Skeletal and cardiac muscles are striated myofibers that contain highly organized sarcomeres for muscle contraction.Recent studies revealed that Smyd1,a lysine methyltransferase,plays a key role in sarcomere assembly ...Skeletal and cardiac muscles are striated myofibers that contain highly organized sarcomeres for muscle contraction.Recent studies revealed that Smyd1,a lysine methyltransferase,plays a key role in sarcomere assembly in heart and trunk skeletal muscles.However,Smyd1 expression and function in craniofacial muscles are not known.Here,we analyze the developmental expression and function of two smyd1 paralogous genes,smyd1 a and smyd1 b,in craniofacial and cardiac muscles of zebrafish embryos.Our data show that loss of smyd1a(smyd1a^(mb5))or smyd1b(smyd1b^(sa15678))has no visible effects on myogenic commitment and expression of myod and myosin heavy-chain m RNA transcripts in craniofacial muscles.However,myosin heavy-chain protein accumulation and sarcomere organization are dramatically reduced in smyd1b^(sa15678) single mutant,and almost completely diminish in smyd1a^(mb5);smyd1b^(sa15678) double mutant,but not in smyd1a^(mb5) mutant.Similar defects are also observed in cardiac muscles of smyd1b^(sa15678) mutant.Defective craniofacial and cardiac muscle formation is associated with an upregulation of hsp90α1 and unc45b mRNA expression in smyd1b^(sa15678) and smyd1a^(mb5);smyd1b^(sa15678) mutants.Together,our studies indicate that Smyd1b,but not Smyd1a,plays a key role in myosin heavy-chain protein expression and sarcomere organization in craniofacial and cardiac muscles.Loss of smyd1b results in muscle-specific stress response.展开更多
Problem Statement: Malaria’s global impact necessitates effective treatments, like dihydroartemisinin-piperaquine (DHA/PQP), though safety concerns, notably drug-induced cardiotoxicity (DICT), persist. A knowledge ga...Problem Statement: Malaria’s global impact necessitates effective treatments, like dihydroartemisinin-piperaquine (DHA/PQP), though safety concerns, notably drug-induced cardiotoxicity (DICT), persist. A knowledge gap exists regarding DHA/PQP’s cardiac effects, warranting a comprehensive investigation. Approach: This study aimed to assess KROSH (DHA/PQP) impact on albino rat heart histology, examining structural changes and potential cardiotoxicity. 40 albino rats were grouped by KROSH dosage and duration, monitored for weight changes, and heart tissues were examined using hematoxylin and eosin (H & E) staining. Statistical analysis compared to control and treated groups. Results: KROSH administration led to varying rat weight effects, yet not statistically significant. Histological analysis revealed dose and duration-dependent cardiac tissue alterations, including distortion, adipose deposits, artery hypertrophy, fibrosis, and necrosis. These contrasts with prior research documenting DHA/PQP’s non-toxic effects. Conclusion/Recommendation: This study highlights potential KROSH (DHA/PQP) cardiotoxicity concerns through histological changes, underscoring the need for further research into underlying mechanisms and human health implications. Given DHA/PQP’s wide use, these findings should inform safety evaluations and administration practices.展开更多
Cardiogenic shock(CS)is a common cause of mortality and treatment remains challenging despite advances in therapeutic options.CS is caused by severe impairment of myocardial performance that results in decreased cardi...Cardiogenic shock(CS)is a common cause of mortality and treatment remains challenging despite advances in therapeutic options.CS is caused by severe impairment of myocardial performance that results in decreased cardiac output,hypoperfusion of the end organ,and hypoxia.Clinically this presents as hypotension refractory to volume resuscitation with features of end-organ hypoperfusion requiring pharmacological or mechanical intervention.Acute myocardial infarction(AMI)accounts for 81%of patients with CS.Heat shock protein family B member 1(HSPB1)is a multifunctional protein induced by various stress factors and has a protective effect on cells.A large number of studies have demonstrated that HSPB1 plays an important role in regulating apoptosis.Recently,some studies have suggested that HSPB1 also participates in the autophagic process.HSPB1 are expressed in many cells of the cardiovascular system such as endothelial cells,cardiac muscle cells,monocytes,and platelets.They are up-regulated in response to inflammation,oxidative stress,or ischemia and protect cells against extracellular stress factors.Here,we explore the involvement of HSPB1 in apoptosis,autophagy,and CS.We speculate that HSPB1 may exert its anti-myocardial injury role via the regulation of apoptosis and autophagy;this may provide the basis for the development of new approaches for the prevention and treatment of CS.展开更多
基金supported by funding from the U.S.National Institute of Health(NIH)National Institute of Arthritis and Musculoskeletal and Skin Diseases(R01AR072703 to S.Du)supported in part by fellowships from the China Scholarship Council。
文摘Skeletal and cardiac muscles are striated myofibers that contain highly organized sarcomeres for muscle contraction.Recent studies revealed that Smyd1,a lysine methyltransferase,plays a key role in sarcomere assembly in heart and trunk skeletal muscles.However,Smyd1 expression and function in craniofacial muscles are not known.Here,we analyze the developmental expression and function of two smyd1 paralogous genes,smyd1 a and smyd1 b,in craniofacial and cardiac muscles of zebrafish embryos.Our data show that loss of smyd1a(smyd1a^(mb5))or smyd1b(smyd1b^(sa15678))has no visible effects on myogenic commitment and expression of myod and myosin heavy-chain m RNA transcripts in craniofacial muscles.However,myosin heavy-chain protein accumulation and sarcomere organization are dramatically reduced in smyd1b^(sa15678) single mutant,and almost completely diminish in smyd1a^(mb5);smyd1b^(sa15678) double mutant,but not in smyd1a^(mb5) mutant.Similar defects are also observed in cardiac muscles of smyd1b^(sa15678) mutant.Defective craniofacial and cardiac muscle formation is associated with an upregulation of hsp90α1 and unc45b mRNA expression in smyd1b^(sa15678) and smyd1a^(mb5);smyd1b^(sa15678) mutants.Together,our studies indicate that Smyd1b,but not Smyd1a,plays a key role in myosin heavy-chain protein expression and sarcomere organization in craniofacial and cardiac muscles.Loss of smyd1b results in muscle-specific stress response.
文摘Problem Statement: Malaria’s global impact necessitates effective treatments, like dihydroartemisinin-piperaquine (DHA/PQP), though safety concerns, notably drug-induced cardiotoxicity (DICT), persist. A knowledge gap exists regarding DHA/PQP’s cardiac effects, warranting a comprehensive investigation. Approach: This study aimed to assess KROSH (DHA/PQP) impact on albino rat heart histology, examining structural changes and potential cardiotoxicity. 40 albino rats were grouped by KROSH dosage and duration, monitored for weight changes, and heart tissues were examined using hematoxylin and eosin (H & E) staining. Statistical analysis compared to control and treated groups. Results: KROSH administration led to varying rat weight effects, yet not statistically significant. Histological analysis revealed dose and duration-dependent cardiac tissue alterations, including distortion, adipose deposits, artery hypertrophy, fibrosis, and necrosis. These contrasts with prior research documenting DHA/PQP’s non-toxic effects. Conclusion/Recommendation: This study highlights potential KROSH (DHA/PQP) cardiotoxicity concerns through histological changes, underscoring the need for further research into underlying mechanisms and human health implications. Given DHA/PQP’s wide use, these findings should inform safety evaluations and administration practices.
文摘Cardiogenic shock(CS)is a common cause of mortality and treatment remains challenging despite advances in therapeutic options.CS is caused by severe impairment of myocardial performance that results in decreased cardiac output,hypoperfusion of the end organ,and hypoxia.Clinically this presents as hypotension refractory to volume resuscitation with features of end-organ hypoperfusion requiring pharmacological or mechanical intervention.Acute myocardial infarction(AMI)accounts for 81%of patients with CS.Heat shock protein family B member 1(HSPB1)is a multifunctional protein induced by various stress factors and has a protective effect on cells.A large number of studies have demonstrated that HSPB1 plays an important role in regulating apoptosis.Recently,some studies have suggested that HSPB1 also participates in the autophagic process.HSPB1 are expressed in many cells of the cardiovascular system such as endothelial cells,cardiac muscle cells,monocytes,and platelets.They are up-regulated in response to inflammation,oxidative stress,or ischemia and protect cells against extracellular stress factors.Here,we explore the involvement of HSPB1 in apoptosis,autophagy,and CS.We speculate that HSPB1 may exert its anti-myocardial injury role via the regulation of apoptosis and autophagy;this may provide the basis for the development of new approaches for the prevention and treatment of CS.
