1.Metabolomics Reveals Mechanism of Abelmoschi Corolla Total Flavonoids in Regulating Endoplasmic Reticulum Stress in IgA Nephropathy
Shuying SONG ; Changqing WEN ; Luwan XING ; Yan ZHANG ; Haitao GE ; Fujiang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):153-161
ObjectiveTo elucidate the mechanism by which total flavonoids of Abelmoschi Corolla (TFA) treat immunoglobulin A (IgA) nephropathy (IgAN) through serum metabolomics analysis. MethodsSPF-grade male SD rats were randomly assigned into six groups (n=10): blank, model, low-dose TFA (TFA-L, 27 mg·kg-1), medium-dose TFA (TFA-M, 54 mg·kg-1), high-dose TFA (TFA-H, 108 mg·kg-1), and losartan potassium (LST, 4.5 mg·kg-1) groups. The remaining five groups, excluding the blank group, were modeled with bovine serum albumin (BSA), lipopolysaccharide (LPS), and carbon tetrachloride (CCl4). Specifically, from weeks 1 to 10, BSA was administered via gavage every other day, and a mixture of castor oil and CCl4 was injected subcutaneously once a week, with LPS injected into the tail vein at weeks 6 and 8. After successful modeling, each intervention group was administrated with the medication prepared with distilled water once daily by gavage for a continuous period of 4 weeks. The levels of 24-hour urinary total protein (24 h UP) and serum creatinine (SCr) were quantified by kits, and the serum IgA level was determined by enzyme-linked immunosorbent assay (ELISA). Renal pathological changes were observed by hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining. Renal IgA deposition was assessed by immunofluorescence (IF). Endoplasmic reticulum (ER) stress was observed by transmission electron microscopy. Western blot and immunohistochemistry (IHC) were employed to detect the expression of ER stress-related factors. Non-targeted metabolomics was used to screen differential metabolites for analysis, and key metabolites arachidonic acid (AA), prostaglandin E2 (PGE2), and cyclooxygenase-2 (COX-2) were validated. ResultsCompared with the blank group, the model group showed increased 24-hour urine protein (24 h UP) and serum creatinine (SCr) levels (P<0.01), obvious renal pathological damage, elevated serum IgA level (P<0.01), increased renal AA and PGE2 levels (P<0.01), and up-regulated protein levels of COX-2, glucose-regulated protein 78 (GRP78), phosphorylated eukaryotic initiation factor 2α (P-EIF2α), activating transcription factor 4 (ATF4), inositol-requiring enzyme 1α (IRE1α), and spliced X-box binding protein 1 (XBP1s) in the renal tissue (P<0.05, P<0.01). Compared with the model group, the intervention groups showed reductions in 24 h UP and SCr levels (P<0.05, P<0.01), alleviated renal pathological injury, decreased serum IgA level (P<0.05, P<0.01), and reduced renal AA and PGE2 levels (P<0.01). Western blot and IHC results showed that TFA reduced the levels of COX-2, GRP78, P-EIF2α, ATF4, IRE1α, and XBP1s in the renal tissue (P<0.05, P<0.01). Metabolomics results indicated that 51 commonly differential metabolites were found among the normal, model, and TFA-M groups. TFA ameliorated IgAN by affecting metabolic pathways related to the biosynthesis of arachidonic acid and arginine through L-aspartic acid, prostaglandin 2α, leukotriene B4, leukotriene D4, among others. ConclusionTFA can regulate the arachidonic acid metabolism pathway, thereby modulating ER stress, reducing renal damage, and ameliorating IgA nephropathy.
2.Exploration on the Molecular Mechanism of Bitter-cold Property of Scutellaria Radix Based on Endogenous Metabolites
Xing LIU ; Qi SONG ; Ran XIE ; Jing MENG ; Mengnan ZANG ; Huanhuan ZHANG ; Haijin SONG ; Miao ZHANG ; Hairu HUO ; Feng SUI
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(4):128-134
Objective To identify biomarkers that characterize its bitter-cold properties of Scutellaria Radix on the basis of evaluating its cold and hot properties,as well as possible metabolic pathways and related targets;To explore its molecular mechanism.Methods Totally 40 mice were randomly divided into a control group and a treatment group,and were orally administered with normal saline and Scutellaria Radix decoction,respectively,for 4 consecutive days.The cold and hot plate differential method was used to evaluate the cold and hot tendencies of the mice;UPLC-MS/MS technology was used to analyze mouse blood samples,differential metabolites were screened using principal component analysis,partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis methods,and metabolic pathway analysis was performed;network modular analysis of differential metabolites was performed using Cytoscape 3.9.0 software to identify potential molecular targets.Results On the second day of administration,the anal temperature of mice in the treatment group decreased significantly compared to the control group(P<0.01);in the cold and hot tendency test,the mice in the treatment group showed an overall increase in high-temperature tendency and a higher proportion of high-temperature zone retention.There was a statistically significant difference(P<0.01,P<0.05)between the treatment group and the control group on the 2nd and 3rd day of treatment;the pattern recognition analysis of serum metabolome data showed that the serum samples of the treatment group and the control group could be completely separated,and a total of 14 differential metabolites were screened out;metabolic pathway analysis identified 16 related pathways,including unsaturated fatty acid biosynthesis,linoleic acid metabolism,citric acid cycle(TCA cycle),arachidonic acid metabolism,glycine,serine and threonine metabolism,steroid hormone biosynthesis,etc.;a total of 16 modules were obtained through network modular analysis,among which the arachidonic acid metabolism pathway and linoleic acid metabolism pathway modules were larger;the nodal degree values of arachidonic acid and linoleic acid were greater than the mean,involving arachidonic acid metabolism and linoleic acid metabolism pathways;by screening 26 genes associated with the cytochrome P450 enzyme system were obtained.Conclusion Scutellaria Radix may regulate the body's energy metabolism,achieve its biological effects,and characterize its medicinal properties by intervening in metabolic pathways such as arachidonic acid and linoleic acid.
3.Exploring the Antidepressant Mechanisms of Citron and Bergamot Based on Network Pharmacology and BDNF/TrkB/CREB Signaling Pathways
Meiqing SONG ; Qian YANG ; Qiming ZHONG ; Yanyan NIU ; Liguo TONG ; Jianyue XING ; Mali FENG ; Lili JIA
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(4):1136-1149
Objective Using network pharmacology research methods and animal pharmacology experiments,explore the mechanism of antidepressant effects of traditional Chinese medicine Citron and Bergamot.Methods Using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),ETCM,Symmap,Swiss Target Prediction,and Uniprot data platforms,screen the active ingredients and corresponding gene targets of Citron and Bergamot.Obtain depression gene targets using OMIM,TTD,and Cenecards data platforms.Using Venny 2.1 online software,draw Venn diagrams of the intersection of active ingredients and gene targets.Draw network diagrams between drugs,active ingredients,targets,and diseases using Cytoscape 3.7.2 software.Construct a protein-protein interaction(PPI)network diagram using the STRING data platform for intersecting genes.Using the Metascape data platform,perform gene ontology(GO)function and Kyoto Encyclopedia of Genesand and Genomes(KEGG)pathway enrichment analysis.A rat depression model was established using chronic unpredictable mild stress(CUMS)combined with solitary care,and animal experiments were conducted to verify the BDNF/TrkB/CREB signaling pathway obtained from network pharmacology research.Results The research results of network pharmacology methods show that there are 57 antidepressant active ingredients in Citron,65 antidepressant active ingredients in Bergamot,and important active ingredients include Acetic acid,3,4,7-trimethoxycoumarin and Citric acid,etc.Through the data platform,2717 depression targets and 430 intersection targets were identified.Through PPI network analysis,key gene targets for antidepressant effects in Citron and Bergamot were identified,including TP53,Protein kinase B1,CREB-binding protein,Brain derived neurotrophic factor,etc.Through KEGG analysis,it was found that important signaling pathways include pathways in cancer,PI3K-Akt signaling pathway,Neurotrophin signaling pathway,etc.By observing the neurotrophic factor BDNF/TrkB/CREB signaling pathway in depressed rats,the results showed that the medium dose groups of Citron and Bergamot could significantly increase serum BDNF content(P<0.05),and each treatment group could improve the damage of hippocampal neurons in rats.The high and medium dose groups of Citron and Bergamot significantly increased the expression of BDNF protein in the hippocampal CA1 region(P<0.05,P<0.01).Except for the low-dose group,which showed no difference in TrkB mRNA gene expression,all other treatment groups significantly increased the mRNA gene expression levels of hippocampal BDNF,TrkB and CREB(P<0.01).The medium dose group of Citron and Bergamot increased the expression of BDNF protein in the hippocampus(P<0.01),while the medium and low dose groups significantly increased the relative expression of TrkB protein in the hippocampus(P<0.05).The medium dose group showed an increasing trend in the relative expression of CREB protein.Conclusion Traditional Chinese medicine Citron and Bergamot have therapeutic effects on depression models in rats,and the mechanism of action may be related to the BDNF/TrkB/CREB signaling pathway.
4.PSO algorithm-based optimization study of water conductivity control system for pharmaceutical water equipment of full membrane process
Lin-yong LIU ; Jun MA ; Hong-bin LIU ; Jian-jun SUN ; Yan-jun ZHANG ; Xiu-guo ZHAO ; Zhen-xing SONG
Chinese Medical Equipment Journal 2025;46(6):14-19
Objective To optimize the design of the existing water conductivity control system for pharmaceutical water equipment of full membrane process so as to solve its problems in precision and long cycle time due to water source,ambient temperature and intermittent working mode.Methods The optimized water conductivity control system was composed of an alkali metering pump,a conductivity sensor and a programmable logic controller(PLC),which used a fuzzy proportional-integral-derivative(PID)controller to regulate the water conductivity of pharmaceutical water equipment of full membrane process,and the particle swarm optimization(PSO)algorithm to optimize the parameters of the fuzzy PID controller.A simulation model was established with MATLAB software to verify the performance of the optimized control system.Results Simulation results showed the optimized control system had reductions in overshoot(by 19%)and adjustment time(by 29%)when compared with the fuzzy PID control system,and enhanced control efficiency effectively.Conclusion The optimized control system optimized by the PSO algorithm improves the quality of produced water,and can meet the demands for rapid and safe production of pharmaceutical water by pharmaceutical water equipment of full membrane process in different conditions.[Chinese Medical Equipment Journal,2025,46(6):14-19]
5.Effects of type and abundance of sialic acid receptors on susceptibility and viral ti-ter of different strains of Newcastle disease virus
Bingmei DONG ; Wenya XU ; Lili SONG ; Yanling XING ; Mengran LI ; Ziye LI ; Xueqing WEN ; Jingran ZHANG ; Jingyu ZHANG ; Qiyuan NING
Chinese Journal of Veterinary Science 2025;45(4):656-661
The receptors of Newcastle disease virus(NDV)are sialic acid receptors that mainly in-clude neu5ac-α-2,3gal-β-1,4Glc(SAα2,3Gal)and neu5ac-2-s-α-2,6Gal10Me(SAα2,6Gal).The distribution and abundance of the two receptors in host cells have important effects on virus sus-ceptibility and intracellular proliferation.In order to further explore the effects of sialic acid recep-tors on susceptibility and proliferation characteristics of NDV different strains,the expression lev-els of SAα2,3Gal and SAα2,6Gal receptors on BHK-21 cell membrane were adjusted by overex-pression and RNAi assays,and the TCID50 values were determined after different BHK-21 cells were inoculated with NDV strains Ⅰ and LaSota.The results suggested that NDV strain LaSota preferentially binds to SAα2,6Gal and strain Ⅰ selectively binds to SAα2,3Gal receptor.Further-more,the viral titers of NDV strains LaSota and Ⅰ in cell culture were positively correlated with the expression levels of SAα2,6Gal and SAα2,3Gal receptors on host cell membrane respectively.In conclusion,our studies provide an understanding of the relationship between infectivity of NDV different strains and receptor types of host cell,and provide a method to increase viral titer of NDV for cell-based vaccine production.
6.Mechanism of Liangxue Tuizi Formula in the treatment of Henoch-Sch?nlein purpura rats via reactive oxygen species-mediated activation of NLRP3 inflammasome
Jinwan SONG ; Xianqing REN ; Qiongqiong XING ; Yifan LI ; Manxiang YANG
Chinese Journal of Comparative Medicine 2025;35(4):21-30
Objective To study the effect of Liangxue Tuizi Formula(LXTZF)on reactive oxygen species(ROS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activation in Henoch-Sch?nlein purpura(HSP)rats,and to explore its possible mechanism in the treatment of HSP.Methods Twenty-four rats were divided randomly into four groups:control,model,LXTZF,and compound glycyrrhizin(CG)groups.Except for the control group,a model of HSP was established in the other groups by heat drugs combined with egg albumin.After successful modeling,rats in the LXTZF group were given LXTZF solution 7.47 g/kg,rats in the CG group were given CG solution 13.5 mg/kg by gavage,and rats in the control and model groups were given normal saline solution by gavage once a day for 4 weeks.Samples were collected 8 hours after the last gavage.Skin histopathology changes were observed by hematoxylin and eosin(HE)staining.Serum interleukin(IL)-18 and IL-1βlevels were detected by enzyme-linked immunosorbent assay(ELISA).Changes in ROS levels in the skin were detected by immunofluorescence.Apoptosis-associated speckle-like protein(ASC),NLRP3,cysteinyl aspartate-specific protease-1(Caspase-1)mRNA and protein expression levels in rat skin were detected by real-time quantitative polymerase chain reaction(RT-PCR)and immunohistochemistry and Western blot,respectively.Results The skin pathology in the model group showed obvious inflammatory cell infiltration compared with the control group.Serum IL-18 and IL-1β levels were significantly increased(P<0.05),skin ROS levels were significantly increased(P<0.05),and skin ASC,NLRP3,Caspase-1 mRNA and protein expression levels were significantly increased(P<0.05).Inflammatory cell infiltration in the skin tissues of rats was alleviated in the LXTZF and CG groups compared with the model group,while serum levels of IL-18 and IL-1β were significantly decreased(P<0.05).ROS levels in the skin were significantly decreased(P<0.05),and mRNA and protein levels of ASC,NLRP3,and Caspase-1 in the skin were significantly decreased(P<0.05).Conclusions The mechanism of LXTZF in HSP may be related to the inhibition of ROS-mediated NLRP3 inflammasome activation.
7.Du Meridian electroacupuncture inhibits ferroptosis and promotes neurorepair in rats with acute cervical spinal cord injury
Rongyan SUN ; Luchun XU ; Guozheng JIANG ; Jiawei SONG ; Yukun MA ; Jiaojiao FAN ; Guanlong WANG ; Yongdong YANG ; Xing YU
Chinese Journal of Tissue Engineering Research 2025;29(29):6228-6236
BACKGROUND:Recent studies have shown that Du Meridian electroacupuncture has a unique effect on alleviating spinal cord injury,but the underlying mechanisms require further clarification.OBJECTIVE:To investigate the regulatory effects and the associated action mechanisms of Du Meridian electroacupuncture on ferroptosis after cervical spinal cord injury in rats.METHODS:One hundred SD rats were randomly divided into sham,model,Du Meridian electroacupuncture,RSL3,and Du Meridian electroacupuncture+RSL3 groups.The sham group underwent only laminectomy.The other four groups were subjected to cervical spinal cord injury by the Allen method.The Du Meridian electroacupuncture group received electroacupuncture after cervical spinal cord injury.The RSL3 group received intraperitoneal injections of glutathione peroxidase 4 inhibitor RSL3 after cervical spinal cord injury.The Du Meridian electroacupuncture+RSL3 group received both electroacupuncture and RSL3 intervention after cervical spinal cord injury.Samples were collected on postoperative days 7 and 28 to assess motor function,histological morphology,neuronal survival,glial scar formation,oxidative stress levels,Fe2+content,glutathione peroxidase 4,and long-chain acyl-CoA synthetase 4 expression.RESULTS AND CONCLUSION:(1)Finally,90 rats completed the follow-up experiment,with 18 rats in each group.(2)FLS and BBB scores were significantly higher in the Du Meridian electroacupuncture group compared with the model and Du Meridian electroacupuncture+RSL3 groups(P<0.05).(3)Compared with the model group,Du Meridian electroacupuncture improved cervical spinal cord tissue morphology and mitochondrial ultrastructure,while these effects were inhibited by RSL3.(4)Du Meridian electroacupuncture increased the expression of microtubule-associated protein 2,glutathione peroxidase 4,glutathione,and superoxide dismutase(P<0.05)and reduced the expression of glial fibrillary acidic protein,long-chain acyl-CoA synthetase 4,reactive oxygen species,malondialdehyde,and Fe2+compared with the model group(P<0.05).However,RSL3 reversed the inhibitory effects of Du Meridian electroacupuncture on ferroptosis,lipid peroxidation and oxidative stress.(5)The results suggest that Du Meridian electroacupuncture inhibits ferroptosis by regulating the glutathione peroxidase 4/long-chain acyl-CoA synthetase 4 axis,thereby reducing secondary neuronal damage and glial scar formation after cervical spinal cord injury and improving neurological function.
8.Genetic Correlation Between Autoimmune Liver Disease and Type 1 Diabetes:A Mendelian Randomization Study
Shuyu SHAO ; Xing ZHOU ; Zifang SONG
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2025;54(1):22-29,100
Objective To investigate the potential causal relationship between autoimmune liver diseases(AILD)and type 1 diabetes(T1D)based on two-sample Mendelian randomization(TSM R)method.Methods Genome-wide association study(GWAS)data were obtained from the Open GWAS database.Forward Mendelian randomization analysis was performed with three types of AILD as exposures and T1D as the outcome,while reverse analysis was conducted with T1D as the exposure and three types of AILD as outcomes.Single nucleotide polymorphism(SNP)that was significantly associated with the exposure was selected as instrumental variable(IV).The inverse variance weighting(IVW)method was employed as the primary analytical ap-proach to explore the bidirectional causal relationships between AILD and T1D.Sensitivity analyses,including heterogeneity tests and horizontal pleiotropy tests,were conducted to ensure the robustness of the results.Results The IVW analysis indica-ted that primary biliary cholangitis(PBC)increased the risk of T1D(OR=1.14,95%CI:1.082-1.201,P=9.41 ×10-7),while no significant associations was observed for primary sclerosing cholangitis(PSC)and autoimmune hepatitis(AIH)with T1D(PSC:OR=1.058,95%CI:0.966-1.159,P=0.223;AIH:OR=0.992,95%CI:0.953-1.033,P=0.706).Conversely,T1D was associated with an increased risk of PBC(OR=1.272,95%CI:1.143-1.416,P=1.024×10-5)and PSC(OR=1.246,95%CI:1.072-1.448,P=0.004),but not AIH(OR=1.032,95%CI:0.931-1.144,P=0.551).Conclusion This study demon-strates a bidirectional causal relationship between PBC and T1D,and T1D also increases the risk of PSC.These findings provide new insights and directions for future research into the molecular mechanisms underlying these associations.
9.Expert consensus:Prevention and treatment of dental implant biological complications
Xing WANG ; Liping WANG ; Qintao WANG ; Rong SHU ; Dongying XUAN ; Yiqun WU ; Lixin QIU ; Derong ZOU ; Yingliang SONG ; Jiang CHEN ; Yan XU ; Jincai ZHANG ; Yucheng SU ; Linhu GE ; Yufeng XIE
STOMATOLOGY 2025;45(11):801-807
Dental implantology has developed rapidly for over half a century,since pure titanium(99.7%)dental cylindrical threaded implants were exploited and osseointegration was introduced in 1960s by Prof.Br?nemark.The long term retention rates of 10 years or more are over 95%.However,the biological complications jeopardize the long term effects of dental implant treatment seriously.The prevalence of dental implant biological complications varies greatly among different reports resulting from the disparities on the defini-tions of dental implant biological complications.After analyzing and summarizing the major opinions proposed internationally in recent years,the consensus for the definition of dental implant biological complications has been reached.Generally the dental implant biologi-cal implications can be classified into early stage(before restoration)biological complications and late stage(after restoration)biological complications.The early stage biological complications include acute and chronic infections,pain,soft tissue deficiency,and osseointegration failure,etc.The late stage complications include peri-implant diseases(peri-implant mucositis and peri-implantitis),soft tissue deficiency around implant,implant loosening and dropping off,etc.The various risk factors related to different dental implant biological complications,the strategies of the prevention and treatment for the dental implant biological complications have been discussed comprehensively,and the consensus has been reached.It is aimed to advocate the dentist to pay more attention to the early prevention of the biological implant complications,to promote more researches on the implant biological complications,and to help elevate the level of dental implantology in our country.
10.Clinical diagnostic value of whole-body bone imaging combined with serum N-Osrteoc and VEGFR2 detection for bone metastasis in elderly patients with lung cancer
Siyuan FENG ; Lei LONG ; Tuo XING ; Lipu YU ; Qitao SONG ; Ruiguo ZHANG
Journal of China Medical University 2025;54(3):214-218
Objective To analyze the clinical diagnostic value of whole-body bone imaging combined with serum N-terminal osteo-calcin(N-Osrteoc)and vascular endothelial growth factor receptor 2(VEGFR2)for evaluating bone metastasis in elderly patients with lung cancer.Methods General data of 100 elderly patients with lung cancer diagnozed for the first time at Tianjin Hospital between December 2021 and December 2023 were retrospectively collected.Based on the pathological results,the patients were separated into a lung cancer bone metastasis group of 42 cases and a lung cancer non-bone metastasis group of 58 cases.Serum N-Osrteoc and VEGFR2 levels were detected by using an enzyme-linked immunosorbent assay(ELISA).All patients underwent whole-body bone imaging using SPECT diagnostic equipment.Receiver operator characteristic(ROC)curve analysis was performed to determine the diagnostic value of serum N-Osrteoc,VEGFR2,and whole-body bone imaging for lung cancer bone metastasis.Furthermore,Kappa test was performed to analyze the consistency between different examination methods for diagnozing lung cancer bone metastasis and pathological diagnosis results.Results The serum N-Osrteoc and VEGFR2 levels in the bone metastasis group were significantly higher than those in the non-bone metastasis group(P<0.05).The area under the curve(AUC)for serum N-Osrteoc and VEGFR2 levels,whole-body bone imaging,and their combination for diagnozing lung cancer bone metastasis were 0.847,0.846,0.907,and 0.956,respectively.Furthermore,com-pared with the pathological results,the numbers of false-positive cases were 14,19,8,and 1,those of false-negative cases were 7,7,2,and 3,and the Kappa values were 0.579,0.487,0.799,and 0.917,respectively(P<0.05).The specificity of whole-body bone imaging combined with serum N-Osrteoc and VEGFR2 in diagnozing lung cancer bone metastasis was significantly higher than alone(P<0.05).Conclusion The combination of whole-body bone imaging and serum N-Osrteoc and VEGFR2 levels is of great significance for early diagnosis of bone metastasis in elderly patients with lung cancer.This combined diagnosis has high sensitivity and specificity and can be widely used in clinical practice.

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