1.Phlorizin Ameliorates Glucose and Lipid Metabolism Disorders in T2DM Rats by Modulating IRS-1/PI3K/Akt Signaling Pathway
Nuer AILI ; Qingyu CAO ; Huan LIU ; Junwei HE ; Weihong ZHONG ; Lan CAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):139-148
ObjectiveTo observe the pharmacodynamic efficacy of phlorizin in improving hepatic glycolipid metabolism disorders in type 2 diabetic mellitus (T2DM) rats and to explore its mechanism of action based on the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. MethodsA high-fat diet and streptozotocin (STZ) were used to establish T2DM rat models. The rats were randomly assigned into six groups: the blank control group, model group, metformin group (300 mg·kg-1), and phlorizin high-dose (100 mg·kg-1) and low-dose groups (25 mg·kg-1). The rats were given intragastric administration for 6 weeks. The changes in body weight and fasting blood glucose (FBG) were observed, and the oral glucose tolerance test (OGTT) was carried out. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glycated serum protein (GSP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in serum were detected by an automatic biochemical analyzer. The levels of fasting insulin (FINS), interleukin (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA). The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by the biochemical assays. The pancreas index, liver index, and insulin resistance index were calculated. Hematoxylin-eosin (HE) staining was used to evaluate the pathological changes in liver and pancreatic tissues. The immunofluorescence method was used to detect the changes in insulin and glucagon in pancreatic tissue. Western blot was used to detect the expression of related proteins in the IRS-1/PI3K/Akt pathway of liver tissue and its downstream glycogen synthase kinase-3β (GSK-3β) and forkhead box transcription factor O1 (FoxO1) proteins. ResultsCompared with the blank control group, the body weight of rats in the model group continued to decrease, while the FBG level increased significantly. The area under the OGTT blood glucose curve (AUC), GSP, TC, TG, LDL-C, IL-1β, IL-6, TNF-α, MDA, pancreatic index and liver index increased significantly, while the levels of HDL-C, SOD, and FINS decreased significantly (P0.05, P0.01). Histological results showed that the pancreatic islets of rats in the model group exhibited atrophy and severe structural abnormalities. The insulin-positive β-cells decreased significantly (P0.01), while the glucagon-positive α-cells increased significantly (P0.01). Inflammatory cell infiltration and partial necrosis were observed in the liver tissues of the model group rats. The expressions of p-IRS-1/IRS-1, p-GSK-3β/GSK-3β, and p-FoxO1/FoxO1 proteins in the liver of the model group increased significantly (P0.01), while the expressions of p-PI3K/PI3K and p-Akt/Akt proteins decreased significantly (P0.01). Compared with the model group, the diabetic symptoms of rats in all administration groups were improved. The changes in body weight and FBG were close to those of the blank control group. The levels of OGTT-AUC, GSP, TC, TG, LDL-C, MDA, IL-1β, IL-6, TNF-α and the pancreatic index, liver index were obviously reduced (P0.05, P0.01), while the levels of HDL-C, SOD, and FINS obviously increased (P0.05, P0.01). The pathological changes of the pancreas and liver in rats in all treatment groups were effectively improved. The insulin-positive β-cells in the pancreas increased significantly (P0.01), while the glucagon-positive α-cells decreased significantly (P0.01). The protein expressions of p-IRS-1/IRS-1, p-GSK-3β/GSK-3β, and p-FoxO1/FoxO1 in the liver were significantly reduced (P0.01), while the protein expressions of p-PI3K/PI3K and p-Akt/Akt significantly increased (P0.01). ConclusionPhlorizin reversed the weight loss and abnormal increase of FBG in T2DM rats, improved blood lipid profiles, oxidative stress, and inflammatory levels, alleviated insulin resistance, and had certain protective effects on the liver and pancreas. The hypoglycemic mechanism may involve regulating the IRS-1/PI3K/Akt signaling pathway to inhibit the activities of GSK-3β and FoxO1, thereby promoting liver glycogen synthesis and suppressing hepatic gluconeogenesis, ultimately improving glycolipid metabolism disorders.
2.Phlorizin Ameliorates Glucose and Lipid Metabolism Disorders in T2DM Rats by Modulating IRS-1/PI3K/Akt Signaling Pathway
Nuer AILI ; Qingyu CAO ; Huan LIU ; Junwei HE ; Weihong ZHONG ; Lan CAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):139-148
ObjectiveTo observe the pharmacodynamic efficacy of phlorizin in improving hepatic glycolipid metabolism disorders in type 2 diabetic mellitus (T2DM) rats and to explore its mechanism of action based on the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. MethodsA high-fat diet and streptozotocin (STZ) were used to establish T2DM rat models. The rats were randomly assigned into six groups: the blank control group, model group, metformin group (300 mg·kg-1), and phlorizin high-dose (100 mg·kg-1) and low-dose groups (25 mg·kg-1). The rats were given intragastric administration for 6 weeks. The changes in body weight and fasting blood glucose (FBG) were observed, and the oral glucose tolerance test (OGTT) was carried out. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glycated serum protein (GSP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in serum were detected by an automatic biochemical analyzer. The levels of fasting insulin (FINS), interleukin (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA). The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by the biochemical assays. The pancreas index, liver index, and insulin resistance index were calculated. Hematoxylin-eosin (HE) staining was used to evaluate the pathological changes in liver and pancreatic tissues. The immunofluorescence method was used to detect the changes in insulin and glucagon in pancreatic tissue. Western blot was used to detect the expression of related proteins in the IRS-1/PI3K/Akt pathway of liver tissue and its downstream glycogen synthase kinase-3β (GSK-3β) and forkhead box transcription factor O1 (FoxO1) proteins. ResultsCompared with the blank control group, the body weight of rats in the model group continued to decrease, while the FBG level increased significantly. The area under the OGTT blood glucose curve (AUC), GSP, TC, TG, LDL-C, IL-1β, IL-6, TNF-α, MDA, pancreatic index and liver index increased significantly, while the levels of HDL-C, SOD, and FINS decreased significantly (P0.05, P0.01). Histological results showed that the pancreatic islets of rats in the model group exhibited atrophy and severe structural abnormalities. The insulin-positive β-cells decreased significantly (P0.01), while the glucagon-positive α-cells increased significantly (P0.01). Inflammatory cell infiltration and partial necrosis were observed in the liver tissues of the model group rats. The expressions of p-IRS-1/IRS-1, p-GSK-3β/GSK-3β, and p-FoxO1/FoxO1 proteins in the liver of the model group increased significantly (P0.01), while the expressions of p-PI3K/PI3K and p-Akt/Akt proteins decreased significantly (P0.01). Compared with the model group, the diabetic symptoms of rats in all administration groups were improved. The changes in body weight and FBG were close to those of the blank control group. The levels of OGTT-AUC, GSP, TC, TG, LDL-C, MDA, IL-1β, IL-6, TNF-α and the pancreatic index, liver index were obviously reduced (P0.05, P0.01), while the levels of HDL-C, SOD, and FINS obviously increased (P0.05, P0.01). The pathological changes of the pancreas and liver in rats in all treatment groups were effectively improved. The insulin-positive β-cells in the pancreas increased significantly (P0.01), while the glucagon-positive α-cells decreased significantly (P0.01). The protein expressions of p-IRS-1/IRS-1, p-GSK-3β/GSK-3β, and p-FoxO1/FoxO1 in the liver were significantly reduced (P0.01), while the protein expressions of p-PI3K/PI3K and p-Akt/Akt significantly increased (P0.01). ConclusionPhlorizin reversed the weight loss and abnormal increase of FBG in T2DM rats, improved blood lipid profiles, oxidative stress, and inflammatory levels, alleviated insulin resistance, and had certain protective effects on the liver and pancreas. The hypoglycemic mechanism may involve regulating the IRS-1/PI3K/Akt signaling pathway to inhibit the activities of GSK-3β and FoxO1, thereby promoting liver glycogen synthesis and suppressing hepatic gluconeogenesis, ultimately improving glycolipid metabolism disorders.
3.Oral Herombopag Olamine and subcutaneous recombinant human thrombopoietin after haploidentical hematopoietic stem cell transplantation
Dai KONG ; Xinkai WANG ; Wenhui ZHANG ; Xiaohang PEI ; Cheng LIAN ; Xiaona NIU ; Honggang GUO ; Junwei NIU ; Zunmin ZHU ; Zhongwen LIU
Chinese Journal of Tissue Engineering Research 2025;29(1):1-7
BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an important treatment for malignant hematological diseases,and delayed postoperative platelet implantation is a common complication that seriously affects the quality of patient survival;however,there are no standard protocols to improve platelet implantation rates and prevent platelet implantation delays. OBJECTIVE:To compare the safety and efficacy of oral Herombopag Olamine versus subcutaneous recombinant human thrombopoietin for promoting platelet implantation in patients with malignant hematological diseases undergoing haploid hematopoietic stem cell transplantation. METHODS:Clinical data of 163 patients with malignant hematological diseases who underwent haploidentical hematopoietic stem cell transplantation from January 2016 to October 2022 were retrospectively analyzed.A total of 72 patients who started to subcutaneously inject recombinant human thrombopoietin at+2 days were categorized into the recombinant human thrombopoietin group;a total of 27 patients who started to orally take Herombopag Olamine at+2 days were categorized into the Herombopag Olamine group;and 64 patients who did not apply Herombopag Olamine or recombinant human thrombopoietin were categorized into the blank control group.The implantation status,incidence of acute graft-versus-host disease of degree II-IV within 100 days,1-year survival rate,1-year recurrence rate,and safety were analyzed in the three groups. RESULTS AND CONCLUSION:(1)The average follow-up time was 52(12-87)months.The implantation time of neutrophils in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group was(12.95±3.88)days,(14.04±3.71)days,and(13.89±2.74)days,respectively,with no statistically significant difference(P=0.352);the implantation time of platelets was(15.16±6.27)days,(17.67±6.52)days,and(17.00±4.75)days,with no statistically significant difference(P=0.287).(2)The complete platelet implantation rate on day 60 was 64.06%,90.28%,and 92.59%,respectively,and the difference was statistically significant(P<0.001).The subgroup analysis showed that the difference between the blank control group and the recombinant human thrombopoietin group was statistically significant(P<0.001),and the difference between the blank control group and the Herombopag Olamine group was statistically significant(P=0.004).The difference was not statistically significant between the recombinant human thrombopoietin group and Herombopag Olamine group(P=0.535).(3)100-day II-IV degree acute graft-versus-host disease incidence in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group were 25.00%,30.56%,and 25.93%,respectively,and the difference was not statistically significant(P=0.752).(4)The incidence of cytomegalovirus anemia,cytomegalovirus pneumonia,and hepatic function injury had no statistical difference among the three groups(P>0.05).(5)During the follow-up period,there was no thrombotic event in any of the three groups of patients.(6)The results showed that recombinant human thrombopoietin and Herombopag Olamine could improve the platelet implantation rate of malignant hematological disease patients after haploidentical hematopoietic stem cell transplantation,with comparable efficacy and good safety.
4.Effect of warm acupuncture on PINK1/Parkin pathway in the skeletal muscle of rats with chronic fatigue syndrome
Huayuan LI ; Chun LI ; Junwei LIU ; Ting WANG ; Long LI ; Yongli WU
Chinese Journal of Tissue Engineering Research 2025;29(8):1618-1625
BACKGROUND:It has been found that mitochondrial function is abnormal in patients with chronic fatigue syndrome,and the administration of coenzymes can improve the symptoms.Warm acupuncture is one of the most important treatments for this disease,but its mechanism of action is unclear. OBJECTIVE:To investigate the effects of warm acupuncture on the phosphatase and tensin inducible kinase 1(PINK1)/Parkin pathway in the skeletal muscle of rats with chronic fatigue syndrome. METHODS:After 3 days of adaptive feeding,32 male Sprague-Dawley rats were randomly divided into normal control,model,warm acupuncture,and coenzyme Q groups with 8 rats in each group.The chronic fatigue syndrome model was established by multiple factors,including swimming exhaustion,chronic immobilization and fasting.After successful modeling,the normal group and the model group were treated with the same fixation and gavage procedures,and the warm acupuncture group was treated with acupuncture at Guanyuan,Zhongwan and Zusanli(bilateral)points,once a day.After the needling was inserted,the moxa pillar was put on the needle handle and ignited,three sessions once.The coenzyme Q group was given 1 mL/kg coenzyme by gavage,once a day for 14 days.The body mass,exhaustive swimming time and food utilization rate during the treatment were recorded.After the treatment,the bilateral gastrocnemius muscles of rats in each group were collected.The pathological morphology of the gastrocnemius muscle was observed by hematoxylin-eosin staining,the mitochondrial morphology and autophagosome of the gastrocnemius muscle were observed by transmission electron microscope.The expression level of microtubule-associated protein light chain 3(LC3)Ⅱ protein in the skeletal muscle was detected by immunohistochemistry.Western blot was used to detect the expression of PINK1,Parkin,LC3 Ⅰ,and LC3 Ⅱ in the skeletal muscle. RESULTS AND CONCLUSION:Compared with the normal group,the gastrocnemius muscle nuclei of the model group were pyknotic,condensed,the number of cells was increased,the cells were arranged disorderly,and the fibers in the gastrocnemius muscle were tightly arranged in the model group.Compared with the model group,the intercellular space became smaller,the nuclei were reduced,and the cell arrangement was orderly in the warm acupuncture group and coenzyme Q group.Compared with the normal group,the skeletal muscle mitochondria in the model group were swollen,fused,and vacuolated seriously,the membrane was partially broken,the matrix was more dissolved,the cristae was broken and disappeared,and autophagy appeared.Compared with the model group,the number of mitochondria increased,the arrangement was relatively neat,mitochondrial vacuolization and rupture of cristae in the gastrocnemius muscle were improved,the membrane structure was relatively intact,and autophagy occurred.Compared with the normal group,the expression of PINK1 protein in the skeletal muscle of the model group was significantly increased(P<0.05),while the expression of Parkin,LC3 Ⅱ and LC3 Ⅱ/Ⅰ protein was slightly upregulated(P>0.05).Compared with the model group,the protein expressions of PINK1,Parkin,LC3 Ⅱ and LC3 Ⅱ/Ⅰ were significantly upregulated in the warm acupuncture and coenzyme Q groups(P<0.05),and the up-regulation was more significant in the warm acupuncture group.To conclude,warm acupuncture can play a role in the treatment of chronic fatigue syndrome by activating the PINK1/Parkin pathway,upregulating LC3 Ⅱ expression,forming mitochondrial autophagosomes,promoting the degradation of damaged mitochondria,and improving mitochondrial quality.
5.Urban-rural disparities in mortality due to stroke subtypes in China and its provinces, 2015-2020.
Yi REN ; Jia YANG ; Peng YIN ; Wei LIU ; Zheng LONG ; Chen ZHANG ; Zixin WANG ; Haijie LIU ; Maigeng ZHOU ; Qingfeng MA ; Junwei HAO
Chinese Medical Journal 2025;138(11):1345-1354
BACKGROUND:
Death burden of stroke is severe with over one-third rural residents in China, but there is still a lack of specific national and high-quality reports on the urban-rural differences in stroke burden, especially for subtypes. We aimed to update the understanding of urban-rural differences in stroke deaths.
METHODS:
This is a descriptive observational study. Data from the national mortality surveillance system, which covers 323.8 million with 605 disease surveillance points (DSPs) across all 31 provinces, municipalities, and autonomous regions in China. All deaths from stroke as the underlying cause from 2015 to 2020 according to DSPs. Crude mortality rate and age-standardized mortality rate (ASMR) were estimated through DSPs. Average annual percentage change was used to explain the change in mortality rate.
RESULTS:
From 2015 to 2020, the majority of deaths from all stroke subtypes occurred in rural areas. There were significant differences between the changes of urban and rural ASMRs. On the whole, the changes in urban areas were evidently better, and the ASMR differences were basically expanding. Stroke ASMR in urban China decreased by 15.5%. The rural ASMR of ischemic stroke increased by 12.9%. The rural and urban ASMRs of intracerebral hemorrhage decreased by 24.9% and 27.4%, and those of subarachnoid hemorrhage decreased by 29.5% and 40.4%, respectively. The highest ASMRs of all stroke subtypes and the increasing trend of ischemic stroke ASMR make rural males the focus of stroke management.
CONCLUSIONS
The death burden of stroke varies greatly between urban and rural China. Rural residents face unique challenges.
Humans
;
China/epidemiology*
;
Stroke/mortality*
;
Rural Population/statistics & numerical data*
;
Male
;
Female
;
Urban Population/statistics & numerical data*
;
Middle Aged
;
Aged
;
Aged, 80 and over
;
Adult
6.Multidisciplinary expert consensus on weight management for overweight and obese children and adolescents based on healthy lifestyle
HONG Ping, MA Yuguo, TAO Fangbiao, XU Yajun, ZHANG Qian, HU Liang, WEI Gaoxia, YANG Yuexin, QIAN Junwei, HOU Xiao, ZHANG Yimin, SUN Tingting, XI Bo, DONG Xiaosheng, MA Jun, SONG Yi, WANG Haijun, HE Gang, CHEN Runsen, LIU Jingmin, HUANG Zhijian, HU Guopeng, QIAN Jinghua, BAO Ke, LI Xuemei, ZHU Dan, FENG Junpeng, SHA Mo, Chinese Association for Student Nutrition & ; Health Promotion, Key Laboratory of Sports and Physical Fitness of the Ministry of Education,〖JZ〗 Engineering Research Center of Ministry of Education for Key Core Technical Integration System and Equipment,〖JZ〗 Key Laboratory of Exercise Rehabilitation Science of the Ministry of Education
Chinese Journal of School Health 2025;46(12):1673-1680
Abstract
In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.
7.Effect of dexmedetomidine on the intraoperative and early postoperative complications of patients undergoing orthotopic liver transplantation
Junwei KANG ; Hui ZHANG ; Yining CHEN ; Zhiying ZHENG ; Xinyang LIU ; Xiongxiong PAN
Chinese Journal of Surgery 2024;62(2):155-161
Objective:To investigate the effect of dexmedetomidine on the intraoperative and early postoperative complications of patients undergoing orthotopic liver transplantation.Methods:This is a retrospective cohort study. The clinical data of 399 patients who underwent orthotopic liver transplantation at the First Affiliated Hospital of Nanjing Medical University from January 2016 to September 2020 were retrospectively collected. There were 319 males and 80 females, aged (50.9±10.2) years (range: 10 to 73 years). These patients were divided into the control group (369 cases) and the dexmedetomidine group (30 cases) according to whether dexmedetomidine was continuously pumped intravenously during the operation until the operation ended. The 1∶2 propensity score matching was used to match the preoperative and intraoperative conditions of the two groups of patients, and the caliper width was 0.2. Outcome indicators included intraoperative postreperfusion syndrome, acute kidney injury and pulmonary complications within 7 days after surgery, length of hospital stay, time of stay in ICU, duration of assisted mechanical ventilation, rate of reintubation, 6-month and 1-year survival and recurrence-free survival rate after surgery. The independent sample t test, χ2 test, Mann-Whitney U test or Fisher exact test was used to statistically analyze the data of the two groups of patients, respectively. Survival curves of overall survival and disease-free-survival were plotted by Kaplan-Meier method, and the survival rate and recurrence-free survival rate were compared by Log-rank test. Results:A total of 78 patients were included after propensity score matching, including 26 in the dexmedetomidine group and 52 in the control group. The incidence of acute kidney injury in the dexmedetomidine group within 7 days after surgery was 0 (0/26), significantly lower than that of the control group (21.2%,11/52)(corrected χ2=4.776, P=0.029). There were no significant differences in the incidence of intraoperative postreperfusion syndrome and pulmonary complications within 7 days after surgery, length of hospital stay, ICU time, the duration of assisted mechanical ventilation, rate of reintubation, 6-month and 1-year survival, and recurrence-free survival rate after surgery between the two groups (all P>0.05). Conclusion:Continuous infusion of dexmedetomidine via intravenous pump during operation may be beneficial in reducing the incidence of acute kidney injury within 7 days after orthotopic liver transplantation.
8.Effect of dexmedetomidine on the intraoperative and early postoperative complications of patients undergoing orthotopic liver transplantation
Junwei KANG ; Hui ZHANG ; Yining CHEN ; Zhiying ZHENG ; Xinyang LIU ; Xiongxiong PAN
Chinese Journal of Surgery 2024;62(2):155-161
Objective:To investigate the effect of dexmedetomidine on the intraoperative and early postoperative complications of patients undergoing orthotopic liver transplantation.Methods:This is a retrospective cohort study. The clinical data of 399 patients who underwent orthotopic liver transplantation at the First Affiliated Hospital of Nanjing Medical University from January 2016 to September 2020 were retrospectively collected. There were 319 males and 80 females, aged (50.9±10.2) years (range: 10 to 73 years). These patients were divided into the control group (369 cases) and the dexmedetomidine group (30 cases) according to whether dexmedetomidine was continuously pumped intravenously during the operation until the operation ended. The 1∶2 propensity score matching was used to match the preoperative and intraoperative conditions of the two groups of patients, and the caliper width was 0.2. Outcome indicators included intraoperative postreperfusion syndrome, acute kidney injury and pulmonary complications within 7 days after surgery, length of hospital stay, time of stay in ICU, duration of assisted mechanical ventilation, rate of reintubation, 6-month and 1-year survival and recurrence-free survival rate after surgery. The independent sample t test, χ2 test, Mann-Whitney U test or Fisher exact test was used to statistically analyze the data of the two groups of patients, respectively. Survival curves of overall survival and disease-free-survival were plotted by Kaplan-Meier method, and the survival rate and recurrence-free survival rate were compared by Log-rank test. Results:A total of 78 patients were included after propensity score matching, including 26 in the dexmedetomidine group and 52 in the control group. The incidence of acute kidney injury in the dexmedetomidine group within 7 days after surgery was 0 (0/26), significantly lower than that of the control group (21.2%,11/52)(corrected χ2=4.776, P=0.029). There were no significant differences in the incidence of intraoperative postreperfusion syndrome and pulmonary complications within 7 days after surgery, length of hospital stay, ICU time, the duration of assisted mechanical ventilation, rate of reintubation, 6-month and 1-year survival, and recurrence-free survival rate after surgery between the two groups (all P>0.05). Conclusion:Continuous infusion of dexmedetomidine via intravenous pump during operation may be beneficial in reducing the incidence of acute kidney injury within 7 days after orthotopic liver transplantation.
9.The mechanism of target regulating of miR-421 to Menin/Caspase-3 pathway for depression
Yonghui LIU ; Qingjing TAN ; Qing CHEN ; Liping WEI ; Junwei YANG ; Kan YANG ; Yuguang GAO
The Journal of Practical Medicine 2024;40(4):453-459
Objective To explore the mechanism of miR-421 affecting the occurrence and development of depression.Methods A depressive rat model was established by single intraperitoneal injection of lipopolysaccharide(LPS),and depressive behavior was detected by glucose preference test and open-field test.miRNA microarray chips and RT-PCR were used to analyze the expression level of miR-421 in hippocampus of the depressed rats.TargetScan database and mi RDB database were used to predict the target genes of miR-421.Dual luciferase reporter gene assay was used to observe the binding of miR-421 to the target genes.The impact of over-expression and inhibition of miR-421 on target genes was observed,then the influence of over-expression and inhibition of target genes on downstream factors was observed,and the related mechanism of miR-421 on depression was explored.Results miRNA microarray chips and RT-PCR assay showed that miR-421 was highly expressed in the hippocampus of the depressed rats(P<0.001),Inhibition of miR-421 expression could significantly restore the body weight and exercise ability of the depressed rats(P<0.001).Binding targets of Menin and miR-421 were predicted by TargetScan database,and interaction between Menin and miR-421 was demonstrated by dual-luciferase reporter gene assay.Menin expression was down-regulated while miR-421 was overexpressed(P<0.001),whereas it was up-regulated as miR-421 was inhibited(P<0.001).qPCR indicated that expressions of Caspase-3 and NF-κB in the hippocampus of the depressed rats was significantly increased(P<0.001),and IL-1β expression in the hippo-campus was significantly increased(P<0.01).When the expression of Menin was inhibited,the expressions of Caspase-3,NF-κB and IL-1β were increased(P<0.001),while the expressions of Caspase-3,NF-κB and IL-1β were decreased when Menin was overexpressed(P<0.001).Conclusions Inhibition of miR-421 expression can increase Menin expression,decrease Caspase-3 content,and reduce neuroinflammatory response,thereby improving depressive symptoms.
10.Effects of theaflavin on ox-LDL-induced foam cell formation and oxidative stress in THP-1 derived macrophages
Mengmeng SHI ; Rui HUANG ; Zile HUANG ; Junwei HU ; Jingjie XIAO ; Yanhong LIU ; Junzhu WU
Chinese Journal of Arteriosclerosis 2024;32(9):747-755
Aim To investigate the effect of theaflavin on oxidized low density lipoprotein(ox-LDL)-induced foam cell formation and oxidative stress in THP-1 macrophages and its mechanism.Methods THP-1 derived macro-phages were pretreated with 50 μmol/L theaflavin and(or)10 μmol/L nuclear factor erythroid 2-related factor 2(NRF2)inhibitor ML385,then 100 mg/L ox-LDL was added to the cells for 24 h to establish the foam cell model.The effect of theaflavin on THP-1 macrophages viability was evaluated by CCK-8 assay and LDH release.The expression of inflamma-tory cytokines interleukin-6(IL-6),interleukin-1 β(IL-1β),tumor necrosis factor-α(TNF-α)were analyzed by real-time quantitative polymerase chain reaction(RT-qPCR)and Western blot.The release of inflammatory cytokines were detected by enzyme linked immunosorbent assay(ELISA).Intracellular lipid accumulation was detected by Oil red O staining,and lipid absorption was observed by DiL-labeled oxidized low density lipoprotein(DiL-ox-LDL)staining.Re-active oxygen species(ROS)level was detected by DCFH-DA probe.The expression of lipid uptake,cholesterol efflux and oxidative stress-related proteins were detected by Western blot and RT-qPCR.Results Treatment with 100 mg/L ox-LDL significantly decreased cell viability and cholesterol efflux-related protein expressions,increased lipid uptake,ac-cumulation and lipid uptake-related protein expressions,and significantly promoted inflammation and ROS level,as well as the expressions of myeloperoxidase(MPO),NADPH oxidase 2(NOX2)in THP-1 macrophages(all P<0.05).After pretreatment with theaflavin,cell viability was increased,intracellular lipid uptake,accumulation and lipid uptake-related protein expressions were significantly reduced,cholesterol efflux-related protein expressions were significantly increased,the expression and release of IL-6,IL-1β and TNF-α were significantly decreased,ROS level was significantly decreased,and the expression of MPO and NOX2 were decreased(all P<0.05).Pretreatment with theaflavin effectively alleviated intracellular oxidative stress by altering the expression of NRF2,heme oxygenase-1(HO-1)and Kelch-like ECH-associated protein 1(KEAP1)in NRF2 signaling pathway,and enhanced the translocation of NRF2 into the nucleus.After pretreat-ment with ML385,the expression levels of NRF2,HO-1,KEAP1 and CD36 were significantly decreased.Conclusion Theaflavin can significantly inhibit ox-LDL-induced foam cell formation,inflammation,and oxidative stress through NRF2/HO-1 signaling pathway in THP-1 macrophages.


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