1.Prevention and Treatment of Cardiovascular-Kidney-Metabolic Syndrome with Traditional Chinese Medicine Based on the Core Pathogenesis Evolution of "Constraint,Heat,Deficiency,Stasis,and Toxin"
Zhichao RUAN ; Jiangteng LIU ; Hua ZHANG ; Weijun HUANG ; Qiang FU ; Shidong WANG ; Jinxi ZHAO
Journal of Traditional Chinese Medicine 2025;66(7):680-684
Traditional Chinese medicine (TCM) offers a rich theoretical foundation and clinical experience for the prevention and treatment of cardiovascular-kidney-metabolic syndrome(CKM), demonstrating unique advantage. Building on previous work in managing diabetes, its complications, and chronic kidney disease, our team has proposed a five-phase evolution theory of "constraint, heat, deficiency, stasis, and toxin" as the core pathogenesis. These phases correspond to the pathological progression of constraint of phlegm-dampness, constraint transforming into heat, heat damaging qi and yin, stasis accumulated in the collateral vessels, and toxin induced by deficiency and stasis. In the prevention and treatment of CKM by TCM, it is emphasized to integrate the concept of "treating disease before it arises" with constitution theory, and incorporate the "2-5-8" prevention and treatment strategy, which combines prevention with treatment, tailors interventions to different phases, and employs comprehensive treatment modalities. Our goal is to leverage TCM's holistic advantages in preventing and treating CKM.
2.Predictive value of von Willebrand factor for venous thromboembolism in critically ill patients based on propensity score matching
Jinxi YUE ; Linjun WAN ; Gang WANG ; Ruiling ZHANG ; Xiaoran ZHANG ; Ouya LIU ; Xiaofan YU ; Qingqing HUANG ; Zongfang REN
Chinese Critical Care Medicine 2024;36(1):73-77
Objective:To analyze the predictive value of von Willebrand factor (vWF) for venous thromboembolism (VTE) of patients in intensive care unit (ICU) by using propensity score matching (PSM).Methods:Patients admitted to ICU of the Second Affiliated Hospital of Kunming Medical University from December 2020 to June 2022 who stayed in ICU for ≥72 hours and underwent daily bedside vascular ultrasound screening were included. Baseline data such as age, gender, primary disease, and chronic comorbidities were collected. Coagulation indexes before admission to ICU and 24 hours and 48 hours after ICU admission were collected, including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalized ratio (INR), fibrinogen (Fib), fibrin monomer (FM), vWF, D-dimer, antithrombin Ⅲ (ATⅢ), etc. Patients were divided into VTE group and non-VTE group according to whether they had VTE or not [diagnosis of VTE: patients underwent daily ultrasound screening of bedside blood vessels (both upper and lower limbs, visceral veins), and those suspected of having thrombosis were confirmed by ultrasonographer or pulmonary angiography]. Using PSM analysis method, the VTE group was used as the benchmark to conduct 1 : 1 matching of age, whether there was malignant tumor, whether there was infection, whether there was diabetes, and coagulation indicators before admission to ICU. Finally, the cases with balanced covariates between the two groups were obtained. The risk factors of VTE were analyzed by multivariate Logistic regression analysis. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of vWF in the occurrence of VTE in critically ill patients.Results:A total of 120 patients were enrolled, of which 18 (15.0%) were diagnosed with VTE within 72 hours after admission to ICU, and 102 (85.0%) were not found to have thrombus in ICU. Before PSM, there were significant differences in age, gender, proportion of malignant tumor and infection, and coagulation indexes between VTE group and non-VTE group. After PSM, 14 pairs were successfully matched, and the unbalanced covariables between the two groups reached equilibrium. Multivariate Logistic regression analysis showed that vWF was an independent risk factor for VTE at 48 hours after ICU admission in critically ill patients [odds ratio ( OR) = 1.165, 95% confidence interval (95% CI) was 1.000-1.025, P = 0.004]. ROC curve analysis showed that the area under the ROC curve (AUC) of vWF at 48 hours after ICU admission for predicting VTE was 0.782, 95% CI was 0.618-0.945, P = 0.007. When the optimal cut-off value was 312.12%, the sensitivity was 67.7% and the specificity was 93.0%. Conclusion:Dynamic monitoring of vWF is helpful to predict the occurrence of VTE in ICU patients, and vWF at 48 hours after ICU admission has certain value in predicting the occurrence of VTE.
3.Study on the Molecular Mechanism of Shema Zhichuan Liquid in the Treatment of Neutrophilic Asthma Based on Network Pharmacology and In Vivo Experiment
Leshen LIAN ; Xingru MENG ; Xiufang HUANG ; Jinxi ZHOU ; Yanxiao XIE ; Hailan TAO ; Ziyun JIANG ; Xiaohong LIU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(2):247-256
Objective To investigate the molecular mechanism of Shema Zhichuan Liquid in the treatment of neutrophilic asthma(NA)based on network pharmacology and in vivo experiments.Methods(1)The TCMSP,literature search and Swiss ADME and Swiss Target Prediction databases were used to search and screen the active components and their targets of Shema Zhichuan Liquid.OMIM,GeneCards,DisGeNET and DrugBank databases were used to search and screen NA disease-related targets.The intersection of the active components and NA disease-related targets of Shema Zhichuan Liquid was obtained through the microbiology platform to obtain the potential targets of Shema Zhichuan Liquid for the treatment of NA(common targets).Cytoscape 3.8 software was used to construct the network of"Chinese medicinals-active components-potential targets".The PPI network of potential targets was established by STRING database,and the core targets were obtained by analysing the built-in Mcode plug-in.The Metascape platform was used to enrich the gene ontology(GO),Kyoto Encyclopaedia of Genes and Genomes(KEGG)pathways for the potential targets.(2)BALB/C mice were acclimatised and fed for 1 week and randomly divided into a blank group,NA model group,low-dose group(2.5 g·kg-1)and high-dose group of Shema Zhichuan Liquid(10 g·kg-1),and control group of Dexamethasone(1 mg·kg-1);the NA mouse model was replicated by intraperitoneal injection of sensitizer(OVA+CFA)and nebulized inhalation excitation.OVA/CFA(20 μg OVA+75 μg CFA,0.3 mL)was injected intraperitoneally to sensitize on days 0,7 and 14 respectively,and 5%OVA suspension was nebulized on days 21-30(8 mL each time,40 minutes each time,once a day);1 hour before nebulisation,each group was administered by gastric gavage,and the Dexamethasone control group was administered by intraperitoneal injection once a day.The pathological changes of mouse lung tissue were observed by HE staining;IL-8 content in alveolar lavage fluid was detected by ELISA;mRNA expression levels of NLRP3 and CXCR2 were detected by RT-qPCR;and p-mTOR protein expression levels was detected by immunohistochemistry.Results(1)A total of 826 active component targets and 154 NA disease-related targets were obtained,and 51 potential targets(common targets)for the treatment of NA were obtained from the intersection of the active component and the NA disease-related targets of Shema Zhichuan Liquid.Through the network analysis of"Chinese medicinals-active components-potential targets",quercetin,lignocerotoxin,kaempferol,stigmasterol,naringenin and other key active components were obtained.The PPI network analysis of potential targets yielded 29 core targets,including AKT1,IL6,TNF,EGFR,NLRP3,RELA,MIF,CXCR2,VEGFA,etc..The GO functional enrichment analysis yielded 882 biological process entries,33 cellular component entries,and 61 molecular function entries;KEGG analysis yielded 142 signaling pathways,mainly involving TNF signaling pathway,influenza A signaling pathway,Toll-like receptor pathway,MAPK signaling pathway,mTOR signaling pathway and so on.(2)Results of animal experiments:compared with the blank group,mice in the NA model group showed obvious damage to the airway mucosa,structural disorders,a large number of inflammatory cells infiltration,mucosal congestion,oedema,obvious thickening of the alveolar wall,and narrowing of the alveolar lumen;the level of the inflammatory factor IL-8 in the alveolar lavage fluid was significantly elevated(P<0.05);the mRNA expressions of NLRP3 and CXCR2 in the lung tissues of the mice were significantly up-regulated(P<0.01),and the protein expression of p-mTOR was significantly increased.Compared with the NA model group,the structural arrangement of bronchial epithelial cells in the mice in the low-and high-dose groups of Shema Zhichuan Liquid was slightly disordered,with a small amount of inflammatory cell infiltration around the airways and blood vessels,and the congestion and edema of the bronchial mucosa were significantly reduced;the mRNA expression of CXCR2 in the lung tissues of the mice was significantly down-regulated(P<0.01),and the level of expression of p-mTOR protein was significantly reduced.The IL-8 level in the vesicular lavage fluid of mice in the high-dose group was significantly reduced(P<0.05);the mRNA expression of NLRP3 in the lung tissue of mice in the low-dose group was significantly down-regulated(P<0.05).Conclusion The therapeutic effect of Shema Zhichuan Liquid on NA may be achieved through the key active components,such as quercetin,lignocerol and kaempferol,acting on the core targets,such as NLRP3 and CXCR2,and regulating the key signaling pathways,such as the TNF signaling pathway,the MAPK signaling pathway,the Toll-like signaling pathway,and the mTOR pathway.
4.Effects of Zuogui Jiangtang Jieyu Formula (左归降糖解郁方) on Dendritic Spines of Hippocampal Dentate Gyrus and Wnt5a/RhoA Signaling Pathway in Diabetic with Depression Model Rats
Hui YANG ; Wei LI ; Shihui LEI ; Fan JIANG ; Jian LIU ; Jinxi WANG ; Yi YANG ; Yuhong WANG
Journal of Traditional Chinese Medicine 2024;65(5):520-528
ObjectiveTo explore the potential mechanism of Zuogui Jiangtang Jieyu Formula (左归降糖解郁方, ZJJF) for diabetic rats with depression. MethodsSixty rats were randomly divided into normal group, model group, wingless MMTV integration site family member 5a (Wnt5a) agonist group, ZJJF group, and ZJJF plus Wnt5a inhibitor group, with 12 rats in each group. Except for the normal group, the rats were fed with high-fat chow, streptozotocin injection, and chronic mild unpredictable stress combination, to establish model of diabetes mellitus complicated with depression. After successful modelling, rats in the Wnt5a agonist group were given bilateral hippocampal stereotactic injections of Wnt5a agonist Foxy-5 with 5 μl each for 7 consecutive days; rats in ZJJF group were given 20.52 g/(kg·d) of ZJJF by gavage; rats in ZJJF plus Wnt5a inhibitor group were given the drug by gavage, and bilateral hippocampal stereotactic injections of Wnt5a inhibitors Box5, with the same dosage and injection method as above. The normal group and model group were given 10 ml/(kg·d) of normal saline by gavage. All groups were gavaged for 4 consecutive weeks. At the end of the intervention, the depression-like behaviour of rats was evaluated using the forced swimming experiment (immobility time) and the absent field experiment (number of activities); the blood glucose and insulin levels of rats were measured and the insulin resistance index was calculated; the dendritic morphology of dentate gyrus neurons in the hippocampus was observed using Golgi staining; the level of dentate gyrus neuron proliferation was measured using 5-bromodeoxyuracil nucleoside (Brdu) injection and immunofluorescence; RT-qPCR and Western blot were used to detect the mRNA and protein expression of Wnt5a, Ras homologue genomic member A (RhoA) and Rho homologue-associated coiled-coil protein kinase 1 (ROCK1) in the dentate gyrus. ResultsCompared with the normal group, rats in the model group had significantly higher blood glucose, insulin and insulin resistance indices, longer immobility time, fewer activities, lower Brdu integral optical density values and Wnt5a, RhoA, ROCK1 protein and mRNA expression in the dentate gyrus of the hippocampus (P<0.05 or P< 0.01); the dendritic branches of rat hippocampal dentate gyrus neurons could be seen to be significantly reduced or broken, and their length shortened. Compared with the model group, the blood glucose, insulin and insulin resistance indices of rats in ZJJF group and the ZJJF plus Wnt5a inhibitor group significantly reduced (P<0.05 or P<0.01); the immobility time of rats in the Wnt5a agonist group and ZJJF group was significantly shortened, the number of activities increased, the Brdu integral optical density values elevated, and the Wnt5a, RhoA, ROCK1 protein and mRNA expression elevated (P<0.05 or P<0.01), and the number of dendritic branches of hippocampal dentate gyrus neurons significantly increased, the length lengthened, and the complexity of dendrites increased. Compared with the Wnt5a agonist group, rats in the ZJJF group showed significant decrease in blood glucose, insulin and insulin resistance indices, prolongation of immobilisation time, reduction in the number of activities, and reduction in the Brdu integral optical density value; except for the Wnt5a mRNA in ZJJF group, Wnt5a, RhoA, ROCK1 protein and mRNA expression reduced in both ZJJF group and ZJJF plus Wnt5a inhibitor group (P<0.05 or P<0.01). Compared with ZJJF group, Wnt5a, RhoA, ROCK1 protein and mRNA expression were reduced in ZJJF plus Wnt5a inhibitor group (P<0.05 or P<0.01). ConclusionZJJF can improve hyperglycemia and depressive-like behaviours in rat models of diabetes with depression, and its antidepressant effects may be related to the activation of hippocampal Wnt5a/RhoA signaling and promotion of dentate gyrus neuron dendritic growth.
5.Mechanism of Zuogui Jiangtang Jieyu Prescription in Treatment of Diabetes with Depression Based on GSEA and STEM
Shihui LEI ; Wei LI ; Jinxi WANG ; Jian LIU ; Pan MENG ; Yuhong WANG ; Hui YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):98-106
ObjectiveTo explore and verify the key pathway of Zuogui Jiangtang Jieyu prescription in the treatment of diabetes with depression by means of gene set enrichment analysis (GSEA) and short time-series expression miner (STEM). MethodSD rats were randomly divided into six groups, including a normal group, a model group, high, medium, and low dose groups of Zuogui Jiangtang Jieyu prescription, and a positive drug group. The model of diabetes with depression was established by high-fat feeding, streptozotocin (STZ) injection, and chronic mild unpredictable stress. The high, medium, and low dose groups of Zuogui Jiangtang Jieyu prescription were orally administered at 20.52, 10.26, and 5.13 g·kg-1 respectively. The positive drug group was orally administered 0.18 g·kg-1 metformin and 1.8 g·kg-1 fluoxetine. The rats in the normal group and model group were administered with an equal volume of distilled water. After 28 days, the animals were tested for depressive-like behaviors and cognitive function using the forced swimming test and Morris water maze. Fasting blood glucose was measured using blood glucose test strips. Cholesterol and triglyceride levels were measured using enzyme-linked immunosorbent assay (ELISA). Three hippocampus samples were randomly selected from the normal group, the model group, the high dose group of Zuogui Jiangtang Jieyu prescription for high-throughput transcriptome sequencing. Differential gene analysis, GSEA analysis, and STEM analysis were used to screen the key pathways and target genes of Zuogui Jiangtang Jieyu prescription in the treatment of diabetes with depression. Key target genes were validated using real-time fluorescence quantitative PCR (Real-time PCR). The expression of the signal protein mediated by the target genes was detected by Western blot. ResultCompared with the results in the normal group, the fasting blood glucose, cholesterol, and triglyceride levels in the model group were significantly increased (P<0.01). Moreover, the immobility time in the forced swimming test was significantly increased, while the time to climb the platform was significantly prolonged, and the search distance in the target quadrant was significantly reduced in the Morris water maze test (P<0.05,P<0.01). Compared with the model group, the high dose of Zuogui Jiangtang Jieyu prescription significantly reduced the levels of blood glucose, cholesterol, and triglycerides in rats with diabetes with depression (P<0.05,P<0.01), reduced the immobility time in the forced swimming test, shortened the stage time in the Morris water maze test, and increased the search distance ratio in the target area (P<0.05,P<0.01). Transcriptome sequencing differential analysis showed that the normal group had 1 366 differentially expressed genes compared to the model group, while the model group had 1 149 differentially expressed genes compared to the high dose group of Zuogui Jiangtang Jieyu prescription, with 581 intersecting genes. The GSEA results showed that there were 9 sets of differentially expressed genes between the normal group and the model group, and 43 sets of differentially expressed genes between the model group and the high dose group of Zuogui Jiangtang Jieyu prescription, with 7 intersecting gene sets. STEM analysis showed that according to the analysis order of the normal group, model group, and high dose group of Zuogui Jiangtang Jieyu prescription, two significantly different trend clustering groups were obtained. One key gene set for axonal guidance, as well as key target signal elements Sema3c, Sema7a, Robo3, Epha8, and Epha7, were identified through synthesizing the three analysis results. Real-time PCR validated that compared with the results in the normal group, the mRNA expression of Robo3, Sema7a, and Epha7 in the hippocampus of the model rats was significantly reduced (P<0.05, P<0.01). Compared with the model group, the high dose of Zuogui Jiangtang Jieyu prescription significantly increased the mRNA expression of Robo3, Sema7a, and Epha7 (P<0.05, P<0.01). Western blot results showed that compared with the results in the normal group, the Sema7a, ITGB1, and FAK protein expression in the hippocampus of the model group was significantly reduced (P<0.01). Compared with the model group, the high dose of Zuogui Jiangtang Jieyu prescription significantly increased the protein expression of Sema7a, ITGB1, and FAK in the hippocampus (P<0.05,P<0.01). ConclusionZuogui Jiangtang Jieyu prescription may treat diabetes with depression by regulating axonal guidance based on the Sema7a/ITGB1 signaling pathway.
6.Pathogenesis and Treatment of Stomach Exuberance and Spleen Deficiency in Metabolic Disease
Wenxuan LUO ; Jinxi ZHAO ; Jinyan WEI ; Jiangteng LIU ; Zhichao RUAN ; Kaitong ZHANG ; Le WANG ; Weijun HUANG ; Yonghua XIAO
Journal of Traditional Chinese Medicine 2024;65(19):2041-2044
Stomach exuberance and spleen deficiency are common pathogenesis of many metabolic diseases. Through analyzing the pathogenesis of stomach exuberance and spleen deficiency, it is believed that its essence is stomach heat and spleen deficiency. Stomach heat includes gastrointestinal heat, spleen and stomach damp-heat, and spleen deficiency is divided into deficiency of spleen yin, deficiency of spleen qi , and deficiency of spleen yang. It is suggested that the metabolic diseases of stomach-exuberance and spleen-deficiency syndrome can be divided into three categories,i.e. stomach-heat and spleen yin-deficiency, stomach-heat and spleen qi-deficiency, and stomach-heat and spleen yang-deficiency, and the main treatment methods are clearing and draining heat, nourishing yin and moistening intestine, clearing dampness and heat, strengthening spleen and qi, clearing dampness and heat, strengthening spleen and warming yang, respectively, with prescriptions as Maziren Pills (麻子仁丸), Qinlian Pingwei Powder (芩连平胃散), and Jiawei Lianli Decoction (加味连理汤) accordingly.
7.Protective mechanism of Paeoniae Radix Alba against chemical liver injury based on network pharmacology, molecular docking, and in vitro experiments
Shuangqiao Liu ; Xin Liu ; Sijia Jiang ; Min Fu ; Jinxi Hu ; Jiaqi Liu ; Xiaoxu Fan ; Yingtong Feng ; Shujing Zhang ; Jingxia Wang
Journal of Traditional Chinese Medical Sciences 2024;11(1):55-66
Objective:
To explore and validate the potential targets of Paeoniae Radix Alba (P. Radix, Bai Shao) in protecting against chemical liver injury through network pharmacology, molecular docking technology, and in vitro cell experiments.
Methods:
Network pharmacology was used to identify the common potential targets of P. Radix and chemical liver injury. Molecular docking was used to fit the components, which were subsequently verified in vitro. A cell model of hepatic fibrosis was established by activating hepatic stellate cell (HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1. The cells were exposed to different concentrations of total glucosides of paeony (TGP), the active substance of P. Radix, and then evaluated using the cell counting kit-8 assay, enzyme-linked immunosorbent assay, and western blot.
Results:
Analysis through network pharmacology revealed 13 key compounds of P. Radix, and the potential targets for preventing chemical liver injury were IL-6, AKT serine/threonine kinase 1, jun proto-oncogene, heat shock protein 90 alpha family class A member 1 (HSP90AA1), peroxisome proliferator activated receptor gamma (PPARG), PTGS2, and CASP3. Gene Ontology (GO) enrichment analysis indicated the involvement of response to drugs, membrane rafts, and peptide binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation. Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1, PTGS2, PPARG, and CASP3. Different concentrations of TGP can inhibit the expression of COL-Ⅰ, COL-Ⅲ, IL-6, TNF-α, IL-1β, HSP-90α, and PTGS2 while increasing the expression of PPAR-γ and CASP3 in activated HSC-LX2 cells.
Conclusion
P. Radix primarily can regulate targets such as HSP90AA1, PTGS2, PPARG, CASP3. TGP, the main active compound of P. Radix, protects against chemical liver injury by reducing the inflammatory response, activating apoptotic proteins, and promoting the apoptosis of activated HSCs.
8.Mechanism of Huogu Muli Prescription in regulating the osteoclast-osteogenesis balance in postmenopausal osteoporosis rats
Sijia JIANG ; Yingtong FENG ; Jiaqi LIU ; Jinxi HU ; Ji'an HUA ; Wei LI ; Jingxia WANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(4):506-515
Objective We aimed to investigate(i)the preventive and therapeutic effects of Huogu Muli Prescription(HGMLP),a Chinese medical compound consisting of epimedii folium,drynariae rhizoma,and ostreae concha,on postmenopausal osteoporosis(PMOP)rats and(ii)whether it exerts its effects by regulating the osteoclast-osteogenesis balance.Methods Forty-eight female Sprague-Dawley rats were randomly divided into the following six groups:(i)the sham-operated group,(ii)the model group,(iii)the Qianggu Capsule group,(iv)the calcium carbonate group,and(v,vi)the HGMLP low-dose and high-dose groups(n = 8 rats per group).After adaptive feeding,rats in all groups except the sham-operated group were treated with bilateral ovarian castration to establish the PMOP model.Each day,rats in the Qianggu Capsule group received 0.054 g/kg Qianggu Capsule suspension intragastrically,rats in the calcium carbonate group received 1.670 g/kg calcium carbonate suspension intragastrically,and rats in the HGMLP low-dose and high-dose groups received 0.188 g/kg and 0.375 g/kg HGMLP intragastrically.Rats in the sham-operated group and the model group received an equal volume of normal saline intragastrically.After 90 consecutive days,serum estradiol(E2),estrogen receptor α(ERα),procollagen typeⅠN propeptide(PINP),and tartrate-resistant acid phosphatase 5b(TRACP-5b)were detected by ELISA.Total antioxidant capacity(T-AOC),superoxide dismutase(SOD),catalase(CAT),and malondialdehyde(MDA)levels were measured by colorimetry.Bone mineral density(BMD),trabecular number(Tb.N),trabecular separation/spacing(Tb.Sp),trabecular thickness(Tb.Th),and structure model index(SMI)were measured by Micro-CT,and the microstructure of cancellous bone was observed.The expressions of osteoprotegerin(OPG),receptor activator of nuclear factor-κB(RANK),RANK ligand(RANKL),phosphorylation of forkhead box O3(FoxO3α),Wnt2,β-catenin,and peroxisome proliferator-activated receptor γ(PPARγ)in rat femur tissue were detected by Western blotting.Results(i)The serum levels of E2 and ERα increased in the Qianggu Capsule group and HGMLP groups,compared with the model group(all P<0.05).(ii)Compared with the model group,the serum levels of PINP,TRACP-5b decreased and PINP/TRACP-5b increased in both the Qianggu Capsule group and HGMLP high-dose group(all P<0.05).(iii)The activities of T-AOC,AOD,and CAT in the Qianggu Capsule group and HGMLP groups were higher than those in the model group,while the content of MDA lower(all P<0.05).(iv)Compared with the model group,the femoral BMD,Tb.Th,and Tb.N increased in the Qianggu Capsule group and HGMLP groups,while the femoral Tb.Sp and SMI decreased(all P<0.05);the femoral BMD increased and the Tb.Sp decreased in the calcium carbonate group(all P<0.05).(v)The protein expressions of RANKL,RANK,FoxO3α,and PPARγ in the Qianggu Capsule group and HGMLP groups were lower than those in the model group,while the protein expressions of OPG,Wnt2,and β-catenin were higher(all P<0.05).Conclusion HGMLP can significantly increase estrogen levels,inhibit osteoclast differentiation,and inhibit bone resorption in the PMOP rats.It also alleviates oxidative stress,promotes osteogenic differentiation,inhibits lipogenic differentiation,improves bone formation,and recovers the balance between osteoclasts and osteoblasts,thus achieving prevention and treatment of PMOP.The potential mechanism of HGMLP may be related to regulation via the OPG/RANKL/RANK or FoxO3α/Wnt2/β-catenin/PPARγ pathways.
9.circRTN4 mediates glomerulosclerosis in lupus nephritis by regulating monocyte-derived TNF-α
Xinyan MIAO ; Shiqi ZHANG ; Yi JU ; Yuexin TIAN ; Jinxi LIU ; Xiaojuan FENG
Chinese Journal of Immunology 2024;40(8):1634-1639
Objective:To investigate whether hsa_circ_0054595(circRTN4)is involved in glomerulosclerosis of lupus nephri-tis(LN)by regulating monocyte-derived TNF-α.Methods:RT-qPCR and immunofluorescence were used to detect the expression of TNF-α in monocytes of LN patients,and fluorescence in situ hybridization(FISH)was used to detect the expression of circRTN4.THP1 cells were transfected with circRTN4-siRNA and negative control NC-siRNA,respectively.RT-qPCR and Western blot were used to detect the expression of TNF-α in THP1cell,and ELISA was used to detect the expression of TNF-α in THP1 culture superna-tant.THP1 cells were transfected with mircoRNA mimics,and the expression of TNF-α was detected by Western blot.The direct bind-ing of miR-486-3p to TNF-α and circRTN4 were verified by reversion experiment and dual luciferase reporter gene experiment.MRL/lpr mice were injected with circRTN4 recombinant adeno-associated virus via tail vein,and the expression of circRTN4 in peripheral blood mononuclear cells of the mice was detected by RT-qPCR.ELISA was used to detect the expression of serum TNF-α.HE staining and PAS staining were used to observe the pathological changes,and immunofluorescence was used to detect the expression of FN.Results:The expressions of TNF-α and circRTN4 were increased in monocytes of LN patients(P<0.05).The expression of TNF-α in THP1 was significantly increased in the LN group(P<0.01).Knockdown of circRTN4 inhibited the expression and secretion of TNF-α(P<0.05),and this effect was achieved by binding to miR-486-3p(P<0.01).In vivo,knockdown of circRTN4 in peripheral blood monocytes of MRL/lpr mice reduced the expression of TNF-α in serum(P<0.05),and improved glomerular cell proliferation and FN deposition.Conclusion:Highly expressed circRTN4 in monocytes promotes the expression of TNF-α by binding to miR-486-3p,and participates in the occurrence and development of glomerulosclerosis in LN.
10.Visual analysis of the role of neutrophils in diabetes based on CiteSpace
Jinxi WANG ; Rong YU ; Juan HUANG ; Yangyang LIU ; Tiantian ZHANG ; Chun GUO ; Wei LI ; Hui YANG ; Shihui LEI
Chinese Journal of Comparative Medicine 2024;34(6):28-39
Objective Th is aim of this review was to clarify the role of neutrophils in diabetes by summarizing the characterization studies,potential trends,and research hotspots relating to neutrophils in the diabetes research field.Methods 2998 relevant studies on neutrophils in the diabetes research field indexed in Web of Science from 2010 to 2023 were retrieved,and a visual analysis of the relevant literature was conducted using CiteSpace 6.1.R6.Results Since 2012,the number of publications on this topic has grown rapidly.Bayat Mohammad,Liu Tong,Amini Abdollah,and Zhang Rui are high-yield authors,with seven related articles published.China and Shanghai Jiao Tong University are the country and institution with the most published papers.The most influential journal in this field is"Nature Medicine".Literature co-citation analysis of topics related to diabetes showed that the greatest focus is currently on"extracellular trap"and"COVID-19 patient".Co-occurrence analysis,clustering analysis,and keyword burst analysis indicated that"lymphocyte ratio"(13.08)and"neutrophil extracellular trap"(7.2)are the most researched topics in the field of neutrophils and diabetes.Literature in this field mainly focuses on"myocardial infarction","endothelial","oxidative stress",and"apoptosis".Conclusions This article highlights the evolving trends in research into neutrophils in the diabetes field using CiteSpace,providing new insights for researchers aiming to conduct research in this area.


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