1.Shionone Inhibits Glomerular Fibirosis by Suppressing NLRP3 Related Inflammasome though SESN2-NRF2/ HO-1 Pathway
Tian XIAO ; Hanzhen ZHAO ; Yucong WANG ; Mengyin CHEN ; Cong WANG ; Chen QIAO
Diabetes & Metabolism Journal 2025;49(1):34-48
Background:
Diabetic nephropathy (DN) is the most common and serious complication of diabetes mellitus. Shionone (SH), an important triterpenoid compound in the root extract of Aster, might exert a protective effect in DN mice and high glucose cultivated glomerular podocytes. The current study aimed to unravel the underlying mechanism by which SH mitigates DN. We postulate that SH stimulates the expression of sestrin-2 (SESN2), a pivotal stress-inducible protein in the anti-inflammasome machinery.
Methods:
We utilized high-fat diet combined with streptozotocin (55 mg/kg intraperitoneal) for DN mice model, and high glucose (30 mM, 48 hours) cultured glomerular podocytes for DN cell model to evaluate the effect of SH. We also preformed experimentation on SESN2 deficiency models (SESN2 knockout mice and SESN2 siRNA in cells) to further prove our hypothesis.
Results:
The results demonstrated that SH effectively suppressed glomerular fibrosis, induced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, and inhibited NLR family pyrin domain containing 3 (NLRP3) activation. Furthermore, our findings revealed that SH exerted its anti-inflammatory effect through Sesn2-dependent nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and subsequent activation of its downstream target heme oxygenase-1 (HO-1).
Conclusion
In summary, our findings suggest that SH serves as a promising therapeutic agent for the treatment of DN-related glomerular fibrosis. SH enhances the expression of SESN2, attenuates α-smooth muscle actin accumulation, and suppresses NLRP3-related inflammation through the Nrf2/HO-1 signaling pathway.
2.Shionone Inhibits Glomerular Fibirosis by Suppressing NLRP3 Related Inflammasome though SESN2-NRF2/ HO-1 Pathway
Tian XIAO ; Hanzhen ZHAO ; Yucong WANG ; Mengyin CHEN ; Cong WANG ; Chen QIAO
Diabetes & Metabolism Journal 2025;49(1):34-48
Background:
Diabetic nephropathy (DN) is the most common and serious complication of diabetes mellitus. Shionone (SH), an important triterpenoid compound in the root extract of Aster, might exert a protective effect in DN mice and high glucose cultivated glomerular podocytes. The current study aimed to unravel the underlying mechanism by which SH mitigates DN. We postulate that SH stimulates the expression of sestrin-2 (SESN2), a pivotal stress-inducible protein in the anti-inflammasome machinery.
Methods:
We utilized high-fat diet combined with streptozotocin (55 mg/kg intraperitoneal) for DN mice model, and high glucose (30 mM, 48 hours) cultured glomerular podocytes for DN cell model to evaluate the effect of SH. We also preformed experimentation on SESN2 deficiency models (SESN2 knockout mice and SESN2 siRNA in cells) to further prove our hypothesis.
Results:
The results demonstrated that SH effectively suppressed glomerular fibrosis, induced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, and inhibited NLR family pyrin domain containing 3 (NLRP3) activation. Furthermore, our findings revealed that SH exerted its anti-inflammatory effect through Sesn2-dependent nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and subsequent activation of its downstream target heme oxygenase-1 (HO-1).
Conclusion
In summary, our findings suggest that SH serves as a promising therapeutic agent for the treatment of DN-related glomerular fibrosis. SH enhances the expression of SESN2, attenuates α-smooth muscle actin accumulation, and suppresses NLRP3-related inflammation through the Nrf2/HO-1 signaling pathway.
3.Shionone Inhibits Glomerular Fibirosis by Suppressing NLRP3 Related Inflammasome though SESN2-NRF2/ HO-1 Pathway
Tian XIAO ; Hanzhen ZHAO ; Yucong WANG ; Mengyin CHEN ; Cong WANG ; Chen QIAO
Diabetes & Metabolism Journal 2025;49(1):34-48
Background:
Diabetic nephropathy (DN) is the most common and serious complication of diabetes mellitus. Shionone (SH), an important triterpenoid compound in the root extract of Aster, might exert a protective effect in DN mice and high glucose cultivated glomerular podocytes. The current study aimed to unravel the underlying mechanism by which SH mitigates DN. We postulate that SH stimulates the expression of sestrin-2 (SESN2), a pivotal stress-inducible protein in the anti-inflammasome machinery.
Methods:
We utilized high-fat diet combined with streptozotocin (55 mg/kg intraperitoneal) for DN mice model, and high glucose (30 mM, 48 hours) cultured glomerular podocytes for DN cell model to evaluate the effect of SH. We also preformed experimentation on SESN2 deficiency models (SESN2 knockout mice and SESN2 siRNA in cells) to further prove our hypothesis.
Results:
The results demonstrated that SH effectively suppressed glomerular fibrosis, induced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, and inhibited NLR family pyrin domain containing 3 (NLRP3) activation. Furthermore, our findings revealed that SH exerted its anti-inflammatory effect through Sesn2-dependent nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and subsequent activation of its downstream target heme oxygenase-1 (HO-1).
Conclusion
In summary, our findings suggest that SH serves as a promising therapeutic agent for the treatment of DN-related glomerular fibrosis. SH enhances the expression of SESN2, attenuates α-smooth muscle actin accumulation, and suppresses NLRP3-related inflammation through the Nrf2/HO-1 signaling pathway.
4.Shionone Inhibits Glomerular Fibirosis by Suppressing NLRP3 Related Inflammasome though SESN2-NRF2/ HO-1 Pathway
Tian XIAO ; Hanzhen ZHAO ; Yucong WANG ; Mengyin CHEN ; Cong WANG ; Chen QIAO
Diabetes & Metabolism Journal 2025;49(1):34-48
Background:
Diabetic nephropathy (DN) is the most common and serious complication of diabetes mellitus. Shionone (SH), an important triterpenoid compound in the root extract of Aster, might exert a protective effect in DN mice and high glucose cultivated glomerular podocytes. The current study aimed to unravel the underlying mechanism by which SH mitigates DN. We postulate that SH stimulates the expression of sestrin-2 (SESN2), a pivotal stress-inducible protein in the anti-inflammasome machinery.
Methods:
We utilized high-fat diet combined with streptozotocin (55 mg/kg intraperitoneal) for DN mice model, and high glucose (30 mM, 48 hours) cultured glomerular podocytes for DN cell model to evaluate the effect of SH. We also preformed experimentation on SESN2 deficiency models (SESN2 knockout mice and SESN2 siRNA in cells) to further prove our hypothesis.
Results:
The results demonstrated that SH effectively suppressed glomerular fibrosis, induced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, and inhibited NLR family pyrin domain containing 3 (NLRP3) activation. Furthermore, our findings revealed that SH exerted its anti-inflammatory effect through Sesn2-dependent nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and subsequent activation of its downstream target heme oxygenase-1 (HO-1).
Conclusion
In summary, our findings suggest that SH serves as a promising therapeutic agent for the treatment of DN-related glomerular fibrosis. SH enhances the expression of SESN2, attenuates α-smooth muscle actin accumulation, and suppresses NLRP3-related inflammation through the Nrf2/HO-1 signaling pathway.
5.A case-control study on the association of Hashimoto’s thyroiditis and anti-thyroid antibodies with oral lichen planus
LIU Yuan ; CHEN Yan ; CONG Zhaoxia ; LI Yiming ; XUE Rui ; ZHAO Jin
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(9):757-764
Objective:
This study aims to explore the association between oral lichen planus (OLP) and Hashimoto’s thyroiditis (HT) and its anti-thyroid antibodies to provide clinical evidence for thyroid disease screening in patients with OLP.
Methods:
This study was approved by the institutional ethics committee. A total of 125 clinically and histopathologically confirmed patients with OLP were enrolled as the case group, and they were matched with 125 non-OLP controls based on sex and age. Demographic data (gender, age, lesion type, and disease duration) were collected from both groups. Serum levels of thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) were measured to analyze their associations with sex, age, lesion type, and disease duration in patients with OLP.
Result:
The prevalence of HT in patients with OLP was 31.20%, significantly higher than that in the control group (9.60%) (χ2=18.504, P<0.001). The prevalence of HT in female patients with OLP (39.13%) was significantly higher than that in male patients (9.09%)(χ2=10.93,P<0.001). The positivity rate of thyroid peroxidase antibodies (TPOAb) in patients with OLP (17.6%) was significantly higher than in the control group (4.0%) (χ2=10.989, P<0.001). The TPOAb positivity rate was significantly higher in female patients (22.83%) than in male patients (3.03%) (χ2=5.210, P=0.014). There was no statistically significant difference in the positivity rate of TgAb between patients with OLP (7.2%) and the control group (3.2%) (P>0.05). Patients with erosive lesions had a significantly higher TPOAb positivity rate (25.0%, 17/68) compared to those with non-erosive lesions (8.77%, 5/57), and the difference was statistically significant (χ2=4.831, P=0.028). Logistic regression analysis revealed that female patients with OLP had an 8.935-fold higher risk of being TPOAb positive compared to males (OR=8.935, 95%CI: 1.134-70.388, P=0.038). Patients with erosive OLP lesions had a 3.199-fold higher risk of TPOAb positivity compared to those with non-erosive lesions (OR=3.199, 95%CI: 1.064-9.618, P=0.038).
Conclusion
The prevalence of HT is higher in patients with OLP, with higher positivity rates of anti-thyroid antibodies observed in female patients and those with erosive OLP lesions. This suggests that thyroid disease screening should be incorporated into the clinical management of patients with OLP, especially for women and patients who present with erosive lesions.
6.Association between prolactin/testosterone ratio and breast cancer in Chinese women.
Qian CAI ; Xiaohan TIAN ; Yuyi TANG ; Han CONG ; Jie LIU ; Song ZHAO ; Rong MA ; Jianli WANG ; Jiang ZHU
Chinese Medical Journal 2024;137(3):368-370
7.Protective mechanism of amifostine on acute radiation injury by regulating gut microbiota
Yue CONG ; Li LI ; Yimeng ZHAO ; Yuanyuan XU ; Jianting GONG ; Jiali GUAN
China Pharmacy 2024;35(4):459-463
OBJECTIVE To explore the protective mechanism of amifostine on acute radiation injury mice. METHODS Thirty C57BL/6J mice were randomly divided into normal control group, model group and amifostine group (150 mg/kg), with 10 mice in each group. Thirty minutes before irradiation, the mice in the amifostine group were intraperitoneally injected with amifostine; normal control group and model group were given constant volume of normal saline intraperitoneally; then acute radiation injury was induced by 4 Gy X-ray radiation in both model group and amifostine group. The white blood cell count (WBC), platelet count and red blood cell (RBC) count in mice were detected 2 hours before irradiation and on days 1, 4, 7, 10 and 14 after irradiation; the changes in the proportion of WBC (neutrophils, lymphocytes and monocytes) on the 7th day after irradiation were analyzed. The 16S rRNA high-throughput sequencing was used to analyze the structure of gut microbiota in mice feces on the 7th day after irradiation, then its correlation with WBC was analyzed. RESULTS The counts of WBC on the 1st, 4th, 7th and 10th day after irradiation, platelet count on the 10th day after irradiation and RBC count on the 1st day after irradiation in the amifostine group were significantly higher than those in model group (P<0.05). Compared with normal control group,β diversity of gut microbiome showed significant change, relative abundance of Firmicutes increased and that of Bacteroidetes decreased in model group. Amifostine could reverse the change in β diversity of gut microbiome, and the relative abundance of Bacteroidetes and Firmicutes. The model group consisted of four distinct species, namely Allobaculum, Erysipelotrichia, Erysipelotrichales and Erysipelotrichaceae, which were significantly negatively correlated with the proportion of peripheral blood lymphocytes (P<0.01); amifostine group consisted of two distinct species, namely Lactobacillus murinus and L. crispatus, which were significantly negatively correlated with the proportion of neutrophils (P<0.05). CONCLUSIONS Amifostine significantly improves irradiation-induced injury by regulating dysbiosis of LY201816) gut microbiota.
8.Historical Evolution and Key Information Research on Pediatric Famous Classical Formula Yigongsan
Jiangmin SU ; Jun ZHANG ; Cong GUO ; Anyi ZHAO ; Liang JIANG ; Heng ZHANG ; Jipeng DI ; Sha CHEN ; Li LIU ; Yan LIU ; An LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):205-214
Yigongsan is derived from Xiaoer Yaozheng Zhijue written by QIAN Yi in the Northern Song dynasty, which is the No. 3 formula in the Catalogue of Ancient Famous Classical Formulas(The Second Batch of Pediatrics) released by the National Administration of Traditional Chinese Medicine(TCM) in September 2022, and it can be developed as a class 3.1 new TCM drug. By referring to ancient medical books and modern literature, this study conducted herbal textual research on Yigongsan from five aspects, including historical evolution, origin and processing, dosage conversion, usage and preparation methods, and functional application, then formed the key information table of this formula, in order to provide reference for the development of reference samples and preparations of Yigongsan. Based on the results of the study, it is recommended that Panax ginseng should be removed the basal part of stem(rhizoma), Poria cocos should be removed the peel, Citrus reticulata should be cut into shreds and Glycyrrhiza uralensis should be used. According to 4.13 g/Qian(钱), 1 g/slice for ginger, 3 g for each jujube and 300 mL/Zhan(盏), the doses of Ginseng Radix, Poria, Atractylodis Macrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma, Citri Reticulatae Pericarpium, Zingiberis Rhizoma Recens, Jujubae Fructus were 1.652, 1.652, 1.652, 1.652, 1.652, 5, 6 g, and the total amount was 19.26 g. The decocting method was to crush the medicinal materials into fine powder with 50-80 mesh, add 300 mL of water and decoct to 210 mL for each dose, then remove the dregs and take it warmly. This formula was recorded in ancient books as the main treatment for the cold-deficiency of spleen and stomach, and Qi stagnation in children with vomiting and diarrhea and lack of appetite. It has been flexibly applied by later generations of physicians, and is often used to treat anorexia, inflammation of the digestive tract, diarrhea and other diseases in children.
9.Evaluation of GRADE Clinical Research Evidence of Chinese Patent Medicine Combined with Western Medicine in Treatment of Hypertension with Dyslipidemia
Jiaheng WANG ; Yukun LI ; Liangyu CUI ; Yilan ZHENG ; Zhiwei ZHAO ; Cong REN ; Tianyue JING ; Tong YIN ; Liying WANG ; Xuejie HAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):95-105
ObjectiveTo evaluate the effect of antihypertensive and lipid-regulating Chinese patent medicine combined with conventional Western medicine in the treatment of hypertension with dyslipidemia. To carry out the evidence synthesis of clinical research and provide evidence-based evidence support for clinical decision-making. MethodThe databases including China National Knowledge Infrastructure (CNKI),Wanfang Data Knowledge Service Platform (WF),VIP,SinoMed,Embase,PubMed,Web of Science (WOS),and the Cochrane Library were searched for randomized controlled trials (RCT) of all listed Chinese patent medicines in the treatment of hypertension with dyslipidemia from the establishment of the databases to April 15,2023. The literature was screened and extracted,and the risk of bias tool 2.0 (RoB2) was used to assess the quality and risk of bias of the methodology. Revman 5.4.1 software was used to analyze the outcome indicators. Grading of Recommendations Assessment,Development and Evaluation (GRADE) was applied to assess the quality of evidence formed by clinical research data. The inclusion and recommendation of Chinese patent medicines in the National Drug Catalogue for Basic Medical Insurance,Work-related Injury Insurance and Maternity Insurance (2022) and domestic guidelines and consensus were searched to form a bubble chart. ResultA total of 15 studies were included. The evaluation of the methodological quality of each study showed that the risk of bias stemmed from the lack of blinding and allocation concealment,and low sample size. The comprehensive analysis of clinical studies showed that Dengzhan Shengmai capsules combined with rosuvastatin and amlodipine besylate,Yindan Xinnaotong capsules combined with simvastatin and levamlodipine tablets,Xiaoshuan Tongluo capsules combined with nifedipine controlled release tablets and pravastatin sodium tablets,Xinshubao capsules combined with atorvastatin calcium tablets and irbesartan,Wenyading capsules combined with enalapril,and Jiangzhining tablets combined with conventional Western medicines were all superior to conventional Western medicines used in the control group in improving systolic blood pressure (SBP),diastolic blood pressure (DBP),cholesterol (TC),triglyceride (TG),low density lipoprotein cholesterol (LDL-C),and high density lipoprotein cholesterol (HDL-C). There was no significant difference in the incidence of adverse reactions between the two groups. The GRADE evaluation of the main outcome indicators showed that the evidence quality of SBP and incidence of adverse reactions was graded as B,that of DBP as C,and that of total TC,TG,LDL-C,and HDL-C as D. The evaluation of Chinese patent medicines covered by medical insurance and recommended by guidelines and consensus showed that Yindan Xinnaotong soft capsules,Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules belonged to class B drugs of medical insurance,and were recommended for 7,6 and 3 times in the guidelines and consensus,respectively. ConclusionCompared with simple medicine treatment,Chinese patent medicine combined with conventional Western medicine has more advantages in improving blood pressure and blood lipid,and shows higher safety. Among them,Yindan Xinnaotong soft capsules,Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules have stronger clinical applicability and economy. All the trials included in this article adhered to the principle of randomization and reported the outcome measures. However,the quality of evidence in related clinical studies was low. In terms of trial design,large-sample,multi-center,blinded randomized controlled trials based on the consolidated standards of reporting trials (CONSORT) statement are still needed for comprehensive trial designs and reporting,to further improve the GRADE quality evaluation and guideline formulation under the guidance of evidence-based medicine,so as to provide higher quality evidence-based research evidence for clinical decision-making.
10.GRADE Clinical Study Evidence Evaluation and Expert Consensus on Antihypertensive Chinese Patent Medicines Combined with Western Medicines for Treatment of Hypertension
Liangyu CUI ; Yukun LI ; Tianyue JING ; Yu WANG ; Cong REN ; Tong YIN ; Zhiwei ZHAO ; Jiaheng WANG ; Chenge SUN ; Dasheng LIU ; Zhizheng XING ; Xuejie HAN ; Liying WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):106-115
ObjectiveTo evaluate the quality of research and evidence related to antihypertensive Chinese patent medicines combined with western medicines for the treatment of hypertension, synthesize and update the evidence, form expert consensus, and provide evidence for clinical decision-making. MethodThe databases of China National Knowledge Infrastructure (CNKI), WanFang Data Knowledge Service Platform (WanFang), Vip Chinese Science and Technology Journal Database (VIP), Chinese Biomedical Literature Service System (Sinomed), National Library of Medicine (PubMed), Cochrane Library, Web of Science, and US Clinical Trials Registry were searched for randomized controlled trials of antihypertensive Chinese medicine combined with western medicine for the treatment of hypertension from database construction to July 31, 2022. The quality of the literature was evaluated using the bias risk assessment tool in Cochrane Handbook 6.3. Evidence synthesis of main outcome indicators was performed using R software. The Grading of Recommendations Assessment, Development, and Evaluation profiler (GRADEprofiler) 3.6 was employed to evaluate the quality of evidence. Expert consensus was formed based on the Delphi method after two rounds of voting. Result64 pieces of literature were included, and the results of literature quality evaluation and risk of bias showed that 70.31% (45/64) of the studies indicated some risks, and 29.69% (19/64) indicated high risks. Compared with conventional western medicines, the combination of Chinese patent medicines with western medicines can significantly lower systolic pressure (SBP) and diastolic pressure (DBP), increase the effective rate of antihypertensive, reduce the incidence of adverse reactions, endothelin-1, and traditional Chinese medicine syndrome scores. Egger's test showed that Songling Xuemaikang capsules reduced SBP and DBP. Tianma Gouteng granules reduced SBP and DBP and increased the effective rate of antihypertensive, and Xinmaitong capsules reduced SBP and increased the effective rate of antihypertensive, without significant publication bias. Songling Xuemaikang capsules increased the effective rate of antihypertensive, and Xinmaitong capsules decreased DBP, with significant publication bias. The results of the GRADE evidence quality evaluation showed that most evidence was at grades B and C. Finally, four strong recommendations and 14 weak recommendations were formed. ConclusionCompared with conventional western medicines for the treatment of hypertension, antihypertensive Chinese patent medicines combined with western medicines have advantages in reducing blood pressure and improving drug use safety, but they are mostly weak recommendations in terms of efficacy, and more high-quality evidence is needed.


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