1.Unveiling the role of Pafah1b3 in liver fibrosis: A novel mechanism revealed.
Lifan LIN ; Shouzhang YANG ; Xinmiao LI ; Weizhi ZHANG ; Jianjian ZHENG
Journal of Pharmaceutical Analysis 2025;15(1):101158-101158
Liver fibrosis is a common outcome of various chronic hepatic insults, characterized by excessive extracellular matrix (ECM) deposition. The precise mechanisms, however, remain largely undefined. This study identified an elevated expression of platelet-activating factor acetylhydrolase 1B3 (Pafah1b3) in liver tissues from both carbon tetrachloride (CCl4)-treated mice and patients with cirrhosis. Deletion of Pafah1b3 significantly attenuated CCl4-induced fibrosis, hepatic stellate cell (HSC) activation, and activation of transforming growth factor-β (TGF-β) signaling. Mechanistically, PAFAH1B3 binds to mothers against decapentaplegic homolog 7 (SMAD7), disrupting SMAD7's interaction with TGF-β receptor 1 (TβR1), which subsequently decreases TβR1 ubiquitination and degradation. Pharmacological inhibition using 3-IN-P11, a specific Pafah1b3 inhibitor, conferred protective effects against CCl4-induced fibrosis in mice. Furthermore, Pafah1b3 deficiency reduced hepatic inflammation. Overall, these results establish a pivotal role for Pafah1b3 in modulating TGF-β signaling and driving HSC activation.
2.Polyphyllin VII promotes hepatic stellate cell ferroptosis via the HIC1/CX3CL1/GPX4 axis.
Feng JIANG ; Xinmiao LI ; Mengyuan LI ; Weizhi ZHANG ; Yifei LI ; Lifan LIN ; Lufan HE ; Jianjian ZHENG
Journal of Pharmaceutical Analysis 2025;15(5):101147-101147
Ferroptosis has been shown to mediate the development of fibrosis. Polyphyllin VII (PP7), a bioactive component of Paris polyphylla, exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis. In this study, treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells (HSCs), which could be suppressed by a ferroptosis inhibitor. In addition, it promoted HSC ferroptosis by suppressing glutathione (GSH) peroxidase 4 (GPX4) and enhanced the expression of CX3C chemokine ligand 1 (CX3CL1). Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4. Notably, CX3CL1 directly interacted with GPX4, triggering HSC ferroptosis. The transcription factor hypermethylated in cancer 1 (Hic1), which binds to the Cx3cl1 promoter, increased the expression of CX3CL1. Its absence resulted in downregulation of CX3CL1, suppressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation. HIC1 was found to directly interact with PP7 at the GLY164 site. Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes. HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis in vivo. These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.
3.Effects of single-session table tennis exercise with different intensities on working memory and event-related potentials in college students with depressive symptoms
Qun ZHAO ; Peng WANG ; Shuqi JIA ; Qing LIU ; Cong LIU ; Shufan LI ; Weizhi LIU ; Lijuan MAO
Academic Journal of Naval Medical University 2025;46(7):898-909
Objective To explore the effects of single-session table tennis exercise with different intensities on working memory and the associated cognitive neural processing mechanisms in college students with depressive symptoms by using event-related potential(ERP)technology.Methods A convenience sampling approach was employed to recruit 100 college students with depressive symptoms from a university.Participants were randomly assigned at a 1∶1∶1∶1 ratio to low-intensity exercise group,moderate-intensity exercise group,high-intensity exercise group,or control group.The exercise groups participated in a single 30-min table tennis intervention at intensities corresponding to 57%-64%of maximum heart rate(HRmax)and rate of perceived exertion(RPE)scores ranging from 9-11,65%-75%HRmax and RPE scores 12-13,and 76%-95%HRmax and RPE scores of 14-17(5-min warm-up,20-min monitored exercise,5-min cool-down).The control group did not receive any exercise intervention.Pre-and post-intervention assessments of verbal working memory(VWM)and spatial working memory(SWM)were performed,alongside the recording of ERP components,including the amplitude and latency of N2 and P3,during the tasks.Results A total of 91 participants(20 in the low-intensity exercise group,25 in the moderate-intensity exercise group,23 in the high-intensity exercise group,and 23 in the control group)were enrolled for analysis.In the VWM task,the main effect of time on accuracy was found to be significant(F(1,89)=5.942,P=0.017,partial η2=0.064).Post-intervention,accuracy was significantly improved in the moderate-intensity and high-intensity exercise groups(change=0.027,95%confidence interval[CI]0.001-0.053,P=0.037;change=0.029,95%CI 0.002-0.055,P=0.040).The main effect of time on reaction time was also significant(F(1,89)=7.244,P=0.009,partial η2=0.077).The interaction between group and time was also significant(F(3,87)=2.844,P=0.042,partial η2=0.089).After the intervention,the reaction time was reduced in the low-intensity and moderate-intensity exercise groups(change=-0.095,95%CI-0.183--0.007,P=0.035;change=-0.079,95%CI-0.158-0,P=0.049).The interaction between time and electrode location in the P3 latency in ERP components was significant(F(3,87)=5.785,P<0.001,partial η2=0.062),while the interactions for other ERP measures were not significant(all P>0.05).In the SWM task,the main effect of time on accuracy was significant(F(1,89)=5.092,P=0.027,partial η2=0.055),while the interaction between group and time was not significant(F(3,87)=0.799,P=0.498,partial η2=0.027).After the intervention,accuracy was improved in the moderate-intensity exercise group(change=0.019,95%CI 0-0.037,P=0.046).The main effect of time on reaction time was significant(F(1,89)=14.322,P<0.001,partial η2=0.141).The interaction between group and time was not significant(F(3,87)=1.521,P=0.215,partial η2=0.050).After the intervention,reaction time was shortened in the moderate-intensity and high-intensity exercise groups(change=-0.082,95%CI-0.136--0.027,P=0.004;change=-0.075,95%CI-0.131--0.018,P=0.029).The interaction between time and electrode location in the P3 amplitude in ERP components was significant(F(3,87)=5.475,P=0.001,partial η2=0.059),while the interactions for other ERP measures were not significant(all P>0.05).Conclusion Single-session table tennis exercise with different intensities has a positive effect on working memory in college students with depressive symptoms.Moderate-to high-intensity exercise can enhance VWM accuracy,while low-to moderate-intensity exercise can reduce VWM reaction time.Furthermore,moderate-intensity exercise can improve SWM accuracy,and moderate-to high-intensity exercise can shorten SWM reaction time.Additionally,high-intensity exercise can lead to greater activation of ERP components.
4.Effect of stigma on symptoms of post-traumatic stress disorder in college students:a propensity score matching analysis
Li ZHANG ; Weizhi LIU ; Qianlan YIN
Academic Journal of Naval Medical University 2025;46(7):950-955
Objective To examine the relationship between stigma and post-traumatic stress disorder(PTSD)symptoms among college students.Methods With cluster random sampling method,1 312 college students were surveyed from various types of higher education institutions.Propensity score matching was employed to control potential confounding variables such as gender,age,and education level.Stigma were compared between the PTSD and non-PTSD groups.Results After matching,the students in the PTSD group(n=139)exhibited significantly higher levels of stigma compared to the non-PTSD group(n=139,P<0.01).Further analysis revealed that stigma significantly affected all PTSD symptom clusters,with the strongest association found for hyperarousal and reactivity symptoms.Conclusion Individuals with PTSD may experience more severe stigma,which in turn may exacerbate their PTSD symptoms.Greater attention should be given to the potential impact of stigma on PTSD symptoms in college students,and effective interventions are needed to address this issue.
5.Study on quality standard of wine-processed Coptidis Rhizoma standard decoction
Huilin YANG ; Kaiwei HUANG ; Yanghua LI ; Suqin CAI ; Shuping XU ; Jiabao WEI ; Hui ZHANG ; Weizhi ZHAO ; Pei TAN
International Journal of Traditional Chinese Medicine 2025;47(9):1285-1292
Objective:To establish the quality standard of the standard decoction of wine-processed Coptidis Rhizoma by studying the extraction rate, fingerprint and component quantitative analysis.Methods:ccording to the Technical Requirements for Quality Control and Standard Formulation of Chinese Medicine Formula Granules, 15 batches of the standard decoction of wine-processed Coptidis Rhizoma were prepared, and the paste rate was determined; HPLC fingerprints of 15 batches of standard decoction of wine-processed Coptidis Rhizoma were established, and evaluated by combining similarity evaluation, clustering analysis, principal component analysis and orthogonal partial least squares discriminant analysis; the contents of berberine, epiberberine, pamadine, and safranine in the samples of the 15 batches were determined and analyzed their transfer rates.Results:A total of 15 batches of standard decoction samples were calibrated with 11 common peaks, referring to the recognition of 8 components. The similarity between the samples and the control product was greater than 0.900; the clustering analysis could cluster the 15 batches of samples into 2 classes; the results of the principal component analysis showed that the cumulative variance contribution rate of the 3 principal component factors was 89.388%; the OPLS-DA screened out the 3 components of the quality difference; the 15 batches of samples out of the paste rate was 15.7% -20.8%, and the mass fractions of berberine, epiberberine, safranine, and palmatine were 18.47%-24.38%, 2.82%-3.49%, 5.08%-6.69%, and 4.84%-6.68%, respectively, with transfer rates of 41.7%-61.7%, 46.9%-68.7%, 39.8%-61.5%, and 43.8%-65.2%.Conclusion:The fingerprint and content determination method established in this study is accurate, stable, simple, and can be used for the quality control and evaluation of the standard decoction of wine-processed Coptidis Rhizoma.
6.Protocatechuic acid alleviates colon injury in ulcerative colitis rats
Ercui LI ; Weizhi LI ; Ning HAN ; Si CHEN ; Huijuan FAN
Basic & Clinical Medicine 2025;45(10):1306-1312
Objective To investigate the effect of protocatechuic acid(PCA)on Toll-like receptor 4(TLR4)/nu-clear factor-kappa B(NF-κB)signal pathway in rats with ulcerative colitis(UC).Methods After modeling,rats were divided into control group,model group(5%trinitrobenzene sulfonic acid(TNBS)induction),low(L-PCA),middle(M-PCA),high(H-PCA)dose protocatechuic acid group(rats were given with PCA at doses of 20,40 and 80 mg/kg respectively),and intervention model group(LPS,rats were given with PCA at doses of 80 mg/kg and 0.8 mg/kg LPS solution intraperitoneally),and 12 rats in each group were given the drug continu-ously for 14 days.After treatment,rats were evaluated by disease activity index(DAI),and the morphology and apoptosis of colon were observed by hematoxylin eosin(HE)staining and TUNEL staining.The protein levels of Occludin,Zona occludens 1(ZO-1),claudin-1,Tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-10,TLR4 and p-p65/p65 in colon were detected by Western blotting.The expression of TLR4 protein in colon was de-tected by immunohistochemical staining.Results Compared with control group,the colon of model group rat showed obvious injury,DAI score and positive rate of TUNEL were increased(P<0.05),the relative protein ex-pression of TNF-α,IL-1β,TLR4 and p-p65 were increased(P<0.05),the relative protein expression of Occlu-din,ZO-1,claudin-1 and IL-10 were decreased(P<0.05).Compared with model group,colonic injury was allevi-ated in L-PCA,M-PCA and H-PCA groups,DAI score and positive rate of TUNEL were decreased(P<0.05),the relative protein expression of TNF-α,IL-1β,TLR4 and p-p65 were decreased(P<0.05),the relative protein expression of Occludin,ZO-1,claudin-1 and IL-10 were increased(P<0.05).Compared with H-PCA group,co-lon injury was aggravated in LPS group,DAI score and positive rate of TUNEL were increased(P<0.05),the rel-ative protein expression of TNF-α,IL-1β,TLR4 and p-p65 was increased(P<0.05),the relative protein expres-sion of Occludin,ZO-1,claudin-1 and IL-10 was decreased(P<0.05).Conclusions Protocatechuic acid can al-leviate TNBS-induced colon injury in UC rats,improve intestinal barrier function,and inhibit colon inflammatory response,the mechanism of which is related to the activation of TLR4/NF-κB signaling pathway.
7.Characteristic spectrum of Rheum tanguticum Maxim,ex Balf.water decoction and analysis of different origins and different processed products
Kaiwei HUANG ; Hui ZHANG ; Shuping XU ; Huiling YANG ; Yanghua LI ; Weizhi ZHAO ; Zhijun GUO ; Pei TAN
Drug Standards of China 2024;25(4):330-338
Objective To establish an ultra-high liquid chromatography(UPLC)characteristic spectrum of Rheum tanguticum Maxim.ex Balf.water decoction and conduct chemical pattern recognition analysis,and to identify the medicinal materials of different origins and different processed products.Methods:UPLC was adopted to establish the characteristic spectra of 15 batches of Rheum tanguticum Maxim.ex Balf.Cluster analysis combined with principal component analysis was used to analyze their quality.Rhei Radix et Rhizoma from different origins and different processed products of Rheum tanguticum Maxim.ex Balf.were identified.Results:The characteristic spectrum of Rheum tanguticum Maxim.ex Balf.water decoction was established,18 common peaks were identi-fied,and 15 batches of Rheum tanguticum Maxim.ex Balf.were divided into 2 categories according to their origins by cluster analysis.The similarity between 15 batches of samples from different origins and the control spectrum was greater than 0.900.According to OPLS-DA analysis,a total of 6 markers(rhein-8-O-β-D-glu-cosid,resveratrol-4'-O-β-D-(6''-O-D-gallyl)glucopyranside,isolindleyin,rhein,epicatechin-3-O-D-gallate,and catechin)affecting the quality of Rheum tanguticum Maxim.ex Balf.water decoction samples were found.Rhei Radix et Rhizoma from different origins and different processed products of Rheum tanguticum Maxim.ex Balf.can be effectively distinguished.Conclusion:The established characteristic spectrum method is easy to operate and has good repeatability.It can be used for the quality control of Rheum tanguticum Maxim.ex Balf.water decoction,and can provide reference for the formulation of quality standard of formula granules of Rhei Radix et Rhizoma.
8.Preliminary exploration of prostate cancer screening mode based on the medical community model in primary hospitals
Liwei ZHENG ; Lingmin SONG ; Gang WANG ; Weizhi ZHU ; Liejun HOU ; Maomao LI ; Jianjun HUANG ; Kewen ZHOU ; Bin ZHENG ; Xiaoming XU ; Guobin WENG
Chinese Journal of Urology 2024;45(6):416-419
Objective:To explore the suitable prostate cancer screening mode under the medical community for primary hospitals.Methods:From April 2021 to April 2022, a total of 16007 male population ≥50 years from 9 branches of the medical community of the second hospital of Yinzhou participated in this study. They were divided into four groups according to age with group 1 of 50-59 years old, group 2 of 60-69 years old, group 3 of 70-79 years old, and group 4 of 80 years old and above. Serum tPSA was added to the routine physical examination, and the screening positive patients were referred to the referral hospital for further diagnosis and treatment under the mode of medical community. We proposed multi-parametric MRI (mpMRI) for those with serum PSA ≥4 ng/ml and suspicious lesions should be scored according to PI-RADS V2. The ultrasound-guided transperineal targeted prostate biopsy was performed for those with PI-RADS ≥3 and those with PI-RADS < 3 but tPSA ≥10 ng/ml. The tPSA follow-up examinations were performed every 6 months for tPSA < 10 ng/ml and PI-RADS < 3 points and once a year for tPSA < 4 ng/ml.Results:Among the 16 007 male population ≥50 years, 2 007(12.54%) were found serum PSA ≥4 ng/ml, and 634(31.59%)were referred to the referral hospital through the medical community system. Combining tPSA and mpMRI, 271 patients underwent ultrasound-guided transperineal targeted prostate biopsy. Among them, 162 were finally diagnosed with PCa, with a biopsy positive rate of 59.78%. The detection rate of PCa in all the subjects was 1.01%. According to the pathological grade, 5(3.08%) were in ISUP group 1, 95(58.64%) in ISUP group 2-3, and 62(38.27%) in ISUP group 4-5. There were 102(62.96%), 39(24.07%) and 21(12.96%) with localized, locally advanced or metastatic PCa, respectively. The levels of tPSA in the four groups were (1.13±1.44)ng/ml, (1.77±3.45)ng/ml, (3.27±17.58)ng/ml, and (4.26±11.48)ng/ml, respectively, with statistically significant differences ( P<0.01). The positive number of biopsy in each group was 1 case(0.06%), 56 cases(0.79%), 81 cases(1.36%) and 24 cases(1.82%) respectively, with statistically significant differences ( P<0.01). The number of ISUP 4-5 grades in each group was 0, 17(30.35%), 29(35.80%), and 16(66.67%) respectively, with statistically significant differences ( P<0.01). Conclusions:Based on the medical community system, according to the tPSA screening results of the primary hospitals, it is feasible and effective to refer suspicious patients to the referral hospitals for mpMRI examination, and screen prostate cancer by ultrasound-guided transperineal prostate fusion biopsy.
9.Quercetin suppresses pyroptosis in mouse fibroblasts by inhibiting the NLRP3/caspase-1/GSDMD pathway
Ping SHU ; Mengke YUAN ; Ke YANG ; Weizhi HE ; Li LIU
Journal of Southern Medical University 2024;44(10):1874-1880
Objective To investigate whether quercetin inhibits pyroptosis of mouse fibroblast NIH-3T3 cells by regulating the NLRP3/caspase-1/GSDMD signaling pathway.Methods NIH-3T3 cells were treated with quercetin or MCC950(a specific inhibitor of NLRP3)before stimulation with lipopolysaccharide(LPS)and ATP to induce cell pyroptosis.The optimal quercetin concentration and duration were screened using the CCK-8assay after testing various concentrations and times.Morphological changes of the treated cells was observed,and the levels of IL-18 and IL-1β in the cell culture supernatant were detected with ELISA;the protein expressions of NLRP3,cleaved caspase-1,and GSDMD-N and the mRNA levels of NLRP3,caspase-1 and GSDMD were detected using Western blotting and qRT-PCR.The changes in cell pyroptosis were examined with TUNEL staining and LDH release assay.Results The CCK-8 assay indicated that 24-hour treatment with 20 μmol/L quercetin yielded the most favorable results.LPS and ATP stimulation of NIH-3T3 cells induced obvious swelling,cell membrane rupture and leakage of cell contents,significantly increased IL-18 and IL-1β levels,and enhanced protein expressions of NLRP3,cleaved caspase-1 and GSDMD-N and mRNA levels of NLRP3,caspase-1 and GSDMD.LPS and ATP stimulation also caused a significant increment of TUNEL-positive cell counts and LDH release in NIH-3T3 cells.Treatment with quercetin or MCC950 significantly reduced cell pyroptosis induced by LPS and ATP,lowered the concentrations of IL-18 and IL-1β,decreased the expression levels of NLRP3,caspase-1/cleaved caspase-1,GSDMD/GSDMD-N,and reduced the number of TUNEL-positive cells and LDH release.Conclusion Quercetin suppresses pyroptosis of mouse fibroblasts stimulated with LPS and ATP and reduces secretion of inflammatory cytokines by inhibiting the NLRP3/caspase-1/GSDMD pathway.
10.Research Progress on Ferroptosis,Ulcerative Colitis and Treatment with Traditional Chinese Medicine
Xiaotong LI ; Jiali LI ; Zhiqun CAO ; Nan KANG ; Weizhi KONG ; Zhidong YOU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(4):861-867
Ulcerative colitis is a chronic,non-specific inflammatory disease.The persistent damage to its intestinal epithelium is key to the development of the disease.In recent years,a new form of cell death has been identified by researchers-iron death-which is thought to be an important contributor to intestinal epithelial cell death.The occurrence of iron death is often associated with abnormal intracellular iron metabolism,reduced cystine/glutamate reverse transporter activity,abnormal lipid metabolism,voltage-dependent anion channel activation and overexpression of the Nrf2 gene.Iron death can lead to smaller mitochondria,increased membrane density and reduced number of cristae,unlike conventional cell death,which does not exhibit specific phenomena.Studies have found that TCM can alleviate iron death in intestinal epithelial cells by reducing intracellular iron content,inhibiting lipid reactive oxygen species production and regulating Nrf2 gene expression,thus acting as a treatment for ulcerative colitis.Therefore,Chinese medicine may become an important tool for the treatment of ulcerative colitis.This paper reviews the relationship between cellular iron death and ulcerative colitis and the research progress of Chinese medicine in treating ulcerative colitis through the iron death pathway.

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