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The genetic regulation of skeletal muscle development: insights from chicken studies

Wen LUO, Bahareldin A. ABDALLA, Qinghua NIE, Xiquan ZHANG

《农业科学与工程前沿（英文）》 2017年第4卷第3期页码 295-304 doi: 10.15302/J-FASE-2017159

摘要： Skeletal muscle development is a complex multi-process trait regulated by various genetic factors. The chicken embryo is an ideal model system for studying skeletal muscle development. However, only a small proportion of the genetic factors affecting skeletal muscle development have been identified in chicken. The aim of this review is to summarize recent knowledge about the genetic factors involved in the regulation of skeletal muscle development in the chicken, such as gene polymorphisms, epigenetic modification, noncoding RNAs and transcription factors, which can influence skeletal muscle development at the genome, epigenome, transcriptome and proteome levels. Research on the regulation of skeletal muscle development in chicken is not yet comprehensive and most of the candidate genes and single nucleotide polymorphisms related to chicken muscle growth remain to be verified in experimental studies. In addition, the data derived from transcriptome sequencing and genome-wide association studies still require further investigation and analysis and comprehensive studies on the regulation of chicken skeletal muscle development will continue as a major research focus.

关键词： chicken epigenetic modification miRNAs skeletal muscle development SNP transcription factor

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The microRNA, miR-29c, participates in muscle development through targeting the

Weiya ZHANG,Wei WEI,Yuanyuan ZHAO,Shuhong ZHAO,Xinyun LI

《农业科学与工程前沿（英文）》 2015年第2卷第4期页码 311-317 doi: 10.15302/J-FASE-2015075

摘要： Previous studies indicated that miR-29c is important for muscle development in mice and human, but its role in pigs is unknown. In this study, we detected the expression of miR-29c in Meishan longissimus lumborum (LL) muscle. The results showed that miR-29c was gradually upregulated during development of skeletal muscle in pig. Moreover, the expression of and genes, which were confirmed to be targeted by miR-29c in mice, was decreased along with muscle development. Furthermore, the expression level of miR-29c was significantly higher in adult Meishan pigs than Large White pigs, while the expression of and genes was significantly lower in Meishan pigs. These results indicated that the expression pattern of miR-29c was opposite to that of and genes in pigs. Also, the luciferase assay indicated that miR-29s can target the gene in pigs. In addition, we identified a T to C mutation in the primary transcript of miR-29c, which was associated with the postmortem muscle pH in pigs. Based on these results, we concluded that miR-29c is also important in skeletal muscle development of pigs.

关键词： pig miR-29c skeletal muscle expression SNP

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Effects of resistin on skeletal glucose metabolism

Fang-Ping LI, Zhi-Zhen LI, Miao ZHANG, Li YAN, Zu-Zhi FU

《医学前沿（英文）》 2010年第4卷第3期页码 329-335 doi: 10.1007/s11684-010-0091-9

摘要： Resistin is an adipokine highly related to insulin resistance (IR). The purpose of our research was to investigate how resistin influences skeletal glucose metabolism and explore its mechanisms. We constructed the recombinant plasmid pcDNA3.1 expressing resistin and then transfected it into C2C12 myocytes. The expression of resistin in C2C12 myocytes was detected by Western blotting. Glucose uptake was measured by H labeled glucose; glucose oxidation and glycogen synthesis was detected with C-labeled glucose. GLUT4 mRNA was measured by reverse transcription polymerase chain reaction (RT-PCR). We observed that resistin was expressed in transfected myocytes, and resistin decreased insulin induced glucose uptake rate by 28%–31% and inhibited the expression of GLUT4 mRNA. However, there was no significant difference in basal glucose uptake, and glucose oxidation and glycogen synthesis remained unchanged in all groups. It is concluded that resistin inhibits insulin induced glucose uptake in myocytes by downregulating the expression of GLUT4 and it has no effects on glucose oxidation and glycogen synthesis. Our findings may provide a clue to understand the roles of resistin in the pathogenesis of skeletal IR.

关键词： resistin insulin resistance skeletal muscle

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短波红外荧光成像活体监测和评估植入的M2巨噬细胞在骨骼肌再生中的作用 Article

陈蓦, 陈雨舟, 冯思嘉, 董世贤, 孙路易, 李惠珠, 陈福春, Nguyen Thi Kim Thanh, 李云霞, 陈世益, 王友, 陈俊

《工程（英文）》 2024年第33卷第2期页码 283-294 doi: 10.1016/j.eng.2023.05.010

摘要：

骨骼肌具有强大的再生能力，但严重损伤、疾病和衰老会影响这种再生能力从而导致骨骼肌相关疾病的发生。因此，改善骨骼肌再生是治疗骨骼肌相关疾病的关键挑战。由于M2型巨噬细胞（M2Mø）在组织再生中所起的重要作用，植入M2Mø具有改善骨骼肌再生的巨大潜力。本研究利用短波红外（short-wave infrared, SWIR）荧光成像技术深入评估了M2Mø植入后对骨骼肌再生效果的活体信息。该技术示踪了小鼠骨骼肌损伤模型中植入的M2Mø。结果表明，植入的M2Mø在损伤部位聚集达两周。随后，血管SWIR荧光成像显示M2Mø植入可改善损伤后第5天（1.09 ± 0.09 vs 0.85 ± 0.05; p = 0.01）和9天（1.38 ± 0.16 vs 0.95 ± 0.03; p = 0.01）的相对灌注率，同时损伤后第13天的骨骼肌再生程度也得以改善。最后，多元线性回归分析明确了损伤后时间和相对灌注率可以作为评估骨骼肌再生的预测指标。这些结果为M2Mø在骨骼肌再生中的作用提供了更多体内细节，明确了M2Mø可促进血管生成和改善骨骼肌修复程度，这将指导未来M2Mø植入改善骨骼肌再生的进一步研究与发展。

关键词：体内短波红外骨骼肌巨噬细胞再生

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低蛋白日粮中添加亮氨酸通过雷帕霉素靶蛋白信号通路增加成年大鼠骨骼肌重量及蛋白质合成

张博, 楚丽翠, 刘宏, 谢春元, 谯仕彦, 曾祥芳

《工程（英文）》 2017年第3卷第5期页码 760-765 doi: 10.1016/J.ENG.2017.03.008

摘要：

低蛋白日粮会减少动物组织中蛋白质沉积，影响骨骼肌增重。本文旨在研究低蛋白日粮中添加亮氨酸对成年大鼠骨骼肌重量和蛋白质合成的影响。试验选取36只平均体重为（214.4 ± 2.4）g的成年SD雄性大鼠，按体重相近原则平均分为3个处理，每个处理12个重复，每个重复1只大鼠。3个处理分别饲喂20%酪蛋白（20%C，CON）、10%酪蛋白 + 丙氨酸（10%C + Ala，R）以及10%酪蛋白 + 亮氨酸（10%C + Leu，RL）日粮，试验期为11 d，其中，10%C + Ala组和10%C + Leu组为等氮日粮组。试验第11天，所有大鼠大剂量一次性腹腔注射L-[ring-2H5]苯丙氨酸注射液，测定血清中的氨基酸含量、比目鱼肌和腓肠肌重量、蛋白质合成速率及mTOR信号通路相关分子的表达。结果表明，在3个处理中，RL组血清亮氨酸含量最高（P < 0.05），而异亮氨酸含量最低（P < 0.05）；CON组的缬氨酸含量低于R和RL组（P < 0.05），但采食量、蛋白质合成速度和4EBP1的磷酸化高于R和RL组（P < 0.05），同时腹脂重量显著下降（P < 0.05）。与R组相比，RL组可以增加腓肠肌重量（P < 0.05），促进S6K1磷酸化（P < 0.05），增加骨骼肌蛋白质合成（P < 0.05）。本文结论如下，在成年大鼠长期采食低蛋白日粮的情况下，日粮中添加亮氨酸可以改善大鼠的生长性能，通过提高mTOR通路中S6K1磷酸化水平，促进大鼠骨骼肌蛋白质合成，抑制蛋白质降解。

关键词：低蛋白日粮亮氨酸生长性能肌肉重量蛋白质合成成年大鼠

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Metabonomic study of the biochemical profiles of heterozygous myostatin knockout swine

Jianxiang XU,Dengke PAN,Jie ZHAO,Jianwu WANG,Xiaohong HE,Yuehui MA,Ning LI

《农业科学与工程前沿（英文）》 2015年第2卷第1期页码 90-99 doi: 10.15302/J-FASE-2015045

摘要： Myostatin is a transforming growth factor-β family member that normally acts to limit skeletal muscle growth. Myostatin gene ( ) knockout (KO) mice show possible effects for the prevention or treatment of metabolic disorders such as obesity and type 2 diabetes. We applied chromatography and mass spectrometry based metabonomics to assess system-wide metabolic response of heterozygous KO ( ) swine. Most of the metabolic data for swine were similar to the data for wild type (WT) control swine. There were, however, metabolic changes related to fatty acid metabolism, glucose utilization, lipid metabolism, as well as BCAA catabolism caused by monoallelic depletion.The statistical analyses suggested that: (1) most metabolic changes were not significant in swine compared to WT swine; (2) only a few metabolic properties were significantly different between KO and WT swine, especially for lipid metabolism. Significantly, these minor changes were most evident in female KO swine and suggested differences in gender sensitivity to myostatin.

关键词： myostatin transforming growth factor-β family skeletal muscle metabolic disorders chromatography mass spectrometry metabonomics

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Impact of diabetes and its treatments on skeletal diseases

null

《医学前沿（英文）》 2013年第7卷第1期页码 81-90 doi: 10.1007/s11684-013-0243-9

摘要：

Diabetes mellitus is an enormous menace to public health globally. This chronic disease of metabolism will adversely affect the skeleton if not controlled. Both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are associated with an increased risk of osteoporosis and fragility fractures. Bone mineral density is reduced in T1DM, whereas patients with T2DM have normal or slightly higher bone density, suggesting impaired bone quality is involved. Detrimental effects of T1DM on the skeleton are more severe than T2DM, probably because of the lack of osteo-anabolic effects of insulin and other pancreatic hormones. In both T1DM and T2DM, low bone quality could be caused by various means, including but not limited to hyperglycemia, accumulation of advanced glycosylation end products (AGEs), decreased serum levels of osteocalcin and parathyroid hormone. Risk for osteoarthritis is also elevated in diabetic population. How diabetes accelerates the deterioration of cartilage remains largely unknown. Hyperglycemia and glucose derived AGEs could contribute to the development of osteoarthritis. Moreover, it is recognized that oral antidiabetic medicines affect bone metabolism and turnover as well. Insulin is shown to have anabolic effects on bone and hyperinsulinemia may help to explain the slightly higher bone density in patients with T2DM. Thiazolidinediones can promote bone loss and osteoporotic fractures by suppressing osteoblastogenesis and enhancing osteoclastogenesis. Metformin favors bone formation by stimulating osteoblast differentiation and protecting them against diabetic conditions such as hyperglycemia. Better knowledge of how diabetic conditions and its treatments influence skeletal tissues is in great need in view of the growing and aging population of patients with diabetes mellitus.

关键词： diabetes bone osteoporosis osteoarthritis

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Relationship of adrenomedullin expression and microvessel density and prognosis in smooth muscle tumor

JIANG Yuan, TIAN Xuehong, YUAN Jie, JIN Yuemei, TAN Yusong

《医学前沿（英文）》 2007年第1卷第4期页码 398-400 doi: 10.1007/s11684-007-0077-4

摘要： The aim of this paper was to investigate the relationship between the expression of adrenomedullin (ADM) and microvessel density (MVD) and prognosis in smooth muscle tumor of uterus. The expression of ADM was detected using immunohistochemical staining in specimens from 15 normal controls, 28 cases of uterine leiomyoma (LE) and 19 cases of uterine leiomyosarcoma (LES). The MVD was assayed by immunostainting with CD. There was a positive correlation between the ADM expression and MVD in LE and LES respectively ( = 0.823, <0.01; = 0.793, <0.01). The expression of ADM in LE was statistically lower than that in LES (<0.05). There was a positive correlation between the ADM expression and mitotic figures in LES (<0.05): the more mitotic figures, the higher levels of the ADM expression and poor prognosis. The ADM is an important angiogenic factor in smooth muscle tumor of uterus. The ADM can be used as an accessory marker in estimating the malignant potency of LE and judging the pro gnosis of LES, and as a novel molecular target of anti-angiogenic and anticarcinogenic strategies.

关键词： anticarcinogenic microvessel density malignant potency muscle uterine leiomyosarcoma

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Endogenous tissue factor pathway inhibitor in vascular smooth muscle cells inhibits arterial thrombosis

null

《医学前沿（英文）》 2017年第11卷第3期页码 403-409 doi: 10.1007/s11684-017-0522-y

摘要：

Tissue factor pathway inhibitor (TFPI) is the main inhibitor of tissue factor-mediated coagulation. TFPI is expressed by endothelial and smooth muscle cells in the vasculature. Endothelium-derived TFPI has been reported to play a regulatory role in arterial thrombosis. However, the role of endogenous TFPI in vascular smooth muscle cells (VSMCs) in thrombosis and vascular disease development has yet to be elucidated. In this TFPI^Flox mice crossbred with Sma–Cre mice were utilized to establish TFPI conditional knockout mice and to examine the effects of VSMC-directed TFPI deletion on development, hemostasis, and thrombosis. The mice with deleted TFPI in VSMCs (TFPI^Sma) reproduced viable offspring. Plasma TFPI concentration was reduced 7.2% in the TFPI^Sma mice compared with TFPI^Flox littermate controls. Plasma TFPI concentration was also detected in the TFPI^Tie2 (mice deleted TFPI in endothelial cells and cells of hematopoietic origin) mice. Plasma TFPI concentration of the TFPI^Tie2 mice was 80.4% lower (P<0.001) than that of the TFPI^Flox mice. No difference in hemostatic measures (PT, APTT, and tail bleeding) was observed between TFPI^Sma and TFPI^Flox mice. However, TFPI^Sma mice had increased ferric chloride–induced arterial thrombosis compared with TFPI^Flox littermate controls. Taken together, these data indicated that endogenous TFPI from VSMCs inhibited ferric chloride–induced arterial thrombosis without causing hemostatic effects.

关键词： arterial thrombosis conditional knockout mice tissue factor pathway inhibitor vascular smooth muscle cells

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Optimal design of steel skeletal structures using the enhanced genetic algorithm methodology

Tugrul TALASLIOGLU

《结构与土木工程前沿（英文）》 2019年第13卷第4期页码 863-889 doi: 10.1007/s11709-019-0523-9

摘要： This study concerns with the design optimization of steel skeletal structures thereby utilizing both a real-life specification provisions and ready steel profiles named hot-rolled I sections. For this purpose, the enhanced genetic algorithm methodology named EGAwMP is utilized as an optimization tool. The evolutionary search mechanism of EGAwMP is constituted on the basis of generational genetic algorithm (GGA). The exploration capacity of EGAwMP is improved in a way of dividing an entire population into sub-populations and using of a radial basis neural network for dynamically adjustment of EGAwMP’s genetic operator parameters. In order to improve the exploitation capability of EGAwMP, the proposed neural network implementation is also utilized for prediction of more accurate design variables associating with a new design strategy, design codes of which are based on the provisions of LRFD_AISC V3 specification. EGAwMP is applied to determine the real-life ready steel profiles for the optimal design of skeletal structures with 105, 200, 444, and 942 members. EGAwMP accomplishes to increase the quality degrees of optimum designations Furthermore, the importance of using the real-life steel profiles and design codes is also demonstrated. Consequently, EGAwMP is suggested as a design optimization tool for the real-life steel skeletal structures.

关键词： design optimization genetic algorithm multiple populations neural network

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Can intravesical bacillus Calmette-Guérin reduce recurrence in patients with non-muscle invasive bladder

null

《医学前沿（英文）》 2014年第8卷第2期页码 241-249 doi: 10.1007/s11684-014-0328-0

摘要：

Approximately 70% of newly diagnosed bladder tumors are non-muscle invasive bladder cancer (NMIBC). NMIBC accounts for approximately 80% of total bladder cancer cases. Bacillus Calmette-Guérin (BCG) instillation and maintenance is considered as the standard adjuvant treatment for superficial bladder cancer. A number of randomized studies have focused on the benefit of maintenance therapy following initial BCG induction. To provide further insights into the effect of intravesical instillation on recurrence in patients with NMIBC, we analyzed this relationship by conducting an updated detailed meta-analysis. Evidence suggested that adjuvant intravesical BCG with maintenance treatment is significantly effective for the prophylaxis of tumor recurrence in patients with NMIBC.

关键词： non-muscle invasive bladder cancer bacillus Calmette-Guérin (BCG) meta-analysis

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Targeting deubiquitinase OTUB1 protects vascular smooth muscle cells in atherosclerosis by modulating

《医学前沿（英文）》 2024年第18卷第3期页码 465-483 doi: 10.1007/s11684-024-1056-8

摘要： Atherosclerosis is a chronic artery disease that causes various types of cardiovascular dysfunction. Vascular smooth muscle cells (VSMCs), the main components of atherosclerotic plaque, switch from contractile to synthetic phenotypes during atherogenesis. Ubiquitylation is crucial in regulating VSMC phenotypes in atherosclerosis, and it can be reversely regulated by deubiquitinases. However, the specific effects of deubiquitinases on atherosclerosis have not been thoroughly elucidated. In this study, RNAi screening in human aortic smooth muscle cells was performed to explore the effects of OTU family deubiquitinases, which revealed that silencing OTUB1 inhibited PDGF-BB-stimulated VSMC phenotype switch. Further in vivo studies using Apoe^−/− mice revealed that knockdown of OTUB1 in VSMCs alleviated atherosclerosis plaque burden in the advanced stage and led to a stable plaque phenotype. Moreover, VSMC proliferation and migration upon PDGF-BB stimulation could be inhibited by silencing OTUB1 in vitro. Unbiased RNA-sequencing data indicated that knocking down OTUB1 influenced VSMC differentiation, adhesion, and proliferation. Mass spectrometry of ubiquitinated protein confirmed that proteins related to cell growth and migration were differentially ubiquitylated. Mechanistically, we found that OTUB1 recognized the K707 residue ubiquitylation of PDGFRβ with its catalytic triad, thereby reducing the K48-linked ubiquitylation of PDGFRβ. Inhibiting OTUB1 in VSMCs could promote PDGFRβ degradation via the ubiquitin–proteasome pathway, so it was beneficial in preventing VSMCs’ phenotype switch. These findings revealed that knocking down OTUB1 ameliorated VSMCs’ phenotype switch and atherosclerosis progression, indicating that OTUB1 could be a valuable translational therapeutic target in the future.

关键词： atherosclerosis vascular smooth muscle cell ubiquitylation deubiquitinase OTUB1 PDGFRβ

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Crk-associated substrate, vascular smooth muscle and hypertension

TANG Dale

《医学前沿（英文）》 2008年第2卷第4期页码 323-331 doi: 10.1007/s11684-008-0062-6

摘要： Hypertension is characterized by vascular smooth muscle constriction and vascular remodeling involving cell migration, hypertrophy and growth. Crk-associated substrate (CAS), the first discovered member of the adapter protein CAS family, has been shown to be a critical cellular component that regulates various smooth muscle functions. In this review, the molecular structure and protein interactions of the CAS family members are summarized. Evidence for the role of CAS in the regulation of vascular smooth muscle contractility is presented. Contraction stimulation induces CAS phosphorylation on Tyr-410 in arterial smooth muscle, creating the binding site for the Src homology (SH) 2/SH3 protein CrkII, which activates neuronal Wiskott-Aldrich syndrome protein (N-WASP)-mediated actin assembly and force development. The functions of CAS in cell migration, hypertrophy and growth are also summarized. Abelson tyrosine kinase (Abl), c-Src, focal adhesion kinase (FAK), proline-rich tyrosine kinase 2 (PYK2), protein tyrosine phosphatase-proline, glutamate, serine and threonine sequence protein (PTP-PEST) and SHP-2 have been documented to coordinate the phosphorylation and dephosphorylation of CAS. The downstream signaling partners of CAS in the context of cell motility, hypertrophy, survival and growth are also discussed. These new findings establish the important role of CAS in the modulation of vascular smooth muscle functions. Furthermore, the upstream regulators of CAS may be new biologic targets for the development of more effective and specific treatment of cardiovascular diseases such as hypertension.

关键词： Contraction stimulation phosphatase-proline molecular structure discovered hypertension

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the formation of atherosclerotic lesions and induces plaque instability by targeting vascular smooth muscle

null

《医学前沿（英文）》 2016年第10卷第3期页码 320-329 doi: 10.1007/s11684-016-0463-x

摘要：

Coronary atherosclerosis is a major complication of chronic kidney disease. This condition contributes to the increased mortality in dialysis patients. p-Cresyl sulfate (PCS) is a prototype of protein-bound uremic toxins that cannot be efficiently removed through routine dialysis procedures. In the present study, ApoE^−/− mice that underwent 5/6 nephrectomy were randomly divided into two groups, namely, vehicle-treated group (n = 20) and PCS-treated group (n = 20). Mice were sacrificed for en face and immunohistological analyses after 8 or 24 weeks of high-fat diet. Rat aortic vascular smooth muscle cells (VSMCs) were treated with phosphate buffer solution or 500 µmol/L PCS for in vitro evaluation. PCS-treated mice were observed to suffer increased atherosclerotic lesions after eight weeks of PCS administration. Moreover, 24 weeks of PCS administration also markedly increased the vulnerability index of aortic plaques. PCS was also observed to facilitate the migration and proliferation of VSMCs during the progression of the disease. Moreover, PCS disturbed the balance between matrix metalloproteinases and tissue inhibitor of metalloproteinases within the plaques. Thus, PCS played a vital role in promoting atherogenesis and disturbing the stability of formed plaques probably by targeting VSMCs.

关键词： p-cresyl sulfate atherosclerosis plaque stability vascular smooth muscle cell

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Molecular dynamic simulation on the conformation of mouse muscle type nAChR

Shengai SUN, Rilei YU, Yanhui ZHANG, Yanni LI,

《化学科学与工程前沿（英文）》 2010年第4卷第3期页码 348-352 doi: 10.1007/s11705-009-0284-4

摘要： A mouse muscle type nAChR model ((α1)βδγ) was built based on the cryoelectron microscopic structure of intact nAChR and the high resolution crystal structure of nAChR-α1 subunit. The conformation of the pentameric nAChR model was investigated by molecular dynamic simulation. The function of water molecule in the hydrophilic interior was clarified. The reason for Tyr127 showing two alternative conformations was discussed in detail.

关键词： pentameric hydrophilic Tyr127 cryoelectron microscopic conformation