Experimental Biology and Medicine最新文献

Myogenin (MyoG) is a core myogenic transcription factor that orchestrates myoblast differentiation and myofiber maturation and has been increasingly implicated in skeletal muscle degeneration and rhabdomyosarcoma, yet its global research landscape has not been systematically characterized. In this study, we performed a bibliometric analysis of MyoG-related publications from 2004 to 2024 retrieved from the Web of Science Core Collection. A total of 402 articles authored by 2,402 researchers from 1,148 institutions across 165 countries and regions were analyzed using VOSviewer, CiteSpace and R-based bibliometric tools. We quantified annual publication output, identified leading countries, institutions, authors and journals, and reconstructed collaboration, co-citation and keyword co-occurrence networks to delineate thematic evolution. The global pattern showed a multipolar structure dominated by the United States and China, with European institutions forming an additional hub and emerging countries contributing with growing but comparatively lower impact. Research hotspots exhibited a clear progression from early work on molecular mechanisms (DNA binding, MyoD family interactions, chromatin remodelling) toward regenerative biology (satellite cell regulation, muscle regeneration) and, more recently, disease-oriented studies focused on muscle atrophy, Duchenne muscular dystrophy and rhabdomyosarcoma. Landmark co-cited studies established MyoG as an indispensable regulator of skeletal muscle differentiation and highlighted its expanding relevance in pathological remodelling and therapeutic targeting. Future work is expected to concentrate on decoding MyoG-centred regulatory networks in degenerative muscle disease, integrating single-cell and spatial transcriptomics with functional genomics and multi-omics, and developing MyoG-based diagnostic and targeted therapeutic strategies. Despite the intrinsic limitations of single-database and citation-based approaches, this study provides a panoramic overview of two decades of MyoG research and offers a structured framework to guide future basic and translational investigations in muscle biology and oncology.

Neuroblastoma constitutes a solid tumor in pediatric populations, characterized by a dismal prognosis and a scarcity of effective therapeutic interventions. Medicinal flora from South Africa represents valuable sources of bioactive phytometabolites with potential relevance to neuroblastoma. This study employed an integrated workflow merging untargeted UPLC-MS/MS metabolomics, mitochondrial functional assays, and in silico absorption, distribution, metabolism, and excretion (ADME) prediction to systematically identify bioactive metabolites from Acorus calamus and Lippia javanica with activity against SH-SY5Y neuroblastoma cells. Cytotoxic effects were quantified utilizing the CCK-8 assay, while mitochondrial membrane potential (ΔΨm) was conducted through JC-1 flow cytometry. Untargeted UPLC-MS/MS profiling yielded metabolomic fingerprints, through PCA, PLS-DA, and OPLS-DA. ADME and drug-likeness were predicted using SWISSADME. Both plant extracts exhibited dose-dependent inhibition of SH-SY5Y cell viability, with IC₅₀ values determined at 0.2886 μg/μL for A. calamus and 0.3066 μg/μL for L. javanica. The ΔΨm assessment indicated enhanced mitochondrial polarization (68.2% and 65.4% compared to 58.8% in untreated controls), implying modulation of mitochondrial functional status. Metabolomic profiling unveiled distinct phytochemical signatures, including flavonoids, phenolics, jasmonates, and alkaloids, exhibiting significant species-level differentiation (F = 936.71, R ² = 0.989, p = 0.005). Notable metabolites such as isopropyl β-glucoside, 6β-hydroxymethandienone, and 7-epi-12-hydroxyjasmonic acid demonstrated favorable ADME characteristics and permeability across the blood-brain barrier. This investigation elucidates that A. calamus and L. javanica possess potential efficacy against neuroblastoma, underscoring the translational potential of African medicinal flora in pediatric oncology and necessitating further preclinical exploration.

This study established a type 1 diabetes (T1DM) mouse model via intraperitoneal injection of streptozotocin (STZ) and examined the effect of regulatory T (Treg) cells on the gut microbiota by comparing its composition and diversity across three groups: control, T1DM, and Treg-treated mice. Forty-one 8-week-old male C57BL/6 mice under specific pathogen-free conditions were divided into a healthy control group, an untreated T1DM group, and a Treg treatment group (receiving low, medium, or high doses). T1DM was induced by administering a low-dose STZ injection over five consecutive days, with diabetes confirmation defined as a blood glucose level ≥300 mg/dL. CD4+CD25+ Treg cells isolated from spleens of healthy mice were used for treatment. Fecal samples collected on days 0, 14, and 34 from three randomly selected mice per group were subjected to 16S rRNA gene sequencing targeting the V3-V4 regions. The results showed significant differences in both alpha and beta diversity among the groups. Dominant bacterial families varied: Ruminococcaceae and others were enriched in the Treg treatment group, Muribaculaceae in the control group, and Lactobacillaceae in the untreated T1DM group. Genus-level abundances also shifted over time. Firmicutes abundance positively correlated with Treg levels (r = 0.70, p = 0.0433) but negatively with IFN-γ, whereas Cyanobacteria exhibited the opposite correlation. The Firmicutes/Bacteroidetes ratio was higher in T1DM mice than in controls and lower in the Treg-treated group. Metabolic pathway analysis indicated that two-component systems and ABC transporters were more prevalent in T1DM mice. In summary, Treg cell treatment altered the diversity, composition, dominant taxa, and Firmicutes/Bacteroidetes ratio of the gut microbiota compared with untreated T1DM mice.

Heterozygous pathogenic variants in ATP2B1 (encoding PMCA1) cause autosomal dominant intellectual developmental disorder 66 (MRD66; OMIM #619910). To date, only 12 pathogenic de novo ATP2B1 variants have been reported in MRD66. This study aimed to identify the genetic etiology in a Chinese infant with a neurodevelopmental disorder characterized by early-onset seizures and global developmental delay (GDD) and functionally characterize a novel ATP2B1 missense variant. Trio-based whole-exome sequencing revealed a heterozygous de novo ATP2B1 variant (c.2140A>C, p.Thr714Pro) in the proband. The proband presented with infantile spasms, GDD (Gesell Developmental Quotient: 65-74), and severe growth restriction (height/weight <-2 SD). To investigate the variant's pathogenicity, the wild-type (WT) and mutant ATP2B1 constructs, N-terminally tagged with mScarlet, were transfected into HEK293T cells. Confocal imaging demonstrated profound cytoplasmic mislocalization of the p.Thr714Pro mutant protein, contrasting sharply with the characteristic plasma membrane localization of WT ATP2B1. Measurement of intracellular Ca²⁺ levels using Fluo-4 AM showed a significant 2.07-fold increase in basal Ca²⁺ levels in cells expressing the mutant compared to WT. This finding expands the spectrum of ATP2B1 variants associated with MRD66 and confirms calcium dyshomeostasis as the core pathomechanism. This case of MRD66 demonstrates a very early onset of seizures, consistent with the recognized phenotypic variability and the critical role of PMCA1 in early neurodevelopment.

Peripheral nerve injury (PNI) presents a significant clinical challenge, frequently leading to long-term neuromuscular dysfunction, muscle atrophy, fibrosis, and chronic pain. Traditional repair strategies, including microsurgical reconnection and neurotrophic support, often yield limited functional recovery, especially in cases of delayed or incomplete reinnervation. In this context, skeletal muscle reprogramming-defined as the intentional modulation of cellular fate, function, or metabolic state in muscle-resident cells-has emerged as a promising strategy to enhance regenerative outcomes. This process involves transcriptional, epigenetic, and metabolic interventions targeting myogenic progenitors, fibro-adipogenic progenitors (FAPs), satellite cells (MuSCs), and the broader muscle microenvironment. Recent studies demonstrate that reprogramming strategies can mitigate denervation-induced muscle atrophy, delay fibrotic remodeling, promote neuromuscular junction (NMJ) reconstruction, and even stimulate endogenous nerve regrowth via retrograde signaling. Mechanistic insights have uncovered pivotal roles for signaling pathways such as Wnt/β-catenin, TGF-β, Notch, and HDAC-regulated chromatin dynamics. Furthermore, innovations in small molecule cocktails, CRISPR-based transcriptional reactivation, and metabolic rewiring have expanded the therapeutic toolkit for muscle preservation and regeneration. This review comprehensively examines the molecular mechanisms, therapeutic roles, and translational challenges of skeletal muscle reprogramming in the context of PNI. We explore how muscle-targeted interventions can address complications of denervation, improve the efficacy of nerve repair, and offer a synergistic axis of regeneration when integrated with nerve-centric strategies. Finally, we identify key knowledge gaps and outline future research directions required to translate reprogramming-based therapies into clinical practice.

The study aims to explore the potential role of ferroptosis and hypoxia in dilated cardiomyopathy (DCM). GSE120895, GSE17800, GSE112556, ferroptosis-related genes (FRGs), and hypoxia-related genes (HRGs) were downloaded from the public dataset. Ferroptosis- and hypoxia-related differentially expressed genes (DEGs) and DCM-related genes were obtained. Subsequentially, hub genes were identified, and their diagnostic values were assessed. Next, immune cell infiltration analysis, drug prediction and molecular docking were carried out based on the hub genes. Finally, the hub gene TGM2 was preliminarily verified in vitro. A total of 18 ferroptosis- and hypoxia-related DEGs and 315 DCM-related genes were acquired. Subsequently, 6 hub genes (PPP1R15A, TGM2, MAP3K5, USP7, SESN2, and ADAM23) were obtained and have potential diagnostic value. Immune infiltration analysis showed that CD56dim natural killer (NK) cells, macrophages, monocytes, NK cells, and NK T cells were significantly infiltrated in DCM patients. Furthermore, the lncRNA-miRNA-mRNA network was constructed. Moreover, 16 drugs were predicted, and the binding energy between atorvastatin and TGM2 was -2.79 kcal/mol. In vitro verification showed that TGM2, PPP1R15A and SESN2 were up-regulated in DOX-induced AC16 cardiomyocyte injury. After knocking down TGM2, the expressions of α-actinin and cTnT were increased, and the expression level of HIF-1α was inhibited. Dual luciferase assay showed that hsa-miR-291-5p exerted its regulatory effect by directly binding to TGM2. Flow cytometry results showed that TGM2 had no significant effect on the apoptosis of AC16 cells. Our findings may provide new ideas for the diagnosis and treatment of DCM.

Peritoneal fibrosis is an adverse effect of cancer therapy leading to progressive organ failure. L-Glutamine supplementation has been shown to attenuate fibrosis and improve wound healing in several types of tissue injuries. The aim of this study was to evaluate the effects of this supplementation on key components of the peritoneal fibrovascular tissue induced by implants in mice treated with 5-Fluorouracil (5-FU) C57BL/6 mice received three intraperitoneal doses of immunosuppressant (60, 40, and 40 mg/kg) on non-consecutive days prior to implantation of polyether-polyurethane sponges into the peritoneal cavity. The group treated with L-Glutamine received 150 mg/kg/day for 7 days (oral gavage) starting 24 h after implantation and the control group received filtered water. Eight days after implantation, implants were removed and processed for inflammatory, angiogenic, and fibrogenic markers. Flow cytometry results showed that L-Glutamine decreased (48%) the frequency/influx of total intra-implant cells. The remaining cell population in the treated group had more neutrophils, lymphocytes, and macrophages than in the control. Immunohistochemistry analysis showed fewer Caspase-3-positive cells in the treated group. Myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAG) activities, TNF-α levels, and mast cell numbers were decreased in the implants of the L-Glutamine-treated group compared with the control. Similarly, angiogenesis (VEGF levels and number of blood vessels) was attenuated by L-Glutamine. Supplementation also decreased the amount of intra-implant collagen and TGF-β1 levels. These results indicate that L-Glutamine attenuates critical inflammatory-angiogenesis and profibrotic pathways involved in fibrosis development in immunosuppression conditions, supporting its potential as an adjunct therapeutic strategy for managing peritoneal healing in cancer.

We explored pharmacotherapeutic response patterns of lipopolysaccharides (LPS)-induced pneumonia and sepsis as direct and indirect acute lung injury (ALI), and efficacy of a combined surfactant (S) and inhaled nitric oxide (iNO), simulating critical care, in rabbits of post-neonatal infancy. Anaesthetized 7-day-old healthy rabbits were injected intratracheally (IT) or intravenously (IV) with LPS (15-20-25 mg/kg, L) or saline as a control (C), and subjected to initial 2-hour mechanical ventilation (MV) with standardized tidal volume to induce ALI. They were then treated with S (200 mg/kg) and iNO (10 ppm, N), or not, thereby allocating to 6 groups (ITC, ITL, ITLSN, IVC, IVL, IVLSN) for another 8 h. Survival time/rate (ST), and variables as biomarkers in lung physiology, histopathology, biochemistry, and pathophysiology were measured. The survival was LPS-route, but not dosing, dependent. Compared to the IVL, ITL had relatively higher ST, lung injury score (LIS), lower intrapulmonary phospholipid pools, mRNA expressions in surfactant proteins (SPs) and pulmonary vascular endothelial cell injury (VEI)-related variables. ITLSN had higher phospholipid pools but no improvement in ST, lung mechanics, LIS or mRNA expression of SPs, proinflammatory mediators and VEI-related variables. IVLSN had improved lung mechanics, LIS, phospholipid pools, and SP-A mRNA expression, but worse ST, metabolic acidosis, higher interleukin mRNA expression in the lungs, liver and kidney, suspected as sepsis-associated multiorgan involvement. Using the infant rabbit LPS-ALI model, we characterized the survival as LPS-route dependent, the lung impairment and response pattern in surfactant and iNO treatment ineffectiveness/failure, as pharmacotherapeutic response patterns, with causal implication pertinent to the underlying pathophysiology of experimental pediatric ARDS.

It is known that gut microbiota dysbiosis can lead to obesity by disrupting energy consumption and metabolism. Probiotic supplements are a potential therapeutic option for improving intestinal homeostasis. The aim of this study was to investigate the effect of a probiotic supplement containing Bifidobacterium bifidum on the intestinal microbiome of people with obesity using high-throughput sequencing on the DNBSEQ-G50 platform. The study demonstrated a positive effect of the supplement on bacterial species such as Bacteroides uniformis, Alistipes putredinis, Alistipes shahii, Dysosmobacter welbionis, and Gemmiger formicilis. Therefore, we suggest the potential use of this bacterial species in the treatment of gut microbiota dysbiosis of obese individuals.

Current therapies slow down advanced features but do not halt or reverse degeneration and neovascularization in dry and wet age-related macular degeneration (AMD). Recent research implicates the gastrointestinal microbiome as a potential critical modulator in AMD pathogenesis through the gut-retina axis. Dysbiosis, characterized by imbalanced microbial diversity, composition and function, can exacerbate systemic and retinal inflammation through microglial priming, inflammasome activation, and secretion of pro-angiogenic cytokines (IL-6, IL-1β, TNF-α, VEGF). Additionally, microbiome-derived metabolites such as short-chain fatty acids and bile acids may exert modulatory roles in host immunity and homeostasis. Their depletion in conjunction with enrichment of specific microbial taxa have been linked to progression of advanced AMD. Together, these complex systems of immune crosstalk in relation to dysbiosis highlight the gut-retina axis as a promising therapeutic target. Dietary modifications, particularly Mediterranean and high-fiber diets, enhance production of protective metabolites and are associated with decreased AMD progression risk compared to Western dietary patterns. Experimental strategies such as fecal microbiota transplantation in animal models and drug repurposing strategies show promise in modulating disease severity. This review synthesizes current mechanistic insights into microbial-immune crosstalk in AMD, emphasizing the interplay of dysbiosis, immune activation, and metabolite signaling.