1.Wogonoside Attenuates Hypertension-Induced Renal Injury Through Modulation of the MAPK Signaling Pathway:A Mechanism Study
Zhi GUO ; Yi XIE ; Hongshu LIU ; Jundan XIAO ; Rongji CHEN ; Meizhu WU ; Jun PENG ; Aling SHEN
Journal of Sichuan University (Medical Sciences) 2025;56(1):41-50
Objective To investigate the potential therapeutic effects,targets,and pathways of wogonoside in hypertension-induced renal injury using the Gene Expression Omnibus(GEO)database and network pharmacology,and to validate the effects of wogonoside intervention on the renal tissues of spontaneously hypertensive rats(SHR),angiotensin Ⅱ(Ang Ⅱ)-stimulated NRK-52E cell apoptosis,and the regulation of relevant pathways through in vivo and in vitro experiments.Methods GEO dataset and network pharmacology analyses were performed to investigate the key therapeutic targets of wogonoside for hypertensive nephropathy.The STRING database was used to analyze protein-protein interactions.Biological functions were annotated via Gene Ontology(GO),and the potential signaling pathways were enriched using the Kyoto Encyclopedia of Genes and Genomes(KEGG).SHR were randomly divided into groups and given low,medium,or high doses of wogonoside(0.075,0.75,and 7.5 mg/kg)via gastric gavage for 10 weeks.Morphological changes in the kidney tissue were assessed by hematoxylin-eosin(HE)staining.Serum levels of inflammatory cytokines,including tumor necrosis factor α(TNF-α),interleukin(IL)-1 β,and IL-6,were measured using ELISA.Apoptosis rates were evaluated by TUNEL staining,and Western blot was performed to determine the expression of Bax,Bcl-2,cleaved caspase-3,and caspase-3,and the expression of phosphorylated and total extracellular signal-regulated kinases(ERK)and p38 mitogen-activated protein kinase(MAPK)proteins.An in vitro model of Ang Ⅱ-stimulated NRK-52E cells was constructed and was treated with wogonoside at different concentrations(25,50,or 100 μmol/L)for 24 h.The apoptosis rates were then assessed by Annexin V staining,and Western blot was performed to validate the expression of apoptosis-related and pathway-associated proteins.Results Analysis of dataset GSE41453 revealed 11673 upregulated and 5902 downregulated genes in the renal tissues of SHR compared to the Wistar Kyoto(WKY)rats,or the WKY control group.Through the analysis of multiple databases,371 potential targets of wogonoside were identified,resulting in 98 overlapping targets.From these,45 core therapeutic targets were identified through further analysis,including TNF,CASP3,etc.GO analysis significantly enriched processes such as the negative regulation of apoptosis.KEGG pathway enrichment analysis highlighted the apoptosis pathway,IL-17 signaling pathway,and MAPK signaling pathway as being significantly enriched.Wogonoside treatment effectively mitigated pathological damage in SHR kidney tissues and significantly inhibited the expression of inflammatory cytokines,including TNF-α,IL-1 β,and IL-6(P<0.05).It also decreased cell apoptosis rates in SHR kidney tissues and Ang Ⅱ-stimulated NRK-52E cells,downregulated the expression of Bax and cleaved caspase-3,and upregulated Bcl-2 expression(P<0.05).Furthermore,wogonoside treatment inhibited the phosphorylation of ERK and p38 MAPK in SHR kidney tissues and Ang Ⅱ-stimulated NRK-52E cells(P<0.05).Conclusion Wogonoside may exert its protective effects against hypertension-induced renal injury by suppressing the inflammatory response and cell apoptosis,potentially through the regulation of the MAPK signaling pathway.
2.Mechanism of Trifolin in Attenuating Hypertension-Induced Renal Cell Apoptosis via Modulation of the MAPK Signaling Pathway
Meizhu WU ; Zhi GUO ; Yi XIE ; Hongshu LIU ; Hong CHEN ; Xinbiao LIN ; Rongji CHEN ; Aling SHEN ; Jun PENG
Journal of Sichuan University (Medical Sciences) 2025;56(5):1273-1280
Objective To investigate the potential therapeutic effects of trifolin on hypertension-induced renal injury,as well as the key targets and pathways involved.Methods The mRNA transcriptional profiles of peripheral blood clinical samples from hypertensive patients were analyzed using Gene Expression Omnibus(GEO),a high-throughput gene expression database.The network pharmacology method was employed to screen key targets of trifolin in treating hypertension-induced renal injury.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted.NRK-52E cells,a rat renal proximal tubular cell line,were used to construct an angiotensin Ⅱ(Ang Ⅱ)-stimulated cell model.Flow cytometry was performed to assess cell apoptosis rates and Western blotting was performed to determine the expression levels of apoptosis-related proteins,including Bax,Bcl-2,cleaved caspase-3,and caspase-3,and the phosphorylation and total protein levels of the key MAPK pathway proteins,including ERK,p38 MAPK,and JNK.Results Analysis of the dataset GSE75360 revealed that,compared with healthy controls,3 331 genes were upregulated and 3 197 genes were downregulated in peripheral blood mononuclear cells of hypertensive patients.According to network pharmacology analysis,472 potential targets of trifolin were identified,including CASP3 and MAPK1.Protein-protein interaction network analysis showed that these targets were closely associated with apoptosis regulatory signaling pathways.GO and KEGG pathway enrichment analyses indicated that trifolin was significantly enriched in pathways associated with negative regulation of apoptosis,apoptotic signaling pathways,and the MAPK signaling pathway.The in vitro experiments confirmed that,compared with the Ang Ⅱ group,trifolin intervention inhibited apoptosis in Ang Ⅱ-stimulated NRK-52E cells,suppressed the expression of Bax and cleaved caspase-3,promoted Bcl-2 expression,and inhibited the phosphorylation of p38 MAPK,ERK,and JNK(P<0.05).Conclusion Trifolin may exert its protective effect against hypertension-induced renal injury by inhibiting Ang Ⅱ-induced NRK-52E cell apoptosis and regulating the MAPK signaling pathway,representing an important mechanism underlying its therapeutic action.
3.Epidemiological characteristics and influencing factor of non-occupational carbon monoxide poisoning during 2007—2018 in Shanghai
Fei’er CHEN ; Meizhu PAN ; Huihui XU ; Chunyang DONG ; Qing GU ; Qi’ang JIN ; Jianghua ZHANG ; Yewen SHI ; Hailei QIAN ; Chen WU
Journal of Environmental and Occupational Medicine 2022;39(8):878-882
Background Non-occupational carbon monoxide (CO) poisoning is a public health problem that seriously affect people’s health and lives. Objective To describe the prevalence of non-occupational CO poisoning during 2007—2018 in Shanghai, analyze its epidemiological characteristics and potential influencing factors, and explore effective prevention and control measures. Methods Daily reported non-occupational CO poisoning cases and meteorological factors from 2007 to 2018 were collected in Shanghai, epidemiological characteristics were analyzed by descriptive epidemiology methods, and a distributed lag nonlinear model was used to assess the association between temperature and non-occupational CO poisoning. Results A total of 2264 non-occupational CO poisoning events and 3866 cases from 2007 to 2018 were reported in Shanghai, including 59 death cases. More than half of the poisoning cases were female (56.3%), and young adults accounted for more cases than any other age group (54.8%). The poisoning events mainly occurred in winter (from December to next February); however, cases reported in summer increased in recent years. The peak period of the events was from 20:00 to 24:00. Households (85.2%) and restaurants (8.0%) were the common places of non-occupational CO poisoning events, and the main cause was improper use of gas water heater (36.9%). A nonlinear curve was found between daily average temperature of current day and the occurrence of non-occupational CO poisoning. Temperature was negatively associated with the risk of non-occupational CO poisoning when the temperature was lower than 9.6 ℃, while a positive association was found during 9.7-26.0 ℃. Conclusion Winter is a high season for non-occupational CO poisoning in Shanghai, rising cases reported in summer is also worthy of attention. Supervision should be strengthened to ban sales of unqualified gas water heaters, and health education on CO poisoning prevention and control should be conducted through multiple channels, in order to reduce the incidence of CO poisoning.
4.Gonadal mosaicism mediated female-biased gender control in mice.
Meizhu BAI ; Dan LIANG ; Yan CHENG ; Guolong LIU ; Qiudao WANG ; Jinsong LI ; Yuxuan WU
Protein & Cell 2022;13(11):863-868
5.Correction to: Gonadal mosaicism mediated female-biased gender control in mice.
Meizhu BAI ; Dan LIANG ; Yan CHENG ; Guolong LIU ; Qiudao WANG ; Jinsong LI ; Yuxuan WU
Protein & Cell 2022;13(12):962-962
6.Correlation between dietary behavior and mental sub-health among Chinese adolescents
ZHOU Meizhu, WU Huipan, ZHANG Ting, YIN Xiaojian, CAO Junfang
Chinese Journal of School Health 2021;42(1):13-17
Objective:
To determine the relationship between mental sub-health and dietary behavior among Chinese adolescents, and to provide a scientific basis for improving adolescent mental sub-health through healthy dietary behavior.
Methods:
A total of 16 545 adolescents aged 13 to 22 years were sampled by random cluster sampling method in six administrative regions of China. A questionnaire survey was conducted to investigate adolescents’ dietary behaviors and mental sub-health status.
Results:
The proportion of boys consuming breakfast, snacks, carbonated drinks, vegetables, fish and dairy products was 76.2%, 20.2%, 19.0%, 78.4%, 52.4% and 59.2%, respectively, while the proportion of girls was 79.2%, 28.6%, 12.6%, 78.3%, 43.2% and 54.9%, respectively. Except for the "vegetable" option, dietary behaviors showed significant sex differences(χ2=20.79,320.10,229.06,150.27,32.21,P<0.01). In terms of mental sub-health, the detection rates of male adolescents’ mental sub-health status, behavioral sub-health and social sub-health were 20.7%, 26.0% and 17.2%, respectively, while those of female adolescents were 18.6%, 24.1% and 14.8%, respectively. The differences between boys and girls were statistically significant (χ2=17.32,7.66,17.46,P<0.01). Controlling for age and gender, breakfast "normally eating" and "occasionally eat", vegetables "normally eating" and "occasionally eat", fish "normally eating" and "occasionally eat", milk, dairy products "normally drink" and "occasional drink",was negatively associated with teenagers’ psychological sub-health (OR=0.60,0.73;0.50,0.65;0.74,0.77;0.73,0.69,P<0.05).
Conclusion
Healthy dietary behavior could be protective to avoid adolescent mental sub-health.Nutritional lectures and guideline books are needed among students and their parents.Nutritionists are encouraged to provide healthy nutritional advice to school canteen.
7.Research progresson neoadjuvant chemoradiotherapy for locally advanced rectal cancer
Yiru WANG ; Yong ZHANG ; Tong WU ; Meizhu SHEN
Chinese Journal of Radiation Oncology 2020;29(3):225-228
Preoperative neoadjuvant chemoradiotherapy NCR) combined with total mesorectal excision (TME) is the standard treatment mode for locally advanced rectal cancer.Compared with postoperative NCR,preoperative NCR increases the tumor down-staging,sphincter-preserving rate and local control rate.Patients who attain pathological complete response (pCR) after preoperative NCR have better prognosis compared with their counterparts.This article reviews the research progress on preoperative NCR in recent years.
8.High glucose induced macrophages polarized into M2 via activation of PI3K/Akt signaling pathway
Yiping RUAN ; Jie WANG ; Jiabin WU ; Fuyuan HONG ; Meizhu GAO
Chinese Journal of Endocrinology and Metabolism 2017;33(11):976-981
Objective To study the mechanism of differentiation of high glucose induced M2 macrophages used by high glucose medium stimulation. Methods Raw264.7 (murine macrophage cell line)was cultured and stimulated by 4. 25% glucose medium, and mannitol medium was used as osmotic pressure control. Cells were harvested at 0h,4h,8h and 12h to examine the expression of CD206 and Arg-1 and the activation of PI3K/Akt signaling pathway. After blocking the PI3K/Akt signaling pathway by LY294002(the specific inhibitor of PI3K),the expression of Arg-1 was examined by western blot. Results The expression of Arg-1 was increased from 8h while CD206 reached the peak at 12h induced by high glucose which indicated the activation of M2 in a time-dependent manner. Akt was phosphorylated at 8h stimulated by high glucose medium. The specific inhibitor of PI3K reduced the expression of Arg-1 by blocking the phosphorylation of Akt. Conclusion High glucose, rather than high osmotic pressure,induced macrophages polarized into M2 via activation of PI3K/Akt signaling pathway.
9.Comparative Study of Several Pattern Recognition Methods in the Identification of Volatile Oils of Tradition-al Chinese Medicine by Infrared Spectroscopy
Xinhua QIU ; Tiexin TANG ; Yan LIU ; Meizhu WU ; Xiongsi TAN ; Kelin GAN ; Weisheng YAO
China Pharmacy 2015;(21):2986-2988
OBJECTIVE:To compare the performance of several pattern recognition methods in the identification of volatile oils of traditional Chinese medicine(TCM)by infrared spectroscopy. METHODS:The volatile oils of several Lonicera and Citrus TCM were determined by infrared spectroscopy. All samples of infrared spectrum were classified by hierarchical clustering,K-mean clustering,artificial neural networks,and support vector machine. RESULTS:The results of hierarchical clustering and K-mean clus-tering were ineffective. Methods of artificial neural networks and support vector machine achieved correct classification rate of 100%. CONCLUSIONS:Artificial neural networks and support vector machine can be combined with infrared spectroscopy to cre-ate chemometric fingerprinting for the identification of volatile oils of TCM.
10.Identification of Lonicerae japonicae flos Volatile Oils by Fourier-transform Infrared Spectroscopy
Yan LIU ; Tiexin TANG ; Xinhua QIU ; Meizhu WU ; Xiongsi TAN ; Kelin GAN ; Weisheng YAO
Chinese Journal of Information on Traditional Chinese Medicine 2013;(11):63-65
Objective To set up a method for identification of Lonicerae japonicae flos volatile oils using Fourier-transform infrared spectroscopy. Methods The volatile oils of Lonicerae japonicae flos and Lonicerae flos was extracted by steam distillation combined with continuous liquid-liquid extraction with hexane. An oil film was prepared for Fourier-transform infrared spectroscopy scanning by dropping the volatile oils solution on the KBr disc and evaporating the solvent. The obtained infrared spectrum was treated by baseline removing and median filter smoothing. The spectral data within 1800-850 cm-1 was selected as the characteristic spectrum for hierarchical cluster analysis. And the volatile oils of Lonicerae japonicae flos and Lonicerae flos were discriminated by the result of hierarchical cluster analysis. Results Enough volatile oils were extracted for obtaining Fourier-transform infrared spectrum from small amount of Lonicerae japonicae flos. The method developed in the study was able to discriminate Lonicerae japonicae flos volatile oils from Lonicerae flos volatile oils. Conclusion The method can be used for identification of Lonicerae japonicae flos volatile oils.


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