Crosstalk among canonical Wnt and Hippo pathway members in skeletal muscle and at the neuromuscular junction

Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.

Role of the Notch Signaling Pathway in Fibrosis of Denervated Skeletal Muscle

In order to investigate the role of the Notch signaling pathway in skeletal muscle fibrosis after nerve injury, 60 Sprague-Dawley rats were selected and divided randomly into a control and two experimental groups. Group A served as controls without any treatment. Rats in groups B were injected intraperitoneally with 0.2 mL PBS and those in group C were injected intraperitoneally with 0.2 mL PBS+100 ymol/L, 0.2 mL N-[N-(3,5-difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester (DAPT, a gamma-secretase inhibitor that suppresses Notch signaling) respectively, on postoperative days 1, 3, 7, 10, and 14 in a model of denervation-induced skeletal muscle fibrosis by right sciatic nerve transection. Five rats from each group were euthanized on postoperative days 1, 7, 14, and 28 to collect the right gastrocnemii, and hematoxylin and eosin (HE) staining, immunohistochemistry test, real-time PCR, and Western blotting were performed to assess connective tissue hyperplasia and fibroblast density as well as expression of Notch 1, Jagged 1, and Notch downstream molecules Hes 1 and collagen I (COL I) on day 28. There was no significant difference in HE-stained fibroblast density between group B and C on postoperative day 1. However, fibroblast density was significantly higher in group B than in group C on postoperative days 7, 14, and 28. Notch 1, Jagged 1, Hes 1, and COL I proteins in the gastrocnemius were expressed at very low levels in group A but at high levels in group B. Expression levels of these proteins were significantly lower in group C than in group B (P<0.05), but they were higher in group C than in group A (P<0.05) on postoperative day 28. We are led to conclude that locking the Notch signaling pathway inhibits fibrosis progression of denervated skeletal muscle. Thus, it may be a new approach for treatment of fibrosis of denervated skeletal muscle.

Yiqi Yangyin and Huatan Quyu granule can improve skeletal muscle energy metabolism in a type 2 diabetic rat model by promoting the AMPK/SIRT/PGC-1α signalling pathway

Objective:To investigate how Yiqi Yangyin and Huatan Quyu granule (YYHO) improves skeletal muscle insulin resistance in a type 2 diabetic rat model and to discover whether the molecular mechanism is related to the promotion of the AMPK/SIRT/PGC-1α signalling pathway.Methods:Rats were randomly divided into 4 groups:the normal group,the model group,the YYHQ granule group,and the pioglitazone group.The type 2 diabetic rat model was established by feeding a high-fat diet for 5 weeks along with a single intraperitoneal injection of 30 mg/kg streptozotocin (STZ).After modelling successfully,the appropriate drug was intragastrically administered to diabetic rats for 2 weeks,once per day.The YYHQ granule group was given a dose of 4.8 g/kg body weight per day,the pioglitazone group was given a dose of 1.35 mg/kg body weight per day.The doses for both groups were equivalent to the clinical equivalent dose based on a previous study.Other groups were gavaged with the same amount of saline water.Body weight,food intake,water intake,urine volume and grip strength were recorded weekly.The fasting blood glucose(FBG) was determined weekly using blood glucose test strips.The related glucose and lipid metabolism indexes,e.g.,fasting insulin (Fins),glycated haemoglobin (GHb),HOMA-IR,ISI,triglycerides (TG),total cholesterol (TC),high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C) and free fatty acid (FFA),were determined using biochemical method.The mRNA expression levels of adenosine monophosphate-activated protein kinase (AMPK),peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α),carnitine palmitoyl transterase-1 (CPT-1),Sirtuin 1 (SIRT1),and Sirtuin 3 (SIRT3) were assessed using quantitative real-time PCR (qRT-PCR).The protein expression levels of creatine kinase (CK),Ca2+ ATPase,α-Actin,AMPK,PGC-1α and CPT-1 were determined using enzyme-linked immunosorbent assay method (ELISA).Results:Body weight decreased significantly (P <.01),food intake,water intake and urine volume increased significantly (P <.01),and grip strength decreased significantly (P <.01) in the model group compared with the normal group.The levels of FBG,Fins,GHb and HOMA-IR increased significantly (P <.01),and the ISI decreased significantly (P <.01) in the model group.The levels of TG,TC,LDL-C and FFA increased significantly (P <.05 or P <.01),and the level of HDL-C decreased significantly (P <.05) in the model group.These changes were reversed after treatment with YYHQ granule or pioglitazone.Compared with the model group,the YYHQ granule and pioglitazone groups significantly improve body weight,water intake and urine volume (P <.05 or P <.01),however,both treatments had no significant effect on food intake (P >.05).The levels of FBG,Fins,GHb,HOMA-IR and ISI were improved significantly (P <.01) and the levels of TG,TC and LDL-C were improved significantly (P <.05 or P <.01),however,both treatments had no significant effect on the levels of HDL-C and FFA (P >.05).Further results indicated that YYHQ granule significantly decreased the mRNA expression of AMPK,PGC-1α,CPT-1,SIRT1 and SIRT3 in skeletal muscle (P <.01) and the pioglitazone group showed similar effects;moreover,the protein expression levels of CK,Ca2+ATPase,α-Actin,AMPK,PGC-1α and CPT-1 in skeletal muscle significantly decreased (P <.01),however,pioglitazone had no significant effect on CK and α-Actin (P >.05).Conclusion:The possible molecular mechanism of YYHQ granule improving skeletal muscle insulin resistance in a type 2 diabetic rat model may be related to the stimulation of energy metabolism in skeletal muscle via the AMPK/SIRT/PGC-1α signalling pathway.

Skeletal muscle as a molecular and cellular biomarker of disease progression in amyotrophic lateral sclerosis:a narrative review

Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.

Functional imaging of skeletal muscle glucose metabolism by ¹⁸FDG PET to characterize insulin resistance in patients at high risk for coronary artery disease

Insulin resistance is associated with several coronary risk factors and is thought to play a critical role for the development of coronary artery disease. Insulin resistance has several causes, including an impaired skeletal muscle glucose utilization rate (SMGU), reduced peripheral blood flow, and altered fatty tissue metabolism, with SMGU being considered the most important. Nonetheless, insulin resistance has only been estimated by the glucose disposal rate (GDR) in previous studies. Methods: Skeletal muscle metabolic imaging with 18FDG and positron emission tomography (PET) was undertaken to measure SMGU during hyperinsulinemiceuglycemic clamping in 22 normotensive type-2 diabetics under no medications (T2- DM), 17 normotensive non-diabetic hypertriglyceridemics, 22 patients with hypertension, and 12 agematched controls. Whole body insulin resistance was assessed by the GDR during hyperinsulinemiceuglycemic insulin clamping. Results: The SMGU and GDR were significantly reduced in T2DM (32.1 ± 16.6 μmol/min/kg and 24.3 ± 13.0 μmol/min/kg, respectively), hypertriglyceridemics (36.5 ± 13.5 μmol/min/ kg and 22.7 ± 8.07 μmol/min/kg respectively) and patients with hypertension (35.4 ± 26.6 μmol/min/kg and 29.0 ± 9.90 μmol/min/kg, respectively) compared with controls (72.2 ± 44.1 μmol/min/kg and 43.0 ± 22.9 μmol/min/kg, p < 0.01, respectively). In all groups studied, SMGU was significantly correlated with GDR (r = 0.76, p < 0.01) and GDR (F = 13.9) was independently related to SMGU (r = 0.81, p < 0.01). Conclusion: Insulin resistance is significantly associated with SMGU to a similar degree among patients with T2DM, essential hypertension and hypertriglyceridemia. 18FDG PET functional imaging allows insulin resistance to be assessed.

Skeletal dysplasias: A radiographic approach and review of common non-lethal skeletal dysplasias

Skeletal dysplasias are not uncommon entities and a radiologist is likely to encounter a suspected case of dysplasia in his practice. The correct and early diagnosis of dysplasia is important for management of complications and for future genetic counselling. While there is an exhaustive classification system on dysplasias, it is important to be familiar with the radiological features of common dysplasias. In this article, we enumerate a radiographic approach to skeletal dysplasias, describe the essential as well as differentiating features of common non-lethal skeletal dysplasias and conclude by presenting working algorithms to either definitively diagnose a particular dysplasia or suggest the most likely differential diagnoses to the referring clinician and thus direct further workup of the patient.

Skeletal muscle-derived cells repair peripheral nerve defects in mice

Skeletal muscle-derived cells have strong secretory function,while skeletal muscle-derived stem cells,which are included in muscle-derived cells,can differentiate into Schwann cell-like cells and other cell types.However,the effect of muscle-derived cells on peripheral nerve defects has not been reported.In this study,5-mm-long nerve defects were created in the right sciatic nerves of mice to construct a peripheral nerve defect model.Adult female C57BL/6 mice were randomly divided into four groups.For the muscle-derived cell group,muscle-derived cells were injected into the catheter after the cut nerve ends were bridged with a polyurethane catheter.For external oblique muscle-fabricated nerve conduit and polyurethane groups,an external oblique muscle-fabricated nerve conduit or polyurethane catheter was used to bridge the cut nerve ends,respectively.For the sham group,the sciatic nerves on the right side were separated but not excised.At 8 and 12 weeks post-surgery,distributions of axons and myelin sheaths were observed,and the nerve diameter was calculated using immunofluorescence staining.The number,diameter,and thickness of myelinated nerve fibers were detected by toluidine blue staining and transmission electron microscopy.Muscle fiber area ratios were calculated by Masson’s trichrome staining of gastrocnemius muscle sections.Sciatic functional index was recorded using walking footprint analysis at 4,8,and 12 weeks after operation.The results showed that,at 8 and 12 weeks after surgery,myelin sheaths and axons of regenerating nerves were evenly distributed in the muscle-derived cell group.The number,diameter,and myelin sheath thickness of myelinated nerve fibers,as well as gastrocnemius muscle wet weight and muscle area ratio,were significantly higher in the muscle-derived cell group compared with the polyurethane group.At 4,8,and 12 weeks post-surgery,sciatic functional index was notably increased in the muscle-derived cell group compared with the polyurethane group.These criteria of the muscle-derived cell group were not significantly different from the external oblique muscle-fabricated nerve conduit group.Collectively,these data suggest that muscle-derived cells effectively accelerated peripheral nerve regeneration.This study was approved by the Animal Ethics Committee of Plastic Surgery Hospital,Chinese Academy of Medical Sciences(approval No.040)on September 28,2016.

Game-changing insights on vertebral skeletal stem cells in bone metastasis and therapeutic horizons

Greenblatt and his team have unveiled vertebral skeletal stem cells(vSSCs)as a critical player in the landscape of bone metastasis.This commentary delves into the transformative discoveries surrounding vSSCs,emphasizing their distinct role in bone metastasis compared to other stem cell lineages.We illuminate the unique properties and functions of vSSCs,which may account for the elevated susceptibility of vertebral bones to metastatic invasion.Furthermore,we explore the exciting therapeutic horizons opened by this newfound understanding.These include potential interventions targeting vSSCs,modulation of associated signaling pathways,and broader implications for the treatment and management of bone metastasis.By shedding light on these game-changing insights,we hope to pave the way for novel strategies that could revolutionize the prognosis and treatment landscape for cancer patients with metastatic bone disease.

Expression of PI3-K,PKB and GSK-3β in the skeletal muscle tissue of gestational diabetes mellitus

Objective:To analyze the expression of phosphatidylinositol 3 kinase(PI3-K),protein kinase B(PKB)and glycogen synthase kinase 3 beta(GSK-3β)in skeletal muscle tissue of gestational diabetes mellitus(GDM).Methods:A total of 90 cases of pregnant women were divided into observation group and control group according to the occurrence of GDM with 45 cases in either,and the expression of PI3-K,PKB,GSK-3βmRNA expression in skeletal muscle tissue was compared between two groups.Results:The total PI3-K p85 protein was significantly higher in the observation group compared with the control group,the activity of PI3-K was lower than that of the latter;The total PKB,GSK-3βprotein in skeletal tissue had no significant difference between two groups,while the serine phosphorylation levels of PKB and GSK-3βwere significantly lower in observation group compared with the control group.Conclusions:The downregulation of PI3-K,PKB and GSK-3βin skeletal tissue of GDM caused by phosphorylation dysfunction of signaling molecules is the reason for insulin resistance and transporter function decline which lead to GDM.

Measurement of lumbar muscle glucose utilization rate can be as useful in estimating skeletal muscle insulin resistance as that of thigh muscle

Background: Skeletal muscle glucose utilization (SMGU) can be accessed by positron emission tomography (PET) and18F-FDG to characterize insulin resistance. The quantity of skeletal muscle in the lumbar is sufficient to indicate that SMGU in the lumbar (SMGU- lumbar) can be measured with18F-FDG PET of the chest instead of obtaining thigh muscle SMGU (SMGU-thigh). This would reduce PET scan time to avoid thigh muscle PET scan. This study was aimed to compare SMGU-lumbar and thigh muscle SMGU under insulin clamping to identify the validity of measurements of SMGU in the lumbar for studies of insulin resistance. Methods: Thirty-three patients underwent sequential dynamic18F-FDG PET of both the thoracic (37 min) and thigh region (22 min) during hyperinsulinemic euglycemic insulin clamping. Both SMGU-lumbar and SMGU-thigh were calculated by Patlak graphical analysis. Whole body insulin resistance was assessed by a whole body glucose disposal rate during hyperinsulinemic euglycemic insulin clamping. Input function was obtained from the time activity curve of the descending aorta and venous blood sampling as previously validated. Results: SMGU-thigh (0.0506 ± 0.0334 μmol/min/g) was comparable to SMGU-lumbar (0.0497 ± 0.0255 μmol/min/g). The Bland-Altman method of difference plot analysis showed a significant correlationship between SMGU- thigh and SMGU-lumbar (r = 0.506, p = 0.0028). There were seen very good significant correlationship between whole body glucose utilization rate in both thigh (r = 0.737, p = 0.0001) and lumbar (r = 0.772, p = 0.0001). Conclusion: These results support the validity of measuring SMGU-lumbar to estimate insulin resistance during PET imaging of the chest.

Skeletal muscle and whole body insulin resistance but not cardiac muscle insulin resistance could be improved by troglitazone therapy within 12 weeks in type-2 diabetes

Background: Existence of myocardial insulin resistance (IR) has been reported in type II diabetics (T2- DM) and coronary artery disease (CAD). Improvement in heart and skeletal muscle IR after thiazolidinedione’s therapy was reported in T2DM and CAD. However effects of troglitazone therapy (TRO) on myocardial IR remain uncertain. To clarify heart and skeletal muscle and whole body IR in T2DM without CAD by TRO to clarify whether TRO would provide different results. Methods: We analyzed data on 15 T2DM patients who underwent dynamic PET with 18F-FDG under insulin clamping before and during TRO (200 mg/day) and 17 controls. Results: Whole body glucose disposal rate (WBGR mg/min/kg) in T2DM before TRO (3.41 ± 1.72) was significantly lower than in controls (9.76 ± 2.97, p < 0.01) as was the skeletal muscle glucose utilization rate (SMGU mg/min/kg);T2DM (0.367 ± 0.217) vs. controls (1.34 ± 0.613, p < 0.01) and myocardial glucose utilization rate (MGU mg/min/kg;T2DM 5.86 ± 2.03 vs. controls 7.34 ± 1.80, p < 0.05). WBGR in T2DM during TRO (5.17 ± 2.75, p < 0.05) was significantly higher than that before TRO, as was the SMGU (0.782 ± 0.20, p < 0.05). The MGU in T2DM during TRO (6.59 ± 0.72) was comparable with that before TRO. Conclusion: Myocardial IR response to TRO differed from that in skeletal muscle and the whole body in T2DM without CAD.

Roles of N-cadherin in cerebral cortical development:cooperation with membrane trafficking and actin cytoskeletal regulation

Cell adhesion plays pivotal roles in the morphogenesis of multicellular organisms.Epithelial cells form several types of cell-to-cell adhesion,including zonula occludens(tight junctions),zonula adhaerens(adherens junctions),and macula adhaerens(desmosomes).Although these adhesion complexes are basically observed only in epithelial cells,cadherins,which are the major cell adhesion molecules of adherens junctions,are expressed in both epithelial and non-epithelial tissues,including neural tissues(Kawauchi,2012).The cadherin superfamily consists of more than 100 members,but classic cadherins.

Skeletal myoblast based delivery of angiogenic growth factors:a comparison between angiopoietin-1 and VEGF gene delivery for therapeutic angiogenesis in the heart

Objectives This study investigated the efficacy of human skeletal myoblasts (SkM) mediated either human vascular endothelial growth factor-165 (hVEGF165) or angiopoietin-1 (Ang-1) on vascular development and myocardial regional perfusion. Methods A porcine heart model of chronic infarction was created in 28 female swine by coronary artery ligation. The animals were randomized into: (1) group-1, DMEM injected (n=6), (2) group-2, Ad-null transduced SkM transplanted (n=6), (3) group-3, Ad-hVEGF165 transduced SkM transplanted (n=8), and (4) group-4, Ad-Ang-1 transduced SkM (n=8). Three weeks later, 5 ml DMEM containing 3×108 SkM carrying exogenous genes were intramyocardially injected into 20 sites in left ventricle in groups-2, -3 and -4. Animals in group-1 were injected 5 ml DMEM without cells. Animals were kept on 5 mg/kg cyclosporine per day for 6 weeks. Regional blood flow was measured using fluorescent microspheres. The heart was explanted at 2, 6 and 12 weeks after transplantation for histological studies. Results Histological examination showed survival of lac-z expressing myoblasts in host tissue. Capillary density based on Von Willebrand factor-VIII (vWF-VIII) at low power field (×100) was 57.13±11.85 in group-3 at 6 weeks and declined to 32.1±5.21 at 12 weeks, while it was 39.9±10.26 at 6 weeks and increased to 45.14±6.54 at 12 weeks in group-4. The mature blood vessel index was highest in group- 4 at 6 and 12 weeks after transplantation. The regional blood flow in the center and peri-infarct area was significantly increased in animals of groups-3 and -4. Conclusions SkM carrying either hVEGF165 or Ang-1 induced neovascularization with increased blood flow. Ang-1 overexpression resulted in mature and stable blood vessel formation and may be a more potent arteriogenic inducer for neovascularization.

Hybrid treatment of varied orthodontic appliances for a patient with skeletal class II and temporomandibular joint disorders:A case report and review of literature

BACKGROUND The relation between orthodontic treatment and temporomandibular disorders(TMDs)is under debate;the management of TMD during orthodontic treatment has always been a challenge.If TMD symptoms occur during orthodontic treatment,an immediate pause of orthodontic adjustments is recommended;the treatment can resume when the symptoms are managed and stabilized.CASE SUMMARY This case report presents a patient(26-year-old,female)with angle class I,skeletal class II and TMDs.The treatment was a hybrid of clear aligners,fixed appliances and temporary anchorage devices(TADs).After 3 mo resting and treatment on her TMD,the patient’s TMD symptom alleviated,but her anterior occlusion displayed deep overbite.Therefore,the fixed appliances with TAD were used to correct the anterior deep-bite and level maxillary and mandibular deep curves.After the levelling,the patient showed dual bite with centric relation and maximum intercuspation discrepancy on her occlusion.After careful examination of temporomandibular joints(TMJ)position,the stable bite splint and Invisible Mandibular Advancement appliance were used to reconstruct her occlusion.Eventually,the improved facial appearance and relatively stable occlusion were achieved.The 1-year follow-up records showed there was no obvious change in TMJ morphology,and her occlusion was stable.CONCLUSION TMD screening and monitoring is of great clinical importance in the TMD susceptible patients.Hybrid treatment with clear aligners and fixed appliances and TADs is an effective treatment modality for the complex cases.

Skeletal extension rate of the reef building coral <i>Porites</i>species from Aqaba and their environmental variables

Annual skeletal extension rates of the sclera-actinian corals Porites species were investigated in 32 colonies from the northern Gulf of Aqaba fringing reef at various depths (1 - 42 m). All corals reveal clear and regular skeletal density banding patterns. Results showed that the high-density annual growth bands were formed during winter and the low-density annual growth bands during summer. The mean annual extension rates of the studied corals reveal a large inter-colony variability with values ranged between 2.36 to 20.0 mm/year. While a general trend of decreasing coral extension rate with depth was observed and best explained by a simple exponential model, the rates clustered into two groups: 10.86 ± 2.54 mm/year in water depths less than 10 m, and 5.23 ± 1.99 mm/year below 12 m. Light intensity seems to be the primary environmental factor responsible for decreasing coral extension rate with depth since the effect of other environmental parameters could be neglected from the Gulf of Aqaba. Time series record of the mean annual coral extension rate showed a slight increasing linear trend which could be linked to increase seawater temperature over the period of time represented.

Biology of Hippo signaling pathway:Skeletal muscle development and beyond

Global demand for farm animals and their meat products i.e.,pork,chicken and other livestock meat,is steadily incresing.With the ongoing life science research and the rapid development of biotechnology,it is a great opportunity to develop advanced molecular breeding markers to efficiently improve animal meat production traits.Hippo is an important study subject because of its crucial role in the regulation of organ size.In recent years,with the increase of research on Hippo signaling pathway,the integrative application of multi-omics technologies such as genomics,transcriptomics,proteomics,and metabolomics can help promote the in-depth involvement of Hippo signaling pathway in skeletal muscle development research.The Hippo signaling pathway plays a key role in many biological events,including cell division,cell migration,cell proliferation,cell differentiation,cell apoptosis,as well as cell adhesion,cell polarity,homeostasis,maintenance of the face of mechanical overload,etc.Its influence on the development of skeletal muscle has important research value for enhancing the efficiency of animal husbandry production.In this study,we traced the origin of the Hippo pathway,comprehensively sorted out all the functional factors found in the pathway,deeply analyzed the molecular mechanism of its function,and classified it from a novel perspective based on its main functional domain and mode of action.Our aim is to systematically explore its regulatory role throughout skeletal muscle development.We specifically focus on the Hippo signaling pathway in embryonic stem cell development,muscle satellite cell fate determination,myogenesis,skeletal muscle meat production and organ size regulation,muscle hypertrophy and atrophy,muscle fiber formation and its transformation between different types,and cardiomyocytes.The roles in proliferation and regeneration are methodically summarized and analyzed comprehensively.The summary and prospect of the Hippo signaling pathway within this article will provide ideas for further improving meat production and muscle deposition and developing new molecular breeding technologies for livestock and poultry,which will be helpful for the development of animal molecular breeding.

Catalpa bignonioides extract improves exercise performance through regulation of growth and metabolism in skeletal muscles

Objective:To evaluate the effects of Catalpa bignonioides fruit extract on the promotion of muscle growth and muscular capacity in vitro and in vivo.Methods:Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Cell proliferation was assessed using a 5-bromo-2’-deoxyuridine(BrdU)assay kit.Western blot analysis was performed to determine the protein expressions of related factors.The effects of Catalpa bignonioides extract were investigated in mice using the treadmill exhaustion test and whole-limb grip strength assay.Chemical composition analysis was performed using high-performance liquid chromatography(HPLC).Results:Catalpa bignonioides extract increased the proliferation of C2C12 mouse myoblasts by activating the Akt/mTOR signaling pathway.It also induced metabolic changes,increasing the number of mitochondria and glucose metabolism by phosphorylating adenosine monophosphate-activated protein kinase.In an in vivo study,the extract-treated mice showed improved motor abilities,such as muscular endurance and grip strength.Additionally,HPLC analysis showed that vanillic acid may be the main component of the Catalpa bignonioides extract that enhanced muscle strength.Conclusions:Catalpa bignonioides improves exercise performance through regulation of growth and metabolism in skeletal muscles,suggesting its potential as an effective natural agent for improving muscular strength.

Surplus dietary isoleucine intake enhanced monounsaturated fatty acid synthesis and fat accumulation in skeletal muscle of finishing pigs

Background: Isoleucine(Ile) has been implicated in the regulation of energy homeostasis and adipogenesis.However,the impact of surplus dietary Ile intake on muscle lipogenesis remains unknown.The present study aimed to investigate the impact of dietary supplementation of extra-Ile on lipogenesis,fatty acid profile and lipid accumulation in skeletal muscle in finishing pigs.Methods: Forty-eight barrows with initial body weight of 77.0 ± 0.1 kg were allotted to one of two groups and fed diets containing 0.39%,0.53% standardized ileal digestible(SID) Ile with six replicates per treatment and four pigs per replicate for 30 d.Results: Dietary Ile intake significantly improved the intramuscular fat(IMF) content and monounsaturated fatty acid(MUFA) concentration in the skeletal muscle(P < 0.05),and decreased the drip loss and shear force(P < 0.05) without influencing the growth performance of pigs(P > 0.05).Moreover,the phosphorylation of adenosine monophosphate activated protein kinase α(AMPKα) and acetyl coenzyme A carboxylase(ACC) proteins that monitor lipid metabolism were decreased in skeletal muscle of pigs offered extra-Ile diet(P < 0.05).The mRNA expression of adipose-specific genes adipocyte determination and differentiation factor 1(ADD1),fatty acid synthase(FAS),and stearoyl-CoA desaturase(SCD) were upregulated and the activity of SCD was increased as well(P < 0.05).Conclusions: Surplus dietary Ile intake could increase IMF accumulation and MUFA synthesis in skeletal muscle through depressing the phosphorylation of AMPKα-ACC and stimulating the expression and activity of SCD,and increasing the capability of lipogenesis in skeletal muscle.

Advances in TCM Treatment of Skeletal Fluorosis

By consulting and collating the relevant literatures on the treatment of fluorosis in Traditional Chinese medicine, the research progress of TCM in the treatment of fluorosis was summarized. This paper summarizes the treatment of fluorosis in traditional Chinese medicine from the aspects of the traceability of TCM theory, etiology and pathogenesis, syndrome differentiation and cure, special disease specialty and foreign medicine, so as to guide clinical practice. TCM treatment of fluorosis more use of tonifying kidney and bone, activating blood circulation stasis, cold moisturizing, Tongluo pain relief and other methods, based on dispelling evil and tonifying kidney, combined with a variety of treatment methods, in relieving clinical symptoms and improving the quality of life of patients have an irreplaceable role, has been widely recognized, but most of the research reports are their own work experience summary, Lack of uniform diagnosis and treatment standards, and small sample size, data repeatability is weak, future research needs to further enhance the scientific and objective of the experiment, for TCM treatment of fluorosis to provide a scientific and reasonable diagnosis and treatment program, give full play to the advantages of TCM therapy.

High-Lard and High-Fish Oil Diets Differ in Their Effects on Insulin Resistance Development, Mitochondrial Morphology and Dynamic Behaviour in Rat Skeletal Muscle

Fish oil (mainly omega 3 polyunsaturated fatty acids), differently from lard (mainly saturated fatty acids) has been suggested to have anti-inflammatory effects associated with amelioration of insulin sensibility. An important role in skeletal muscle insulin resistance development has been recently attributed to mitochondrial dynamic behavior. Mitochondria are dynamic organelles that frequently undergo fission/fusion processes and a shift toward fission process has been associated with skeletal muscle mitochondrial dysfunction and insulin resistance development. The present work aimed to evaluate if the replacement of lard with fish oil in high-fat diet positively affect skeletal muscle mitochondrial dynamic behavior in association with the improvement of insulin-resistance. Body weight gain, systemic insulin-resistance (glucose/insulin ratio), serum TNFα levels and skeletal muscle lipid content were assessed in rats fed a high-lard or high-fish-oil diet for 6 weeks. In skeletal muscle sections, immunohistochemical analysis were performed to detect the presence of insulin receptor substrate 1 (IRS1) and tyrosine phosphorylated IRS1 (key factor in insulin signalling pathway) as well as to detect the main proteins involved in mitochondrial fusion (MFN2 and OPA1) and fission (DRP1 and Fis1) processes. Skeletal muscle mitochondrial ultrastructural features were assessed by electron microscopy. High-fish oil feeding induced lower body weight gain, systemic inflammation and insulin-resistance development as well as skeletal muscle lipid accumulation compared to high-lard feeding. Skeletal muscle sections from high-fish oil fed rats exhibited a greater number of immunoreactive fibers for MFN2 and OPA1 proteins as well as weaker immunostaining for DRP1 and Fis1 compared to sections from high-lard fed rats. Electron microscopy observations suggested a prominent presence of fission events in L rats and fusion events in F rats. The positive effect of the replacement of lard with fish oil in high-fat diet on systemic and skeletal muscle insulin sensibility was associated to changes in mitochondrial dynamic behavior.