1.T5MHCII: deep learning-based model for MHC-II peptide binding affinity prediction
Zheng GAO ; Xiangdong GAO ; Wenbing YAO ; Hong TIAN
Journal of China Pharmaceutical University 2025;56(3):368-375
To address the current issue of low performance in predicting the binding affinity between antigenic peptides and specific MHC class II molecules, which fails to meet clinical requirements, we proposed T5MHCII, a deep learning-based prediction model for the affinity of MHC II class molecules to peptides. The model employed the knowledge previously acquired from the protein language model ProtT5 to extract the amino acid sequences via a transfer learning approach, thereby generating high-quality characterizations. This knowledge was then integrated with the robust learning abilities of deep learning to develop a novel model with enhanced predictive capabilities. The results of the five-fold cross-validation demonstrated that the model exhibited superior performance compared to NetMHCIIpan-3.2, PUFFIN, DeepMHCII, and RPEMH, with an AUC of 0.893±0.003 and a PCC of 0.780±0.006. The leave-one-out cross-validation (LOOCV) further demonstrated that the model exhibited enhanced generalization capabilities. This study proposes a novel approach to enhance the precision of peptide-MHCII prediction in the context of limited data affinity through the application of deep learning techniques.
2.Effects of Dahuang Tangluo Pills on Intestinal Inflammatory Injury in Type 2 Diabetes Rats Based on TLR4/NF-κB Signaling Pathway
Zhongtang LIU ; Yonglin LIANG ; Xiangdong ZHU ; Dong AN ; Yankui GAO ; Min BAI ; Sichen ZHAO ; Yunhui ZHAO ; Xiaoli PEI
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(2):91-98
Objective To explore the effects and mechanism of Dahuang Tangluo Pills on intestinal inflammatory injury in type 2 diabetes mellitus(T2DM)rats based on TLR4/NF-κB signaling pathway.Methods Eight ZDF(fa/+)rats were used as the blank group,and 40 ZDF(fa/fa)rats were fed with high-fat diet and then randomly divided into model group,metformin group(0.18 g/kg metformin)and TCM high-,medium-and low-dosage groups(2.16,1.08,0.54 g/kg Dahuang Tangluo Pills),respectively.The medication groups were gavaged with corresponding dosages for 12 consecutive weeks.The body mass and fasting blood glucose(FBG)of rats before and after intervention were detected.After the intervention,an oral glucose tolerance test(OGTT)was performed,the serum glucose(GLU),glycosylated serum protein(GSP),triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)contents were detected.ELISA was used to detect serum fasting insulin(FINS),free fatty acids(FFA)and tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-22,lipopolysaccharide(LPS),secreted immunoglobulin A(SIgA)contents in colonic tissue.HE staining was used to observe the morphology of colonic tissue,and Western blot was used to detect the expressions of Toll like receptor 4(TLR4),nuclear factor-κB p65(NF-κB p65),p-NF-κB p65,NF-κB inhibitor α(IκBα),p-IκBα,myeloid differentiation factor 88(MyD88)and zona pellucida protein-1(ZO-1)in colonic tissue.Results Compared with the blank group,the body mass and FBG significantly increased in the model group(P<0.01),blood glucose significantly increased at all time points of OGTT(P<0.01),serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly increased,serum HDL-C and colonic tissue SIgA contents significantly decreased(P<0.01),with colonic tissue nuclear condensation,cytoplasmic dissolution,inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly increased,while the protein expressions of IκBα and ZO-1 significantly decreased(P<0.01).Compared with the model group,the body mass and FBG significantly decreased in metformin group,TCM high-and medium-dosage groups(P<0.01),blood glucose decreased at different time points of OGTT,and serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly decreased,serum HDL-C and colonic tissue SIgA contents significantly increased(P<0.05,P<0.01),with significant improvement in colonic tissue structure and reduction in inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly decreased,while the proteins expression of IκBα and ZO-1 significantly increased(P<0.05,P<0.01).Conclusion Dahuang Tangluo Pills may inhibit the activation of the TLR4/NF-κB signaling pathway,reduce the release of inflammatory factors,improve intestinal inflammatory injury,restore intestinal homeostasis,thereby improving glucose and lipid metabolism and exerting therapeutic effects on T2DM.
3.Effects of Dahuang Tangluo Pills on Intestinal Inflammatory Injury in Type 2 Diabetes Rats Based on TLR4/NF-κB Signaling Pathway
Zhongtang LIU ; Yonglin LIANG ; Xiangdong ZHU ; Dong AN ; Yankui GAO ; Min BAI ; Sichen ZHAO ; Yunhui ZHAO ; Xiaoli PEI
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(2):91-98
Objective To explore the effects and mechanism of Dahuang Tangluo Pills on intestinal inflammatory injury in type 2 diabetes mellitus(T2DM)rats based on TLR4/NF-κB signaling pathway.Methods Eight ZDF(fa/+)rats were used as the blank group,and 40 ZDF(fa/fa)rats were fed with high-fat diet and then randomly divided into model group,metformin group(0.18 g/kg metformin)and TCM high-,medium-and low-dosage groups(2.16,1.08,0.54 g/kg Dahuang Tangluo Pills),respectively.The medication groups were gavaged with corresponding dosages for 12 consecutive weeks.The body mass and fasting blood glucose(FBG)of rats before and after intervention were detected.After the intervention,an oral glucose tolerance test(OGTT)was performed,the serum glucose(GLU),glycosylated serum protein(GSP),triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)contents were detected.ELISA was used to detect serum fasting insulin(FINS),free fatty acids(FFA)and tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-22,lipopolysaccharide(LPS),secreted immunoglobulin A(SIgA)contents in colonic tissue.HE staining was used to observe the morphology of colonic tissue,and Western blot was used to detect the expressions of Toll like receptor 4(TLR4),nuclear factor-κB p65(NF-κB p65),p-NF-κB p65,NF-κB inhibitor α(IκBα),p-IκBα,myeloid differentiation factor 88(MyD88)and zona pellucida protein-1(ZO-1)in colonic tissue.Results Compared with the blank group,the body mass and FBG significantly increased in the model group(P<0.01),blood glucose significantly increased at all time points of OGTT(P<0.01),serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly increased,serum HDL-C and colonic tissue SIgA contents significantly decreased(P<0.01),with colonic tissue nuclear condensation,cytoplasmic dissolution,inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly increased,while the protein expressions of IκBα and ZO-1 significantly decreased(P<0.01).Compared with the model group,the body mass and FBG significantly decreased in metformin group,TCM high-and medium-dosage groups(P<0.01),blood glucose decreased at different time points of OGTT,and serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly decreased,serum HDL-C and colonic tissue SIgA contents significantly increased(P<0.05,P<0.01),with significant improvement in colonic tissue structure and reduction in inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly decreased,while the proteins expression of IκBα and ZO-1 significantly increased(P<0.05,P<0.01).Conclusion Dahuang Tangluo Pills may inhibit the activation of the TLR4/NF-κB signaling pathway,reduce the release of inflammatory factors,improve intestinal inflammatory injury,restore intestinal homeostasis,thereby improving glucose and lipid metabolism and exerting therapeutic effects on T2DM.
4.Efficacy of Neuroform Atlas stent-assisted coil embolization in ruptured anterior communicating wide-necked aneurysms
Zongfei JIANG ; Zhenrui LIU ; Fengjia LI ; Feng SI ; Jun ZHU ; Yong GAO ; Xiangdong LU ; Chunyu SONG
Chinese Journal of Neuromedicine 2024;23(5):484-488
Objective:To explore the efficacy and safety of Neuroform Atlas stent-assisted coil embolization in ruptured anterior communicating wide-necked aneurysms.Methods:Thirty-two patients with ruptured anterior communicating wide-necked aneurysms accepted Neuroform Atlas stent assisted coil embolization in Department of Neurosurgery, People's Hospital Affiliated to Shandong First Medical University from January 2022 to June 2023 were chosen. DSA was performed immediately after surgery, and aneurysm embolization was assessed using Raymond grading. Prognoses were assessed by modified Rankin Scale (mRS, mRS scores≤2 as good prognosis and mRS scores>2 as poor prognosis) at last follow-up. DSA was performed again 6 months after surgery to assess the aneurysm healingResults:Neuroform Atlas stents were successfully implanted in all 32 patients; Postoperative DSA showed that aneurysm embolization reached Raymond grading I in all 32 patients(100%). No such complications as in-stent thrombosis, cerebral vasospasm, or poor opening of the stent were noted excepted for one with intraoperative aneurysm rupture hemorrhage. At the last follow-up, 31 patients had good prognosis and 1 had poor prognosis; in 22 patients underwent DSA re-examination, Raymond grading I was noted in 20 patients (90.91%) and grading II in 2 (9.09%).Conclusion:Neuroform Atlas stent-assisted coil embolization for ruptured anterior communicating wide-necked aneurysms seems safe and effective.
5.Disease burden of Parkinson's disease in China: a conclusion from 1990 to 2021 and a prediction from 2022 to 2030
Zongfei JIANG ; Wenping YANG ; Feng SI ; Jun ZHU ; Siquan ZHU ; Zhenrui LIU ; Xiangdong LU ; Yong GAO ; Chunyu SONG
Chinese Journal of Neuromedicine 2024;23(12):1205-1210
Objective:To analyze the disease burden of Parkinson's disease (PD) in China from 1990 to 2021 and predict the disease burden of PD from 2022 to 2030.Methods:Based on the data of PD incidence in China from the Global Burden of Disease Study 2021 (GBD 2021), changes in PD disease burden from 1990 to 2021 were analyzed. Age-period-cohort model was used to analyze the independent influences of age, period and cohort in PD incidence (according to age group of 5 years, patients were divided into 15 groups: group of 20-24 years, group of 25-29 years..., and group of 90-94 years; according to a 5-year period, patients were divided into 6 groups: group of 1992-1996, group of 1997-2001..., and group of 2017-2021; because of birth cohort=period-age, patients were divided into 20 birth cohorts: birth cohort of 1897-1906, birth cohort of 1902-1911..., and birth cohort of 1992-2001). Nordpred model was used to predict the disease burden of PD from 2022 to 2030.Results:(1) From 1990 to 2021, number of PD patients, and PD incidence and standardized incidence in China showed upward trends. The standardized incidence increased by 89.68% for the total population, 89.71% for males, and 77.64% for females. (2) PD incidence was low in young subjects and increased obviously in subjects aged 60 years. PD incidence in subjects aged 20-24 years or 90-94 years was 0.07/100 000 and 643.31/100 000, respectively. Compared with female subjects, male subjects aged 60-94 years had higher PD incidence. (3) The onset relative risk increased from 0.71 (95% CI: 0.69-0.73) in group of 1992-1996 to 1.17 (95% CI: 1.16-1.19) in group of 2017-2021 in the total population, increased from 0.68 (95% CI: 0.66-0.70) to 1.18 (95% CI: 1.16-1.21) in males, and increased from 0.75 (95% CI: 0.73-0.77) to 1.14 (95% CI: 1.12-1.16) in females. (4) Onset relative risk was 0.40 (95% CI: 0.33-0.48) in the earliest birth cohort (1897-1906), which increased to 1.81 (95% CI: 0.95-3.43) in the latest birth cohort (1992-2001). (5) Number of PD patients in males, females and total population in China would increase to 455 010, 301 173 and 756 183, respectively, and the standardized incidence would increase to 56.45/100 000, 32.28/100 000 and 43.40/100 000, respectively, till 2030. Conclusion:PD disease burden in China from 1990 to 2021 is severe, particularly among males and the elderly; the disease burden is projected to continue rising up till 2030.
6.A Multicenter, Randomized, Double-blind, and Placebo-parallel Controlled Trial of Tibetan Medicine Ruyi Zhenbaowan in Treatment of Knee Osteoarthritis
Chunquan SUN ; Yanming XIE ; Jinghua GAO ; Weiheng CHEN ; Lianxin WANG ; Shangquan WANG ; Xiangdong TIAN ; Zujian XU ; Yuxin ZHENG ; Mingwang ZHOU ; Chungen LI ; Zhanwang XU ; Jiayi GUO ; Shuangqing DU ; Qigang CHEN ; Quan JI ; Zhiqiang BAI ; Jing XIAO ; Wanli QI ; Weiyi YANG ; Jingxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):57-67
ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan(RYZBW)in the treatment of initial and early knee osteoarthritis (KOA) through a prospective multicenter,randomized,double-blind,and placebo-parallel controlled trial. MethodFrom October 13th, 2021 to December 25th, 2021, 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital, Chinese Academy of Chinese Medical Sciences, and they were randomly divided into observation group and control group, with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education, and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks, and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score (WOMAC score), and the secondary outcome measures were the response rate of visual scale (VAS) pain score, WOMAC sub item scores (joint pain, joint stiffness, and joint function), quality of life (SF-12) score, and traditional Chinese medicine (TCM) syndrome score. Result(1) Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW, and the difference was statistically significant (P<0.05). There was no significant difference between the two groups in improving VAS score response rate, WOMAC function score, WOMAC stiffness score, SF12-PCS (quality of life-physical health) score, SF12-MCS (quality of life-mental health) score, and TCM syndrome score. (2) Subgroup analysis. ① In terms of VAS score response rate, the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of (4, 5], and the difference was statistically significant (P<0.05). ② In terms of TCM syndrome score, for subjects aged [56, 60] and [61, 65], the decrease in total TCM syndrome score in the observation group was better than that in the control group, and the difference was statistically significant (P<0.05). ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score, VAS score response rate, WOMAC pain score, WOMAC function score, and TCM syndrome score for patients with initial and early KOA, which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.
7.Effect of Modified Dahuang Huanglian Xiexintang on Oxidative Stress Injury of Liver in Type 2 Diabetes Mellitus Rats Based on Nrf2/HO-1 Axis
Chengjun MA ; Fengzhe YAN ; Lixia YANG ; Yonglin LIANG ; Xiangdong ZHU ; Dong AN ; Yankui GAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):121-130
ObjectiveTo explore the effects and mechanisms of modified Dahuang Huanglian Xiexintang on hepatic oxidative stress injury in type 2 diabetes mellitus (T2DM) rats based on the nuclear factor erythroid 2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) axis. MethodSix ZDF (fa/+) rats were as assigned to the blank group, and 30 ZDF (fa/fa) rats were used to induce the T2DM model by feeding a high-fat diet. After successful modeling, the rats were randomly divided into the model group, metformin group (0.18 g·kg-1), and low, medium, and high dose groups of modified Dahuang Huanglian Xiexintang (0.54, 1.08, 2.16 g·kg-1), with six rats in each group. After 12 weeks of drug intervention, the body mass, liver mass, fasting blood glucose (FBG), and oral glucose tolerance test (OGTT) levels were measured. Serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were detected using an automatic biochemical analyzer. The pathological changes of liver tissue were observed by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the activity of superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione peroxidase (GSH-Px), and the level of malondialdehyde (MDA) in liver tissues. Immunohistochemistry was used to detect the expression of Nrf2 in the liver. Real time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the mRNA and protein expression levels of Nrf2 and HO-1 in liver tissues. ResultCompared with the normal group, the model group showed a significant increase in body mass, liver mass, and liver index (P<0.01). Compared with the model group, the metformin group and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed a significant decrease in body weight, liver mass, and liver index (P<0.01). Compared with the normal group, the model group showed significantly increased TC, TG, and LDL levels (P<0.01), and significantly decreased HDL levels (P<0.01). Compared with the model group, the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly reduced TC levels (P<0.01), and significantly reduced TG levels (P<0.05). The medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced LDL levels (P<0.05). The metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased HDL levels (P<0.05). Compared with the normal group, the model group showed significantly increased ALT and AST activities (P<0.01). Compared with the model group, all doses of modified Dahuang Huanglian Xiexintang and the metformin group showed significantly reduced ALT activities (P<0.05) and significantly reduced AST activities (P<0.01). Compared with normal group, the model group showed significantly increased FBG at all time points (P<0.01). Compared with the model group, the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly reduced FBG at 8, 10, 12 weeks. The OGTT results showed that compared with the normal group, the model group had significantly increased blood glucose at all time points (P<0.01). Compared with the model group, the metformin group showed significantly reduced blood glucose at all time points (P<0.01), and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced blood glucose at 90, 120 min (P<0.01). HE pathology showed clear and regular liver cell structure in the normal group, while the model group showed disordered liver cell structure with visible fat vacuoles and a large number of deformed necrotic cells. The liver tissue structure improved in the metformin group and all doses of modified Dahuang Huanglian Xiexintang, with fewer necrotic cells. Compared with the normal group, the model group showed significantly reduced SOD and GSH-Px levels (P<0.01), and significantly increased ROS and MDA levels (P<0.01). Compared with the model group, the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased SOD and GSH-Px levels (P<0.01), and significantly reduced MDA levels (P<0.01). The medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced ROS levels (P<0.05). Compared with the normal group, the model group showed significantly reduced Nrf2 and HO-1 mRNA expression levels (P<0.01). Compared with the model group, the metformin group and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly increased Nrf2 and HO-1 mRNA expression levels (P<0.05). Immunohistochemistry showed that compared with the normal group, the model group had significantly reduced positive expression of Nrf2 and HO-1 (P<0.05). Compared with the model group, the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed increased positive expression of Nrf2 and HO-1, with a significant increase in brown-yellow granules around the cell nucleus (P<0.05). Western blot results showed that compared with the normal group, the model group had significantly reduced protein expression of Nrf2 and HO-1 (P<0.01). Compared with the model group, the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased protein expression of Nrf2 and HO-1 (P<0.01). ConclusionModified Dahuang Huanglian Xiexintang can significantly improve the general condition and pathological changes of liver tissues in T2DM model rats. This improvement is likely achieved through ameliorating hepatic oxidative stress injury via regulating the Nrf2/HO-1 axis.
8.Effect of Modified Dahuang Huanglian Xiexintang on Mitochondrial Autophagy and Browning of Visceral Fat in Obese Type 2 Diabetes Mellitus Rats
Dong AN ; Yonglin LIANG ; Yankui GAO ; Fengzhe YAN ; Sichen ZHAO ; Zhongtang LIU ; Chengjun MA ; Xiangdong ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):131-140
ObjectiveTo observe the effect of modified Dahuang Huanglian Xiexintang on mitochondrial autophagy and browning of visceral adipose tissue in obese type 2 diabetes mellitus (T2DM) model ZDF rats. MethodForty ZDF rats were induced with a high-fat diet to establish an obese T2DM model. The rats were randomly divided into five groups: Model group, metformin group (0.18 g·kg-1), and high, medium, and low dose groups of modified Dahuang Huanglian Xiexintang (2.16, 1.08, 0.54 g·kg-1), with eight rats in each group. Additionally, eight ZDF (fa/+) rats were assigned to the normal group. All groups received an intragastric volume of 10 mL·kg-1, with the model and normal groups receiving the same volume of purified water once daily for 12 weeks. Fasting blood glucose (FBG) was regularly measured. After 12 weeks of intervention, the body weight, epididymal fat weight, and serum levels of glucose (GLU), glycated serum protein (GSP), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured. Hematoxylin-eosin (HE) staining was used to observe pathological changes in epididymal fat tissue. Transmission electron microscopy (TEM) was employed to observe mitochondrial autophagy in adipocytes. Real-time PCR was used to detect the mRNA expression of hypoxia-inducible factor-1α (HIF-1α), Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), microtubule-associated protein 1 light chain 3B (LC3B), p62/SQSTM1, uncoupling protein 1 (UCP1), iodothyronine deiodinase 2 (Dio2), and PR domain containing 16 (Prdm16) in epididymal fat. Western blot was used to detect the protein expression of HIF-1α, BNIP3, LC3B, p62, and UCP1 in epididymal fat. ResultCompared with the normal group, the model group showed pathological changes in epididymal fat, with adipocyte mitochondrial condensation and numerous autophagosomes indicating mitochondrial autophagy. The model group also exhibited significantly increased body weight, epididymal fat weight, FBG, GLU, GSP, TC, TG, and LDL-C levels (P<0.01), significantly decreased HDL-C levels (P<0.01), significantly elevated mRNA and protein expression of HIF-1α, BNIP3, and LC3B (P<0.01), significantly reduced mRNA and protein expression of p62 and UCP1 (P<0.01), and significantly reduced mRNA expression of Dio2 and Prdm16 (P<0.01). Compared with the model group, all intervention groups showed varying degrees of improvement in epididymal fat pathology. The metformin group and high-dose modified Dahuang Huanglian Xiexintang group displayed intact mitochondrial morphology, clear cristae, uniform matrix, and few autophagosomes and autophagosomes in the adipocyte cytoplasm. The metformin group and high- and medium-dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced body weight and epididymal fat weight (P<0.01). The epididymal fat index was reduced in all intervention groups (P<0.05), and FBG was lowered in all intervention groups (P<0.01).Serum GSP, GLU, TG, and LDL-C levels were reduced in the metformin group and the high- and medium-dose groups of modified Dahuang Huanglian Xiexintang (P<0.05, P<0.01). The serum TC level was significantly reduced in the metformin group and high-dose group of modified Dahuang Huanglian Xiexintang (P<0.01), and HDL-C levels were significantly increased in all intervention groups (P<0.05, P<0.01). The mRNA and protein expression of HIF-1α, BNIP3, and LC3B were significantly reduced, and UCP1 protein expression was significantly increased in the metformin group and high- and medium-dose groups of modified Dahuang Huanglian Xiexintang (P<0.05, P<0.01). The mRNA and protein expression of p62, Dio2, and Prdm16 were significantly increased in the metformin group and high-dose group of modified Dahuang Huanglian Xiexintang (P<0.05, P<0.01). ConclusionModified Dahuang Huanglian Xiexintang may inhibit mitochondrial autophagy and promote the browning of visceral adipose tissue through the HIF-1α/BNIP3/LC3B pathway, thereby improving glucose and lipid metabolism in obese T2DM rats.
9.Dahuang Huanglian Xiexintang and Its Modified Prescription Improve Type 2 Diabetes Mellitus: A Review
Dong AN ; Yanhui ZHAI ; Yankui GAO ; Rong LIU ; Qi ZHOU ; Xiangdong ZHU ; Yonglin LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):141-151
Type 2 diabetes mellitus (T2DM) is based on insulin resistance (IR) and insulin secretion deficiency, with the specific mechanisms still unclear. Current research involves mechanisms such as glycolipid toxicity, inflammatory response, oxidative stress damage, and mitochondrial dysfunction. Modern traditional Chinese medicine (TCM) scholars have named it "blood glucose collateral disease" based on the clinical characteristics and natural progression of T2DM. This condition is primarily manifested as abnormal blood sugar levels in the early stages, and as the disease progresses, it gradually causes widespread damage to the body's veins and collaterals, ultimately leading to lesions in vessels and collaterals. Among these, "spleen heat" (obesity type) is the most common clinical type of T2DM. The concept of "internal heat-induced elimination" runs through both the onset and complications of T2DM, with internal heat being a key factor in its pathogenesis. The clinical application of Dahuang Huanglian Xiexintang and its modifications has achieved significant therapeutic effects. This paper reviews the origins and treatment characteristics of Dahuang Huanglian Xiexintang, along with clinical application research and experimental studies related to T2DM treatment, involving mechanisms for regulating glucose and lipid metabolism disorders, improving IR, modulating inflammatory responses, combating oxidative stress damage, regulating autophagy-related signaling pathways, modulating intestinal flora, inhibiting pyroptosis, and alleviating endoplasmic reticulum stress, with the purpose to provide direction for further research on the prevention and treatment of T2DM and its related complications, to offer reference for developing Dahuang Huanglian Xiexintang as a rapid hypoglycemic Chinese patent medicine for obese T2DM, and to better guide the clinical promotion of this drug.
10.Inhibitory effect of IL-27 on the overactivation of microglia
Lingxi WU ; Yixuan DU ; Xiangdong GAO
Journal of China Pharmaceutical University 2024;55(6):801-808
Neuroinflammation mediated by microglia is essential for the occurrence and development of Alzheimer’s disease (AD). Through the analysis of the GEO database, it was found that IL-27 expression decreased in both the cerebral cortex and hippocampus of AD patients. In this study, the AD cell model of BV-2 cells injured by Aβ1-42, the inflammatory cell model of BV-2 cells damaged by LPS, and the inflammatory animal model were established and the effects of IL-27 after its administration in the above models in regulating microglial phenotype and neuroinflammation were evaluated. In the animal models, the number of Iba1+ microglia in the hippocampus was detected by immunohistochemistry, the expression of pro-inflammatory factors such as TNF-α, IL-1β and IL-6 was detected by qPCR, ELISA and Western blot, and the expression of M1/M2 phenotypic markers in microglia was detected by qPCR. To further explore the action mechanism of IL-27, Western blot was used to detect the expression levels of NF-κB, p-NF-κB, IκBα and p-IκBα in microglia after administration of IL-27 and Aβ1-42. The results showed that IL-27 alleviated the abnormal activation of microglia induced by lipopolysaccharide (LPS), decreased the expression of pro-inflammatory factors such as TNF- α, IL-1β and IL-6, transformed microglia induced by LPS or Aβ1-42 from neurotoxic M1 to neuroprotective M2, and improved the abnormal phosphorylation of NF-κB and IκBα induced by Aβ1-42. The research suggested that IL-27 can regulate the M1/M2 polarization of microglia induced by Aβ1-42 or LPS, and alleviate neuroinflammation.

Result Analysis
Print
Save
E-mail