Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immun...Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.展开更多
Crosstalk between the nervous system and cancer plays an important role in tumor metastasis yet is poorly understood.Recently,Padmanaban et al.demonstrated a novel mechanism for nerve-induced metastasis.Sensory nerve-...Crosstalk between the nervous system and cancer plays an important role in tumor metastasis yet is poorly understood.Recently,Padmanaban et al.demonstrated a novel mechanism for nerve-induced metastasis.Sensory nerve-derived substance P could induce apoptosis in breast cancer cells that overexpressed tachykinin receptors.Single-stranded RNAs(ssRNAs)leaking from dying cells subsequently interact with toll-like receptor 7(TLR7)on other cancer cells and finally promoted metastasis.This notable study displays a delicate loop between the nervous system and cancer and,more importantly,amplifies the conception of apoptosis-induced metastasis.Over the past years,a mass of breakthrough studies have proven the pivotal role of the nervous system in tumorigenesis and cancer progression thereby contributing to the creation of a new disciplinecancer neuroscience[1].Hanahan and Monje discussed in detail the interactions between the nervous system and tumors based on the theoretical framework of the cancer hallmarks,focused on nerve-mediated proliferation,angiogenesis,immune evasion,cell death resistance,and metastasis[2].展开更多
The published article titled“MicroRNA-98-5p Inhibits Cell Proliferation and Induces Cell Apoptosis in Hepatocellular Carcinoma via Targeting IGF2BP1”has been retracted from Oncology Research,Vol.25,No.7,2017,pp.1117...The published article titled“MicroRNA-98-5p Inhibits Cell Proliferation and Induces Cell Apoptosis in Hepatocellular Carcinoma via Targeting IGF2BP1”has been retracted from Oncology Research,Vol.25,No.7,2017,pp.1117–1127.展开更多
The aim of this study is to investigate the mechanism of magnesium isoglycyrrhizinate(MgIG)in the treatment of myocardial remodeling induced by isoproterenol(ISO)in mice.We assessed the impact of MgIG on ISO-induced m...The aim of this study is to investigate the mechanism of magnesium isoglycyrrhizinate(MgIG)in the treatment of myocardial remodeling induced by isoproterenol(ISO)in mice.We assessed the impact of MgIG on ISO-induced myocardial remodeling by activating the PI3K/AKT1 pathway.The cardiac function of mice was evaluated by echocardiography,revealing that MgIG could improve left ventricular function.Pathological staining analysis showed that MgIG could reduce the degree of myocardial injury caused by ISO.Serum data detected by ELISA demonstrated that MgIG could decrease the levels of CK-MB,MDA,and LDH while increasing the activity of GSH-Px.Western blotting analysis revealed that protein expression levels of Collagen I,BNP,Bax,cleaved caspase-3,p-PI3K,and p-AKT1 were decreased,whereas the protein expressions of Bcl-2,COX2,and SOD1 were increased upon MgIG treatment.However,the activation of the PI3K pathway reversed the cardioprotective effects of MgIG,as evidenced by the addition of PI3K activators.Taken together,our comprehensive results suggested that MgIG could improve ISO-induced myocardial remodeling,potentially through its mechanism of inhibiting the PI3K/AKT1 pathway to regulate apoptosis and oxidative stress.展开更多
Objective Emerging evidence suggests that exposure to ultrafine particulate matter(UPM,aerodynamic diameter<0.1μm)is associated with adverse cardiovascular events.Previous studies have found that Shenlian(SL)extra...Objective Emerging evidence suggests that exposure to ultrafine particulate matter(UPM,aerodynamic diameter<0.1μm)is associated with adverse cardiovascular events.Previous studies have found that Shenlian(SL)extract possesses anti-inflammatory and antiapoptotic properties and has a promising protective effect at all stages of the atherosclerotic disease process.In this study,we aimed to investigated whether SL improves UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis.Methods We established a mouse model of MI+UPM.Echocardiographic measurement,measurement of myocardialinfarct size,biochemical analysis,enzyme-linked immunosorbent assay(ELISA),histopathological analysis,Transferase dUTP Nick End Labeling(TUNEL),Western blotting(WB),Polymerase Chain Reaction(PCR)and so on were used to explore the anti-inflammatory and antiapoptotic effects of SL in vivo and in vitro.Results SL treatment can attenuate UPM-induced cardiac dysfunction by improving left ventricular ejection fraction,fractional shortening,and decreasing cardiac infarction area.SL significantly reduced the levels of myocardial enzymes and attenuated UPM-induced morphological alterations.Moreover,SL significantly reduced expression levels of the inflammatory cytokines IL-6,TNF-α,and MCP-1.UPM further increased the infiltration of macrophages in myocardial tissue,whereas SL intervention reversed this phenomenon.UPM also triggered myocardial apoptosis,which was markedly attenuated by SL treatment.The results of in vitro experiments revealed that SL prevented cell damage caused by exposure to UPM combined with hypoxia by reducing the expression of the inflammatory factor NF-κB and inhibiting apoptosis in H9c2 cells.Conclusion Overall,both in vivo and in vitro experiments demonstrated that SL attenuated UPMaggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis.The mechanisms were related to the downregulation of macrophages infiltrating heart tissues.展开更多
Diabetic kidney disease(DKD)has a high incidence and mortality rate and lacks effective preventive and therapeutic methods.Apoptosis is one of the main reasons for the occurrence and development of DKD.Mesenchymal ste...Diabetic kidney disease(DKD)has a high incidence and mortality rate and lacks effective preventive and therapeutic methods.Apoptosis is one of the main reasons for the occurrence and development of DKD.Mesenchymal stem cells(MSCs)have shown great promise in tissue regeneration for DKD treatment and have protective effects against DKD,including decreased blood glucose and urinary protein levels and improved renal function.MSCs can directly differ-entiate into kidney cells or act via paracrine mechanisms to reduce apoptosis in DKD by modulating signaling pathways.MSC-derived extracellular vesicles(MSC-EVs)mitigate apoptosis and DKD-related symptoms by transferring miRNAs to target cells or organs.However,studies on the regulatory mechanisms of MSCs and MSC-EVs in apoptosis in DKD are insufficient.This review compre-hensively examines the mechanisms of apoptosis in DKD and research progress regarding the roles of MSCs and MSC-EVs in the disease process.展开更多
Background Higher embryonic mortality,especially in aged breeding hens,is associated with insufficient hepatic functionality in maintaining redox homeostasis.Our previous study demonstrated that egg exosome-derived mi...Background Higher embryonic mortality,especially in aged breeding hens,is associated with insufficient hepatic functionality in maintaining redox homeostasis.Our previous study demonstrated that egg exosome-derived miRNAs may play a key role in modulating embryonic oxidation-reduction process,whereas the exact function and mechanism were still poorly understood.The present study aimed to investigate the roles of egg exosome miRNAs in maintaining dynamic equilibrium of free radicals and peroxide agents in embryonic liver,as well as demonstrate the specific mechanism using oxidative stress-challenged hepatocytes.Results Compared to 36-week-old breeding hens,decreased hatchability and increased embryonic mortality were observed in 65-week-old breeding hens.Meanwhile,the older group showed the increased MDA levels and decreased SOD and GSH-Px activities in embryonic liver,muscle and serum.Embryonic mortality was significantly positively correlated with MDA level and negatively correlated with GSH-Px activity in embryonic liver.In addition,363 differentially expressed genes(DEGs)were identified in embryonic liver,13 differentially expressed miRNAs(DE-miRNAs)were identified in egg exosomes.These DEGs and DE-miRNAs were involved in oxidoreductase activity,glutathione metabolic process,MAPK signaling pathway,apoptosis and autophagy.miRNA-mRNA network analysis further found that DEGs targeted by DE-miRNAs were mainly enriched in programmed cell death,such as apoptosis and autophagy.Wherein,MAPK10 with highest MCC and AUC values was significantly related to GSH-Px activity and MDA level,and served as the target gene of miR-145-5p based on dual luciferase reporter experiment and correlation analysis.Bioinformatics analysis found that miR-145-5p/MAPK10 axis might alleviate peroxide generation and apoptosis.In primary hepatocytes of chick embryos,miR-145-5p transfection significantly reversed H_(2)O_(2)-induced mitochondrial ROS increase,MAPK10,BAX and CASP3 overexpression and excessive apoptosis.Conclusion Exosome miR-145-5p in eggs could target MAPK10 and decrease mitochondrial ROS,attenuating oxidative damage and apoptosis in hepatocytes of chick embryos.These findings may provide new theoretical basis for the improvement of maternal physiological status to maintain embryonic redox homeostasis by nutritional or genetic modifications.展开更多
Background:The outcomes of pediatric patients with acute lymphoblastic leukemia(ALL)remain far less than favorable.While apigenin is an anti-cancer agent,studies on the mechanism by which it regulates ALL cell cycle p...Background:The outcomes of pediatric patients with acute lymphoblastic leukemia(ALL)remain far less than favorable.While apigenin is an anti-cancer agent,studies on the mechanism by which it regulates ALL cell cycle progression are inadequate.Ferroptosis and AMP-activated protein kinase(AMPK)signaling are important processes for ALL patients.However,it remains unclear whether apigenin works by affecting AMPK and apoptosis.Materials and Methods:SUP-B15 and T-cell Jurkat ALL cells were treated with apigenin,and cell viability and apoptosis were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assays,respectively.The thiobarbituric acid-reactive substances(TBARS)assay was used to evaluate lipid peroxidation.Intracellular Fe2+levels were measured using a commercial kit.Corresponding proteins were detected by western blotting.Results:Results showed that apigenin reduced cell viability and the levels of Ki67 and proliferating cell nuclear antigen(PCNA)expression in a concentration-dependent manner in both types of ALL cells.Apigenin also exerted anti-apoptotic effects on SUP-B15 and Jurkat cells.Apigenin activated AMP-activated protein kinase(AMPK)signaling and induced ferroptosis,and those effects were attenuated by inhibition of AMPK.Eventually,the reduced cell proliferation and increased cell apoptosis caused by apigenin in ALL cells were partly abolished by AMPK inhibition.Conclusion:In summary,apigenin exerted anti-leukemia activity in ALL cells,and that effect was partially achieved by activation of AMPK signaling.Our findings suggest apigenin as a potential drug for treatment of ALL.展开更多
OBJECTIVE:To investigate the effect and mechanism of Yishen Tongluo formula(益肾通络方,YSTLF)in streptozotocin-induced diabetic kidney disease mice(DKD)mice.METHODS:Thirty Institute of Cancer Research mice(specific pa...OBJECTIVE:To investigate the effect and mechanism of Yishen Tongluo formula(益肾通络方,YSTLF)in streptozotocin-induced diabetic kidney disease mice(DKD)mice.METHODS:Thirty Institute of Cancer Research mice(specific pathogen free,SPF grade)were divided into five groups(n=6 per group):control,DKD model,DKD model with YSTLF(4.9 g/kg),DKD model with YSTLF(9.8 g/kg),and DKD model with captopril.DKD was induced through a single intraperitoneal injection of streptozotocin(150 mg/kg).Body weight,fasting blood glucose and urine C-peptide levels were measured to assess metabolic regulation by YSTLF.Renal function was evaluated using indicators of glomerular and tubular health.Liver function was assessed by measuring aspartate aminotransferase and alanine aminotransferase levels.Renal pathological changes were examined using hematoxylin/eosin staining and transmission electron microscopy.Inflammatory and apoptosis-related factors were analyzed through enzyme-linked immunosorbent assay,immunohistochemistry,and Western blot analysis.RESULTS:In DKD mice,fasting blood glucose,Cpeptide,24-hour urine protein(UP)levels,and renal damage were elevated,accompanied by increased inflammation and apoptosis.YSTLF significantly reduced 24-hour UP and C-peptide levels and improved kidney and liver function in DKD mice.YSTLF also mitigated glomerular hypertrophy,basement membrane thickening,and podocyte foot process effacement.It upregulated the expression of the podocyte marker podocalyxin.Furthermore,YSTLF alleviated inflammation and apoptosis,likely by reducing the overexpression of monocyte chemoattractant protein(MCP-1),Bax,and Caspase-3 in the kidneys of DKD mice.CONCLUSIONS:These findings suggest that YSTLF ameliorates kidney injury by modulating the expression of inflammatory cytokine MCP-1 and the Bax/Caspase-3 apoptosis pathway,providing a potential therapeutic approach for DKD.展开更多
Artemisia annua L.is a medicinal herb with multiple therapeutic applications,whereas its antiinfluenza A virus(IAV)efficiency and mechanism of action are still unclear.Here,we investigated the inhibition activity and ...Artemisia annua L.is a medicinal herb with multiple therapeutic applications,whereas its antiinfluenza A virus(IAV)efficiency and mechanism of action are still unclear.Here,we investigated the inhibition activity and mechanism of A.annua leaf methanol extracts(AALME)against IAV in vitro and in vivo.Our results revealed that AALME exhibits potent anti-IAV activity by interacting with IAV particles.Mechanistically,AALME directly targets the IAV nucleoprotein(NP)protein and abolishes the nuclear import of IAV NP.AALME profoundly suppresses IAV-induced mitochondrial apoptosis via suppressing ROS-mediated AIF-dependent pathways.More importantly,we found that AALME plays a crucial role in protecting mice from IAV infection and mitigating IAV pathogenicity.This current work provides mechanistic insight into the mechanism by which AALME controls IAV infection in vitro and in vivo,potentially contributing to the development of antiviral treatments for IAV infection.展开更多
Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-asso...Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.展开更多
Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ab...Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ability,the arginine-glycine-aspartic(RGD)peptide and the epidermal growth factor receptor interference(EGFRi)peptide were fused with MAP30,which was named ELRL-MAP30.The efficiency of targeted therapy for triple-negative breast cancer(TNBC)MDA-MB-231 cells,which lack the expression of estrogen receptor(ER),Progesterone receptor(PgR)and human epidermal growth factor receptor-2(HER2),is limited.In this study,we focus on exploring the effect and mechanism of ELRL-MAP30 on TNBC MDA-MB-231 cells.First,we discovered that ELRL-MAP30 significantly inhibited the migration and invasion of MDA-MB-231 cells and induced MDA-MB-231 cell apoptosis.Moreover,ELRL-MAP30 treatment resulted in a significant increase in Bax expression and a decrease in Bcl-2 expression.Furthermore,ELRL-MAP30 triggered apoptosis via the Fak/EGFR/Erk and Ilk/Akt signaling pathways.In addition,recombinant ELRL-MAP30 can inhibit chicken embryonic angiogenesis,and also inhibit the tube formation ability of human umbilical vein endothelial cells(HUVECs),indicating its potential therapeutic effects on tumor angiogenesis.Collectively,these results indicate that ELRL-MAP30 has significant tumor-targeting properties in MDA-MB-231 cancer cells and reveals potential therapeutic effects on angiogenesis.These findings indicate the potential role of ELRL-MAP30 in the targeted treatment of the TNBC cell line MDA-MB-231.展开更多
Morusin is a flavonoid compound isolated and extracted from the root bark of Morus alba L.Studies have reported that morusin exerts anti-tumor effects by inhibiting cancer cell invasion and proliferation,as well as in...Morusin is a flavonoid compound isolated and extracted from the root bark of Morus alba L.Studies have reported that morusin exerts anti-tumor effects by inhibiting cancer cell invasion and proliferation,as well as inducing tumor cell apoptosis.This article comprehensively reviews recent research on the anti-tumor effects of morusin and its related molecular mechanisms,aiming to provide theoretical support for further studies and new drug development of morusin.展开更多
Objective:To investigate the protective effects of Lepidium draba L.(L.draba)on cyclophosphamide(CP)-induced hepatotoxicity and nephrotoxicity in rats.Methods:A total of 36 rats were divided into six groups as follows...Objective:To investigate the protective effects of Lepidium draba L.(L.draba)on cyclophosphamide(CP)-induced hepatotoxicity and nephrotoxicity in rats.Methods:A total of 36 rats were divided into six groups as follows:the sham control group,the CP group(CP 100 mg/kg i.p.on days 1,7,14,21,28,and 35),the CP groups treated with L.draba extract(100,200 and 400 mg/kg of L.draba extract for 28 d),and the L.draba extract alone group(400 mg/kg of L.draba extract for 28 d).Serum parameters of renal and hepatic function,as well as pro-inflammatory and anti-inflammatory cytokines associated with liver and kidney damage were measured.Moreover,Bax,Bcl-2,and caspase-3 gene expression and histopathological changes were assessed.Results:L.draba extract alleviated CP-induced hepatotoxicity and nephrotoxicity by decreasing nitric oxide,TBARS,IL-6,TNF-α,and IL-1βlevels,as well as increasing superoxide dismutase,catalase and glutathione peroxidase activities,and FRAP,MIF,and TGF-βlevels.In addition,the extract downregulated the expression of pro-apoptotic genes(Bax and caspase-3)and mitigated the destruction of glomeruli and renal tubules as well as the degeneration of hepatocytes.Conclusions:L.draba extract can protect hepatic and renal structure and function against CP-induced toxicities,and may be used as a therapeutic agent for CP-induced hepatotoxicity and nephrotoxicity.展开更多
Ferroptosis, an iron-dependent type of cell death, is being considered for new clinical treatments of malignant tumors that are difficult to treat with apoptosis inducers. Although several reports have attempted to in...Ferroptosis, an iron-dependent type of cell death, is being considered for new clinical treatments of malignant tumors that are difficult to treat with apoptosis inducers. Although several reports have attempted to increase the sensitivity of cells to cell death by combining ferroptosis and apoptosis inducers using a single treatment, detailed elucidation of the respective mechanisms of ferroptosis and apoptosis during cell death remains unclear. Here, we evaluated combined treatment effectiveness using the apoptosis-sensitive rat insulinoma INS-1 cell lines. DNA laddering, an indicator of camptothecin (CPT)-induced apoptosis, was abolished by adding RSL3 and ML-162, but not erastin. We found that when the cells were treated with the apoptosis inducer CPT or the ferroptosis inducer RSL3, respectively, the degree of cytotoxicity observed increased dose-dependently. However, a combined CPT and RSL3 treatment did not show a synergistic decrease in cell viability. Camptothecin did not significantly affect increases in intracellular lipid peroxidation and reactive oxygen species or increases in mitochondrial and cytoplasmic free iron levels that were induced by treatment with RSL3 alone. Moreover, deferoxamine and α-tocopherol were found to inhibit RSL3-induced cytotoxicity but did not protect against CPT or CPT and RSL3-induced cytotoxicity. Finally, the exogenous addition of tert-butyl hydroperoxide inhibited DNA ladder formation that is induced by CPT, while the addition of hydrogen peroxide or ferrous ammonium sulfate had no effect. Taken together, these results suggest that lipid peroxides generated during ferroptosis may suppress cell death induced by apoptotic mechanisms.展开更多
D-D’-A type aza-borondipyrromethenes(aza-BODIPYs)were prepared by Suzuki cross-coupling reaction.Photothermal conversion efficiency of self-assemble aza-BODIPY-based nanoparticles(DA-azaBDP-NPs)with NIR-Ⅱ emission(...D-D’-A type aza-borondipyrromethenes(aza-BODIPYs)were prepared by Suzuki cross-coupling reaction.Photothermal conversion efficiency of self-assemble aza-BODIPY-based nanoparticles(DA-azaBDP-NPs)with NIR-Ⅱ emission(λ_(em)=1065 nm)was 37.2%under near infrared(NIR)irradiation,and the outstanding cytotoxicity was triggered by coexistence of DA-azaBDP-NPs and the NIR irradiation,with the decrease of glioblastoma migration and the inhibition of glioblastoma proliferation.DA-azaBDP-NPs could promote glioblastoma autophagy and accelerate the process of cell death.The photothermal therapy(PTT)of DAazaBDP-NPs can effectively induce glioblastoma death by apoptosis under the NIR irradiation,which is highly promising to be applied in vivo experiments of brain.展开更多
Background Ochratoxin A(OTA)is a toxin widely found in aquafeed ingredients,and hypoxia is a common prob-lem in fish farming.In practice,aquatic animals tend to be more sensitive to hypoxia while feeds are contaminate...Background Ochratoxin A(OTA)is a toxin widely found in aquafeed ingredients,and hypoxia is a common prob-lem in fish farming.In practice,aquatic animals tend to be more sensitive to hypoxia while feeds are contaminated with OTA,but no studies exist in this area.This research investigated the multiple biotoxicities of OTA and hypoxia combined on the liver of grass carp and explored the mitigating effect of curcumin(CUR).Methods A total of 720 healthy juvenile grass carp(11.06±0.05 g)were selected and assigned randomly to 4 experi-mental groups:control group(without OTA and CUR),1.2 mg/kg OTA group,400 mg/kg CUR group,and 1.2 mg/kg OTA+400 mg/kg CUR group with three replicates each for 60 d.Subsequently,32 fish were selected,divided into nor-moxia(18 fish)and hypoxia(18 fish)groups,and subjected to hypoxia stress for 96 h.Results CUR can attenuate histopathological damage caused by coming to OTA and hypoxia by reducing vacu-olation and nuclear excursion.The alleviation of this damage was associated with the attenuation of apoptosis in the mitochondrial pathway by decreasing the expression of the pro-apoptotic proteins Caspase 3,8,9,Bax,and Apaf1 while increasing the expression of the anti-apoptotic protein Bcl-2,and attenuation of endoplasmic reticulum stress(ERS)by reducing Grp78 expression and chop levels.This may be attributed to the fact that the addi-tion of CUR increased the levels of catalase(CAT)and glutathione reductase(GSH),increased antioxidant capacity,and ensured the proper functioning of respiratory chain complexes I and II,which in turn reduced the high produc-tion of reactive oxygen species(ROS),thus alleviating apoptosis and ERS.Conclusions In conclusion,our data demonstrate the effectiveness of CUR in attenuating liver injury caused by the combination of OTA and hypoxia.This study confirms the feasibility and efficacy of adding natural products to mitigate toxic damage to aquatic animals.展开更多
Background Heat stress(HS)poses a significant threat to male goat reproduction.Sertoli cells(SCs)provide both structural and nutritional support necessary for germ cells.HS induces physiological and biochemical change...Background Heat stress(HS)poses a significant threat to male goat reproduction.Sertoli cells(SCs)provide both structural and nutritional support necessary for germ cells.HS induces physiological and biochemical changes in SCs.Nevertheless,the molecular mechanisms involved are still not fully understood.Melatonin is a classic antioxidant that can alleviate HS-induced male reproductive damage.However,the underlying molecular mechanisms by which melatonin mitigates damage to goat testicular SCs remain unclear and require further investigation.Results In this study,an in vivo heat stress model was established in goats.The results showed that HS exposure led to testicular injury,abnormal spermatogenesis and apoptosis of SCs.To elucidate the mechanism of HS-induced SC apoptosis,primary SCs were isolated and cultured from goat testes,then exposed to HS.HS exposure increased the production of reactive oxygen species(ROS),decreased adenosine triphosphate(ATP)synthesis,and reduced mitochondrial membrane potential in SCs.Additionally,HS increased the expression of mitochondrial fission proteins 1(FIS1)and dynamin-related protein 1(DRP1)while decreasing the expression of mitochondrial fusion proteins Mitofusin 1(MFN1),Mitofusin 2(MFN2),and optic atrophy 1(OPA1).This resulted in excessive mitochondrial fission and mitochondria-dependent apoptosis.Mdivi-1(DRP1 inhibitor)reduces mitochondria-dependent apoptosis by inhibiting excessive mitochondrial fission.Mitochondrial fission is closely related to mitophagy.HS activated upstream mitophagy but inhibited autophagic flux,disrupting mitophagy and exacerbating mitochondria-dependent apoptosis.Finally,the classical antioxidant melatonin was shown to reduce mitochondria-dependent apoptosis in SCs exposed to HS by decreasing ROS levels,restoring mitochondrial homeostasis,and normalizing mitophagy.Conclusions In summary,these findings indicated that the mechanism of HS-induced mitochondria-dependent apoptosis in SCs is mediated by hyperactivation of the ROS-DRP1-mitochondrial fission axis and inhibition of mitochondrial autophagy.Melatonin inhibited HS-induced mitochondria-dependent apoptosis in SCs by restoring mitochondrial homeostasis.This study enhances the understanding of the mechanisms through which heat stress triggers apoptosis and provides a vision for the development of drugs against HS by targeting mitochondria in goats.展开更多
Premature ovarian insufficiency(POI)caused by chemotherapy is a common complication in female cancer survivors of childbearing age.Traditional methods,including mesenchymal stem cell(MSC)transplant and hormone replace...Premature ovarian insufficiency(POI)caused by chemotherapy is a common complication in female cancer survivors of childbearing age.Traditional methods,including mesenchymal stem cell(MSC)transplant and hormone replacement therapy,have limited clinical application because of their drawbacks,and more methods need to be developed.In the current study,the potential effects and underlying mechanisms of human umbilical cord MSC-derived extracellular vesicles(h UCMSC-EVs)were investigated in a cisplatin(CDDP)-induced POI mouse model and a human granulosa cell(GC)line.The results showed that h UCMSC-EVs significantly attenuated body weight loss,ovarian weight loss,ovary atrophy,and follicle loss in moderate-dose(1.5 mg/kg)CDDP-induced POI mice,similar to the effects observed with h UCMSCs.We further found that the h UCMSCEVs inhibited CDDP-induced ovarian GC apoptosis by upregulating anti-apoptotic mi RNA levels in GCs,thereby downregulating the m RNA levels of multiple pro-apoptotic genes.In general,our findings indicate that the moderate-dose chemotherapy may be a better choice for clinical oncotherapy,considering effective rescue of the oncotherapy-induced ovarian damage with h UCMSC-EVs.Additionally,multiple mi RNAs in h UCMSC-EVs may potentially be used to inhibit the chemotherapy-induced ovarian GC apoptosis,thereby restoring ovarian function and improving the life quality of female cancer patients.展开更多
Pristimerin,which is one of the compounds present in Celastraceae and Hippocrateaceae,has antitumor effects.However,its mechanism of action in esophageal squamous cell carcinoma(ESCC)remains unclear.This study aims to...Pristimerin,which is one of the compounds present in Celastraceae and Hippocrateaceae,has antitumor effects.However,its mechanism of action in esophageal squamous cell carcinoma(ESCC)remains unclear.This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo.The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays.Cell apoptosis was evaluated by flow cytometry.Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction(qRT-PCR),Western blotting,and immunohistochemistry.RNA sequencing(RNA-Seq)was employed to identify significantly differentially expressed genes(DEGs).Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin's effect.Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo.Pristimerin inhibited cell growth and induced apoptosis in ESCC cells.Upregulation of Noxa was crucial for pristimerin-induced apoptosis.Pristimerin activated the Forkhead box O3a(FoxO3a)signaling pathway and triggered FoxO3a recruitment to the Noxa promoter,leading to Noxa transcription.Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis.Pristimerin treatment suppressed xenograft tumors in nude mice,but these effects were largely negated in Noxa-KO tumors.Furthermore,the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa.This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation.These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82573045,82460602,82560459)the Hainan Provincial Graduate Student Innovative Research Project(No.Qhys2024-440).
文摘Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.
文摘Crosstalk between the nervous system and cancer plays an important role in tumor metastasis yet is poorly understood.Recently,Padmanaban et al.demonstrated a novel mechanism for nerve-induced metastasis.Sensory nerve-derived substance P could induce apoptosis in breast cancer cells that overexpressed tachykinin receptors.Single-stranded RNAs(ssRNAs)leaking from dying cells subsequently interact with toll-like receptor 7(TLR7)on other cancer cells and finally promoted metastasis.This notable study displays a delicate loop between the nervous system and cancer and,more importantly,amplifies the conception of apoptosis-induced metastasis.Over the past years,a mass of breakthrough studies have proven the pivotal role of the nervous system in tumorigenesis and cancer progression thereby contributing to the creation of a new disciplinecancer neuroscience[1].Hanahan and Monje discussed in detail the interactions between the nervous system and tumors based on the theoretical framework of the cancer hallmarks,focused on nerve-mediated proliferation,angiogenesis,immune evasion,cell death resistance,and metastasis[2].
文摘The published article titled“MicroRNA-98-5p Inhibits Cell Proliferation and Induces Cell Apoptosis in Hepatocellular Carcinoma via Targeting IGF2BP1”has been retracted from Oncology Research,Vol.25,No.7,2017,pp.1117–1127.
基金Jiangxi Provincial Department of Education Science and Technology Project(Grant No.GJJ2401615)Jiangxi Provincial Department of Education Teaching Reform Project(Grant No.JXJG-24-15-15).
文摘The aim of this study is to investigate the mechanism of magnesium isoglycyrrhizinate(MgIG)in the treatment of myocardial remodeling induced by isoproterenol(ISO)in mice.We assessed the impact of MgIG on ISO-induced myocardial remodeling by activating the PI3K/AKT1 pathway.The cardiac function of mice was evaluated by echocardiography,revealing that MgIG could improve left ventricular function.Pathological staining analysis showed that MgIG could reduce the degree of myocardial injury caused by ISO.Serum data detected by ELISA demonstrated that MgIG could decrease the levels of CK-MB,MDA,and LDH while increasing the activity of GSH-Px.Western blotting analysis revealed that protein expression levels of Collagen I,BNP,Bax,cleaved caspase-3,p-PI3K,and p-AKT1 were decreased,whereas the protein expressions of Bcl-2,COX2,and SOD1 were increased upon MgIG treatment.However,the activation of the PI3K pathway reversed the cardioprotective effects of MgIG,as evidenced by the addition of PI3K activators.Taken together,our comprehensive results suggested that MgIG could improve ISO-induced myocardial remodeling,potentially through its mechanism of inhibiting the PI3K/AKT1 pathway to regulate apoptosis and oxidative stress.
基金supported by CACMS Innovation Fund(No CI2021A04611,CI2021A05106)Scientific and technological innovation project of China Academy of Chinese Medical Sciences(CI2021B015)+1 种基金Scientific and technological innovation project of China Academy of Chinese Medical Sciences(CI2023E001TS01)Fundamental research funds for the central public welfare research institutes(L2022035).
文摘Objective Emerging evidence suggests that exposure to ultrafine particulate matter(UPM,aerodynamic diameter<0.1μm)is associated with adverse cardiovascular events.Previous studies have found that Shenlian(SL)extract possesses anti-inflammatory and antiapoptotic properties and has a promising protective effect at all stages of the atherosclerotic disease process.In this study,we aimed to investigated whether SL improves UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis.Methods We established a mouse model of MI+UPM.Echocardiographic measurement,measurement of myocardialinfarct size,biochemical analysis,enzyme-linked immunosorbent assay(ELISA),histopathological analysis,Transferase dUTP Nick End Labeling(TUNEL),Western blotting(WB),Polymerase Chain Reaction(PCR)and so on were used to explore the anti-inflammatory and antiapoptotic effects of SL in vivo and in vitro.Results SL treatment can attenuate UPM-induced cardiac dysfunction by improving left ventricular ejection fraction,fractional shortening,and decreasing cardiac infarction area.SL significantly reduced the levels of myocardial enzymes and attenuated UPM-induced morphological alterations.Moreover,SL significantly reduced expression levels of the inflammatory cytokines IL-6,TNF-α,and MCP-1.UPM further increased the infiltration of macrophages in myocardial tissue,whereas SL intervention reversed this phenomenon.UPM also triggered myocardial apoptosis,which was markedly attenuated by SL treatment.The results of in vitro experiments revealed that SL prevented cell damage caused by exposure to UPM combined with hypoxia by reducing the expression of the inflammatory factor NF-κB and inhibiting apoptosis in H9c2 cells.Conclusion Overall,both in vivo and in vitro experiments demonstrated that SL attenuated UPMaggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis.The mechanisms were related to the downregulation of macrophages infiltrating heart tissues.
基金Supported by Science and Technology Research Program of Jilin Provincial Department of Education,No.JJKH20231218KJProject of the Jilin Provincial Administration of Traditional Chinese Medicine,No.2024111.
文摘Diabetic kidney disease(DKD)has a high incidence and mortality rate and lacks effective preventive and therapeutic methods.Apoptosis is one of the main reasons for the occurrence and development of DKD.Mesenchymal stem cells(MSCs)have shown great promise in tissue regeneration for DKD treatment and have protective effects against DKD,including decreased blood glucose and urinary protein levels and improved renal function.MSCs can directly differ-entiate into kidney cells or act via paracrine mechanisms to reduce apoptosis in DKD by modulating signaling pathways.MSC-derived extracellular vesicles(MSC-EVs)mitigate apoptosis and DKD-related symptoms by transferring miRNAs to target cells or organs.However,studies on the regulatory mechanisms of MSCs and MSC-EVs in apoptosis in DKD are insufficient.This review compre-hensively examines the mechanisms of apoptosis in DKD and research progress regarding the roles of MSCs and MSC-EVs in the disease process.
基金supported by China Agriculture Research System of MOF and MARA(CARS-40)the National Natural Science Foundation of China(32302776)。
文摘Background Higher embryonic mortality,especially in aged breeding hens,is associated with insufficient hepatic functionality in maintaining redox homeostasis.Our previous study demonstrated that egg exosome-derived miRNAs may play a key role in modulating embryonic oxidation-reduction process,whereas the exact function and mechanism were still poorly understood.The present study aimed to investigate the roles of egg exosome miRNAs in maintaining dynamic equilibrium of free radicals and peroxide agents in embryonic liver,as well as demonstrate the specific mechanism using oxidative stress-challenged hepatocytes.Results Compared to 36-week-old breeding hens,decreased hatchability and increased embryonic mortality were observed in 65-week-old breeding hens.Meanwhile,the older group showed the increased MDA levels and decreased SOD and GSH-Px activities in embryonic liver,muscle and serum.Embryonic mortality was significantly positively correlated with MDA level and negatively correlated with GSH-Px activity in embryonic liver.In addition,363 differentially expressed genes(DEGs)were identified in embryonic liver,13 differentially expressed miRNAs(DE-miRNAs)were identified in egg exosomes.These DEGs and DE-miRNAs were involved in oxidoreductase activity,glutathione metabolic process,MAPK signaling pathway,apoptosis and autophagy.miRNA-mRNA network analysis further found that DEGs targeted by DE-miRNAs were mainly enriched in programmed cell death,such as apoptosis and autophagy.Wherein,MAPK10 with highest MCC and AUC values was significantly related to GSH-Px activity and MDA level,and served as the target gene of miR-145-5p based on dual luciferase reporter experiment and correlation analysis.Bioinformatics analysis found that miR-145-5p/MAPK10 axis might alleviate peroxide generation and apoptosis.In primary hepatocytes of chick embryos,miR-145-5p transfection significantly reversed H_(2)O_(2)-induced mitochondrial ROS increase,MAPK10,BAX and CASP3 overexpression and excessive apoptosis.Conclusion Exosome miR-145-5p in eggs could target MAPK10 and decrease mitochondrial ROS,attenuating oxidative damage and apoptosis in hepatocytes of chick embryos.These findings may provide new theoretical basis for the improvement of maternal physiological status to maintain embryonic redox homeostasis by nutritional or genetic modifications.
基金supported by The National Natural Science Foundation of China(No.31902283)Research Foundation for Master students at the Affiliated Hospital of Zunyi Medical College(No.22-2018).
文摘Background:The outcomes of pediatric patients with acute lymphoblastic leukemia(ALL)remain far less than favorable.While apigenin is an anti-cancer agent,studies on the mechanism by which it regulates ALL cell cycle progression are inadequate.Ferroptosis and AMP-activated protein kinase(AMPK)signaling are important processes for ALL patients.However,it remains unclear whether apigenin works by affecting AMPK and apoptosis.Materials and Methods:SUP-B15 and T-cell Jurkat ALL cells were treated with apigenin,and cell viability and apoptosis were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assays,respectively.The thiobarbituric acid-reactive substances(TBARS)assay was used to evaluate lipid peroxidation.Intracellular Fe2+levels were measured using a commercial kit.Corresponding proteins were detected by western blotting.Results:Results showed that apigenin reduced cell viability and the levels of Ki67 and proliferating cell nuclear antigen(PCNA)expression in a concentration-dependent manner in both types of ALL cells.Apigenin also exerted anti-apoptotic effects on SUP-B15 and Jurkat cells.Apigenin activated AMP-activated protein kinase(AMPK)signaling and induced ferroptosis,and those effects were attenuated by inhibition of AMPK.Eventually,the reduced cell proliferation and increased cell apoptosis caused by apigenin in ALL cells were partly abolished by AMPK inhibition.Conclusion:In summary,apigenin exerted anti-leukemia activity in ALL cells,and that effect was partially achieved by activation of AMPK signaling.Our findings suggest apigenin as a potential drug for treatment of ALL.
基金National Key Research and Development Plan:Evidence-Based Evaluation and Therapeutic Mechanism Cooperation Study of Yishen Tongluo Formula for Preventing Diabetes Kidney Disease(Phase 3)(No.2020YFE0201800)Key Science and Technology Projects of Henan Province:Research on Innovative Drug Cooperation of Traditional Chinese Medicine Yishen Tongluo Concentrated Pills(益肾通络浓缩丸)(No.221111520300)+1 种基金Key scientific and technological projects of Henan province:Study on the Pharmacodynamic Mechanism of Yishen Tongluo Formula in Treatment of Diabetes Kidney Disease based on the Interaction Regulation of Protein Phosphorylation and Acylation Modification(No.212102310347)to WU SuhuiNational Natural Science Foundation of China:the Mechanism of Yishen Tongluo Formula Intervention in Diabetic Kidney Disease based on(Yin-Yang-1/Nuclear Factor Erythroid 2-Related Factor 2 Mediated Endothelial Podocyte Interaction Response(No.82474495)to XU Jiangyan。
文摘OBJECTIVE:To investigate the effect and mechanism of Yishen Tongluo formula(益肾通络方,YSTLF)in streptozotocin-induced diabetic kidney disease mice(DKD)mice.METHODS:Thirty Institute of Cancer Research mice(specific pathogen free,SPF grade)were divided into five groups(n=6 per group):control,DKD model,DKD model with YSTLF(4.9 g/kg),DKD model with YSTLF(9.8 g/kg),and DKD model with captopril.DKD was induced through a single intraperitoneal injection of streptozotocin(150 mg/kg).Body weight,fasting blood glucose and urine C-peptide levels were measured to assess metabolic regulation by YSTLF.Renal function was evaluated using indicators of glomerular and tubular health.Liver function was assessed by measuring aspartate aminotransferase and alanine aminotransferase levels.Renal pathological changes were examined using hematoxylin/eosin staining and transmission electron microscopy.Inflammatory and apoptosis-related factors were analyzed through enzyme-linked immunosorbent assay,immunohistochemistry,and Western blot analysis.RESULTS:In DKD mice,fasting blood glucose,Cpeptide,24-hour urine protein(UP)levels,and renal damage were elevated,accompanied by increased inflammation and apoptosis.YSTLF significantly reduced 24-hour UP and C-peptide levels and improved kidney and liver function in DKD mice.YSTLF also mitigated glomerular hypertrophy,basement membrane thickening,and podocyte foot process effacement.It upregulated the expression of the podocyte marker podocalyxin.Furthermore,YSTLF alleviated inflammation and apoptosis,likely by reducing the overexpression of monocyte chemoattractant protein(MCP-1),Bax,and Caspase-3 in the kidneys of DKD mice.CONCLUSIONS:These findings suggest that YSTLF ameliorates kidney injury by modulating the expression of inflammatory cytokine MCP-1 and the Bax/Caspase-3 apoptosis pathway,providing a potential therapeutic approach for DKD.
基金supported by grants from the National Natural Science Foundation of China(32170937)Shenzhen Medical Research Fund(SMRF,A2303015)+3 种基金Pearl River Talent Project of Guangdong Province(2021QN02Y426)Shenzhen Peacock Plan Project(827/000655)to Liang Yethe Yunnan Provincial Key Areas Science and Technology Plan Project(202303AC100025)Yunnan Scholar of Yunling(YNWRYLXZ-2019-019)to Rongping Zhang.
文摘Artemisia annua L.is a medicinal herb with multiple therapeutic applications,whereas its antiinfluenza A virus(IAV)efficiency and mechanism of action are still unclear.Here,we investigated the inhibition activity and mechanism of A.annua leaf methanol extracts(AALME)against IAV in vitro and in vivo.Our results revealed that AALME exhibits potent anti-IAV activity by interacting with IAV particles.Mechanistically,AALME directly targets the IAV nucleoprotein(NP)protein and abolishes the nuclear import of IAV NP.AALME profoundly suppresses IAV-induced mitochondrial apoptosis via suppressing ROS-mediated AIF-dependent pathways.More importantly,we found that AALME plays a crucial role in protecting mice from IAV infection and mitigating IAV pathogenicity.This current work provides mechanistic insight into the mechanism by which AALME controls IAV infection in vitro and in vivo,potentially contributing to the development of antiviral treatments for IAV infection.
基金supported by the National Natural Science Foundation of China,Nos.82071008(to BL)and 82004001(to XJ)Medical Science and Technology Program of Health Commission of Henan Province,No.LHGJ20210072(to RQ)Science and Technology Department of Henan Province,No.212102310307(to XJ)。
文摘Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.
文摘Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ability,the arginine-glycine-aspartic(RGD)peptide and the epidermal growth factor receptor interference(EGFRi)peptide were fused with MAP30,which was named ELRL-MAP30.The efficiency of targeted therapy for triple-negative breast cancer(TNBC)MDA-MB-231 cells,which lack the expression of estrogen receptor(ER),Progesterone receptor(PgR)and human epidermal growth factor receptor-2(HER2),is limited.In this study,we focus on exploring the effect and mechanism of ELRL-MAP30 on TNBC MDA-MB-231 cells.First,we discovered that ELRL-MAP30 significantly inhibited the migration and invasion of MDA-MB-231 cells and induced MDA-MB-231 cell apoptosis.Moreover,ELRL-MAP30 treatment resulted in a significant increase in Bax expression and a decrease in Bcl-2 expression.Furthermore,ELRL-MAP30 triggered apoptosis via the Fak/EGFR/Erk and Ilk/Akt signaling pathways.In addition,recombinant ELRL-MAP30 can inhibit chicken embryonic angiogenesis,and also inhibit the tube formation ability of human umbilical vein endothelial cells(HUVECs),indicating its potential therapeutic effects on tumor angiogenesis.Collectively,these results indicate that ELRL-MAP30 has significant tumor-targeting properties in MDA-MB-231 cancer cells and reveals potential therapeutic effects on angiogenesis.These findings indicate the potential role of ELRL-MAP30 in the targeted treatment of the TNBC cell line MDA-MB-231.
基金Supported by Heilongjiang Provincial Key Research and Development Program(Guided Category)(GZ20220039)Central Government Funds for Local University Reform and Development(Talent Cultivation Program)(2020GSP16).
文摘Morusin is a flavonoid compound isolated and extracted from the root bark of Morus alba L.Studies have reported that morusin exerts anti-tumor effects by inhibiting cancer cell invasion and proliferation,as well as inducing tumor cell apoptosis.This article comprehensively reviews recent research on the anti-tumor effects of morusin and its related molecular mechanisms,aiming to provide theoretical support for further studies and new drug development of morusin.
基金supported by the Basic Research Joint Special General Project of Yunnan Provincial Local Universities(part)(No:202301BA070001-029,202301BA070001-044)Yunnan Province High-level Scientific and Technological Talents and Innovation Team Selection Special Young and Middle-aged Academic and Technical Leaders Reserve Talent Project(No:202405AC350067).
文摘Objective:To investigate the protective effects of Lepidium draba L.(L.draba)on cyclophosphamide(CP)-induced hepatotoxicity and nephrotoxicity in rats.Methods:A total of 36 rats were divided into six groups as follows:the sham control group,the CP group(CP 100 mg/kg i.p.on days 1,7,14,21,28,and 35),the CP groups treated with L.draba extract(100,200 and 400 mg/kg of L.draba extract for 28 d),and the L.draba extract alone group(400 mg/kg of L.draba extract for 28 d).Serum parameters of renal and hepatic function,as well as pro-inflammatory and anti-inflammatory cytokines associated with liver and kidney damage were measured.Moreover,Bax,Bcl-2,and caspase-3 gene expression and histopathological changes were assessed.Results:L.draba extract alleviated CP-induced hepatotoxicity and nephrotoxicity by decreasing nitric oxide,TBARS,IL-6,TNF-α,and IL-1βlevels,as well as increasing superoxide dismutase,catalase and glutathione peroxidase activities,and FRAP,MIF,and TGF-βlevels.In addition,the extract downregulated the expression of pro-apoptotic genes(Bax and caspase-3)and mitigated the destruction of glomeruli and renal tubules as well as the degeneration of hepatocytes.Conclusions:L.draba extract can protect hepatic and renal structure and function against CP-induced toxicities,and may be used as a therapeutic agent for CP-induced hepatotoxicity and nephrotoxicity.
文摘Ferroptosis, an iron-dependent type of cell death, is being considered for new clinical treatments of malignant tumors that are difficult to treat with apoptosis inducers. Although several reports have attempted to increase the sensitivity of cells to cell death by combining ferroptosis and apoptosis inducers using a single treatment, detailed elucidation of the respective mechanisms of ferroptosis and apoptosis during cell death remains unclear. Here, we evaluated combined treatment effectiveness using the apoptosis-sensitive rat insulinoma INS-1 cell lines. DNA laddering, an indicator of camptothecin (CPT)-induced apoptosis, was abolished by adding RSL3 and ML-162, but not erastin. We found that when the cells were treated with the apoptosis inducer CPT or the ferroptosis inducer RSL3, respectively, the degree of cytotoxicity observed increased dose-dependently. However, a combined CPT and RSL3 treatment did not show a synergistic decrease in cell viability. Camptothecin did not significantly affect increases in intracellular lipid peroxidation and reactive oxygen species or increases in mitochondrial and cytoplasmic free iron levels that were induced by treatment with RSL3 alone. Moreover, deferoxamine and α-tocopherol were found to inhibit RSL3-induced cytotoxicity but did not protect against CPT or CPT and RSL3-induced cytotoxicity. Finally, the exogenous addition of tert-butyl hydroperoxide inhibited DNA ladder formation that is induced by CPT, while the addition of hydrogen peroxide or ferrous ammonium sulfate had no effect. Taken together, these results suggest that lipid peroxides generated during ferroptosis may suppress cell death induced by apoptotic mechanisms.
基金supported by the National Natural Science Foundation of China(Nos.22078201,U1908202)Liaoning&Shenyang Key Laboratory of Functional Dye and Pigment(Nos.2021JH13/10200018,21-104-0-23).
文摘D-D’-A type aza-borondipyrromethenes(aza-BODIPYs)were prepared by Suzuki cross-coupling reaction.Photothermal conversion efficiency of self-assemble aza-BODIPY-based nanoparticles(DA-azaBDP-NPs)with NIR-Ⅱ emission(λ_(em)=1065 nm)was 37.2%under near infrared(NIR)irradiation,and the outstanding cytotoxicity was triggered by coexistence of DA-azaBDP-NPs and the NIR irradiation,with the decrease of glioblastoma migration and the inhibition of glioblastoma proliferation.DA-azaBDP-NPs could promote glioblastoma autophagy and accelerate the process of cell death.The photothermal therapy(PTT)of DAazaBDP-NPs can effectively induce glioblastoma death by apoptosis under the NIR irradiation,which is highly promising to be applied in vivo experiments of brain.
基金financially supported by the earmarked fund for CARS(CARS-45)National Natural Science Foundation of China(32273144,32072985)National Key R&D Program of China(2019YFD0900200).
文摘Background Ochratoxin A(OTA)is a toxin widely found in aquafeed ingredients,and hypoxia is a common prob-lem in fish farming.In practice,aquatic animals tend to be more sensitive to hypoxia while feeds are contaminated with OTA,but no studies exist in this area.This research investigated the multiple biotoxicities of OTA and hypoxia combined on the liver of grass carp and explored the mitigating effect of curcumin(CUR).Methods A total of 720 healthy juvenile grass carp(11.06±0.05 g)were selected and assigned randomly to 4 experi-mental groups:control group(without OTA and CUR),1.2 mg/kg OTA group,400 mg/kg CUR group,and 1.2 mg/kg OTA+400 mg/kg CUR group with three replicates each for 60 d.Subsequently,32 fish were selected,divided into nor-moxia(18 fish)and hypoxia(18 fish)groups,and subjected to hypoxia stress for 96 h.Results CUR can attenuate histopathological damage caused by coming to OTA and hypoxia by reducing vacu-olation and nuclear excursion.The alleviation of this damage was associated with the attenuation of apoptosis in the mitochondrial pathway by decreasing the expression of the pro-apoptotic proteins Caspase 3,8,9,Bax,and Apaf1 while increasing the expression of the anti-apoptotic protein Bcl-2,and attenuation of endoplasmic reticulum stress(ERS)by reducing Grp78 expression and chop levels.This may be attributed to the fact that the addi-tion of CUR increased the levels of catalase(CAT)and glutathione reductase(GSH),increased antioxidant capacity,and ensured the proper functioning of respiratory chain complexes I and II,which in turn reduced the high produc-tion of reactive oxygen species(ROS),thus alleviating apoptosis and ERS.Conclusions In conclusion,our data demonstrate the effectiveness of CUR in attenuating liver injury caused by the combination of OTA and hypoxia.This study confirms the feasibility and efficacy of adding natural products to mitigate toxic damage to aquatic animals.
基金supported by the National Key Research and Development Program of China(No.2022YFD1300200)Basic Research Program of Jiangsu Province(BK20220315)+1 种基金Key Research and Development Project in Shaanxi Province(No.2022QCY-LL-52,No.2024NC-ZDCYL-03-02)Core and Key technological breakthroughs Project in agriculture of Shanxi Province(No.2023NYGG005).
文摘Background Heat stress(HS)poses a significant threat to male goat reproduction.Sertoli cells(SCs)provide both structural and nutritional support necessary for germ cells.HS induces physiological and biochemical changes in SCs.Nevertheless,the molecular mechanisms involved are still not fully understood.Melatonin is a classic antioxidant that can alleviate HS-induced male reproductive damage.However,the underlying molecular mechanisms by which melatonin mitigates damage to goat testicular SCs remain unclear and require further investigation.Results In this study,an in vivo heat stress model was established in goats.The results showed that HS exposure led to testicular injury,abnormal spermatogenesis and apoptosis of SCs.To elucidate the mechanism of HS-induced SC apoptosis,primary SCs were isolated and cultured from goat testes,then exposed to HS.HS exposure increased the production of reactive oxygen species(ROS),decreased adenosine triphosphate(ATP)synthesis,and reduced mitochondrial membrane potential in SCs.Additionally,HS increased the expression of mitochondrial fission proteins 1(FIS1)and dynamin-related protein 1(DRP1)while decreasing the expression of mitochondrial fusion proteins Mitofusin 1(MFN1),Mitofusin 2(MFN2),and optic atrophy 1(OPA1).This resulted in excessive mitochondrial fission and mitochondria-dependent apoptosis.Mdivi-1(DRP1 inhibitor)reduces mitochondria-dependent apoptosis by inhibiting excessive mitochondrial fission.Mitochondrial fission is closely related to mitophagy.HS activated upstream mitophagy but inhibited autophagic flux,disrupting mitophagy and exacerbating mitochondria-dependent apoptosis.Finally,the classical antioxidant melatonin was shown to reduce mitochondria-dependent apoptosis in SCs exposed to HS by decreasing ROS levels,restoring mitochondrial homeostasis,and normalizing mitophagy.Conclusions In summary,these findings indicated that the mechanism of HS-induced mitochondria-dependent apoptosis in SCs is mediated by hyperactivation of the ROS-DRP1-mitochondrial fission axis and inhibition of mitochondrial autophagy.Melatonin inhibited HS-induced mitochondria-dependent apoptosis in SCs by restoring mitochondrial homeostasis.This study enhances the understanding of the mechanisms through which heat stress triggers apoptosis and provides a vision for the development of drugs against HS by targeting mitochondria in goats.
基金Financial support for the current study was provided by the grant from"Blue Engineering"Excellent Young Teacher Foundation in Colleges and Universities of Jiangsu Province(Grant No.KY101R202207 to Xiaojun Chen)。
文摘Premature ovarian insufficiency(POI)caused by chemotherapy is a common complication in female cancer survivors of childbearing age.Traditional methods,including mesenchymal stem cell(MSC)transplant and hormone replacement therapy,have limited clinical application because of their drawbacks,and more methods need to be developed.In the current study,the potential effects and underlying mechanisms of human umbilical cord MSC-derived extracellular vesicles(h UCMSC-EVs)were investigated in a cisplatin(CDDP)-induced POI mouse model and a human granulosa cell(GC)line.The results showed that h UCMSC-EVs significantly attenuated body weight loss,ovarian weight loss,ovary atrophy,and follicle loss in moderate-dose(1.5 mg/kg)CDDP-induced POI mice,similar to the effects observed with h UCMSCs.We further found that the h UCMSCEVs inhibited CDDP-induced ovarian GC apoptosis by upregulating anti-apoptotic mi RNA levels in GCs,thereby downregulating the m RNA levels of multiple pro-apoptotic genes.In general,our findings indicate that the moderate-dose chemotherapy may be a better choice for clinical oncotherapy,considering effective rescue of the oncotherapy-induced ovarian damage with h UCMSC-EVs.Additionally,multiple mi RNAs in h UCMSC-EVs may potentially be used to inhibit the chemotherapy-induced ovarian GC apoptosis,thereby restoring ovarian function and improving the life quality of female cancer patients.
基金supported by the Projects of International Cooperation and Exchanges(Nos.G2022027004L,G2022027012L)the Hubei Province Natural Science Foundation of China(No.2022CFB481)+3 种基金the Natural Science Foundation of Hubei Provincial Department of Education(No.T2022021)the Advantages Discipline Group(Biology and Medicine)Project in Higher Education of Hubei Province(2021-2025)(Nos.2025BMXKQY2,2024XKQY26)the Innovative Research Program for Graduates of Hubei University of Medicine(No.YC2024003,YC2022033)the Student's Platform for Innovation and Entrepreneurship Training Program(Nos.202410929010,202210929005)。
文摘Pristimerin,which is one of the compounds present in Celastraceae and Hippocrateaceae,has antitumor effects.However,its mechanism of action in esophageal squamous cell carcinoma(ESCC)remains unclear.This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo.The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays.Cell apoptosis was evaluated by flow cytometry.Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction(qRT-PCR),Western blotting,and immunohistochemistry.RNA sequencing(RNA-Seq)was employed to identify significantly differentially expressed genes(DEGs).Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin's effect.Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo.Pristimerin inhibited cell growth and induced apoptosis in ESCC cells.Upregulation of Noxa was crucial for pristimerin-induced apoptosis.Pristimerin activated the Forkhead box O3a(FoxO3a)signaling pathway and triggered FoxO3a recruitment to the Noxa promoter,leading to Noxa transcription.Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis.Pristimerin treatment suppressed xenograft tumors in nude mice,but these effects were largely negated in Noxa-KO tumors.Furthermore,the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa.This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation.These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
