Zinc Alleviates Diabetic Muscle Atrophy via Modulation of the SIRT1/FoxO1 Autophagy Pathway Through GPR39.

Background: Muscle atrophy is a severe complication of diabetes, with autophagy playing a critical role in its progression. Zinc has been shown to alleviate hyperglycaemia and several diabetes-related complications, but its direct role in mediating diabetic muscle atrophy remains unclear. This study explores the potential role of zinc in the pathogenesis of diabetic muscle atrophy.

Causal role of immune cells in muscle atrophy: mendelian randomization study.

Immune system and inflammation had a great influence on the progression of muscle atrophy. However, the causal relationship with specific immune cell traits remained uncertain. The aim of this study was to elucidate the genetic influences on these associations, providing insights into the underlying mechanisms of muscle atrophy.

JAK inhibition with tofacitinib rapidly increases contractile force in human skeletal muscle.

Reduction in muscle contractile force associated with many clinical conditions incurs serious morbidity and increased mortality. Here, we report the first evidence that JAK inhibition impacts contractile force in normal human muscle. Muscle biopsies were taken from patients who were randomized to receive tofacitinib (n = 16) or placebo (n = 17) for 48 h.

Canagliflozin inhibits PASMCs proliferation via regulating SGLT1/AMPK signaling and attenuates artery remodeling in MCT-induced pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) was a devastating disease characterized by artery remodeling, ultimately resulting in right heart failure. The aim of this study was to investigate the effects of canagliflozin (CANA), a sodium-glucose cotransporter 2 inhibitor (SGLT2i) with mild SGLT1 inhibitory effects, on rats with PAH, as well as its direct impact on pulmonary arterial smooth muscle cells (PASMCs). PAH rats were induced by injection of monocrotaline (MCT) (40 mg/kg), followed by four weeks of treatment with CANA (30 mg/kg/day) or saline alone.

[Application of extended trochanter osteotomy wire fixation combined with autologous bone graft in revision of total hip arthroplasty].

Objective: To investigate the clinical effect of using lengthened trochanteric osteotomy wire fixation combined with autologous bone graft in patients undergoing revision total hip arthroplasty.

Methods: From December 2010 to December 2018, 18 patients underwent revision of total hip arthroplasty with extended trochanteric osteotomy wire fixation and autogenous bone graft, including 8 males and 10 females with an average age of (78.89±3.

[A follow up study on the treatment of tibial fractures with intramedullary interlocking nail through the suprapatellar approach].

Objective: To investigate the short-term effect of suprapatellar interlocking intramedullary nail in the treatment of tibial fractures.

Methods: Eighty patients with tibial fractures treated from January 2016 to June 2018 were treated with interlocking intramedullary nail, who were divided into observation group (suprapatellar approach) and control group (patellar ligament approach) according to different surgical approaches. There were 40 cases in the observation group, including 28 males and 12 females, aged 28 to 67 years with a mean of (46.

Logistic regression analysis of drug compliance and influencing factors in elderly osteoporosis patients.

A cross-sectional study was conducted to understand the medication compliance of elderly osteoporosis patients and to further analyze the influencing factors of drug compliance. The elderly osteoporosis patients who were admitted to the First People's Hospital of Huzhou, Zhejiang from March 2015 to January 2017 were selected as the research subjects. Subsequently, the three months, six months and 12 months of follow-up were performed from the group of subjects who prescribe anti-osteoporosis drugs to determine the patient's medication status.

mTORC1 underlies age-related muscle fiber damage and loss by inducing oxidative stress and catabolism.

Aging leads to skeletal muscle atrophy (i.e., sarcopenia), and muscle fiber loss is a critical component of this process.

The Signaling Network Resulting in Ventilator-induced Diaphragm Dysfunction.

Mechanical ventilation (MV) is a life-saving measure for those incapable of adequately ventilating or oxygenating without assistance. Unfortunately, even brief periods of MV result in diaphragm weakness (i.e.

Smad3 initiates oxidative stress and proteolysis that underlies diaphragm dysfunction during mechanical ventilation.

Prolonged use of mechanical ventilation (MV) leads to atrophy and dysfunction of the major inspiratory muscle, the diaphragm, contributing to ventilator dependence. Numerous studies have shown that proteolysis and oxidative stress are among the major effectors of ventilator-induced diaphragm muscle dysfunction (VIDD), but the upstream initiator(s) of this process remain to be elucidated. We report here that periodic diaphragm contraction via phrenic nerve stimulation (PNS) substantially reduces MV-induced proteolytic activity and oxidative stress in the diaphragm.

CRISPR/Cas-mediated genome editing to treat EGFR-mutant lung cancer: a personalized molecular surgical therapy.

While substantial progress has been made in the treatment of lung cancer with the development of tyrosine kinase inhibitors (TKIs) that target tumor‐driving mutations in the epidermal growth factor receptor (EGFR), nearly all patients treated with TKIs ultimately develop drug resistance due to resistance‐conferring genomic mutations. CRISPR/Cas9‐mediated genome editing is a powerful new technique that allows precise changes to be made to cells’ genomes. This technology is currently used widely in research laboratories, but it has yet to make an impact in the clinics.

The JAK-STAT pathway is critical in ventilator-induced diaphragm dysfunction.

Mechanical ventilation (MV) is one of the lynchpins of modern intensive-care medicine and is life saving in many critically ill patients. Continuous ventilator support, however, results in ventilation-induced diaphragm dysfunction (VIDD) that likely prolongs patients' need for MV and thereby leads to major associated complications and avoidable intensive care unit (ICU) deaths. Oxidative stress is a key pathogenic event in the development of VIDD, but its regulation remains largely undefined.

mTORC1 promotes denervation-induced muscle atrophy through a mechanism involving the activation of FoxO and E3 ubiquitin ligases.

Skeletal muscle mass and function are regulated by motor innervation, and denervation results in muscle atrophy. The activity of mammalian target of rapamycin complex 1 (mTORC1) is substantially increased in denervated muscle, but its regulatory role in denervation-induced atrophy remains unclear. At early stages after denervation of skeletal muscle, a pathway involving class II histone deacetylases and the transcription factor myogenin mediates denervation-induced muscle atrophy.

Coronin 6 regulates acetylcholine receptor clustering through modulating receptor anchorage to actin cytoskeleton.

The maintenance of a high density of neurotransmitter receptors at the postsynaptic apparatus is critical for efficient neurotransmission. Acetylcholine receptors (AChRs) are neurotransmitter receptors densely packed on the postsynaptic muscle membrane at the neuromuscular junction (NMJ) via anchoring onto the actin cytoskeletal network. However, how the receptor-associated actin is coordinately regulated is not fully understood.

[Comparison between pavlik harness and bryant traction for femoral shaft fractures in infants].

Objective: To compare clinical effects between Pavlik harness and Bryant traction in treating femoral shaft fractures in infants,including the time of hospitalization, expense of treatment, complications,time of bone union.

Methods: From May 2005 to August 2010,the clinical data of 42 infants with femoral shaft fractures were retrospectively analyzed. Among the patients, 23 cases were treated with Pavlik harness(Pavlik harness group),there were 14 males and 9 females,ranging in age from 1 to 12 months with an average of (5.

Diaphragm muscle atrophy in the mouse after long-term mechanical ventilation.

Introduction: Mechanical ventilation (MV) is a life-saving measure, but full ventilator support causes ventilator-induced diaphragm atrophy (VIDA). Previous studies of VIDA have relied on human biopsies or a rat model. If MV can induce diaphragm atrophy in mice, then mechanistic study of VIDA could be explored via genetic manipulation.

Oxidative stress-responsive microRNA-320 regulates glycolysis in diverse biological systems.

Glycolysis is the initial step of glucose catabolism and is up-regulated in cancer cells (the Warburg Effect). Such shifts toward a glycolytic phenotype have not been explored widely in other biological systems, and the molecular mechanisms underlying the shifts remain unknown. With proteomics, we observed increased glycolysis in disused human diaphragm muscle.

Intrinsic apoptosis in mechanically ventilated human diaphragm: linkage to a novel Fos/FoxO1/Stat3-Bim axis.

Mechanical ventilation (MV) is a life-saving measure in many critically ill patients. However, prolonged MV results in diaphragm dysfunction that contributes to the frequent difficulty in weaning patients from the ventilator. The molecular mechanisms underlying ventilator-induced diaphragm dysfunction (VIDD) remain poorly understood.

A histone deacetylase 4/myogenin positive feedback loop coordinates denervation-dependent gene induction and suppression.

Muscle activity contributes to formation of the neuromuscular junction and affects muscle metabolism and contractile properties through regulated gene expression. However, the mechanisms coordinating these diverse activity-regulated processes remain poorly characterized. Recently, it was reported that histone deacetylase 4 (HDAC4) can mediate denervation-induced myogenin and nicotinic acetylcholine receptor gene expression.

Activity-dependent gene regulation in skeletal muscle is mediated by a histone deacetylase (HDAC)-Dach2-myogenin signal transduction cascade.

Muscle activity contributes to muscle development and function largely by means of regulated gene expression. Many genes crucial to neuromuscular synapse formation, such as MuSK and nAChRs, are induced before muscle innervation or after muscle denervation, and this induction requires expression of the E-box binding, basic helix-loop-helix muscle-specific transcription factor, myogenin (Mgn). The mechanism by which muscle activity is coupled to gene expression is poorly defined.

Characterization of a muscle-specific enhancer in human MuSK promoter reveals the essential role of myogenin in controlling activity-dependent gene regulation.

Neuromuscular synaptogenesis is initiated by the release of agrin from motor neurons and the activation of the receptor tyrosine kinase, MuSK, in the postsynaptic membrane. MuSK gene expression is regulated by nerve-derived agrin and muscle activity. Agrin stimulates synapse-specific MuSK gene expression by activating GABP(alphabeta) transcription factors in endplate-associated myonuclei.

CaM kinase II-dependent phosphorylation of myogenin contributes to activity-dependent suppression of nAChR gene expression in developing rat myotubes.

During development of the neuromuscular junction (NMJ), extrajunctional expression of genes, whose products are destined for the synapse, is suppressed by muscle activity. One of the best-studied examples of activity-dependent gene regulation in muscle are those encoding nicotinic acetylcholine receptor (nAChR) subunits. We recently showed that nAChR gene expression is inhibited by calcium/calmodulin-dependent protein kinase II (CaMKII) and CaMKII inhibitors block activity-dependent suppression of these genes.