Search Results (767)

The puff adder (Bitis arietans) is a clinically relevant viper species found throughout Africa, and it is responsible for a greater incidence of health-related envenomations than all other snake species on the continent combined. Unresolved skeletal muscle damage is a common consequence of B. arietans envenomation that can result in long-term morbidity and even death. Antivenom treatment can mitigate the systemic effects of the venom but offers little protection against local tissue damage. Identifying the mechanisms through which B. arietans venom induces tissue damage and impedes skeletal muscle regeneration could identify possible treatment alternatives that could help alleviate the long-term consequences of envenomation. Skeletal muscle has an innate ability to regenerate, but constituents within the venom can impede multiple stages of this regeneration process. In this study, we employed a combination of biochemical analyses, cell-based assays, and in vivo experiments to assess the toxicological implications of B. arietans envenomation and its impacts on key processes of regeneration. Our findings demonstrate that the pathological characteristics of permanent muscle damage resulting from B. arietans envenomation may be attributed to the venom’s effects on muscle stem cell precursors, the extracellular matrix (ECM), and the influence of blood-borne proteins that promote fibrosis. Full article

Background/Objectives: Total hip arthroplasty (THA) is a widely accepted and effective intervention for advanced degenerative hip disease. However, prosthetic dislocation remains one of the most common postoperative complications. This study aimed to evaluate the biomechanical consequences of implant positioning variations and their influence on prosthetic stability. Methods: A three-dimensional finite element model (FEM) of the pelvis and hip joint was developed using SolidWorks Professional 2025, based on CT imaging of an anatomically normal adult. Multiple implant configurations were simulated, varying acetabular cup inclination and anteversion angles, femoral stem depth, and femoral offset. Muscle force vectors replicating single-leg stance conditions were applied according to biomechanical reference data. The mechanical performance of each configuration was quantified using the safety factor (SF), defined as the ratio of allowable material stress to calculated stress in the model. Results: The configuration with 45° cup inclination, 15° anteversion, standard femoral offset, and optimal stem depth demonstrated the highest SF values (9–12), indicating a low risk of mechanical failure or dislocation. In contrast, malpositioned implants—particularly those with low or high anteversion, excessive offset, or shallow stem insertion—resulted in a marked decrease in SF values (2–5), especially in the anterosuperior and posterosuperior quadrants of the acetabular interface. Conclusions: The findings underscore the critical importance of precise implant alignment in THA. Even moderate deviations from optimal positioning can substantially compromise biomechanical stability and increase the risk of dislocation. These results support the need for individualized preoperative planning and the use of assistive technologies during surgery to enhance implant placement accuracy and improve clinical outcomes. Full article

Background/Objectives: Sarcopenia, defined as the progressive loss of muscle mass and function, is increasingly recognized in pediatric cancer patients as a significant clinical and prognostic factor. Sarcopenia in children arises from malignancy-related inflammation, malnutrition, and treatment toxicity, negatively affecting treatment response, recovery, and quality of life. Methods: We searched MEDLINE and Scopus for English-written articles published over the last five years using synonyms for the terms “sarcopenia” and “pediatric cancer”. Screening and data extraction were performed in a duplicate-blinded method. We qualitatively synthesized eligible articles. Results: Recent studies identify pre-treatment sarcopenia as a marker of poor prognosis, especially in hepatoblastoma and neuroblastoma. Total psoas muscle area (tax) and skeletal muscle index (SMI) are emerging diagnostic tools, though standardized methods remain lacking. Sarcopenia’s etiology is multifactorial, involving impaired mitochondrial metabolism, chemotherapy-induced appetite loss, and systemic inflammation. Sarcopenic obesity is common, particularly among leukemia survivors, often masked by normal BMI. Survivors also face reduced bone density, impaired immunity, and persistent muscle loss, linked to prior therapies such as radiotherapy and hematopoietic stem cell transplantation. Increase in muscle mass post-treatment correlates with better survival outcomes. Conclusions: Early detection of sarcopenia can support timely interventions such as nutritional support and physical activity. Yet, significant diagnostic heterogeneity across existing studies hampers definitive conclusions regarding its true prevalence and the optimal assessment method. Standardized diagnostic criteria are urgently needed to enable more reliable prevalence estimates and evidence-based clinical strategies. Full article

Transportation, environmental changes, and overcrowding can induce short-term stress in livestock, leading to physiological imbalances even within a short period. Cortisol is a stress-response hormone and its concentration in the blood can rapidly fluctuate depending on the individual and situation. This study evaluated the short-term effects of cortisol by applying blood cortisol concentrations that mimicked the normal and stress-induced levels observed in Korean native cattle (Hanwoo) to the culture medium of Hanwoo muscle stem cells (HWSC). Treatments were designed with five cortisol concentrations (0, 5, 10, 30, and 70 ng/mL) and four treatment times (0.5, 1, 2, and 3 h), based on the CCK-8 and viable cell count results. The expression levels of cortisol receptor-related genes (NR3C1, HSP70, and HSP90AA1) increased and reached a peak at 30 min post-treatment. After 30 min, the expression of these genes gradually decreased. However, in the case of HSP70, expression tended to increase again after 3 h of treatment. This could be seen as the regulation of cortisol inflow into the HWSC. Upon examining the oxidative effects of cortisol on superoxide dismutase 1 (SOD1), glutathione peroxidase (GPX), catalase (CAT), and oxygen consumption rate (OCR), the expression of antioxidant factors increased and peaked at 30 min of treatment. Following this peak, their levels generally began to decrease. However, in the 70 ng/mL group, the expression of these factors remained at a high level compared to the control group even after 30 min. In addition, the cellular respiration index and ATP production increased as the treatment prolonged, regardless of the concentration, as shown by the OCR analysis. These results can be considered a phenomenon corresponding to the accumulation of oxidative by products, such as Reactive Oxygen Species (ROS), caused by cortisol. The gene expression of apoptosis factors (p53, BAX, Caspase-3) temporarily increased at 30 min but then decreased. Caspase-3 protein activity was elevated at 30 min in the 70 ng/mL group, which later reduced. These results suggested that short-term cortisol administration had no effect on apoptosis in muscle cell culture. Therefore, the study findings elucidating the effects of short-term cortisol treatment on HWSC suggest that short-term stress may not have a significant negative effect on Hanwoo muscle. However, as this study was limited to muscle stem cells derived from Hanwoo, further investigation is required to determine whether the observed responses are consistent across different species and in vivo environments. Full article

Background: Sarcopenia is characterized by a loss of muscle mass and strength, resulting in functional limitations and an increased risk of falls, injuries and fractures. The aim of this study was to obtain detailed information on skeletal muscle changes in patients with multiple myeloma (MM) during treatment. Methods: A total of 51 patients diagnosed with MM who had undergone whole-body low-dose computed tomography acquisition prior to induction therapy (T1) and post autologous stem cell transplantation (T2) were examined retrospectively. Total volume (TV), muscle volume (MV) and intramuscular adipose tissue volume (IMAT) of the autochthonous back muscles, the iliopsoas muscle and the gluteal muscles were evaluated on the basis of the resulting masks of the BOA tool with the fully automated combination of TotalSegmentator and a body composition analysis. An in-house trained artificial intelligence network was used to obtain a fully automated three-dimensional segmentation assessment. Results: Patients’ median age was 58 years (IQR 52–66), 38 were male and follow-up CT-scans were performed after a mean of 11.8 months (SD ± 3). Changes in MV and IMAT correlated significantly with Body-Mass-Index (BMI) (r = 0.7, p < 0.0001). Patients (n = 28) with a decrease in BMI (mean −2.2 kg/m²) during therapy lost MV (T1: 3419 cm³, IQR 3176–4000 cm³ vs. T2: 3226 cm³, IQR 3014–3662 cm³, p < 0.0001) whereas patients (n = 20) with an increased BMI (mean +1.4 kg/m²) showed an increase in IMAT (T1: 122 cm³, IQR 96.8–202.8 cm³ vs. T2: 145.5 cm³, IQR 115–248 cm³, p = 0.0002). Loss of MV varied between different muscle groups and was most prominent in the iliopsoas muscle (−9.8%) > gluteus maximus (−9.1%) > gluteus medius (−5.8%) > autochthonous back muscles (−4.3%) > gluteus minimus (−1.5%). Increase in IMAT in patients who gained weight was similar between muscle groups. Conclusions: The artificial intelligence-based three-dimensional segmentation process is a reliable and time-saving method to acquire in-depth information on sarcopenia in MM patients. Loss of MV and increase in IMAT were reliably detectable and associated with changes in BMI. Loss of MV was highest in muscles with more type 2 muscle fibers (fast-twitch, high energy) whereas muscles with predominantly type 1 fibers (slow-twitch, postural control) were less affected. This study provides valuable insight into muscle changes of MM patients during treatment, which might aid in tailoring exercise interventions more precisely to patients’ needs. Full article

A subset of chondrocytes in various human cartilage tissues, including neoplastic, regenerative, and normal cartilage, expresses α-smooth muscle actin (α-SMA), a protein typically found in smooth muscle cells. These α-SMA-containing chondrocytes, termed myochondrocytes and myochondroblasts, may play important roles in cartilage physiology, regeneration, and structural integrity, particularly in auricular and articular cartilage. This review synthesizes current knowledge regarding the terminology, distribution, and biological significance of these cells across normal, osteoarthritic, transplanted, and neoplastic cartilage. We summarize key findings from immunohistochemical studies using markers such as S-100, α-SMA, and SOX9, along with ultrastructural confirmation of myofilament bundles via electron microscopy. Current evidence suggests that myochondrocytes exhibit enhanced regenerative potential and contribute to matrix remodeling. Furthermore, their presence reflects the inherent cellular heterogeneity of cartilage, potentially arising from transdifferentiation processes involving fibroblasts, mesenchymal stem cells, or chondroblasts. Finally, TGF-β1 and PDGF-BB are identified as a critical modulator of α-SMA expression and chondrocyte phenotype. A deeper understanding of nature and function of myochondrocytes and myochondroblasts may improve interpretations of cartilage pathology and inform strategies for tissue engineering and cartilage repair. This review highlights the need for further investigation into the molecular regulation and functional roles of these cells in both physiological and pathological contexts. Full article

Synthetic biomaterials are widely used as bone graft substitutes, but their osteogenic capacity is limited as they lack osteogenic growth factors. This study aimed to enhance the osteogenesis of a novel hydroxyapatite/aragonite (HAA) biomaterial by incorporating decellularized bone matrix and bone morphogenetic protein (BMP)-2 and BMP-7 (BMP-2/7). Human umbilical mesenchymal stem cells (MSCs) were able to proliferate and differentiate on HAA. HEK-293T cells exogenously expressing BMP-2/7 successfully secreted BMP-2/7, which was assessed by enzyme-linked immunosorbent assay. By establishing a co-culture of MSCs with HEK-293T cells expressing BMP-2/7, we successfully created an artificial allograft that integrates both synthetic biomaterials and functional organic components, offering the potential to enhance osteogenesis. The decellularized (by freeze/thawing) functional HAA was implanted between the tibia and anterior tibialis muscle in murine models and assessed the induced bone formation via micro-computer tomography, histology, and osteogenic markers mRNA expression by a reverse transcription-quantitative polymerase chain reaction. A significant increase in new bone formation was seen in the functional HAA implanted group. In conclusion, this study revealed that bone formation following the HAA implantation can be enhanced by a functional decellularized matrix, comprising BMP-2/7, via in vitro tissue engineering using MSCs and HEK-293T cells expressing BMP-2/7. Full article

Reduced oxygen availability, or hypoxia, is an environmental stress factor that modulates cellular and systemic functions. It plays a significant role in both physiological and pathological conditions, including tissue regeneration, where it influences angiogenesis, metabolic adaptation, inflammation, and stem cell activity. Hypoxia-inducible factors (HIFs) orchestrate these responses by activating genes that promote survival and repair, although HIF-independent mechanisms, particularly those related to mitochondrial function, are also involved. Depending on its duration and severity, hypoxia may exert either beneficial or harmful effects, ranging from enhanced regeneration to fibrosis or maladaptive remodeling. This review explores the systemic and cellular effects of acute, chronic, intermittent, and preconditioning hypoxia in the context of tissue regeneration. Hypoxia-driven responses are examined across tissues, organs, and complex structures, including the heart, muscle, bone, vascular structures, nervous tissue, and appendages such as tails. We analyze findings from animal models and in vitro studies, followed by biomedical and pharmacological strategies designed to modulate hypoxia and their initial exploration in clinical settings. These strategies involve regulatory molecules, signaling pathways, and microRNA activity, which are investigated across species with diverse regenerative capacities to identify mechanisms that may be conserved or divergent among taxa. Lastly, we emphasize the need to standardize hypoxic conditions to improve reproducibility and highlight their therapeutic potential when precisely controlled. Full article

Cardiac ischemia causes a shortage of blood flow and oxygen to the heart muscle (i.e., myocardial infarction, MI), causing cell damage/death that initiates a cascade of healing processes. Every year, more than one million people in the United States die as a result of MI. After MI, approximately 40% of patients develop maladaptive myocardial remodeling that associates with decreasing cardiac function levels. Collagen treatment, particularly the use of collagen-based biomaterials as well as collagen supplementation, has shown promise in treating cardiac ischemia by supporting processes involved in blood pressure regulation, arterial health, and cholesterol management, mechanical support, increasing stem cell retention, and improving bioactive chemical delivery for myocardial repair and regeneration. In this review, we evaluate collagen treatment in myocardial ischemia based on existing studies and propose a missing link for future research. Full article

Cultured meat is produced through cellular agriculture and tissue engineering and has emerged as a promising alternative to conventional animal-based meat production. Cultured meat, produced through cellular agriculture and tissue engineering, offers a sustainable alternative to conventional meat production. This review outlines the potential of diverse stem cell sources, including satellite cells, embryonic stem cells, and induced pluripotent stem cells, for producing muscle and adipose tissue. Advances in bioprocess development, biomaterials, and bioreactor design are discussed, with an emphasis on scalability, cost reduction, and regulatory considerations. Despite progress, key challenges remain: replicating the nutritional composition and sensory qualities of conventional meat, developing serum-free media, and ensuring consistent large-scale production. Recent studies report cost reductions of up to 90% in culture media and successful bioreactor expansions beyond 50 L, yet industrial translation is still limited. Consumer acceptance and clear regulatory frameworks are also critical for commercialization. Future work should focus on integrating cellular innovations with scalable technologies to overcome current bottlenecks and accelerate market readiness. Full article

Mesenchymal stromal/stem cells (MSCs) are known to secrete a wide range of pleiotropic molecules promoting tissue repair and regeneration. Recent advances in cell sheet technology have demonstrated significant improvements in the regenerative capacity of MSCs within the sheet, retaining appropriate microenvironmental cues, and have suggested an instructing role of extracellular matrix (ECM). We previously found that the secretome of MSCs cultured on a decellularized MSC-derived ECM (dECM) was significantly enriched in dozens of cytokines, chemokines and growth factors compared to the secretome of MSCs grown on standard plastic dishes. The enriched secretome has been shown to have enhanced chemotactic and angiogenic properties, stimulate C2C12 myoblast proliferation and promote skeletal muscle regeneration in a murine in vivo model. Here, we report novel findings about dECM-induced changes in the miRNA profile of MSCs. We performed miRNA-seq and found 17 differentially expressed miRNAs in endometrial MSCs (MESCs) with miR-146a-5p being the most upregulated. Additionally, we investigated miR-146a-5p expression in MSCs of various origins after exposure to dECM, and found a correlation between miR-146a-5p upregulation and the general dECM-induced paracrine response. Furthermore, we demonstrated that miR-146a-5p mimics, transfected into C2C12 myoblasts, promoted their proliferation, suggesting a role for miR-146a-5p in myotropic effects mediated by the enriched secretome. These findings provide new insights into how ECM as a component of the MSC niche influences the secretory phenotype and modulates therapeutic properties of MSCs. Full article

Plectin is a key cytolinker protein that functions as an integrator of the cytoskeletal networks by crosslinking intermediate filaments with actin filaments and microtubules. Mutations or function deficiencies of plectin lead to tissue disorders, particularly affecting the skin, muscle, and nervous tissues. Interestingly, plectin dysregulation in cancer, characterized by aberrant expression and mislocalization, has been increasingly observed, suggesting distinct roles in tumorigenesis and progression. Here, we focus on recent advances regarding the roles of plectin dysregulation in promoting cell proliferation, suppressing cell apoptosis, sustaining the stemness of cancer stem cells, and driving invasion and metastasis. We also discuss its bidirectional interplay with the tumor microenvironment, including modulating immune and inflammatory responses, promoting angiogenesis, sensing and transmitting mechanical cues from the extracellular matrix, and contributing to matrix remodeling. Finally, we highlight emerging therapeutic strategies that target plectin dysregulation with anticancer activity. By summarizing these advances, we aim to enhance the understanding of plectin dysregulation in cancer and illuminate its potential as a therapeutic target. Full article

Skeletal muscle, the primary meat-producing tissue in bovines, is regulated by a complex transcriptional network during development. The role of Thrombospondin 3 (THBS3) and its associated super-enhancer (SE) in this process remains largely unknown. Here, by integrating multi-omics data, we identified THBS3 as a novel core regulator of myogenesis, orchestrated by a cognate super-enhancer (THBS3-SE). Functional assays demonstrated that THBS3 knockdown significantly promoted the proliferation and myogenic differentiation of bovine muscle stem cells (MuSCs) and accelerated their commitment to a fast-twitch fiber fate. Transcriptomic analysis linked THBS3 function to key signaling pathways controlling muscle growth, especially the mechanistic target of rapamycin (mTOR) signaling pathway. Mechanistically, we found that distal enhancers within the THBS3-SE loop to the THBS3 promoter drive its transcription, and CRISPR-based interference of these enhancers recapitulated the pro-myogenic effects of THBS3 knockdown. Collectively, our findings unveiled a THBS3-SE-mediated regulatory axis that critically governed bovine MuSCs’ fate. Targeting this axis may offer a novel strategy for improving beef production efficiency. Full article

Peripheral nerve injuries (PNIs) are common and often result in sensorimotor deficits, chronic pain and decreased quality of life. While the peripheral nervous system has greater regenerative capacity than the central nervous system, recovery is often limited by intrinsic changes in the nerve and muscle. This review summarizes the process of nerve regeneration, with a focus on the role of the vasculature, following PNI and examines current bioengineering approaches to enhance peripheral nerve regeneration through modification of the nerve microenvironment and optimization of neurovascular interactions. The primary areas of translational research discussed in this review include vascularized nerve grafts, nerve conduits and scaffolds, bioactive peptides, nanoparticles, extracellular vesicles, stem cells, and gene therapy. Full article

Duchenne muscular dystrophy (DMD) is a lethal inherited muscle disease caused by mutations in the DMD gene, and the development of gene therapies targeting DMD is rapidly progressing. Patient-derived induced pluripotent stem cells and animal models that mimic patient-specific mutations have significantly contributed to the advancement of precision medicine based on individual genetic profiles. Currently, no approved disease-specific therapy exists for DMD cardiomyopathy, which remains one of the leading causes of death in DMD patients. Therefore, the development of effective cardiac therapies represents a critical milestone in DMD research. In this review, we provide an overview of essential cellular and animal models used in DMD research, with a specific focus on the heart. We describe their key characteristics, advantages, and limitations. It is considered that a comprehensive and strategic integration of these models—based on a clear understanding of their respective strengths and weaknesses—will be important for advancing the development and clinical application of targeted therapies for DMD cardiomyopathy. Full article