Hypogonadism contributes to limb skeletal muscle atrophy by increasing rates of muscle protein breakdown.  https://www.selleckchem.com/products/pclx-001-ddd86481.html  Androgen depletion increases markers of the autophagy protein breakdown pathway in the limb muscle that persist throughout the diurnal cycle. However, the regulatory signals underpinning the increase in autophagy markers remain ill-defined. The purpose of this study was to characterize changes to autophagy regulatory signals in the limb skeletal muscle following androgen depletion. Male mice were subjected to a castration surgery or a sham surgery as a control. Seven weeks post-surgery, a subset of mice from each group was sacrificed every 4 hr over a 24 hr period. Protein and mRNA from the Tibialis Anterior (TA) were subjected to Western blot and RT-PCR. Consistent with an overall increase in autophagy, the phosphorylation pattern of Uncoordinated Like Kinase 1 (ULK1) (Ser555) was elevated throughout the diurnal cycle in the TA of castrated mice. Factors that induce the progression of autophagy were also increased in the TA following androgen depletion including an increase in the phosphorylation of c-Jun N-terminal Kinase (JNK) (Thr183/Tyr185) and an increase in the ratio of BCL-2 Associated X (BAX) to B-cell lymphoma 2 (BCL-2). Moreover, we observed an increase in the protein expression pattern of p53 and the mRNA of the p53 target genes Cyclin-Dependent Kinase Inhibitor 1A (p21) and Growth Arrest and DNA Damage Alpha (Gadd45a), which are known to increase autophagy and induce muscle atrophy. These data characterize novel changes to autophagy regulatory signals in the limb skeletal muscle following androgen deprivation.A large number of long non-coding RNAs have been confirmed to play vital roles in regulating various biological processes. Abnormal expression of growth arrest-specific transcript 5 (GAS5) is reported to be involved in the development of atherosclerosis (AS). This work is to explore the detailed mechanism underling how GAS5 regulates AS progression. We found that the abundance of GAS5 was markedly increased, and miR-135a was decreased in AS patient serums and ox-LDL-induced human THP-1 cells dose and time dependently. Interference of GAS5 suppressed inflammation and oxidative stress induced by ox-LDL in THP-1 cells. Mechanistically, GAS5 acted as a molecular sponge of microRNA-135a (miR-135a). Rescue assays indicated that knockdown of miR-135a partially rescued small interference RNA for GAS5-inhibited inflammatory cytokines release and oxidative stress in ox-LDL-triggered THP-1 cells. In conclusion, the absence of GAS5-inhibited inflammatory response and oxidative stress induced by ox-LDL in THP-1 cells via sponging miR-135a, providing a deep insight into the molecular target for AS treatment.Shortly after the identification of a novel coronavirus, the coronavirus disease 2019, or COVID-19, a global pandemic was declared. There have been conflicting data about the severity of COVID-19 disease course in pregnant women, with most US data suggesting an increase in severity and increased need for hospitalization and intubation in obstetric patients. In the general population, the disease is more common among racial and ethnic minority populations, and severity is increased with comorbid conditions and obesity. The purpose of this study is to characterize COVID-19 infection in pregnancy in a population of women getting prenatal care at an urban safety-net hospital. Beginning in April, 2020, all women were tested at admission for delivery, and additionally as an outpatient if presenting with COVID-19 symptoms. In three months, there were 208 discrete women tested and 23 (11.1%) who were positive for COVID-19. The incidence of COVID-19 was 5.1% in asymptomatic women being screened upon admission to the hospital. There was a high prevalence of obesity (68.2%) and other comorbid conditions (43.5%) in this population, and all patients were racial/ethnic minorities. Despite these risk factors, the patients uniformly had either mild or asymptomatic disease. No symptomatic patients required hospitalization for their infection. In this population of pregnant women at high risk for severe COVID-19 infection, only mild disease was observed.The aim of this study was to evaluate the effects of glutamine supplementation or exercise on gastric emptying and intestinal inflammation in rats with ulcerative colitis (UC). Strength exercise consisted of jump training 4 × 10 repetitions/5 days a week/8 weeks with progressive overload. Endurance exercise consisted of swimming without overload for a period of 1 h a day/5 days a week/8 weeks. Another group (sedentary) of animals was supplemented with L-glutamine (1 g/kg of body weight) orally for 8 weeks before induction of UC. Colitis was induced by intra-colonic administration of 1 mL of 4% acetic acid. We assessed gastric emptying, macroscopic and microscopic scoring, oxidative stress markers, and IL-1β, IL-6, and (TNF-α) levels. The UC significantly increased (p less then 0.05) the gastric emptying compared with the saline control group. We observed a significantly decrease (p less then 0.05) in body weight gain in UC rats compared with the control groups. Both exercise interventions and L-glutamine supplementation significantly prevented (p less then 0.05) weight loss compared with the UC group. Strength and endurance exercises significantly prevented (p less then 0.05) the increase of microscopic scores and oxidative stress (p less then 0.05). L-glutamine supplementation in UC rats prevented hemorrhagic damage and improved oxidative stress markers (p less then 0.05). Strength and endurance exercises and glutamine decreased the concentrations of inflammatory cytokines IL-1β, IL-6, and TNF-α compared with the UC group (p less then 0.05). Strength and endurance exercises and L-glutamine supplementation prevented intestinal inflammation and improved cytokines and oxidative stress levels without altering gastric dysmotility in rats with UC.
  Cytokine storm, an uncontrolled overproduction of inflammatory cytokines contributing to an aberrant systemic inflammatory response, is a major pathological feature of acute respiratory distress syndromes being severe manifestations of COVID-19, thus highlighting its potential as a biomarker and therapeutic target for COVID-19. We aimed to determine associations of circulating levels of inflammatory cytokines with severity and mortality of COVID-19 by systematic review and meta-analysis.
 
  A comprehensive literature search in electronic databases consisting of PubMed, Scopus, and Cochrane Library and in a hand searching of reference lists from inception to July 31, 2020, was performed using the following search terms COVID-19, interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α). Mean difference (MD) from individual studies was pooled using a random-effects model. Quality assessment, publication bias, meta-regression, subgroup, and sensitivity analyses were performed.
 
  A total of 6212 COVID-19 patients from 24 eligible studies were included.