhoul Nakhoul, Erez Bakshi, Shiri Shulman, Michaella Goldstein, Dan Ramon, Marina Anouk and Zohar Habot-Wilner Show full author list Hide full author list

Biomedicines 2023, 11(2), 624; https://doi.org/10.3390/biomedicines11020624 - 19 Feb 2023

Cited by 2 | Viewed by 1674

Abstract

Behçet disease (BD) is a multisystemic disease that commonly involves the eyes. Although it affects patients in all age groups, data on ocular disease by age of onset are limited. This retrospective, multicenter study aimed to compare epidemiology, systemic and ocular manifestations, treatments [...] Read more.

Behçet disease (BD) is a multisystemic disease that commonly involves the eyes. Although it affects patients in all age groups, data on ocular disease by age of onset are limited. This retrospective, multicenter study aimed to compare epidemiology, systemic and ocular manifestations, treatments and outcomes between three age groups: juvenile (<18 years), adult (18–39 years) and late (≥40 years) disease onset. The study included 175 ocular BD patients (303 eyes) from Israel and Palestine: juvenile-onset (n = 25, 14.3%), adult-onset (n = 120, 68.6%) and late-onset (n = 30, 17.1%). Most patients in all groups were male. Systemic manifestations were similar in all groups. Systemic co-morbidities were more common in late-onset patients. Bilateral panuveitis was the most common ocular manifestation in all patients. Non-occlusive retinal vasculitis, peripheral vessel occlusions, cataract and elevated intraocular pressure were found more commonly among juvenile-onset eyes. Anterior uveitis and macular ischemia were most common among late-onset eyes, while branch retinal vein occlusion was most common in adult and late-onset eyes. All patients were treated with corticosteroids. Methotrexate, immunomodulatory combinations and biologic treatments were more commonly used for juvenile-onset patients. All groups had a similar visual outcome. Our study showed that patients with ocular BD have varied ocular manifestations and require different treatments according to age of disease onset, but visual outcome is similar. Full article

(This article belongs to the Special Issue Chronic Noninfectious Uveitis: From Pathophysiology to Management)

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13 pages, 1646 KiB

Open AccessArticle

Smooth Muscle Cells of Dystrophic (mdx) Mice Are More Susceptible to Hypoxia; The Protective Effect of Reducing Ca²⁺ Influx

by Arkady Uryash, Alfredo Mijares, Eric Estève, Jose A. Adams and Jose R. Lopez

Biomedicines 2023, 11(2), 623; https://doi.org/10.3390/biomedicines11020623 - 19 Feb 2023

Cited by 1 | Viewed by 1210

Abstract

Duchenne muscular dystrophy (DMD) is an inherited muscular disorder caused by mutations in the dystrophin gene. DMD patients have hypoxemic events due to sleep-disordered breathing. We reported an anomalous regulation of resting intracellular Ca²⁺ ([Ca²⁺]_i) in vascular smooth [...] Read more.

Duchenne muscular dystrophy (DMD) is an inherited muscular disorder caused by mutations in the dystrophin gene. DMD patients have hypoxemic events due to sleep-disordered breathing. We reported an anomalous regulation of resting intracellular Ca²⁺ ([Ca²⁺]_i) in vascular smooth muscle cells (VSMCs) from a mouse (mdx) model of DMD. We investigated the effect of hypoxia on [Ca²⁺]_i in isolated and quiescent VSMCs from C57BL/10SnJ (WT) and C57BL/10ScSn-Dmd (mdx) male mice. [Ca²⁺]_i was measured using Ca²⁺-selective microelectrodes under normoxic conditions (95% air, 5% CO₂) and after hypoxia (glucose-free solution aerated with 95% N2-5% CO₂ for 30 min). [Ca²⁺]_i in mdx VSMCs was significantly elevated compared to WT under normoxia. Hypoxia-induced [Ca²⁺]_i overload, which was significantly greater in mdx than in WT VSMCs. A low Ca²⁺ solution caused a reduction in [Ca²⁺]_i and prevented [Ca²⁺]_i overload secondary to hypoxia. Nifedipine (10 µM), a Ca²⁺ channel blocker, did not modify resting [Ca²⁺]_i in VSMCs but partially prevented the hypoxia-induced elevation of [Ca²⁺]_i in both genotypes. SAR7334 (1 µM), an antagonist of TRPC3 and TRPC6, reduced the basal and [Ca²⁺]_i overload caused by hypoxia. Cell viability, assessed by tetrazolium salt (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, was significantly reduced in mdx compared to WT VSMCs. Pretreatment with SAR7341 increases cell viability in normoxic mdx (p < 0.001) and during hypoxia in WT and mdx VSMCs. These results provide evidence that the lack of dystrophin makes VSMCs more susceptible to hypoxia-induced [Ca²⁺]_i overload, which appears to be mediated by increased Ca²⁺ entry through L-type Ca²⁺ and TRPC channels. Full article

(This article belongs to the Collection Feature Papers in Cell Biology and Pathology)

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18 pages, 2168 KiB

Open AccessArticle

A Retrospective Clinical Trial Regarding Oral Rehabilitation Diagnosis Strategies Based on Stomatognathic System Pathology

by Iulian Costin Lupu, Laura Elisabeta Checherita, Magda Ecaterina Antohe, Ovidiu Stamatin, Silvia Teslaru, Tudor Hamburda, Eugenia Larisa Tarevici, Bogdan Petru Bulancea, Mioara Trandafirescu, Cristina Gena Dascalu, Magdalena Cuciureanu, Irina Gradinaru, Lucian Stefan Burlea and Alina Elena Jehac

Biomedicines 2023, 11(2), 622; https://doi.org/10.3390/biomedicines11020622 - 19 Feb 2023

Cited by 1 | Viewed by 1470

Abstract

Introduction: Orofacial pain is a common occurrence in daily dental practice; it is frequently attributed to temporomandibular dysfunction, one of its major causes, followed by pathology of the salivary glands, without avoiding interference at the level of the pain pathways caused by complications [...] Read more.

Introduction: Orofacial pain is a common occurrence in daily dental practice; it is frequently attributed to temporomandibular dysfunction, one of its major causes, followed by pathology of the salivary glands, without avoiding interference at the level of the pain pathways caused by complications of periodontal pathology. The main objective of this study is to identify an important cause of pain in the oral–maxillofacial territory by quantifying the changes at the salivary glandular level using stereological methods. The secondary objective of the present research is to identify the implications of periodontal changes as a consequence of salivary quantitative and qualitative changes, quantified using periodontal indices, on the balance of the temporomandibular joint, dysfunction of it being an important cause of facial pain and having a profound impact on the complex oral rehabilitation algorithm of each clinical case, a condition evaluated with the analysis of the results of the Souleroy questionnaire. Material and methods: In a retrospective study, we evaluated the clinical results obtained after applying complex rehabilitation treatment to 35 subjects, 20 women and 15 men with salivary and TMJ dysfunctions, selected between 2020 and 2021 from the Clinic of Maxillofacial Surgery, Iasi. Results and discussion: The most common symptoms of temporomandibular disorders (TMDs) that were identified through the Souleroy questionnaire were pain and different types of damage to the masticatory muscles. The most significant changes in elders are reported in the case of serous cells, which reduced their percentage volume from 46.7% to 37.4%. Conclusion: As regards stereological analysis in conjunction with histological images, there were significant changes in diameters, perimeters, and longitudinal axes in the adult patients as opposed to the elderly patients, which were also influenced by the type of pathology at this level. The scores recorded on the diagnostic Souleroy scale indicated a large number of patients with low efficiency and maximum stress levels: 20.0% in level 1, 25.7% in level 2, and 25.7% in level 3. Full article

(This article belongs to the Special Issue Chronic Pain: From Prevention to Therapeutic Strategies)

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12 pages, 287 KiB

Open AccessArticle

The Associations between Polysomnographic Parameters and Memory Impairment among Patients with Obstructive Sleep Apnea: A 10-Year Hospital-Based Longitudinal Study

by Wei-Chen Chien, Chung-Wei Lin, Ching-Kuan Liu, Shiou-Lan Chen, Mei-Chuan Chou and Chung-Yao Hsu

Biomedicines 2023, 11(2), 621; https://doi.org/10.3390/biomedicines11020621 - 18 Feb 2023

Cited by 3 | Viewed by 1932

Abstract

Obstructive sleep apnea (OSA) has been associated with cognitive decline via several mechanisms, including intermittent hypoxemia, sleep fragmentation, and neuroinflammation. The neurological consequences of OSA have evolved into a major biopsychosocial concern in the elderly, especially memory impairment. We aimed to identify the [...] Read more.

Obstructive sleep apnea (OSA) has been associated with cognitive decline via several mechanisms, including intermittent hypoxemia, sleep fragmentation, and neuroinflammation. The neurological consequences of OSA have evolved into a major biopsychosocial concern in the elderly, especially memory impairment. We aimed to identify the polysomnographic (PSG) parameters capable of predicting memory impairment among OSA patients at or over age 50 with OSA. We reviewed the 10-year electronic medical records of OSA patients and compared the initial PSG parameters between those presenting and not presenting self-reported memory impairment. We conducted subgroup analyses based on OSA severity and performed multivariate analysis to correlate PSG parameters with memory impairment. The result showed that 25 out of the 156 (16%) investigated patients experienced self-reported memory impairment during follow-up. As compared to OSA patients without self-reported memory impairment, those reported with self-reported memory impairment had a higher oxygen desaturation index (ODI) (23.9 ± 17.8 versus 18.2 ± 12.0, p = 0.048). Regarding the associations between apnea-hypopnea index (AHI) as well as ODI and self-reported memory impairment among OSA subgroups classified by severity, the associations were only evident in the severe OSA subgroup in both univariate (p < 0.001; p = 0.005) and multivariate analyses (p = 0.014; p = 0.018). We concluded that AHI and ODI are the most relevant PSG parameters in predicting memory impairment in severe OSA patients. Full article

(This article belongs to the Special Issue New Insights in Chronic Sleep Disorders)

13 pages, 1727 KiB

Open AccessReview

Allergic Reactions to Vaccines in Children: From Constituents to Specific Vaccines

by Ming-Han Tsai and Chih-Yung Chiu

Biomedicines 2023, 11(2), 620; https://doi.org/10.3390/biomedicines11020620 - 18 Feb 2023

Cited by 1 | Viewed by 2194

Abstract

Vaccination is an essential public health measure that helps to reduce the burden of infectious diseases in children. Although vaccines have an excellent safety record and the association of severe allergic reactions is rare, public concerns about vaccine safety can lead to incomplete [...] Read more.

Vaccination is an essential public health measure that helps to reduce the burden of infectious diseases in children. Although vaccines have an excellent safety record and the association of severe allergic reactions is rare, public concerns about vaccine safety can lead to incomplete vaccination coverage in children with or without allergies. Therefore, it is important to understand the mechanisms and implications of allergic reactions to vaccines and define strategies to manage them to provide the safest care for vaccine recipients. In this review, we provide an overview on the types of allergic reactions that can occur after vaccination, including those caused by various vaccine constituents. We also discuss the mechanisms underlying these allergic reactions and the recommended diagnosis and management strategies for children with a history of suspected allergic reactions to vaccines. An improved understanding of allergic reactions to vaccines can aid in the enhancement of the safety and effectiveness of vaccination. Full article

(This article belongs to the Special Issue Hypersensitivity to Drugs and Vaccines: Molecular Basis and Translational Research)

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21 pages, 739 KiB

Open AccessReview

Gut-on-a-Chip Models: Current and Future Perspectives for Host–Microbial Interactions Research

by Moran Morelli, Dorota Kurek, Chee Ping Ng and Karla Queiroz

Biomedicines 2023, 11(2), 619; https://doi.org/10.3390/biomedicines11020619 - 18 Feb 2023

Cited by 10 | Viewed by 4254

Abstract

The intestine contains the largest microbial community in the human body, the gut microbiome. Increasing evidence suggests that it plays a crucial role in maintaining overall health. However, while many studies have found a correlation between certain diseases and changes in the microbiome, [...] Read more.

The intestine contains the largest microbial community in the human body, the gut microbiome. Increasing evidence suggests that it plays a crucial role in maintaining overall health. However, while many studies have found a correlation between certain diseases and changes in the microbiome, the impact of different microbial compositions on the gut and the mechanisms by which they contribute to disease are not well understood. Traditional pre-clinical models, such as cell culture or animal models, are limited in their ability to mimic the complexity of human physiology. New mechanistic models, such as organ-on-a-chip, are being developed to address this issue. These models provide a more accurate representation of human physiology and could help bridge the gap between clinical and pre-clinical studies. Gut-on-chip models allow researchers to better understand the underlying mechanisms of disease and the effect of different microbial compositions on the gut. They can help to move the field from correlation to causation and accelerate the development of new treatments for diseases associated with changes in the gut microbiome. This review will discuss current and future perspectives of gut-on-chip models to study host-microbial interactions. Full article

(This article belongs to the Special Issue Gut Dysbiosis: Molecular Mechanisms and Therapies 2.0)

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19 pages, 1541 KiB

Open AccessReview

The Role of Autophagy in Breast Cancer Metastasis

by Hye Min Kim and Ja Seung Koo

Biomedicines 2023, 11(2), 618; https://doi.org/10.3390/biomedicines11020618 - 18 Feb 2023

Cited by 4 | Viewed by 3343

Abstract

Patient morbidity and mortality is significantly increased in metastatic breast cancer. The metastasis process of breast cancer is very complicated and is delicately controlled by various factors. Autophagy is one of the important regulatory factors affecting metastasis in breast cancer by engaging in [...] Read more.

Patient morbidity and mortality is significantly increased in metastatic breast cancer. The metastasis process of breast cancer is very complicated and is delicately controlled by various factors. Autophagy is one of the important regulatory factors affecting metastasis in breast cancer by engaging in cell mobility, metabolic adaptation, tumor dormancy, and cancer stem cells. Here, we discuss the effects of autophagy on metastasis in breast cancer and assess the potential use of autophagy modulators for metastasis treatment. Full article

(This article belongs to the Collection Autophagy in Cancer and Metastasis)

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16 pages, 1728 KiB

Open AccessReview

HIV Latency and Nanomedicine Strategies for Anti-HIV Treatment and Eradication

by Mickensone Andre, Madhavan Nair and Andrea D. Raymond

Biomedicines 2023, 11(2), 617; https://doi.org/10.3390/biomedicines11020617 - 18 Feb 2023

Cited by 5 | Viewed by 2317

Abstract

Antiretrovirals (ARVs) reduce Human Immunodeficiency Virus (HIV) loads to undetectable levels in infected patients. However, HIV can persist throughout the body in cellular reservoirs partly due to the inability of some ARVs to cross anatomical barriers and the capacity of HIV-1 to establish [...] Read more.

Antiretrovirals (ARVs) reduce Human Immunodeficiency Virus (HIV) loads to undetectable levels in infected patients. However, HIV can persist throughout the body in cellular reservoirs partly due to the inability of some ARVs to cross anatomical barriers and the capacity of HIV-1 to establish latent infection in resting CD4⁺ T cells and monocytes/macrophages. A cure for HIV is not likely unless latency is addressed and delivery of ARVs to cellular reservoir sites is improved. Nanomedicine has been used in ARV formulations to improve delivery and efficacy. More specifically, researchers are exploring the benefit of using nanoparticles to improve ARVs and nanomedicine in HIV eradication strategies such as shock and kill, block and lock, and others. This review will focus on mechanisms of HIV-1 latency and nanomedicine-based approaches to treat HIV. Full article

(This article belongs to the Topic Nanomedical Research)

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Open AccessArticle

Oral Administration of Vitamin D3 Prevents Corneal Damage in a Knock-Out Mouse Model of Sjögren’s Syndrome

by Maria Consiglia Trotta, Hildegard Herman, Cornel Balta, Marcel Rosu, Alina Ciceu, Bianca Mladin, Carlo Gesualdo, Caterina Claudia Lepre, Marina Russo, Francesco Petrillo, Gorizio Pieretti, Francesca Simonelli, Settimio Rossi, Michele D’Amico and Anca Hermenean

Biomedicines 2023, 11(2), 616; https://doi.org/10.3390/biomedicines11020616 - 18 Feb 2023

Cited by 1 | Viewed by 1662

Abstract

Background: Vitamin D deficiency has been associated with dry eye development during Sjögren’s syndrome (SS). Here, we investigated whether repeated oral vitamin D3 supplementation could prevent the corneal epithelium damage in an SS mouse model. Methods: 30 female mouse knock-out for the thrombospondin [...] Read more.

Background: Vitamin D deficiency has been associated with dry eye development during Sjögren’s syndrome (SS). Here, we investigated whether repeated oral vitamin D3 supplementation could prevent the corneal epithelium damage in an SS mouse model. Methods: 30 female mouse knock-out for the thrombospondin 1 gene were randomized (six per group) in untreated mice euthanized at 6 weeks as negative control (C−) or at 12 weeks as the positive control for dry eye (C+). Other mice were sacrificed after 6 weeks of oral vitamin D3 supplementation in the drinking water (1000, 8000, and 20,000 IU/kg/week, respectively). Results: The C+ mice showed alterations in their corneal epithelial morphologies and thicknesses (p < 0.01 vs. C−), while the mice receiving 8000 (M) and 20,000 (H) IU/kg/week of vitamin D3 showed preservation of the corneal epithelium morphology and thickness (p < 0.01 vs. C+). Moreover, while the C+ mice exhibited high levels and activity of corneal tumor necrosis factor alpha converting enzyme (TACE), neovascularization and fibrosis markers; these were all reduced in the M and H mice. Conclusions: Oral vitamin D3 supplementation appeared to counteract the negative effect of TACE on corneal epithelium in a mouse model of SS-associated dry eye. Full article

(This article belongs to the Special Issue Recent Advances in Vitamin D)

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Biomedicines, Volume 11, Issue 2 (February 2023) – 412 articles

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