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.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease associated with an increased risk of cardiovascular diseases (CVD), leading to elevated mortality rates among patients. We aimed to evaluate the levels of cardio-ankle vascular index (CAVI), global longitudinal strain (GLS), ventricular-arterial coupling (VAC) and high-sensitivity cardiac troponin (hsTn), in SLE patients and to explore their relationship with clinical parameters. Methods: This cross-sectional study enrolled 82 SLE patients without evident cardiac or kidney impairment and 41 age- and sex matched healthy controls. We comparatively evaluated CAVI, GLS, VAC, and hsTn between SLE patients and controls, and we assessed their association among SLE patients with disease activity based on the SELENA-SLEDAI Activity Index. Multivariate regression analysis was performed to identify independent predictors of CAVI and hsTn within the SLE cohort. Results: In comparison to healthy controls, SLE patients presented with significantly higher CAVI, GLS and hsTn levels, while VAC was significantly reduced (p<0.001). Further, SLE patients with active disease (SELENA-SLEDAI≥4) exhibited higher levels of CAVI and troponin than those with inactive disease (p<0.001). SLEDAI was an independent predictor of CAVI, while VAC and SLEDAI were independent determinants of hsTn in SLE cohort. Conclusion: SLE patients displayed abnormal levels of CAVI, VAC, GLS, and troponin compared to healthy individuals. Our findings implicate the potential of those CV novel CVD risk factors to refine screening and therapeutic strategies for this specific population.

A warning sign for impending cardio-vascular events is not fully established. In the process to plaque rupture, formation of vulnerable plaque is important, and oxidized cholesterols play important role in its progression. Furthermore, the significance of vasa vasorum penetrating medial smooth muscle layer and rich in atheromatous lesion should be paid attention. Cardio-ankle vascular index (CAVI) is new arterial stiffness index of the arterial tree from the origin of the aorta to the ankle. CAVI reflects functional stiffness in addition to structural stiffness. Rapid rise of CAVI means medial smooth muscle cell contraction, and strangling vasa vasorum. We reported rapid rise of CAVI in peoples after big earthquake, following high frequency of cardiovascular events. And we met several cases who showed rapid rise of CAVI a few weeks or months before suffering cardiovascular events. To explain these sequences of events, we proposed a hypothesis; A rapid rise of CAVI means medial smooth muscle contraction, strangling vasa vasorum, leading ischemia, necrosis of vulnerable plaque, then, the plaque ruptures. In individuals having high CAVI, further rapid rise of CAVI might be a warning sign for impending cardiovascular events. In such case, treatments to decrease CAVI had better to be taken soon.

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.

Chronic kidney disease patients treated by hemodialysis present a high cardio-vascular morbidity and mortality. There is an imperative need for novel biomarkers in identifying and to offer possible therapeutically intervention in these patients. We performed a prospective observational cohort study on 77 patients in the period October 2021 – October 2023. We measured serum plasma levels of Interleukin 1-Beta, Galectin 3, human suppression of tumorigenicity factor 2, bone morphogenetic protein 2 and fibroblastic growth factor 23 at the inclusion. We evaluated the correlations of these biomarkers with cardiac function and structure evaluated by echocardiography. Mean age was 61.02 (±11.81) years, 45 (56.2%) males and with a dialysis vintage of 4.95 (2.4-7.8) years. Median ejection fraction was 51 (43-54 %) and more than two thirds of the patients presented valvular calcifications. Overall mortality was 22%. Interleukin 1-Beta correlated positively with ejection fraction and global longitudinal strain and negatively with left atrium diameter and left ventricle tele systolic diameter. Galectin 3 values negatively correlated with aortic valve fibrosis and mitral valve calcifications and human suppression tumorigenity factor 2 negatively correlated with mitral valve calcifications. Some of these novel biomarkers could be used to better asses the cardio-vascular disease in patients on maintenance hemodialysis.

Venous thromboembolism (VTE) is a prevalent medical condition with high morbidity, mortality, and associated cost. Anticoagulation remains the main treatment for VTE, though the decision on when, how, and for how long to administer anticoagulants is increasingly complex. This review highlights the different phases of VTE management, special circumstances for consideration such as antiphospholipid syndrome, coronary artery disease, cancer associated thrombus and COVID, and future anticoagulation options. Anticoagulation management will continue to be a complex decision, applying evidence-based medicine to individual patients with the hope to maximize effectiveness while minimizing risks.

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.

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 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.

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.

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.

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.

Purpose: Cardiovascular disease (CVD) is a major risk factor for mortality in patients with osteoarthritis, and comorbidities increase postoperative complications after total knee arthroplasty (TKA). Arteriosclerosis plays a major role in hemodynamic dysfunction and CVD; however, arteriosclerosis has not been preoperatively evaluated before TKA using the cardio–ankle vascular index (CAVI). In this study, we evaluated the degree of preoperative arteriosclerosis using the CAVI in patients undergoing TKA, as well as its correlations with several preoperative patient factors. Methods: Arteriosclerosis was evaluated in 209 consecutive patients (251 knees) with osteoarthritis who underwent TKA at our institution between May 2011 and June 2022. The CAVI was measured in the supine position 1 day before TKA, and the correlations between the CAVI and several clinical factors were analyzed. A p value of <0.05 was considered statistically significant. Results: The CAVI was normal in 62 knees (25%), borderline in 71 knees (28%), and abnormal in 118 knees (47%). Univariate analysis revealed a moderate positive correlation between preoperative CAVI and age (r = 0.451, p < 0.001) and a weak negative correlation between preoperative CAVI and body weight (r = −0.306, p < 0.001) and body mass index (BMI) (r = −0.319, p < 0.001). Multivariate analysis showed that age (β = 0.349, p < 0.001) and BMI (β = −0.235, p < 0.001) were significantly correlated with preoperative CAVI. Conclusion: Arteriosclerosis should be carefully managed intraoperatively and postoperatively in patients with osteoarthritis undergoing TKA, particularly in older patients and patients with a low BMI.

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.

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.

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.

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.

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.

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.

As times goes, the survival was improved attributed to target therapy and chemotherapy. Metastasis to skeletal muscle tissue is rare. Herein, we reported a case presenting with deep venous thrombosis but skeletal muscle metastasis. Though it was rare, oncologist shoud be keep in mind due to worse prognosis .

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.

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.

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.

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.

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.

The aim of the study was to examine the long-term prognostic value of changes in cardio-ankle vascular index (CAVI) within a year after coronary artery bypass grafting (CABG). Methods. Patients with coronary artery disease (n = 251) in whom cardio-ankle vascular index (CAVI) was assessed using the VaSera VS-1000 device before and in a year after CABG. Groups with improved CAVI (CAVI decreased from pathological value to normal or the index remained within normal values) or worsened CAVI (persistent pathological index value or an increase in CAVI to pathological values or an increase of 1 unit or more) were identified. The groups were compared for the following events at 10-year follow-up: death from all causes, myocardial infarction, stroke/transient ischemic attack, and the combined endpoint. Results. A year after CABG surgery, 45% of patients showed positive dynamics or stable normal CAVI values. Death from all causes was significantly more common in the group with CAVI progression - 32 (27.6%) than in the group with CAVI improvement - 14 (14.8%; p = 0.029). Patients with CAVI progression were more likely to have MACE (death, MI, stroke/TIA) in 49 (42.2%) cases, compared with patients with CAVI improvement - in 23 (24.5%; p=0.008). Negative dynamics of CAVI (p = 0.024), number of shunts (p = 0.006), and the presence of carotid stenosis more than 30% (p = 0.051) were independent predictors of death from all causes at 10-year follow-up after CABG. The presence of carotid stenosis more than 30% (p = 0.002) and the group with negative dynamics of CAVI after a year (p = 0.008) were independent predictors of the development of the combined endpoint during long-term follow-up. Conclusions. Patients with negative dynamics of CAVI one year after CABG were more likely to experience death from all causes and combined endpoint in the long-term follow-up than patients with normal CAVI. In further studies, it is advisable to evaluate the dynamics of CAVI and, based on this, identify the most effective interventions to improve the prognosis of patients after CABG.

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

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.

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.

Mutations in the LMNA gene (encoding lamin A/C proteins) cause several human cardiac diseases, including dilated cardiomyopathies (LMNA-DCM). The main clinical risks in LMNA-DCM patients are sudden cardiac death and progressive left ventricular ejection fraction deterioration, and therefore most human and animal studies have sought to define the mechanisms through which LMNA mutations provoke cardiac alterations, with particular focus on cardiomyocytes. To investigate if LMNA mutations also cause vascular alterations that might contribute to the etiopathogenesis of LMNA-DCM, we generated and characterized Lmnaflox/floxSM22αCre mice, which constitutively lack lamin A/C in vascular smooth muscle cells (VSMCs), cardiac fibroblasts, and cardiomyocytes. Like mice with whole body or cardiomyocyte-specific lamin A/C ablation, Lmnaflox/floxSM22αCre mice recapitulated the main hallmarks of human LMNA-DCM, including ventricular systolic dysfunction, cardiac conduction defects, cardiac fibrosis, and premature death. These alterations were associated with hyperactivation of Smad3 and elevated expression of the proapoptotic protein caspase 3 in the heart. Lmnaflox/floxSM22αCre mice also exhibited perivascular fibrosis in the coronary arteries, and a switch of aortic VSMCs from the ‘contractile’ to the ‘synthetic’ phenotype. Ex vivo wire myography in isolated aortic rings revealed impaired maximum contraction capacity and an altered response to vasoconstrictor and vasodilator agents in Lmnaflox/floxSM22αCre mice. To our knowledge, our results provide the first evidence of phenotypic alterations in VSMCs that might contribute significantly to the pathophysiology of some forms of LMNA-DCM. Future work addressing the mechanisms underlying vascular defects in LMNA-DCM may open new therapeutic avenues for these diseases.

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.

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.

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.

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.

The diagnosis of Cardio-Vascular diseases (CVD) is highly dependent on analysis of ECG signals. ECG analysis can be helpful in estimating the underlying cause and condition of heart in cardiac abnormality. The effectiveness of ECG signal analysis in detection of CVDs is widely accepted by professional healthcare service provider. Many algorithms have been proposed but almost all of them have some kind of limitations, and these limitations largely influence the effectiveness of ECG analysis. The performed research work is dedicated for design of unique self-organizing maps (SOMs) based neural network for classification of arrhythmia according to a particular ECG signal, the generation of SOMs is based on the certain unique signatures of ECG signals and have potential to classify different cardiac conditions. For extraction of unique features from ECG signals, we have proposed to use Fast Discrete Stockwell Transform (FDST). Since the proposed technique is a result of combining two different techniques hence called as hybrid technology. The purpose of using FDST is to identify unique signatures of ECG signals in a more improved manner than existing one, the term improved is used because it has several advantages over existing techniques such as wavelet and Fourier Transform based methods. Results obtained from the implementation of the technique are capable in visualizing the ECG sinus rhythm and arrhythmia conditions in form of unique SOM for each associated arrhythmia condition. This unique SOM based classification makes them ideal for being used as a diagnostic tool. This ability of arrhythmia classification using FDST and SOMs makes the technique unique and useful providing valuable information about patient condition. Using proposed technology a portable diagnosis tool for monitoring of patient at their site may be facilitated later, that will improve the quality of life of the patient by diagnosing cardiac condition.

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.

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.

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.

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.

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.

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.

A key feature of pulmonary arterial hypertension (PAH) is the hyperplastic proliferation exhibited by the vascular smooth muscle cells from patients (HPASMC). The growth inducers FOXM1 and PLK1 are highly upregulated in these cells. The mechanism by which these two proteins direct aberrant growth in these cells is not clear. Herein we identify cyclin dependent kinase 1 (CDK1) also termed cell division cycle protein 2 (CDC2), as having a primary role in promoting progress of the cell cycle leading to proliferation in HPASMC. HPASMC obtained from PAH patients and pulmonary arteries from Sugen/hypoxia rats were investigated for their expression of CDC2. Protein levels of CDC2 were much higher in PAH than in cells from normal donors. Knocking down FOXM1 or PLK1 protein expression with siRNA or pharmacological inhibitors lowered the cellular expression of CDC2 considerably. However, knockdown of CDC2 with siRNA or inhibiting its activity with RO-3306 did not reduce the protein expression of FOXM1 or PLK1. Expression of CDC2 and FOXM1 reached its maximum at G1/S, while PLK1 reached its maximum at G2/M phase of the cell cycle. The expression of other CDKs such as CDK2, CDK4, CDK6, CDK7 and CDK9 did not change in PAH HPASMC. Moreover, inhibition via Wee1 inhibitor adavosertib or siRNAs targeting Wee1, Myt1, CDC25A, CDC25B, or CDC25C led to dramatic decreases in CDC2 protein expression. Lastly, we found CDC2 expression at the RNA and protein level to be upregulated in pulmonary arteries during disease progression Sugen/hypoxia rats. In sum, our present results illustrate that the increased expression of FOXM1 and PLK1 in PAH leads directly to increased expression of CDC2 resulting in a potentiated growth hyperactivity of PASMC from patients with pulmonary hypertension. Our results further suggest that the regulation of CDC2, or associated regulatory proteins, will prove beneficial in the treatment of this disease.

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.

Background: Cancer therapy-related cardiac dysfunction (CTRCD) is a growing concern for public health, with a growing incidence due to improved survival rates for patients with hematological malignancies due to diagnostic and therapeutic advances. Identification of patients at risk CTRCD is vital to develop preventive strategies. Methods: A single-center retrospective cohort study was conducted between 1 January 2017 and 15 February 2023. Medical records of patients with lymphoma treated with first-line anthracyclines were reviewed. Demographic data, cardiovascular risk factors, biomarkers of myocardial damage and echocardiographic information were collected. Results: A total of 200 patients were included. The incidence of CTRCD was 17.4 % (35/200). Patients with CTRCD were older than those without CTRCD, with a mean age of 65.17 years vs 56.77 (p = 0.008). Dyslipidemia (DL) (31.4% vs 13.4% p = 0.017) and previous cardiovascular disease (40% vs 13.3%, p< 0.001) were more frequent in the group who developed an event. Mean baseline NT-proBNP levels in the subgroup with cardiovascular events were 388.73 kg /L ± 101.02, and 251.518 kg /L ± 26.22 in those who did not (p = 0.004). Differences in Troponin I levels were identified during and after treatment without exceeding the laboratory’s upper reference limit. Patients were followed for a median of 51.83 months (0.76-73.49). The presence of a CTCRD event had a negative impact on overall mortality from any cause (HR = 2.23 (95% CI 1.08-2.93), p = 0.031). Conclusions: Early identification of risk factors is crucial to manage patients at risk for CTRCD.

Atrial fibrillation (AF) is an increasingly recognized comorbidity in patients with can-cer. Indeed, cancer patients have a significantly higher incidence of AF than that ob-served in the general population. A reciprocal relationship between these two diseases has been observed, as much as some assume AF as a marker for occult cancer screen-ing, especially in older adults. The pathophysiological mechanisms are many and var-ied, including the underlying pro-inflammatory state, specific treatments (chemo and radiotherapy) and surgery. The therapeutic management of patients with cancer and AF involves the same rhythm and frequency control strategies as the general popula-tion; however, the numerous interactions with chemotherapeutics, which lead to a sig-nificant increase in side effects, as well as the extreme fragility of the patient should be considered. Anticoagulant therapy is also a complex challenge to address, as bleeding and stroke risk scores have not been fully assessed in this subpopulation. Furthermore, in large studies establishing the efficacy of direct oral anticoagulants (DOACs), cancer patients have been underrepresented. In this review, we elaborate on mechanisms linking AF to cancer patients with a particular focus on therapeutic challenges in this population.

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.

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.

Advances in cardiovascular therapies and cancer treatments result in longer patient survival. The coexistence of cancer and cardiovascular disease has been recognized as a complex clinical scenario. Beside cardiovascular disease, older people with cancer are at greater risk of experiencing multimorbidity and the geriatric syndromes such as frailty. In older people, the concurrent presence of cancer and cardiovascular disease increased the risk of mortality, and the presence of frailty can exacerbate their conditions and hinder the treatment effectiveness. Given the significant intersection among frailty, cardiovascular disease and cancer in older people, this paper aims to provide an overview of the current research in this field and identifies gaps in research to understand the burden and impact of frailty in these populations. While many studies have examined the prevalence and impact of frailty on adverse outcomes in patients with cancer or with cardiovascular disease, evidence of frailty in individuals with both conditions is lacking. There is no universally accepted definition of frailty, which leads to inconsistencies in identifying and measuring frailty in older adults with cardiovascular disease and cancer. The frailty index seems to be a preferred frailty definition in studies in patients with cancer, while the frailty phenotype seems to be more commonly used in cardiovascular research. However, differences in how the frailty index was categorised and in how patients were classified as ‘frail’ depending on the cut points may have negative effect on understanding the impact of frailty in the studied populations. This makes it challenging to compare findings across different studies and limits our understanding of the prevalence and impact of frailty in these populations. Addressing these research gaps will contribute to our understanding of the burden of frailty in older people with cardiovascular disease and cancer, and improved clinical care protocols in this vulnerable population.

(1) Infective endocarditis is a severe inflammatory disease associated with substantial mortality and morbidity. Alkaline phosphatase (AP) levels have been shown to change significantly during sepsis additionally we previously found higher initial AP drop after cardiac surgery is associat-ed with unfavorable outcomes. Therefore, the course of AP after surgery for endocarditis is of special interest. (2) 314 patients with active isolated left-sided infective endocarditis at the De-partment of Cardiac Surgery (Medical University of Vienna, Austria) between 2009 and 2018 were enrolled in this retrospective analysis. Blood samples were analyzed at different time points (baseline, postoperative day 1-7, postoperative days 14, and 30). Patients were categorized ac-cording to relative alkaline phosphatase drop (≥30% vs. <30%). (3) The rate of postoperative renal replacement therapy with or without prior renal replacement therapy (7.4 vs. 21.8%; p=0.001 and 6.7 vs. 15.6%; p=0.015, respectively) and extracorporeal membrane oxygenation (2.2 vs. 19.0%; p=0.000) was observed after a higher initial alkaline phosphatase drop. Short-term (30-day mor-tality 3.0 vs. 10.6%; p=0.010) and long-term mortality (p=0.008) were significantly impaired after a higher initial alkaline phosphatase drop. (4) The higher initial alkaline phosphatase drop was accompanied by impaired short and long-term outcomes after cardiac surgery for endocarditis. Future risk assessment scores for cardiac surgery should consider alkaline phosphatase.

Term vascular dysfunctional refers to a wide spectrum of vascular abnormalities including pathogenesis of tumors, their proliferation and leading to malfunctioned conditions. The treatment of most of the vascular anomalies including peripheral arterial disease and cardiac disease is multi factor procedure which include the embolic therapy, laser-based treatments and coagulation are all plating important role in managing the disease associated with vascular breakdown. The research proposal defines the treatment and diagnosis procedures involved in treatment of vascular abnormalities with a deep emphasis on techniques, efficiency and complications resulted from various other procedure and use of mapping and sequencing techniques based on genetics of variants of selected genes PIk3CA which will ultimately be more effective.

Cardiopulmonary lesions, which manifest from various types of diseases such as pulmonary arterial hypertension, atherosclerosis, pulmonary arteriovenous malformations, lymphangioleiomyomatosis, and peripheral arterial disease, pose a public health problem. Vascular remodeling, which refers to alternations to the structure of the vessel is an important pathophysiological feature of these diseases. The Inhibitor of DNA-binding/Differentiation-3 (ID3), which is part of the ID family of transcriptional regulators, has been demonstrated to contribute to an essential role in the vasculature and therefore may influence the alterations of these lesions. This review will cover the existing understanding of how ID3 may contribute to cardiopulmonary lesion perturbations via involvement in vascular remodeling. Furthermore, based on the accumulative quantity of reports that indicate oxidative stress plays a essential function in the pathophysiology of vascular remodeling, we will also consider the impact of exposure to estrogenic endocrine disruptors (EEDs) such as polychlorinated biphenyls (PCBs) and bisphenol A (BPA) on ID3 & cardiopulmonary disease. Improved understanding of how ID3 pathways contributes to these molecular mechanisms in the lesion will prospectively deliver beneficial information in the mediation of vascular remodeling associated with ID3 & EED exposure, which may play an essential role in cardiopulmonary disease prevalence.

New technologies have resulted in a better understanding of blood and lymphatic vascular heterogeneity at the cellular and molecular levels. Meanwhile, we still need to learn more about the heterogeneity of the cardiovascular and lymphatic systems between different species at the anatomical and functional levels. Even the deceptively simple question of the functions of fish lymphatic vessels has yet to be conclusively answered. The most common interpretation assumes a similar dual setup of the vasculature in zebrafish and mammals: on the one hand, there is the cardiovascular, circulatory system, and on the other hand, the lymphatic vascular system, in which the unidirectional flow is derived from surplus interstitial fluid and returned into the cardiovascular system. A competing interpretation questions the identity of the lymphatic vessels in fish as at least some of them receive their flow from arteries via specialised anastomoses, neither requiring an interstitial source for the lymphatic flow nor stipulating unidirectionality. In this alternative view, the “fish lymphatics” are a specialised subcompartment of the cardiovascular system, called the “secondary vascular system” (SVS). Many of the contradictions found in the literature appear to stem from the fact that the SVS develops in part or its entirety from an embryonic lymphatic vascular system by transdifferentiation. Future research needs to establish the extent of embryonic transdifferentiation of lymphatics into SVS blood vessels. Similarly, more insight is needed into the molecular regulation of vascular development in fish. Most fish do feature more than the five VEGF genes and three VEGF receptor genes that we know from mice or humans, and the relative tolerance of fish to whole genome and gene duplications could underlie the evolutionary diversification of the vasculature. This review discusses the key elements of the fish lymphatics versus the SVS and attempts to draw a picture coherent with the existing data, including the phylogenetic knowledge.

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.

Background: The current standard technique for vascular grafting in cerebral revascularization surgery is through the interposition of an autologous blood vessel. Technical complications have necessitated the development of a synthetic alternative, but classical biomaterials are not suited for small caliber vascular grafting due to neointimal hyperplasia and thrombosis. Electrospinning of polymers is a promising technique for the development of small vascular grafts. The in vivo performance and efficacy of electrospun polyurethane (ePU) grafts with an internal diameter of < 1.5 mm have thus far not been evaluated. Methods: We developed a novel ePU graft with a diameter of 1.25 mm for implantation into the infrarenal aorta of rats. Results: Patency rates of grafts after a four-month-period were equal to those reported in other studies with larger ePU graft diameters, and equal or higher than in studies with other biomaterials. We observed some loss in flow velocity throughout the grafts, which suggests a decreased elasticity of the graft compared to native rat aorta. However, the grafts demonstrated good neo-endothelialization and minimal neointimal hyperplasia. Their porosity promoted cellular infiltration, as shown on tissue slide examination. Conclusion: Our results show that ePU vascular grafts with internal diameter of < 1.5 mm are promising candidates for vascular grafting in cerebral revascularization surgery.

Hispidulin is a natural bioactive flavonoid that has been studied for its potential therapeutic properties, including its anti-inflammatory, antioxidant, and neuroprotective effects. The aim of this study was to explore whether hispidulin could inhibit endothelial inflammation triggered by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS). The adhesion of monocytes to vascular endothelium was evaluated by in vitro and ex vivo monocyte adhesion assays. We analyze the migration of monocytes across the endothelial layer using transmigration assay. The result showed that treatment with hispidulin decreased P. gingivalis LPS-induced the adhesion of monocytes to endothelial cells and their migration by suppressing P. gingivalis LPS-triggered expression of intercellular adhesion molecule-1 (ICAM-1) through downregulating nuclear factor-қB (NF-қB). In addition, hispidulin inhibited P. gingivalis LPS-induced mitogen-activated protein kinases (MAPKs) and AKT in endothelial cells. Altogether, the results indicate that hispidulin suppresses vascular inflammation induced by P. gingivalis LPS. Mechanistically, it prevents the adhesion of monocytes to the vascular endothelium and migration and inhibits NF-қB, MAPKs, and AKT signaling in endothelial cells.

Abstract Background: Most cardiac metastases emerge from primary lung, breast, and hematologic malignancies. The clinical manifestations of cardiac metastasis vary depending on tumor location and size. Cardiac metastasis from cervical squamous cell carcinoma is extremely rare and is mostly found on autopsy. We report a case of cervical cancer metastasis to the interventricular septum. Case Summary. This report discusses the case of a 48-year-old woman with interventricular septal metastases, originating from squamous cell carcinoma of the cervix. The woman came to our hospital after experiencing a fainting spell. Her hospital stay was notable for a brief syncopal event during a 30-second asystole episode, which ended spontaneously. Upon awakening, she reported severe chest pain. In response, she was quickly taken to the catheterization laboratory. There, a coronary angiography revealed an 80% blockage in her left anterior descending artery. Two years prior, our patient was diagnosed with invasive squamous cell cervical carcinoma with PET/CT showing no evidence of metastatic disease. A repeat PET/CT scan was done following cardiac catheterization and was significant for a mass along the interventricular septum of the heart. Discussion. Cardiac metastasis from primary cervical squamous cell carcinomas is scarcely reported in medical literature. Among these rare cases, the majority involved the right ventricle, with only three involving the left ventricle. There are no documented instances of metastasis to the interventricular septum. To our knowledge, this would be the first such case.

Soluble cell adhesion molecules (sCAMs) are secreted ectodomain fragments of surface adhesion molecules, ICAM1 and VCAM1. sCAMs have diverse immune functions beyond their primary function, impacting immune cell recruitment and activation. Elevated sVCAM1 levels have been associated with poor cardiovascular disease (CVD) outcomes, supporting its role as a potential diagnostic marker and therapeutic target. Inhibiting sVCAM1 release or interaction with immune cells could offer cardioprotection in conditions such as diabetes. Membrane bound surface adhesion molecules are widely expressed in a wide variety of cell types with higher expression in endothelial cells (ECs), but the source of sCAMs in the circulation is not clear. Hypothesizing that endothelial cells (ECs) could be a potential source of sCAMs, this study investigated whether dysfunctional EC signaling mechanisms during diabetes cause VCAM1 ectodomain shedding. Our results from samples from a inducible diabetic mouse model revealed increased sVCAM1 plasma levels in diabetes. Protein analysis indicated upregulated VCAM1 expression and metalloproteases ADAM10 and ADAM17 in diabetic ECs. ADAMs are known for proteolytic cleavage of adhesion molecules, contributing to inflammation. GSK3β, implicated in EC VCAM1 expression, was found to be activated in diabetic ECs. GSK3β overexpression in control ECs increased ADAM10/17 and VCAM1. A GSK3β inhibitor reduced active GSK3β and VCAM1 ectodomain shedding. These findings suggest that diabetic ECs with elevated GSK3β activity led to VCAM1 upregulation and ADAM10/17-mediated sVCAM1 shedding. This mechanism underscores the potential therapeutic role of GSK3β inhibition in reducing the levels of circulating sVCAM1. The complex roles of sCAMs extend well beyond CVD. Thus, unraveling the intricate involvement of sCAMs in the initiation and progression of vascular disease particularly in diabetes, holds significant therapeutic potential.

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.

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.

The most frequent cause of cardiac failure globally is ischemic heart disease, with chemothera-py-related cardiovascular side effects emerging as the second most frequent cause. Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT pro-longation, torsades de pointes, pericardial effusion and hypotension, as well as chronic conditions, such as hypertension, systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovas-cular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovas-cular side effect continues even after the causative medication is stopped, it is referred to as cardi-otoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even with very low medication dosages, and can show up as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome and myocardi-tis caused by cancer therapy.

The prognosis of cancer patients has greatly improved in the last years, owing to the development of novel chemotherapeutic agents. However, this progress comes with an increasing occurrence of cardiovascular adverse reactions. A serious side effect is arterial hypertension, which is the most frequent comorbidity encountered in cancer patients, influencing the outcomes in cancer survivors. Even though secondary hypertension related to specific chemotherapeutic agents, such as vascular endothelial growth factor inhibitors, is usually mild and reversible, in rare instances it can be severe, leading to discontinuation of chemotherapy. In addition, hypertension per se has been studied as a potential risk factor for cancer development. The relationship is even more complex than previously thought, as concerning evidence recently highlighted the potential oncogenic effects of antihypertensive drugs, such as thiazide diuretics predisposing to skin cancer. As a result, under the light of the similar risk factors and overlapping pathophysiological mechanisms between hypertension and cancer, a promising concept of onco-hypertension has emerged, aiming to improve the understanding of the complicated interplay between these two pathologies and maintain a balance between the efficacy and risks of both antihypertensive drugs and chemotherapy agents.

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.

Cirrhosis is a chronic disease with multiple etiologies, multiple manifestations, and multi-organ involvement. Affects about 200 million people worldwide. Its main complication is Portal hypertension (PHT). Cirrhotic cardiomyopathy is a consequence of PHT, with heart failure (HF) being the main manifestation. On the other hand, for people with cardiopathy due to other reasons beyond cirrhosis, the presence of the last could act as a trigger to acute HF. Finally, when HF and cirrhosis coexist, the renal system suffers the most, originating from type-5 cardio-renal syndrome, a complex entity with many challenges in diagnosis and treatment. This entity was recently defined and there is a lack of data on the epidemiology of this syndrome. A 77-year-old woman, with cardiovascular risk factors; heart failure with reduced ejection fraction (HFrEF), secondary ischemic and valvular cardiopathy, chronic Kidney disease (CKD), and stable decompensated cirrhosis, went to the emergency department after progressive abdominal perimeter augmentation, legs’ edema and hematochezia. It was assumed acute decompensated cirrhosis and acute decompensated chronic kidney disease, had triggered digestive bleeding and the patient stayed hospitalized. Intravenous diuretic therapy was started but, the ascites and kidney function got worse, the Nt pro-BNP grew until 1125000 pg/ml, and a transthoracic echocardiography showed important signs of congestion, isolated right ventricular dysfunction, with normal cardiac output. After teamwork’s discussion, a type-5 cardio-renal syndrome was assumed deciding not to act on tricuspid regurgitation due to the maladaptive RV remodeling. Hepatorenal syndrome treatment was begun (oral terlipressin and intravenous albumin), followed by decongestion therapy, resulting in a marked improvement in clinical presentation. The kidney, heart, and liver recovered to these basal states. With this clinical case, the authors want to show how multidisciplinary management is important to face tricuspid regurgitation and right ventricular dysfunction.

Aortic valve stenosis and malignancy frequently coexist and share the same risk factors as atherosclerotic disease. Data reporting the prognosis of patients with severe aortic stenosis and cancer are limited. Tailoring the correct and most optimal care for cancer patients with severe aortic stenosis is complex. Cancer patients may be further disadvantaged by aortic stenosis if it interferes with their treatment by increasing the risk associated with oncologic surgery and compounding the risks associated with cardiotoxicity and heart failure (HF). Nowadays, several therapeutic options are available for aortic valve stenosis (surgical valve replacement , transcatheter valve implantation, balloon valvuloplasty, or medical therapy), but in presence of malignancy, the use of one of these versus the others should be decided on a case-by-case approach, depending on cancer stage and associated treatment, expected outcome, comorbidities and after an accurate physical examination and Doppler-echocardiography which are the key tools for diagnosing and evaluating aortic stenosis. The current review considers the available data on the association between aortic stenosis and cancer, and therapeutic options.

Background: Anthracyclines form the backbone of many systemic chemotherapy regimens but dose-limiting cardiotoxicity can also lead to reduction in cardiac function and an increased risk of heart failure. Methods: This review was conducted in accordance with PRISMA guidelines and registered on PROSPERO (CRD42022373496). Results: 26 studies met the eligibility criteria including a total of 910 patients. Overall reduction in pooled mean left ventricular ejection fraction (LVEF) post‐anthracyclines in the placebo arms of included randomised-controlled trials was 4.6% (95% CI, 2.7 to 6.6). The trend in LVEF showed a progressive decline until approximately 180 days after which there was no significant change. Those receiving a cumulative anthracycline dose 300 mg/m2 experienced a more profound reduction. The risk of a 10% absolute decline in LVEF from baseline or decline to an LVEF below 50%, the overall pooled risk was 16% (95% CI: 11 to 21; I2 = 77%). Sensitivity analyses by baseline LVEF and trastuzumab treatment status did not yield significant differences. Conclusion: While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines are required.

We explored how dietary behaviors (sucrose, fructose, sodium, and potassium consumption) and endured psychological stress in young adult males and females impact the vascular aging index (VAI) and CVD risk by mid-life. Data were obtained from the Coronary Artery Risk Development in Young Adults Study, an ongoing longitudinal study. Included participants (n=2,656) had un-dergone carotid artery ultrasound at year 20 allowing VAIs to be calculated. Demographics, di-etary data and depression scores were obtained at baseline and year 20. Regression analyses were used to assess the predictors of VAI. Cox regression analyses were conducted to assess the risk of CVD, stroke and all-cause mortality. Predictors of vascular aging were found to be sex-specific. In females, CES-D scores at baseline were positively associated with VAI (B-weight=0.063, p=0.015). In males, sodium intake at year 20 positively predicted VAI (B-weight=0.145, p=0.003) and potassium intake inversely predicted VAI (B-weight=-0.160, p<0.001). BMI significantly predicted CVD, stroke, and death. Fructose consumption at year 20 was a significant predictor of CVD risk while having high blood pressure at baseline was signif-icantly associated with stroke risk. Our findings support the promotion of nutrient- specific be-havior changes to prevent vascular aging in early adulthood and CVD risk in mid-life.

The endothelium is a monolayer of cells lining the inner blood vessels. Endothelial cells (ECs) play indispensable roles in angiogenesis, homeostasis, and immune response under normal physiological conditions, and their dysfunction is closely associated with pathologies such as cardiovascular diseases. Abnormal EC metabolism, especially fatty acid (FA) dysfunctional metabolism, contributes to the development of many diseases including pulmonary hypertension (PH). In this review, we focus on discussing the latest advances in FA metabolism in ECs under normal and pathological conditions with an emphasis on PH. We also highlight areas of research that warrant further investigation.

Cardiovascular diseases remain the leading cause of mortality worldwide. Although new therapies are actively being developed and used for cardiovascular pathologies, these attempts have not significantly decreased mortality rates. Regenerative medicine has made enormous progress and set promising approaches over the past half-century. However, since autologous (donor-derived) vascular grafts are lacking, an alternative prosthesis must be constructed for cardiovascular disease patients. In vascular tissue manufacturing and regenerative medicine, scientists seek to improve this significant clinical challenge using bio-fabrication techniques combining additive manufacturing, biomaterials science, and advanced cellular biology. In the last few decades, many improvements and changes in various approaches have helped develop bioengineered concepts that reflect native blood vessels’ structure and function. However, numerous challenges must be overcome to clinically translate the next generation of tissue-engineered vascular transplants. This review provides update on the cell sources, scaffold essential for cardiovascular tissue engineering, and tissue engineering approaches as prospective options for curative therapy for blood vessel disease.

: For a long time, atherosclerosis has been regarded as a mere lipid deposit in the blood vessels. However, in the recent years a growing body of experimental and clinical evidence have highlighted the role of inflammation and immunity as a central mechanism of disease. Moreover, in the last decade the coming of next-generation sequencing and its application to large human population has broken the barrier between inflammation and cancer. Indeed, acquired mutation in key genes related to the control of hematopoiesis and myeloproliferation have paved the way to establish the new concept of clonal hematopoiesis of indeterminate potential. This phenomenon is being considered not such “indeterminate”, but as an emerging cardiovascular risk factor. Thus, this may explain the mechanisms of myeloproliferation and inflammation in atherosclerosis. And in a bidirectional journey, it has helped to explain the extremely high cardiovascular risk in cancer survivors, in particular in myeloprolfierative neoplasm patients. A deeper understanding of these mechanisms may pave the way for the future early diagnosis and potential preemptive treatments of the leading worldwide cause of death.

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.

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.

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.

Previous studies have revealed the microbial metabolism of dietary choline in the gut, leading to its conversion into trimethylamine (TMA), a precursor of the cardiovascular inflammatory marker trimethylamine N-oxide (TMAO). Polymethoxyflavones (PMFs), exemplified by tangeretin, demonstrate efficacy in mitigating TMAO-induced cardiovascular inflammation. However, the specific mechanism by which these compounds exert their effects, particularly in modulating the gut microbiota, remains uncertain. This investigation focused on tangeretin, a representative PMFs, exploring its influence on the gut microbiota and the choline-TMA conversion process. Experimental results showed that tangeretin treatment attenuated the population of CutC-active bacteria, specifically Clostridiaceae and Lactobacillus, induced by choline chloride in rat models. This inhibition resulted in reduced efficiency in choline conversion to TMA, thereby ameliorating cardiovascular inflammation resulting from prolonged choline consumption. In conclusion, tangeretin's preventive action against cardiovascular inflammation is intricately linked to its targeted modulation of TMA-producing bacterial activity.

Background: Retinal vascular abnormalities may be associated with glaucomatous damage. Adaptive optics (AO) is a new technology that enables analysis of retinal vasculature at the cellular level in vivo. The purpose of this study is to evaluate retinal arteriolar parameters using the adaptive optics fundus camera (AO -FC) rtx1 in patients with primary open-angle glaucoma (POAG) at different stages and to investigate the relationship between these parameters and changes in optical coherence tomography (OCT) and perimetry. We wanted to assess whether vascular changes could be a cause or effect of glaucomatous damage. Methods: Parameters of retinal supratemporal and infratemporal arterioles (wall thickness (WT), lumen diameter (LD), total diameter (TD), wall-to-lumen ratio (WLR), and cross-sectional area of the vascular wall (WCSA)) were analysed with the rtx1 in 111 POAG eyes, divided into three groups according to the severity of disease and 70 healthy eyes in correlation of structural defects in retinal nerve fibre layer and visual fields defects. Results: Compared with the control group, the POAG groups showed significantly smaller TD and LD values (p<0,05) and significantly higher WLR and WT values (p<0,05) for supratemporal and infratemporal arterioles. Rtx1 parameters significantly correlated with OCT parameters (retinal nerve fibre layer, ganglion cell complex and rim area) and visual field parameters (mean deviation and pattern standard deviation) (p<0.05). Conclusion:  The results suggest that vascular dysfunction may be involved in POAG pathogenesis and neurodegenerative damage, even at the very early stage of glaucoma, without visual field defects.

In response to injury, vascular smooth muscle cells (VSMCs) of the arterial wall dedifferentiate into a proliferative and migratory phenotype, leading to intimal hyperplasia. The ERK1/2 pathway participates in cellular proliferation and migration while dual-specificity phosphatase 6 (DUSP6, also named MKP3) can dephosphorylate activated ERK1/2. We showed that DUSP6 was expressed in low baseline levels in normal arteries; however, arterial injury significantly increased DUSP6 levels in the vessel wall. Compared with wild-type mice, Dusp6-deficient mice had smaller neointima. In vitro, IL-1β induced DUSP6 expression and increased VSMC proliferation and migration. Lack of DUSP6 diminished IL-1β-induced VSMC proliferation and migration. DUSP6 deficiency did not affect IL-1β-stimulated ERK1/2 activation. Instead, ERK1/2 inhibitor U0126 prevented DUSP6 induction by IL-1beta, indicating that ERK1/2 functions upstream of DUSP6 to regulate DUSP6 expression in VSMCs rather than downstream as a DUSP6 substrate. IL-1β decreased levels of cell cycle inhibitor p27 and cell-cell adhesion molecule N-cadherin in VSMCs whereas lack of DUSP6 prevented their downregulation, revealing novel functions of DUSP6 in regulating these two molecules. Taken together, our results indicate that lack of DUSP6 attenuated neointima formation following arterial injury by reducing VSMC proliferation and migration, which were likely mediated via maintaining p27 and N-cadherin levels.

Background and Objectives: Blood flow restriction (BFR) has been investigated as an alternative method combined with resistance training or AT to promote different health benefits for older people. Nevertheless, no study analyzed chronic effects of BFR on muscle activation in this population, and in some investigations, the application of BFR has been employed arbitrary pressures, which can be a serious methodological error, both from the results and of the risk to the health of the older. Thus, this study analyzed the effect of 24 weeks of walking with BFR on activation and muscle strength in elderly women with osteoporosis. Materials and Methods: Thirty older women (66.0±4.6 years) performed randomly to one of three training groups: WALK (moderate-intensity walking), WALK+BFR (low-intensity walking with BFR), or BFR (BFR alone). Muscle activation (sEMG) and strength of knee flexors and extensors were measured pre-intervention and after 12 and 24 weeks. Results: Only a trivial effect size (ES) for the WALK+BFR (ES= 0.16) was observed in sEMG of the knee flexors compared to WALK. A moderate effect was observed in sEMG of the knee extensors (ES= 0.65) for the WALK+BFR compared to the WALK. However, adverse effects were found in the strength of the knee flexors for the BFR (ES= −0.86) and WALK+BFR (ES= −0.69) compared to WALK. Adverse and null effects, respectively for the BFR (ES= −0.16) and WALK+BFR (ES= 0.06) groups, were also observed on the strength gain of the knee extensors. Conclusions: Low-intensity walk combined with BFR does not provide relevant chronic effects on strength gain or even limit muscle strength gain, however, due to greater activation of knee extensors over 24 weeks, it is possible to benefit from the use of similar strategies to obtain neuromuscular gains in the long‐term for elderly women with osteopenia and osteoporosis.

The lack of suitable autologous grafts and poor compliance of existing prostheses have prompted the study of novel materials for vascular graft design. Polyurethanes (PUs) were used in the past because they have high compliance and properties that are similar to those of native tissue. In this work, the mechanical properties of a group of PUs in two states (non-hydrated and hydrated) were studied using uniaxial tensile tests, strain sweep tests, and multi-step creep recovery tests. Additionally, a hyper-elastic model based on the Mooney–Rivlin strain density function was fitted and used to model the performances of the PUs under physiological pressure and geometry conditions. The tensile tests revealed a softening phenomenon after hydration, which could potentially reduce patient discomfort and risk of vascular trauma. The ultimate strength values after hydration were similar to those reported for other vascular conduits. The strain sweep showed a strong strain dependency of the modulus indicating non-linear viscoelasticity. In the creep-recovery tests, increasing the polyethylene glycol(PEG) content enhanced the viscous flow, while the elastic behavior was enhanced with the largest concentration of polycaprolactone diol (PCL). On the other hand, under simulated physiological conditions, the compliance of the PUs showed a cyclic behavior with the time and pressure but was not affected by the radii and thickness variation, which could increase the graft compliance and geometry mismatch. Nevertheless, the compliance could be tuned using the material composition. This paper studied the biomechanics of a group of materials under simulated physiological conditions (Temperature, hydration, and pressure) to select those that could perform better for further vascular graft design.

Patients with chronic renal failure and vascular diseases require the vascular access for hemodialysis procedure to be performed with the most possible comfort for the patient. Native vein graft has a longer-lasting term in the patients’ limb, lower risk of graft infection and lower price. Native vein graft is constructed from the great saphenous vein, if the diameter of the vessel is smaller than the diameters of vessels (brachial artery, cephalic vein) it is connected to in the cubital fossa region due to the risk of graft folding, that might occur, if the graft diameter is bigger than the diameter of one or both vessels, on which anastomosis is made. The most important sizes, that were taken before graft placement, are the length of the forearm compartment, the distance between the brachial artery and cephalic vein in the cubital fossa region, distance from an expected incision in the brachial artery to the middle of the forearm compartment, the distance between incision in cephalic vein to the middle of the forearm compartment, length of the great saphenous vein (the graft) and diameters of blood vessels, used in the procedure. Finally, the right position of the graft should be determined for the successful outcome of anastomosis creating procedure.

Background: Genome-wide association studies have identified the chromosome 9p21 locus as one of the most important genetic risk factors for cardiovascular disease. However, the mechanism by which this locus promotes disease remains unclear due to difficulty identifying the causal genes and lack of a suitable animal model. Methods and Results: A total of 180 coronary artery autopsy specimens were analyzed histopathologically. The genotype of 9p21 (rs1333049) was not associated with any coronary risk factors nor the vulnerable plaque phenotype, but carriers of 9p21 risk allele did demonstrate more lesional calcification. To extend these studies into an animal model, mice with a targeted deletion of the orthologous 70-kb non-coding interval on chromosome 4 (chr4^D70kb/D70kb) were bred onto ApoE^-/- and fed with high fat diet. Targeted deletion of the 9p21 risk interval increased susceptibility to atherosclerotic plaque progression, but did not affect plaque rupture in the tandem stenosis model. Coronary risk factors such as body weight, blood pressure, lipid, and glucose levels did not differ between genotypes. Von Kossa staining revealed that chr4^D70kb/D70kb, ApoE^-/- developed more calcification in the plaque compared with chr4^+/+, ApoE^-/- mice, and that this this change was accompanied by increased aortic mRNA expression of Runx2, a key osteogenic transcription factor. Primarily cultured smooth muscle cells from chr4^D70kb/D70kb were hyperproliferative, and showed a calcification-prone phenotype after exposure to high-phosphate medium. Treatment with Palbociclib, a selective inhibitor of cyclin-dependent kinase 4/6, reduced mRNA expression of osteogenic genes in smooth muscle cells. Conclusion: Results from human and mouse studies indicate that the 9p21 non coding risk interval is associated with larger atherosclerotic plaque burden, but not with plaque rupture. 9p21 may promote lesion expansion by inducing the proliferation of de-differentiated and osteogenic smooth muscle cells.

Nucleotide-binding domain like receptor protein 3 (NLRP3) inflammasome in the kidney and the heart is increasingly being suggested to play a key role in mediating inflammation. In the kidney, NLRP3 activation has been associated with the progression of diabetic kidney disease. In the heart, activation of the NLRP3 inflammasome has been related to enhanced release of interleukin-1β (IL-1β) and the subsequent induction of atherosclerosis and heart failure. Apart from their glucose-lowering effects, SGLT-2 Inhibitors have been documented to attenuate activation of the NLRP3, thus, resulting in the constellation of an anti-inflammatory milieu. In this review, we will focus on the interplay between SGLT-2 Inhibitors and the inflammasome in the kidney, the heart and the neurons in the context of diabetes mellitus and its complications.

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.

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.

According to the World Health Organization, cardiovascular disease (CVD) is the leading cause of death among women worldwide, yet its magnitude is often underestimated. Biological and gender differences affect health, diagnosis, and healthcare in numerous ways. The lack of sex and gender awareness in health research and healthcare is an ongoing issue and affects not only research, but also treatment and outcomes. The importance of recognising the impact of both sex and gender on health and of knowing the differences between the two in healthcare is beginning to gain ground. There is more appreciation of the role that biological differences (sex) and sociocultural power structures (gender) have, and both sex and gender affect health behaviour, the development of diseases, their diagnosis, management, and long-term effects of an illness. An important issue is the knowledge and awareness of women about vascular diseases. The risk of cardiovascular events is drastically underestimated by women themselves, as well as by those around them. The purpose of this review is to draw attention to improving the medical care and treatment of women with vascular diseases.

(1) Background: Most patients with atrial fibrillation, on warfarin therapy, are at higher risk of morbidity and mortality. However, data targeting patients with atrial fibrillation, who take warfarin therapy, are limited in Jordan. This study aimed to provide in-depth analysis of a cohort of patients with atrial fibrillation on warfarin regarding patients’ characteristics, atrial fibrillation related symptoms, interventions, comorbidities, and 12-months outcomes. (2) Methods: The study enrolled 645 patients with atrial fibrillation, on warfarin, from 28 health settings across Jordan. Standardized clinical data form was utilized to collect data upon enrollment, at one, six, and 12 months post initial assessment. Descriptive statistics were used for the description of variables. (3) Results: The most commonly reported symptoms were palpitation (41.4%) shortness of breath (39.1%) and fatigue (26.2%). The prevalent comorbidities associated with atrial fibrillation were congestive heart failure (22.5%), valvular heart diseases (16.6%), and cerebral vascular accident (16.3%). The embolic (32.4%) and thrombotic cerebral vascular accident (16.2%) were the most common type. Major bleeding associated with hospitalization was the most frequent type of bleeding (10 out of 24). (4) Conclusions: Jordanians, using anticoagulation, need to be constantly monitored in terms of their characteristics, symptoms, and any potential complications, to ensure its optimal therapeutic dose and prevent any potential health complications.

Pulmonary Hypertension (PH) is a terminal disease characterized by severe pulmonary vascular remodeling. Unfortunately, targeted therapy to prevent disease progression is limited. Here, the vascular cell populations that contribute to the molecular and morphological changes of PH in conjunction with current animal models for studying vascular remodeling in PH will be examined. The status quo of epigenetic targeting for treating vascular remodeling in different PH subtypes will be dissected, while parallel epigenetic threads between pulmonary hypertension and pathogenic cancer provide insight into future therapeutic PH opportunities.

This study presents a case report demonstrating an anomalous origin of the right subclavian artery from the aortic arch, accompanied by proximal dilation and a retro-esophageal course, characteristic of arteria lusoria and Kommerell's diverticulum. The research highlights the clinical significance of this anomaly and discusses its management strategies, emphasizing the importance of precise surgical intervention in addressing this condition.

The Translationally Controlled Tumor Protein (TCTP) is a multifunctional protein found in most eukaryotic taxa. In plants, TCTP regulates cell-cycle progression as well as programmed cell death and is involved in plant regeneration and responses to abiotic and biotic stress, among other functions. Additionally, there is evidence that the transcript and protein are transported over long-distance. Potatoes are a crop of agricultural interest that can reproduce asexually by regeneration from stolons and tubers. Therefore, in this study the effect of transient expression of Solanum tuberosum TCTP (StTCTP) on tuberization was analyzed. StTCTP mRNA was shown to be transported long-distance. Additionally, transient overexpression of StTCTP resulted in tuber bearing shoots with a greater diameter compared to control plants. Furthermore, the early stages of tuberization were induced compared to control plants, in which only mature tubers were observed.

Leukotrienes are proinflammatory mediators that participate in the process of atherogenesis and contribute to the development of symptomatic peripheral arterial disease. The aim was to evaluate the relationship between leukotriene E4 (LTE4) and B4 (LTB4) with parameters reflecting endothelial vascular function in patients with chronic lower limb ischemia. This prospective observational study enrolled 50 consecutive patients undergoing endovascular treatment due to chronic lower limb ischemia (Rutherford 3). All participants were followed-up for one year (after 1, 3, 6 and 12 months), with a sequential assessment of urinary LTE4 and LTB4, as well as measures of endothelial and vascular function: Flow-Mediated Dilatation (FMD), Intima-Media Thickness (IMT), corrected Augmentation Index (AI75), Shear Rate (SR), Ankle-Brachial Index (ABI), Toe-Brachial Index (TBI). There was a significant relationship between LTE4 and measures of vascular function: FMD (R2 = 0.69, P&lt;0.001), IMT (R2=0.12, P&lt;0.01), AI75 (R2=0.43, P&lt;0.001), SR (R2=0.48, P&lt;0.001). Similar findings were noted for LTB4: FMD (R2=0.47, p&lt;0.001), IMT (R2=0.23, P&lt;0.001), AI75 (R2=0.61, P&lt;0.001) and SR (R2=0.33, P&lt;0.001). Alterations in parameters were significantly related: ΔLTE4 vs ΔFMD(R2=0.63, P&lt;0.001), ΔSR (R2=0.42, P&lt;0.001) and ΔLTB4 vs AI75(R2=0.40, P&lt;0.001), SR(R2=0. 29, P&lt;0.001). We conclude, that increasing concentrations of LTE4 and LTB4 are associated with impairment of vascular and endothelial function, which may lead to worse endovascular treatment clinical outcomes.

Yellow fever (YF) is a pansystemic disease caused by the yellow fever virus (YFV), the prototype species of the family Flaviviridae and genus Flavivirus, and has a highly complex host-pathogen relationship, in which endothelial dysfunction reflects viral disease tropism. In this study, the in situ endothelial response was evaluated. Liver tissue samples were collected from 21 YFV-positive patients who died due to the disease and five flavivirus-negative controls who died of other causes and whose hepatic parenchyma architecture was preserved. Immunohistochemical analysis of tissues in the hepatic parenchyma of YF cases showed significantly higher expression of E-selectin, P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and very late antigen-4 in YFV-positive cases than in flavivirus-negative controls. These results indicate that endothelium activation aggravates the inflammatory response by inducing the expression of adhesion molecules that contribute to the rolling, recruitment, migration, and construction of the inflammatory process in the hepatic parenchyma in fatal YF cases.

Thoracic aortic calcium (TAC) appears to be a subclinical marker of cardiovascular disease (CVD) and to predict CV mortality. However, studies on TAC use tomographic scans obtained for coronary artery calcium (CAC) score, which does not include the aortic arch. This study evaluates TAC prevalence in aortic arch (AAC), ascending (ATAC) and descending thoracic aorta (DTAC) and verify whether they are associated with the same CV risk factors. Cross-sectional analysis, including 2,427 participants (mean age 55.6 ± 8.7; 54,1% women) of the ELSA-Brasil cohort. Nonenhanced ECG-gated tomographies were performed in 2015-2016. Multivariable logistic regression estimated the CV risk factors associated with calcium in each segment. Overall prevalence of ATAC, AAC and DTAC was, 23,1%, 62.1%, and 31.2%, respectively. About 90.4% of the individuals with TAC had AAC and only 19.5% had calcium in all segments. In the multivariable analysis, increasing age, lower levels of schooling, current smoking, higher body mass index, and hypertension remained associated with calcium in all segments. No sex or race/ethnicity differences were found in any aortic segment. Diabetes and Dyslipidemia were associated with ATAC and DTAC, but not with AAC, suggesting that AAC may reflect an overlap of mechanisms that impact vascular health, including atherosclerosis.

Background We aimed to compare the retinal, optic disc vascular density (ODVD) values, and acircularity index (AI) of patients with idiopathic macular telangiectasia type 2 (IMT) and healthy individuals using the optical coherence tomography angiography(OCTA) device. Methods The study included 39 patients with IMT and 37 healthy controls. The OCTA findings of the patients and controls were examined. Results The total, parafoveal and perifoveal vascular density of the superficial capillary plexus, choriocapillaris blood flow, inside-disc ODVD, retinal nerve fiber layer (RNFL), and retinal thicknesses were found to be statistically significantly lower and the foveal avascular zone value was statistically significantly higher in the IMT group compared to the control group (p=0.001, p=0.01, p=0.02, p=0.01, p=0.009, p=0.002, p=0.02, respectively).There was a statistically significant negative correlation between best-corrected visual acuity (BCVA) and AI (p=0.02), a statistically significant positive correlation between peripapillary vascular density and BCVA(p=0.04). Conclusion We consider that the lower retinal, choriocapillaris, and ODVD values, retinal and RNFL thicknesses in the patients with IMT compared to the controls were due to vascular damage, remodeling, fibrosis, proliferation, and Müller cell damage. Ellipsoid zone defect, AI, and peripapillary vascular density are important indicators in the evaluation of visual acuity in these patients.

Endothelial cells form a powerful interface between tissues and immune cells. In fact, one of the underappreciated roles of endothelial cells is to orchestrate immune attention to specific sites. Tumor endothelial cells have a unique ability to dampen the immune responses and thereby maintain an immunosuppressive microenvironment. Recent approaches to trigger immune responses in cancers have focused on activating nucleic acid sensors such as cGAS/STING in combination with immunotherapies. In this review, we present a case for targeting nucleic acid sensing pathways within the tumor vasculature to invigorate tumor immune responses. We introduce two specific nucleic acid sensors, the DNA sensor TREX1 and the RNA sensor RIG-I and discuss their functional roles in the vasculature. Finally, we present perspectives on how these nucleic acid sensors in the tumor endothelium can be targeted in an antiangiogenic and immune activation context. We believe understanding the role of nucleic acid sensing in the tumor vasculature can enhance our ability to design more effective therapies targeting the tumor microenvironment.

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.

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.