YBX1 inhibits mitochondrial-mediated apoptosis in ischemic heart through the PI3K/AKT signaling pathway

Background:Myocardial infarction(MI)is associated with higher morbidity and mortality in the world,especially in cold weather.YBX1 is an RNA-binding protein that is required for pathological growth of cardiomyocyte by regulating cell growth and protein synthesis.But YBX1,as an individual RNA-binding protein,regulates cardiomyocytes through signaling cascades during myocardial infarction remain largely unexplored.Methods:In vivo,the mouse MI model was induced by ligating the left anterior descending coronary artery(LAD),and randomly divided into sham operation group,MI group,MI+YBX1 knockdown/overexpression group and MI+negative control(NC)group.The protective effect of YBX1 was verified by echocardiography and triphenyltetrazolium chloride staining.In vitro,mitochondrial-dependent apoptosis was investigated by using CCK8,TUNEL staining,reactive oxygen species(ROS)staining and JC-1 staining in hypoxic neonatal mouse cardiomyocytes(NMCMs).Results:YBX1 expression of cardiomyocytes was downregulated in a mouse model and a cellular model on the ischemic condition.Compared to mice induced by MI,YBX1 overexpression mediated by adeno-associated virus serotype 9(AAV9)vector reduced the infarcted size and improved cardiac function.Knockdown of endogenous YBX1 by shRNA partially aggravated ischemia-induced cardiac dysfunction.In hypoxic cardiomyocytes,YBX1 overexpression decreased lactic dehydrogenase(LDH)release,increased cell viability,and inhibited apoptosis by affecting the expression of apoptosis related proteins,while knockdown of endogenous YBX1 by siRNA had the opposite effect.Overexpression of YBX1 restored mitochondrial dysfunction in hypoxic NMCMs by increasing mitochondrial membrane potential and ATP content and decreasing ROS.In hypoxic NMCMs,YBX1 overexpression increased the expression of phosphorylated phosphatidylinositol 3 kinase(PI3K)/AKT,and the anti-apoptosis effect of YBX1 was eliminated t by LY294002,PI3K/AKT inhibitor.Conclusion:YBX1 protected the heart from ischemic damage by inhibiting the mitochondrial-dependent apoptosis through PI3K/AKT pathway.It is anticipated that YBX1 may serve as a novel therapeutic target for MI.

Notum protects against myocardial infarction-induced heart dysfunction by alleviating cardiac fibrosis

Background and Objective:Cardiac fibrosis is a pathological reparative process that follows myocardial infarctionand is associated with compromised cardiac systolic and reduced cardiac compliance.The Wnt signaling pathway is closely implicated in organ fibrosis,and Notum,a highly conserved secreted inhibitor,modulates Wnt signaling.The objective of this study was to explore the role and mechanism of Notum in cardiac fibrosis.Methods:A mouse model of cardiac remodeling was established through left coronary artery ligation surgery,with the addition of Notum injection following myocardial infarction surgery.The protective effect of Notum on myocardial infarction was assessed by evaluating cardiac function,including survival rate,echocardiographic assessment,and cardiac contraction analyses.Inflammatory cell necrosis and infiltration were confirmed through H&E and Masson staining.The expression of fibrosis-related genes andβ-catenin pathway markers was detected using Western blot quantificational RT-PCR(qRT-PCR).Additionally,EdU,wound healing,and immunofluorescence staining analyses were performed to detect the effect of Notum's in transforming growth factor beta-1(TGF-β1)induced myofibroblast transformation.Results:The administration of Notum treatment resulted in enhanced survival rates,improved cardiac function,and decreased necrosis and infiltration of inflammatory cells in mice subjected to left coronary artery ligation.Furthermore,Notum effectively impeded the senescence of cardiac fibroblasts and hindered their pathological transformation into cardiac fibroblasts.Additionally,it significantly reduced collagen production and attenuated the activation of the Wnt/β-catenin pathway.Our preliminary investigations successfully demonstrated the therapeutic potential of Notum in both fibroblasts in vitro and in a mouse model of myocardial infarction-induced cardiac fibrosis in vivo.Conclusion:Notum inhibition of the Wnt/β-catenin signaling pathway and cardiac fibroblast senescence ultimately hampers the onset of cardiac fibrosis.Our findings suggest that Notum could represent a new therapeutic strategy for the treatment of cardiac fibrosis.

Development status of novel spectral imaging techniques and application to traditional Chinese medicine

Traditional Chinese medicine(TCM)is a treasure of the Chinese nation,providing effective solutions to current medical requisites.Various spectral techniques are undergoing continuous development and provide new and reliable means for evaluating the efficacy and quality of TCM.Because spectral techniques are noninvasive,convenient,and sensitive,they have been widely applied to in vitro and in vivo TCM evaluation systems.In this paper,previous achievements and current progress in the research on spectral technologies(including fluorescence spectroscopy,photoacoustic imaging,infrared thermal imaging,laser-induced breakdown spectroscopy,hyperspectral imaging,and surface enhanced Raman spectroscopy)are discussed.The advantages and disadvantages of each technology are also presented.Moreover,the future applications of spectral imaging to identify the origins,components,and pesticide residues of TCM in vitro are elucidated.Subsequently,the evaluation of the efficacy of TCM in vivo is presented.Identifying future applications of spectral imaging is anticipated to promote medical research as well as scientific and technological explorations.

CPAL, as a New Mediator of Cardiomyocyte Metabolic Alterations and Pyroptosis, Regulates Myocardial Infarction Injury in Mice

Myocardial infarction (MI), the most serious of the ischemic heart diseases, is accompanied by myocardial metabolic disorders and the loss of cardiomyocytes. Increasing evidence has shown that long noncoding RNAs (lncRNAs) are involved in various pathological conditions such as cancer and cardiovascular diseases (CVDs), and are emerging as a novel biomarker for these disorders. This study aims to investigate the regulatory role and mechanisms of lncRNAs in myocardial remodeling in the setting of MI. We find that post-infarcted hearts exhibit a reduction of adenosine triphosphate (ATP) and an alteration of the glucose and lipid metabolism genes cluster of differentiation 36 (CD36), hexokinase 1 (HK1), and clucose transporter 4 (GLUT4), accompanied by cardiomyocyte pyroptosis. We then identify a previously unknown conserved lncRNA, AK009126 (cardiomyocyte pyroptosis-associated lncRNA, CPAL), which is remarkably upregulated in the myocardial border zone of MI mice. Importantly, the adeno-associated virus 9 (AAV9)-mediated silencing of endogenous CPAL by its short hairpin RNA (shRNA) partially abrogates myocardial metabolic alterations and cardiomyocyte pyroptosis during MI in mice. Mechanistically, CPAL is shown to bind directly to nuclear factor kappa B (NFκB) and to act as an activator of NFκB to induce NFκB phosphorylation in cardiomyocytes. We also find that CPAL upregulates caspase-1 expression at the transcriptional level and consequently promotes the release of interleukin (IL)-18 and IL-1β from cardiomyocytes. Collectively, our findings reveal the conserved lncRNA CPAL as a new regulator of cardiac metabolic abnormalities and cardiomyocyte pyroptosis in the setting of MI and suggest CPAL as a new therapeutic target to protect cardiomyocytes against ischemic injury in infarcted hearts.

LncRNA ZFAS1 regulates cardiomyocyte differentiation of human embryonic stem cells

Background:Cardiomyocytes derived from human embryonic stem cells(hESCs)are regulated by complex and stringent gene networks during differentiation.Long non-coding RNAs(lncRNAs)exert critical epigenetic regulatory functions in multiple differentiation processes.However,the involvement of lncRNAs in the differentiation of hESCs into cardiomyocytes has not yet been fully elucidated.Here,we identified the key roles of ZFAS1(lncRNA zinc finger antisense 1)in the differentiation of cardiomyocytes from hESCs.Methods:A model of cardiomyocyte differentiation from stem cells was established using the monolayer differentiation method,and the number of beating hESCs-derived cardiomyocytes was calculated.Gene expression was analyzed by quantitative real-time PCR(qRTPCR).Immunofluorescence assays were performed to assess the expression of cardiac troponin T(cTnT)andα-actinin protein in cardiomyocytes.Results:qRT-PCR showed that ZFAS1 expression in the mesoderm was significantly higher than that in embryonic stem cells,cardiac progenitor cells,and cardiomyocytes.Knockdown of ZFAS1 inhibited cardiomyocyte differentiation from hESCs,which was characterized by reduced expression of the cardiac-specific markers cTnT,α-actinin,myosin heavy chain 6(MYH6),and myosin heavy chain 7(MYH7).In contrast,ZFAS1 overexpression remarkably increased the percentage of spontaneously beating cardiomyocytes.In terms of the mechanism,we found that ZFAS1 is an antisense lncRNA at the 5′end of the protein-coding gene ZNFX1.Knockdown of ZFAS1 could increase the mRNA expression level of ZNFX1.Furthermore,qRT-PCR demonstrated that the silencing of ZNFX1 led to an increase in cardiac-specific markers that predicted the promotion of cardiomyocyte differentiation.Conclusion:Altogether,these data suggest that lncRNA-ZFAS1 is required for cardiac differentiation by functionally inhibiting the expression of ZNFX1,which may provide a reference for the treatment of heart disease to a certain extent.

Hydroxychloroquine induces long QT syndrome by blocking hERG channel

Objective:In March 2022,more than 600 million cases of Corona Virus Disease 2019(COVID-19)and about 6 million deaths have been reported worldwide.Unfortunately,while effective antiviral therapy has not yet been available,chloroquine(CQ)/hydroxychloroquine(HCQ)has been considered an option for the treatment of COVID-19.While many studies have demonstrated the potential of HCQ to decrease viral load and rescue patients'lives,controversial results have also been reported.One concern associated with HCQ in its clinical application to COVID-19 patients is the potential of causing long QT interval(LQT),an electrophysiological substrate for the induction of lethal ventricular tachyarrhythmias.Yet,the mechanisms for this cardiotoxicity of HCQ remained incompletely understood.Materials and methods:Adult New Zealand white rabbits were used for investigating the effects of HCQ on cardiac electrophysiology and expression of ion channel genes.HEK-293T cells with sustained overexpression of human-ether-a-go-go-related gene(hERG)K+channels were used for whole-cell patch-clamp recordings of hERG K+channel current(IhERG).Quantitative RT-PCR analysis and Western blot analysis were employed to determine the expression of various genes at mRNA and protein levels,respectively.Results:electrocardiogram(ECG)recordings revealed that HCQ prolonged QT and RR intervals and slowed heart rate in rabbits.Whole-cell patch-clamp results showed that HCQ inhibited the tail current of hERG channels and slowed the reactivation process from inactivation state.HCQ suppressed the expression of hERG and hindered the formation of the heat shock protein 90(Hsp90)/hERG complex.Moreover,the expression levels of connexin 43(CX43)and Kir2.1,the critical molecular/ionic determinants of cardiac conduction thereby ventricular arrythmias,were decreased by HCQ,while those of Cav1.2,the main Ca2+handling proteins,remained unchanged and SERCA2a was increased.Conclusion:HCQ could induce LQT but did not induce arrhythmias,and whether it is suitable for the treatment of COVID-19 requires more rigorous investigations and validations in the future.

Growth differentiation factor 11 promotes macrophage polarization towards M2 to attenuate myocardial infarction via inhibiting Notch1 signaling pathway

Background:Myocardial infarctions(MI)is a major threat to human health especially in people exposed to cold environment.The polarization of macrophages towards different functional phenotypes(M1 macrophages and M2 macrophages)is closely related to MI repairment.The growth differentiation factor 11(GDF11)has been reported to play a momentous role in inflammatory associated diseases.In this study,we examined the regulatory role of GDF11 in macrophage polarization and elucidated the underlying mechanisms in MI.Methods:In vivo,the mice model of MI was induced by permanent ligation of the left anterior descending coronary artery(LAD),and mice were randomly divided into the sham group,MI group,and MI+GDF11 group.The protective effect of GDF11 on myocardial infarction and its effect on macrophage polarization were verified by echocardiography,triphenyl tetrazolium chloride staining and immunofluorescence staining of heart tissue.In vitro,based on the RAW264.7 cell line,the effect of GDF11 in promoting macrophage polarization toward the M2 type by inhibiting the Notch1 Signaling pathway was validated by qRT-PCR,Western blot,and flow cytometry.Results:We found that GDF11 was significantly downregulated in the cardiac tissue of MI mice.And GDF11 supplementation can improve the cardiac function.Moreover,GDF11 could reduce the proportion of M1 macrophages and increase the accumulation of M2 macrophages in the heart tissue of MI mice.Furthermore,the cardioprotective effect of GDF11 on MI mice was weakened after macrophage clearance.At the cellular level,application of GDF11 could inhibit the expression of M1 macrophage(classically activated macrophage)markers iNOS,interleukin(IL)-1β,and IL-6 in a dose-dependent manner.In contrast,GDF11 significantly increased the level of M2 macrophage markers including IL-10,CD206,arginase 1(Arg1),and vascular endothelial growth factor(VEGF).Interestingly,GDF11 could promote M1 macrophages polarizing to M2 macrophages.At the molecular level,GDF11 significantly down-regulated the Notch1 signaling pathway,the activation of which has been demonstrated to promote M1 polarization in macrophages.Conclusions:GDF11 promoted macrophage polarization towards M2 to attenuate myocardial infarction via inhibiting Notch1 signaling pathway.

Acute cold exposure triggers thermogenic memory in brown adipose tissue

1 Introduction Infants are born with a substantial amount of brown adipose tissue(BAT),primarily clustered around their upper back,shoulders,and upper chest[1].As age progresses,the primary BAT gradually diminishes,and concomitantly,de novo lipogenesis(DNL)continues to occur in subcutaneous adipose tissue throughout the body.The abundance of BAT in young children enhances their thermogenic capacity,making weight gain challenging and increasing resistance to cold temperatures.In adults.

Unveiling metabolic flux changes during acute cold exposure

Controlling energy expenditure during acute cold exposure is a fundamental aspect of metabolic dynamics in organisms.However,prior studies on cold-induced thermogenesis faced limitations,primarily focusing on brown adipose tissue(BAT)and lacking precise in vivo flux measurements.This editorial aims to highlight the recent research by Bornstein et al.providing a comprehensive and quantitative insight into the intricate alterations in metabolic flux that drive this phenomenon[1].

Computation-aided novel epitope prediction by targeting spike protein's functional dynamics in Omicron

1 The ever-growing crisis imposed by Omicron The global corona virus disease 2019(COVID-19)pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has lasted for more than 3 years and resulted in about 657 million infections and 6.6 million deaths as of date 05 January,2023(https://covid19.who.int/).The latest variant of concern(VoC),Omicron,is leading a new wave of infections globally[1].Although small molecule inhibitors are emerging to show antiviral activities for SARS-CoV-2[2-3],only limited drugs have been approved(e.g.,remdesivir and baricitinib).Vaccination remains the preferred protection method,however,extra vaccine dose is often required to effectively neutralize Omicron[4];especially for the continuous evolution SARS-CoV-2 variants by constant mutations,escape from neutralizing antibodies is still a major concern that challenges the effectiveness of existing vaccines[5].This global public health crisis urgently demands developing effective antibodies against the Omicron.

Melatonin prevents endothelial cell pyroptosis via regulation of long noncoding RNA MEG3/miR-223/NLRP3 axis

OBJECTIVE To investigate the anti-pyroptotic effects of melatonin in atherosclerotic endothelium and to elucidate the potential mechanisms.METHODS ApoE-/-mice were randomly divid.ed into four groups(n=8):the normal-diet group(ND),the normal-diet group treated with melatonin(10 mg·kg^(-1))(ND+MLT),the high-fat-diet group(HFD),and the high-fat-diet group treated with melatonin(HFD+MLT).After 12 weeks,the expression levels of pyroptosis related genes including NLRP3,ASC,cleaved-caspase 1,GSDMD-N,IL-1β and IL-18 were examined in aortic endothelium by Western blotting,qRT-PCR and immunofluorescent staining.Besides,levels of MEG3 and miR-223 were also tested by qRT-PCR.The interaction between MEG3 and miR-223 was detected by luciferase assay.For in vitro study,human aortic endothelial cells(HAECs) were transiently transfected with miR-223 mimic,miR-223 inhibitor(AMO-223),MEG3-overexpressing plasmid or negative controls.After 6 h of transfection,the medium was replaced by fresh medium with or without ox-LDL(25 μg·mL-1) for 24 h and then treated with or without melatonin(10 μmol·L^(-1)) for 48 h.Cell pyroptosis was evaluated by Hoechst 33342/PI staining and differentially expressed pyroptosis related genes.RESULTS Melatonin markedly reduced the atherosclerotic plaque in aorta of ApoE-/-mice.Meanwhile,melatonin also attenuated the expression NLRP3,ASC,cleaved-caspase1,NF-κB/GSDMD,GSDMD-N termini,IL-1β,and IL-18 in aortic endo.thelium.Consistent anti-pyroptotic effects were also observed in ox-LDL-treated HAECs.We found that lncRNAMEG3 enhanced pyroptosis in HAECs.Moreover,MEG3 acted as an endogenous sponge by sequence complementarity to suppress the function of miR-223 and to increase NLRP3 expression and enhance endothelial cell pyroptosis.Furthermore,knockdown of miR-223 blocked the anti-pyroptotic actions of melatonin in ox-LDL-treated HAECs.CONCLUSION Melatonin prevents endothelial cell pyroptosis via MEG3/miR-223/NLRP3 axis in atherosclerosis and therefore melatonin replacement might be considered a new strategy for protecting endothelium against pyroptosis thereby for the treat.ment of atherosclerosis associated with pyroptosis.

Immunohistochemical evidence of axonal regrowth across polyethylene glycol-fused cervical cords in mice

It is generally accepted that a severed spinal cord is associated with permanent paralysis.Recently,a spinal cord fusion protocol（GEMINI）has been proposed,whereby an acutely controlled,sharp,operative transection of the spinal cord is carried out.

The ionic mechanisms of long QT interval in diabetic rabbits

Objective Abnormal QT prolongation associated with arrhythmias is considered the major cardiac electrical disorder and a significant predictor of mortality in diabetic patients. The precise ionic mechanisms for diabetic QT prolongation remained unclear. The present study was designed to analyze the changes of ventricular repolarization and the underlying ionic mechanisms in diabetic rabbit hearts. Methods Diabetes was induced by a single injection ofalloxan （145mg/kg, Lv. ）. After the development of diabetes （10 weeks）, ECG was measured. Whole-cell patch-clamp technique was applied to record the action potential duration （APD50, APD90）, slowly activating outward rectifying potassium current （IKs）, L-type calcium current （ICa-L） and inward rectifying potassium current （IK1）. Results The action potential duration （APD50 and APD90） of ventricular myocytes was obviously prolonged from 271.5＋32.3 ms and 347.8＋36.3 ms to 556.6~72.5 ms and 647.9~72.2 ms respectively （P〈 0.05）. Meanwhile the normalized peak current densities of IKs in ventricular myocytes investigated by whole-cell patch clamp was smaller in diabetic rabbits than that in control group at test potential of＋50mV （1.27~0.20 pA/pF vs 3.08~0.67 pA/pF, P〈0.05）. And the density of the ICa-L was increased apparently at the test potential of 10 mV （-2.67~0.41 pA/pF vs -5.404-1.08 pA/pF, P〈0.05）. Conclusion Ventricular repolarization was prolonged in diabetic rabbits, it may be partly due to the increased L-type calcium current and reduced slow delayed rectifier K＋ current （IKs） （J Geriatr Cardio12010; 7：25-29）.

Mitochondria are an important target of photobiomodulation in cardiomyocytes

Photobiomodulation(PBM)has been shown to delay the pathological process of heart failure,but the exact mechanism of action is not clear.Mitochondria occupy one-third of the volume of mammalian cardiomyocytes(CMs)and are central transport stations for CM energy metabolism.Therefore,in this study,we explored the regulatory effects of 630 nm light-emitting diodes(LED-Red)on the mitochondria of CMs.The results show that LED-Red-based PBM promotes adenosine triphosphate(ATP)synthesis by upregulating the expression of glycolipid metabolizing enzymes.Correspondingly,there was an improvement in the activity of succinate dehydrogenase(SDH),a key enzyme in the mitochondrial electron transport chain,and the mitochondrial membrane potential.Meanwhile,LED-Red affected the state of mitochondrial oxidative stress and promoted the generation of reactive oxygen species(ROS),but the increased ROS production did not damage the CMs.In addition,mitochondrial division and fusion were also affected by the stimulation of LED-Red.Finally,PBM treatment led to a significant increase in transcript levels of mitochondrial transcription factor A(TFAM),which controls the stability of the mitochondrial genome.Collectively,irradiation with LEDs at 630 nm played a regulatory role in mitochondrial function,suggesting that mitochondria appear to be the recipients of PBM treatment.This study provides more insights into the mechanisms underlying PBM treatment in heart diseases.

Antidiabetic agents:Do they hit the right targets?

Diabetes mellitus(DM)is a progressive metabolic disease characterized by chronic hyperglycemia and caused by different degree of pancreatic islet dysfunction and/or insulin resistance(IR).Long course DM can lead to a variety of macrovascular and microvascular complications which involve artery vessels,heart,kidney,retina,nervous system,etc.In recent years,DM has attracted more and more attention due to its high morbidity and mortality.In addition to achieve effective glycemic control,prevention of complications has also been considered a priority for type 2 diabetes mellitus(T2DM)management.Herein,we provide a comprehensive overview on the pharmacotherapeutics for T2DM and perspectives on the future directions of basic and translational research on anti-diabetic therapy and pharmatheutical development of new drugs.

Apelin aggravates the migration and invasion of non-small cell lung cancer cells via YAP1

Background:Apelin,an endogenous ligand of G-protein coupled receptor(GPCR),is a secreted peptide involved in the development of various tumors.However,the relationship between apelin and non-small cell lung cancer(NSCLC)is not quite clear.This study was designed to investigate the effect and mechanism of apelin on cell proliferation,migration and invasion of NSCLC cells.Methods:Twelve NSCLC specimens were collected for hematoxylin-eosin(HE)staining and immunohistochemistry analyses.Cell proliferation was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and cell migration and invasion were assessed using wound-healing and transwell assays.The subcellular location of yes associated protein 1(YAP1)in A549 cells was determined by immunofluorescence.The mRNA and protein levels in NSCLC tissues and cell lines were measured by qRT-PCR and western blot,respectively.Results:Apelin was upregulated in tumor tissues compared with the adjacent tissues.Apelin promoted proliferation,migration,and invasion of A549 and H460 cells,which was reversed by competitive apelin receptor(APJ)antagonist ML221.Additionally,apelin upregulated YAP1 expression,whereas silence of YAP1 by small interfering RNA(siRNA)attenuated apelin-induced cell proliferation,migration and invasion and suppressed epithelial-mesenchymal transition progression.Conclusion:Apelin promotes NSCLC cells proliferation,migration,and invasion by modulating YAP1 and might be a potential therapeutic target for NSCLC treatment.

Direct evidence of VEGF-mediated neuroregulation and afferent explanation of blood pressure dysregulation during angiogenic therapy

Objective:Oncocardiology is increasingly hot research field/topic in the clinical management of cancer with anti-angiogenic therapy of vascular endothelial growth factor(VEGF)that may cause cardiovascular toxicity,such as hypertension via vascular dysfunction and attenuation of eNOS/NO signaling in the baroreflex afferent pathway.The aim of the current study was to evaluate the potential roles of VEGF/VEGF receptors(VEGFRs)expressed in the baroreflex afferent pathway in autonomic control of blood pressure(BP)regulation.Methods:The distribution and expression of VEGF/VEGFRs were detected in the nodose ganglia(NG)and nucleus of tractus solitary(NTS)using immunostaining and molecular approaches.The direct role of VEGF was tested by NG microinjection under physiological and hypertensive conditions.Results:Immunostaining data showed that either VEGF or VEGFR2/VEGFR3 was clearly detected in the NG and NTS of adult male rats.Microinjection of VEGF directly into the NG reduced the mean blood pressure(MBP)dose-dependently,which was less dramatic in renovascular hypertension(RVH)rats,suggesting the VEGF-mediated depressor response by direct activation of the 1st-order baroreceptor neurons in the NG under both normal and disease conditions.Notably,this reduced depressor response in RVH rats was directly caused by the downregulation of VEGFR2,which compensated the up regulation of VEGF/VEGFR3 in the NG during the development of hypertension.Conclusion:It demonstrated for the first time that the BP-lowering property of VEGF/VEGFRs signaling via the activation of baroreflex afferent function may be a common target/pathway leading to BP dysregulation in anti-angiogenic therapy.

Traditional Chinese medicine in the treatment of high incidence diseases in cold areas: the thrombotic diseases

Thrombotic diseases are the leading causes of death worldwide,especially in cold climates.Traditional Chinese medicine(TCM)-based therapies have gained increasing popularity worldwide,but also raised some concerns about its efficacy,safety profile and exact mechanisms.TCM has been traditionally used in the management of thrombosis and convincingly proven effective in modifying thrombosis progression,particularly the platelet function,coagulation system and fibrinolytic system.This review article focuses on TCM regulation of thrombosis with brief discussion on the fundamental aspects and relevant background information for better understanding of the subject.In addition to its antithrombotic effects,we will dive insight into the cellular and molecular mechanisms of TCM as pharmacological regulators of platelet aggregation,coagulation,and fibrinolysis.With increasing awareness and understanding of the benefits and potentials of TCM,TCM products will in no doubt gain its broader applications in the treatment of thrombosis and associated disorders,which in turn will deepen our understanding of its pharmacological and molecular mechanisms.Finally,current review provides a perspective view on the future directions to TCM research on thrombosis.

Overexpression of microRNA-135b-5p attenuates acute myocardial infarction injury through its anti-oxidant and anti-apptotic properties

Objective:Myocardial infarction(MI)remains the leading cause of morbidity and mortality due partly to the limited regenerative capacity of cardiomyocytes to replace cardiomyocyte lost due to apoptosis.Inhibiting cardiomyocyte apoptosis is recognized as an effective therapeutic approach for MI.MicroRNAs(miRNAs,miRs),which regulate target genes at the post-transcriptional level,play a significant role in the regulation of cardiovascular diseases such as MI.MicroRNA-135b(miR-135b)has a protective effect on cardiomyocytes.However,the role of miR-135b in cardiomyocyte apoptosis in infarct myocardium needs further clarification.Methods:We generatedα-MHC-miR-135b transgenic mice to investigate the role of miR-135b in myocardial injury after MI.MiR-135b mimic and negative control(NC)were transfected into H2O2-induced cardiomyocytes to evaluate the effect of overexpression of miR-135b on the levels of reactive oxygen species(ROS)and apoptosis.Results:Our results showed that overexpression of miR-135b had protective effect on cardiomyocyte injury both in vivo and in vitro.MiR-135b inhibited cardiomyocyte apoptosis and ROS generation,downregulated pro-apoptosis proteins(cleaved-caspase-3 and Bax),and increased anti-apoptosis protein(Bcl-2).Moreover,miR-135b showed an inhibitory effect on apoptosis-related protein target transient receptor potential vanilloid-type 4(TRPV4)cation channel.Conclusion:MiR-135b might be considered a new molecular target for potential replacement therapy as antiapoptotic cardioprotection in the setting of MI.