Background:Renalfibrosis is an important process in the development of chronic kidney disease.Understanding the pathogenesis andfinding effective treatments for renalfibrosis is crucial.This study aims to investigate whe...Background:Renalfibrosis is an important process in the development of chronic kidney disease.Understanding the pathogenesis andfinding effective treatments for renalfibrosis is crucial.This study aims to investigate whether a newly discovered long non-coding RNA(lncRNA)called LOC103694972 could be a potential target for treatingfibrosis of NRK-49F cells.Methods:LncRNA Chip was used to identify differentially expressed lncRNAs between TGF-β1-induced NRK-49F cells and normal cells.The dual-luciferase assay confirmed the binding between miR-29c-3p and signal transducer and activator of transcription(STAT3),as well as between miR-29c-3p and lncRNA LOC103694972.Si-LOC103694972 and miR-29c-3p mimic were then transfected into TGF-β1-induced NRK-49F cells.Results:The study found that LOC103694972 was highly expressed in TGF-β1-induced NRK-49F cells.These cells exhibited increased cell length and activity compared to the control group.The expression levels of Collagen I,α-Smooth muscle actin(α-SMA),and tissue inhibitor of metalloproteinase(TIMP-1)were increased,while matrix Metalloproteinase 2(MMP2)and matrix Metalloproteinase 9(MMP9)expression was decreased.However,transfection with si-LOC103694972 and miR-29c-3p mimics restored cell morphology and reduced cell viability.This led to a decrease in the levels of Collagen I,α-SMA,and TIMP-1,as well as an increase in MMP2 and MMP9 expression.Additionally,TGF-β1-induced NRK-49F cells transfected with miR-29c-3p mimics activated the STAT3-Smad3/CTGF pathway.Conclusion:Based on thesefindings,lncRNA LOC103694972 shows promise as a target for treating renalfibrosis.It negatively regulates miR-29c-3p and activates the STAT3-Smad3/CTGF pathway.展开更多
BACKGROUND The specific benefits of Yangxinshi tablet(YXST)in the treating chronic heart failure(CHF)remain uncertain.AIM To systematically evaluate the efficacy and safety of YXST in the treatment of CHF.METHODS Rand...BACKGROUND The specific benefits of Yangxinshi tablet(YXST)in the treating chronic heart failure(CHF)remain uncertain.AIM To systematically evaluate the efficacy and safety of YXST in the treatment of CHF.METHODS Randomized controlled trials(RCTs)investigating YXST for CHF treatment were retrieved from eight public databases up to November 2023.Meta-analyses of the included clinical studies were conducted using Review Manager 5.3.RESULTS Twenty RCTs and 1845 patients were included.The meta-analysis results showed that the YXST combination group,compared to the conventional drug group,significantly increased the clinical efficacy rate by 23%[relative risk(RR)=1.23,95%CI:1.17-1.29],(P<0.00001),left ventricular ejection fraction by 6.69%[mean difference(MD)=6.69,95%CI:4.42-8.95,P<0.00001]and 6-min walk test by 49.82 m(MD=49.82,95%C:38.84-60.80,P<0.00001),and reduced N-terminal pro-Btype natriuretic peptide by 1.03 ng/L[standardized MD(SMD)=-1.03,95%CI:-1.32 to-0.74,P<0.00001],brain natriuretic peptide by 80.95 ng/L(MD=-80.95,95%CI:-143.31 to-18.59,P=0.01),left ventricular end-diastolic diameter by 3.92 mm(MD=-3.92,95%CI:-5.06 to-2.78,P<0.00001),and left ventricular endsystolic diameter by 4.34 mm(MD=-4.34,95%CI:-6.22 to-2.47,P<0.00001).Regarding safety,neither group reported any serious adverse events during treatment(RR=0.54,95%CI:0.15-1.90,P=0.33).In addition,Egger's test results indicated no significant publication bias(P=0.557).CONCLUSION YXST effectively improves clinical symptoms and cardiac function in patients with CHF while maintaining a favorable safety profile,suggesting its potential as a therapeutic strategy for CHF.展开更多
BACKGROUND The effects of viral hepatitis(VH)on type 2 diabetes(T2D)remain controversial.AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization(MR).METHODS Single nuc...BACKGROUND The effects of viral hepatitis(VH)on type 2 diabetes(T2D)remain controversial.AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization(MR).METHODS Single nucleotide polymorphisms of VH,chronic hepatitis B(CHB),chronic hepatitis C(CHC)and T2D were obtained from the BioBank Japan Project,European Bioinformatics Institute,and FinnGen.Inverse variance weighted,MREgger,and weighted median were used to test exposure-outcome associations.The MR-Egger intercept analysis and Cochran’s Q test were used to assess horizontal pleiotropy and heterogeneity,respectively.Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results.RESULTS The MR analysis showed no significant causal relationship between VH and T2D in Europeans[odds ratio(OR)=1.028;95%confidence interval(CI):0.995-1.062,P=0.101].There was a negative causal association between CHB and T2D among East Asians(OR=0.949;95%CI:0.931-0.968,P<0.001),while there was no significant causal association between CHC and T2D among East Asians(OR=1.018;95%CI:0.959-1.081,P=0.551).Intercept analysis and Cochran’s Q test showed no horizontal pleiotropy or heterogeneity(P>0.05).Sensitivity analysis showed that the results were robust.CONCLUSION Among East Asians,CHB is associated with a reduced T2D risk,but this association is limited by HBV load and cirrhosis.Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D,focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHCmediated pathways of hepatic steatosis,liver fibrosis,and cirrhosis.展开更多
Guided by the theory of traditional Chinese medicine(TCM),TCM formula granules are made through the optimal process of extraction,concentration,drying,and granulation by combining modern new preparation technologies a...Guided by the theory of traditional Chinese medicine(TCM),TCM formula granules are made through the optimal process of extraction,concentration,drying,and granulation by combining modern new preparation technologies and pharmaceutical technologies.TCM formula granules are stable,safe,convenient,and effective.Compared with TCM decoction pieces,TCM formula granules can achieve the full process control of its industry chain from field to workshop and standardize the management of the origin of medicinal materials,processing of decoction pieces,processing technology,quality inspection,sales,and products distribution.TCM formula granules can partially replace Chinese patent medicines.Only available for around 800 common varieties of TCM,TCM formula granules cannot replace decoction pieces for many types which are not commonly used in clinical practice.A large number of formula granules are used in clinical and animal studies so that investigators no longer need to extract and control the quality of TCM decoction pieces.How to improve the production process,establish the quality standard,perfect the regulatory system,and expand the clinical application are the problems we need to solve as soon as possible for the better development of formula granules.展开更多
Developmental dysplasia of hip seriously affects the health of children,and pelvic osteotomy is an important part of surgical treatment.Improving the shape of the acetabulum,preventing or delaying the progression of o...Developmental dysplasia of hip seriously affects the health of children,and pelvic osteotomy is an important part of surgical treatment.Improving the shape of the acetabulum,preventing or delaying the progression of osteoarthritis is the ultimate goal of pelvic osteotomies.Re-directional osteotomies,reshaping osteotomies and salvage osteotomies are the three most common types of pelvic osteotomy.The influence of different pelvic osteotomy on acetabular morphology is different,and the acetabular morphology after osteotomy is closely related to the prognosis of the patients.But there lacks comparison of acetabular morphology between different pelvic osteotomies,on the basis of retrospective analysis and measurable imaging indicators,this study predicted the acetabular shape after developmental dysplasia of the hip pelvic osteotomy in order to help clinicians make reasonable and correct decisions and improve the planning and performance of pelvic osteotomy.展开更多
Background:The development and prognosis of breast cancer are intricately linked to psychological stress.In addition,depression is the most common psychological comorbidity among breast cancer survivors,and reportedly...Background:The development and prognosis of breast cancer are intricately linked to psychological stress.In addition,depression is the most common psychological comorbidity among breast cancer survivors,and reportedly,Fang-Xia-Dihuang decoction(FXDH)can effectively manage depression in such patients.However,its pharmacological and molecular mechanisms remain obscure.Methods:Public databases were used for obtaining active components and related targets.Main active components were further verified by ultra-high-performance liquid chromatography-high-resolution mass spectrometry(UPLC-HRMS).Protein–protein interaction and enrichment analyses were taken to predict potential hub targets and related pathways.Molecule docking was used to understand the interactions between main compounds and hub targets.In addition,an animal model of breast cancer combined with depression was established to evaluate the intervention effect of FXDH and verify the pathways screened by network pharmacology.Results:174 active components of FXDH and 163 intersection targets of FXDH,breast cancer,and depression were identified.Quercetin,methyl ferulate,luteolin,ferulaldehyde,wogonin,and diincarvilone were identified as the principal active components of FXDH.Protein–protein interaction and KEGG enrichment analyses revealed that the phosphoinositide-3-kinase–protein kinase B(PI3K/AKT)and Janus kinase/signal transducer and activator of transcription(JAK2/STAT3)signaling pathways played a crucial role in mediating the efficacy of FXDH for inhibiting breast cancer progression induced by depression.In addition,in vivo experiments revealed that FXDH ameliorated depression-like behavior in mice and inhibited excessive tumor growth in mice with breast cancer and depression.FXDH treatment downregulated the expression of epinephrine,PI3K,AKT,STAT3,and JAK2 compared with the control treatment(p<0.05).Molecular docking verified the relationship between the six primary components of FXDH and the three most important targets,including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),AKT,and STAT3.Conclusion:This study provides a scientific basis to support the clinical application of FXDH for improving depression-like behavior and inhibiting breast cancer progression promoted by chronic stress.The therapeutic effects FXDH may be closely related to the PI3K/AKT and JAK2/STAT3 pathways.This finding helps better understand the regulatory mechanisms underlying the efficacy of FXDH.展开更多
BACKGROUND No guideline recommends antiviral therapy for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus(HBV)DNA...BACKGROUND No guideline recommends antiviral therapy for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus(HBV)DNA viral load.AIM To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection.METHODS In total,395 patients(30–65 years old)with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk.Endpoints to evaluate therapeutic efficacy included:(1)HBV DNA levels decreased to less than 4 log10 IU/mL at weeks 48 and 96;and(2)HBeAg clearance and seroconversion rates at weeks 48 and 96.RESULTS HBV DNA levels≤4 log10 IU/mL were 10.05%at week 48 and 18.59%at week 96 in the treatment group.The HBeAg clearance and conversion rates were 8.54%and 8.04%at week 48 and 16.08%and 14.57%at week 96,respectively.However,HBV DNA levels≤4 log10 IU/mL were 2.55%and 2.55%at weeks 48 and 96,respectively,and the HBeAg clearance rates were 3.06%and 5.61%at weeks 48 and 96,respectively,in the control group.The quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBeAg clearance.CONCLUSION High rates of HBV DNA reduction,HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments,and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase.The ability of the compound to modulate host immune function probably contributed to this effect.展开更多
Accumulating evidence indicates that glaucoma is a multifactorial neurodegenerative disease characterized by the loss of retinal ganglion cells(RGC), resulting in gradual and progressive permanent loss of vision.Reduc...Accumulating evidence indicates that glaucoma is a multifactorial neurodegenerative disease characterized by the loss of retinal ganglion cells(RGC), resulting in gradual and progressive permanent loss of vision.Reducing intraocular pressure(IOP) remains the only proven method for preventing and delaying the progression of glaucomatous visual impairment.However, the specific role of IOP in optic nerve injury remains controversial, and little is known about the biomechanical mechanism by which elevated IOP leads to the loss of RGC. Published studies suggest that the biomechanical properties of the sclera and scleral lamina cribrosa determine the biomechanical changes of optic nerve head, and play an important role in the pathologic process of loss of RGC and optic nerve damage. This review focuses on the current understanding of biomechanics of sclera in glaucoma and provides an overview of the possible interactions between the sclera and IOP. Treatments and interventions aimed at the sclera are also discussed.展开更多
Objective:To systematically evaluate the cllinical efficacy of Duhuo Jisheng decoction(DHJSD)combined with non-surgical therapy on lumbar disc herniation(LDH).Methods:China Science and Technology Journal Database(VIP)...Objective:To systematically evaluate the cllinical efficacy of Duhuo Jisheng decoction(DHJSD)combined with non-surgical therapy on lumbar disc herniation(LDH).Methods:China Science and Technology Journal Database(VIP),Chinese National Knowledge Infrastructure(CNKI),WanFang Data,PubMed were searched and eligible randomized controlled clinical trials(RCTs)were included.Two reviewers evaluated the quality of the included RCTs and extracted data independently.Then,data analysis was performed with RevMetn 4.2 software.Results:A total of 18 RCTs were enrolled,including 1682 patients.Meta-analysis results showed that the overall response rate of DHJSD combined with non-operative therapy group(treatment group)in the treatment of LDH was better than that of the non-operative therapy group(control group)[OR=4.29,95%CI(3.19,5.76),P<0.001].JOA score of the treatment group was significantly higher than that of control group[OR=3.96,95%CI(3.4,4.52),P<0.001].VAS score was dramatically lower in the treatment group than the control group[OR=-1.58,95%CI(-1.97,-1.18),P<0.001].Conclusion:The clinical efficacy of DHJSD combined with non-surgical therapy is better than that of non-surgical therapy alone.However,due to the low quality of the included literatures,large-scale and high-quality RCTs are still needed for further confirmation.展开更多
Background:As described in Tao Te Ching,Tao does nothing but can accomplish everything.Methods:Exploring this artistic concept through the image“valley spirit dies not”,we see it produce“Names”from“Having No Name...Background:As described in Tao Te Ching,Tao does nothing but can accomplish everything.Methods:Exploring this artistic concept through the image“valley spirit dies not”,we see it produce“Names”from“Having No Name”.Results:The role of essence in the body is similar to the“Doing Nothing”way of Tao,and through strengthening Yang,Yang Qi can be unblocked so as to restore the nature of“Doing Nothing”and generate Qi,essence,blood,and bodily fluids to treat disease.展开更多
OBJECTIVE:To study the effect of Jiangzhi Xiaoban tablet(降脂消斑片,JZXB)on toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/Nod-like receptor protein 3(NLRP3)signaling pathway expression in atherosclerosis(A...OBJECTIVE:To study the effect of Jiangzhi Xiaoban tablet(降脂消斑片,JZXB)on toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/Nod-like receptor protein 3(NLRP3)signaling pathway expression in atherosclerosis(AS)mice by establishing a mouse model of AS,and to explore its mechanism of prevention and treatment of AS.METHODS:Sixty-four male C57BL/6J mice were randomly divided into two groups,12 in the normal control group and 52 in the model group(MOD).Seven weeks later,two mice in each of the above two groups were randomly sacrificed,and the whole aortic tissue of the mice was taken out for hematoxylin-eosin staining.After successful modeling,50 mice in the modeling group were randomly divided into 5 groups:MOD,atorvastatin group(ATO),low-dose group of JZXB(JZXB-L),middle-dose group of JZXB(JZXB-M),and high-dose group of JZXB(JZXB-H),10 mice in each group.The mice in each group were killed after 6 weeks of preventive administration.HE staining was used to observe the pathological changes of aorta in AS mice.The levels of serum triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were detected by automatic biochemical analyzer.The levels of inflammatory factor interleukin-1β(IL-1β)were detected by enzyme linked immunosorbent assay.The expression of TLR4,NF-κB and NLRP3 proteins in aortic tissue was detected by immunohistochemistry.RESULTS:Compared with the MOD,the levels of serum TC,TG and LDL-C in the JZXB-H and ATO were significantly decreased,while the level of HDL-C was significantly increased.The levels of serum TG,LDL-C in the JZXB-M were significantly decreased,and the level of HDL-C was significantly increased.Compared with the MOD,the levels of IL-1βwere significantly decreased,aortic lesions were significantly improved,and the expression of TLR4,NF-κB,and NLRP3 proteins in the aortic tissue was significantly decreased in the JZXB-H,JZXB-M,and ATO.CONCLUSION:JZXB has inhibitory effect on atherosclerosis in mice,and its mechanism may be through regulating the TLR4/NF-κB/NLRP3 signaling pathway and reducing the inflammatory response,so as to play a role in inhibiting atherosclerosis.展开更多
BACKGROUND The phosphoinositide 3-kinase/protein kinase-B/mechanistic target of rapamycin(PI3K/Akt/mTOR) signalling pathway is crucial for cell survival, differentiation, apoptosis and metabolism. Xihuang pills(XHP) a...BACKGROUND The phosphoinositide 3-kinase/protein kinase-B/mechanistic target of rapamycin(PI3K/Akt/mTOR) signalling pathway is crucial for cell survival, differentiation, apoptosis and metabolism. Xihuang pills(XHP) are a traditional Chinese preparation with antitumour properties. They inhibit the growth of breast cancer, glioma, and other tumours by regulating the PI3K/Akt/mTOR signalling pathway. However, the effects and mechanisms of action of XHP in hepatocellular carcinoma(HCC) remain unclear. Regulation of the PI3K/Akt/mTOR signalling pathway effectively inhibits the progression of HCC. However, no study has focused on the XHPassociated PI3K/Akt/mTOR signalling pathway. Therefore, we hypothesized that XHP might play a role in inhibiting HCC through the PI3K/Akt/mTOR signalling pathway.AIM To confirm the effect of XHP on HCC and the possible mechanisms involved.METHODS The chemical constituents and active components of XHP were analysed using ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS). Cellbased experiments and in vivo xenograft tumour experiments were utilized to evaluate the effect of XHP on HCC tumorigenesis. First, SMMC-7721 cells were incubated with different concentrations of XHP(0, 0.3125, 0.625, 1.25, and 2.5 mg/mL) for 12 h, 24 h and 48 h. Cell viability was assessed using the CCK-8 assay, followed by an assessment of cell migration using a wound healing assay.Second, the effect of XHP on the apoptosis of SMMC-7721 cells was evaluated. SMMC-7721 cells were stained with fluorescein isothiocyanate and annexin V/propidium iodide. The number of apoptotic cells and cell cycle distribution were measured using flow cytometry. The cleaved protein and mRNA expression levels of caspase-3 and caspase-9 were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction(RT-qPCR), respectively.Third, Western blotting and RT–qPCR were performed to confirm the effects of XHP on the protein and mRNA expression of components of the PI3K/Akt/mTOR signalling pathway.Finally, the effects of XHP on the tumorigenesis of subcutaneous hepatocellular tumours in nude mice were assessed.RESULTS The following 12 compounds were identified in XHP using high-resolution mass spectrometry:Valine, 4-gingerol, myrrhone, ricinoleic acid, glycocholic acid, curzerenone, 11-keto-β-boswellic acid, oleic acid, germacrone, 3-acetyl-9,11-dehydro-β-boswellic acid, 5β-androstane-3,17-dione, and 3-acetyl-11-keto-β-boswellic acid. The cell viability assay results showed that treatment with 0.625mg/mL XHP extract decreased HCC cell viability after 12 h, and the effects were dose-and timedependent. The results of the cell scratch assay showed that the migration of HCC cells was significantly inhibited in a time-dependent manner by the administration of XHP extract(0.625mg/mL). Moreover, XHP significantly inhibited cell migration and resulted in cell cycle arrest and apoptosis. Furthermore, XHP downregulated the PI3K/Akt/mTOR signalling pathway, which activated apoptosis executioner proteins(e.g., caspase-9 and caspase-3). The inhibitory effects of XHP on HCC cell growth were determined in vivo by analysing the tumour xenograft volumes and weights.CONCLUSION XHP inhibited HCC cell growth and migration by stimulating apoptosis via the downregulation of the PI3K/Akt/mTOR signalling pathway, followed by the activation of caspase-9 and caspase-3.Our findings clarified that the antitumour effects of XHP on HCC cells are mediated by the PI3K/Akt/mTOR signalling pathway, revealing that XHP may be a potential complementary therapy for HCC.展开更多
BACKGROUND Helicobacter pylori(H.pylori)is the most important infectious agent and plays an important role in the progression of chronic gastritis and the development of gastric cancer.AIM To identify efficient therap...BACKGROUND Helicobacter pylori(H.pylori)is the most important infectious agent and plays an important role in the progression of chronic gastritis and the development of gastric cancer.AIM To identify efficient therapeutic agents or strategies that can treat H.pylori infection.METHODS We performed literature analysis,experimental validation,and network pharmacology.First,traditional Chinese medicine(TCM)prescriptions for the treatment of H.pylori infection were obtained from the China National Knowledge Infrastructure,China Biology Medicine,China Science and Technology Journal Database,and WanFang databases.In addition,we conducted a relevant search by Reference Citation Analysis(RCA)(https://www.referencecitationanalysis.com).Next,we used TCM Inheritance Support System V2.5 to identify core drug combinations in the TCM prescriptions.Then,an H.pylori-associated chronic mouse model of gastritis was established.The antibacterial properties and antiinflammatory potential of the core drug combination were evaluated by the rapid urease test,modified Warthin-Starry silver staining,histopathological analysis,and enzyme linked immunosorbent assay.Finally,the active compounds,hub targets,and potential signaling pathways associated with the core drug combination were analyzed by network pharmacology.RESULTS The TCM treatment of H.pylori was mainly based on reinforcing the healthy Qi and eliminating pathogenic factors by simultaneously applying pungent dispersing,bitter descending,cold and warm drugs.The combination of Coptis,Pinellia,and Scutellaria(CPS)was identified as the core drug combination from 207 prescriptions and 168 herbs.This drug combination eradicated H.pylori,alleviated the gastric pathology induced by H.pylori infection,and reduced the expression levels of tumor necrosis factor-α(P=0.024)and interleukin-1β(P=0.001).Moreover,a total of 35 compounds and 2807 targets of CPS were identified using online databases.Nine key compounds(tenaxin I,neobaicalein,norwogonin,skullcapflavone II,baicalein,5,8,2'-trihydroxy-7-methoxyflavone,acacetin,panicolin,and wogonin)and nine hub target proteins(EGFR,PTGS2,STAT3,MAPK3,MAPK8,HSP90AA1,MAPK1,MMP9,and MTOR)were further explored.Seventy-seven signaling pathways were correlated with H.pylori-induced inflammation and carcinogenesis.CONCLUSION In summary,we showed that CPS is the core drug combination for treating H.pylori infection.Animal experiments demonstrated that CPS has bacteriostatic properties and can reduce the release of inflammatory cytokines in the gastric mucosa.Network pharmacology predictions further revealed that CPS showed complex chemical compositions with multi-target and multipathway regulatory mechanisms.Although the results derived from network pharmacology are not necessarily comprehensive,they still expand our understanding of CPS for treating H.pylori infection.展开更多
Objective:To investigate the distribution and drug resistance of pathogens isolated from 4142 blood cultures, and provide a scientific foundation for guiding clinical rational use of antimicrobial agents for bloodstre...Objective:To investigate the distribution and drug resistance of pathogens isolated from 4142 blood cultures, and provide a scientific foundation for guiding clinical rational use of antimicrobial agents for bloodstream infections.Methods: Blood cultures obtained from 4142 inpatients and outpatients who were hospitalized from Jan 2015 to Dec 2016. The culture was detected by automatic BACT/ALERT 3D blood culture system of biomerieux. Bacteria isolated from positive blood cultures were further identified, and the drug susceptibility tests were conducted by VITEK-2 Compact automatic microbial analysis system and ATB Expression microbial analysis system. The drug susceptibility results were evaluated according to CLSI 2014 standard. Statistical analysis was performed by using WHONET 5.6 software. Results:A total of 396 unique strains were isolated from 4142 blood cultures, and the positive rate is 9.6%. Among the positive blood cultures, 194 (49.0%) strains were identified as Gram-positive, 185 (46.7%) strains were identified as Gram-negative, and 17(4.3%) strains were identified as fungi. The coagulase-negative Staphylococcus were the most frequently detectable (29.2%), followed by Escherichia coli (18.4%), Klebsiella pneumonia (7.3%), Staphylococcus aureus (5.1%), Acinetobacter baumannii(5.1%), and Enterococcus genera (5.1%). The incidences of methicillin resistant coagulase negative staphylococcus (MRCNS) and methicillin resistant staphylococcus aureus (MRSA) were 81.9% and 50.0% respectively. However, vancomycin resistant staphylococcus and enterococcus were not detected. The prevalence of extended spectrumβ lactamases (ESBLs) in E. coli and K. pneumoniae were 56.2% and 37.9%, respectively. All the E. coli strains were sensitive to amikacin, piperacillin/tazobactam, imipenem and meropenem, and the sensitive rate of K. pneumoniae strains to imipenem and meropenem were 93.1% and 89.7%, respectively.Conclusions MRCNS stains were the most frequently detected pathogens in blood cultures in the present study. The characteristic of drug resistance for the pathogens indicated that monitoring of imipenem and meropenem resistant K. pneumoniae should be underlined to prevent nosocomial outbreak. Fungi bloodstream infections of ward such as ICU and department of hemopathology should be enhanced monitored.展开更多
Objective To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis(RA).Methods Tumor necrosis factor(TNF)-α-induced fibroblast-like synoviocytes(FLS)was exposed to additional isorhamnetin(10...Objective To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis(RA).Methods Tumor necrosis factor(TNF)-α-induced fibroblast-like synoviocytes(FLS)was exposed to additional isorhamnetin(10,20 and 40µmol/L).Overexpression vectors for matrix metalloproteinase-2(MMP2)or MMP9 or SRC were transfected to explore their roles in isorhamnetin-mediated RA-FLS function.RA-FLS viability,migration,and invasion were evaluated.Moreover,a collagen-induced arthritis(CIA)rat model was established.Rats were randomly divided to sham,CIA,low-,medium-,and high-dosage groups using a random number table(n=5 in each group)and administed with normal saline or additional isorhamnetin[2,10,and 20 mg/(kg·day)]for 4 weeks,respectively.Arthritis index was calculated and synovial tissue inflammation was determined in CIA rats.The levels of MMP2,MMP9,TNF-α,interleukin-6(IL-6),and IL-1β,as well as the phosphorylation levels of SRC,extracellular regulated kinase(ERK),and cyclic adenosine monophosphate response element-binding(CREB),were detected in RA-FLS and synovial tissue.Molecular docking was also used to analyze the binding of isorhamnetin to SRC.Results In in vitro studies,isorhamnetin inhibited RA-FLS viability,migration and invasion(P<0.05).Isorhamnetin downregulated the levels of MMP2,MMP9,TNF-α,IL-6,and IL-1βin RA-FLS(P<0.05).The overexpression of either MMP2 or MMP9 reversed isorhamnetin-inhibited RA-FLS migration and invasion,as well as the levels of TNF-α,IL-6,and IL-1β(P<0.05).Furthermore,isorhamnetin bound to SRC and reduced the phosphorylation of SRC,ERK,and CREB(P<0.05).SRC overexpression reversed the inhibitory effect of isorhamnetin on RA-FLS viability,migration and invasion,as well as the negative regulation of MMP2 and MMP9(P<0.05).In in vivo studies,isorhamnetin decreased arthritis index scores(P<0.05)and alleviated synovial inflammation.Isorhamnetin reduced the levels of MMP2,MMP9,TNF-α,IL-6,and IL-1β,as well as the phosphorylation of SRC,ERK,and CREB in synovial tissue(P<0.05).Notably,the inhibitory effect of isorhamnetin was more pronounced at higher concentrations(P<0.05).Conclusion Isorhamnetin exhibited anti-RA effects through modulating SRC/ERK/CREB and MMP2/MMP9 signaling pathways,suggesting that isorhamnetin may be a potential therapeutic agent for RA.展开更多
Background:Puerarin(Pue)has been reported to be a natural active ingredient with multiple antifibrotic properties.This work aimed at exploring the function of Pue in oral submucousfibrosis(OSF)treatment.Methods:Human or...Background:Puerarin(Pue)has been reported to be a natural active ingredient with multiple antifibrotic properties.This work aimed at exploring the function of Pue in oral submucousfibrosis(OSF)treatment.Methods:Human oral mucosafibroblasts(hOMF)were induced with transforming growth factor beta1(TGF-β1)and intervened with Pue.Expressions offibrosis-related markers were analyzed by Western blot and IF staining.Cell viability was characterized by the CCK-8 assay.Expressions of miR-30 family members were quantified by qRT-PCR.The correlation betweenfibroblast activation protein(FAP)and miR-30 family expression was evaluated by the Pearson correlation coefficient.Bioinformatics prediction and dual-luciferase reporter assay were employed to verify the regulation between FAP and miR-30b-5p.The specific mechanism of Pue on OSF was explored through the promotion or inhibition of miR-30b-5p.Results:After induction by TGF-β1,hOMF showed upregulated Collagen I,Collagen III,and FAP expressions,while miR-30 family expression was downregulated with miR-30b-5p being the most significant.Pue intervention inhibited the excessive proliferation of TGF-β1-induced hOMF,downregulated FAP,collagen type 3(COL3A1),collagen type 1(COL1A1),matrix metalloproteinase 1(MMP1),and matrix metalloproteinase 3(MMP3)expressions,and restored miR-30 family expression.Bioinformatics prediction and dual-luciferase reporter assay revealed that miR-30b-5p selectively inhibited FAP expression.Mechanistically,miR-30b-5p mimic suppressed the excessive proliferation of TGF-β1-induced hOMF and declinedfibrosis levels.Pue intervention significantly reversed the promotion of TGF-β1-induced OSF by miR-30b-5p inhibition.Conclusion:Pue mediated miR-30b-5p targeting FAP against OSF,which provided a theoretical basis for the pathogenesis research and Pue application in OSF.展开更多
Background:To explored whether moxa cone moxibustion can reduce peritoneal inflammation by increasing the content of peritoneal macrophages and B cells via interferon-gamma.Methods:The mice were randomly divided into ...Background:To explored whether moxa cone moxibustion can reduce peritoneal inflammation by increasing the content of peritoneal macrophages and B cells via interferon-gamma.Methods:The mice were randomly divided into three groups with six mice in each group:the control group,model group,and moxibustion group,and the model was established in mice using cyclophosphamide.In the moxibustion group,the mice received moxa cone moxibustion at Zusanli(ST36)for 7 days.Analysis of Peritoneal cell were detected by flow cytometry and immunofluorescence,the protein expression level in the peritoneal fluid were measured with mouse cytokine antibody arrays and verified by enzyme linked immuno sorbent assay test,and RNA-Sequencing was used for peritoneal cell RNA analysis.Results:Our results showed that moxa cone moxibustion could reduce the loss of large peritoneal macrophages and B1 cells(P<0.05).With the cytokine array analysis and enzyme linked immuno sorbent assay test of peritoneal fluid,we found that IFN‐γwas up-regulated in moxibustion group(P<0.05).There were 169 genes were down-regulated in the model group and up-regulated in the moxibustion group while 19 genes that were up-regulated in the model group and down-regulated in the moxibustion group via RNA-sequencing.Kyoto Encyclopedia of Genes and Genomes pathway analysis of 188 intersect differentially expressed genes were found that the top 3 pathways with the highest enrichment of up-regulated genes included Hematopoietic cell lineage,Inflammatory bowel disease and Malaria.The differentially expressed genes visualization protein-protein interaction network shows the top 10 genes including Ifng,Grb2,CCR7,CTLA4,CXCR5,Foxp3,kit,PRF1,CD5 and klrg1.Conclusion:These findings showed that moxa cone moxibustion can alleviate chemotherapy-induced diarrhea by reducing the loss of large peritoneal macrophages and B1 cells in the peritoneal cavity,possibly through up-regulating inflammatory bowel disease signaling pathway via interferon-gamma to regulate the survival and function of large peritoneal macrophages and B1 cells.展开更多
Ischemic stroke is a major public health problem worldwide.Although the circadian clock is involved in the process of ischemic stroke,the exact mechanism of the circadian clock in regulating angiogenesis after cerebra...Ischemic stroke is a major public health problem worldwide.Although the circadian clock is involved in the process of ischemic stroke,the exact mechanism of the circadian clock in regulating angiogenesis after cerebral infarction remains unclear.In the present study,we determined that environmental circadian disruption(ECD)increased the stroke severity and impaired angiogenesis in the rat middle cerebral artery occlusion model,by measuring the infarct volume,neurological tests,and angiogenesis-related protein.We further report that Bmal1 plays an irreplaceable role in angiogenesis.Overexpression of Bmal1 promoted tube-forming,migration,and wound healing,and upregulated the vascular endothelial growth factor(VEGF)and Notch pathway protein levels.This promoting effect was reversed by the Notch pathway inhibitor DAPT,according to the results of angiogenesis capacity and VEGF pathway protein level.In conclusion,our study reveals the intervention of ECD in angiogenesis in ischemic stroke and further identifies the exact mechanism by which Bmal1 regulates angiogenesis through the VEGF-Notch1 pathway.展开更多
In the peripheral nervous system,the activation of Sirtuin 1 can improve insulin resistance;however,the role played by Sirtuin 1 in the central nervous system remains unknown.In this study,rat models of diabetes melli...In the peripheral nervous system,the activation of Sirtuin 1 can improve insulin resistance;however,the role played by Sirtuin 1 in the central nervous system remains unknown.In this study,rat models of diabetes mellitus were generated by a single injection of streptozotocin.At 8 weeks after streptozotocin injection,the Morris water maze test and western blot assays confirmed that the diabetic model rats had learning and memory deficits,insulin resistance,and Sirtuin 1 expression could be detected in the hippocampus.Insulin and the insulin receptor inhibitor S961 were intranasally administered to investigate the regulatory effects of insulin signaling on Sirtuin 1.The results showed that insulin administration improved the impaired cognitive function of diabetic model rats and increased the expression levels of phosphorylated insulin receptor,phosphorylated insulin receptor substrate 1,and Sirtuin 1 in the hippocampus.Conversely,S961 administration resulted in more severe cognitive dysfunction and reduced the expression levels of phosphorylated insulin receptor,phosphorylated insulin receptor substrate 1,and Sirtuin 1.The Sirtuin 1 activator SRT2104 and the inhibitor Sirtinol were injected into the lateral ventricle,which revealed that the activation of Sirtuin 1 increased the expression levels of target of rapamycin complex 1,phosphorylated cAMP-response elementbinding protein,and brain-derived neurotrophic factor.Hippocampal dendritic length and spine density also increased in response to Sirtuin 1 activation.In contrast,Sirtinol decreased the expression levels of target of rapamycin complex 1,phosphorylated cAMP-response elementbinding protein,and brain-derived neurotrophic factor and damaged the dendritic structure.These findings suggest that the Sirtuin 1 signaling pathway plays an important role in the development of insulin resistance-related cognitive deficits in diabetic rats.This study was approved by the Animal Ethics Welfare Committee of the First Affiliated Hospital of Hunan University of Chinese Medicine(approval No.ZYFY201811207)in November 2018.展开更多
Macrophages are important antigen-presenting cells to combat tumor via both innate and adaptive immunity,while they are programmed toM2 phenotype in established tumors and instead promote cancer development and metast...Macrophages are important antigen-presenting cells to combat tumor via both innate and adaptive immunity,while they are programmed toM2 phenotype in established tumors and instead promote cancer development and metastasis.Here,we develop a nanomedicine that can re-educate M2 polarized macrophages to restore their anti-tumor activities.The nanomedicine has a core-shell structure to co-load IPI549,a PI3Kγinhibitor,and CpG,a Toll-like receptor 9 agonist.Specifically,the hydrophobic IPI549 is self-assembled into a pure drug nano-core,while MOF shell layer is coated for CpG encapsulation,achieving extra-high total drugs loading of 44%.Such nanosystem could facilitate intracellular delivery of the payloads but without any cytotoxicity,displaying excellent biocompatibility.After entering macrophages,the released IPI549 and CpG exert a synergistic effect to switch macrophages from M2 to M1 phenotype,which enables anti-tumor activities via directly engulfing tumor cells or excreting tumor killing cytokines.Moreover,tumor antigens released from the dying tumor cells could be effectively presented by the re-educated macrophages owing to the up-regulation of various antigen presenting mediators,resulting in infiltration and activation of cytotoxic T lymphocytes.As a result,the nanosystem triggers a robust antitumor immune response in combination with PD-L1 antibody to inhibit tumor growth and metastasis.This work provides a non-cytotoxic nanomedicine to modulate tumor immune microenvironment by reprograming macrophages.展开更多
基金This work was supported by the Hunan Provincial Education Department General Project Research Fund(No.20C1412)the Hunan Graduate Scientific Research Innovation Project(No.CX2018B474)the National Famous Elderly Chinese Medicine Experts Xinyu Chen Inheritance Workshop Construction Project(No.[2022]75).
文摘Background:Renalfibrosis is an important process in the development of chronic kidney disease.Understanding the pathogenesis andfinding effective treatments for renalfibrosis is crucial.This study aims to investigate whether a newly discovered long non-coding RNA(lncRNA)called LOC103694972 could be a potential target for treatingfibrosis of NRK-49F cells.Methods:LncRNA Chip was used to identify differentially expressed lncRNAs between TGF-β1-induced NRK-49F cells and normal cells.The dual-luciferase assay confirmed the binding between miR-29c-3p and signal transducer and activator of transcription(STAT3),as well as between miR-29c-3p and lncRNA LOC103694972.Si-LOC103694972 and miR-29c-3p mimic were then transfected into TGF-β1-induced NRK-49F cells.Results:The study found that LOC103694972 was highly expressed in TGF-β1-induced NRK-49F cells.These cells exhibited increased cell length and activity compared to the control group.The expression levels of Collagen I,α-Smooth muscle actin(α-SMA),and tissue inhibitor of metalloproteinase(TIMP-1)were increased,while matrix Metalloproteinase 2(MMP2)and matrix Metalloproteinase 9(MMP9)expression was decreased.However,transfection with si-LOC103694972 and miR-29c-3p mimics restored cell morphology and reduced cell viability.This led to a decrease in the levels of Collagen I,α-SMA,and TIMP-1,as well as an increase in MMP2 and MMP9 expression.Additionally,TGF-β1-induced NRK-49F cells transfected with miR-29c-3p mimics activated the STAT3-Smad3/CTGF pathway.Conclusion:Based on thesefindings,lncRNA LOC103694972 shows promise as a target for treating renalfibrosis.It negatively regulates miR-29c-3p and activates the STAT3-Smad3/CTGF pathway.
基金Supported by Hunan Provincial Chinese Medicine Research Program Commissioned Key Projects,No.D2023005。
文摘BACKGROUND The specific benefits of Yangxinshi tablet(YXST)in the treating chronic heart failure(CHF)remain uncertain.AIM To systematically evaluate the efficacy and safety of YXST in the treatment of CHF.METHODS Randomized controlled trials(RCTs)investigating YXST for CHF treatment were retrieved from eight public databases up to November 2023.Meta-analyses of the included clinical studies were conducted using Review Manager 5.3.RESULTS Twenty RCTs and 1845 patients were included.The meta-analysis results showed that the YXST combination group,compared to the conventional drug group,significantly increased the clinical efficacy rate by 23%[relative risk(RR)=1.23,95%CI:1.17-1.29],(P<0.00001),left ventricular ejection fraction by 6.69%[mean difference(MD)=6.69,95%CI:4.42-8.95,P<0.00001]and 6-min walk test by 49.82 m(MD=49.82,95%C:38.84-60.80,P<0.00001),and reduced N-terminal pro-Btype natriuretic peptide by 1.03 ng/L[standardized MD(SMD)=-1.03,95%CI:-1.32 to-0.74,P<0.00001],brain natriuretic peptide by 80.95 ng/L(MD=-80.95,95%CI:-143.31 to-18.59,P=0.01),left ventricular end-diastolic diameter by 3.92 mm(MD=-3.92,95%CI:-5.06 to-2.78,P<0.00001),and left ventricular endsystolic diameter by 4.34 mm(MD=-4.34,95%CI:-6.22 to-2.47,P<0.00001).Regarding safety,neither group reported any serious adverse events during treatment(RR=0.54,95%CI:0.15-1.90,P=0.33).In addition,Egger's test results indicated no significant publication bias(P=0.557).CONCLUSION YXST effectively improves clinical symptoms and cardiac function in patients with CHF while maintaining a favorable safety profile,suggesting its potential as a therapeutic strategy for CHF.
基金Supported by National Natural Science Foundation of China,No.U21A20411.
文摘BACKGROUND The effects of viral hepatitis(VH)on type 2 diabetes(T2D)remain controversial.AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization(MR).METHODS Single nucleotide polymorphisms of VH,chronic hepatitis B(CHB),chronic hepatitis C(CHC)and T2D were obtained from the BioBank Japan Project,European Bioinformatics Institute,and FinnGen.Inverse variance weighted,MREgger,and weighted median were used to test exposure-outcome associations.The MR-Egger intercept analysis and Cochran’s Q test were used to assess horizontal pleiotropy and heterogeneity,respectively.Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results.RESULTS The MR analysis showed no significant causal relationship between VH and T2D in Europeans[odds ratio(OR)=1.028;95%confidence interval(CI):0.995-1.062,P=0.101].There was a negative causal association between CHB and T2D among East Asians(OR=0.949;95%CI:0.931-0.968,P<0.001),while there was no significant causal association between CHC and T2D among East Asians(OR=1.018;95%CI:0.959-1.081,P=0.551).Intercept analysis and Cochran’s Q test showed no horizontal pleiotropy or heterogeneity(P>0.05).Sensitivity analysis showed that the results were robust.CONCLUSION Among East Asians,CHB is associated with a reduced T2D risk,but this association is limited by HBV load and cirrhosis.Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D,focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHCmediated pathways of hepatic steatosis,liver fibrosis,and cirrhosis.
文摘Guided by the theory of traditional Chinese medicine(TCM),TCM formula granules are made through the optimal process of extraction,concentration,drying,and granulation by combining modern new preparation technologies and pharmaceutical technologies.TCM formula granules are stable,safe,convenient,and effective.Compared with TCM decoction pieces,TCM formula granules can achieve the full process control of its industry chain from field to workshop and standardize the management of the origin of medicinal materials,processing of decoction pieces,processing technology,quality inspection,sales,and products distribution.TCM formula granules can partially replace Chinese patent medicines.Only available for around 800 common varieties of TCM,TCM formula granules cannot replace decoction pieces for many types which are not commonly used in clinical practice.A large number of formula granules are used in clinical and animal studies so that investigators no longer need to extract and control the quality of TCM decoction pieces.How to improve the production process,establish the quality standard,perfect the regulatory system,and expand the clinical application are the problems we need to solve as soon as possible for the better development of formula granules.
基金Supported by Scientific Research Project of Hunan Education Department,No.21A0054.
文摘Developmental dysplasia of hip seriously affects the health of children,and pelvic osteotomy is an important part of surgical treatment.Improving the shape of the acetabulum,preventing or delaying the progression of osteoarthritis is the ultimate goal of pelvic osteotomies.Re-directional osteotomies,reshaping osteotomies and salvage osteotomies are the three most common types of pelvic osteotomy.The influence of different pelvic osteotomy on acetabular morphology is different,and the acetabular morphology after osteotomy is closely related to the prognosis of the patients.But there lacks comparison of acetabular morphology between different pelvic osteotomies,on the basis of retrospective analysis and measurable imaging indicators,this study predicted the acetabular shape after developmental dysplasia of the hip pelvic osteotomy in order to help clinicians make reasonable and correct decisions and improve the planning and performance of pelvic osteotomy.
基金supported by the Xiamen High-Level Health Talents Introduction and Training Project(Xiaweidang 2021-124)the National Natural Science Foundation of China(No.81774319).
文摘Background:The development and prognosis of breast cancer are intricately linked to psychological stress.In addition,depression is the most common psychological comorbidity among breast cancer survivors,and reportedly,Fang-Xia-Dihuang decoction(FXDH)can effectively manage depression in such patients.However,its pharmacological and molecular mechanisms remain obscure.Methods:Public databases were used for obtaining active components and related targets.Main active components were further verified by ultra-high-performance liquid chromatography-high-resolution mass spectrometry(UPLC-HRMS).Protein–protein interaction and enrichment analyses were taken to predict potential hub targets and related pathways.Molecule docking was used to understand the interactions between main compounds and hub targets.In addition,an animal model of breast cancer combined with depression was established to evaluate the intervention effect of FXDH and verify the pathways screened by network pharmacology.Results:174 active components of FXDH and 163 intersection targets of FXDH,breast cancer,and depression were identified.Quercetin,methyl ferulate,luteolin,ferulaldehyde,wogonin,and diincarvilone were identified as the principal active components of FXDH.Protein–protein interaction and KEGG enrichment analyses revealed that the phosphoinositide-3-kinase–protein kinase B(PI3K/AKT)and Janus kinase/signal transducer and activator of transcription(JAK2/STAT3)signaling pathways played a crucial role in mediating the efficacy of FXDH for inhibiting breast cancer progression induced by depression.In addition,in vivo experiments revealed that FXDH ameliorated depression-like behavior in mice and inhibited excessive tumor growth in mice with breast cancer and depression.FXDH treatment downregulated the expression of epinephrine,PI3K,AKT,STAT3,and JAK2 compared with the control treatment(p<0.05).Molecular docking verified the relationship between the six primary components of FXDH and the three most important targets,including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),AKT,and STAT3.Conclusion:This study provides a scientific basis to support the clinical application of FXDH for improving depression-like behavior and inhibiting breast cancer progression promoted by chronic stress.The therapeutic effects FXDH may be closely related to the PI3K/AKT and JAK2/STAT3 pathways.This finding helps better understand the regulatory mechanisms underlying the efficacy of FXDH.
基金Supported by the National Natural Science Foundation of China,No.81174263National Science and Technology Major Project during the 12th Five-year Plan Period,No.2012ZX1005006+1 种基金Sanming Project of Medicine in Shenzhen,Guangdong Province,China,No.SZSM201612074and Science and Technology Planning Project of Guangdong Province,China,No.2017A020213016.
文摘BACKGROUND No guideline recommends antiviral therapy for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus(HBV)DNA viral load.AIM To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection.METHODS In total,395 patients(30–65 years old)with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk.Endpoints to evaluate therapeutic efficacy included:(1)HBV DNA levels decreased to less than 4 log10 IU/mL at weeks 48 and 96;and(2)HBeAg clearance and seroconversion rates at weeks 48 and 96.RESULTS HBV DNA levels≤4 log10 IU/mL were 10.05%at week 48 and 18.59%at week 96 in the treatment group.The HBeAg clearance and conversion rates were 8.54%and 8.04%at week 48 and 16.08%and 14.57%at week 96,respectively.However,HBV DNA levels≤4 log10 IU/mL were 2.55%and 2.55%at weeks 48 and 96,respectively,and the HBeAg clearance rates were 3.06%and 5.61%at weeks 48 and 96,respectively,in the control group.The quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBeAg clearance.CONCLUSION High rates of HBV DNA reduction,HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments,and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase.The ability of the compound to modulate host immune function probably contributed to this effect.
基金Supported by National Natural Science Foundation of China(No.81370913)
文摘Accumulating evidence indicates that glaucoma is a multifactorial neurodegenerative disease characterized by the loss of retinal ganglion cells(RGC), resulting in gradual and progressive permanent loss of vision.Reducing intraocular pressure(IOP) remains the only proven method for preventing and delaying the progression of glaucomatous visual impairment.However, the specific role of IOP in optic nerve injury remains controversial, and little is known about the biomechanical mechanism by which elevated IOP leads to the loss of RGC. Published studies suggest that the biomechanical properties of the sclera and scleral lamina cribrosa determine the biomechanical changes of optic nerve head, and play an important role in the pathologic process of loss of RGC and optic nerve damage. This review focuses on the current understanding of biomechanics of sclera in glaucoma and provides an overview of the possible interactions between the sclera and IOP. Treatments and interventions aimed at the sclera are also discussed.
文摘Objective:To systematically evaluate the cllinical efficacy of Duhuo Jisheng decoction(DHJSD)combined with non-surgical therapy on lumbar disc herniation(LDH).Methods:China Science and Technology Journal Database(VIP),Chinese National Knowledge Infrastructure(CNKI),WanFang Data,PubMed were searched and eligible randomized controlled clinical trials(RCTs)were included.Two reviewers evaluated the quality of the included RCTs and extracted data independently.Then,data analysis was performed with RevMetn 4.2 software.Results:A total of 18 RCTs were enrolled,including 1682 patients.Meta-analysis results showed that the overall response rate of DHJSD combined with non-operative therapy group(treatment group)in the treatment of LDH was better than that of the non-operative therapy group(control group)[OR=4.29,95%CI(3.19,5.76),P<0.001].JOA score of the treatment group was significantly higher than that of control group[OR=3.96,95%CI(3.4,4.52),P<0.001].VAS score was dramatically lower in the treatment group than the control group[OR=-1.58,95%CI(-1.97,-1.18),P<0.001].Conclusion:The clinical efficacy of DHJSD combined with non-surgical therapy is better than that of non-surgical therapy alone.However,due to the low quality of the included literatures,large-scale and high-quality RCTs are still needed for further confirmation.
基金This study is supported by the National Natural Science Foundation of China(81704093)Scientific Research Project(Key)of Hunan Provincial Department of Education(19A384)+1 种基金Open Fund for First-Class Disciplines of Integrated Traditional Chinese and Western Medicine(2010ZXYJH14)of Hunan University of Traditional Chinese MedicineProject Funding for 225 High-level Health Talents in Hunan Province(XWH20196).
文摘Background:As described in Tao Te Ching,Tao does nothing but can accomplish everything.Methods:Exploring this artistic concept through the image“valley spirit dies not”,we see it produce“Names”from“Having No Name”.Results:The role of essence in the body is similar to the“Doing Nothing”way of Tao,and through strengthening Yang,Yang Qi can be unblocked so as to restore the nature of“Doing Nothing”and generate Qi,essence,blood,and bodily fluids to treat disease.
基金Supported by Youth Fund Project of Hunan Natural Science Foundation Committee:to Explore the Protective Effect of Chaihu Sanshen Capsule on Myocardial Ischemia Reperfusion Injury Based on Iron Death and Inflammatory Response of Myocardial Cells Induced by Mixed lineage kinase 3 Signaling Pathway(No.2021JJ40419)Project of Traditional Chinese Medicine Administration of Hunan Province:to Explore the Mechanism of the Protective Effect of Chaihu Sanshen Capsule on Myocardial Ischemia Reperfusion Injury based on Micro RNA-145-5p Inhibition of Iron Death and Inflammatory Response of Myocardial Cells Induced by Mixed Lineage Kinase 3 Signaling Pathway(No.B2023019)+1 种基金Project of Health Commission of Hunan Province:to Explore the Mechanism of Chaihu Sanshen Capsule in Reducing Myocardial Ischemia Reperfusion Injury Based on Nuclear Factor Erythroid 2-related Factor 2/Heme Oxygenase-1 Pathway Inhibiting Iron Death of Myocardial Cells(No.2021116001377)Project of Hunan University of Chinese Medicine:To Explore the Intervention Effect of Zhenwu Decoction on the Model of Heart and Kidney Yang Deficiency in Rats with Cardiorenal Syndrome through Micro RNA-214/Receptor-interacting Protein Kinase 1-mediated Tumor Necrosis Factor Signal Pathway(No.2020XJJJ038)。
文摘OBJECTIVE:To study the effect of Jiangzhi Xiaoban tablet(降脂消斑片,JZXB)on toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/Nod-like receptor protein 3(NLRP3)signaling pathway expression in atherosclerosis(AS)mice by establishing a mouse model of AS,and to explore its mechanism of prevention and treatment of AS.METHODS:Sixty-four male C57BL/6J mice were randomly divided into two groups,12 in the normal control group and 52 in the model group(MOD).Seven weeks later,two mice in each of the above two groups were randomly sacrificed,and the whole aortic tissue of the mice was taken out for hematoxylin-eosin staining.After successful modeling,50 mice in the modeling group were randomly divided into 5 groups:MOD,atorvastatin group(ATO),low-dose group of JZXB(JZXB-L),middle-dose group of JZXB(JZXB-M),and high-dose group of JZXB(JZXB-H),10 mice in each group.The mice in each group were killed after 6 weeks of preventive administration.HE staining was used to observe the pathological changes of aorta in AS mice.The levels of serum triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were detected by automatic biochemical analyzer.The levels of inflammatory factor interleukin-1β(IL-1β)were detected by enzyme linked immunosorbent assay.The expression of TLR4,NF-κB and NLRP3 proteins in aortic tissue was detected by immunohistochemistry.RESULTS:Compared with the MOD,the levels of serum TC,TG and LDL-C in the JZXB-H and ATO were significantly decreased,while the level of HDL-C was significantly increased.The levels of serum TG,LDL-C in the JZXB-M were significantly decreased,and the level of HDL-C was significantly increased.Compared with the MOD,the levels of IL-1βwere significantly decreased,aortic lesions were significantly improved,and the expression of TLR4,NF-κB,and NLRP3 proteins in the aortic tissue was significantly decreased in the JZXB-H,JZXB-M,and ATO.CONCLUSION:JZXB has inhibitory effect on atherosclerosis in mice,and its mechanism may be through regulating the TLR4/NF-κB/NLRP3 signaling pathway and reducing the inflammatory response,so as to play a role in inhibiting atherosclerosis.
基金Supported by National Natural Science Foundation of China, No. U20A20408 and No. 82074450Natural Science Foundation of Hunan Province, No. 2020JJ4066+4 种基金Hunan Province"Domestic First-class Cultivation Discipline"Integrated Traditional Chinese and Western Medicine Open Fund Project, No. 2020ZXYJH34 and No. 2020ZXYJH35Hunan Graduate Scientific Research Innovation Project, No. QL20210173 and No. CX20210730Hunan Province Science and Technology Innovation Talents Plan College Students Science and Technology Innovation and Entrepreneurship Project, No. 2020RC1004Guangzhou Health Science and Technology Project, No. 20221A011102Hunan Traditional Chinese Medicine Scientific Research Project, No. 202101
文摘BACKGROUND The phosphoinositide 3-kinase/protein kinase-B/mechanistic target of rapamycin(PI3K/Akt/mTOR) signalling pathway is crucial for cell survival, differentiation, apoptosis and metabolism. Xihuang pills(XHP) are a traditional Chinese preparation with antitumour properties. They inhibit the growth of breast cancer, glioma, and other tumours by regulating the PI3K/Akt/mTOR signalling pathway. However, the effects and mechanisms of action of XHP in hepatocellular carcinoma(HCC) remain unclear. Regulation of the PI3K/Akt/mTOR signalling pathway effectively inhibits the progression of HCC. However, no study has focused on the XHPassociated PI3K/Akt/mTOR signalling pathway. Therefore, we hypothesized that XHP might play a role in inhibiting HCC through the PI3K/Akt/mTOR signalling pathway.AIM To confirm the effect of XHP on HCC and the possible mechanisms involved.METHODS The chemical constituents and active components of XHP were analysed using ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS). Cellbased experiments and in vivo xenograft tumour experiments were utilized to evaluate the effect of XHP on HCC tumorigenesis. First, SMMC-7721 cells were incubated with different concentrations of XHP(0, 0.3125, 0.625, 1.25, and 2.5 mg/mL) for 12 h, 24 h and 48 h. Cell viability was assessed using the CCK-8 assay, followed by an assessment of cell migration using a wound healing assay.Second, the effect of XHP on the apoptosis of SMMC-7721 cells was evaluated. SMMC-7721 cells were stained with fluorescein isothiocyanate and annexin V/propidium iodide. The number of apoptotic cells and cell cycle distribution were measured using flow cytometry. The cleaved protein and mRNA expression levels of caspase-3 and caspase-9 were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction(RT-qPCR), respectively.Third, Western blotting and RT–qPCR were performed to confirm the effects of XHP on the protein and mRNA expression of components of the PI3K/Akt/mTOR signalling pathway.Finally, the effects of XHP on the tumorigenesis of subcutaneous hepatocellular tumours in nude mice were assessed.RESULTS The following 12 compounds were identified in XHP using high-resolution mass spectrometry:Valine, 4-gingerol, myrrhone, ricinoleic acid, glycocholic acid, curzerenone, 11-keto-β-boswellic acid, oleic acid, germacrone, 3-acetyl-9,11-dehydro-β-boswellic acid, 5β-androstane-3,17-dione, and 3-acetyl-11-keto-β-boswellic acid. The cell viability assay results showed that treatment with 0.625mg/mL XHP extract decreased HCC cell viability after 12 h, and the effects were dose-and timedependent. The results of the cell scratch assay showed that the migration of HCC cells was significantly inhibited in a time-dependent manner by the administration of XHP extract(0.625mg/mL). Moreover, XHP significantly inhibited cell migration and resulted in cell cycle arrest and apoptosis. Furthermore, XHP downregulated the PI3K/Akt/mTOR signalling pathway, which activated apoptosis executioner proteins(e.g., caspase-9 and caspase-3). The inhibitory effects of XHP on HCC cell growth were determined in vivo by analysing the tumour xenograft volumes and weights.CONCLUSION XHP inhibited HCC cell growth and migration by stimulating apoptosis via the downregulation of the PI3K/Akt/mTOR signalling pathway, followed by the activation of caspase-9 and caspase-3.Our findings clarified that the antitumour effects of XHP on HCC cells are mediated by the PI3K/Akt/mTOR signalling pathway, revealing that XHP may be a potential complementary therapy for HCC.
基金Supported by the Domestic First-class Construction Disciplines of the Hunan University of Chinese Medicine,No. 2018[03]the Key Scientific Research Project of Hunan Provincial Education Board,No. 20A371the Key Programs of Administration of Traditional Chinese Medicine of Hunan Province,No. C2022016
文摘BACKGROUND Helicobacter pylori(H.pylori)is the most important infectious agent and plays an important role in the progression of chronic gastritis and the development of gastric cancer.AIM To identify efficient therapeutic agents or strategies that can treat H.pylori infection.METHODS We performed literature analysis,experimental validation,and network pharmacology.First,traditional Chinese medicine(TCM)prescriptions for the treatment of H.pylori infection were obtained from the China National Knowledge Infrastructure,China Biology Medicine,China Science and Technology Journal Database,and WanFang databases.In addition,we conducted a relevant search by Reference Citation Analysis(RCA)(https://www.referencecitationanalysis.com).Next,we used TCM Inheritance Support System V2.5 to identify core drug combinations in the TCM prescriptions.Then,an H.pylori-associated chronic mouse model of gastritis was established.The antibacterial properties and antiinflammatory potential of the core drug combination were evaluated by the rapid urease test,modified Warthin-Starry silver staining,histopathological analysis,and enzyme linked immunosorbent assay.Finally,the active compounds,hub targets,and potential signaling pathways associated with the core drug combination were analyzed by network pharmacology.RESULTS The TCM treatment of H.pylori was mainly based on reinforcing the healthy Qi and eliminating pathogenic factors by simultaneously applying pungent dispersing,bitter descending,cold and warm drugs.The combination of Coptis,Pinellia,and Scutellaria(CPS)was identified as the core drug combination from 207 prescriptions and 168 herbs.This drug combination eradicated H.pylori,alleviated the gastric pathology induced by H.pylori infection,and reduced the expression levels of tumor necrosis factor-α(P=0.024)and interleukin-1β(P=0.001).Moreover,a total of 35 compounds and 2807 targets of CPS were identified using online databases.Nine key compounds(tenaxin I,neobaicalein,norwogonin,skullcapflavone II,baicalein,5,8,2'-trihydroxy-7-methoxyflavone,acacetin,panicolin,and wogonin)and nine hub target proteins(EGFR,PTGS2,STAT3,MAPK3,MAPK8,HSP90AA1,MAPK1,MMP9,and MTOR)were further explored.Seventy-seven signaling pathways were correlated with H.pylori-induced inflammation and carcinogenesis.CONCLUSION In summary,we showed that CPS is the core drug combination for treating H.pylori infection.Animal experiments demonstrated that CPS has bacteriostatic properties and can reduce the release of inflammatory cytokines in the gastric mucosa.Network pharmacology predictions further revealed that CPS showed complex chemical compositions with multi-target and multipathway regulatory mechanisms.Although the results derived from network pharmacology are not necessarily comprehensive,they still expand our understanding of CPS for treating H.pylori infection.
文摘Objective:To investigate the distribution and drug resistance of pathogens isolated from 4142 blood cultures, and provide a scientific foundation for guiding clinical rational use of antimicrobial agents for bloodstream infections.Methods: Blood cultures obtained from 4142 inpatients and outpatients who were hospitalized from Jan 2015 to Dec 2016. The culture was detected by automatic BACT/ALERT 3D blood culture system of biomerieux. Bacteria isolated from positive blood cultures were further identified, and the drug susceptibility tests were conducted by VITEK-2 Compact automatic microbial analysis system and ATB Expression microbial analysis system. The drug susceptibility results were evaluated according to CLSI 2014 standard. Statistical analysis was performed by using WHONET 5.6 software. Results:A total of 396 unique strains were isolated from 4142 blood cultures, and the positive rate is 9.6%. Among the positive blood cultures, 194 (49.0%) strains were identified as Gram-positive, 185 (46.7%) strains were identified as Gram-negative, and 17(4.3%) strains were identified as fungi. The coagulase-negative Staphylococcus were the most frequently detectable (29.2%), followed by Escherichia coli (18.4%), Klebsiella pneumonia (7.3%), Staphylococcus aureus (5.1%), Acinetobacter baumannii(5.1%), and Enterococcus genera (5.1%). The incidences of methicillin resistant coagulase negative staphylococcus (MRCNS) and methicillin resistant staphylococcus aureus (MRSA) were 81.9% and 50.0% respectively. However, vancomycin resistant staphylococcus and enterococcus were not detected. The prevalence of extended spectrumβ lactamases (ESBLs) in E. coli and K. pneumoniae were 56.2% and 37.9%, respectively. All the E. coli strains were sensitive to amikacin, piperacillin/tazobactam, imipenem and meropenem, and the sensitive rate of K. pneumoniae strains to imipenem and meropenem were 93.1% and 89.7%, respectively.Conclusions MRCNS stains were the most frequently detected pathogens in blood cultures in the present study. The characteristic of drug resistance for the pathogens indicated that monitoring of imipenem and meropenem resistant K. pneumoniae should be underlined to prevent nosocomial outbreak. Fungi bloodstream infections of ward such as ICU and department of hemopathology should be enhanced monitored.
基金Supported by the Natural Science Foundation of Hunan Province(Nos.2022JJ80086 and 2023JJ60342)the Project of Hunan Provincial Health and Health Commission(No.D202302078705)+4 种基金the Project of Hunan Provincial Student Innovation and Entrepreneurship Training Program(No.2022-5313)the Hunan Provincial Administration of Traditional Chinese Medicine Scientific Research Program(No.2021161)the Hunan University of Traditional Chinese Medicine Primary Discipline Open Fund Project in Chinese Medicine(No.2020ZYX01)the Key Discipline Project on Chinese Pharmacology of Hunan University of Chinese Medicine(No.202302)the Scientific Research Project of Hunan Provincial Administration of Traditional Chinese Medicine(No.B2023150)。
文摘Objective To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis(RA).Methods Tumor necrosis factor(TNF)-α-induced fibroblast-like synoviocytes(FLS)was exposed to additional isorhamnetin(10,20 and 40µmol/L).Overexpression vectors for matrix metalloproteinase-2(MMP2)or MMP9 or SRC were transfected to explore their roles in isorhamnetin-mediated RA-FLS function.RA-FLS viability,migration,and invasion were evaluated.Moreover,a collagen-induced arthritis(CIA)rat model was established.Rats were randomly divided to sham,CIA,low-,medium-,and high-dosage groups using a random number table(n=5 in each group)and administed with normal saline or additional isorhamnetin[2,10,and 20 mg/(kg·day)]for 4 weeks,respectively.Arthritis index was calculated and synovial tissue inflammation was determined in CIA rats.The levels of MMP2,MMP9,TNF-α,interleukin-6(IL-6),and IL-1β,as well as the phosphorylation levels of SRC,extracellular regulated kinase(ERK),and cyclic adenosine monophosphate response element-binding(CREB),were detected in RA-FLS and synovial tissue.Molecular docking was also used to analyze the binding of isorhamnetin to SRC.Results In in vitro studies,isorhamnetin inhibited RA-FLS viability,migration and invasion(P<0.05).Isorhamnetin downregulated the levels of MMP2,MMP9,TNF-α,IL-6,and IL-1βin RA-FLS(P<0.05).The overexpression of either MMP2 or MMP9 reversed isorhamnetin-inhibited RA-FLS migration and invasion,as well as the levels of TNF-α,IL-6,and IL-1β(P<0.05).Furthermore,isorhamnetin bound to SRC and reduced the phosphorylation of SRC,ERK,and CREB(P<0.05).SRC overexpression reversed the inhibitory effect of isorhamnetin on RA-FLS viability,migration and invasion,as well as the negative regulation of MMP2 and MMP9(P<0.05).In in vivo studies,isorhamnetin decreased arthritis index scores(P<0.05)and alleviated synovial inflammation.Isorhamnetin reduced the levels of MMP2,MMP9,TNF-α,IL-6,and IL-1β,as well as the phosphorylation of SRC,ERK,and CREB in synovial tissue(P<0.05).Notably,the inhibitory effect of isorhamnetin was more pronounced at higher concentrations(P<0.05).Conclusion Isorhamnetin exhibited anti-RA effects through modulating SRC/ERK/CREB and MMP2/MMP9 signaling pathways,suggesting that isorhamnetin may be a potential therapeutic agent for RA.
基金This work was supported by the National Natural Science Foundation of China(Nos.81874496,82374530)the Clinical Medical Technology Innovation Guide Project of Hunan Province(No.2020SK53206)+3 种基金the Natural Science Foundation of Hunan Province(No.2021JJ70062)the Changsha Natural Science Foundation Project(No.kq2014019)the Health Special Fund Research Project of Hunan Province(No.B2020-07)the Clinical Pharmaceutical Research Fund of Hunan Medical Association(No.B202012).
文摘Background:Puerarin(Pue)has been reported to be a natural active ingredient with multiple antifibrotic properties.This work aimed at exploring the function of Pue in oral submucousfibrosis(OSF)treatment.Methods:Human oral mucosafibroblasts(hOMF)were induced with transforming growth factor beta1(TGF-β1)and intervened with Pue.Expressions offibrosis-related markers were analyzed by Western blot and IF staining.Cell viability was characterized by the CCK-8 assay.Expressions of miR-30 family members were quantified by qRT-PCR.The correlation betweenfibroblast activation protein(FAP)and miR-30 family expression was evaluated by the Pearson correlation coefficient.Bioinformatics prediction and dual-luciferase reporter assay were employed to verify the regulation between FAP and miR-30b-5p.The specific mechanism of Pue on OSF was explored through the promotion or inhibition of miR-30b-5p.Results:After induction by TGF-β1,hOMF showed upregulated Collagen I,Collagen III,and FAP expressions,while miR-30 family expression was downregulated with miR-30b-5p being the most significant.Pue intervention inhibited the excessive proliferation of TGF-β1-induced hOMF,downregulated FAP,collagen type 3(COL3A1),collagen type 1(COL1A1),matrix metalloproteinase 1(MMP1),and matrix metalloproteinase 3(MMP3)expressions,and restored miR-30 family expression.Bioinformatics prediction and dual-luciferase reporter assay revealed that miR-30b-5p selectively inhibited FAP expression.Mechanistically,miR-30b-5p mimic suppressed the excessive proliferation of TGF-β1-induced hOMF and declinedfibrosis levels.Pue intervention significantly reversed the promotion of TGF-β1-induced OSF by miR-30b-5p inhibition.Conclusion:Pue mediated miR-30b-5p targeting FAP against OSF,which provided a theoretical basis for the pathogenesis research and Pue application in OSF.
基金The authors acknowledge the support of the National Natural Science Foundation of China(No.81804171)Project of Guangdong Provincial Administration of Traditional Chinese Medicine(No.20241049)The Scientific Research Projects of Medical and Health Institutions of Longhua District,Shenzhen(No.2023063).
文摘Background:To explored whether moxa cone moxibustion can reduce peritoneal inflammation by increasing the content of peritoneal macrophages and B cells via interferon-gamma.Methods:The mice were randomly divided into three groups with six mice in each group:the control group,model group,and moxibustion group,and the model was established in mice using cyclophosphamide.In the moxibustion group,the mice received moxa cone moxibustion at Zusanli(ST36)for 7 days.Analysis of Peritoneal cell were detected by flow cytometry and immunofluorescence,the protein expression level in the peritoneal fluid were measured with mouse cytokine antibody arrays and verified by enzyme linked immuno sorbent assay test,and RNA-Sequencing was used for peritoneal cell RNA analysis.Results:Our results showed that moxa cone moxibustion could reduce the loss of large peritoneal macrophages and B1 cells(P<0.05).With the cytokine array analysis and enzyme linked immuno sorbent assay test of peritoneal fluid,we found that IFN‐γwas up-regulated in moxibustion group(P<0.05).There were 169 genes were down-regulated in the model group and up-regulated in the moxibustion group while 19 genes that were up-regulated in the model group and down-regulated in the moxibustion group via RNA-sequencing.Kyoto Encyclopedia of Genes and Genomes pathway analysis of 188 intersect differentially expressed genes were found that the top 3 pathways with the highest enrichment of up-regulated genes included Hematopoietic cell lineage,Inflammatory bowel disease and Malaria.The differentially expressed genes visualization protein-protein interaction network shows the top 10 genes including Ifng,Grb2,CCR7,CTLA4,CXCR5,Foxp3,kit,PRF1,CD5 and klrg1.Conclusion:These findings showed that moxa cone moxibustion can alleviate chemotherapy-induced diarrhea by reducing the loss of large peritoneal macrophages and B1 cells in the peritoneal cavity,possibly through up-regulating inflammatory bowel disease signaling pathway via interferon-gamma to regulate the survival and function of large peritoneal macrophages and B1 cells.
基金This work was supported by the National Natural Science Foundation for Young Scholars of China(82004346 and 82104766)the Natural Science Foundation of Hunan Province(2021JJ30521 and 2021JJ40424)+2 种基金the Open Fund for the First-class Discipline of Integrated Traditional Chinese and Western Medicine of Hunan University of Chinese Medicine(2020ZXYJH38 and 2020ZXYJH39)Natural Science Foundation of Changsha(kq2208202)the University-level Fund Project of Hunan University of Chinese Medicine(2021XJJJ039).
文摘Ischemic stroke is a major public health problem worldwide.Although the circadian clock is involved in the process of ischemic stroke,the exact mechanism of the circadian clock in regulating angiogenesis after cerebral infarction remains unclear.In the present study,we determined that environmental circadian disruption(ECD)increased the stroke severity and impaired angiogenesis in the rat middle cerebral artery occlusion model,by measuring the infarct volume,neurological tests,and angiogenesis-related protein.We further report that Bmal1 plays an irreplaceable role in angiogenesis.Overexpression of Bmal1 promoted tube-forming,migration,and wound healing,and upregulated the vascular endothelial growth factor(VEGF)and Notch pathway protein levels.This promoting effect was reversed by the Notch pathway inhibitor DAPT,according to the results of angiogenesis capacity and VEGF pathway protein level.In conclusion,our study reveals the intervention of ECD in angiogenesis in ischemic stroke and further identifies the exact mechanism by which Bmal1 regulates angiogenesis through the VEGF-Notch1 pathway.
基金This study was supported by the National Natural Science Foundation of China,No.81874464(to YHW)the Natural Science Foundation of Hunan Province of China,No.2019JJ50464(to HY)the Open Fund of the Domestic First-class Discipline Construction Project of Chinese Medicine of Hunan University of Chinese Medicine,No.2018ZYX46(to HY).
文摘In the peripheral nervous system,the activation of Sirtuin 1 can improve insulin resistance;however,the role played by Sirtuin 1 in the central nervous system remains unknown.In this study,rat models of diabetes mellitus were generated by a single injection of streptozotocin.At 8 weeks after streptozotocin injection,the Morris water maze test and western blot assays confirmed that the diabetic model rats had learning and memory deficits,insulin resistance,and Sirtuin 1 expression could be detected in the hippocampus.Insulin and the insulin receptor inhibitor S961 were intranasally administered to investigate the regulatory effects of insulin signaling on Sirtuin 1.The results showed that insulin administration improved the impaired cognitive function of diabetic model rats and increased the expression levels of phosphorylated insulin receptor,phosphorylated insulin receptor substrate 1,and Sirtuin 1 in the hippocampus.Conversely,S961 administration resulted in more severe cognitive dysfunction and reduced the expression levels of phosphorylated insulin receptor,phosphorylated insulin receptor substrate 1,and Sirtuin 1.The Sirtuin 1 activator SRT2104 and the inhibitor Sirtinol were injected into the lateral ventricle,which revealed that the activation of Sirtuin 1 increased the expression levels of target of rapamycin complex 1,phosphorylated cAMP-response elementbinding protein,and brain-derived neurotrophic factor.Hippocampal dendritic length and spine density also increased in response to Sirtuin 1 activation.In contrast,Sirtinol decreased the expression levels of target of rapamycin complex 1,phosphorylated cAMP-response elementbinding protein,and brain-derived neurotrophic factor and damaged the dendritic structure.These findings suggest that the Sirtuin 1 signaling pathway plays an important role in the development of insulin resistance-related cognitive deficits in diabetic rats.This study was approved by the Animal Ethics Welfare Committee of the First Affiliated Hospital of Hunan University of Chinese Medicine(approval No.ZYFY201811207)in November 2018.
基金supported by National Natural Science Foundation of China (Nos. 21804144, 81974000, U1903125, 82073799)Natural Science Foundation of Hunan province in China (Nos. 2021JJ10077, 2021JJ20084, 2022JJ30903)+1 种基金Natural Science Foundation of Changsha City in Hunan province,China (No. kq2202421)the Science and Technology Innovation Program of Hunan Province (No. 2021RC3020)
文摘Macrophages are important antigen-presenting cells to combat tumor via both innate and adaptive immunity,while they are programmed toM2 phenotype in established tumors and instead promote cancer development and metastasis.Here,we develop a nanomedicine that can re-educate M2 polarized macrophages to restore their anti-tumor activities.The nanomedicine has a core-shell structure to co-load IPI549,a PI3Kγinhibitor,and CpG,a Toll-like receptor 9 agonist.Specifically,the hydrophobic IPI549 is self-assembled into a pure drug nano-core,while MOF shell layer is coated for CpG encapsulation,achieving extra-high total drugs loading of 44%.Such nanosystem could facilitate intracellular delivery of the payloads but without any cytotoxicity,displaying excellent biocompatibility.After entering macrophages,the released IPI549 and CpG exert a synergistic effect to switch macrophages from M2 to M1 phenotype,which enables anti-tumor activities via directly engulfing tumor cells or excreting tumor killing cytokines.Moreover,tumor antigens released from the dying tumor cells could be effectively presented by the re-educated macrophages owing to the up-regulation of various antigen presenting mediators,resulting in infiltration and activation of cytotoxic T lymphocytes.As a result,the nanosystem triggers a robust antitumor immune response in combination with PD-L1 antibody to inhibit tumor growth and metastasis.This work provides a non-cytotoxic nanomedicine to modulate tumor immune microenvironment by reprograming macrophages.
