Search

Alcohol misuse in people with human immunodeficiency virus (HIV) (PWH) and chronic binge alcohol (CBA) administration in simian immunodeficiency virus (SIV)-infected macaques are associated with increased physical frailty and impaired functional skeletal muscle mass, respectively. Previous studies by our group demonstrate that muscle-enriched microRNAs (myomiRs) are differentially expressed in skeletal muscle (SKM) from CBA-administered SIV-infected male macaques and their altered expression contributes to impaired differentiation of SKM stem cells or myoblasts. MicroRNAs can be transported in extracellular vesicles (EVs) to mediate numerous cellular responses through intercellular communication. The present study tested the hypothesis that EV-mediated delivery of miR-206 can ameliorate CBA-mediated decreases in myoblast differentiation. Myoblasts were isolated from SKM of female SIV-infected, antiretroviral therapy-treated macaques that received either CBA (2.5 g/kg/day, CBA/SIV) or water (VEH/SIV) for 14.5 mo. Myotube and myotube-derived EV myomiR expression, including miR-206, was lower in the CBA/SIV group. Overexpression of miR-206 decreased histone deacetylase 4 ( HDAC4 ) and paired box 7 ( PAX7 ) expression in myotubes and increased fusion index, a differentiation index, in CBA/SIV-derived myotubes. Similarly, EV-mediated delivery of miR-206 increased both fusion index and myotube density of CBA/SIV-derived myoblasts. These results support the potential therapeutic utility of EVs in delivering myomiRs to improve SKM stem cell differentiation. NEW & NOTEWORTHY Alcohol decreases skeletal muscle myoblast differentiation into myotubes, which is associated with decreased expression of microRNA-206. We show that delivering exogenous miR-206 in plasma-derived extracellular vesicles (EVs) to myoblasts derived from alcohol-administered animals increases myotube differentiation. These results support the potential therapeutic utility of EVs in delivering muscle-enriched microRNAs to improve skeletal muscle stem cell differentiation.

Aims: As the interactions of alcohol and HIV/SIV infection and their impact on liver metabolic homeostasis remain to be fully elucidated, this study aimed to determine alcohol-mediated hepatic adaptations of metabolic pathways in SIV/ART-treated female rhesus macaques fed a nutritionally balanced diet., Methods: Macaques were administered chronic binge alcohol (CBA; 13-14 g ethanol/kg/week for 14.5 months; n = 7) or vehicle (VEH; n = 8) for 14.5 months. Livers were excised following an overnight fast. Gene and protein expression, enzymatic activity, and lipid content were determined using frozen tissue and histological staining was performed using paraffin-embedded tissue., Results: CBA/SIV macaques showed increased hepatic protein expression of electron transport Complex III and increased gene expression of glycolytic (phosphofructokinase and aldolase) and gluconeogenic (pyruvate carboxylase) enzymes and of genes involved in lipid turnover homeostasis (perilipin 1, peroxisome proliferator-activated receptor gamma, carbohydrate responsive binding protein, and acetyl-CoA carboxylase B) as compared to that of livers from the VEH/SIV group. Plasma triglyceride concentration had a significant positive association with liver triglyceride content in the CBA/SIV group., Conclusions: These results reflect CBA-associated alterations in expression of proteins and genes involved in glucose and lipid metabolism homeostasis without significant evidence of steatosis or dysglycemia. Whether these changes predispose to greater liver pathology upon consumption of a high fat/high sugar diet that is more aligned with dietary intake of PWH and/or exposure to additional environmental factors warrants further investigation., (© The Author(s) 2024. Medical Council on Alcohol and Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: With an ongoing demand for transplantable organs, optimization of donor management protocols, specifically in trauma populations, is important for obtaining a high yield of viable organs per patient. Endocrine management of brain-dead potential organ donors (BPODs) is controversial, leading to heterogeneous clinical management approaches. Previous studies have shown that when levothyroxine was combined with other treatments, including steroids, vasopressin, and insulin, BPODs had better organ recovery and survival outcomes were increased for transplant recipients., Aim: To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma patients., Methods: A retrospective review of adult BPODs from a single level 1 trauma center over ten years was performed. Exclusion criteria included patients who were not solid organ donors, patients who were not declared brain dead (donation after circulatory death), and patients who did not receive steroids in their hospital course. Levothyroxine and steroid administration, the number of organs donated, the types of organs donated, and demographic information were recorded. Univariate analyses were performed with P < 0.05 considered to be statistically significant., Results: A total of 88 patients met inclusion criteria, 69 (78%) of whom received levothyroxine and steroids (ST/LT group) vs 19 (22%) receiving steroids without levothyroxine (ST group). No differences were observed between the groups for gender, race, pertinent injury factors, age, or other hormone therapies used ( P > 0.05). In the ST/LT group, 68.1% ( n = 47) donated a high yield (3-5) of organ types per donor compared to 42.1% ( n = 8) in the ST group ( P = 0.038). There was no difference in the total number of organ types donated between the groups ( P = 0.068)., Conclusion: This study suggests that combining levothyroxine and steroid administration increases high-yield organ donation per donor in BPODs in the trauma patient population. Limitations to this study include the retrospective design and the relatively small number of organ donors who met inclusion criteria. This study is unique in that it mitigates steroid administration as a confounding variable and focuses specifically on the adjunctive use of levothyroxine., Competing Interests: Conflict-of-interest statement: Dr. Smith reports personal fees from Prytime Medical, personal fees from Aroa Biosurgery, grants from 3M, grants from MiMedX, and grants from Dynocardia outside the submitted work., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The synthesis of proinflammatory leukotrienes implicated in asthma, allergic rhinitis, and atherosclerosis is initiated by the enzyme 5-lipoxygenase (5-LOX). The crystal structure of human Stable-5-LOX revealed a conformation where the catalytic iron was inaccessible to bulk solvent as two aromatic residues on a conserved helix-α2 (Hα2) plugged the substrate access portal. Whether 5-LOX can also adopt a more open conformation has not been resolved. Here, we present a new conformation of 5-LOX where Hα2 adopts an elongated conformation equivalent to that described in other animal lipoxygenase structures. Our observation of the sigmoidal kinetic behavior of 5-LOX, which is indicative of positive cooperativity, is consistent with a substrate-induced conformational change that shifts the ensemble of enzyme populations to favor the catalytically competent state. Strategic point mutations along Hα2 designed to unlock the closed conformation and elongate Hα2 resulted in improved kinetic parameters, altered limited proteolysis data, and a drastic reduction in the length of the lag phase yielding the most active Stable-5-LOX to date. Structural predictions by AlphaFold2 of these variants statistically favor an elongated Hα2 and reinforce a model in which improved kinetic parameters correlate with a more readily adopted open conformation. Taken together, these data provide valuable insights into the synthesis of leukotrienes., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Obesity is a disease characterized by an inflammatory process in the adipose tissue due to diverse infiltrated immune cells, an increased secretion of proinflammatory molecules, and a decreased secretion of anti-inflammatory molecules. On the other hand, obesity increases the risk of several diseases, such as cardiovascular diseases, diabetes, and cancer. Their treatment is based on nutritional and pharmacological strategies. However, natural products are currently implemented as complementary and alternative medicine (CAM). Polyphenols and fiber are naturally compounds with potential action to reduce inflammation through several pathways and play an important role in the prevention and treatment of obesity, as well as in other non-communicable diseases. Hence, this review focuses on the recent evidence of the molecular mechanisms of polyphenols and dietary fiber, from Scopus, Science Direct, and PubMed, among others, by using key words and based on recent in vitro and in vivo studies.

Silymarin (SM) is a mixture of flavolignans extracted from the seeds of species derived from Silybum marianum , commonly known as milk thistle or St. Mary'sthistle. These species have been widely used in the treatment of liver disorders in traditional medicine since ancient times. Several properties had been attributed to the major SM flavolignans components, identified as silybin, isosilybin, silychristin, isosilychristin, and silydianin. Previous research reported antioxidant and protective activities, which are probably related to the activation of the nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2), known as a master regulator of the cytoprotector response. Nrf2 is a redox-sensitive nuclear transcription factor able to induce the downstream-associated genes. The disruption of Nrf2 signaling has been associated with different pathological conditions. Some identified phytochemicals from SM had shown to participate in the Nrf2 signaling pathway; in particular, they have been suggested as activators that disrupt interactions in the Keap1-Nrf2 system, but also as antioxidants or with additional actions regarding Nrf2 regulation. Thus, the study of these molecules makes them appear attractive as novel targets for the treatment or prevention of several diseases., Competing Interests: The authors declare no conflict of interest.

Cardiovascular diseases (CVDs) are the leading causes of death in the world, and epidemiological evidence points to dietary habits, stress, and obesity as major risk factors promoting pathological conditions like atherosclerosis, hypertension, and thrombosis. Current therapeutic approaches for CVDs rely on lifestyle changes and/or the use of drug agents. However, since the efficacy of such interventions is often limited by poor compliance and/or significant side effects, continued research on new preventive and therapeutic approaches is much needed. Our study is aimed to determine the bioaccessibility, total content of phenolic compounds, and antioxidant capacity (DPPH·, ABTS ·+ ) of a methanolic extract from Mangifera indica L. leaves (MEM), and its lipid-lowering effect on an induced dyslipidemia model in Wistar rats. Our results showed that mangiferin is the main component of MEM. The extract showed a total content of polyphenol compounds of 575.28 gallic acid equivalents per dry matter basis (GAE/g db), antioxidant activity 77.68 μmol Trolox equivalents per gram (TE/g) db as measured by DPPH· and 20,630 μmol TE/g db by ABTS ·+ , and 12% of phenolic compounds were bioaccessible, and 100 mg/kg of MEM reduced hyperlipidemia levels induced in Wistar rats. Further study on the potential use of MEM as a nutraceutical to prevent CVDs in high-fat diet consumers is required.