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.

Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathway

Neonatal growth is characterized by a high protein synthesis rate that is largely due to an enhanced sensitivity to the postprandial rise in insulin and amino acids, especially leucine. The mechanism of leucine＇s action in vivo is not well understood. In this study, we investigated the effect of leucine infusion on protein synthesis in skeletal muscle and liver of neonatal pigs. To evaluate the mode of action of leucine, we used rapamycin, an inhibitor of mammalian target of rapamycin （mTOR） complex-1 （mTORC1）. Overnight-fasted 7-day-old piglets were treated with rapamycin for 1 hour and then infused with leucine （400 μmol·kg^-1·h^-1） for 1 hour. Leucine infusion increased the rate of protein synthesis, and ribosomal protein S6 kinase 1 （S6K1） and eukaryotic initiation factor （elF） 4E-binding protein-1 （4E-BP1） phosphorylation in gastrocnemius and masseter muscles （P 〈 0.05）, but not in the liver. The leucine-induced stimulation of protein synthesis and S6K1 and 4E-BP1 phosphorylation were completely blocked by rapamycin, suggesting that leucine action is by an mTORC1-dependent mechanism. Neither leucine nor rapamycin had any effect on the activation of the upstream mTQRC1 regulators, AMP-activated protein kinase and protein kinase B, in skeletal muscle or liver. The activation of elF2α and elongation factor 2 was not affected by leucine or rapamycin, indicating that these two pathways are not limiting steps of leucine-induced protein synthesis. These results suggest that leucine stimulates muscle protein synthesis in neonatal pigs by inducing the activation of mTORC1 and its downstream pathway leading to mRNA translation.

The landscape of chromatin accessibility in skeletal muscle during embryonic development in pigs

Background:The development of skeletal muscle in pigs during the embryonic stage is precisely regulated by transcriptional mechanisms,which depend on chromatin accessibility.However,how chromatin accessibility plays a regulatory role during embryonic skeletal muscle development in pigs has not been reported.To gain insight into the landscape of chromatin accessibility and the associated genome-wide transcriptome during embryonic muscle development,we performed ATAC-seq and RNA-seq analyses of skeletal muscle from pig embryos at 45,70 and 100 days post coitus(dpc).Results:In total,21,638,35,447 and 60,181 unique regions(or peaks)were found across the embryos at 45 dpc(LW45),70 dpc(LW70)and 100 dpc(LW100),respectively.More than 91%of the peaks were annotated within−1 kb to 100 bp of transcription start sites(TSSs).First,widespread increases in specific accessible chromatin regions(ACRs)from embryos at 45 to 100 dpc suggested that the regulatory mechanisms became increasingly complicated during embryonic development.Second,the findings from integrated ATAC-seq and RNA-seq analyses showed that not only the numbers but also the intensities of ACRs could control the expression of associated genes.Moreover,the motif screening of stage-specific ACRs revealed some transcription factors that regulate muscle developmentrelated genes,such as MyoG,Mef2c,and Mef2d.Several potential transcriptional repressors,including E2F6,OTX2 and CTCF,were identified among the genes that exhibited different regulation trends between the ATAC-seq and RNA-seq data.Conclusions:This work indicates that chromatin accessibility plays an important regulatory role in the embryonic muscle development of pigs and regulates the temporal and spatial expression patterns of key genes in muscle development by influencing the binding of transcription factors.Our results contribute to a better understanding of the regulatory dynamics of genes involved in pig embryonic skeletal muscle development.

Transcriptomic analysis elucidates the enhanced skeletal muscle mass, reduced fat accumulation, and metabolically benign liver in human follistatin-344 transgenic pigs

Follistatin(FST) is an important regulator of skeletal muscle growth and adipose deposition through its ability to bind to several members of the transforming growth factor-β(TGF-β) superfamily, and thus may be a good candidate for future animal breeding programs. However, the molecular mechanisms underlying the phenotypic changes have yet to be clarified in pig. We generated transgenic(TG) pigs that express human FST specifically in skeletal muscle tissues and characterized the phenotypic changes compared with the same tissues in wild-type pigs. The TG pigs showed increased skeletal muscle growth, decreased adipose deposition, and improved metabolism status(P<0.05). Transcriptome analysis detected important roles of the PIK3–AKT signaling pathway, calcium-mediated signaling pathway, and amino acid metabolism pathway in FST-induced skeletal muscle hypertrophy, and depot-specific oxidative metabolism changes in psoas major muscle. Furthermore, the lipid metabolism-related process was changed in adipose tissue in the TG pigs. Gene set enrichment analysis revealed that genes related to lipid synthesis, lipid catabolism, and lipid storage were down-regulated(P<0.01) in the TG pigs for subcutaneous fat, whereas genes related to lipid catabolism were significantly up-regulated(P<0.05) in the TG pigs for retroperitoneal fat compared with their expression levels in wild-type pigs. In liver, genes related to the TGF-β signaling pathway were over-represented in the TG pigs, which is consistent with the inhibitory role of FST in regulating TGF-β signaling. Together, these results provide new insights into the molecular mechanisms underlying the phenotypic changes in pig.

Effects of dietary protein restriction on muscle fiber characteristics and m TORC1 pathway in the skeletal muscle of growing-finishing pigs

Background： To investigate the effects of dietary crude protein（CP） restriction on muscle fiber characteristics and key regulators related to protein deposition in skeletal muscle, a total of 18 growing-finishing pigs（62.30 ± 0.88 kg）were allotted to 3 groups and fed with the recommended adequate protein（AP, 16 % CP） diet, moderately restricted protein（MP, 13 % CP） diet and low protein（LP, 10 % CP） diet, respectively. The skeletal muscle of different locations in pigs, including longissimus dorsi muscle（LDM）, psoas major muscle（PMM） and biceps femoris muscle（BFM） were collected and analyzed.Results： Results showed that growing-finishing pigs fed the MP or AP diet improved（P 〈 0.01） the average daily gain and feed： gain ratio compared with those fed the LP diet, and the MP diet tended to increase（P = 0.09） the weight of LDM. Moreover, the ATP content and energy charge value were varied among muscle samples from different locations of pigs fed the reduced protein diets. We also observed that pigs fed the MP diet up-regulated（P 〈 0.05） muscular m RNA expression of all the selected key genes, except that myosin heavy chain（My HC） IIb,My HC IIx, while m RNA expression of ubiquitin ligases genes was not affected by dietary CP level. Additionally, the activation of mammalian target of rapamycin complex 1（m TORC1） pathway was stimulated（P 〈 0.05） in skeletal muscle of the pigs fed the MP or AP diet compared with those fed the LP diet.Conclusion： The results suggest that the pigs fed the MP diet could catch up to the growth performance and the LDM weight of the pigs fed the AP diet, and the underlying mechanism may be partly due to the alteration in energy status, modulation of muscle fiber characteristics and m TORC1 activation as well as its downstream effectors in skeletal muscle of different locations in growing-finishing pigs.

Transcriptional response of porcine skeletal muscle to feeding a linseed-enriched diet to growing pigs

Background： To investigate the effect of feeding a linseed-enriched diet to growing-finishing pigs on gene expression in skeletal muscle, pigs were fed with a linseed-enriched diet for 0, 30, 60 and 90 d. Transcriptional profiles of longissimus dorsi muscle were measured using Affymetrix Genechip.Results： Results showed that 264 genes were identified as differentially expressed genes（DEGs）. The strongest transcriptional response was clearly observed at 30 d. DEGs were assigned to several main functional terms,including transcription, apoptosis, intracellular receptor-mediated signaling, muscle organ development, fatty acid metabolic process, cell motion, regulation of glucose metabolic process, spermatogenesis and regulation of myeloid cell differentiation. We also found that transcriptional changs of several transcription cofactors might contribute to n-3 PUFAs regulated gene expression. In addition, the increased expression of IGF-1, insulin signaling pathway and the metabolism of amino acids might involve in the muscle growth induced by feeding a linseedenriched diet. The results also provide the new evidence that the expression changes of PTPN1, HK2 and PGC-1αmight contribute to the regulation of insulin sensitivity by n-3 PUFAs.Conclusions： Our finding provided correlative evidence that feeding the linseed enriched diet affact expression of genes involved in insulin signaling pathway and the metabolism of amino acids.

Gestational heat stress alters skeletal muscle gene expression profiles and vascularity in fetal pigs in a sexually dimorphic manner

Background: There is evidence that sow heat stress(HS) during gestation affects fetal development with implications for impaired muscle growth. We have previously demonstrated that maternal HS during early to midgestation compromised muscle fibre hyperplasia in developing fetal pigs. Thus, we hypothesised these phenotypic changes are associated with a change in expression of genes regulating fetal skeletal muscle development and metabolism. To test this, at d 60 of gestation, RNA sequencing and immunohistochemistry were performed on fetal longissimus dorsi(LD) muscle biopsies collected from pregnant gilts that had experienced either thermoneutral control(CON, 20 ℃, n = 7 gilts, 18 LD samples) or controlled HS(cyclic 28 to 33 ℃, n = 8 gilts, 23 LD samples)conditions for 3 weeks.Results: A total of 282 genes were differentially expressed between the HS and CON groups in female LD muscles(false discovery rate(FDR) ≤ 0.05), whereas no differentially expressed genes were detected in male LD muscles between the two groups(FDR > 0.05). Gestational HS increased the expression of genes associated with transcription corepressor activity, adipogenesis cascades, negative regulation of angiogenesis and pro-inflammatory signalling in female LD muscles. Immunohistochemical analyses revealed a decreased muscle vascularity density in fetuses from HS group for both sexes compared to those from the CON group(P = 0.004).Conclusions: These results reveal gilt HS during early to mid-gestation altered gene expression profiles in fetal LD muscles in a sexually dimorphic manner. The molecular responses, including transcription and angiogenesis repressions and enhanced adipogenesis cascades, were exclusively observed in females. However, the associated reductions in muscle vascularity were observed independently of sexes. Collectively this may indicate female fetal pigs are more adaptive to gestational HS in terms of gene expression changes, and/or there may be sexually dimorphic differences with respect to the timing of muscle molecular responses to gestational HS.

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.

Low skeletal muscle mass and high visceral adiposity are associated with recurrence of acute cholecystitis after conservative management:A propensity score-matched cohort study

Background:Recurrent acute cholecystitis(RAC)can occur after non-surgical treatment for acute cholecystitis(AC),and can be more severe in comparison to the first episode of AC.Low skeletal muscle mass or adiposity have various effects in several diseases.We aimed to clarify the relationship between RAC and body parameters.Methods:Patients with AC who were treated at our hospital between January 2011 and March 2022 were enrolled.The psoas muscle mass and adipose tissue area at the third lumbar level were measured using computed tomography at the first episode of AC.The areas were divided by height to obtain the psoas muscle mass index(PMI)and subcutaneous/visceral adipose tissue index(SATI/VATI).According to median VATI,SATI and PMI values by sex,patients were divided into the high and low PMI groups.We performed propensity score matching to eliminate the baseline differences between the high PMI and low PMI groups and analyzed the cumulative incidence and predictors of RAC.Results:The entire cohort was divided into the high PMI(n=81)and low PMI(n=80)groups.In the propensity score-matched cohort there were 57 patients in each group.In Kaplan-Meier analysis,the low PMI group and the high VATI group had a significantly higher cumulative incidence of RAC than their counterparts(log-rank P=0.001 and 0.015,respectively).In a multivariate Cox regression analysis,the hazard ratios of low PMI and low VATI for RAC were 5.250(95%confidence interval 1.083-25.450,P=0.039)and 0.158(95%confidence interval:0.026-0.937,P=0.042),respectively.Conclusions:Low skeletal muscle mass and high visceral adiposity were independent risk factors for RAC.

In vivo imaging and computational modeling of nonlinear shear waves in living skeletal muscles

How the state of living muscles modulates the features of nonlinear elastic waves generated by external dynamic loads remains unclear because of the challenge of directly observing and modeling nonlinear elastic waves in skeletal muscles in vivo,considering their active deformation behavior.Here,this important issue is addressed by combining experiments performed with an ultrafast ultrasound imaging system to track nonlinear shear waves(shear shock waves)in muscles in vivo and finite element analysis relying on a physically motivated constitutive model to study the effect of muscle activation level.Skeletal muscle was loaded with a deep muscle stimulator to generate shear shock waves(SSWs).The particle velocities,second and third harmonics,and group velocities of the SSWs in living muscles under both passive and active states were measured in vivo.Our experimental results reveal,for the first time,that muscle states have a pronounced effect on wave features;a low level of activation may facilitate the occurrence of both the second and third harmonics,whereas a high level of activation may inhibit the third harmonic.Finite element analysis was further carried out to quantitatively explore the effect of active muscle deformation behavior on the generation and propagation of SSWs.The simulation results at different muscle activation levels confirmed the experimental findings.The ability to reveal the effects of muscle state on the features of SSWs may be helpful in elucidating the unique dynamic deformation mechanism of living skeletal muscles,quantitatively characterizing diverse shock wave-based therapy instruments,and guiding the design of muscle-mimicking soft materials.

SWIR FluorescenceImaging In Vivo Monitoring and Evaluating Implanted M2 Macrophages in Skeletal Muscle Regeneration

Skeletal muscle has a robust regeneration ability that is impaired by severe injury,disease,and aging.resulting in a decline in skeletal muscle function.Therefore,improving skeletal muscle regeneration is a key challenge in treating skeletal muscle-related disorders.Owing to their significant role in tissue regeneration,implantation of M2 macrophages(M2MФ)has great potential for improving skeletal muscle regeneration.Here,we present a short-wave infrared(SWIR)fluorescence imaging technique to obtain more in vivo information for an in-depth evaluation of the skeletal muscle regeneration effect after M2MФtransplantation.SWIR fluorescence imaging was employed to track implanted M2MФin the injured skeletal muscle of mouse models.It is found that the implanted M2MФaccumulated at the injury site for two weeks.Then,SWIR fluorescence imaging of blood vessels showed that M2MФimplantation could improve the relative perfusion ratio on day 5(1.09±0.09 vs 0.85±0.05;p=0.01)and day 9(1.38±0.16 vs 0.95±0.03;p=0.01)post-injury,as well as augment the degree of skeletal muscle regencration on day 13 post-injury.Finally,multiple linear regression analyses determined that post-injury time and relative perfusion ratio could be used as predictive indicators to evaluate skeletal muscle regeneration.These results provide more in vivo details about M2MФin skeletal muscle regeneration and confirm that M2MФcould promote angiogenesis and improve the degree of skeletal muscle repair,which will guide the research and development of M2MФimplantation to improve skeletal muscle regeneration.

Temporal and spatial regulation of biomimetic vascularization in 3D-printed skeletal muscles

In the intricate skeletal muscle tissue,the symbiotic relationship between myotubes and their supporting vasculature is pivotal in delivering essential oxygen and nutrients.This study explored the complex interplay between skeletal muscle and endothelial cells in the vascularization ofmuscle tissue.By harnessing the capabilities of three-dimensional(3D)bioprinting and modeling,we developed a novel approach involving the co-construction of endothelial and muscle cells,followed by their subsequent differentiation.Our findings highlight the importance of the interaction dynamics between these two cell types.Notably,introducing endothelial cells during the advanced phases of muscle differentiation enhanced myotube assembly.Moreover,it stimulated the development of the vascular network,paving the way for the early stages of vascularized skeletal muscle development.The methodology proposed in this study indicates the potential for constructing large-scale,physiologically aligned skeletal muscle.Additionally,it highlights the need for exploring the delicate equilibrium and mutual interactions between muscle and endothelial cells.Based on the multicell-type interaction model,we can predict promising pathways for constructing even more intricate tissues or organs.

Acupotomy ameliorates knee osteoarthritis-related collagen deposition and fibrosis in rabbit skeletal muscle through the TGF-β/Smad pathway

Objective:To investigate the effects of acupotomy on skeletal muscle fibrosis and collagen deposition in a rabbit knee osteoarthritis(KOA)model.Methods: Rabbits(n=18)were randomly divided into control,KOA,and KOA+acupotomy(Apo)groups(n=6).The rabbits in the KOA and Apo groups were modeled using the modified Videman's method for 6 weeks.After modeling,the Apo group was subjected to acupotomy once a week for 3 weeks on the vastus medialis,vastus lateralis,rectus femoris,biceps femoris,and anserine bursa tendons around the knee.The behavior of all animals was recorded,rectus femoris tissue was obtained,and histomorphological changes were observed using Masson staining and transmission electron microscopy.The expression of transforming growth factor-β1(TGF-β1),Smad 3,Smad 7,fibrillar collagen types I(Col-I)and III(Col-III)was detected using Western blot and real-time polymerase chain reaction(RT-PCR).Results: Histological analysis revealed that acupotomy improved the microstructure and reduced the collagen volume fraction of rectus femoris,compared with the KOA group(P=.034).Acupotomy inhibited abnormal collagen deposition by modulating the expression of fibrosis-related proteins and mRNA,thus preventing skeletal muscle fibrosis.Western blot and RT-PCR analysis revealed that in the Apo group,Col-I,and Col-III protein levels were significantly lower than those in the KOA group(both P<.01),same as Col-I and Col-III mRNA levels(P=.0031;P=.0046).Compared with the KOA group,the protein levels of TGF-β1 and Smad 3 were significantly reduced(both P<.01),as were the mRNA levels of TGF-β1 and Smad 3(P=.0007;P=.0011).Conversely,the levels of protein and mRNA of Smad 7 were significantly higher than that in the KOA group(P<.01;P=.0271).Conclusion: Acupotomy could alleviate skeletal muscle fibrosis and delay KOA progress by inhibiting collagen deposition through the TGF-β/Smad pathway in the skeletal muscle of KOA rabbits.

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.

Mitochondrial dysfunction in type 2 diabetes:A neglected path to skeletal muscle atrophy

Over the course of several decades,robust research has firmly established the significance of mitochondrial pathology as a central contributor to the onset of skeletal muscle atrophy in individuals with diabetes.However,the specific intricacies governing this process remain elusive.Extensive evidence highlights that individuals with diabetes regularly confront the severe consequences of skeletal muscle degradation.Deciphering the sophisticated mechanisms at the core of this pathology requires a thorough and meticulous exploration into the nuanced factors intricately associated with mitochondrial dysfunction.

Exploring the therapeutic effect of Xiaoyan d ecoction on lung cancer cachexia skeletal muscle atrophy based on L3-SMI

Background:Lung cancer cachexia has received widespread attention as one of the most common complications in patients with advanced lung cancer.As a multifactorial syndrome,lung cancer cachexia is characterized by a persistent decline in muscle mass that cannot be reversed by conventional nutrition Xiaoyan d ecoction can promote appetite and improve skeletal muscle mass in patients with lung cancer cachexia,while the third lumbar skeletal muscle index(L3-SMI)is able to determine whole-body skeletal muscle mass.To analyze the relationship between L3-SMI and hematological indexes and lung cancer cachexia,and to study the clinical efficacy of Xiaoyan decoction on skeletal muscle atrophy in lung cancer cachexia patients,with the aim of providing a reference basis for the early diagnosis and treatment of lung cancer cachexia patients and skeletal muscle atrophy.Methods:148 patients who were diagnosed with lung cancer in the Department of Oncology of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from January 2020 to December 2022 were included,and were divided into cachexia and non-cachexia groups according to the diagnostic criteria of cachexia,and analyzed the differences of hematological indexes and L3-SMI between cachexia patients and non-cachexia patients.And the patients with cachexia were divided into control group and treatment group,analyzed and compared the changes of body mass index(BMI),L 3-SMI,Karnofsky functional status score,albumin and other hematological indexes of the two groups before and after the treatment,and evaluated the safety of the Xiaoyan decoction in the treatment of cachexia.Results:A total of 148 lung cancer patients were included in this study,including 67 patients in the cachexia group and 81 patients in the non-cachexia group.According to the pre-treatment statistical analysis,the BMI of patients in the cachexia group was lower than that of patients in the non-cachexia group(P<0.05);among the biochemical function indexes,the proportions of creatinine(P<0.05),total protein(P<0.05),The levels of albumin in the cachexia group were significantly lower(P<0.05)compared to the non-cachexia group;in the cachexia group,both males and females had lower L3-SMIs than in the non-cachexia group(P<0.05).A total of 62 cases of lung cancer cachexia were studied,30 cases in the control group and 32 cases in the treatment group,according to statistical analysis,BMI was significantly different before and after treatment(P<0.05);L3-SMI was significantly different in the treatment group before and after treatment(P<0.05);Karnofsky significantly differed in the treatment group before and after treatment(P<0.05);and there was a significant difference in albumin before and after(P<0.05).Conclusion:Cachexia patients had significantly lower third lumbar skeletal muscle mass than non-cachexia patients,according to this study;Xiaoyan decoction was able to improve skeletal muscle mass,nutritional status as well as functional status of patients with cachexia in lung cancer,among others.

Comparison of Muscle Fiber Growth from F1Generations of Large Yorkshire Pig andErhualian Pig by Reciprocal Cross

[ Objective] To compare the muscle fiber growth between F1 generations of large Yorkshire pig and Erhualian pig by reciprocal cross, and provide a theoretical basis for the integrated breeding of meat quality traits and growth performances by rational utilization of hybrid combination. [ Method] The hybrid pigs of large Yorkshire pig and Erhualian pig were fed and managed in the same conditions. The reciprocal combinations were Erhualian pig ♀ × Yorkshire pigd, and Yorkshire pig ♀ × Erhualian pig♂ , respectively. At the age of 20, 70, 120 and 180 d, the Iongissimus dorsi muscle and thigh muscle were collected and made into frozen sections for hematoxylin and eosin （HE） staining, and then the muscle fiber area was determined. [ Result] The muscle fiber was thickened gradually with increasing age; and the absolute growth curve of muscle fiber area was presented as ＂S＂ shape. The diameter, perimeter and area of Iongissimus dorsi muscle and thigh muscle fibers in the reciprocal combination of Yorkshire pig ♀ × Erhualian pig♂ were higher than those in the reciprocal combination of Erhualian pig ♀ × Yorkshire pig♂ （P 〈 0.01 ）. The thigh muscle grew faster than Iongissimus dorsi muscle at the age of 20 -120 d; but at the age of 120 -180 d, the growth rate of Iongissimus dorsi muscle was higher than that of thigh muscle; and at the age of 180 d, the muscle fiber area had no significant difference between the Iongissimus dorsi muscle and the thigh muscle. The muscle fiber area had extremely significant difference between the reciprocal combinations at the age of 20 d; but no significant difference was found at the age of 180 d. [ Conclusion] The reciprocal combinations can affect the muscle fiber growth of hybrid pigs of Yorkshire pig and Erhualian pig, but the affect degree reduces with the increasing age.

CIDE gene expression in adipose tissue,liver,and skeletal muscle from obese and lean pigs

The expression of the cell death-inducing DNA fragmentation factorα-like effector（CIDE）family including Cidea,Cideb,and Cidec was significantly increased in mouse and human models of obesity.However,there was less information on these genes’expression in pigs.Here,we hypothesized that different fat accumulation between lean（Duroc×Landrace×Yorkshire gilts,DLY）and obese（Lantang）pigs was attributed to porcine CIDE-modulating lipid metabolism.Our data showed that Cidea and Cidec were expressed at a high level in adipose tissue,and at a relatively high level in skeletal muscle,whereas Cideb was mainly expressed in the liver in both breeds of pig.Lantang pigs had higher white adipose and skeletal muscle Cidea and Cidec mR NA abundance,and hepatic and muscle Cideb mR NA than DLY pigs.Lipid metabolism-related genes including sterol regulatory element binding protein 1c（SREBP-1c）,hepatocyte nuclear factor-4α（HNF-4α）,peroxisome proliferator-activated receptorγcoactivator-1α（PGC-1α）,fatty acid synthase（FASN）,diacylglycerol O-acyltransferase 1（DGAT1）,and DGAT2 showed a higher expression level in adipose tissue from obese pigs than in that from lean pigs.Lantang pigs exhibited higher mR NA abundance for liver SREBP-1c,HNF-4α,and PGC-1α,and higher skeletal muscle SREBP-1c,HNF-4α,PGC-1α,and DGAT2 expression,as compared with DLY pigs.However,the perlipin2 mR NA levels in adipose tissues,liver,and skeletal muscle were significantly lower in obese pigs than in their lean counterparts.Furthermore,plasma non-esterified fatty acid（NEFA）,glucose,and triacylglycerol（TAG）levels were greater in obese pigs than in lean pigs.Finally,data from correlation analysis further found that CIDE mR NA expression was positively correlated with back fat thickness（BFT）,abdominal fat mass（AFM）,and the levels of NEFA,TAG,and glucose in the two breeds.Collectively,these data revealed that the porcine CIDEs possibly modulated lipid metabolism and contributed to the development of fat deposition and obesity in Lantang pigs.

Effect of cholecystokinin and secretin on contractile activity of isolated gastric muscle strips in guinea pigs

AIM To study the effect of cholecystokinin-octapeptide（CCK-8）and secretin on contractileactivity of isolated gastric muscle strips inguinea pigs.METHODS Each isolated gastric muscle stripwas suspended in a tissue chamber containing5 mL Krebs solution constantly warmed by waterjacked at 37℃ and supplied with a mixed gas of95% O2 and 5% CO2 After incubating for lhunder 1 g tension,varied concentrations of CCK-8 and secretin were added respectively in thetissue chamber and the contractile response wasmeasured isometrically on ink-writing recorders.RESULTS CCK-8 could increase①all regionalcircular and longitudinal muscular tension at rest（fundus LM 19.7%±2.1%,P【0.01;fundus CM16.7%±2.2%,P【0.01;gastric body LM 16.8%±2.3%,P【0.01;body CM 12.7%±2.6%,P【0.01;antrum LM 12.3%±1.3%,P【0.01;antrum CM 16.7%±4.5%,P【0.01;pylous CM12.7%±5.0%,P【0.05）;②contractilefrequencies of body LM,both LM and CM ofantrum and pylorus CM（5.1/min±0.2/min to5.6/min±0.2/min,5.9/min±0.2/min to 6.6/min±0.l/min,5.4/min±0.3/min to 6.3/min±0.4/rain,1.3/min±0.2/min to 2.3/min±0.3/min,respectively,P【0.05）;③the mean contractileamplitude of antral circular muscle（58.6%±18.4%,P【0.05）and ④the motility index ofpylorus CM（145.0%±23.8%,P【0.01）,butdecrease the mean contractile amplitude ofgastric body and antral LM（-10.3%±3.3%,-10.5%±4.6%,respectively,P【0.05）.All the CCK-8 effects were not blocked by atropine orindomethacin.Secretin had no effect on gastricsmooth muscle activity.CONCLUSION CCK-8 possessed bothexcitatory and inhibitory action on contractileactivity of different regions of stomach in guineapigs.Its action was not mediated via cholinergicM receptor and endogenous prostagiandinreceptor,

Effects of rhubarb on isolated gastric muscle strips of guinea pigs

AIM:To study the effects of rhubarb (dried root of Rheum officinale Baill.) on contractile activity of isolated gastric muscle strips of guinea pigs and its possible mechanism. METHODS: A total of 48 guinea pigs were killed to remove the whole stomach. Then, the stomach was opened and the mucosal layer was removed. Parallel to the circular fibers, muscle strips were cut from the body. Each isolated gastric muscle strip was suspended in a tissue chamber containing 5 mL Krebs solution, constantly warmed by water jacket at 37℃ and bubbled continuously with a mixed gas of 950 mL/L O2 and 50 mL/L CO2. After being incubated for 1 h with 1 g tension, rhubarb of varied concentrations (1%, 2%, 7%, 20% and 70%) was added cumulatively into the tissue chamber at intervals of 2 min. Atropine (10-6 mol/L) or isoptin (5x10-8 mol/L) or hexamethonium (10-5 mol/L) was given 2 min before the administration of rhubarb. The isometrical response was measured with an ink-writing recorder. RESULTS: Rhubarb dose dependently increased the resting tension of gastric body circular muscle (CM) (r = 0.726, P<0.05). Atropine (r= 0.829, A:0.05), isoptin (r= 0.764, A;0.05) and hexamethonium (r = 0.797, P<0.05) did not affect its action in a dose-related manner. Atropine apparently reduced the increasing action of 1%, 3%, 10%, 30% and 100% rhubarb on the resting tension of gastric body CM. Isoptin inhibited the effect of 10%, 30% and 100% rhubarb on the resting tension of gastric body CM. Hexamethonium reduced the increasing action of 1%, 10%, 30% and 100% rhubarb on the resting tension of gastric body CM. Rhubarb increased the contractile frequency of CM of body. While atropine, isoptin and hexamethonium did not inhibit the contractile frequency of gastric body CM in comparison with rhubarb at the same concentration, rhubarb at the highest concentration (100%) decreased the mean contractile amplitude of gastric body CM. Atropine, isoptin and hexamethonium did not affect the mean contractile amplitude of gastric body CM compared to rhubarb at the same concentration. CONCLUSION: Rhubarb has exciting actions on isolated gastric smooth muscle strips of guinea pig. The exciting action of rhubarb is partly mediated via cholinergic M receptor, cholinergic N receptor and L-type calcium channel.