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.Formulation and Analysis on the Standard of Off-label Drug Use
Rongji LIU ; Wei ZUO ; Jiancun ZHEN ; Wei ZHANG ; Ling JIANG ; Xiaoyang LU ; Qianzhou LYU ; Zhiqing ZHANG ; Ying CHEN ; Bo ZHANG
Herald of Medicine 2024;43(7):1065-1069
Off-label use means that the intended use of the drug is not included in the instructions approved by the National Medical Products Administration,including unapproved indication,dosage,the course of treatment,route of administration,or population.The formulation of Pharmaceutical Supply Services-Key Medications Management-Off-label Uses is based on relevant laws,regulations,normative documents,guidelines,literatures,and expert opinions,and follows the principles of scientificity,versatility,instructiveness,and operability.This standard regulates and standardizes the institutional and organizational construction,process management,and the whole process of quality management and evaluation improvement of off-label uses,which is the basis for medical institutions to carry out off-label uses management.This article introduced the formulation process of the off-label uses standard and analyzed the key contents of the standard,which would help medical institutions to better comply with and meet the requirements of this standard in the practice of off-label use management.
4.Current situation of remote pharmaceutical care at home and abroad
Ziran NIU ; Yang HU ; Xuelian YAN ; Jinghan QU ; Rongji LIU ; Liping DU ; Ziyu BAI ; Jiantao LI ; Xiaoli DU ; Bo ZHANG
China Pharmacy 2022;33(16):2028-2031
Remote pharmaceutical care refers to the process that pharmacists provide pharmaceutical care to patients remotely through information technology. Remote pharmaceutical care in China starts late and develops slowly. Therefore ,this paper discusses the pharmaceutical care modes that pharmacists at home and abroad can provide under the remote mode by collecting literature. The results show that foreign remote pharmaceutical care starts early and is relatively mature. The service mainly included remote follow-up and intervention ,24-hour online prescription and order review ,24-hour online drug reorganization ,and guidance on rational drug use in remote areas or community hospitals. The service population covers patients with cardiovascular disease , diabetes,asthma,AIDS and so on. Some hospitals have established an integrated pharmaceutical care system of “Internet+Medical Consortium”in China ,with which pharmacists can provide patients with pharmaceutical care such as remote follow-up and intervention,drug consultation and so on. With the promotion of telemedicine ,domestic pharmacists can gradually expand the scope of services ,expand pharmaceutical services such as remote consultation and remote popular science push ,and realize the sharing of high-quality pharmaceutical care for the whole people.
5.Attitude and medical insurance coverage for off-label use in various countries
Rongji LIU ; Ziran NIU ; Wei ZUO ; Yang HU ; Bo ZHANG
Chinese Journal of Hospital Administration 2021;37(10):838-842
Off-label drug use is a global problem in clinical practice. The management status, attitude and medical insurance coverage of off-label drug use are different in various countries. By analyzing the management and reimbursement policy of off-label drug use in other countries, the authors suggested that China should speed up the institutional arrangements of off-label drug use and establish relevant management systems, and strengthen the supervision of off-label drug use, so as to guarantee the rights of patients to the best treatment.
6.Study on extraction process and antioxidant activity of iridoid glycosides in Damnacanthus officinarum Huang
Jinhui DUAN ; Yang LIU ; Rongji HUANG ; Yang HU ; Jinlan RUAN
Journal of Pharmaceutical Practice 2020;38(4):346-349
Objective To optimize the extraction process of main iridoid glycosides in Damnacanthus officinarum Huang and evaluate the antioxidant activity of Damnacanthus officinarum Huang in vitro. Methods The classical heating-reflux extraction method was selected. The volume fraction of ethanol, the volume of solvent and extraction time were taken as the evaluation factors. The comprehensive score of extraction yield and the monotropein content were used as the evaluation indexes. An orthogonal test was designed to select the best extraction conditions. The total reducing capacity, DPPH clearance rate and hydroxyl radical scavenging rate were measured to determine its antioxidant activity in vitro. Results The optimal extraction process was the reflux with 6 times volume of 60% ethanol for 2 hours. Damnacanthus officinarum Huang has certain antioxidant capacity, and the activity of ethyl acetate part had the best effect. Conclusion The optimized extraction process is stable and feasible, which can be used for extraction of the iridoid glycosides from Damnacanthus officinarum Huang. This study has proved that Damnacanthus officinarum Huang has certain antioxidant activity.
7.Investigation of iodine nutrition among different populations after adjusting the salt iodine concentration in Dali City of Yunnan Province
Haitao ZHANG ; Anwei WANG ; Xiuqin LIU ; Feng YE ; Yuxi GUO ; Shujuan LI ; Rongji CAO ; Wenli HUANG
Chinese Journal of Endemiology 2019;38(2):130-133
Objective After implementation of new standard iodized salt,to comprehensively assess the iodine nutrition levels of different populations in Dali City of Yunnan Province.Methods From 2012 to 2015,in Dali City,there were 5 districts divided into east,west,south,north and middle,each district selected 1 township (town),and each township (town) selected 4 administrative villages,15 households for edible salt in each administrative village were sampled,and the salt iodine content was measured by "General Test Method in Salt Industry Determination of Iodine" (GB/T 13025.7-2012).In 2014,in the five districts of east,west,south,north and middle of Dali City,one township (town) was selected,and 20 pregnant women in the early,middle and late stages,respectively,20 lactating women,20 ordinary healthy adults and 20 children aged 0 to 4 were selected from each township (town);one primary school in each township (town) was selected in each district,and 40 students aged 8-10 years old were selected from each primary school as the survey objects.The urine samples of the survey objects were collected,and the urinary iodine content was measured by "Method for Determination of Iodine in Urine by As3+-Ce4+ Catalytic Spectrophotometry" (WS/T 107-2006).In 2015,in each administrative village of Dali,a water source with the largest number of drinking people was investigated,and water iodine was detected by the "Method of Water Iodine Detection Suitable for Iodine Deficiency and High Iodine Areas".Through questionnaires,the sources of iodine supplementation for pregnant and lactating women were investigated.Results The qualified iodized salt consumption rate of residents was higher than 90% per year from 2012 to 2015,and median of salt iodine decreased from 29.38 mg/kg (2012) to 24.96 mg/kg (2015).The medians of urinary iodine in different populations were 136.85 μg/L for pregnant women (n =356),102.63 μg/L for lactating women (n =111),164.03 μg/L for adults (n =163),209.61 μg/L for 8-10 years old children (n =200),157.27 μg/L for children aged 0-< 2 years old (n =57),and 134.08 μg/L for 2-4 years old children (n =50).The median of iodine content of drinking water (n =142) in Dali was 0.62 μg/L,the range of iodine content was 0.00-9.92 μg/L.The average intake frequencies of iodine-rich seaweed for pregment women and lacting women were 0.99,1.07 time/month,respectively,only 1.99% (9/453) of the population supplemented iodine through multivitamin and minerals tablets.Conclusions After reduction of salt iodine content,the iodine nutrition of populations in Dali City (a low water iodine region) is generally at an appropriate level.Maintaining a higher level of qualified iodized salt consumption rate,strengthening the monitoring of different populations and promotion of healthy behaviors are key steps in prevention and control of the disease in the future.

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