Objective: To reveal the special feature of calponin (CaP) on myosins of different states. Methods: Myosin phosphorylation determination, myosin Mg^(2+)-ATPase measurement and protein binding assay were used in this s...Objective: To reveal the special feature of calponin (CaP) on myosins of different states. Methods: Myosin phosphorylation determination, myosin Mg^(2+)-ATPase measurement and protein binding assay were used in this study. The lowest CaP/myosin ratio used in the assay was 1/10000(mol/mol), which was 10 thousands-fold lower than the CaP/myosin ratio used in previous studies. Results: In the absence of actin, micro-amount of calponin (MAC) stimulated the Mg^(2+)-ATPase activities of myosin in different states slightly but significantly; and more importantly, MAC significantly increased the precipitations of unphosphorylated myosin, Ca^(2+)-dependently and independently phosphorylated myosins by MLCK but not the myosin phosphorylated by PKA. Conclusion: MAC has a high efficient and selective effect on myosin in the absence of actin.展开更多
Plant organelles are highly motile, with speed values of 3-71μm/s in cells of land plants and about 20-60 μm/s in characean algal cells. This movement is believed to be important for rapid distribution of materials ...Plant organelles are highly motile, with speed values of 3-71μm/s in cells of land plants and about 20-60 μm/s in characean algal cells. This movement is believed to be important for rapid distribution of materials around the cell, for the plant＇s ability to respond to environmental biotic and abiotic signals and for proper growth. The main machinery that propels motility of organelles within plant cells is based on the actin cytoskeleton and its motor proteins the myosins.Most plants express multiple members of two main classes： myosin VIII and myosin XI. While myosin VIII has been characterized as a slow motor protein, myosins from class XI were found to be the fastest motor proteins known in all kingdoms. Paradoxically, while it was found that myosins from class XI regulate most organelle movement, it is not quite clear how or even if these motor proteins attach to the organelles whose movement they regulate.展开更多
Hypertrophic cardiomyopathy(HCM)is a major contributor to cardiovascular diseases(CVD),the leading cause of death globally.HCM can precipitate heart failure(HF)by causing the cardiac tissue to weaken and stretch,there...Hypertrophic cardiomyopathy(HCM)is a major contributor to cardiovascular diseases(CVD),the leading cause of death globally.HCM can precipitate heart failure(HF)by causing the cardiac tissue to weaken and stretch,thereby impairing its pumping efficiency.Moreover,HCM increases the risk of atrial fibrillation,which in turn elevates the likelihood of thrombus formation and stroke.Given these significant clinical ramifications,research into the etiology and pathogenesis of HCM is intensifying at multiple levels.In this review,we discuss and synthesize the latest findings on HCM pathogenesis,drawing on key experimental studies conducted both in vitro and in vivo.We also offer our insights and perspectives on these mechanisms,while highlighting the limitations of current research.Advancing fundamental research in this area is essential for developing effective therapeutic interventions and enhancing the clinical management of HCM.展开更多
Background : Cancer-associated cardiac cachexia(CACC) refers to cardiac injury in cancer patients in a malignant state, but preclinical animal models remain inadequately developed. Methods : This study established CAC...Background : Cancer-associated cardiac cachexia(CACC) refers to cardiac injury in cancer patients in a malignant state, but preclinical animal models remain inadequately developed. Methods : This study established CACC models in C57BL/6J and BALB/c mice using orthotopic, intra-abdominal, and hematogenous metastatic tumor induction. Multimodal cardiac assessments, including echocardiography, transmission electron microscopy for myocardial ultrastructural and mitochondrial analysis, and ex vivo cardiomyocyte contractility assays, were systematically applied. Results : Metastatic burden triggered CACC characterized by cardiac mass reduction, epicardial fat depletion, interstitial fibrosis, and electrocardiographic abnormalities. Histopathological analysis revealed cardiomyocyte atrophy, myofibrillar disarray, mitochondrial dysfunction, and ubiquitin-mediated Myh6 degradation via Mu RF-1, accompanied by compensatory Myh7 upregulation. These findings mechanistically link tumor-induced cachexia to cardiac dysfunction through contractile protein remodeling. Conclusion : This work establishes a preclinical framework for targeting ubiquitin pathways to mitigate the morbidity of cancer-related cardiopathy. Our integrated approach delineates a hierarchical progression from subcellular dysfunction to macroscopic cardiac deterioration.展开更多
Myosin heavy chain 9(MYH9),a non-muscle myosin heavy chain protein,has been identified as a significant factor in gastrointestinal(GI)oncology,with its overexpression in various GI malignancies such as esophageal,gast...Myosin heavy chain 9(MYH9),a non-muscle myosin heavy chain protein,has been identified as a significant factor in gastrointestinal(GI)oncology,with its overexpression in various GI malignancies such as esophageal,gastric,and co-lorectal cancers being associated with poor prognosis and playing a role in tumor invasion and metastasis.This comprehensive review synthesizes the current body of knowledge regarding MYH9’s role in GI tumors,focusing on its molecular mechanisms,including its interaction with key signaling pathways like the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin axis,which suggests a role in cancer cell survival,proliferation,and epithelial-mesenchymal transition.The review also explores MYH9’s potential as a therapeutic target,with preclinical models demonstrating promising results in inhibiting tumor growth and enhancing chemosensitivity.The evidence suggests that MYH9 is a multifaceted protein with significant implications in GI tumor biology,warranting further research to elucidate its mechanisms of action and develop targeted therapies that could improve patient outcomes.展开更多
Background:Colorectal cancer(CRC)is common and deadly,often leading to metastasis,challenging treatment,and poor outcomes.Understanding its molecular basis is crucial for developing effective therapies.Aims:This study...Background:Colorectal cancer(CRC)is common and deadly,often leading to metastasis,challenging treatment,and poor outcomes.Understanding its molecular basis is crucial for developing effective therapies.Aims:This study aimed to investigate the role of Myosin Heavy Chain 11(MYH11)in CRC progression,especially its effects on epithelial-mesenchymal transition(EMT)and cell behavior,and to explore its potential regulation by the EMT transcription factor zinc finger E-box binding homeobox 1(ZEB1).Methods:Differential expression analysis was performed in the GSE123390 and TCGA-READ datasets,and 317 intersection genes were identified.The hub gene MYH11 was identified based on Protein-protein interaction(PPI)analysis and expression validation.The effects of MYH11 and the EMT transcription factor(ZEB1)on the behavior of CRC cells were investigated in vitro.Results:Bioinformatics research revealed that MYH11 was considerably downregulated in CRC samples as compared to normal samples.Overexpression of MYH11 inhibited the proliferation,migration,and invasion of CRC cells.Western blotting(WB)testing showed that MYH11 overexpression inhibited EMT by elevating E-cadherin levels while suppressing ZEB1,vimentin,and N-cadherin expressions.By contrast,overexpression of ZEB1 promoted EMT and enhanced migration,invasion,and proliferation of CRC cells.The negative impacts of MYH11 affecting EMT markers and cell behaviors were partially mitigated by co-overexpression of MYH11 and ZEB1,indicating that MYH11 regulates EMT and CRC progression through ZEB1.Conclusion:Our study shows MYH11 curbs CRC growth by blocking EMT and invasion,but ZEB1 overexpression reduces this effect.It uncovers key CRC pathways and suggests MYH11’s therapeutic potential.展开更多
背景:将中医中药与干细胞移植学科相结合,开辟了传统中药学在干细胞移植学科应用方面的新道路,希望可以采用中药干预的方法来提高耳蜗干细胞的存活比率和分化为毛细胞的比例。目的:观察归芪地黄汤干预对耳蜗干细胞治疗感音性耳聋的影响...背景:将中医中药与干细胞移植学科相结合,开辟了传统中药学在干细胞移植学科应用方面的新道路,希望可以采用中药干预的方法来提高耳蜗干细胞的存活比率和分化为毛细胞的比例。目的:观察归芪地黄汤干预对耳蜗干细胞治疗感音性耳聋的影响。方法:将感音性耳聋豚鼠分成耳蜗干细胞移植+中药干预组,干细胞移植组和空白对照组,分别向内耳耳蜗移植含有药物血清的耳蜗干细胞悬液,耳蜗干细胞悬液和生理盐水。于移植后7,28,56 d 3个时间点进行ABR检测和免疫荧光观测实验。结果与结论:(1)在耳蜗干细胞移植+中药干预组和干细胞移植组观测到Nestin阳性细胞和MyosinⅦA阳性细胞,耳蜗干细胞移植+中药干预组的Nestin阳性细胞和MyosinⅦA阳性细胞数量要多于干细胞移植组;(2)耳蜗干细胞移植+中药干预组和干细胞移植组ABR检测数值都下调,耳蜗干细胞移植+中药干预组豚鼠的听力恢复优于干细胞移植组;(3)结果表明,归芪地黄汤干预可以显著提高耳蜗干细胞的存活率和分化为毛细胞的比例。展开更多
The aims of the present study are to investigate the effect of vasoconstriction and to explore the mechanism of rutae- carpine. The research findings showed that rutaecarpine could induce contractions of the rat thora...The aims of the present study are to investigate the effect of vasoconstriction and to explore the mechanism of rutae- carpine. The research findings showed that rutaecarpine could induce contractions of the rat thoracic aorta in vitro. The inhibitors of Rho-kinase and inositol 1,4,5-triphosphate receptor （IP 3 R） could suppress the effect of rutaecarpine-induced vasoconstriction. In the study of A7r5 cells （a line of smooth muscle cells）, 300 μg/L rutaecarpine promoted the concentration of intracellular Ca 2＋ and enhanced the IP 3 R expression, which connects with 1,4,5-triphosphate to evoke the release of Ca 2＋ from the intracellular stores. Rutaecarpine increased the RhoA mRNA expression when the cells were pretreated with inhibitor H-1152, and improved the levels of phosphorylation of myosin light chain phosphatase （MLCP） and myosin light chain （MLC）. These results suggest that rutaecarpine plays a role in vasoconstriction relative to the RhoA/MLCP-MLC signaling pathway, which denotes a new field of rutaecarpine in pharmacology.展开更多
The molecular structure of a higher plant myosin with two 174 kD heavy chains purified from the tendrils of Luffa cylindrica (L.) Roem. was viewed by electron microscopy. The myosin exhibited actin_activated MgATP...The molecular structure of a higher plant myosin with two 174 kD heavy chains purified from the tendrils of Luffa cylindrica (L.) Roem. was viewed by electron microscopy. The myosin exhibited actin_activated MgATPase activity and could be recognized immunologically by a monoclonal antibody against the skeletal muscle myosin. Electron micrographs of rotary shadowed images of this protein revealed that it had two heads with size and shape similar to those of the skeletal muscle myosin and a relatively short tail in comparison with the conventional myosin. Luffa tendril actin filaments were also visualized and occasionally other Luffa myosin_like proteins with globular structure at the tail ends were also observed. The structural similarity and immunological cross reactivity with antibodies against muscle myosin demonstrate that the 174 kD Luffa tendril myosin is a double_headed myosin. The possible involvement of myosin_actin interactions in Luffa tendril contact coiling will be the subject of further research.展开更多
文摘Objective: To reveal the special feature of calponin (CaP) on myosins of different states. Methods: Myosin phosphorylation determination, myosin Mg^(2+)-ATPase measurement and protein binding assay were used in this study. The lowest CaP/myosin ratio used in the assay was 1/10000(mol/mol), which was 10 thousands-fold lower than the CaP/myosin ratio used in previous studies. Results: In the absence of actin, micro-amount of calponin (MAC) stimulated the Mg^(2+)-ATPase activities of myosin in different states slightly but significantly; and more importantly, MAC significantly increased the precipitations of unphosphorylated myosin, Ca^(2+)-dependently and independently phosphorylated myosins by MLCK but not the myosin phosphorylated by PKA. Conclusion: MAC has a high efficient and selective effect on myosin in the absence of actin.
基金a grant from the Israeli Science Foundation (ISF) 401/09
文摘Plant organelles are highly motile, with speed values of 3-71μm/s in cells of land plants and about 20-60 μm/s in characean algal cells. This movement is believed to be important for rapid distribution of materials around the cell, for the plant＇s ability to respond to environmental biotic and abiotic signals and for proper growth. The main machinery that propels motility of organelles within plant cells is based on the actin cytoskeleton and its motor proteins the myosins.Most plants express multiple members of two main classes： myosin VIII and myosin XI. While myosin VIII has been characterized as a slow motor protein, myosins from class XI were found to be the fastest motor proteins known in all kingdoms. Paradoxically, while it was found that myosins from class XI regulate most organelle movement, it is not quite clear how or even if these motor proteins attach to the organelles whose movement they regulate.
基金supported by Henan Provincial Key Technologies R&D Program(Grant No.25202310242)Henan Provincial Medical Science and Technology Tackling Program(Grant No.LHGJ20240150).
文摘Hypertrophic cardiomyopathy(HCM)is a major contributor to cardiovascular diseases(CVD),the leading cause of death globally.HCM can precipitate heart failure(HF)by causing the cardiac tissue to weaken and stretch,thereby impairing its pumping efficiency.Moreover,HCM increases the risk of atrial fibrillation,which in turn elevates the likelihood of thrombus formation and stroke.Given these significant clinical ramifications,research into the etiology and pathogenesis of HCM is intensifying at multiple levels.In this review,we discuss and synthesize the latest findings on HCM pathogenesis,drawing on key experimental studies conducted both in vitro and in vivo.We also offer our insights and perspectives on these mechanisms,while highlighting the limitations of current research.Advancing fundamental research in this area is essential for developing effective therapeutic interventions and enhancing the clinical management of HCM.
基金National Natural Science Foundation of China,Grant/Award Number:81970219, 82170261, 82200289 and 82370283National Key Research and Development Program of China,Grant/Award Number:2023YFF0724900。
文摘Background : Cancer-associated cardiac cachexia(CACC) refers to cardiac injury in cancer patients in a malignant state, but preclinical animal models remain inadequately developed. Methods : This study established CACC models in C57BL/6J and BALB/c mice using orthotopic, intra-abdominal, and hematogenous metastatic tumor induction. Multimodal cardiac assessments, including echocardiography, transmission electron microscopy for myocardial ultrastructural and mitochondrial analysis, and ex vivo cardiomyocyte contractility assays, were systematically applied. Results : Metastatic burden triggered CACC characterized by cardiac mass reduction, epicardial fat depletion, interstitial fibrosis, and electrocardiographic abnormalities. Histopathological analysis revealed cardiomyocyte atrophy, myofibrillar disarray, mitochondrial dysfunction, and ubiquitin-mediated Myh6 degradation via Mu RF-1, accompanied by compensatory Myh7 upregulation. These findings mechanistically link tumor-induced cachexia to cardiac dysfunction through contractile protein remodeling. Conclusion : This work establishes a preclinical framework for targeting ubiquitin pathways to mitigate the morbidity of cancer-related cardiopathy. Our integrated approach delineates a hierarchical progression from subcellular dysfunction to macroscopic cardiac deterioration.
文摘Myosin heavy chain 9(MYH9),a non-muscle myosin heavy chain protein,has been identified as a significant factor in gastrointestinal(GI)oncology,with its overexpression in various GI malignancies such as esophageal,gastric,and co-lorectal cancers being associated with poor prognosis and playing a role in tumor invasion and metastasis.This comprehensive review synthesizes the current body of knowledge regarding MYH9’s role in GI tumors,focusing on its molecular mechanisms,including its interaction with key signaling pathways like the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin axis,which suggests a role in cancer cell survival,proliferation,and epithelial-mesenchymal transition.The review also explores MYH9’s potential as a therapeutic target,with preclinical models demonstrating promising results in inhibiting tumor growth and enhancing chemosensitivity.The evidence suggests that MYH9 is a multifaceted protein with significant implications in GI tumor biology,warranting further research to elucidate its mechanisms of action and develop targeted therapies that could improve patient outcomes.
基金funded by Outstanding Leaders Training Programof Pudong Health Commission of Shanghai(No.PWR12023-03)In-house Project of Shanghai Pudong NewArea People’sHospital(No.E24-02).
文摘Background:Colorectal cancer(CRC)is common and deadly,often leading to metastasis,challenging treatment,and poor outcomes.Understanding its molecular basis is crucial for developing effective therapies.Aims:This study aimed to investigate the role of Myosin Heavy Chain 11(MYH11)in CRC progression,especially its effects on epithelial-mesenchymal transition(EMT)and cell behavior,and to explore its potential regulation by the EMT transcription factor zinc finger E-box binding homeobox 1(ZEB1).Methods:Differential expression analysis was performed in the GSE123390 and TCGA-READ datasets,and 317 intersection genes were identified.The hub gene MYH11 was identified based on Protein-protein interaction(PPI)analysis and expression validation.The effects of MYH11 and the EMT transcription factor(ZEB1)on the behavior of CRC cells were investigated in vitro.Results:Bioinformatics research revealed that MYH11 was considerably downregulated in CRC samples as compared to normal samples.Overexpression of MYH11 inhibited the proliferation,migration,and invasion of CRC cells.Western blotting(WB)testing showed that MYH11 overexpression inhibited EMT by elevating E-cadherin levels while suppressing ZEB1,vimentin,and N-cadherin expressions.By contrast,overexpression of ZEB1 promoted EMT and enhanced migration,invasion,and proliferation of CRC cells.The negative impacts of MYH11 affecting EMT markers and cell behaviors were partially mitigated by co-overexpression of MYH11 and ZEB1,indicating that MYH11 regulates EMT and CRC progression through ZEB1.Conclusion:Our study shows MYH11 curbs CRC growth by blocking EMT and invasion,but ZEB1 overexpression reduces this effect.It uncovers key CRC pathways and suggests MYH11’s therapeutic potential.
文摘背景:将中医中药与干细胞移植学科相结合,开辟了传统中药学在干细胞移植学科应用方面的新道路,希望可以采用中药干预的方法来提高耳蜗干细胞的存活比率和分化为毛细胞的比例。目的:观察归芪地黄汤干预对耳蜗干细胞治疗感音性耳聋的影响。方法:将感音性耳聋豚鼠分成耳蜗干细胞移植+中药干预组,干细胞移植组和空白对照组,分别向内耳耳蜗移植含有药物血清的耳蜗干细胞悬液,耳蜗干细胞悬液和生理盐水。于移植后7,28,56 d 3个时间点进行ABR检测和免疫荧光观测实验。结果与结论:(1)在耳蜗干细胞移植+中药干预组和干细胞移植组观测到Nestin阳性细胞和MyosinⅦA阳性细胞,耳蜗干细胞移植+中药干预组的Nestin阳性细胞和MyosinⅦA阳性细胞数量要多于干细胞移植组;(2)耳蜗干细胞移植+中药干预组和干细胞移植组ABR检测数值都下调,耳蜗干细胞移植+中药干预组豚鼠的听力恢复优于干细胞移植组;(3)结果表明,归芪地黄汤干预可以显著提高耳蜗干细胞的存活率和分化为毛细胞的比例。
基金National Natural Science Foundation of China (Grant No.30801523,30973896,and 81073092)the Projects of Science Research for the 11th Five-Year Plan of the Ministry of Science and Technology of China (Grant No.2006BAI08B03-09)+1 种基金the China's Post-Doctoral Science Fund (Grant No.20080440418)the National S&T Major Special Project for New Drug R&D of China (Grant No.2012ZX09102-201-008,2012ZX09103-201-041and2011ZX09101-002-11)
文摘The aims of the present study are to investigate the effect of vasoconstriction and to explore the mechanism of rutae- carpine. The research findings showed that rutaecarpine could induce contractions of the rat thoracic aorta in vitro. The inhibitors of Rho-kinase and inositol 1,4,5-triphosphate receptor （IP 3 R） could suppress the effect of rutaecarpine-induced vasoconstriction. In the study of A7r5 cells （a line of smooth muscle cells）, 300 μg/L rutaecarpine promoted the concentration of intracellular Ca 2＋ and enhanced the IP 3 R expression, which connects with 1,4,5-triphosphate to evoke the release of Ca 2＋ from the intracellular stores. Rutaecarpine increased the RhoA mRNA expression when the cells were pretreated with inhibitor H-1152, and improved the levels of phosphorylation of myosin light chain phosphatase （MLCP） and myosin light chain （MLC）. These results suggest that rutaecarpine plays a role in vasoconstriction relative to the RhoA/MLCP-MLC signaling pathway, which denotes a new field of rutaecarpine in pharmacology.
文摘The molecular structure of a higher plant myosin with two 174 kD heavy chains purified from the tendrils of Luffa cylindrica (L.) Roem. was viewed by electron microscopy. The myosin exhibited actin_activated MgATPase activity and could be recognized immunologically by a monoclonal antibody against the skeletal muscle myosin. Electron micrographs of rotary shadowed images of this protein revealed that it had two heads with size and shape similar to those of the skeletal muscle myosin and a relatively short tail in comparison with the conventional myosin. Luffa tendril actin filaments were also visualized and occasionally other Luffa myosin_like proteins with globular structure at the tail ends were also observed. The structural similarity and immunological cross reactivity with antibodies against muscle myosin demonstrate that the 174 kD Luffa tendril myosin is a double_headed myosin. The possible involvement of myosin_actin interactions in Luffa tendril contact coiling will be the subject of further research.
