S-ketamine is recognized as a rapid-acting antidepressant, exerting its effects primarily through activation of the mTOR signaling pathway in the brain, which plays a key role in neuroplasticity. Given the shared molecular mechanisms between brain and skeletal muscle, we investigated whether S-ketamine can also modulate regulatory proteins involved in muscle protein synthesis (MPS) and muscle protein breakdown (MPB) in skeletal muscle. Adult female Flinders Sensitive Line rats received a single intraperitoneal injection of S-ketamine (20mg/kg) or saline, and soleus and extensor digitorum longus (EDL) muscles were collected two hours post-injection for protein analysis using Western blot. S-ketamine significantly increased phosphorylated mTOR (p-mTORSer2448) in both soleus and EDL, while total ULK1 protein expression was elevated in soleus. These findings suggest that S-ketamine can stimulate mTOR-related signaling in skeletal muscle, potentially enhancing MPS, although the activation was limited to specific signaling proteins. The results provide novel insights into the peripheral effects of S-ketamine beyond the central nervous system, highlighting the potential relevance for skeletal muscle physiology and anabolic regulation. Future studies are warranted to determine the temporal dynamics of these effects, the dose-dependence, and the impact of repeated administration on muscle hypertrophy. Overall, this study expands understanding of S-ketamine's systemic actions and raises new questions regarding its potential as a modulator of skeletal muscle protein metabolism.

Corilagin is a type of ellagitannin that exhibits inhibitory effects on the proliferation of vascular smooth muscle cells (VSMCs). However, the mechanism underlying this inhibition remains unclear. The study utilized a balloon injury-induced rat carotid artery model to investigate the effects of corilagin on the prevention of restenosis following vascular injury. VSMCs were isolated from the carotid arteries of rats post-balloon injury and treated with PDGF-BB and various concentrations of corilagin. Western blotting was employed to assess the phosphorylation levels of MAPK in VSMCs. Two weeks of treatment with corilagin or a control vehicle was conducted on the injury model, and the area of neointima formation and collagen density in the intima were evaluated histopathologically. Our results revealed that corilagin dose-dependently inhibited VSMCs migration and phenotypic transformation, suppressing extracellular matrix deposition by upregulating matrix metalloproteinases (MMPs) and reducing collagen (COL) protein synthesis. In vivo, this result showed a significantly lower intimal thickness and intima/media ratio in the corilagin group compared to the control group. Corilagin inhibits the proliferation and migration of VSMCs by reducing the phosphorylation of ERK, p38, and JNK, and this effect can be weakened by the ERK/MAPK pathway activator C6 ceramide. Corilagin may be a promising drug that could provide a new approach to preventing and treating post-interventional restenosis.

Fluorescence Lifetime Imaging Microscopy (FLIM) of endogenous fluorophores has recently emerged as a powerful, marker-free, and non-invasive tool for investigating cellular metabolism. This cutting-edge imaging technique provides valuable insights into cellular energy states by measuring the fluorescence lifetimes of intrinsically fluorescent redox cofactors. The lifetimes of these cofactors reflect their binding states to enzymes, thus indicating enzymatic activity within specific metabolic pathways. As a result, FLIM can help to reveal the overall redox status of the cell and, to some extent, shifts between oxidative phosphorylation and glycolysis. The application of FLIM in metabolic research has shown significant progress across a diverse range of pathological contexts, including cancer, diabetes, neurodegenerative disorders, and various forms of cardiopathology.The aim of this mini-review is to introduce the methodology of NAD(P)H and FAD/FMN FLIM, outline its underlying principles, and demonstrate its ability to reveal changes in cellular metabolism. Additionally, this mini-review highlights FLIM's potential for understanding cellular redox states, detecting metabolic shifts in various disease models, and contributing to the development of therapeutic strategies.

Recent years have seen enormous progress in the field of advanced therapeutics for the progressive muscle wasting disease Duchenne muscular dystrophy (DMD). In particular, four antisense oligonucleotide (ASO) therapies targeting various DMD-causing mutations have achieved FDA approval, marking major milestones in the treatment of this disease. These compounds are designed to induce alternative splicing events that restore the translation reading frame of the dystrophin gene, leading to the generation of internally-deleted, but mostly functional, pseudodystrophin proteins with the potential to compensate for the genetic loss of dystrophin. However, the efficacy of these compounds is very limited, with delivery remaining a key obstacle to effective therapy. There is therefore an urgent need for improved ASO technologies with better efficacy, and with applicability to a wider range of patient mutations. Here we discuss recent developments in ASO therapies for DMD, and future prospects with a focus on ASO chemical modification and bioconjugation strategies.

In the lower urinary tract, coordinated function between the bladder and urethra is essential for normal micturition, requiring smooth muscle contraction and relaxation in a tightly regulated cycle. During the bladder filling phase, the bladder remains relaxed while the urethra stays contracted to prevent leakage. During voiding, this coordination reverses, and the bladder contracts to expel urine while the relaxed urethra allows urine flow. These functions are essential for proper micturition and two key molecular regulators of this process are the large-conductance calcium activated potassium (BK) channels and ryanodine receptors (RyRs), both of which modulate smooth muscle excitability and calcium dynamics. This review provides an overview of the roles of BK channels and RyR mediated signaling in regulating smooth muscle activity in the bladder and urethra, with a focus on their contributions to lower urinary tract physiology and pathophysiology. BK channels act as negative feedback modulators, dampening myogenic and nerve-evoked contractions of the detrusor and urethra. RyRs play a role in regulating intracellular calcium signaling that supports both muscle relaxation and contraction. This review highlights alterations in the function of these channels in lower urinary tract dysfunction, and as potential targets for other factors such as environmental exposures to disrupt voiding function. BK channels and RyRs are plausible targets for therapeutic strategies aimed at improving bladder and urethra function in certain patients, particularly those with lower urinary tract symptoms caused by factors such as aging and environmental chemical exposure.

In some neurological conditions, like Parkinson’s disease (PD) and Cerebral Palsy (CP), as well as with ageing, muscle spindles have been mentioned as participating in the pathological response of observed muscles. The aim of this review has therefore been to examine what is known about muscle spindle receptors, their function and how they are involved in regulating precise muscle movement in relation to these two conditions. Data from acoustic myography (AMG) studies with healthy controls (HC), CP and PD subjects have been re-examined with a view to identifying possible effects of changes in muscle movement which could be related to muscle spindle receptor function. Studies of muscle spindles have shown that during shortening and lengthening contractions the fusimotor system is activated differently with different discharge frequencies and sensitivities. With increasing age comes a loss of precise proprioception, something that coincides with a change in the AMG E-score towards lower values, indicating a reduced level of coordination and efficiency of muscle use. With PD and CP there is likewise a documented decrease in proprioception, also showing lower E-values than age-matched HC subjects. We conclude that the decrease in proprioception observed in these subjects must be partly due to a change in the muscle spindle / C-centre feedback system.

The muscular dystrophy with myositis (mdm) mouse model results in a severe muscular dystrophy due to an 83-amino-acid deletion in the N2A region of titin, an expanded sarcomeric protein that functions as a molecular spring which senses and modulates the response to mechanical forces in cardiac and skeletal muscles. ANKRD1 is one of the muscle ankyrin repeat domain proteins (MARPs) a family of titin-associated, stress-response molecules and putative transducers of stretch-induced signaling in skeletal muscle. The aberrant over-activation of Nuclear factor Kappa B (NF-κB) and the Ankyrin-repeat domain containing protein 1 (ANKRD1) occurs in several models of progressive muscle disease including Duchenne muscular dystrophy. We hypothesized that mechanical regulation of ANKRD1 is mediated by NF-κB activation in skeletal muscles and that this mechanism is perturbed by small deletion of the stretch-sensing titin N2A region in the mdm mouse. We applied static mechanical stretch of the mdm mouse diaphragm and cyclic mechanical stretch of C2C12 myotubes to examine the interaction between NF-κΒ and ANKRD1 expression utilizing Western blot and qRTPCR. As seen in skeletal muscles of other severe muscular dystrophies, an aberrant increased basal expression of NF-κB and ANKRD1 were observed in the diaphragm muscles of the mdm mice. Our data show that in the mdm diaphragm, basal levels of NF-κB are increased, and pharmacological inhibition of NF-κB does not alter basal levels of ANKRD1. Alternatively, NF-κB inhibition did alter stretch-induced ANKRD1 upregulation. These data show that NF-κB activity is at least partially responsible for the stretch-induced expression of ANKRD1.

Neuromuscular junctions are the synapses between motor neurons and skeletal muscle fibers, which mediate voluntary muscle movement. Since neuromuscular junctions are also tightly associated with the capping function of terminal Schwann cells, these synapses have been classically regarded as tripartite chemical synapses. Although evidences from sympathetic innervation of neuromuscular junctions was described approximately a century ago, the essential presence and functional relevance of sympathetic contribution to the maintenance and modulation of neuromuscular junctions was demonstrated only recently. These findings shed light on the pathophysiology of different clinical conditions and can optimize surgical and clinical treatment modalities for skeletal muscle disorders.

The transcriptional regulation of skeletal muscle (SKM) development (myogenesis) has been documented for over 3 decades and served as a paradigm for tissue-specific cell type determination and differentiation. Myogenic stem cells (MuSC) in embryos and adult SKM are regulated by the transcription factors Pax3 and Pax7 for their stem cell characteristics, while their lineage determination and terminal differentiation are both dictated by the myogenic regulatory factors (MRF) that comprise Mrf4, Myf5, Myogenin, and MyoD. The myocyte enhancer factor Mef2c is activated by MRF during terminal differentiation and collaborates with them to promote myoblast fusion and differentiation. Recent studies have found critical regulation of these myogenic transcription factors at mRNA level, including subcellular localization, stability, and translational regulation. Therefore, the regulation of Pax3/7, MRFs and Mef2c mRNAs by RNA-binding factors and non-coding RNAs (ncRNA), including microRNAs and long non-coding RNAs (lncRNA), will be the focus of this review and the impact of this regulation on myogenesis will be further addressed. Interestingly, the stem cell characteristics of MuSC has been found to be critically regulated by ncRNAs, implying the involvement of ncRNAs in SKM homeostasis and regeneration. Current studies have further identified that some ncRNAs are implicated in the etiology of some SKM diseases and can serve as valuable tools/indicators for prediction of prognosis. The roles of ncRNAs in the MuSC biology and SKM disease etiology will also be discussed in this review.