Nine crossbred finishing barrows randomly assigned to 3 dietary treatments were used to investigate the effects of dietary lysine on muscle growth related metabolic and signaling pathways. Muscle samples were collected from the longissimus dorsi of individual pigs after feeding the lysine-deficient, lysine-adequate, or lysine-excess diet for 5 weeks, and the total RNA was extracted afterwards. Affymetrix Porcine Gene 1.0 ST Array was used to quantify the expression levels of 19,211 genes. A total of 674 transcripts were differentially expressed (P ≤ 0.05); 60 out of 131 transcripts (P ≤ 0.01) were annotated in the NetAffx database. Ingenuity pathway analysis showed that dietary lysine deficiency may lead to (1) increased muscle protein degradation via the ubiquitination pathway as indicated by the up-regulated DNAJA1, HSP90AB1 and UBE2B mRNA, (2) reduced muscle protein synthesis via the up-regulated RND3 and ZIC1 mRNA, (3) increased serine and glycine synthesis via the up-regulated PHGDH and PSPH mRNA, and (4) increased lipid accumulation via the up-regulated ME1, SCD, and CIDEC mRNA. Dietary lysine excess may lead to (1) decreased muscle protein degradation via the down-regulated DNAJA1, HSP90AA1, HSPH1, and UBE2D3 mRNA, and (2) reduced lipid biosynthesis via the down-regulated CFD and ME1 mRNA.

Abstract Background: Temporomandibular disorders (TMD) are a range of clinical problems related to the temporomandibular joint (TMJ), chewing muscles, and surrounding facial structures. Functional magnetic resonance studies suggest that these disorders affect over 5% of the population. The relationship between dental occlusion and TMD has been a topic of debate in dentistry; some researchers suggest using lateral cephalograms and cephalometric data to identify which morphological profiles and types of malocclusion are most likely to cause TMD. The aim of this study is to identify the morphological profiles and associated skeletal malocclusions that have the greatest influence on the development of TMD. This will be accomplished through the analysis of cephalometric data obtained from cephalograms and condylar section images of patients from the Orthognathodontics Department of Chieti, who underwent low-dose cbct during their initial visit. Matherial and methods: This study, conducted at the Orthognathodontics Department of Gabriele D’Annunzio University in Chieti, examined a group of 67 patients (both males and females) presenting with signs of temporomandibular joint disorders (TMD). The inclusion criteria for the study were first-time TMD diagnosis, age 18 and above, and accessible medical records, wide field of view cone beam low dosage, and photographs. Patients with a history of tumor, trauma, surgical interventions in the jaw and facial area, fractures, and other craniofacial anomalies were excluded from the study. The aim of the study is to further understand the morphological profiles and associated skeletal malocclusions that contribute to TMD. Results: male patients: sagittal profile: 56% exhibited a skeletal Class II profile due to mandibular retrognathia. Vertical Profile: 73% were brachyfacial with a hypodivergent pattern. Dental Relationships: Increased overjet and a tendency towards deep bite were observed. 23% exhibited deep bite, 20% were normodivergent, and 8% were dolichofacial. The soft tissue profile tended towards flatness. Condyle Position: in Class II hypodivergent males, the condyle was non-concentric and positioned more posteriorly. In mesiodivergent males, the condyle was concentric, while in hyperdivergent males, it was slightly anterior. Female Patients: Sagittal Profile: 79% had a skeletal Class II profile with mandibular retrognathia. Vertical Profile: 47% were hypodivergent with reduced anterior facial height (105°). Dental Relationships: 17% exhibited deep bite, and 48% of those with a Class II profile had increased overjet. 43% were mesofacial, and 10% were dolichofacial. Condyle Position: In Class II hypodivergent and normodivergent females, the condyle was non-concentric and positioned more posteriorly. In hyperdivergent females, the condyle was positioned more anteriorly and higher in the fossa. Conclusion: The study highlighted significant differences in cephalometric parameters and condyle positions between male and female patients with TMD. A posteriorly positioned condyle was associated with a flattened condylar head, particularly in Class II hypodivergent profiles. These findings underscore the importance of individualized diagnostic and treatment approaches based on detailed cephalometric and condylar assessments. Further research is needed to explore the implications of these variations for TMD management and outcomes.

We have previously demonstrated that the acute ingestion of essential amino acids may augment net protein balance in the elderly. Using a double blind, randomized controlled trial, our objective was to compare an experimental meal replacement enriched with essential amino acids (EMR) compared to a commercial meal replacement (Optifast®) provided once/day (q.d.) for four weeks on body composition and physical function in older, obese participants. Twenty-seven individuals (69±5 yrs; body mass index of 32±4 kg/m2) were randomly assigned to EMR (n=13) or Optifast® (n=15) supplementation. Measurements of body composition, skeletal muscle cross-sectional area (CSA), intrahepatic lipid and physical function were completed pre- and post-supplementation. Body mass, fat mass, and visceral fat mass were reduced with EMR but not altered with Optifast®. Thigh muscle CSA increased ( 4.1 ± 1.9 cm2, P = 0.03) with EMR but not Optifast®. There was a significant increase in the distance covered during the six-minute walk test with EMR ( 21±26 m) but no change in Optifast® ( 22±54 m). Improvements in body composition and physical function support the efficacious use of EMR-based meal replacements in the obese elderly.

Currently, there is an increase in the aging of the population, which represents a risk factor for many diseases, including sarcopenia. Sarcopenia involves progressive loss of mass, strength, and function of the skeletal muscle. Some mechanisms include alterations in muscle structure, reduced regenerative capacity, oxidative stress, mitochondrial dysfunction, and inflammation. The zebrafish has emerged as a new model for studying skeletal muscle aging because of its numerous advantages, including histological and molecular similarity to human skeletal muscle. In this study, we used fish of 2, 10, 30, and 60 months of age. The older fish showed a higher frailty index because of reduced locomotor activity and alterations in biometric measurements. We observed changes in muscle structure with a decreased number of myocytes and an increase in collagen with aging, corresponding to alterations in the synthesis, degradation, and differentiation pathways. These changes were accompanied by mitochondrial alterations, such as a decrease in intermyofibrillar mitochondria, increased mitochondrial damage, and reduced mitochondrial dynamics. Overall, we demonstrated a similarity in the aging processes of muscle aging between zebrafish and mammals.

The normal growth and development of skeletal muscle is essential for the health of the body. The regulation of skeletal muscle by intestinal microorganisms and their metabolites has been continuously revealed. Acetate is the predominant short-chain fatty acid synthesized by gut microbiota through the fermentation of dietary fiber, however, the underlying molecular mechanisms governing the interaction between acetate and skeletal muscle during rapid growth stage remain to be further elucidated; Here, specific pathogen-free (SPF) mice, germ-free (GF) mice, and germ-free mice supplemented with sodium acetate (GS) were used to evaluate the effects of acetate on skeletal muscle growth and development of young mice with gut microbiota deficiency; We found the concentration of serum acetate, body mass gain, succinate dehydrogenase activity and expression of myogenesis maker gene of skeletal muscle in the GS group was higher than GF group following sodium acetate supplement. Furthermore, the transcriptome analysis revealed that acetate activated biological processes regulating skeletal muscle growth and development in GF group that are inhibited due to gut microbiota deficiency. In vitro experiment, we proved that acetate up-regulated Gm16062 to promote skeletal muscle cell differentiation; Overall, our findings proved that acetate promote skeletal muscle growth and development in young mice via increase Gm16062 expression.

This study proposes a cephalometric analysis that can be used for biomechanical simulation by considering the important and complex relationship between craniofacial morphology and masseter muscle (MM) size and inclination and by including muscle values. The MM line of action drawn between the Gonion (Go) and Orbital (Or) point relative to dental and skeletal references (occlusal and Frankfort planes) were analyzed. A total of 510 pre-treatment lateral cephalometric tracings (217 males, 293 females, 6-50 years) and lateral Bolton standard tracings (6-18 years) were analyzed. The study examined the following: a) skeletal-cutaneous class (linear distance in mm between the projections of points A' and B' on the occlusal plane), b) the angle between the perpendicular line to the occlusal plane and the Go-Or line at the molar occlusal point, and c) the angle between the Go-Or line and the Frankfort plane. The skeletal classes of the patients ranged from -14.5 to 15.5 mm and did not differ by sex or age; the angle between the Go-Or line and the normal to the occlusal plane averaged 39° (range 15° to 53°) and decreased with age, while the angle between the Go-Or line and the Frankfort plane averaged 42° (range 30° to 54°), increased in older patients. No effect of gender was observed. The two angles were also significantly correlated with each other, but not with sagittal jaw discrepancy. Similar results were obtained with Bolton tracings; the positional relationship of the Go-Or line to the teeth and skeletal landmarks is partially consistent with the literature. The present cephalometric analysis can be usefully used to estimate the mechanical advantage of MM in biomechanical simulations of masticatory muscle performance.

Tissue engineering, also called “regenerative medicine”, refers to attempt to create functional human tissue from cells in laboratory. This is a field that uses living cells, biocompatible materials, suitable biochemical and physical factors and their combinations, to create tissue-like structures.. To date, no tissue engineered skeletal muscle implants have been developed for clinical use, but it may represent a valid alternative to treat volumetric muscle loss in the near future. Herein, we reviewed the literature and showed different techniques to produce synthetic tissues with the same architectural, structural and functional properties of native tissues.

Mutations in the calcium channel gene Transient Receptor Potential cation channel subfamily V member 4 (TRPV4) cause autosomal dominant skeletal dysplasia, with phenotypes ranging from mild to perinatal lethality. A recent report detailed murine thrombocytosis in the absence of functional TRPV4, but no prior reports have described platelet count abnormalities in the context of human TRPV4 disease. Here, we report a case of prolonged thrombocytosis in the context of TRPV4-associated metatropic dysplasia that was lethal in the infantile period.

Background: Knee joint is a common site for injury among younger people, the purpose of this study is to measure the skeletal muscle endurance and strength on people with prior knee reconstruction surgery. Methods: Young healthy female subjects were tested who reported having knee reconstruction surgery of over one year prior to testing. The skeletal muscle endurance index of the hamstring and quadriceps muscles was determined as the decline in the specific muscle acceleration in response to 2, 4, and 6 Hz electrical stimulation. Maximal isometric muscle strength (MVC) was measured in the hamstring and quadriceps muscles. Results: The hamstring muscles in the affected leg had less endurance than the non-affected leg at 6 Hz stimulation (55.5 ± 13.2% versus 78.0 ± 13.3%, P = 0.01). Muscle endurance was not reduced in the quadriceps muscles in the affected leg compared to the non-affected leg at 6 Hz stimulation (78.0 ± 13.3% versus 80.3 ± 10.0%, P = 0.69). There were no differences in MVC between the affected and non-affected legs for either the hamstring (P= 0.20) or quadriceps muscles (p = 0.67). Conclusions: Muscle endurance is reduced in the hamstring muscles at least one-year post injury, while hamstring strength is not. Reduced hamstring muscle endurance could be a result of a lack of focus on muscle endurance during rehabilitation after injury and may contribute to re-injury in the particular muscle even in people who have recovered muscle strength.

Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in ischemic condition is also presented.

We examined changes in skeletal muscle protein lactylation and acetylation in response to acute resistance exercise, chronic resistance training (RT), and a single endurance cycling bout. Additionally, we performed in vitro experiments to determine if different sodium lactate treatments affect myotube protein lactylation and acetylation. The acute and chronic RT study (n=12 college-aged participants) consisted of 10 weeks of unilateral leg extensor RT with vastus lateralis (VL) biopsies taken at baseline, 24-hours following the first RT bout, and the morning of the last day of the RT bout. For the acute cycling study (n=9 college-aged participants), VL biopsies were obtained before, 2 hours, and 8 hours after 60 minutes of cycling. For in vitro experiments, C2C12 myotubes were treated with varying levels of sodium lactate including LOW (1mM for 24-hours), HIGH (10mM for 24 hours), and PULSE (10mM for 30 minutes followed by 1 mM for 23.5-hours). Neither acute nor chronic RT significantly affected nuclear or cytoplasmic protein lactylation. However, cytoplasmic protein acetylation was significantly reduced following one RT bout (-15%, p=0.002) and chronic RT (-16%, p=0.006). Cycling did not acutely alter post-exercise global protein lactylation or acetylation patterns. Lastly, varying 24-hour lactate treatments did not alter nuclear or cytoplasmic protein lactylation or acetylation, cytoplasmic protein synthesis levels, or myotube diameters. These findings continue to support that exercise induces changes in skeletal muscle protein acetylation but not lactylation.

Aim: To determine the prevalence of skeletal muscle alterations (SMA) in patients with meta-bolic dysfunction-associated steatotic liver disease (MASLD) and to assess the significance of circulating myokines as potential biomarkers of SMA in patients with MASLD. Material and methods: Measurements of both skeletal muscle strength and skeletal muscle mass parameters, anthropometric and metabolic features as well as serum levels of different myokines were per-formed in a cohort of 62 MASLD patients and then compared according to the stage of liver fi-brosis and hepatosteatosis degree both diagnosed by transitional elastography. Results: No sig-nificant differences were found in skeletal muscle strength and skeletal muscle mass in MASLD patients stratified according to the stage of liver fibrosis. Noteworthy, serum levels of FGF21 were significantly higher in MASLD patients with advanced hepatic fibrosis (F3-F4) than in those with lower stages of hepatic fibrosis (F0-F2) (197.49±198.27 pg/ml vs 95.62±83.67 pg/ml, p=0.049, respectively). MASLD patients with severe hepatosteatosis (S3) had significantly higher serum levels of irisin (1116.87±1161.86 pg/ml) than those with lower grades (S1-S2) (385.21±375.98 pg/ml, p=0.001). Conclusion: SMA were uncommon in our MASLD patients, particularly in those with lower stages of liver fibrosis. An increase in serum FGF21 was detected in patients with a higher stage of fibrosis with possible therapeutic implications in MASLD.

In the 21st century, museums have come to realize that the human skeletons they display might have problematic origins. The older anthropological skeletal collections typically originate from anatomical dissection of the executed and the very poor, or from scavenged graves of indigenous people. Such collections are currently being re-evaluated in many countries, and reburying or repatriating museum skeletons have become viable options. A particularly difficult question is what to do with human remains of unknown origins. Here, we present and discuss one such case, where a human skeleton of unclear origin in the 1930’s was brought to a local museum in Bollnäs, Sweden, under likely unethical circumstances. Most of the bones have now been lost, except for the skull, the sacrum and one lumbar vertebra, which in 2007 were transferred to the Museum of Ethnography in Stockholm. The skull was there put on display as the “Bollnäs skull”, and was presented to the public to illustrate the dilemmas involved in handling human remains in the post-colonial era. The original gift letter from 1934 stated that the skeleton came from San Nicolas Island outside the California coast, but this letter contained numerous instances of incorrect information and was therefore deemed not trustworthy. However, our critical examination of the skull and its background information indicates that San Nicolas Island is a plausible origin, and we suggest that a bioarchaeological comparison should be made between the skull and living descendants of the San Nicolas Island population, and/or with archaeological human skeletons excavated from the island.

The proliferation and differentiation of mammalian skeletal muscle satellite cells (MuSCs) are highly complicated. Apart from the regulatory signaling cascade driven by the protein-coding genes, non-coding RNAs like microRNAs (miRNA) and circular RNAs (circRNAs) play essential roles in this biological process. However, circRNA functions in MuSCs proliferation and differentiation remain largely to be elucidated. Here, we screened for an exonic circTCF4 based on our previous RNA-Seq data, specifically expressed during the development of the longest dorsal muscle in goats. Subsequently, the circular structure and whole sequence of circTCF4 were verified using Sanger sequencing. Besides, circTCF4 was spatiotemporally expressed in multiple tissues from goats but strikingly enriched in muscles. Furthermore, circTCF4 suppressed MuSCs proliferation and differentiation, independent of AGO2 binding. Finally, we conducted Poly(A) RNA-Seq using cells treated with small interfering RNA targeting circTCF4 and found that circTCF4 would affect multiple signaling pathways, including insulin signaling pathway and AMPK signaling pathway related to muscle differentiation. Our results provide additional solid evidence for circRNA regulating skeletal muscle formation.

Background: In physiotherapy, a classic muscle-bone concept is used to translate basic and clinical anatomy. By defining the anatomical structures from superficial to deeper layers which frame the ArthroMyoFascial complex, our aim is to offer clinicians a comprehensive concept of fasciae within the muscle-bone concept. Method: Narrative review and ultrasound observation. Results: Based on literature and ultrasound skeletonization, the ArthroMyoFascial complex has been defined. This model clarifies fascial continuity at the joint level, describing anatomical structures from skin to deeper layers, including superficial fascia, deep fascia, myofascia including skeletal muscle fibers, and arthrofascia all connected via connective tissue linkages. This model enhances understanding of the muscle-bone concept within the larger ArthroMyoFascial complex. Conclusion: The ArthroMyofascial complex consists of multiple layers from superficial to deeper anatomical structures, namely the skin, superficial fascia, deep fascia, myofascia including muscle fibers, and arthrofascia, all linked within a connective tissue matrix. This model indicates that it is a force-transmitting system from the skin to the bone. This information is crucial for manual thera-pists, including physiotherapists, osteopaths, chiropractors, and massage therapists, as they all work with fasciae within the musculoskeletal domain. Understanding fascia within the mus-cle-bone concept enhances clinical practice, aiding in therapeutic testing, treatment, reporting, and multidisciplinary communication, which is vital for musculoskeletal and orthopedic rehabilitation.

Duchenne muscular dystrophy (DMD) is caused by genetic mutations in the cytoskeletal-sarcolemmal anchor protein dystrophin. Repeated cycles of sarcolemmal tearing and repair lead to a variety of secondary cellular and physiological stressors that are thought to contribute to weakness, atrophy, and fibrosis. Collectively, these stressors can contribute to a pro-inflammatory milieu in locomotor, cardiac, and respiratory muscles. Given the many unwanted side effects that accompany current anti-inflammatory steroid-based approaches for treating DMD (e.g., glucocorticoids), there is a need to develop new therapies that address inflammation and other cellular dysfunctions. Adiponectin receptor (AdipoR) agonists, which stimulate AdipoR1 and R2 isoforms on various cell types, have emerged as therapeutic candidates for DMD due to their anti-inflammatory, anti-fibrotic, and pro-myogenic properties in pre-clinical human and rodent DMD models. Although these molecules represent a new direction for therapeutic intervention, the mechanisms through which they elicit their beneficial effects are not yet fully understood, and DMD-specific data is limited. The overarching goal of this review is to investigate how adiponectin signaling may ameliorate pathology associated with dystrophin deficiency through inflammatory-dependent and -independent mechanisms, and to determine if current data supports their future progression to clinical trials.

FacioScapuloHumeral Dystrophy (FSHD) is one of the most prevalent inherited muscle disorders, and is linked to the inappropriate expression of the DUX4 transcription factor in adult muscles. The deregulated molecular network causing FSHD skeletal muscle dysfunction and pathology is still not well understood. It has been shown that the hypoxia response factor HIF1α is critically disturbed in FSHD and has a major role in DUX4 induced cell death. In this study, we further explore the relationship between DUX4 and HIF1α. We found that the DUX4 and HIF1α link differed according to the stage of myogenic differentiation and was conserved between human and mouse muscle. Furthermore, we found that HIF1α knock-down in a mouse model of DUX4 local expression exacerbated DUX4-mediated muscle fibrosis. Our data indicate that the suggested role of HIF1α in DUX4 toxicity is complex and that targeting HIF1α might be challenging in the context of FSHD therapeutic approaches.

Epitranscriptomics refers to post-transcriptional regulation of gene expression via RNA modifications and editing that affect RNA functions. Many kinds of modifications of mRNA have been described, among which N6-Methyladenosine (m6A), N1-methyladenosine (m1A), 7-methylguanosine (m7G), pseudouridine (Ψ), 5-methylcytidine (m5C). They alter mRNA structure and consequently stability, localization and translation efficiency. Perturbation of the epitranscriptome is associated with human diseases, thus opening the opportunity for potential manipulations as therapeutic approach. In this review, we overview the functional roles of epitranscriptomic marks in the skeletal muscle system, in particular in embryonic myogenesis, muscle cell differentiation and muscle homeostasis processes. Further, we explored high throughput epitranscriptome sequencing data to identify RNA chemical modifications in muscle-specific genes and we discuss the possible functional role and the potential therapeutic applications.

Skeletal muscle is a specialized tissue consisting of nondividing and multinucleated muscle fibers. Skeletal muscle-specific myostatin (MSTN) is a secreted protein that acts as a negative regulator of muscle mass by inhibiting proliferation and differentiation of myoblasts. In this study, we established a screening platform to monitor myostatin promoter activity in rat L8 myoblasts. Extract of Glycyrrhiza uralensis (GUE), an oriental herbal medicine, was identified through this screening platform and, the active fractions of GUE were identified by process-scale liquid column chromatography system. For in vivo study, the GUE as a feed additive was investigated in growth-finishing pigs. The results showed that GUE significantly increased body weight, carcass weight and lean content in pigs. Microbiota analysis indicated that GUE did not affect the composition of gut microbiota in pigs. In summary, this established rodent myoblast screening platform was used to identify a myogenesis-related phytogenic, GUE, and further demonstrated that the active fractions inhibited MSTN expression. These finding suggest a novel application for GUE in growth performance enhancement through modulation of MSTN expression. Furthermore, this established screening platform has great potential for identification and evaluation of a wide variety of phytogenics involving in myogenesis.

The facultative loss of muscle mass and function during aging (sarcopenia) poses a serious threat to our independence and health. Much of what we know about sarcopenia derive from studies on small rodents which serve as models for the human condition. Here we used outbred male rats to study the natural history of sarcopenia with the aim to compare behavioral motor deficits with degree of muscle wasting and to find processes underlying the preclinical phase of sarcopenia. Selected metrics were validated in female rats. We used the soleus muscle because of its long duty cycles in everyday life and significance for postural control. The results show that gait and coordination remain intact through middle age (12-18 months; 40%-60% of median lifespan) when muscle mass relative to body weight is largely maintained. The muscle, however, show multiple signs of remodeling with a shift in myofiber-type composition towards type I, increased number of hybrid fibers and fibers expressing embryonic myosin. In parallel with the shift in fiber type prevalence, fiber type clustering increased. The latter combined with a transcriptional upregulation of nicotinic acetylcholine receptor subunit  (CHRN ), NCAM and Myogenin (MYOG) suggests a remodeling driven by myofiber denervation. Additional stigmata were increased number of central nuclei, transcriptional upregulation of Smad3, FBXO32, and MuRF1mRNAs; unaltered density of satellite cells (SC) and Catenin mRNA. In early (25-month-old) and advanced (30-month-old) aging, gait and coordination deteriorate as loss of muscle mass progresses. In late middle age and early aging because of a type II atrophy (>50%), followed by type I atrophy (>50%). Number of myofiber did not correlate with this process. At advance age, the atrophy is accompanied by a decrease in SC and Catenin mRNA while several transcripts upregulated earlier-on were downregulated. In contrast, glial-derived nerve growth factor (GDNF) mRNA abundance peaked at endpoint. We conclude that sarcopenia in the rat as in humans, has a long preclinical phase where the muscle undergoes extensive remodeling to preserve muscle mass and function. The data supports the notion that myofiber denervation is the instigating mechanism, initially affecting large type II motor units (MUs) and at more advanced stage also the smaller type I MUs.

Type 2 diabetes mellitus (T2DM) has emerged as a major health care concern in modern society, primarily due to lifestyle changes and dietary habits. Obesity-induced insulin resistance is considered as the major pathogenic factor in T2DM. In this study, we have investigated the effect of vindoline, an indole alkaloid of Catharanthus roseus on insulin resistance, oxidative stress and inflammatory responses in high glucose induced insulin resistant L6-myoblast cells, and dexamethasone (IR inducer)/1L-β (inflammation inducer) induced dysfunctional 3T3-L1 adipocytes. Results showed that dexamethasone induced dysfunctional 3T3-L1 adipocytes treated with different concentrations of vindoline significantly enhanced basal glucose consumption, accompanied by increased expression of GLUT-4, IRS-1 and adiponectin. Vindoline treatment significantly suppressed the ROS production and upregulated pro-inflammatory mediators in IL-1β induced dysfunctional adipocytes. Similarly, vindoline treated insulin resistant L6 myoblasts exhibited significantly enhanced glycogen content accompanied with upregulation of IRS-1 and GLUT-4. Thus, in vitro studies of vindoline in insulin resistant skeleton muscle and dysfunctional adipocytes confirmed that vindoline treatment significantly mitigate insulin resistance in myotubes and improves functional status of adipocytes. These results demonstrated that vindoline has the potential to be used as a therapeutic agent to ameliorate obesity-induced T2DM associated insulin resistance profile in adipocytes and skeletal muscles.

Calorie restriction (CR), defined as a reduction of the total calorie intake of 30% to 60% without malnutrition, is the only nutritional strategy that has proven to extend lifespan, prevent or delay the onset of age-associated diseases, and delay the functional decline in a wide range of species. However, little is known about the effects of CR when started early in life. We sought to analyze the effects of CR in the skeletal muscle of young Wistar rats. For this, 3-month-old male and female rats were subjected to 40% CR or fed ad libitum for 3 months. Gastrocnemius muscles were used to extract RNA and total protein. Western blot and RT-qPCR were performed to evaluate the expression of key markers/pathways modulated by CR and affected by aging. CR decreased body and skeletal muscle weight in both sexes. No differences were found in most senescence, antioxidant, and nutrient sensing pathways analyzed. However, we found a sexual dimorphism in markers of oxidative stress, inflammation, apoptosis, and mitochondrial function in response to CR. Our data show that young female rats treated with CR exhibit similar expression patterns of key genes/pathways associated with healthy aging when compared to old animals treated with CR, while in male rats these effects are reduced. Additional studies are needed to understand how early or later life CR exerts positive effects on health- and lifespan.

Matrix metalloproteinases have been implicated in muscular dystrophy progression and recent studies described the role of MMP-10 in skeletal muscle pathology of young dystrophic mice. Nevertheless, its implication in dystrophin deficient hearts is still missing. Here, we aimed at investigating MMP-10 implication in severe muscular dystrophic progression and characterize MMP-10 loss in skeletal and cardiac muscles of aged dystrophic mice. We examined the histopathological effect of MMP-10 ablation in aged mdx mice, both in the hind limb muscles and heart tissues. We have found that MMP-10 loss compromises survival rates of aged mdx mice, with skeletal and cardiac muscles developing a chronic inflammatory response. Our findings indicate that MMP-10 is implicated in severe muscular dystrophy progression, identifying a new area of investigation that could lead to future therapies for dystrophic muscles.

Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities and neutrophil bacterial killing. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to impairment of homeostasis in the inter-tissue metabolism of amino acids. For this reason, glutamine is currently part of clinical nutrition supplementation protocols and/or recommended for immune suppressed individuals. However, in a wide range of catabolic/hypercatabolic situations (e.g. ill/critically ill, post-trauma, sepsis, exhausted athletes) it is currently difficult to determine whether glutamine parenteral or enteral supplementation should be recommended based on the amino acid plasma concentration (glutaminemia). Although the beneficial immune based effects of glutamine supplementation is already established, many questions and evidence for positive in vivo outcomes still remain to be presented. Therefore, this paper provides an integrated review on how glutamine metabolism in key organs is important to cells of the immune system. We also discuss glutamine metabolism, action and important issues related to the effects of glutamine supplementation in catabolic situations.

A cross-sectional study was organised to investigate the range, prevalence, and associated factors for occupational health problems related to dental practice among Cambodian dentists; Participants underwent a face-to-face interview to explore dentists work-related health problems; 106 Cambodian dentists participated in this study, 68.9% were male. Ages ranged from 29 to 71 years, averaging 36.1 years, with the majority (77.4%) in the 29-40 age group. They had 5 to 18 years of practice experience, and worked an average of 52.2 hours per week. Commonly reported health issues included back pain (88.7%), headaches (81.1%), shoulder pain (78.3%), arm/hand pain (57.5%), and eye problems (48.1%). 38.7% of participants felt stressed and 19.8% depressed. Some reported suicidal thoughts and taking medication for depression. Despite these challenges, 91.5% enjoyed practicing dentistry; Findings highlight the need for interventions and strategies to address the physical and mental well-being of Cambodian dentists. By addressing these issues, steps can be taken to enhance the working conditions and professional satisfaction of dental professionals, ultimately benefiting both the practitioners and their patients.

Colorectal cancer is third most common malignancy. For metastasis of rectal cancer, metastasis to skeletal muscle tissue is rare. In this case report, we describe a 51-year-old male patient with rectal cancer with neoadjuvant concurrent radiotherapy and chemotherapy followed by transanal total mesorectal excision with ileostomy. However, he had deep venous thrombosis of left leg after operation and skeletal muscle metastasis was diagnosed via tissue proof. Therefore, less possibility of metastasis increased included brain, duodenum, bone, and nervous system. The prognosis of metastasis to skeletal muscle is poor in contrast to liver or lung metastasis.

TMEM16A is a Ca2+-activated Cl- channel expressed in various species and tissues. In mammalian skeletal muscle precursors, the activity of these channels is still poorly investigated. Here, we characterized TMEM16A channels and investigated if the pharmacological activation of Piezo1 channels could modulate the TMEM16A currents in mouse myogenic precursors. Whole-cell patch-clamp recordings combined with the pharmacological agents Ani9, T16inh-A01 and Yoda1 were used to characterize TMEM16A-mediated currents and the possible modulatory effect of Piezo1 activity on TMEM16A channels. Western blot analysis was also carried out to confirm the expression of TMEM16A and Piezo1 channel proteins. We found that TMEM16A channels were functionally expressed in fusion-competent mouse myogenic precursors. The pharmacological blockage of TMEM16A inhibited myocyte fusion into myotubes. Moreover, the specific Piezo1 antagonist Yoda1 positively regulated TMEM16A currents. The findings demonstrate, for the first time, a sarcolemmal TMEM16A channel activity and its involvement at the early stage of mammalian skeletal muscle differentiation. In addition, the results suggest a possible role of mechanosensitive Piezo1 channels in the modulation of TMEM16A currents.

Background and objectives: Musculoskeletal (MSK) pain significantly impacts physical activity and quality of life in the elderly, potentially influencing mortality. This study explored the relationship between MSK pain, physical activity, muscle mass, and mortality among older adults. Material and Methods: We studied 1000 participants of the Korean Longitudinal Study on Health and Aging (KLoSHA), a prospective, population-based cohort study of people aged 65 years or older. Survival status was tracked over a 5-year period. Correlations between Low back pain (LBP), knee pain, regular exercise, appendicular skeletal muscle mass (ASM), and other variables were analyzed. Logistic regression analyzes were used to identify independent risk factors for mortality. Results: Of the total participants, 829 (82.9%) survived after a 5-year period. Survivors tended to be younger, had a higher BMI, and were more active in regular exercise. In contrast, non-survivors exhibited a higher prevalence of both LBP and knee pain, along with increased instances of multiple MSK pain. Lower ASM correlated moderately with LBP and knee pain, whereas higher ASM was associated with regular exercise Lower ASM was moderately associated with LBP and knee pain, while higher ASM correlated with engagement in regular exercise. There was a moderate correlation between LBP and knee pain, both of which were associated with a lack of regular exercise. Age, sex, ASM, and regular exercise were significant predictors, even though MSK pain itself did not directly predict all-cause mortality. Conclusions: This study demonstrated the independent association between ASM, regular exercise, and mortality. Although MSK pain did not directly correlate with all-cause mortality, the non-survivor group had higher levels of both single and multiple MSK pain. Recognizing the interplay of MSK pain, physical activity, and muscle mass for older adults, the research underscores the need for holistic strategies to enhance health outcomes in older individuals with MSK pain.

The natural variation in estrogen secretion throughout the female menstrual cycle impacts various organs, including estrogen receptor (ER)-expressed skeletal muscle. Many women commonly experience increased fatigue or reduced energy levels in the days leading up to and during menstruation when blood estrogen levels decline. Yet, it remains unclear whether endogenous 17β-estradiol, a major estrogen component, directly affects energy metabolism in skeletal muscle due to the intricate and fluctuating nature of female hormones. In this study, we employed 3D 31P FID-MRSI to investigate phosphoryl metabolites in the soleus muscle of a cohort of young females (average age: 28 ± 6 years, n = 7) during the early follicular (EF) and peri-ovulation (PO) phases when their blood 17β-estradiol levels differ significantly (EF: 28 ± 18 pg/mL vs. PO: 71 ± 30 pg/mL, p < 0.05), while the levels of other potentially interfering hormones remain relatively invariant. Our findings reveal a reduction in ATP-referenced phosphocreatine (PCr) levels in the EF phase compared to the PO phase for all participants (5.4 ± 4.3%). Furthermore, we observe a linear correlation between muscle PCr levels and blood 17β-estradiol concentrations (r = 0.64, p = 0.014). Conversely, inorganic phosphate Pi and phospholipid metabolite GPC levels remain independent of 17β-estradiol but display a high correlation between EF and PO phases (p = 0.015 for Pi and p = 0.0008 for GPC).The robust association we have identified between ATP-referenced PCr and 17β-estradiol suggests that 17β-estradiol plays a modulatory role in the energy metabolism of skeletal muscle.

Epicatechin has been described as a polyphenol compound that promotes skeletal muscle restructuring, by expressing muscle regulation factors, activation of satellite cells and modulation of the main pathways associated with catabolism. However, the literature shows contrasting results of therapeutic effects and treatment protocols. Thus, the aim of this systematic review was to analyze the current literature addressing the molecular mechanism and clinical protocol of epicatechin on skeletal muscular atrophy in humans and animals. A search was conducted in PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library databases. The qualitative analysis showed a prevalence of the inhibitory action of epicatechin in myostatin expression and atrogenes FOXO, MAFbx and MuRF1. Epicatechin showed positive effects on increased follistatin and on the activation of the myogenic regulatory factors (Myf5, MyoD and myogenin). In addition, the studies evidenced the impact of epicatechin on the mitochondrias' biosynthesis in muscle fibers, activation of the signaling pathway of AKT/mTOR protein synthesis, and improvement of skeletal musculature performance, particularly when associated with physical training. Epicatechin showed promising clinical applicability through beneficial results under conditions that negatively affect the skeletal musculature. However, there is no protocol standardization allowing to draw more specific conclusions on its therapeutic use.

Recently, fasting has been spotlighted from a healthcare perspective. However, the de-tailed biological mechanisms and significance by which the effects of fasting confer health benefits are not yet clear. Due to certain advantages of zebrafish, as a vertebrate model widely utilized in biological studies, we used mRNA-sequencing and bioinformatics analysis to examine comprehensive gene expression changes in skeletal muscle tissues during fasting-refeeding. Our results produced a novel set of nutrition-related genes under a fasting-refeeding protocol. We found five dramatically upregulated genes in each fasting (for 24 hours) and refeeding (after 3 hours), exhibiting a rapid response to the provided conditional changes. The assessment of the gene length revealed, the gene set whose expression was elevated only after 3 hours of refeeding had a shorter length, suggesting that nutrition-related gene function is associated with gene length. Taken together, our results from bioinformatics analyses provide new insights into biological mechanisms induced by fasting-refeeding conditions within zebrafish skeletal muscle.

Muscle mass, strength and physical function are known to decline with age. This is associated with the development of geriatric syndromes including sarcopenia and frailty. These conditions are associated with disability, falls, longer hospital stay, higher readmission rates, institutionalisation, osteoporosis, and death. Moreover, they are associated with reduced quality of life, as well as substantial costs to health services around the world. Dietary protein is essential for skeletal muscle function. Older adults have shown evidence of anabolic resistance, where greater amounts of protein are required to stimulate muscle protein synthesis and therefore require higher daily amounts of dietary protein. Research shows that resistance exercise has the most beneficial effect on preserving skeletal muscle. A synergistic effect has been noted when this is combined with dietary protein, yet studies in this area lack consistency. This is due, in part, to the variation that exists within dietary protein, in terms of dose, quality, source, amino acid composition and timing. Research has targeted participants that are replete in dietary protein with negative results. Inconsistent measures of muscle mass, muscle function, physical activity and diet are used. This review attempts to summarise these issues, as well as introduce the possible role of the gut microbiome and its metabolome in this area.

The hyperactivation of the sympathetic nervous system (SNS) is linked to obesity, hypertension, and type 2 diabetes, with elevated norepinephrine (NE) levels being a key feature. Previous research has shown increased sodium-glucose cotransporter 1 (SGLT1) protein in kidneys of hypertensive rodents, prompting investigation into SGLT1 expression in other tissues such as skeletal muscle. This study aimed to assess: i) whether skeletal muscle cells and tissue express SGLT1 and SGLT2 protein; ii) if NE increases SGLT1 in skeletal muscle cells and iii) whether skeletal muscle of neurogenically hypertensive mice exhibits increased SGLT1 expression. We found that i) skeletal muscle cells and tissue are a novel source of SGLT2 protein and ii) NE significantly elevated SGLT1 in skeletal muscle cells. As SGLT2 inhibition (SGLT2i) with Empagliflozin increased SGLT1, in vivo studies with the dual SGLT1/2i, Sotagliflozin were warranted. Treatment of neurogenically hypertensive mice with Sotagliflozin significantly reduced blood pressure. Our findings suggest that SNS activity upregulates the therapeutic target, SGLT1 in skeletal muscle, potentially worsening cardiometabolic control. As clinical trial data suggests cardiorenal benefits with SGLT2i, future studies should aim to utilize sole SGLT1i which may offer a therapeutic strategy for conditions with heightened SNS activity, such as hypertension, diabetes and obesity.

Skeletal muscle (SKM), despite comprising ~40% of body mass, is rare. This review explores the mechanisms that help to explain this rarity, including unique SKM architecture and function, which prohibits development of new cancer as well as negates potential metastasis to SKM. SKM also presents a unique immune environment that may magnify the anti-tumorigenic effect. Moreover, the SKM microenvironment manifests characteristics such as decreased extracellular matrix stiffness and altered lactic acid, pH, and oxygen levels that may interfere with tumor development. SKM also secretes anti-tumorigenic myokines and other molecules. Collectively, these mechanisms help account for the rarity of SKM cancer.

Low efficiency of in vivo transfection of a few fibers revealed a novel tissue network which temporally amplified growth stimulation in the entire regenerating rat soleus muscle. This acupuncture-like effect was demonstrated when the fibers began to grow after complete fiber degradation, synchronous inflammation, myoblast and myotube formation. The first detection of neonatal sarcoplasmic/endoplasmic reticulum ATPase (SERCA1b) has been made in this system. The neonatal, fast and slow SERCA isoforms displayed consequent change with innervation and differentiation, recapitulating events in muscle development. In vivo transfection of myotubes with plasmids expressing dominant negative Ras or a calcineurin inhibitor peptide (Cain/cabin) proved that the expression of the slow myosin heavy chain and the slow muscle type SERCA2a are dif-ferently regulated. In vivo transfection of a few nuclei of myotubes with dnRas or SER-CA1b shRNA stimulated fiber size growth in the whole regenerating muscle but only until the full size had been reached. Growth stimulation by Ras and SERCA1b antisense was abolished in co-transfection with Cain or in case of perimuscular injection with IL4 antibody. This revealed a novel signalling network resembling to scale-free networks which, starting from transfected fiber myonuclei as “hubs”, can amplify growth stimula-tion uniformly in the entire regenerating muscle.

Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, temporary clamping of the aorta in aortic surgery, and acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress. Cerium oxide (CeO2) nanoparticles mimic the antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO2 has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n=6), diabetes group (group D, n=8), diabetes-CeO2 (group DCO, n=8), diabetes-ischemia/reperfusion (group DIR, n=8), and diabetes-ischemia/reperfusion-CeO2 (group DIRCO, n=8). DCO and DIRCO groups were given doses of CeO2 0.5mg/kg intraperitoneally 30 minutes before the IR procedure. A 120-minute ischemia-120-minute reperfusion period with 100% O2 was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p=0.047 and p=0.022, respectively). In group DIRCO and total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p

Issues of fairness and consistency in Taekwondo poomsae evaluation have emerged owing to the lack of an objective evaluation method. This study proposes a three-dimensional (3D) convolutional neural network (CNN)-based action recognition model for the objective evaluation of Taekwondo poomsae. The model exhibits robust recognition performance regardless of variation in perspective by reducing the discrepancies between training and test images. The model uses 3D skeletons of the poomsae unit action collected using a full-body motion-capture suit to generate synthesized two-dimensional (2D) skeletons from the desired perspective. This approach aids in obtaining 2D skeletons from diverse perspectives as part of the training dataset and ensures consistent recognition performance regardless of the viewpoint. The model was trained using 2D skeletons projected from diverse viewpoints, and its performance was evaluated using various test datasets, including projected 2D skeletons and RGB images captured from various viewpoints. Comparison of the performance of the proposed model with that of previously reported action recognition models demonstrated the superiority of the model, underscoring its effectiveness in recognizing and classifying Taekwondo poomsae actions.

In China, the demand for rabbit meat is also increasing, and the production for rabbit meat is important. However, the underlying mechanisms of regulate skeletal muscle growth and development in rabbits remain unclear. The purpose of this study was to identify candidate genes related to skeletal muscle growth in rabbits and explore their potential regulatory mechanisms. RNA-seq technique was used to compare the differences of skeletal muscle transcriptome in Fujian white rabbits at different developmental stages (day 20 and 26 of embryos and birth 1, 30 and 60-day-olds) with a total of 25 individual selected. A total of 9737 DEGs that were acquired from the five groups were annotated into three ontologies of the GO database: biological process (BP), cell component (CC), and molecular function (MF). For KEGG analysis, there are 8249 genes were enriched in 1148 pathways, of which 67 pathways were significantly enriched, mainly in Hypertrophic cardiomyopathy (HCM), the PPAR signaling pathway, MAPK signaling pathway. Among all comparison groups, SE was the most abundant AS event. Real-time PCR verified that the expression patterns of differential genes were consistent with the transcriptome sequencing results. These results will provide a molecular regulation mechanism of muscle growth and development in Fujian white rabbits, and should serve an important theoretical basis for improving meat performance and growth rate of Chinese local meat rabbit breeds.

The lordosis of the haemal part of the vertebral column is a frequent abnormality in reared fish. Haemal lordosis develops during the late larval and early juvenile period, mainly due to the high swimming activity of the fish in the rearing tanks. In the present study we examined whether haemal lordosis recovers during the growth of European sea bass. Furthermore, we aimed to develop simple morphometric indices (PrAn1 and PrAn2) that could link the severity of lordosis at the juvenile stage with fish morphological quality at harvesting. At 111 days post-hatching (dph, 53±4 mm standard length, SL), 600 seabass juveniles with lordotic (L, 200 fish) or normal (N, 400 fish) external morphology were selected and introduced in a common tank. At 150 dph (75±7 mm SL), 350 fish were randomly selected, pit-tagged and transferred in a sea cage for on-growing up to 502 dph (234±16 mm SL). The morphological examination of the fish at 150 and 502 dph revealed that the 60% (46 out of 77) of L juveniles turned into normal phenotype by the end of on-growing period. Interestingly, 56% of the fish with recovered external morphology (N-Rec) presented either a completely normal vertebral column (31%) or minor abnormalities of individual vertebrae (25%). Following the results of geometric morphometric analysis, the differences in the body shape between N-Rec and N fish were not significant (p&gt;0.05, canonical variate analysis). The examined morphometric indices were effective in discriminating the normal fish from the 58% (PrAn1) to 65% (PrAn2) of lordotic juveniles. Results are discussed with respect to the mechanism of lordosis recovery, as well as to their application for the quality control and cull out of the abnormal fish in the commercial hatcheries.

Oleuropein, glycosylated secoiridoid present in olive leaves is known to be an important antioxidant phenolic compound. We studied the antioxidant effect of low doses of oleuropein aglycone (3,4-DHPEA-EA) and oleuropein aglycone peracetylated (3,4-DHPEA-EA(P)) in murine C2C12 myocytes treated with hydrogen peroxide (H2O2). Both compounds were used at a concentration of 10 μM and were able to inhibit cell death induced by the H2O2 treatment, with 3,4-DHPEA-EA(P) being more. Under our experimental conditions, H2O2 efficiently induced the phosphorylated-active form of JNK and of its downstream target c-Jun. We demonstrated, by Western blot analysis, that 3,4-DHPEA-EA(P) was efficient in inhibiting the phospho-active form of JNK. This data suggests that the growth arrest and cell death of C2C12 proceeds via the JNK/c-Jun pathway. Moreover, we demonstrated that 3,4-DHPEA-EA(P) affects the myogenesis of C2C12 cells; because MyoD mRNA levels and the differentiation process are restored with 3,4-DHPEA-EA(P) after treatment. Overall, the results indicate that 3,4-DHPEA-EA(P) prevents ROS-mediated degenerative process in a genomic and epigenomic manner by functioning as an efficient antioxidant.

Oleuropein, glycosylated secoiridoid present in olive leaves is known to be an important antioxidant phenolic compound. We studied the antioxidant effect of low doses of oleuropein aglycone (3,4-DHPEA-EA) and oleuropein aglycone peracetylated (3,4-DHPEA-EA(P)) in murine C2C12 myocytes treated with hydrogen peroxide (H2O2). Both compounds were used at a concentration of 10 μM and were able to inhibit cell death induced by the H2O2 treatment, with 3,4-DHPEA-EA(P) being more. Under our experimental conditions, H2O2 efficiently induced the phosphorylated-active form of JNK and of its downstream target c-Jun. We demonstrated, by Western blot analysis, that 3,4-DHPEA-EA(P) was efficient in inhibiting the phospho-active form of JNK. This data suggests that the growth arrest and cell death of C2C12 proceeds via the JNK/c-Jun pathway. Moreover, we demonstrated that 3,4-DHPEA-EA(P) affects the myogenesis of C2C12 cells; because MyoD mRNA levels and the differentiation process are restored with 3,4-DHPEA-EA(P) after treatment. Overall, the results indicate that 3,4-DHPEA-EA(P) prevents ROS-mediated degenerative process in a genomic and epigenomic manner by functioning as an efficient antioxidant.

In this study we used a recently developed ex vivo-in vitro model to assess the effect of feeding older adults a casein protein hydrolysate (CPH) compared with non-bioactive non-essential amino acid (NEAA) supplement on Muscle Protein Synthesis (MPS) and Breakdown (MPB). Serum from six healthy older males following overnight fast and 60 min postprandial ingestion of CPH or NEAA (0.33 g.kg^-1 body mass) was used to condition C2C12 myotube media. CPH-fed serum significantly increased MPS compared to fasted serum. In addition, CPH-fed serum induced myotube growth and markedly suppressed atrogin-1, but not MuRF1, expression. Comparatively, no change in MPS, myotube growth and gene expression was observed following NEAA-fed serum treatment. CPH-fed serum from older adults stimulated de novo MPS, suppressed markers of protein breakdown and resulted in myotube growth, indicating a potential role for CPH as a dietary protein source to prevent age-related sarcopenia.

Oleuropein, glycosylated secoiridoid present in the olive leaves, is known as an important antioxidant phenolic compound. We studied the antioxidant effect of low dose of oleuropein aglycone (3,4-DHPEA-EA) and oleuropein aglycone peracetylated (3,4-DHPEA-EA(P)) in murine C2C12 myocytes treated with hydrogen peroxide (H2O2). Both compounds were used at a concentration of 10 μM and were able to inhibit cell death induced by H2O2 treatment, with 3,4-DHPEA-EA(P) being more. Under our experimental conditions H2O2 efficiently induced the phosphorylated-active form of JNK and of its downstream target c-Jun. We demonstrated, by Western blot analysis, that 3,4-DHPEA-EA(P) was efficient in inhibiting the phospho-active form of JNK. This data suggest that growth arrest and cell dead of C2C12 proceeds via the JNK/c-Jun pathway. Moreover, we demonstrated that 3,4-DHPEA-EA(P) affects myogenesis of C2C12 cells; because the MyoD mRNA levels and the differentiation process are restored after treatment with 3,4-DHPEA-EA(P). Overall, the results indicate that 3,4-DHPEA-EA(P) prevents ROS-mediated degenerative process by functioning as an efficient antioxidant.

Near-Infrared Spectroscopy (NIRS) has been used to measure muscle mitochondrial capacity. The current method requires as many as 22 short ischemic occlusions to generate a recovery curve for mitochondrial capacity. PURPOSE: To determine the effectiveness of using a 6-occlusion analysis protocol to study muscle mitochondrial capacity. METHOD: Two independent, unidentified data sets were analyzed (bicep n=48, forearm n=41) from previous studies using a NIRS device (Artinis, Ltd.). Both data sets had two recovery tests that included 22 ischemic occlusions. A recovery rate used to indicate mitochondrial capacity was calculated two different ways (simultaneously). Each sample was analyzed with a MATLAB program; with a curve-fit for the 22 ischemic occlusions and curve matching for the first six ischemic cuffs and an end resting value. The two resulting rate constants were compared using correlations, both for the two data sets, good and bad fitting data, using the best 5 of 6 points for the 6 cuff approach. RESULTS: The rate constants were not significantly different between the 22 cmuff and 6 cuff for the total data sets: bicep (1.43+0.32min^-1, 1.44+0.35min^-1, p=0.56), forearm (1.94+0.42min^-1, 1.95+0.44min^-1, p=0.76). The average bicep rate constants, when compared to each other, had an equation of y=1.07x-0.09, R²=0.90. The average forearm rate constants, when compared to each other, had an equation of 0.98x+0.02, R²=0.93. CONCLUSIONS: The 6-Cuff analysis provided the same results as the longer 22-cuff. The 6-cuff approach is both shorter in time and uses less ischemic occlusion periods, increasing the practicality of the NIRS mitochondrial capacity test.

NIRS uses the relative absorption of light at 850nm and 760nm, to determine skeletal muscle oxygen saturation. Previous studies have used the ratio of both signals to report muscle oxygen saturation. Purpose: To evaluate the different approaches used to represent muscle oxygen saturation, and to evaluate the pulsations of the O₂heme and Heme signal. Method: Twelve participants, ages 20-29years were tested on the forearm flexor muscles using continuous wave NIRS at rest. Measurements were taken during 2-3mins rest, during physiological calibration (5-minuts Ischemia) and during reperfusion. Results: There was a significant difference in pulse size between O₂heme and Heme signal at the three locations (p < 0.05). Resting oxygen saturation was 58.8+9.2%, 69.6+3.9%, and 89.2+6.9% when calibrated using O₂heme, TSI, and Heme, respectively. Conclusion: The difference in magnitude of O₂heme and Heme pulse with each heartbeat might suggest different anatomical locations of these signals, which propose calibrating with just one of the signals instead of the ratio of both. Calculations of physiological calibration must account for increased blood volume in the tissue, because of the changes in blood volume which appear to be primarily from the O₂heme signal. Resting oxygen levels calibrated with Heme agrees with theoretical oxygen saturation.

Kinect is a device that has been widely used in many areas since it was released in 2010. Kinect SDK was announced in 2011 and used in many other areas than its original purpose, which was a controller for gaming. In particular, it has been used by a number of artists in digital media art since it is inexpensive and has a fast recognition rate. However, there is a problem. Kinect create 3D coordinates with a single 2D RGB image for x, y value - single depth image for z value. And this creates a significant limitation on the installation for interactivity of media art. Because the Cartesian XY coordinate and the spherical Z coordinate system are used in combination, depth error depending on the distance is generated, which makes real-time rotation recognition and coordinate correction difficult above coordinate system. This paper proposes a real-time calibration method of Kinect recognition range expansion for useful application in the digital media art area. The proposed method can recognize the viewer accurately by calibrating a coordinate in any direction in front of the viewer. 3,400 datasets witch acquire from experiment were measured as five stances: the 1m attention stance, 1m hands-up stance, 2m attention stance, 2m hands-up stance, and 2m hands-half-up stance, which were taken and recorded every 0.5 sec. The experimental results showed that the accuracy rate was improved about 11.5% compared with front measurement data according to Kinect reference installation method.

Purpose: The aim of this article is to analyze the incidence of undiagnosed obstructive sleep apnea OSA in patients affected by dento-skeletal malformation. We also evaluated the patterns most affected by the condition and calculated the post surgical changes. Methods: We conducted a retrospective cohort study on 71 patients including 35 men and 36 women. Patients were evaluated with Polysomnography before surgery and at least 6 months after surgery to assess any improvement or worsening of the apnea hypopnea index AHI index. Regarding AHI evaluation criteria an AHI > 5 was considered indicative of OSA, 4 5, com-pared to 20.5% described in the Italian population. Conclusion: In patients who receive orthognathic surgery the presence of Obstructive Sleep Apnea is significantly higher than in the general population. When planning the surgical correction of a dentoskeletal malformation, the surgeon must aim not only to the aesthetics results, but also to a proper stomatognathic and respiratory function, this cannot be done without taking poly-somnography information into account.

Pigs are susceptible to cold stress due to the absence of brown fat caused by the partial deletion of uncoupling protein 1 during their evolution. Some local pig breeds in China, exhibit potential cold adaptability, but research has primarily focused on fat and intestinal tissues. Skeletal muscle plays a key role in adaptive thermogenesis in mammals, yet the molecular mechanism of cold adaptation in porcine skeletal muscle remains poorly understood. This study investigated the cold adaptability of two pig breeds, Mashen pigs (MS) and Large White pigs (LW), in a 4-day cold (4°C) or room temperature (25°C) environment. We recorded phenotypic changes and collected blood, and longissimus dorsi muscle for transcriptome sequencing. Finally, a candidate gene was randomly selected for functional exploration in porcine skeletal muscle satellite cells. A decrease in body temperature and body weight in both LW and MS pigs under cold stress, accompanied by increased shivering frequency and respiratory frequency. However, MS pigs demonstrated stable physiological homeostasis, indicating a certain level of cold adaptability. LW pigs primarily responded to cold stress by regulating heat production and Glycolipid energy metabolism. MS pigs exhibited a distinct response to cold stress, involving regulation of heat production, energy metabolism pathways, robust fatty acid oxidation ability, and stronger immune response. Furthermore, the functional exploration of PRSS8 in porcine skeletal muscle satellite cells revealed it affected cellular energy metabolism and thermogenesis by regulating ERK phosphorylation. These findings shed light on the diverse transcriptional responses of skeletal muscle in LW and MS pigs under cold stress, offering valuable insights into the molecular mechanisms underlying cold adaptation in pigs.

The development of sarcopenia in the elderly is associated to many potential factors and/or processes, that impair the renovation and the maintenance of skeletal muscle mass and strength as ageing progresses. Among them, a defect by skeletal muscle to respond to anabolic stimuli is to be considered. Common anabolic stimuli/signals in skeletal muscle are hormones (insulin, growth hormones, IGF-1, androgens, β-agonists such epinephrine), substrates (amino acids as protein precursors on top, but also glucose and fat, as source of energy), metabolites (such as β-agonists and HMB), some cytokines, various biochemical/ intracellular mediators), physical exercise, neurogenic and immune-modulating factors, etc. Each of them may exhibit a reduced effect upon skeletal muscle as ageing progresses. In this review article, we will concisely overview the effects of anabolic signals on muscle metabolism, as well as currently available evidence of a resistance, at skeletal muscle level, to any of the above-mentioned anabolic factors, from both in vitro and in vivo studies.

The combined muscle-skeletal traumas (MST) are very frequent over the last few years. The emergency care try to save the life of the patient and to receive resuscitation treatment. The role of Trauma surgeon is to choose the right moment for surgery. Aim: To present the management of patient with combined height injury, fracture stabilization, partial foot amputation, local flaps, skin grafting and HIFU – thermotherapy as scar treatment. Materials and methods: 40 years old mail patient, injured after a fall from 8 meters in an elevator shaft. After resuscitation treatment to control the shock the Imaging results are: burst fracture of L3 with spinal canal stenosis, fracture of the sacral bone Denis I, fracture of the right humerus in the proximal third, Monteggia fracture of the left arm, fracture of the proximal third of the right tibia as well as comminuted fractures of both calves and of both heel bones. Results: After a few operations his final result was well healed bone fractures and a good quality soft tissue coverage allowing the patient a satisfactory quality of life. Conclusions: Combined traumas of the muscle- skeletal system are severe, serious and difficult to manage. The good outcome in their treatment requires a team approach between the different medical specialists.

Age-related disorders of the musculoskeletal system including sarcopenia, osteoporosis and arthritis represent some of the most common chronic conditions worldwide, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. Collectively, these conditions involve multiple tissues, including skeletal muscle, bone, articular cartilage and the synovium within the joint lining. In this review, we discuss the potential for oligonucleotide therapies to combat the unmet clinical need in musculoskeletal disorders by evaluating the successes of oligonucleotides to modify candidate pathological gene targets and cellular processes in relevant tissues and cells of the musculoskeletal system. Further, we discuss the challenges that remain for the clinical development of oligonucleotides therapies for musculoskeletal disorders and evaluate some of the current approaches to overcome these.

Skeletal myopathy encompasses both atrophy and dysfunction and is a prominent event in cancer and chemotherapy-induced cachexia. Here, we investigate the effects of chemotherapeutic agent, 5-fluorouracil (5FU), on skeletal muscle mass and function, and whether small molecule therapeutic candidate, BGP-15, could be protective against the chemotoxic challenge exerted by 5FU. Additionally, we explore the molecular signature of 5FU treatment. Male Balb/c mice received metronomic tri-weekly intraperitoneal delivery of 5FU (23 mg/kg), with and without BGP-15 (15 mg/kg), 6 times in total over a 15-day treatment period. We demonstrated that neither 5FU, nor 5FU combined with BGP-15, affected body composition indices, skeletal muscle mass or function. Adjuvant BGP-15 treatment did, however, prevent the 5FU-induced phosphorylation of p38 MAPK and p65 NF-κB subunit, signalling pathways involved in cell stress and inflammatory signalling, respectively. This as associated with mitoprotection. 5FU reduced the expression of the key cytoskeletal proteins, desmin and dystrophin, which was not prevented by BGP-15. Combined, these data show that metronomic delivery of 5FU does not elicit physiological consequences to skeletal muscle mass and function but is implicit in priming skeletal muscle with a molecular signature for myopathy. BGP-15 has modest protective efficacy against the molecular changes induced by 5FU.

Although sarcopenia is known to be a risk factor for non-alcoholic fatty liver disease (NAFLD), whether NAFLD is a risk factor for the development of sarcopenia is not clear. We investigated bidirectional relationships between NAFLD and low skeletal muscle mass index (LSMI) using three different datasets. Participants were classified into LSMI and normal groups. LSMI was defined as a body mass index (BMI)-adjusted appendicular skeletal muscle mass &lt;0.789 in men and &lt;0.512 in women or as the sex-specific lowest quintile of BMI-adjusted total skeletal muscle mass. NAFLD was determined according to NAFLD liver fat score or abdominal ultrasonography. The NAFLD groups showed a higher hazard ratios (HRs) with 95% confidence intervals (CIs) for LSMI than the normal groups (HRs=1.213, 95% CIs=1.050–1.402). The LSMI groups also showed a higher HRs with 95% CIs for NAFLD than normal groups (HRs=1.564, 95% CIs=1.378–1.775). Participants with NAFLD had consistently less skeletal muscle mass over 12 years of follow-up. In conclusion, LSMI and NAFLD showed a bidirectional relationship. Maintaining muscle mass should be emphasized in the management of NAFLD.

FER zeolites has a unique framework structure and acid distribution, and is widely studied as a catalyst for reactions such as n-butene skeletal isomerization and dimethyl ether carbonylation. The BAS located in the 10-MR of FER zeolites serves as the active site for the isomerization reaction of n-butene skeletal to produce isobutene. In contrast, the acid site found in the 8-MR is prone to side reactions, such as polymerization and cracking, which can adversely affect the selectivity of isobutene. This study prepared five types of FER zeolites using different method, inducing Na-form or H-form crystal seeds without organic structure directing agents (OSDAS), using pyridine alone as a template, and combining the seeds with pyridine. The differences in the structure and acid distribution of the five zeolites were investigated, as well as their catalytic performance for the the skeletal isomerization of n-Butene. Experiments and characterization results showed that under hydrothermal synthesis conditions, the FER-PY+SH zeolites synthesized by using both H-form zeolites seeds and pyridine exhibited the highest aluminum concentrations at T1 and T3 positions, along with the greatest BAS of 10-MR. This unique composition contributed to the highest selectivity of isobutene. The FER-PY+SH catalyst was continuously used for 720 hours at 350 ℃, 0.1 MPa, and n-butene mass space velocity of 2.0 h^-1 for three recycles on 2160 h. During this period, the conversion of n-butene over 39%, while the selectivity of isobutene exceeded 95%.The catalyst exhibited excellent stability and activity.

Introduction: Obesity affects over 650 million individuals worldwide and it is a major public health problem. Bariatric surgery is the most effective treatment for severe obesity, resulting in significant weight reduction and improvement in obesity-related conditions. However, the weight loss achieved through bariatric surgery often correlates with a notable decrease in skeletal muscle. This correlation suggests an elevated risk of sarcopenia among patients after surgery. The aim of this study was to evaluate the effects of obesity and bariatric surgery on sarcopenia-related indicators and diagnosis before and after surgery. Methods: A total of 17 bariatric surgery patients were included in this prospective study. The parameters to diagnose sarcopenia were determined for each participant, based on EWGSOP2 and EASO/ESPEN consensuses. All evaluations were performed on the five moments of this study: before surgery and at 1, 6, 12 and 18 months after surgery. Results: In this study, 88.2% of the subjects were female, the mean BMI was 42.9 kg/m² and the mean weight was 105.9 kg. After surgery, the mean weight consistently decreased, with all differences from baseline being statistically significant (p<0.001). When using the SARC-F questionnaire for screening, the risk of sarcopenia increased post-surgery, and decreased at 12 months, declining to zero at 18 months. Muscle strength decreased significantly (p=0.002) at the 1 month after surgery assessment, with slight variations thereafter, none statistically significant. Muscle mass was normal before surgery but decreased significantly post-surgery (p<0.001). When applying the ESPEN/EASO consensus cut-off criteria for sarcopenic obesity, 35.3% of the patients met the criteria preoperatively. After surgery, the results increased to 70.6% in the first month but decreased afterward to 41.2% at 6 months. Discussion: This study evaluated the impact of bariatric surgery on sarcopenia and sarcopenic obesity, for a duration of up to 18 months after surgery, using the EWGSOP2 and ESPEN/EASO consensuses criteria. Bariatric surgery, the most effective treatment for severe obesity, often results in muscle mass loss alongside fat loss. Handgrip strength, a key sarcopenia indicator, showed a significant early post-surgery decline, whereas the weight-dependent sit-to-stand test did not. This suggests weight loss impacts different muscle function tests variably. Muscle mass decreased continuously after surgery. However, other indicators had mixed results. Applying ESPEN/EASO guidelines, the study found a temporary post-surgery increase in sarcopenic obesity, peaking at one month and returning to pre-surgery levels by six months. However, different criteria led to different results. Conclusion: The results indicate a clear deleterious impact of bariatric surgery on muscle strength and mass, the most important indicators of sarcopenia. Also, the impact seems to occur very early after surgery, indicating that the appropriate timeframe to try to prevent this effect may be the prehabilitation period followed by the post-surgery timeframe.

Chikungunya (CHIKV) and Mayaro (MAYV) viruses are arthritogenic alphaviruses that promote an incapacitating and long-lasting inflammatory muscle-articular disease. Despite studies pointing out the importance of skeletal muscle (SkM) in viral pathogenesis, the long-term consequences on its physiology after acute injury and the mechanism of persistence of symptoms are still poorly understood. Combining molecular, morphological, Nuclear Magnetic Resonance Imaging, and histological analysis, we conduct a temporal investigation of CHIKV and MAYV replication in a wild-type mice model, focusing on the impact on SkM composition, structure, and repair in the acute and late phases of infection. We found that viral replication and induced-inflammation promote fast loss of muscle mass and reduction of fibers cross sectional area, by inducing muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin expression, that trigger protein breakdown, resulting in acute SkM fibers atrophy. After temporal reduction of inflammation and clearance of infectious viral particles, SkM atrophy persists until the late phase of infection. The genomic CHIKV and MAYV RNAs were still detected in SkM at the late phase, along with increased levels of chemokines and anti-inflammatory cytokines expression. In agreement with the involvement of inflammatory mediators on induced atrophy, neutralization of TNF and the reduction of oxidative stress using monomethyl fumarate, an agonist of Nrf2, decreases atrogens expression and atrophic fibers, while increasing weight gain in treated mice. Taken together, these data indicate that arthritogenic alphavirus infection could chronically impact body SkM composition and also harm repair machinery, contributing to a better understanding of mechanisms of arthritogenic alphaviruses pathogenesis and with description of potentially new targets of therapeutic intervention.

Background Sarcopenia is a state with progressive and generalized loss of skeletal muscle mass and strength. It is a serious complication occurring in chronic kidney disease (CKD) patients which increases morbidity and mortality rate. Sarcopenia is diagnosed when loss of both compartments - muscle strength and skeletal muscle quality or quantity are present. However, there are still numerous patients, also with CKD, diagnosed as pre-sarcopenic individuals with low muscle strength and normal skeletal muscle quality or quantity and conversely, with correct muscle strength and decreased skeletal muscle mass, who are prone to develop sarcopenia in future life. It is crucial to examine numerous variables possibly associated with changes of skeletal muscle mass and muscle strength in terms of preventing the development of sarcopenia. The aim of the study was to investigate anthropometric and clinical correlates and sources of variation in both skeletal muscle mass and muscle strength in advanced stages of CKD. Methods The study sample consisted of 84 non-dialysis dependent patients of both sexes (including 45.2% of women) with eGFR < 45 ml/min/1.73m²: 26.2% with eGFR 30-44 mL/min/1.73 m², 65.5% with eGFR 15-29 mL/min/1.73 m² and 8.3% with eGFR < 15 mL/min/1.73 m². Muscle strength was estimated by measuring hand grip strength (HGS) with the use of handheld hydraulic dynamometer. Muscle quantity was measured by bioimpedance spectroscopy using Body Composition Monitor. Appendicular skeletal muscle mass (ASM) was calculated according to Lin’s formula. Serum creatinine, urea, uric acid and albumin were measured. Results In bivariate analysis we found that ASM significantly and positively correlated with anthropometric variables such as body mass (r=0.903, p<0.001), NH weight (r=0.882, p<0.001), height (r=0.694, p<0.001), body mass index (BMI) (r=0.701, p<0.001), lean tissue mass (LTM) (r=0.664, p<0.001), lean tissue index (LTI) (r=0.433, p<0.001), fat mass (r=0.614, p<0.001) and fat tissue index (FTI) (r=0.449, p<0.001), and was negatively associated with clinical variable such as hydration status (p<0.001). HGS significantly and positively correlated with anthropometric parameters such as body mass (r=0.319, p=0.003), NH weight (r=0.315, p=0.004), height (r=0.666, p<0.001), LTM (r=0.490, p<0.001), LTI (r=0.238, p=0.029), and ASM (r=0.501, p<0.001), and was negatively associated with clinical variables like uric acid (p=0.039) and urea (p<0.001). After adjustment for age, sex and height, HGS remained significantly and negatively related with uric acid (β=-1.078, p=0.041) and hydration status (β=-0.805, p=0.042). Conclusions In CKD patients, ASM is determined mainly by anthropometric parameters but HGS - both by anthropometric and clinical variables specific for CKD.

Static and functional occlusal relationships are the well-defined objectives of orthodontic therapy. To accomplish it, the jaws must be positioned in centric relation (CR)/ Central occlusion (CO) and appropriately proportioned in three space planes. Orthodontists have well-established techniques when analyzing the skeletal connection between the maxilla and mandible in both sagittal and vertical planes. Although there exist multiple analyses for the skeletal transverse dimension (STD), their inclusion in conventional orthodontic diagnosis is not widely acknowledged. Transverse tooth compensations have been visually represented in prosthodontic literature using a crosshatch arch that passes through the buccal and palatal cusps of maxillary molars, known as the Wilson curve. An inflated Wilson curve has long been seen as a prosthetic maxim, increasing the possibility of working and non-working side interferences. Research has indicated a connection between higher masticatory muscle activity and posterior occlusal contacts or interferences. When skeletal transverse issues are concealed by dental expansion, there is an elevated susceptibility to gingival recession in orthodontic patients who have a small Maxilla or constricted upper jaw. The temporomandibular joints, muscles, periodontal tissue, and airway might all suffer in a susceptible patient with a transverse insufficiency brought on by a narrow maxilla. As for orthodontists, the objective is to create skeletal connections and functional occlusion that are as near ideal as feasible. This will reduce the likelihood of occlusion-related inconsistencies exacerbating the negative consequences on the dentition, periodontium, or joints. An accurate skeletal and dental diagnostic in all three space planes is required. Our goal is to explain all approaches to enable readers to use a transverse skeletal diagnostic in their practice regardless of the technological level at their disposal. The initial step is to ascertain the kind and presence of deficiencies in the maxilla. Since fewer soft tissue alterations are caused by maxilla hypoplasia in the transverse direction, skeletal transverse dimension (STD) assessment is a more significant challenge than vertical or sagittal discrepancy assessment. Model analysis, clinical assessments, radiographic measurements, and occlusograms have all proven successful in producing accurate assessments. Most of the time, surgically assisted maxillary expansion (SARME) is reported to have higher stability than orthopedic maxillary expansion (OME). We examine and discourse on possible research opportunities using the Collaborative Cross (CC) mouse model as a substitute research model.

Sodium butyrate (NaB) is one of the short-chain fatty acids and is notably produced in large amounts from dietary fiber in the gut. Recent evidence suggests that NaB induces cell proliferation and apoptosis. The skeletal muscle is rich in plenty of mitochondrial. However, it is unclear how NaB acts on host muscle cells and whether it is involved in mitochondria-related functions in myocytes. The present study aimed to investigate the role of NaB treatment on the proliferation, apoptosis, and mitophagy of bovine skeletal muscle satellite cells (BSCs). The results showed that NaB inhibited the proliferation and promoted apoptosis of BSCs, and promoted mitophagy in a time and dose-dependent manner in BSCs. In addition, 1mM NaB increased the mitochondrial ROS level, decreased the mitochondrial membrane potential (MMP), increased the number of autophagic vesicles in mitochondria, and increased the mitochondrial DNA(mtDNA) and ATP level. The effects of the mTOR pathway on BSCs were investigated, and the results showed that 1mM NaB inhibited the mRNA and protein expression of mTOR and genes AKT1, FOXO1, and EIF4EBP1 in the mTOR signaling pathway, while the addition of PP242, an inhibitor of the mTOR signaling pathway, also inhibited mRNA and protein expression levels of mTOR, AKT1, FOXO1, and EIF4EBP1, and promoted mitophagy and apoptosis, which were consistent with the effect of NaB treatment. In conclusion, NaB might promote mitophagy and apoptosis in BSCs by inhibiting the mTOR signaling pathway. Our results would expand the knowledge of sodium butyrate on bovine skeletal muscle cell state and mitochondrial function.

Valley fever or coccidioidomycosis is a pulmonary infection caused by several species of coccidi-oides (Cocci) fungi that is endemic to California and Arizona. Skeletal coccidioidomycosis ac-counts for about half of disseminated infections, with the vertebral spine being the preferred site of dissemination. Most cases of skeletal coccidioidomycosis progress to bone destruction or spread to adjacent structures such as joints, tendons, and other soft tissues causing significant pain and restricting mobility. Manifestations of such cases are usually non-specific, making di-agnosis very challenging, especially in non-endemic areas. In this review, we explore case reports of dissemination of coccidioidomycosis to bones and/or joints to highlight key differential fea-tures with other conditions or diseases and highlight opportunities for mechanistic and pre-clinical studies that can help improve diagnostics, prognostics, and treatments.

The ryanodine receptor (RyR) is a Ca2+ release channel in the sarcoplasmic reticulum of skeletal and cardiac muscles and plays a key role in excitation-contraction coupling. The activity of the RyR is regulated by many intracellular factors such as divalent cations (Ca2+ and Mg2+), nucleotides, associated proteins, and reactive oxygen species. Since these intracellular factors change depending on the condition of the muscle, e.g., exercise, fatigue, or disease states, the RyR channel activity will be altered accordingly. In this review, we describe how the RyR channel is regulated under various conditions and discuss the possibility that the RyR acts as a sensor for change in the cellular environment of muscles.

Mesenchymal stem cells (MSCs) showed in vitro mesoderm-lineage differentiation and self-renew capacity. However, no comparative study was reported on the biological characteristics of stem cells derived from skeletal muscle (SM-MSCs), dermal skin (DS-MSCs), and adipose tissues (A-MSCs) from a single donor in camels. The present study aimed to evaluate the influence of MSCs source on stem cell characteristics. We evaluated proliferation capacity and mesoderm-lineage differentiation potential from SM-MSCs, DS-MSCs, and A-MSCs. They showed spindle-like morphology after homogenization. The proliferation ability was no significant difference in all groups. Furthermore, the portion of the cell cycle and expression of pluripotent markers (Oct4, Sox2, and Nanog) were similar in all cell lines at passage 3. The differentiation capacity of A-MSCs into adipocytes was significantly higher than that of SM-MSCs and DS-MSCs. However, the osteoblast differentiation capacity of A-MSCs was significantly lower than that of SM-MSCs and DS-MSCs. Additionally, after osteoblast differentiation, the ALP activity and calcium content was significantly decreased in A-MSCs as compared to SM-MSCs and DS-MSCs. To the best of our knowledge, we primally established MSCs from the single camel and demonstrated their comparative characteristics including expression of pluripotent factors and proliferation, and in vitro differentiation capacity into adipocytes and osteoblasts.

Myostatin inhibition therapy has held much promise for the treatment of muscle wasting disorders. This is particularly true for the fatal myopathy, Duchenne Muscular Dystrophy (DMD). Following on from promising pre-clinical data in dystrophin-deficient mice and dogs, several clinical trials were initiated in DMD patients using different modality myostatin inhibition therapies. All failed to show modification of disease course as dictated by the primary and secondary outcomes measures selected: the myostatin inhibition story thus far, is a failed clinical story. These trials have recently been extensively reviewed and reasons why pre-clinical data collected in animal models has failed to translate into clinical benefit to patients has been purported. However, the biological mechanisms underlying translational failure need to be examined to ensure future myostatin inhibitor development endeavors do not meet with the same fate. Here, we explore the biology which could explain the failed translation of myostatin inhibitors in the treatment of DMD.

This study presents a novel technique utilizing high frequency vibration to shorten treatment time and preserve alveolar bone in challenging orthodontic cases treated with Invisalign® clear aligners. Four non-growing orthodontic patients (age range 14-47 years old) with Class II skeletal patterns (convex profiles with retrognathic mandibles) who sought correction of their crowded teeth and non-surgical correction of their convex profiles were included in this study. These patients were treated using Invisalign clear aligners together with high frequency vibration (HFV) devices (120 Hz) (VPro5™) that were used by all patients for five minutes per day during active orthodontic treatment. Vertical control and forward rotation of the mandible for each patient was achieved through pre-programming the Invisalign to produce posterior teeth intrusion. Successful forward rotation of the mandibles achieved in all patients led to improvement of their facial convex profiles (ANB improved 2.1 + 0.5 degrees; FMA improved 1.2 +1.1 degrees). Dental decompensation was achieved by lingual tipping of the lower incisors and palatal root torque of upper incisors. The use of HFV together with Invisalign facilitated achieving these results within a 12+6 month period. In addition, more bone labial to the lower incisors after their lingual movement was noted. In conclusion, the use of HFV concurrent with SmartTrack Invisalign aligners allowed complex tooth movement and forward projection without surgery in non-growing patients with skeletal Class II relationships. The clinical impact and implications of this case series is that the use of HFV facilitates complex orthodontic tooth movement including posterior teeth intrusion and incisor decompensation in addition to increased bone formation labial to lower incisors that may minimize future gum recession due to their labial inclination.

Aging associates with progressive loss of skeletal muscle function leading up to sarcopenia, a process characterized by impaired mobility and weakening of muscle strength. Molecular mechanisms underpinning sarcopenia are still poorly characterized. Since aging associates with profound epigenetic changes, epigenetic landscape alteration analysis in the skeletal muscle promises to highlight molecular mechanisms of age-associated sarcopenia. The study was conducted exploiting the short-lived turquoise killifish Nothobranchius furzeri (Nfu), a relatively new model for aging studies. The epigenetic analysis suggested for a less accessible and more condensed chromatin in old Nfu skeletal muscle. Specifically, an accumulation of heterochromatin regions was observed as consequence of increased levels of H3K27me3, HP1alpha, polycomb complex subunits and senescence associated heterochromatic foci (SAHFs). Consistently, euchromatin histone marks, including H3K9ac, decreased. The integrative bioinformatics analysis of RNASeq and ChIPSeq, related to skeletal muscle of Nfu at different ages, revealed a down-modulation of genes involved in cell cycle, differentiation and DNA repair and an up-regulation of inflammation and senescence genes. Undoubtedly, more studies are needed to disclose the detailed mechanisms, but this approach revealed an unprecedented specific features of Nfu skeletal muscle aging, potentially associated with sarcopenia onset and consequent impairment of swimming and mobility typical of old Nfu.

Although fragility fractures, osteoporosis, sarcopenia and frailty are becoming more prevalent in our aging society the treatment options are limited and preventative strategies are needed. Despite magnesium being integral bone and muscle physiology the relationship between dietary magnesium and skeletal muscle and bone health has not been investigated concurrently before. We analysed cross-sectional associations between dietary magnesium and skeletal muscle mass (as fat free mass – FFM), grip strength and bone density (BMD) in 156,575 men and women aged 39-72 years from the UK Biobank cohort. FFM was measured with bioelectrical impedance and expressed as the percentage of body weight (FFM%) or divided by body mass index (FFM_BMI). Adjusted mean grip strength, FFM%, FFM_BMI, and BMD were calculated according quintiles of dietary magnesium, correcting for covariates. Significant inter-quintile differences across intakes of magnesium existed in men and women respectively of 1.1% and 2.4% for grip strength, 3.0% and 3.6% for FFM%, 5.1% and 5.5% for FFM_BMI, and 2.9% and 0.9% for BMD. These associations are as great or greater than annual measured losses of these musculoskeletal outcomes indicating potential clinical significance. Our study suggests that dietary magnesium may play a role in musculoskeletal health and have relevance for population prevention strategies for sarcopenia, osteoporosis and fractures.

Little is known about skeletal muscle thickness, echogenicity, and muscle quality (handgrip strength /muscle thickness) in breast cancer-related lymphedema (BCRL). Using B-mode ultrasound, we recorded the raw radiofrequency data of the affected (AA) and unaffected (UA) arms of women (n=20) with BCRL, and in 20 control women with no lymphedema (CA). The data were converted into images and measurements of skin, subcutaneous fat and muscle thickness were obtained. Within a designated region of interest, muscle echo-intensity was assessed using computer graded grey scale and muscle thickness was measured using ImageJ2. Handgrip strength was measured using standard dynamometry. We found that forearm muscle thickness was similar among AA, UA, and CA. When compared to the unaffected and control arms, the affected arm had a significantly higher (p 0.013) muscle echo-intensity. When compared to the AA, handgrip strength was similar to UA (p 0.401) but lower than CA (p 0.05). We conclude that the use of B-mode ultrasound is a reliable method to assess muscle thickness and EI in BCRL. When comparing AA to UA, the elevated levels of muscle EI in AA did not influence strength or muscle quality. The elevated EI in AA is a marker of abnormal health that needs to be further explored.

Skeletal muscles are crucial for voluntary movements, and impairments in their function significantly impact our activity. Dysferlin, a protein predominantly present in skeletal muscle, is a focal point of extensive research due to its vital role in muscle repair and maintenance. This study investigates Dysferlin's levels and function in skeletal muscles, emphasizing its significance and the potential effects of its dysregulation on fast and slow muscle fibers. We employed Western blotting on two different rat muscles. The results revealed distinct expressions of Dysferlin in fast and slow fibers, as demonstrated by Western blotting. We propose that Dysferlin may have a metabolic role in addition to its involvement in the repair mechanism.

The advent of AI in medicine has transformed various medical specialties, including orthodontics. AI has shown promising results in enhancing the accuracy of diagnoses, treatment planning, and predicting treatment outcomes. With the growing number of AI applications and commercially available tools, there is an increase in their usage in orthodontic practices worldwide. This review aims to explore the principles of artificial intelligence (AI), its applications in the diagnostic process of modern orthodontic practices, and concerns associated with the implementation of AI algorithms in clinical practice. A comprehensive review of the literature was conducted, focusing on five categories where AI has been applied in orthodontics: dental diagnostics, cephalometric evaluation, skeletal age determination, temporomandibular joint (TMJ) evaluation, and extraction decision making. AI has demonstrated high efficacy in all those fields. However, variations in performance and the necessity of manual supervision indicate that AI should be used cautiously in clinical settings. Nevertheless, the high complexity and potential unpredictability of AI algorithms call for cautious implementation and regular manual validation of results. Continuous AI learning, proper governance, and addressing privacy and ethical concerns are crucial for the successful integration of AI into orthodontic practice.

Hypoxia-inducible factor (HIF)-1α represents the oxygen-sensitive subunit of HIF transcriptional factor, usually degraded in normoxia and stabilized in hypoxia to regulate several target gene expression. Nevertheless, in the skeletal muscle satellite stem cells (SCs), an oxygen level-independent regulation of HIF-1α has been observed. Although HIF-1α has been highlighted as SC function regulator, its spatio-temporal expression and role during myogenic progression remain controversial. We herein analyzed HIF-1α expression and localization in differentiating murine C2C12 myoblasts and SCs under normoxia and evaluated matrix metalloproteinase (MMP)-9 as a HIF-1α target, by biomolecular, biochemical, morphological and electrophysiological analyses. HIF-1α expression increased after 24/48 h of differentiating culture and tended to decline after 72 h/5 days. Committed and proliferating mononuclear myoblasts exhibited nuclear HIF-1α expression, differently from the more elongated and parallel-aligned cells, likely ready to fuse with each other, which show mainly a cytoplasmic localization of the factor. Multinucleated myotubes displayed both a nuclear and cytoplasmic HIF-1α expression. The MMP-9 and MyoD (myogenic activation marker) expression synchronized with that of HIF-1α, increasing after 24 h of differentiation. Short-interfering RNA silencing of HIF-1α and MMP-9 and MMP-9 pharmacological inhibition unraveled MMP-9 as HIF-1α downstream effector and HIF-1α/MMP-9 axis essential for the morpho-functional cell myogenic commitment.

Sarcopenia is an age-related condition that involves a progressive decline in muscle mass and function, leading to increased risks of falls, frailty, and mortality. Although the exact mechanisms are not fully understood, aging-related processes like inflammation, oxidative stress, reduced mitochondrial capacity, and cell apoptosis contribute to this decline. Disruption of the circadian system with age may initiate these pathways in skeletal muscle, preceding the onset of sarcopenia. At present, there is no pharmacological treatment for sarcopenia, only resistance exercise and proper nutrition may delay its onset. Melatonin, derived from tryptophan, emerges as an exceptional candidate for treating sarcopenia due to its chronobiotic, antioxidant, and anti-inflammatory properties. Its impact on mitochondria, organelle where it is synthesized and crucial in aging skeletal muscle, further highlights its potential. In this review, we discuss the influence of clock genes in muscular aging, with special reference to peripheral clock genes in the skeletal muscle, as well as their relationship with melatonin, which is proposed as a potential therapy against sarcopenia.

Adenylosuccinic acid (ASA) is a small molecule dicarboxylate that could be a strong clinical development candidate for inherited myopathies involving dysregulated purine nucleotide metabo-lism. Currently, there are no published pharmacokinetic/dynamic or toxicology data available, albeit 10-year clinical trial data in Duchenne muscular dystrophy patients suggests a chronically safe drug. In this study, we tested the toxicity of ASA to cultured myoblasts in vitro and acute systemic toxicity in mice. ASA is a non-toxic small molecule with an LD50> 5000mg/kg. Some background necrotic foci in the liver, kidney and gastrointestinal tract were shown that are likely incidental but warrant follow-up sub-/chronic oral exposure studies.

Limb girdle muscular dystrophies (LGMD), caused by mutations in 29 different genes, are the fourth most prevalent group of genetic muscle diseases, leading to progressive weakness and atrophy of the skeletal muscles. Although the link between LGMD and their genetic origins has been determined, LGMD still represent an unmet medical need. In this paper, we describe a platform for modeling LGMD based on the use of human induced pluripotent stem cells (hiPSC). Thanks to the self-renewing and pluripotency properties of hiPSC, this platform provides an alternative and renewable source of skeletal muscle cells (skMC) to primary, immortalized or overexpressing cells. We report that skMC derived from hiPSC express the majority of the genes and proteins causing LGMD. As a proof of concept, we demonstrate the importance of this cellular model for studying LGMDR9 by evaluating disease-specific phenotypes in skMC derived from hiPSC obtained from four patients.

Although sarcopenia is characterized by a loss of muscle strength and skeletal muscle mass, few studies have evaluated the effect of muscle strength on hepatocellular carcinoma (HCC) patients. We separately evaluated the impact of sarcopenia-related factors (grip strength [GS] and the skeletal muscle index [SMI]) on the survival among lenvatinib-treated unresectable HCC (u-HCC) patients. This single-center cohort study was conducted at a university hospital. The study population included 63 lenvatinib-treated u-HCC patients managed between April 2018 and April 2020. A decreased GS and decreased SMI were found in 21 (33.3%) and 22 (34.9%) patients, respectively. The overall survival (OS) of the normal GS group was significantly higher than that of the decreased GS group, while that of the normal and decreased SMI groups did not differ markedly. There were no significant differences in the progression-free survival between the normal GS and decreased GS groups or the normal SMI and decreased SMI groups. A multivariate Cox proportional hazards model showed that ALBI2b (hazard ratio [HR] 4.39) and a decreased GS (HR 3.55) were independently associated with an increased risk of poor prognosis. In addition to the hepatic functional reserve, a decreased GS was a poor prognostic factor in lenvatinib-treated u-HCC patients.

Rho guanosine triphosphatases (GTPases) are key regulators in a number of cellular functions, including actin cytoskeleton remodeling and vesicle traffic. Traditionally, Rho GTPases are studied because of their function in cell migration and cancer, while their roles in metabolism are less documented. However, emerging evidence implicates Rho GTPases as regulators of processes of crucial importance for maintaining metabolic homeostasis. Thus, the time is now ripe for reviewing Rho GTPases in the context of metabolic health. Rho GTPase-mediated key processes include the release of insulin from pancreatic β-cells, glucose uptake into skeletal muscle and adipose tissue, and muscle mass regulation. Through the current review, we cast light on the important role of Rho GTPases in skeletal muscle, adipose tissue, and the pancreas and mechanisms by which Rho GTPases act to regulate glucose metabolism in health and disease. We also describe challenges and goals for future research.

The present study is the second step (concerning the normal-diet restoration) of the our previous one (concerning the calcium-free diet) to determine whether the normal-diet restoration, with/without concomitant PTH(1-34) administration, can influence amounts and deposition sites of the total bone mass. Histomorphometric evaluations and immunohistochemical analysis for Sclerostin expression were conducted on the vertebral bodies and femurs in rat model. The final goals are: i) to define timing and manners of bone mass changes when calcium is restored in the diet; ii) to analyze the different involvement of the two bony architectures having different metabolism (i.e. trabecular versus cortical bone); iii) to verify the eventual role of PTH(1-34) administration. Results evidenced the greater involvement of the trabecular bone with respect to the cortical one, in answering to different calcium diet content, and the effect of PTH mostly in the recovery of trabecular bony architecture. The main findings emerged from the present study are: i) the importance of the interplay between mineral homeostasis and skeletal homeostasis in modulating and guiding bone answers to dietary/metabolic alterations and ii) the evidence that the more involved bony architecture is the trabecular one, the most susceptible to the dynamical balance of the two homeostases.

Introduction: maxillary hypoplasia and mandibular asymmetry may be corrected with orthognathic surgery at the completion of growth. Many patients require segmental Le Fort I osteotomies to obtain the most stable results. Unfortunately, if Invisalign is chosen for pre-surgical preparation, ClinCheck © software does not allow for prediction when these complex surgeries are planned. The objective of this paper was to show the potential of aligners beyond its software in most complex cases like multiple-piece maxillary osteotomies in cleft and non-cleft patients. Method: Thirteen patients who underwent pre-surgical treatment with clear aligners-Invisalign (study group) were matched in terms of diagnosis, surgical procedure, and orthodontic complexity with thirteen patients treated using fixed appliances (control group). A technique based on simple superimposition was devised to enhance the software for creating a suitable occlusion for segmental pre-surgical treatments. Virtual curves following the lower arch were employed to guide the correct pre-surgical positions of the upper teeth. The amount of impressions required in both groups to achieve satisfactory pre-surgical alignment of the segmented arches was compared. Results: one or no refinement phase were needed in the Invisalign group to reach an acceptable pre-surgical occlusion while the amount of pre-surgical impressions taken in order to reach adequate coordination with fixed appliance treatment was slightly higher. The average overall treatment duration did not show a statistically significant variation between the groups. Conclusions: it appears that clear aligner could serve as an effective treatment for individuals with skeletal discrepancies, including cleft and craniofacial anomalies, necessitating segmental Le Fort I osteotomies when aided by the suggested superimposition approach during digital pre-surgical movement simulations. More sophisticated softwares will certainly be implemented in the future.

The relationship between arterial stiffness and oxygen uptake (VO2) in patients with acute myocardial infarction (AMI) remains unclear. We aimed to investigate this relationship and factors contributing to VO2 in patients with AMI. The role of arterial stiffness in cardiac-skeletal muscle coupling during exercise was then elucidated. The exercise capacity via cardiopulmonary exercise testing (CPX), cardio-ankle vascular index (CAVI), and body composition of 101 patients with AMI were measured at discharge. Patients were categorized based on their CAVI into three groups: (i) normal (CAVI: ≤7.9), (ii) borderline (CAVI: 8.0–8.9), and (iii) abnormal (CAVI: ≥9.0). Subsequently, VO2 was compared among these groups. The relationship between the CAVI and peak VO2 (VO2 Peak) during CPX and factors contributing to VO2 Peak were investigated. The abnormal CAVI group had a significantly lower VO2 Peak than the normal and borderline groups. The CAVI was associated with VO2 Peak in patients with AMI. Furthermore, the CAVI was found to be a factor contributing to VO2 Peak. These findings suggest that arterial stiffness in tissue blood distribution and blood supply defines systemic exercise limits in patients with AMI. This suggested that arterial stiffness plays a significant role in cardio-vascular-skeletal muscle coupling.

Calcium (Ca2+) ions act as second messenger, regulating several cell functions. Mitochondria are critical organelles for the regulation of intracellular Ca2+. Mitochondrial calcium (mtCa2+) uptake is ensured by the presence in the inner mitochondrial membrane (IMM) of the mitochondrial calcium uniporter (MCU) complex, a macromolecular structure composed of pore-forming and regulatory subunits. MtCa2+ uptake plays a crucial role in the regulation of oxidative metabolism and cell death. Many evidences demonstrate that dysregulation of mtCa2+ homeostasis can have serious pathological outcomes. In this review, we briefly discuss the molecular structure and the function of the MCU complex and then we focus our attention on human diseases in which a dysfunction in mtCa2+ has been showed.

The model of obesity induced by monosodium glutamate cytotoxicity on the hypothalamic nuclei is widely used in the literature. However, MSG promotes persistent muscle changes and there is a significant lack of studies that seek to elucidate the mechanisms by which damage refractory to reversal is established. This study aimed to investigate the early and chronic effects of MSG in-duction of obesity upon systemic and muscular parameters of Wistar rats. Animals were exposed to MSG subcutaneously (4 mg.g-1 b.w.) or saline (1.25 mg.g-1 b.w.) daily from PND01 to PND05 (n = 24). After, in PND15, 12 animals were euthanized to determine the plasma and inflammatory profile and to assess muscle damage. In PND142, the remaining animals were euthanized, and samples for histological and biochemical analyses were obtained. Our results suggest that early exposure to MSG reduced growth, and increased adiposity, induction hyperinsulinemia, and a pro-inflammatory scenario. In adulthood were found, peripheral insulin resistance, reduced muscle mass, oxidative capacity, neuromuscular junctions, increased fibrosis, and oxidative distress. Thus, we can conclude that the condition found in adult life and the difficulty in restoring the muscle profile are related to the metabolic damages established early.

Background: Appendicular skeletal muscle (or lean) mass (ALM) estimated using dual-energy X-ray absorptiometry (DXA) is considered to be a preferred method for sarcopenia studies. However, DXA is expensive, has limited portability, and requires radiation exposure. Bioelectrical impedance analysis (BIA) is inexpensive, easy to use, and portable; thus BIA might be useful in sarcopenia investigations. However, a large variety of models have been commercially supplied by different companies, and for most consumer products, the equations estimating ALM are not disclosed. It is therefore difficult to use these equations for research purposes. In particular, the BIA equation is often age-dependent, which leads to fundamental difficulty in examining age-related ALM loss. The aims of the current study were as follows: (1) to develop and validate an equation to estimate ALM using multi-frequency BIA (MF-BIA) based on theoretical models, and (2) to establish sarcopenia cutoff values using the equation for the Japanese population. Methods: We measured height (Ht), weight, and ALM obtained using DXA and a standing-posture 8-electrode MF-BIA (5, 50, 250 kHz) in 756 Japanese individuals aged 18 to 86-years-old (222 men and 301 women as developing equation group and 97 men and 136 women as a cross validation group). The traditional impedance index (Ht²/Z₅₀) and impedance ratio of high and low frequency (Z₂₅₀/Z₅) of hand to foot values were calculated. Multiple regression analyses were conducted with ALM as dependent variable in men and women separately. Results: We created the following equations: ALM = (0.6947 × (Ht²/Z₅₀)) + (−55.24 × (Z₂₅₀/Z₅)) + (−10,940 × (1/Z₅₀)) + 51.33 for men, and ALM = (0.6144 × (Ht²/Z₅₀)) + (−36.61 × (Z₂₅₀/Z₅)) + (−9332 × (1/Z₅₀)) + 37.91 for women. Additionally, we conducted measurements in 1624 men and 1368 women aged 18 to 40 years to establish sarcopenia cutoff values in the Japanese population. The mean values minus 2 standard deviations of the skeletal muscle mass index (ALM/Ht²) in these participants were 6.8 and 5.7 kg/m² in men and women, respectively. Conclusion: The current study established and validated a theoretical and age-independent equation using MF-BIA to estimate ALM and provided reasonable sarcopenia cutoff values.

The interplay between Diffuse Idiopathic Skeletal Hyperostosis (DISH) and the gut microbiota represents a compelling area of research, offering insights into the relationship between spinal degenerative diseases and the gut's microbial inhabitants. This comprehensive review seeks to unravel the complex connection, shedding light on its implications for human health and potential therapeutic avenues. A crucial section dives into the world of gut microbiota (GM), exploring its impact on human health, featuring its defining characteristics, and highlighting its role in metabolism, immunomodulation, host interaction, and how its composition changes over time. The subsequent portion delves into the relationship between microbiome composition and pathological bone development, including the link between Intervertebral Disc Degeneration (IDD) and gut inflammation, emphasizing how gut inflammation and GM dysbiosis play pivotal roles. Further dissecting the interconnections, various axes of influence, including the gut-spine axis, gut-bone axis, gut-joint axis, gut-disc axis (specific to DISH), gut-ligament axis, and gut-muscle axis, are discussed. Of particular interest is the section on the impact of GM on DISH-derived pain, addressing a critical aspect of the condition's manifestation. The review discusses the potential of GM modulation as a treatment for DISH, providing hope for therapeutic advancements. Additionally, it highlights the positive impact of lifestyle interventions, such as dietary modifications, sleep optimization, and exercise regimens, in mitigating GM dysbiosis and potentially improving DISH outcomes. Lastly, the intriguing prospect of fecal microbiome transplant and its implications for DISH management is examined, opening new avenues for research and therapeutic interventions. In conclusion, this comprehensive review underscores the intricate interplay between DISH and the gut microbiota, offering a fresh perspective on the impact of GM on spinal degenerative diseases. It emphasizes the potential for innovative treatments, such as GM modulation and lifestyle interventions, and presents fecal microbiome transplant as an exciting area for future exploration.

Arjunolic acid (AA) is a triterpenoid saponin majorly found in the Terminalia arjuna and is claimed to exert the cardiovascular protective effects as a phytomedicine. However, it is unclear how AA exerts the effects at the molecular level. Hence, this study used an in vitro model using lipopolysaccharide (LPS)-stimulated H9C2 and C2C12 myotubes to investigate the cardioprotective effects of arjunolic acid (AA) via MyD88-dependant TLR4 downstream signaling markers expression. The myotubes were developed by differentiating rat H9C2 and mouse C2C12 myoblast cells. The MTT viability assay was used to assess the cytotoxicity of AA. LPS induced in vitro cardiovascular disease model was developed in H9C2 and C2C12 myotubes. The treatment groups were designed such as control (untreated), LPS control, positive control (LPS+ pyrrolidine dithiocarbamate (PDTC)-25 µM), and treatment groups were co-treated with LPS and three doses of AA (50, 75, and 100 µM). The changes in the expression of TLR4 downstream signaling markers were evaluated through High Content Screening (HCS) and Western Blot (WB) analysis. The outcomes demonstrated that the expression of MyD88, MAPK, JNK, and NFκB markers were significantly upregulated in the LPS-treated groups compared to the untreated control. Evidently, the HCS analysis revealed that MyD88, NF-κB, p38, and JNK were significantly downregulated in the H9C2 myotube in the AA treated groups (50, 75, and 100 µM). For, the C2C12 myotube, the expression of NFκB was downregulated. TLR4 marker expression in H9C2 and C2C12 myotubes was subsequently decreased by AA treatment, suggesting possible cardioprotective effects of AA.

Background: Evaluating muscle mass and function among stroke patients is important. However, evaluating muscle volume and function is not easy due to the disturbance of consciousness and paresis. Temporal muscle thickness (TMT) has been introduced as a novel surrogate marker for muscle mass, function, and nutritional status. We herein performed a narrative literature review on temporal muscle and stroke to understand the current meaning of the TMT in the clinical stroke practice. Methods: The search was performed in PubMed, last updated in October 2021. Report on temporal muscle morphomics and stroke-related diseases or clinical entities were collected. Results: Four studies reported on TMT and subarachnoid hemorrhage, 2 intracerebral hemorrhage, 2 ischemic stroke, 2 standard TMT values, and 2 nutritional status. TMT was reported as a prognostic factor for several diseases, surrogate markers for skeletal muscle mass, and an indicator of nutritional status. Computed tomography, magnetic resonance imaging, and ultrasonography were used to measure TMT. Conclusions: TMT is gradually used as a prognostic factor of stroke or surrogate marker for skeletal muscle mass and nutritional status. Establishing standard methods to measure TMT and large prospective studies to investigate the further relationship between TMT and diseases are needed.

Abstract Although we know something about single cell neuromuscular junction, It is still mysterious how multiple skeletal muscle cells coordinate to complete the intricate spatial curve movement. Here I propose a hypothesis that skeletal muscle cell populations with action potentials are alligned according to a curved manifolds on space(a curved shape on space) and the skeletal muscle also moves according to this corresponding shape(manifolds) when an specific motor nerve impulses are transmitted. the action potential of motor nerve fibers has the characteristics of time curve manifold and this time manifold curve of motor nerve fibers come from visual cortex in which a spatial geometric manifolds are formed within the synaptic connection of neurons. This spatial geometric manifolds of the synaptic connection of neurons orginate from spatial geometric manifolds in outside nature that are transmitted to brain through the cone cells and ganglion cells of the retina.Further,the essence of life is that life is an object that can move autonomously and the essence of life's autonomous movement is the movement of proteins. theoretically, due to the infinite diversity of geometric manifold shapes in nature, the arrangement and combination of 20 amino acids should have infinite diversity, and the geometric manifold formed by protein three-dimensional spatial structure should also have infinite diversity.

Extensive limb lengthening (ELL) was completed in 75 patients: 66 achondroplasia and 9 hypochondroplasia. The average lengthening was 27cm for achondroplasia (12-40cm) and 17cm for hypochondroplasia (range 10-25cm). There were 48 females and 27 males. Lengthening was done either by 2-segment (14 patients; both tibias and/or both femurs) or by serial 4-segment lengthenings (64 patients; both femurs and tibias same time). Most patients also had bilateral humeral lengthening. Lengthenings were either juvenile-onset (31), adolescent-onset (38) or adult-onset (6). The average age at final follow-up was 26 years old (range 17-43 years). There were few permanent sequelae of complications. The most serious was one paraparesis. All patients returned to activities of normal living and only one was made worse by the surgery (paraparesis). This is the first study to show that ELL can lead to increase of height into the normal height range. Previous studies showed mean increases of height of up to 20cm, while this study consistently showed an average increase of 30 cm (range 15-40cm) for juvenile-onset and increase of 26cm (range 15-30cm) for adolescent-onset. This results in lower normal height at skeletal maturity for males and females. The adult-onset had a mean increase of 16.8 (range 12-22cm). This long-term follow-up study shows ELL can be done safely even with large lengthenings and that 4-segment lengthening may offer advantages over 2-segment lengthening. While the majority of cases were performed using external fixation, implantable limb lengthening promises to be an excellent alternative and perhaps an improvement.

The aim of this paper was to evaluate the changes in the mean bone density values of the midpalatal suture in 392 young patients treated with the Rapid Palatal Expander appliance according to sex, gender, vertical and sagittal skeletal patterns. Materials and Methods. The evaluations were performed using the low-dose protocol cone-beam computed tomography scans at t0 (preoperatively) and t1 (1 year after the beginning of the therapy). The region of interest was used to calculate bone density in Hounsfield units (HU) in the area between the maxillary incisors. Results. CBCT scan data of 196 females and 196 males (mean age of 11,7 years) showed homogeneous and similar density values of the MPS at T0 (547.59 HU - 565.85 HU) and T1 (542.31 - 554.20 HU). Class III skeletal individuals showed a significant higher BD than the II class group at T0, but not at T1. Females showed significantly higher BD than males at t0 and t1. No significant differences were found between the other groups and between two-time points in terms of bone density values of the MPS. Conclusions. Females and III class groups showed significantly higher bone density values than males and II class, respectively. No statistically significant differences were found from T0 to T1 in any groups, suggesting that a similar rate of suture reorganization occurs after the use of the RPE, following reorganization and bone deposition along with the MPS.

Skeletal metastases of unknown primary (SMUP) represent a clinical challenge dealing with patients diagnosed with bone metastases. The management have improved significantly in the past years, however fraught with lack of evidences, approach to these patients held out hope for more systematic and tailored treatment—and some patients can achieve impressive gains. Nevertheless, in real-life practice the outlook at the beginning of the take in charge of SMUP is decidedly more somber. An incomplete translational relevance of pathological and clinical data on the mortality and morbidity rate has had unsatisfactory consequences for SMUP patients and their physicians. We examined several approaches to confront the available evidences and highlighted three key points that emerge. The characterization of the SMUP biologic profile is essential to drive clinical decisions, integrating genetic and molecular profile into a multi-step diagnostic work-up. Nonetheless, pragmatic investigation plan and therapy of SMUP cannot follow a single template; it must be adapted to different pathophysiological dynamics and coordinated with efforts of a systematic algorithm and high-quality data derived from statistically powered clinical trials within. This review argues that greater efforts are required to face the unmet need dealing with SMUP patients in oncology. Finally, we provide an original functional network analysis, identifying novel therapeutic targets.

Large animal experiments are important for preclinical studies of regenerative stem cell transplantation therapy. Therefore, we investigated the differentiation capacity of pig skeletal muscle-derived stem cells (Sk-MSCs) as an intermediate model between mice and humans for nerve muscle regenerative therapy. Enzymatically extracted cells were obtained from green-fluorescence transgenic micro-mini pigs (GFP-Tg MMP) and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN) fractions. The ability to differentiate into skeletal muscle, peripheral nerve, and vascular cell lineages was examined by in vitro cell culture and in vivo cell transplantation into the damaged tibialis anterior muscle and sciatic nerves of nude mice and rats. Protein and mRNA levels were analyzed using RT-PCR, immunohistochemistry, and immunoelectron microscopy. The myogenic potential, which was tested by Pax7 and MyoD expression and the formation of muscle fibers, was higher in Sk-DN cells than in Sk-34 cells but remained weak in the latter. In contrast, the capacity to differentiate into peripheral nerve and vascular cell lineages was totally stronger in Sk-34 cells. In particular, Sk-DN cells did not engraft to the damaged nerve, whereas Sk-34 cells showed active engraftment and differentiation into perineurial/endoneurial cells, endothelial cells, and vascular smooth muscle cells, similar to the human case, as previously reported. Therefore, we concluded that Sk-34 and Sk-DN cells in pigs were closer to those in humans than to those in mice.

In this report, we establish a straightforward method for estimating the equilibrium constant for the CK reaction over wide but physiologically and experimentally relevant ranges of pH, Mg2+ and temperature. Our empirical formula for CK Keq” is based on experimental measurements. It can be used to estimate [ADP] when [ADP] is below the resolution of experimental measurements, a typical situation because [ADP] is on the order of micromolar concentrations in living cells, and may be much lower in many in vitro experiments. Accurate prediction of [ADP] is essential for in vivo studies of cellular energetics and metabolism, and for in vitro studies of ATP-dependent enzyme function under near-physiological conditions. With [ADP], we could estimate ΔGATP. Application to actomyosin force generation in muscle provides support for the hypothesis that, when [Pi] varies but not when pH is altered, maximum Ca2+-activated isometric force depends on ΔGATP in both living and permeabilized muscle preparations. Further analysis of the pH studies introduces a novel hypothesis for the role of submicromolar ADP in force generation.

The skeletal muscle plays a critical role in regulating systemic blood glucose homeostasis. Impaired skeletal muscle glucose homeostasis associated with type 2 diabetes mellitus (T2DM) has been observed to significantly affect the whole-body glucose homeostasis, thereby resulting in other diabetic complications. T2DM does not only affect skeletal muscle glucose homeostasis, but it also affects skeletal muscle structure and functional capacity. Given that T2DM is a global health burden, there is an urgent need to develop therapeutic medical therapies that will aid in the management of T2DM. Prediabetes is a prominent risk factor of T2DM that usually goes unnoticed in many individuals as it is an asymptomatic condition. Hence, research on prediabetes is essential because establishing diabetic biomarkers during the prediabetic state would aid in preventing the development of T2DM, as prediabetes is a reversible condition if it is detected in the early stages. Literature predominantly documents the changes in skeletal muscle during T2DM, but the changes in skeletal muscle during prediabetes remain unknown. In this review, we seek to review the existing literature on prediabetic and T2DM associated changes in skeletal muscle function.

KLHL genes and the related KBTBD genes encode components of the Cullin-E3 ubiquitin ligase complex and typically target tissue-specific proteins for degradation, thereby affecting differentiation, homeostasis, metabolism, cell signaling, and the oxidative stress response. Despite their importance in normal cell function and in disease (KLHL40, KLHL41, KBTBD13, KEAP1, and ENC1), previous studies that examined epigenetic factors affecting transcription were predominantly limited to promoter DNA methylation. Using diverse tissue and cell culture whole-genome profiles, we examined 17 KLHL or KBTBD genes preferentially expressed in skeletal muscle or brain to identify tissue-specific enhancer and promoter chromatin, open chromatin (DNaseI hypersensitivity), and DNA hypomethylation. Sixteen of the 17 genes displayed muscle- or brain-specific enhancer chromatin in their gene bodies, and most exhibited specific intergenic enhancer chromatin as well. Seven genes were embedded in a super-enhancer. The enhancer chromatin regions typically displayed foci of DNA hypomethylation at peaks of open chromatin. In addition, we found evidence that gene neighbors (HHATL and FBXO32) of KLHL40 and KLHL38 harbor enhancer chromatin that likely upregulates the adjacent KLHL gene. Many KLHL/KBTBD genes had tissue-specific promoter chromatin at their 5’ ends, but surprisingly, two (KBTBD11 and KLHL31) had constitutively unmethylated promoter chromatin in their 3’ exons that overlaps a retrotransposed KLHL gene. Our findings demonstrate the importance of expanding epigenetic analyses beyond the 5’ ends of genes in studies of normal and abnormal gene regulation.

Direct measurement of strain within muscle is important for understanding muscle function in health and disease. Current technology (kinematics, dynamometry, electromyography) provides limited ability to measure strain within muscle. Regional fiber orientation and length are related with active/passive strain within muscle. Currently, ultrasound imaging provides the only non-invasive means of observing regional fiber orientation within muscle during dynamic tasks. Previous attempts to automatically estimate fiber orientation from ultrasound are not adequate, often requiring manual region selection, feature engineering, providing low-resolution estimations (one angle per muscle), and deep muscles are often not attempted. Here, we propose deconvolutional neural networks (DCNN) for estimating fiber orientation at the pixel-level. Dynamic ultrasound images sequences of the calf muscles were acquired (25 Hz) from 8 healthy volunteers (4 male, ages: 25–36, median 30). A combination of expert annotation and interpolation/extrapolation provided labels of regional fiber orientation for each image. We then trained DCNNs both with and without dropout using leave one out cross-validation. Our results demonstrated robust estimation of regional fiber orientation with approximately 3° error, which was an improvement on previous methods. The methods presented here provide new potential to study muscle in disease and health.

Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. Circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women and who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: 37 elderly women were separated into an elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using 1H-NMR and also insulin-dependent tissue specific glucose uptake in skeletal muscle were assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the 22:6 docosahexaenoic acid percentage of the total long chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (P = 0.015). DHA/FA associated significantly to skeletal muscle GU (P = 0.031) and M-value in the OLM group only (P = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and that this association is significantly weakened in the offspring of obese mothers.

Trans-arterial radioembolization (TARE) is a form of radiation therapy performed for hepatocellular carcinoma (HCC) via selective intra-arterial injection of Yttrium-90 loaded microspheres. This was a multicenter retrospective study of consecutive patients with HCC who underwent TARE between July 2009 and May 2019. Using pre-treatment computed tomography imaging, the total cross-sectional area (cm2) of the abdominal skeletal muscle at the third lumbar vertebra was measured. The skeletal muscle index (SMI) was calculated by normalizing the muscle area to patient height. In total, 347 patients (median age, 65 years; 284 male) were included in the study. A total of 108 (31.1%) patients had portal vein tumor thrombus (PVTT) and 126 (36.3%) were classified as sarcopenic. The median overall survival (OS) was 28.1 months (95% CI, 24.8-35.7) and median progression-free survival was 8.0 months (95% CI, 6.4-9.4). Multivariate Cox regression analysis revealed that sarcopenia (hazard ratio [HR], 1.36; 95% CI, 1.00-1.85, p = 0.05), PVTT (HR, 1.82; 95% CI, 1.33-2.49, p &lt; 0.01), alpha-fetoprotein (AFP) (≥200 ng/mL) (HR 1.41; 95% CI, 1.04-1.92, p = 0.03), and albumin-bilirubin grade (2-3) (HR 1.74; 95% CI, 1.24-2.43, p &lt; 0.01) were independently associated with poor OS. TARE provided favorable long-term outcomes for patients with advanced HCC. Pre-treatment sarcopenia independently associated with survival, suggesting its utility as a surrogate biomarker for identifying TARE candidates.

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) frequently require primary radiochemotherapy (RCT). Despite intensity-modulation, desired radiation-induced effects observed in HNSCC, may also be observed as side-effects in healthy tissue e.g. the sternocleidomastoideus muscle (SCM). These side-effects (e.g. tissue fibrosis) depend on the interval between completion of RCT and restaging-CT. For salvage surgery, the optimal time window for surgery is currently postulated between 6 and 12 weeks after completion of RCT. Thus, no extensive tissue fibrosis is to be expected. This interval is based on studies exploring surgical complications. Studies directly exploring radiation-induced changes of the SCM in HNSCC-patients are sparse. The present study quantifies tissue alterations in SCM and paravertebral musculature (PVM) after RCT applying radiomics to determine the optimal time window for salvage surgery. Three radiomic key parameters 1) volume, 2) mean positivity of pixels (MPP) and 3) uniformity were extracted with mint lesionTM in the staging-CTs and restaging-CTs of 98 HNSCC-patients. Of these, 25 were female, the mean age was 62 (±9.6) years and 80.9% were UICC Stage IV. The mean restaging-interval was 55 (±28; range29-229) days. Only the mean volume significantly decreased after RCT from 9.0 to 8.4 and 96.5 to 91.9 ml for SCM and PVM, respectively (both p=0.007, both Cohen’s d=0.28). In addition, the mean body mass index (BMI) decreases from 23.9 (±4.2) to 21.0 (±3.6) kg/m² (p<0.001); Cohen's d = 0.9). The mean BMI-decrease significantly correlated with the volume decrease for SCM (r=0.27; p=0.007) and PVM (r=0.41; p<0.001). If t-test p-values were adjusted for the BMI-decrease, no significant change in volumes for SCM and PVM was observed (both p>0.05). The present data supports the postulated optimal interval for salvage surgery of 6 to 12 weeks. Irrespective of the remaining risk-benefit ratio of salvage surgery, the risk of additional surgical complications due to fibrosis is not supported by the present observations.

Objectives: Multicentric Osteolysis, Nodulosis, and Arthropathy (MONA) syndrome is a rare genetic skeletal dysplasia. Its diagnosis can be deceptively similar to childhood-onset genetic skeletal dysplasias and juvenile idiopathic arthritis. We aimed to report the syndrome’s clinical and radiologic features with emphasis on skeletal manifestations. And establish relevant phenotype-genotype correlations. Methods: We evaluated two boys, 4-and-7-years-old with MONA syndrome. Both patients had consanguineous parents. We verified the diagnosis by correlating the outcomes of clinical, radiologic and molecular analysis. We specifically evaluated the craniofacial morphology and clinical and radiographic skeletal abnormalities. We contextualized the resultant phenotype-genotype correlations to publications on MONA and its differential diagnosis. Results: Skeletal manifestations were the presenting symptoms and mostly restricted to hands and feet in terms of fixed extension deformity of the metacarpophalangeal and flexion deformity of the interphalangeal joints with extension deformity of big toes. There were arthritic symptoms in the older patient especially of the wrists and minute pathologic fractures. The skeletal radiographs showed osteopenia/dysplastic changes of hands and feet. Both patients had variants in the matrix metalloproteinase2 gene which conformed to phenotype of previously reported literature in one patient while the other had a novel variant which conformed to MONA phenotype. Craniofacial abnormalities were present. However, minimal extra-skeletal manifestations. Conclusion: Overall, there is an emerging distinctive skeletal pattern of involvement in terms of both clinical and radiographic features. This includes age of onset and location of presenting skeletal manifestations, chronological order of joint affection, longitudinal disease progression, specifics of skeletal radiographic pathology and craniofacial features. Nevertheless, physicians are cautioned against differential diagnosis of similar genetic skeletal dysplasias and juvenile idiopathic arthritis.

Gigantism in theropods represents one of the most intriguing phenomena in dinosaur evolution, showcasing extreme adaptations in body size and ecological roles. This literature review focuses on Giganotosaurus carolinii, one of the largest known theropods to have ever existed, to explore its unique aspects of gigantism and the subsequent ecological impacts. By analyzing features such as its skeletal morphology, comparative anatomy, and paleoenvironmental data, we assess the evolutionary pressures and biological constraints that shaped the gigantism observed in Giganotosaurus. We discover that the species exhibited a combination of physiological and ecological adaptations that allowed it to thrive as an apex predator in its Cretaceous environment. We will also further examine the implications of its size on prey dynamics, competition with other large theropods, and the overall ecosystem structure. Through a thorough, multidisciplinary approach, this research enhances our understanding of how gigantism influenced theropod behavior, interspecies interactions, and the broader paleoecological landscape.

Therizinosaurs, a unique clade of theropod dinosaurs, are characterized by their distinct morphological features and enigmatic ecological role. This review provides a comprehensive analysis of the functional morphology and ecological significance of these remarkable dinosaurs. Therizinosaurs are distinguished by their elongated, often curved claws, robust postcranial skeletons, and herbivorous diet, which starkly contrasts with their carnivorous theropod relatives. We explore the evolutionary implications of their morphology, focusing on adaptations such as their specialized feeding apparatus and limb structure. These features suggest a complex interplay between their herbivorous lifestyle and ecological niche. The review synthesizes recent findings from fossil evidence, including detailed studies of cranial and postcranial anatomy, to elucidate the functional mechanisms behind their unique adaptations. Additionally, we discuss the broader ecological role of therizinosaurs within their Mesozoic ecosystems, highlighting their interactions with contemporaneous flora and fauna. By integrating paleontological data with comparative anatomy and ecological modeling, this review aims to shed light on the evolutionary trajectory of therizinosaurs and their impact on our understanding of theropod diversity and adaptation. This focused review contributes to a more nuanced appreciation of therizinosaurs' place in dinosaur evolution and their adaptive strategies in prehistoric environments.