An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease prog...An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.展开更多
Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal sur...Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.展开更多
Objective To investigate the effect of mucin 1(MUC1)on the proliferation and apoptosis of nasopharyngeal carcinoma(NPC)and its regulatory mechanism.Methods The 60 NPC and paired para-cancer normal tissues were collect...Objective To investigate the effect of mucin 1(MUC1)on the proliferation and apoptosis of nasopharyngeal carcinoma(NPC)and its regulatory mechanism.Methods The 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital.The expression of MUC1 was measured by real-time quantitative PCR(qPCR)in the patients with PNC.The 5-8F and HNE1 cells were transfected with siRNA control(si-control)or siRNA targeting MUC1(si-MUC1).Cell proliferation was analyzed by cell counting kit-8 and colony formation assay,and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells.The qPCR and ELISA were executed to analyze the levels of TNF-αand IL-6.Western blot was performed to measure the expression of MUC1,NFкB and apoptosis-related proteins(Bax and Bcl-2).Results The expression of MUC1 was up-regulated in the NPC tissues,and NPC patients with the high MUC1 expression were inclined to EBV infection,growth and metastasis of NPC.Loss of MUC1 restrained malignant features,including the proliferation and apoptosis,downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells.Conclusion Downregulation of MUC1 restrained biological characteristics of malignancy,including cell proliferation and apoptosis,by inactivating NF-κB signaling pathway in NPC.展开更多
Vaccarin,a flavonoid glycoside isolated from Vaccaria segetalis,is non-toxic to 3T3-L1 cells up to concentrations of 200μM.Accordingly,we investigated the effects of this natural product on adipogenesis and lipolysis...Vaccarin,a flavonoid glycoside isolated from Vaccaria segetalis,is non-toxic to 3T3-L1 cells up to concentrations of 200μM.Accordingly,we investigated the effects of this natural product on adipogenesis and lipolysis in 3T3-L1 adipocytes.Our results revealed that vaccarin significantly inhibited lipid accumulation by suppressing the adipogenesis-related transcription factors peroxisome proliferator-activated receptorγ(PPARγ)and the CCAAT/enhancer-binding proteinα(C/EBPα).Specifically,lipid accumulation decreased by up to 27.7±2.7%when 3T3-L1 adipocytes were treated with a 10μM concentration of vaccarin.Mechanistic studies showed that the compound inhibited adipogenesis through activation of the Hedgehog(Hh)signaling pathway and so restoring Smo and Gli1 expression at an early stage of differentiation.In mature 3T3-L1 cells,vaccarin significantly increased the secretion of glycerol into the surrounding medium and thus indicating that it accelerated the degradation of triglycerides.In addition,vaccarin,was shown to enhance lipolysis through stimulation of the transcription levels of lipoprotein lipase,monoglycerides lipase,adipose triacylglyceride lipase,hormone-sensitive lipase and adipose differentiated-related protein.All told,vaccarin suppressed lipid accumulation and enhanced lipolysis during adipocyte differentiation by restoring Hh signaling.As such,it is a phytochemical capable of halting adipocyte hyperplasia and,thereby,ameliorating the effects of obesity.展开更多
Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we...Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we established a rat model of T10 moderate spinal cord injury using an NYU Impactor ModerⅢand performed intraperitoneal injection of argatroban for 3 consecutive days.Our results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal cord.RNA sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway,which is involved in astrogliosis and glial scar formation.Western blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal pathway.Argatroban also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal cord.Taken together,these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway,thereby promoting the recovery of neurological function after spinal cord injury.展开更多
BACKGROUND Fanlian Huazhuo Formula(FLHZF)has the functions of invigorating spleen and resolving phlegm,clearing heat and purging turbidity.It has been identified to have therapeutic effects on type 2 diabetes mellitus...BACKGROUND Fanlian Huazhuo Formula(FLHZF)has the functions of invigorating spleen and resolving phlegm,clearing heat and purging turbidity.It has been identified to have therapeutic effects on type 2 diabetes mellitus(T2DM)in clinical application.Non-alcoholic fatty liver disease(NAFLD)is frequently diagnosed in patients with T2DM.However,the therapeutic potential of FLHZF on NAFLD and the underlying mechanisms need further investigation.AIM To elucidate the effects of FLHZF on NAFLD and explore the underlying hepatoprotective mechanisms in vivo and in vitro.METHODS HepG2 cells were treated with free fatty acid for 24 hours to induce lipid accumulation cell model.Subsequently,experiments were conducted with the different concentrations of freeze-dried powder of FLHZF for 24 hours.C57BL/6 mice were fed a high-fat diet for 8-week to establish a mouse model of NAFLD,and then treated with the different concentrations of FLHZF for 10 weeks.RESULTS FLHZF had therapeutic potential against lipid accumulation and abnormal changes in biochemical indicators in vivo and in vitro.Further experiments verified that FLHZF alleviated abnormal lipid metabolism might by reducing oxidative stress,regulating the AMPKα/SREBP-1C signaling pathway,activating autophagy,and inhibiting hepatocyte apoptosis.CONCLUSION FLHZF alleviates abnormal lipid metabolism in NAFLD models by regulating reactive oxygen species,autophagy,apoptosis,and lipid synthesis signaling pathways,indicating its potential for clinical application in NAFLD.展开更多
Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related t...Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.展开更多
BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM T...BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM To assess the therapeutic potential of ginsenoside Rg1 on AA,specifically its protective effects,while elucidating the mechanism at play.METHODS We employed a model of myelosuppression induced by cyclophosphamide(CTX)in C57 mice,followed by administration of ginsenoside Rg1 over 13 d.The invest-igation included examining the bone marrow,thymus and spleen for pathological changes via hematoxylin-eosin staining.Moreover,orbital blood of mice was collected for blood routine examinations.Flow cytometry was employed to identify the impact of ginsenoside Rg1 on cell apoptosis and cycle in the bone marrow of AA mice.Additionally,the study further evaluated cytokine levels with enzyme-linked immunosorbent assay and analyzed the expression of key proteins in the MAPK signaling pathway via western blot.RESULTS Administration of CTX led to significant damage to the bone marrow’s structural integrity and a reduction in hematopoietic cells,establishing a model of AA.Ginsenoside Rg1 successfully reversed hematopoietic dysfunction in AA mice.In comparison to the AA group,ginsenoside Rg1 provided relief by reducing the induction of cell apoptosis and inflammation factors caused by CTX.Furthermore,it helped alleviate the blockade in the cell cycle.Treatment with ginsenoside Rg1 significantly alleviated myelosuppression in mice by inhibiting the MAPK signaling pathway.CONCLUSION This study suggested that ginsenoside Rg1 addresses AA by alleviating myelosuppression,primarily through modulating the MAPK signaling pathway,which paves the way for a novel therapeutic strategy in treating AA,highlighting the potential of ginsenoside Rg1 as a beneficial intervention.展开更多
Five stems of rapeseed with abundant black microsclerotia were collected from Huangyuan County of Qinghai Province,China,and fungal isolates were obtained from the stems.They were identified based on morphology,molecu...Five stems of rapeseed with abundant black microsclerotia were collected from Huangyuan County of Qinghai Province,China,and fungal isolates were obtained from the stems.They were identified based on morphology,molecular features and specific PCR detection.The results showed that the 10 fungal isolates belonged to Verticillium longisporum lineage A1/D3.One of the 10 isolates(HW7-1)was tested for virulence on three species of rapeseed,including B.napus Zhongshuang 9,B.rapa Qingyou 9 and B.juncea Tayou 2 by conidia inoculation of HW7-1 on roots of young seedlings.Control seedlings were inoculated with V.dahliae conidia or water alone.The seedlings of these treatments were transplanted in culture mix and incubated in a growth chamber(20℃).Results suggested that the control seedlings of three cultivars appeared quite healthy,while the seedlings inoculated with HW7-1 turned yellowing leaves,seedling stunting or even death after 22 days post-inoculation.V.longisporum was re-isolated from he yellow leaves,thus fulfilling Koch's postulates.Moreover,compared to the control treatments,inoculation with HW7-1 caused flowering delay and seed yield reduction on Tayou 2 with production of microsclerotia on the stems.To our knowledge,this is the first report of V.longisporum lineage A1/D3 on rapeseed in northwestern China.展开更多
Background Homocysteine(Hcy)is a risk factor for hypertension,although the mechanisms are poorly understood.Methods We first explored the relationship between Hcy levels and blood pressure(BP)by analyzing the clinical...Background Homocysteine(Hcy)is a risk factor for hypertension,although the mechanisms are poorly understood.Methods We first explored the relationship between Hcy levels and blood pressure(BP)by analyzing the clinical data of primary hypertensive patients admitted to our hospital.Secondly,we explored a rat model to study the effect of Hcy on blood pressure and the role of H2S.An hyperhomocysteinemia(HHcy)rat model was induced to explore the effect of Hcy on blood pressure and the possible mechanism.We carried out tissue histology,extraction and examination of RNA and protein.Finally,we conducted cell experiments to determine a likely mechanism through renin-angiotensin-aldosterone system(RAAS)and extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway.Results In primary hypertensive inpatients with HHcy,blood pressure was significantly higher as compared with inpatient counterparts lacking HHcy.In the rat model,blood pressure of the Wistar rats was significantly increased with increases in serum Hcy levels and decreased after folate treatment.Angiotensin converting enzyme 1(ACE1)expression in the Wistar Hcy group was enhanced comparing to controls,but was decreased in the Wistar folate group.Angiotensin II receptor type 1(AGTR1)levels in the kidney tissue increased in the Wistar folate group.Both serum H2S and kidney cystathionineγ-lyase decreased with elevated levels of serum Hcy.In vitro,increased concentrations and treatment times for Hcy were associated with increased expression of collagen type 1 and AGTR1.This dose and time dependent response was also observed for p-STAT3 and p-ERK1/2 expression.Conclusion Endogenous H2S might mediate the process of altered blood pressure in response to changes in serum Hcy levels,in a process that is partly dependent on activated RAAS and ERK1/2-STAT3 signaling pathway.展开更多
Brassinosteroids （BRs） are perceived by transmembrane receptors and play vital roles in plant growth and development, as well as cell in responses to environmental stimuli. The transmemhrane receptor BRI1 can direct...Brassinosteroids （BRs） are perceived by transmembrane receptors and play vital roles in plant growth and development, as well as cell in responses to environmental stimuli. The transmemhrane receptor BRI1 can directly bind to brassinolide （BL）, and BAK1 interacts with BRI1 to enhance the BRI1-mediated BR signaling. Our previous studies indicated that a membrane steroid-binding protein 1 （MSBP1） could bind to BL in vitro and is negatively involved in BR signaling. To further elucidate the underlying mechanism, we here show that MSBPI specifically interacts with the extraeellular domain of BAK1 in vivo in a BL-independent manner. Suppressed cell expansion and BR responses by increased expression of MSBP1 can be recovered by overexpressing BAK1 or its intracellnlar kinase domain, sug- gesting that MSBP1 may suppress BR signaling through interacting with BAK1. Subcellular localization studies re- vealed that both MSBPI and BAK1 are localized to plasma membrane and endocytic vesicles and MSBP1 accelerates BAK1 endocytosis, which results in suppressed BR signaling by shifting the equilibrium of BAKI toward endosomes. Indeed, enhanced MSBP1 expression reduces the interaction between BRI1 and BAK1 in vivo, demonstrating that MSBP1 acts as a negative factor at an early step of the BR signaling pathway.展开更多
Objective Curcuma wenyujin,named Ezhu in Chinese,a traditional Chinese medicine,which has been shown to possess anticarcinogenic activity and used for the treatment of tumor in China,for example,hepatic cancer and leu...Objective Curcuma wenyujin,named Ezhu in Chinese,a traditional Chinese medicine,which has been shown to possess anticarcinogenic activity and used for the treatment of tumor in China,for example,hepatic cancer and leukemia.β-elemene,a component of Curcuma wenyujin,was largely reported as a main active component for anti-tumor effect of Curcuma wenyujin.However,furanodiene,another main component of Curcuma wenyujin,was seldom investigated for its anti-tumor activities.In the present study,we aim to investigate the effect of furanodiene on human leukemia HL60 cells and to study the accurate molecular mechanisms of its action.Methods Trypan blue exclusion experiment was used for cell growth inhibition assay.The apoptotic characterizations were assessed by flow cytometry analysis,AO/EB staining assay and agarose gel electrophoresis assay.The expression of apoptosis-related proteins and the release of cytochrome c from mitochondrial were detected by western blotting,and the mRNA levels of TNF-α and TNFR1 were probed by RT-PCR.Formation of TNFR1 complex was analyzed by using immunoprecipitation of TNFR1 with TRRF1/2 and RIP.Results Furanodiene(10-100 μM)treatment inhibited the growth of HL60 cells in a concentration-dependent manner.The effect of furanodiene on HL60 cells was associated with the induction of apoptosis,which was characterized by DNA fragmentation,cleavage of poly(ADP-ribose)polymerase(PARP),caspase-3,caspase-8 and caspase-9.In the Bcl-2 family proteins,Bid protein(a substrate of caspase-8)was activated by furanodiene,but Bcl-2,Bax and Bcl-xL proteins were not inuenced by furanodiene stimulation.Furanodiene elicited cytochrome c release from mitochondria into the cytosol.Moreover,furanodiene treatment caused the upregulation of TNFR1,the formation of TNFR1 complex and an obvious production of TNF-α in HL60 cells.The soluble TNFR1 receptor effectively inhibited furanodiene-induced apoptosis.Conclusions Furanodiene inhibited the growth of HL60 leukemia cells via induction of apoptosis.Furanodiene-induced apoptosis in HL60 cells is mediated by upregulation of TNF receptor 1 as well as induction of TNF-α production to activate TNFR1 signaling pathway.Our research provides insight into the molecular mechanisms on furanodiene-induced cell death,and may aid to the development of furanodiene as a new anti-tumor agent.展开更多
Background:The current study was conducted to investigate the individual and combined occurrence of aflatoxin B_(1)(AFB_(1)),deoxynivalenol(DON)and zearalenone(ZEN)in feeds from various Provinces of China during 2018 ...Background:The current study was conducted to investigate the individual and combined occurrence of aflatoxin B_(1)(AFB_(1)),deoxynivalenol(DON)and zearalenone(ZEN)in feeds from various Provinces of China during 2018 to 2020.A total of 3,507 feed samples,including 2,090 feed ingredients and 1,417 complete feed samples,were collected from different areas of China for mycotoxins analysis.Results:The individual contamination of AFB_(1),DON and ZEN were present in more than 81.9%,96.4% and 96.9% of feed samples,respectively,with average concentration ranges of AFB_(1) between 1.2-27.4μg/kg,DON between 458.0-1,925.4μg/kg and ZEN between 48.1-326.8μg/kg.Notably,0.9%,0.5% and 0.1% of feed ingredients,and 1.2-12.8%,0.9-2.9% and 0-8.9% of complete feeds for pigs,poultry and ruminants with AFB_(1),ZEN and DON that exceeded China’s safety standards,respectively.Moreover,more than 81.5%of feed ingredients and 95.7% of complete feeds were co-contaminated with various combinations of these mycotoxins.Conclusion:This study indicates that the feeds in China were universally contaminated with AFB_(1),DON and ZEN during the past 3 years.These findings highlight the significance of monitoring mycotoxin contaminant levels in the domestic animal feed,and the importance of carrying out feed administration and remediation strategies for mycotoxin control.展开更多
BACKGROUND Wnt1-inducible signaling pathway protein 1(WISP1)is upregulated in several types of human cancer,and has been implicated in cancer progression.However,its clinical implications in gastric cancer(GC)remain u...BACKGROUND Wnt1-inducible signaling pathway protein 1(WISP1)is upregulated in several types of human cancer,and has been implicated in cancer progression.However,its clinical implications in gastric cancer(GC)remain unclear.AIM To explore the expression pattern and clinical significance of WISP1 in GC.METHODS Public data portals,including Oncomine,The Cancer Genome Atlas database,Coexpedia,and Kaplan-Meier plotter,were analyzed for the expression and clinical significance of WISP1 mRNA levels in GC.One hundred and fifty patients who underwent surgery for GC between February 2010 and October 2012 at the Affiliated Hospital of Jiangnan University were selected for validation study.WISP1 levels were measured at both the mRNA and protein levels by RTqPCR,Western blot analysis,and immunohistochemistry(IHC).In addition,the in situ expression of WISP1 in the GC tissues was determined by IHC,and the patients were accordingly classified into high-and low-expression groups.The correlation of WISP1 expression status with patient prognosis was then determined by univariate and multivariate Cox regression analyses.WISP1 was knocked down by RNA interference.The 50%inhibitory concentration of oxaliplatin was detected by CellTiter-Blue assay.RESULTS WISP1 levels at both the mRNA and protein levels were remarkably upregulated in GC tissues compared to normal tissues.Moreover,IHC revealed that WISP1 expression was associated with T stage and chemotherapy outcome,but not with lymph node metastasis,age,gender,histological grade,or histological type.GC patients with high WISP1 expression showed a poor overall survival.Multivariate survival analysis indicated that WISP1 was an important prognostic factor for GC patients.Mechanistically,knock-down of WISP1 expression enhanced sensitivity to oxaliplatin by reducing DNA repair and enhancing DNA damage.CONCLUSION Significantly upregulated WISP1 expression is associated with cancer progression,chemotherapy outcome,and prognosis in GC.Mechanistically,knock-down of WISP1 expression enhances oxaliplatin sensitivity by reducing DNA repair and enhancing DNA damage.WISP1 may be a potential therapeutic target for GC treatment or a potential biomarker for diagnosis and prognosis.展开更多
Objective:To explore the mechanism of Profilin-1 in regulating eNOS/NO pathway and its role in the development of myocardial hypertrophy.Methods:Spontaneously hypertensive rats(SHR) aged 5 weeks were injected with dif...Objective:To explore the mechanism of Profilin-1 in regulating eNOS/NO pathway and its role in the development of myocardial hypertrophy.Methods:Spontaneously hypertensive rats(SHR) aged 5 weeks were injected with different adenovirus vectors to induce Profilin-1expression knockdown(SHR-I) or over express(SHR-H) or to use as control(SHR-C).All these treatment were compared with Wistar-Kyoto rats(SKY) treated with control adenovirus vectors(WKY-C).The same injection was executed at the sixth week during the experiment of 12 weeks.After experiment,the left ventricular weight-to-heart weight ratio(LVW/HW)and left ventricular long axis(LVLA) were measured.Meanwhile.NO contents in blood and myocardium,Profilin-1,eNOS and Caveolin-3 niRNA and protein levels and phosphorylated eNOS(P-eNOS) protein level in myocardium were determined.Results:Compared with WKY-C group,the SHR-C group was statistically higher in LVW/HW(0.79±0.03).LVLA(11.82±0.58 mm) and Profilin-1 niRNA and prolein level(P<0.05).but lower in NO content[(18.63±6.23) μmol/L| in blood and[(2.71±0.17) μmol/L]in myocardium).eNOS activity and Caveolin-3 expression(P<0.05).The over expressing Profilin-1 led SHR-H group to a higher value of LVW/HW[(0.93±0.03) mm and LVLA(14.17±0.69) mm]in comparison with SHR-C group(P<0.05).and to a lower value of NO content(in myocardium).eNOS activity and Caveolin-3 expression(P<0.05):however,this phenomenon was reversed by the knockdown Profilin-1 expression(SHR-I group).Conclusions:Profilin-1 expression,being negative in regulating Caveolin-3 expression and eNOS/NO pathway activity,promotes the development of myocardial hypertrophy which can be reversed by Profilin-1 silencing.展开更多
Drought and salt stresses,the major environmental abiotic stresses in agriculture worldwide,affect plant growth,crop productivity,and quality.Therefore,developing crops with higher drought and salt tolerance is highly...Drought and salt stresses,the major environmental abiotic stresses in agriculture worldwide,affect plant growth,crop productivity,and quality.Therefore,developing crops with higher drought and salt tolerance is highly desirable.This study reported the isolation,biological function,and molecular characterization of a novel maspardin gene,OsMas1,from rice.The OsMas1 protein was localized to the cytoplasm.The expression levels of OsMas1 were up-regulated under mannitol,PEG6000,NaCl,and abscisic acid(ABA) treatments in rice.The OsMas1 gene was introduced into the rice cultivar Zhonghua 11(wild type,WT).OsMas1-overexpression(OsMas1-OE) plants exhibited significantly enhanced salt and drought tolerance;in contrast,OsMas1-interference(OsMas1-RNAi) plants exhibited decreased tolerance to salt and drought stresses,compared with WT.OsMas1-OE plants exhibited enhanced hypersensitivity,while OsMas1-RNAi plants showed less sensitivity to exogenous ABA treatment at both germination and post-germination stages.ABA,proline and K+ contents and superoxide dismutase(SOD),catalase(CAT),peroxidase(POD),and photosynthesis activities were significantly increased.In contrast,malonaldehyde(MDA),hydrogen peroxide(H2O2),superoxide anion radical(O2-··),and Na+ contents were significantly decreased in OsMas1-OE plants compared with OsMas1-RNAi and WT plants.Overexpression of OsMas1 up-regulated the genes involved in ABA signaling,proline biosynthesis,reactive oxygen species(ROS)-scavenging system,photosynthesis,and ion transport under salt and drought stresses.Our results indicate that the OsMas1 gene improves salt and drought tolerance in rice,which may serve as a candidate gene for enhancing crop resistance to abiotic stresses.展开更多
基金supported by a grant from Ministry of Science,Technological Development and Innovation,Serbia,No.451-03-68/2022-14/200178(to NN)University of Defence,No.MFVMA/02/22-24(to MN)。
文摘An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.
基金supported by the National Natural Science Foundation of China(Youth Science Fund Project),No.81901292(to GC)the National Key Research and Development Program of China,No.2021YFC2502100(to GC)the National Natural Science Foundation of China,No.82071183(to ZZ).
文摘Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.
文摘Objective To investigate the effect of mucin 1(MUC1)on the proliferation and apoptosis of nasopharyngeal carcinoma(NPC)and its regulatory mechanism.Methods The 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital.The expression of MUC1 was measured by real-time quantitative PCR(qPCR)in the patients with PNC.The 5-8F and HNE1 cells were transfected with siRNA control(si-control)or siRNA targeting MUC1(si-MUC1).Cell proliferation was analyzed by cell counting kit-8 and colony formation assay,and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells.The qPCR and ELISA were executed to analyze the levels of TNF-αand IL-6.Western blot was performed to measure the expression of MUC1,NFкB and apoptosis-related proteins(Bax and Bcl-2).Results The expression of MUC1 was up-regulated in the NPC tissues,and NPC patients with the high MUC1 expression were inclined to EBV infection,growth and metastasis of NPC.Loss of MUC1 restrained malignant features,including the proliferation and apoptosis,downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells.Conclusion Downregulation of MUC1 restrained biological characteristics of malignancy,including cell proliferation and apoptosis,by inactivating NF-κB signaling pathway in NPC.
基金This work was graciously supported by the Chinese National Natural Science Foundation(Grant 31901725 and 32201933)the Science and Technology Projects in Guangzhou(Grant 202201010170).
文摘Vaccarin,a flavonoid glycoside isolated from Vaccaria segetalis,is non-toxic to 3T3-L1 cells up to concentrations of 200μM.Accordingly,we investigated the effects of this natural product on adipogenesis and lipolysis in 3T3-L1 adipocytes.Our results revealed that vaccarin significantly inhibited lipid accumulation by suppressing the adipogenesis-related transcription factors peroxisome proliferator-activated receptorγ(PPARγ)and the CCAAT/enhancer-binding proteinα(C/EBPα).Specifically,lipid accumulation decreased by up to 27.7±2.7%when 3T3-L1 adipocytes were treated with a 10μM concentration of vaccarin.Mechanistic studies showed that the compound inhibited adipogenesis through activation of the Hedgehog(Hh)signaling pathway and so restoring Smo and Gli1 expression at an early stage of differentiation.In mature 3T3-L1 cells,vaccarin significantly increased the secretion of glycerol into the surrounding medium and thus indicating that it accelerated the degradation of triglycerides.In addition,vaccarin,was shown to enhance lipolysis through stimulation of the transcription levels of lipoprotein lipase,monoglycerides lipase,adipose triacylglyceride lipase,hormone-sensitive lipase and adipose differentiated-related protein.All told,vaccarin suppressed lipid accumulation and enhanced lipolysis during adipocyte differentiation by restoring Hh signaling.As such,it is a phytochemical capable of halting adipocyte hyperplasia and,thereby,ameliorating the effects of obesity.
基金supported by the Key Project of the National Natural Science Foundation of China,No.81930070(to SF)the National Natural Science Foundation of China,No.81972074(to XY)the Key Program of Natural Science Foundation of Tianjin,No.19JCZDJC34900(to XY)。
文摘Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we established a rat model of T10 moderate spinal cord injury using an NYU Impactor ModerⅢand performed intraperitoneal injection of argatroban for 3 consecutive days.Our results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal cord.RNA sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway,which is involved in astrogliosis and glial scar formation.Western blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal pathway.Argatroban also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal cord.Taken together,these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway,thereby promoting the recovery of neurological function after spinal cord injury.
基金Supported by Basic and Applied Basic Research Found of Guangdong Province,No.2022A1515011307。
文摘BACKGROUND Fanlian Huazhuo Formula(FLHZF)has the functions of invigorating spleen and resolving phlegm,clearing heat and purging turbidity.It has been identified to have therapeutic effects on type 2 diabetes mellitus(T2DM)in clinical application.Non-alcoholic fatty liver disease(NAFLD)is frequently diagnosed in patients with T2DM.However,the therapeutic potential of FLHZF on NAFLD and the underlying mechanisms need further investigation.AIM To elucidate the effects of FLHZF on NAFLD and explore the underlying hepatoprotective mechanisms in vivo and in vitro.METHODS HepG2 cells were treated with free fatty acid for 24 hours to induce lipid accumulation cell model.Subsequently,experiments were conducted with the different concentrations of freeze-dried powder of FLHZF for 24 hours.C57BL/6 mice were fed a high-fat diet for 8-week to establish a mouse model of NAFLD,and then treated with the different concentrations of FLHZF for 10 weeks.RESULTS FLHZF had therapeutic potential against lipid accumulation and abnormal changes in biochemical indicators in vivo and in vitro.Further experiments verified that FLHZF alleviated abnormal lipid metabolism might by reducing oxidative stress,regulating the AMPKα/SREBP-1C signaling pathway,activating autophagy,and inhibiting hepatocyte apoptosis.CONCLUSION FLHZF alleviates abnormal lipid metabolism in NAFLD models by regulating reactive oxygen species,autophagy,apoptosis,and lipid synthesis signaling pathways,indicating its potential for clinical application in NAFLD.
基金supported by the National Natural Science Foundation of China,No.81971097(to JY)。
文摘Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.
基金Supported by Hangzhou Municipal Bureau of Science and Technology,No.2021WJCY366.
文摘BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM To assess the therapeutic potential of ginsenoside Rg1 on AA,specifically its protective effects,while elucidating the mechanism at play.METHODS We employed a model of myelosuppression induced by cyclophosphamide(CTX)in C57 mice,followed by administration of ginsenoside Rg1 over 13 d.The invest-igation included examining the bone marrow,thymus and spleen for pathological changes via hematoxylin-eosin staining.Moreover,orbital blood of mice was collected for blood routine examinations.Flow cytometry was employed to identify the impact of ginsenoside Rg1 on cell apoptosis and cycle in the bone marrow of AA mice.Additionally,the study further evaluated cytokine levels with enzyme-linked immunosorbent assay and analyzed the expression of key proteins in the MAPK signaling pathway via western blot.RESULTS Administration of CTX led to significant damage to the bone marrow’s structural integrity and a reduction in hematopoietic cells,establishing a model of AA.Ginsenoside Rg1 successfully reversed hematopoietic dysfunction in AA mice.In comparison to the AA group,ginsenoside Rg1 provided relief by reducing the induction of cell apoptosis and inflammation factors caused by CTX.Furthermore,it helped alleviate the blockade in the cell cycle.Treatment with ginsenoside Rg1 significantly alleviated myelosuppression in mice by inhibiting the MAPK signaling pathway.CONCLUSION This study suggested that ginsenoside Rg1 addresses AA by alleviating myelosuppression,primarily through modulating the MAPK signaling pathway,which paves the way for a novel therapeutic strategy in treating AA,highlighting the potential of ginsenoside Rg1 as a beneficial intervention.
基金supported by the Earmarked Fund for CARS-12 from National Modern Agricultural Technology System.
文摘Five stems of rapeseed with abundant black microsclerotia were collected from Huangyuan County of Qinghai Province,China,and fungal isolates were obtained from the stems.They were identified based on morphology,molecular features and specific PCR detection.The results showed that the 10 fungal isolates belonged to Verticillium longisporum lineage A1/D3.One of the 10 isolates(HW7-1)was tested for virulence on three species of rapeseed,including B.napus Zhongshuang 9,B.rapa Qingyou 9 and B.juncea Tayou 2 by conidia inoculation of HW7-1 on roots of young seedlings.Control seedlings were inoculated with V.dahliae conidia or water alone.The seedlings of these treatments were transplanted in culture mix and incubated in a growth chamber(20℃).Results suggested that the control seedlings of three cultivars appeared quite healthy,while the seedlings inoculated with HW7-1 turned yellowing leaves,seedling stunting or even death after 22 days post-inoculation.V.longisporum was re-isolated from he yellow leaves,thus fulfilling Koch's postulates.Moreover,compared to the control treatments,inoculation with HW7-1 caused flowering delay and seed yield reduction on Tayou 2 with production of microsclerotia on the stems.To our knowledge,this is the first report of V.longisporum lineage A1/D3 on rapeseed in northwestern China.
基金supported by the Beijing Natural Science Foundation Program(Grant number:5102040)the Open Foundation of the Beijing Key Laboratory of Hypertension Research(Grant number:2015GXYB01)
文摘Background Homocysteine(Hcy)is a risk factor for hypertension,although the mechanisms are poorly understood.Methods We first explored the relationship between Hcy levels and blood pressure(BP)by analyzing the clinical data of primary hypertensive patients admitted to our hospital.Secondly,we explored a rat model to study the effect of Hcy on blood pressure and the role of H2S.An hyperhomocysteinemia(HHcy)rat model was induced to explore the effect of Hcy on blood pressure and the possible mechanism.We carried out tissue histology,extraction and examination of RNA and protein.Finally,we conducted cell experiments to determine a likely mechanism through renin-angiotensin-aldosterone system(RAAS)and extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway.Results In primary hypertensive inpatients with HHcy,blood pressure was significantly higher as compared with inpatient counterparts lacking HHcy.In the rat model,blood pressure of the Wistar rats was significantly increased with increases in serum Hcy levels and decreased after folate treatment.Angiotensin converting enzyme 1(ACE1)expression in the Wistar Hcy group was enhanced comparing to controls,but was decreased in the Wistar folate group.Angiotensin II receptor type 1(AGTR1)levels in the kidney tissue increased in the Wistar folate group.Both serum H2S and kidney cystathionineγ-lyase decreased with elevated levels of serum Hcy.In vitro,increased concentrations and treatment times for Hcy were associated with increased expression of collagen type 1 and AGTR1.This dose and time dependent response was also observed for p-STAT3 and p-ERK1/2 expression.Conclusion Endogenous H2S might mediate the process of altered blood pressure in response to changes in serum Hcy levels,in a process that is partly dependent on activated RAAS and ERK1/2-STAT3 signaling pathway.
基金Acknowledgments This study was supported by the Chinese Academy of Sciences and National Natural Science Foundation of China （Grants 30425029, 30421001, 90717001）. We greatly thank Prof Hong Ma （Penn. State University, USA） for critical reading and writing improvement and Prof Nam-Hai Chua （The Rockefeller University, USA） for helpful comments. We thank the Salk Institute Genomic Analysis Laboratory for providing the sequence-indexed Arabidopsis T-DNA insertion mutants, and Prof Sheng Luan （University of California, Berkeley, USA） for providing the construct pATC940. We thank Prof Hong-Quan Yang （SIPPE, CAS） for providing LexA yeast two-hybrid system and Prof Zhi-Yong Wang （The Stanford University, USA） for providing the BRI1 antibody. We thank Mr Xiao-Shu Gao for the help on Confocal Laser Scanning Microscopy.
文摘Brassinosteroids （BRs） are perceived by transmembrane receptors and play vital roles in plant growth and development, as well as cell in responses to environmental stimuli. The transmemhrane receptor BRI1 can directly bind to brassinolide （BL）, and BAK1 interacts with BRI1 to enhance the BRI1-mediated BR signaling. Our previous studies indicated that a membrane steroid-binding protein 1 （MSBP1） could bind to BL in vitro and is negatively involved in BR signaling. To further elucidate the underlying mechanism, we here show that MSBPI specifically interacts with the extraeellular domain of BAK1 in vivo in a BL-independent manner. Suppressed cell expansion and BR responses by increased expression of MSBP1 can be recovered by overexpressing BAK1 or its intracellnlar kinase domain, sug- gesting that MSBP1 may suppress BR signaling through interacting with BAK1. Subcellular localization studies re- vealed that both MSBPI and BAK1 are localized to plasma membrane and endocytic vesicles and MSBP1 accelerates BAK1 endocytosis, which results in suppressed BR signaling by shifting the equilibrium of BAKI toward endosomes. Indeed, enhanced MSBP1 expression reduces the interaction between BRI1 and BAK1 in vivo, demonstrating that MSBP1 acts as a negative factor at an early step of the BR signaling pathway.
文摘Objective Curcuma wenyujin,named Ezhu in Chinese,a traditional Chinese medicine,which has been shown to possess anticarcinogenic activity and used for the treatment of tumor in China,for example,hepatic cancer and leukemia.β-elemene,a component of Curcuma wenyujin,was largely reported as a main active component for anti-tumor effect of Curcuma wenyujin.However,furanodiene,another main component of Curcuma wenyujin,was seldom investigated for its anti-tumor activities.In the present study,we aim to investigate the effect of furanodiene on human leukemia HL60 cells and to study the accurate molecular mechanisms of its action.Methods Trypan blue exclusion experiment was used for cell growth inhibition assay.The apoptotic characterizations were assessed by flow cytometry analysis,AO/EB staining assay and agarose gel electrophoresis assay.The expression of apoptosis-related proteins and the release of cytochrome c from mitochondrial were detected by western blotting,and the mRNA levels of TNF-α and TNFR1 were probed by RT-PCR.Formation of TNFR1 complex was analyzed by using immunoprecipitation of TNFR1 with TRRF1/2 and RIP.Results Furanodiene(10-100 μM)treatment inhibited the growth of HL60 cells in a concentration-dependent manner.The effect of furanodiene on HL60 cells was associated with the induction of apoptosis,which was characterized by DNA fragmentation,cleavage of poly(ADP-ribose)polymerase(PARP),caspase-3,caspase-8 and caspase-9.In the Bcl-2 family proteins,Bid protein(a substrate of caspase-8)was activated by furanodiene,but Bcl-2,Bax and Bcl-xL proteins were not inuenced by furanodiene stimulation.Furanodiene elicited cytochrome c release from mitochondria into the cytosol.Moreover,furanodiene treatment caused the upregulation of TNFR1,the formation of TNFR1 complex and an obvious production of TNF-α in HL60 cells.The soluble TNFR1 receptor effectively inhibited furanodiene-induced apoptosis.Conclusions Furanodiene inhibited the growth of HL60 leukemia cells via induction of apoptosis.Furanodiene-induced apoptosis in HL60 cells is mediated by upregulation of TNF receptor 1 as well as induction of TNF-α production to activate TNFR1 signaling pathway.Our research provides insight into the molecular mechanisms on furanodiene-induced cell death,and may aid to the development of furanodiene as a new anti-tumor agent.
基金supported by the Chinese Natural Science Foundation projects(32072775 and 31772636)National Key Research and Development Program of China(2016YFD0501207)JiangSu Aomai Bio-Technology Co.,Ltd.(Nanjing,China).
文摘Background:The current study was conducted to investigate the individual and combined occurrence of aflatoxin B_(1)(AFB_(1)),deoxynivalenol(DON)and zearalenone(ZEN)in feeds from various Provinces of China during 2018 to 2020.A total of 3,507 feed samples,including 2,090 feed ingredients and 1,417 complete feed samples,were collected from different areas of China for mycotoxins analysis.Results:The individual contamination of AFB_(1),DON and ZEN were present in more than 81.9%,96.4% and 96.9% of feed samples,respectively,with average concentration ranges of AFB_(1) between 1.2-27.4μg/kg,DON between 458.0-1,925.4μg/kg and ZEN between 48.1-326.8μg/kg.Notably,0.9%,0.5% and 0.1% of feed ingredients,and 1.2-12.8%,0.9-2.9% and 0-8.9% of complete feeds for pigs,poultry and ruminants with AFB_(1),ZEN and DON that exceeded China’s safety standards,respectively.Moreover,more than 81.5%of feed ingredients and 95.7% of complete feeds were co-contaminated with various combinations of these mycotoxins.Conclusion:This study indicates that the feeds in China were universally contaminated with AFB_(1),DON and ZEN during the past 3 years.These findings highlight the significance of monitoring mycotoxin contaminant levels in the domestic animal feed,and the importance of carrying out feed administration and remediation strategies for mycotoxin control.
文摘BACKGROUND Wnt1-inducible signaling pathway protein 1(WISP1)is upregulated in several types of human cancer,and has been implicated in cancer progression.However,its clinical implications in gastric cancer(GC)remain unclear.AIM To explore the expression pattern and clinical significance of WISP1 in GC.METHODS Public data portals,including Oncomine,The Cancer Genome Atlas database,Coexpedia,and Kaplan-Meier plotter,were analyzed for the expression and clinical significance of WISP1 mRNA levels in GC.One hundred and fifty patients who underwent surgery for GC between February 2010 and October 2012 at the Affiliated Hospital of Jiangnan University were selected for validation study.WISP1 levels were measured at both the mRNA and protein levels by RTqPCR,Western blot analysis,and immunohistochemistry(IHC).In addition,the in situ expression of WISP1 in the GC tissues was determined by IHC,and the patients were accordingly classified into high-and low-expression groups.The correlation of WISP1 expression status with patient prognosis was then determined by univariate and multivariate Cox regression analyses.WISP1 was knocked down by RNA interference.The 50%inhibitory concentration of oxaliplatin was detected by CellTiter-Blue assay.RESULTS WISP1 levels at both the mRNA and protein levels were remarkably upregulated in GC tissues compared to normal tissues.Moreover,IHC revealed that WISP1 expression was associated with T stage and chemotherapy outcome,but not with lymph node metastasis,age,gender,histological grade,or histological type.GC patients with high WISP1 expression showed a poor overall survival.Multivariate survival analysis indicated that WISP1 was an important prognostic factor for GC patients.Mechanistically,knock-down of WISP1 expression enhanced sensitivity to oxaliplatin by reducing DNA repair and enhancing DNA damage.CONCLUSION Significantly upregulated WISP1 expression is associated with cancer progression,chemotherapy outcome,and prognosis in GC.Mechanistically,knock-down of WISP1 expression enhances oxaliplatin sensitivity by reducing DNA repair and enhancing DNA damage.WISP1 may be a potential therapeutic target for GC treatment or a potential biomarker for diagnosis and prognosis.
基金funded by Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai(No.PWZxq2014-01)Natural Science Foundation of China(No.81401428)the fund of the Academic Leaders Training Program of Pudong Health Bureau of Shanghai(No.PWRd2013-02)
文摘Objective:To explore the mechanism of Profilin-1 in regulating eNOS/NO pathway and its role in the development of myocardial hypertrophy.Methods:Spontaneously hypertensive rats(SHR) aged 5 weeks were injected with different adenovirus vectors to induce Profilin-1expression knockdown(SHR-I) or over express(SHR-H) or to use as control(SHR-C).All these treatment were compared with Wistar-Kyoto rats(SKY) treated with control adenovirus vectors(WKY-C).The same injection was executed at the sixth week during the experiment of 12 weeks.After experiment,the left ventricular weight-to-heart weight ratio(LVW/HW)and left ventricular long axis(LVLA) were measured.Meanwhile.NO contents in blood and myocardium,Profilin-1,eNOS and Caveolin-3 niRNA and protein levels and phosphorylated eNOS(P-eNOS) protein level in myocardium were determined.Results:Compared with WKY-C group,the SHR-C group was statistically higher in LVW/HW(0.79±0.03).LVLA(11.82±0.58 mm) and Profilin-1 niRNA and prolein level(P<0.05).but lower in NO content[(18.63±6.23) μmol/L| in blood and[(2.71±0.17) μmol/L]in myocardium).eNOS activity and Caveolin-3 expression(P<0.05).The over expressing Profilin-1 led SHR-H group to a higher value of LVW/HW[(0.93±0.03) mm and LVLA(14.17±0.69) mm]in comparison with SHR-C group(P<0.05).and to a lower value of NO content(in myocardium).eNOS activity and Caveolin-3 expression(P<0.05):however,this phenomenon was reversed by the knockdown Profilin-1 expression(SHR-I group).Conclusions:Profilin-1 expression,being negative in regulating Caveolin-3 expression and eNOS/NO pathway activity,promotes the development of myocardial hypertrophy which can be reversed by Profilin-1 silencing.
基金supported by the Natural Science Foundation of Jiangsu Province, China (BK20191483)the Natural Science Fund for Colleges and Universities in Jiangsu Province, China (20KJA180004)+2 种基金the Postgraduate Practice Innovation Program of Jiangsu Province, China (SJCX20_1339)the College Student Practice Innovation Program of Jiangsu Province, China (202111049104H, 202211049133H and 202211049138H)the Talent Introduction Research Project of Huaiyin Institute of Technology, China (Z301B16534)。
文摘Drought and salt stresses,the major environmental abiotic stresses in agriculture worldwide,affect plant growth,crop productivity,and quality.Therefore,developing crops with higher drought and salt tolerance is highly desirable.This study reported the isolation,biological function,and molecular characterization of a novel maspardin gene,OsMas1,from rice.The OsMas1 protein was localized to the cytoplasm.The expression levels of OsMas1 were up-regulated under mannitol,PEG6000,NaCl,and abscisic acid(ABA) treatments in rice.The OsMas1 gene was introduced into the rice cultivar Zhonghua 11(wild type,WT).OsMas1-overexpression(OsMas1-OE) plants exhibited significantly enhanced salt and drought tolerance;in contrast,OsMas1-interference(OsMas1-RNAi) plants exhibited decreased tolerance to salt and drought stresses,compared with WT.OsMas1-OE plants exhibited enhanced hypersensitivity,while OsMas1-RNAi plants showed less sensitivity to exogenous ABA treatment at both germination and post-germination stages.ABA,proline and K+ contents and superoxide dismutase(SOD),catalase(CAT),peroxidase(POD),and photosynthesis activities were significantly increased.In contrast,malonaldehyde(MDA),hydrogen peroxide(H2O2),superoxide anion radical(O2-··),and Na+ contents were significantly decreased in OsMas1-OE plants compared with OsMas1-RNAi and WT plants.Overexpression of OsMas1 up-regulated the genes involved in ABA signaling,proline biosynthesis,reactive oxygen species(ROS)-scavenging system,photosynthesis,and ion transport under salt and drought stresses.Our results indicate that the OsMas1 gene improves salt and drought tolerance in rice,which may serve as a candidate gene for enhancing crop resistance to abiotic stresses.
