Objective To explore the potential effects of endothelial progenitor cells (EPCs)-angiogenesis on mechanism of alleviating cognitive dysfunction in rats subjected to cerebral ischemia-reperfusion (I/R) injury. Methods A total of 121 male Sprague–Dawley (SD) rats were randomly divided into four groups:Sham group (n=31), focal I/R(MCAO, 0.9%saline 10μL, n=30) group, MCAO+Vehicle (sodium azide, 0.1%Vehicle 10μL, n=30) group and MCAO+HPX (1.86 g/L HPX 10μL, n=30) group. The modified neurological severity scores (mNSS) was carried out to determine neurological function deficit after I/R. Morris water maze (MWM) was carried out to assess learning and memory abilities after I/R. The circulating EPCs after I/R were counted by flowcytometry (FCM) combined with double-immunofluorescence staining of CD34 and CD133. Angiogenesis in rat penumbra cortex after I/R was assessed by immunohistochemical technique combined with immunofluorescent chromogenic detection of CD31 and vWF. Results Compared with sham group, the mNSS scores, the escape latency and the circulating EPCs count were increased after I/R, the time percentage spent in target quadrant was reduced, and the new vessel density in penumbra cortex was increased after I/R in MCAO group (P < 0.05 respectively). There were no significant differences in mNSS score, the escape latency, the time percentage spent in target quadrant, the circulating EPCs count and the new vessel density in penumbra cortex between MCAO group and MCAO+Vehicle group ( P>0.05). The mNSS score and the escape latency were significantly decreased, the circulating EPCs count and new vessel density in penumbra cortex were significantly increased after I/R in MCAO+HPX group compared with those of MCAO+Vehicle and MCAO group (P<0.05). Conclusion EPCs-angiogenesis signaling plays positive effects on HPX alleviating cognitive dysfunction in rats subjected to focal cerebral ischemia reperfusion injury.

Objective:To evaluate the role of heme oxygenase-1 (HO-1) in hemopexin (HPX)-induced reduction of cerebral ischemia-reperfusion (I/R) injury in rats.Methods:One hundred and eighty male Sprague-Dawley rats, aged 7-8 weeks, weighing 250-280 g, were divided into 5 groups ( n=36 each) using a random number table method: sham operation group (group SH), I/R group, vehicle group (group V), HPX group, and HPX plus HO-1 specific inhibitor ZnPPIX(HZ group). Local cerebral I/R was produced by middle cerebral artery occlusion for 120 min followed by reperfusion in anesthetized rats.In I/R, V, HPX and HZ groups, 0.9% normal saline 10 μl, 0.1% NaN 3 10 μl, 1.86 g/L HPX (diluted to 10 μl in 0.1% NaN 3 solution), and 1.86 g/L+ ZnPPIX 20 μmol/L (diluted to 10 μl in 0.1% NaN 3 solution) were injected through the lateral ventricle, respectively, immediately after onset of reperfusion.Morris water maze test was used to detect the cognitive function on day 1 before ischemia and day 2 of reperfusion.Rats were sacrificed, brains were removed and brain tissues were obtained for determination of the permeability ratio of Evans blue (EB), brain water content, expression of VE-cadherin in ischemic penumbra (by Western blot), and expression of angiopoietin-1 (Ang1) mRNA and Ang2 mRNA (by real-time polymerase chain reaction). Ang1 mRNA/Ang2 mRNA ratio was calculated.CD31/vWF double labeling immunofluorescence was used to detect the density of neovascularization in hippocampal tissues in the ischemic penumbra. Results:Compared with SH group, the escape latency was significantly prolonged at 2-7 days of reperfusion, the percentage of time of staying at the target quadrant was decreased, the frequency of crossing the platform was decreased, the permeability ratio of EB in brain tissues was increased at day 7 of reperfusion, and the brain water content, Ang1 mRNA/Ang2 mRNA ratio, expression of VE-cadherin and density of neovascularization were decreased in I/R, V, HPX and HZ groups ( P<0.05). Compared with I/R group, the escape latency was significantly shortened at 2-7 days of reperfusion, the percentage of time of staying at the target quadrant was increased, the frequency of crossing the platform was increased, the permeability ratio of EB in brain tissues was decreased at day 7 of reperfusion, and the brain water content, Ang1 mRNA/Ang2 mRNA ratio, expression of VE-cadherin and density of neovascularization were increased in HPX group ( P<0.05), and no significant change was found in the parameters mentioned above in V and HZ groups ( P>0.05). Compared with HPX group, the escape latency was significantly prolonged at 2-7 days of reperfusion, the percentage of time of staying at the target quadrant was decreased, the frequency of crossing the platform was decreased, the permeability ratio of EB in brain tissues was increased at day 7 of reperfusion, and the brain water content, Ang1 mRNA/Ang2 mRNA ratio, expression of VE-cadherin and density of neovascularization were decreased in HZ group ( P<0.05). Conclusion:HO-1 is involved in HPX-induced reduction of cerebral I/R injury in rats.

This study was to investigate the protective effects of Jinqi Jiangtang tablets on diabetic complications of cardiovascular disease in Drosophila. The effects of Jinqi Jiangtang tablets on hypolipidemia and hypoglycemia by high fat diet(HFD)induced model organism Drosophila with the content of triglyceride and trehalose in Drosophila as indexes, were investigated. And the Drosophila heart function was detected by high speed EM-CCD; cell signaling pathways were detected by Western blot and RT-PCR. The results showed that high fat diet could induce the appearance of hyperglycemia and hyperlipidemia on Drosophila model. Jinqi Jiangtang tablets could significantly reduce triglyceride and trehalose and protect heart function of Drosophila induced by high fat diet. Jinqi Jiangtang tablets could also increase the expression of 4ebp mRNA, while decreasing p-4EBP protein and pepck mRNA expression. This study demonstrated that Jinqi Jiangtang tablets have a protective effect on HFD-induced dyslipidemic-diabetic and cardiac dysfunction, which may be related to mTOR/4EBP pathway.

Fibrosis refers to the final outcome of damage in multiple-type tissue and the imbalance of tissue repair especially in the process of chronic inflammatory response diseases.Fibrosis can occur in various organ tissues.Its continuous progression may lead to organ dysfunction and failure,which is a huge threat to human health.Traditional Chinese medicine has significant therapeutic effects in preventing and treating fibrosis.Due to its characteristics of multiple components,pathways,and targets,it has become a hot research topic in the field of fibrosis.Astragali Radix,a Chinese medicinal for supplementing qi,is the root of Astragalus membranaceus(Fisch.)Bge.var.mongholicus Hisao or Astragalus membranaceus(Fisch.)Bge.It has the effects of replenishing qi and elevating yang,generating fluid and nourishing blood,expelling toxin and draining pus,astringing sore and promoting granulation.It has found that Astragali Radix contains many chemical components such as polysaccharides,saponins,and flavonoids,which have good anti-inflammatory and antioxidant effects.Astragali Radix can effectively intervene in the fibrosis process of multiple organ tissues such as the heart,kidney,liver,and lung.Therefore,this article reviews the anti-fibrotic effects and mechanisms of Astragali Radix and its chemical components,hoping to provide ideas and references for the development and utilization of Astragali Radix.

Signal transducer and activator of transcription 3(STAT3)is known to modulate the expression of genes related to cell transformation,proliferation,and survival,making it a significant target for cancer therapy.Recent research has also highlighted the crucial involvement of aberrant STAT3 activation in the pathogenesis of diabetic kidney disease(DKD).Accordingly,this article focuses on the therapeutic potential of targeting STAT3 in DKD.The structure of STAT3,its mechanisms of activity regulation,mechanisms of abnormal STAT3 activation in DKD,and a summary of the current research is provided.The review aims provide a reference for research into the pathogenesis of DKD and the development of new drugs.

Objective:To explore the effect and possible mechanism of Zexie Tang(ZXT)regulate the balance of M1/M2 polarization in macrophage cells.Methods:Lipid metabolism disorder mouse model was induced by Western diet(WD)in vivo,RAW264.7 cell M1/M2 macrophage model was induced by LPS/IL-4 in vitro,set up blank group,model group and ZXT group.The flu-orescence intensity of M1 and M2 macrophage markers in adipose tissue and RAW264.7 cells was observed by immunofluorescence staining;protein levels of p-AKT,AKT and COX-2 were measured by Western blot;levels of macrophage marker gene mRNAs of M1 and M2 were analysed by qPCR;IL-1β and IL-10 were measured by ELISA;content of NO was detected by Griess;binding of active components of Alismatis Rhizoma and Atractylodes Macrocephala with PI3K protein was analyzed by Docking.Results:Compared with WD group,expression of CD11c was significantly decreased in ZXT group,while expression of CD206 was significantly up-regulated;ZXT reversed LPS-induced increased in CD80 expression,down-regulated mRNA levels of M1 macrophage marker gene iNOS,etc,decreased the expression of COX-2 protein,and inhibited the secretion of IL-1β(P<0.001);ZXT promoted IL-4-induced CD206 expression,up-regulation of M2 macrophage marker gene Arg-1 and other mRNAs levels and secretion of IL-10;ZXT reversed the LPS-induced increased in NO release;p-AKT/AKT protein level increased in vivo and in vitro after ZXT administration;Docking re-sults show that many active ingredients in Alismatis Rhizoma and Atractylodes Macrocephala could form hydrogen bonds stably with PI3K protein.Conclusion:ZXT regulates the M1/M2 polarization balance of macrophages,and its mechanism may be related to the regulation of PI3K/AKT pathway.

Objective To investigate the mechanism of astragaloside Ⅰ,the active constituent of milkvetch root,in inhibiting podocyte injury and improving diabetic kidney disease.Methods According to the body weight,60 male db/db mice were randomly divided into the model group,astragaloside Ⅰ low-dose group(10 mg/kg),astragaloside Ⅰ medium-dose group(20 mg/kg),astragaloside Ⅰ high-dose group(40 mg/kg),and valsartan group(10mg/kg),with 12 mice per group.Twelve db/db littermate control db/m mice were used as the control group.The drug was administered by gavage for 8 weeks.Transmission electron microscope was used to observe the ultrastructure of the kidney;immunohistochemistry and Western blotting were used to detect the expression of nephrotic protein(nephrin),a marker of renal podocytes;enzyme-linked immunosorbent assay was used to detect the contents of interleukin-1β(IL-1β)and interleukin-18(IL-18)in the serum of mice;Western blotting was used to detect the protein expressions of NOD-like receptor thermoprotein domain-related protein 3(NLRP3),cysteinyl aspartate specific proteinase 1(Caspase-1),and Gasdermin D(GSDMD)in kidney tissue.Results Compared with the control group,the glomeruli of the model group showed obvious podocyte loss and foot process fusion;the protein expression of nephrin was decreased(P＜0.05);the contents of IL-1 β and IL-18 in serum were increased(P＜0.05);the protein expressions of NLRP3,Cleaved-Caspase-1,and GSDMD-N were increased(P＜0.05).Compared with the model group,the renal pathological damage in the astragaloside Ⅰ administration groups were alleviated;the protein expression of nephrin was increased(P＜0.05);the contents of IL-1β and IL-18 in serum were decreased(P＜0.05);the protein expressions of NLRP3,Cleaved-Caspase-1,and GSDMD-N were decreased(P＜0.05).Conclusion Astragaloside Ⅰ may play a role in intervening diabetic kidney disease by inhibiting pyroptosis and improving podocyte injury.

Objective To explore prescription medication rules and potential mechanism of traditional Chinese medicine(TCM)in the treatment of alcoholic liver disease(ALD)based on the technology of data mining and network pharmacology.Methods The prescriptions related to the treatment of ALD were retrieved in Chinese National Knowledge Infrastructure,Wanfang,Chinese Biomedical Literature and VIP databases.After the data were collated according to the filter criteria,IBM SPSS Statistics 27.0 and IBM SPSS Modeler 18 software were used to analyze the prescription rules and association rules.Then,the medication rules of TCM in the treatment of ALD were summarized,and the core drug combinations were obtained.Active ingredients in the core drug combinations for ALD and their targets were screened by network pharmacology.GO and KEGG analysis were performed on the main targets,and molecular docking technique was used to verify the binding ability of active ingredients to main targets.Results A total of 143 prescription for ALD were screened,involving 222 Chinese medicine,among which 28 high-frequency Chinese medicine were used with a frequency≥25 times.Eight core drug combinations were obtained by associations rule analysis.It has been found that there are 215 intersection targets between"Poria-Atractylodis macrocephalae Rhizoma-Hearba Artemisiae Scopariae"and ALD,including six core targets of AKT1,TNF,VEGFA,IL-1β,SRC,EGFR.One hundred and sixty-eight of signaling pathways are involved,including cancer pathways,PI3K/AKT signaling pathways,chemical carcinogenesis-reactive oxygen species,lipid and atherosclerosis,etc.Molecular docking results showed that the main active components including cerevisterol,genkwanin and demethoxycapillarisin had good binding ability to AKT1.Conclusion The main active ingredients in"Poria-Atractylodis macrocephalae Rhizoma-Hearba Artemisiae Scopariae"can participate in the regulation of key signaling pathways such as PI3K/AKT by acting on key target proteins(AKT1,TNF,and VEGFA).Subsequently,they play a role in inhibiting inflammatory response and apoptosis,slowing down liver fibrosis,and promoting hepatocyte repair.This study provides data support and theoretical guidance for the study of TCM in the treatment of ALD.

OBJECTIVE To explore the effect mechanism of ethanol extract from Atractylodes macrocephala （EEAM） on microglial phagocytosis and degradation of amyloid β （Aβ） based on peroxisome proliferator-activated receptor γ （PPAR- γ） signaling pathway. METHODS Taking neuromicroglial cell BV2 as subjects， confocal microscopy was used to observe the effects of EEAM （0.3， 0.4， 0.5 mg/mL， similarly hereinafter） on phagocytosis and degradation of Aβ in microglia. Human embryonic kidney cell HEK293 was used to investigate the effects of EEAM on luciferase transcriptional activity of PPAR-γ. The effect of EEAM on nuclear translocation of PPAR-γ was investigated by immunofluorescence. Alzheimer’s disease BV2 cell model was induced by Aβ1-42， and quantitative polymerase chain reaction was used to investigate the effects of EEAM on mRNA expressions of PPAR-γ downstream target genes （Lxra， Lxrb， Abca1， Abcg1， Cd36， Sra and Apoe）. RESULTS The results of Aβ uptake experiment showed that after the intervention of medium and high doses of EEAM， fluorescence intensity of Aβ in BV2 cells increased significantly （P＜0.05）. The degradation experiment of Aβ showed that after the intervention of medium and high doses of EEAM， fluorescence intensity of Aβ in BV2 cells decreased significantly （P＜0.05）. After the intervention of different doses of EEAM， luciferase transcriptional activity of PPAR-γ in HEK293 cells increased significantly （P＜0.05）； fluorescence intensity of PPAR-γ in BV2 cells and nuclei （except for low-dose group） increased significantly （P＜0.05）. mRNA expressions of Lxra， Lxrb， Abca1， Abcg1， Cd36， Sra and Apoe in BV2 cells were increased significantly （P＜0.05）. CONCLUSIONS EEAM can promote the uptake and degradation of Aβ in microglia by activating PPAR-γ signaling pathway， thus improving Alzheimer’s disease.