1.Effect of lncRNA-TNFRSF13C on hypoxia-inducible factor 1alpha in periodontal cells by modulation of miR-1246
Jing BAI ; Xue ZHANG ; Yan REN ; Yuehui LI ; Xiaoyu TIAN
Chinese Journal of Tissue Engineering Research 2025;29(5):928-935
BACKGROUND:LncRNA-TNFRSF13C,an important factor in B cell development and function,is expressed in periodontal tissues of patients with periodontitis,but the specific mechanism is still unclear. OBJECTIVE:To investigate the mechanism of lncRNA-TNFRSF13C regulating miR-1246 on hypoxia-inducible factor 1α in periodontal cells. METHODS:Human periodontal ligament cells(hPDLCs)were treated with lipopolysaccharide and divided into group A(hPDLCs cell lines without transfection),group B(hPDLCs cell lines transfected with TNFRSF13C NC-siRNA),group C(hPDLCs cell lines transfected with TNFRSF13C-siRNA),group D(hPDLCs cell line transfected with miR-1246 mimics),group E(hPDLCs cell line transfected with miR-1246 siRNA),group F(hPDLCs cell line transfected with TNFRSF13C-siRNA+miR-1246 mimics),and group G(hPDLCs cell line transfected with TNFRSF13C-siRNA+miR-1246 siRNA).The relative expression of lncRNA-TNFRSF13C and miR-1246 in each group was detected by qRT-PCR.Cell counting kit-8 assay was used to detect cell viability.Apoptosis was detected by flow cytometry.Expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins was detected by western blot.The correlation between lncRNA-TNFRSF13C and miR-1246 was analyzed by Pearson,and the targeting relationship was analyzed by dual-luciferase reporter assay. RESULTS AND CONCLUSION:There was no significant difference in human periodontal ligament cell activity,apoptosis rate and protein indexes between groups A and B(P>0.05).Compared with group B,hPDLCS cell activity in group C was increased,and apoptosis rate and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins were decreased(P<0.05).Compared with group C,hPDLCS cell activity in group D was decreased,and apoptosis rate and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins were increased(P<0.05).Compared with group D,the cell activity of group E was increased(P<0.05).The cell activity in group F was lower than that in group E,and the apoptosis rate was reduced in both groups E and F(P<0.05).Compared with group F,the cell activity of group G was increased,and the apoptosis rate and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor were decreased(P<0.05).LncRNA-TNFRSF13C was positively correlated with miR-1246(P<0.05).Compared with the TNFRSF13C-siRNA group,the fluorescence activity of miR-1246-wt in the TNFRSF13C-NC group was reduced(P>0.05);compared with the miR-1246-NC group,the fluorescence activities of hypoxia-inducible factor 1α-wt and vascular endothelial growth factor-wt in the miR-1246 mimics group were increased(P<0.05).To conclude,down-regulation of lncRNA-TNFRSF13C can promote the activity of periodontal cells treated with lipopolysaccharide,reduce apoptosis,and inhibit hypoxia-inducible factor 1α and vascular endothelial growth factor.The mechanism is related to the regulation of miR-1246 activity.
2.Research status of quality assessment of hospice care for children with cancer abroad
Jing WU ; Xianhong ZHANG ; Lu WEI ; Xiaochuan ZHU
Chinese Medical Ethics 2025;38(3):275-280
The effectiveness and professionalism of hospice care services for children with cancer are of great significance for improving their quality of life and reducing the mental and economic burden on their families. Currently, a relatively complete quality evaluation system for hospice care for children with cancer has been established abroad, while research in this field in China is still in its infancy. By elaborating on the concept and connotation of quality assessment of hospice care for children with cancer in detail, systematically reviewing the research status of quality assessment of hospice care for children with cancer abroad, and addressing the problems and challenges faced by quality assessment of hospice care for children with cancer in China, corresponding inspirations and improvement strategies were proposed, aiming to provide a reference for improving the quality of hospice care for children with cancer in China.
3.Protective Effect and Mechanism of Anmeidan against Neuronal Damage in Rat Model of Sleep Deprivation Based on Hippocampal Neuroinflammation
Guangjing XIE ; Zixuan XU ; Junlu ZHANG ; Jian ZHANG ; Jing XIA ; Bo XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):65-71
ObjectiveTo investigate the effects of Anmeidan (AMD) on neuroinflammation in the hippocampus of sleep-deprived rats. MethodsSD rats were randomly divided into four groups (n = 10 per group): control group, model group, AMD group, and melatonin group. A sleep deprivation model was established using the modified multiple platform water environment method. The AMD group received AMD at a dose of 18.18 g·kg-1·d-1, the melatonin group received melatonin at 100 mg·kg-1·d-1, and the control and model groups were given an equal volume of pure water. All treatments were administered by gavage for four weeks. Spontaneous activity was assessed using an animal behavior video system. Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). Hippocampal pyramidal neuron morphology was examined using hematoxylin-eosin (HE) staining, and ultrastructural changes of hippocampal neurons were observed via transmission electron microscopy. Immunofluorescence was used to detect the expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus. Western blot analysis was performed to measure the expression of nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), NOD-like receptor protein 3 (NLRP3), and Caspase-1 proteins. ResultsCompared with the control group, the model group showed a significant increase in activity duration and frequency (P<0.01), increased hippocampal pyramidal cell structural damage and decreased cell count, aggravated hippocampal ultrastructural damage, mitochondrial cristae disruption, and exacerbated vacuolization. The expression of p-NF-κB p65, NLRP3, and Caspase-1 proteins was upregulated, serum IL-1β, IL-6, and TNF-α levels were significantly elevated (P<0.01), and the fluorescence intensity of BDNF and NGF proteins was significantly reduced (P<0.01). Compared with the model group, the AMD group showed a significant reduction in activity duration and frequency (P<0.01), increased hippocampal pyramidal cell count with reduced structural damage, alleviated hippocampal ultrastructural damage, significantly downregulated p-NF-κB p65, NLRP3, and Caspase-1 protein expression (P<0.01), decreased serum IL-1β, IL-6, and TNF-α levels (P<0.01), and significantly increased the fluorescence intensity of BDNF and NGF proteins (P<0.01). ConclusionAnmeidan alleviates hippocampal neuronal damage in sleep-deprived rats, potentially by downregulating the NLRP3 signaling pathway, reducing inflammatory cytokine release, and increasing neurotrophic factor levels.
4.Evaluation of the performance of the artificial intelligence - enabled snail identification system for recognition of Oncomelania hupensis robertsoni and Tricula
Jihua ZHOU ; Shaowen BAI ; Liang SHI ; Jianfeng ZHANG ; Chunhong DU ; Jing SONG ; Zongya ZHANG ; Jiaqi YAN ; Andong WU ; Yi DONG ; Kun YANG
Chinese Journal of Schistosomiasis Control 2025;37(1):55-60
Objective To evaluate the performance of the artificial intelligence (AI)-enabled snail identification system for recognition of Oncomelania hupensis robertsoni and Tricula in schistosomiasis-endemic areas of Yunnan Province. Methods Fifty O. hupensis robertsoni and 50 Tricula samples were collected from Yongbei Township, Yongsheng County, Lijiang City, a schistosomiasis-endemic area in Yunnan Province in May 2024. A total of 100 snail sample images were captured with smartphones, including front-view images of 25 O. hupensis robertsoni and 25 Tricula samples (upward shell opening) and back-view images of 25 O. hupensis robertsoni and 25 Tricula samples (downward shell opening). Snail samples were identified as O. hupensis robertsoni or Tricula by schistosomiasis control experts with a deputy senior professional title and above according to image quality and morphological characteristics. A standard dataset for snail image classification was created, and served as a gold standard for recognition of snail samples. A total of 100 snail sample images were recognized with the AI-enabled intelligent snail identification system based on a WeChat mini program in smartphones. Schistosomiasis control professionals were randomly sampled from stations of schistosomisis prevention and control and centers for disease control and prevention in 18 schistosomiasis-endemic counties (districts, cities) of Yunnan Province, for artificial identification of 100 snail sample images. All professionals are assigned to two groups according the median years of snail survey experiences, and the effect of years of snail survey experiences on O. hupensis robertsoni sample image recognition was evaluated. A receiver operating characteristic (ROC) curve was plotted, and the sensitivity, specificity, accuracy, Youden’s index and the area under the curve (AUC) of the AI-enabled intelligent snail identification system and artificial identification were calculated for recognition of snail sample images. The snail sample image recognition results of AI-enabled intelligent snail identification system and artificial identification were compared with the gold standard, and the internal consistency of artificial identification results was evaluated with the Cronbach’s coefficient alpha. Results A total of 54 schistosomiasis control professionals were sampled for artificial identification of snail sample image recognition, with a response rate of 100% (54/54), and the accuracy, sensitivity, specificity, Youden’s index, and AUC of artificial identification were 90%, 86%, 94%, 0.80 and 0.90 for recognition of snail sample images, respectively. The overall Cronbach’s coefficient alpha of artificial identification was 0.768 for recognition of snail sample images, and the Cronbach’s coefficient alpha was 0.916 for recognition of O. hupensis robertsoni snail sample images and 0.925 for recognition of Tricula snail sample images. The overall accuracy of artificial identification was 90% for recognition of snail sample images, and there was no significant difference in the accuracy of artificial identification for recognition of O. hupensis robertsoni (86%) and Tricula snail sample images (94%) (χ2 = 1.778, P > 0.05). There was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (88%) and downward shell openings (92%) (χ2 = 0.444, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less (75%) and more than 6 years (90%) (χ2 = 7.792, P < 0.05). The accuracy, sensitivity, specificity and AUC of the AI-enabled intelligent snail identification system were 88%, 100%, 76% and 0.88 for recognition of O. hupensis robertsoni snail sample images, and there was no significant difference in the accuracy of recognition of O. hupensis robertsoni snail sample images between the AI-enabled intelligent snail identification system and artificial identification (χ2 = 0.204, P > 0.05). In addition, there was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (90%) and downward shell openings (86%) (χ2 = 0.379, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less and more than 6 years (χ2 = 5.604, Padjusted < 0.025). Conclusions The accuracy of recognition of snail sample images is comparable between the AI-enabled intelligent snail identification system and artificial identification by schistosomiasis control professionals, and the AI-enabled intelligent snail identification system is feasible for recognition of O. hupensis robertsoni and Tricula in Yunnan Province.
5.Management status and influencing factors of disease stabilization in patients with severe mental disorders in Luzhou City, Sichuan Province
Xuemei ZHANG ; Bo LI ; Benjing CAI ; Youguo TAN ; Bo XIANG ; Jing HE ; Qidong JIANG ; Jian TANG
Sichuan Mental Health 2025;38(2):131-137
BackgroundSevere mental disorders represent a major public health concern due to the high disability rates and substantial disease burden, which has garnered significant national attention and prompted their inclusion in public health project management systems. However, credible evidence regarding the current status of disease management and factors influencing disease stabilization among patients with severe mental disorders in Luzhou City, Sichuan Province, remains limited. ObjectiveTo investigate the current management status of patients with severe mental disorders in Luzhou City, Sichuan Province, and to analyze influencing factors of disease stabilization among patients under standardized care, so as to provide evidence-based insights for developing targeted management strategies to optimize clinical interventions for this patient population. MethodsIn March 2023, data were extracted from the Sichuan Mental Health Service Comprehensive Management Platform for patients with severe mental disorders in Luzhou City who received management between December 2017 and December 2022. Information on mental health service utilization and clinical status changes was collected. Trend analysis was conducted to evaluate temporal changes in key management indicators for severe mental disorders in Luzhou City. Logistic regression analysis was employed to identify factors influencing the disease stabilization or fluctuation of these patients. ResultsThis study enrolled a total of 20 232 patients. In Luzhou City, the stabilization rate and standardized management rate of severe mental disorders were 94.89% and 79.36% in 2017, respectively, which increased to 95.33% and 96.92% by 2022. The regular medication adherence rate rose from 34.42% in 2018 to 86.81% in 2022. In 2022, the regular medication adherence rate was 71.80% for schizophrenia, 55.26% for paranoid psychosis, and 51.43% for schizoaffective disorder. Multivariate analysis identified the following protective factors for disease stabilization: age of 18~39 years (OR=0.613, 95% CI: 0.409~0.918), age of 40~65 years (OR=0.615, 95% CI: 0.407~0.931), urban residence (OR=0.587, 95% CI: 0.478~0.720), and regular medication adherence (OR=0.826, 95% CI: 0.702~0.973). Risk factors for disease fluctuation included poor (OR=1.712, 95% CI: 1.436~2.040), non-inclusion in care-support programs (OR=1.928, 95% CI: 1.694~2.193), non-participation in community rehabilitation (OR=2.255, 95% CI: 1.930~2.634), and intermittent medication adherence (OR=3.893, 95% CI: 2.548~5.946). ConclusionThe stability rate, standardized management rate, and regular medication adherence rate of patients with severe mental disorders in Luzhou City have shown a year-by-year increase. Age, household registration status, economic condition, medication compliance, and community-based rehabilitation were identified as influencing factors for disease fluctuation in these patients. [Funded by Luzhou Science and Technology Plan Project (number, 2022-ZRK-186)]
6.Effects of isorhamnetin on the development of gastric cancer by up-regulating SLC25A25-AS1
Yang ZHANG ; Jing WANG ; Lisha NA ; Aoran ZENG ; Bowen PANG ; Yulin LIU
China Pharmacy 2025;36(8):932-938
OBJECTIVE To explore the effects of isorhamnetin on the development of gastric cancer through up-regulation of solute carrier family 25 member 25 antisense RNA 1(SLC25A25-AS1). METHODS Using BALB/c nude mice as the subjects, the xenograft tumor model was established by subcutaneously inoculating human gastric cancer MKN28 cells into the axillary region. The effects of low and high doses of isorhamnetin (20 and 40 mg/kg) on the tumor volume and mass in nude mice were investigated. MKN28 cells were selected and divided into control group, isorhamnetin group (70 μmol/L, similarly hereinafter), isorhamnetin+knocking down negative control group, isorhamnetin+knocking down SLC25A25-AS1 group, isorhamnetin+ overexpression negative control group and isorhamnetin+overexpressing SLC25A25-AS1 group. Effects of knocking down/ overexpressing SLC25A25-AS1 on viability, apoptosis, migration and invasion ability of isorhamnetin-treated cells were detected. After verifying the targeting relationships between microRNA-212-3p (miR-212-3p) and SLC25A25-AS1, as well as phosphatase and tensin homologue deleted on chromosome 10 (PTEN), the effects of knocking down/overexpressing SLC25A25-AS1 on the expression of miR-212-3p, PTEN mRNA, and PTEN protein in isorhamnetin-treated cells were investigated. RESULTS Compared with the model control group, tumor volume and mass of nude mice in the isorhamnetin low-dose and high-dose groups were reduced significantly, and the isorhamnetin high-dose group was significantly lower than the isorhamnetin low-dose group (P<0.05). miR-212-3p had targeting relationships with SLC25A25-AS1 and PTEN. Compared with the control group, the cell viability (intervened for 24, 48 h), migration number, invasion number and miR-212-3p expression of cells in the isorhamnetin group, isorhamnetin+knocking down negative control group and isorhamnetin+overexpressing negative control group were significantly reduced or decreased or down-regulated, while the apoptosis rate, mRNA and protein expressions of PTEN were significantly increased or up-regulated (P<0.05). Compared with isorhamnetin group and isorhamnetin+knocking down negative control group, the cell viability, migration number, invasion number and miR-212-3p expression of cells in the isorhamnetin+knocking down SLC25A25-AS1 group were significantly increased or up- regulated, while the apoptosis rate, mRNA and protein expressions of PTEN were significantly reduced or down-regulated (P< 0.05). Compared with isorhamnetin group and isorhamnetin+overexpressing negative control group, the cell viability, migration number, invasion number and miR-212-3p expression of cells in isorhamnetin+overexpressing SLC25A25-AS1 group were significantly reduced or decreased or down-regulated, while the apoptosis rate, PTEN mRNA and protein expressions were significantly increased or up-regulated (P<0.05). CONCLUSIONS Isorhamnetin may inhibit the development of gastric cancer by up-regulating the expression of SLC25A25-AS1, down-regulating miR-212-3p, and up-regulating the expression of PTEN, which is a downstream target of miR-212-3p.
7.Association between placental cortisol and neurodevelopment in 3-month-old infants
Shuangjie YU ; Jinfang ZHANG ; Ye LI ; Jing FAN ; Can LIU ; Suzhen GUAN
Journal of Environmental and Occupational Medicine 2025;42(4):420-426
Background During pregnancy, negative emotions such as anxiety and depression may induce cortisol disruption. Cortisol can be transmitted to the fetus through the placental barrier, thereby affecting the neurodevelopment of the offspring. Objective To investigate the relationship between placental cortisol, maternal depression during pregnancy, and neurodevelopment of 3-month-old infants. Methods From September 2022 to September 2023, 171 pregnant women ordered routine prenatal checks at the obstetrics outpatient department of a tertiary hospital in Ningxia were selected using a prospective cohort design. After providing informed consent, these women participated in a questionnaire survey that covered general individual characteristics, prenatal depression, and sleep quality. At birth, placental samples were collected to measure cortisol levels using ELISA kits. Follow-up assessments on the neurodevelopmental of 3-month-old infants were conducted using the Warning Sign for Children Mental and Behavioral Development. LASSO regression analysis was conducted to screen the influencing factors of depression during pregnancy. Huber regression analysis was then applied to assess potential linear relationship between depression during pregnancy and placental cortisol levels. Log-binomial regression was used to analyze the linear relationships between cortisol levels and neurodevelopmental delay in 3-month-old infants. Additionally, a mediation effect model was fitted using R 4.3.3 to assess possible mediating role of cortisol in the association between prenatal depression and neurodevelopmental delay in 3-month-old infants. Results The positive rate of prenatal depression was 33.33%. Nine factors affecting prenatal depression were identified by LASSO regression, including rural residence, high school education or above, extroverted personality characteristics, moderate early pregnancy reactions, baby sex expectation, prenatal anxiety, family dysfunction, exposure to stressful life events during pregnancy, and moderate prenatal sleep quality. The Huber regression model showed a positive linear correlation between prenatal depression and placental cortisol (P<0.05). With or without controlling confounding factors, the results of log-binomial regression modeling showed that cortisol levels were associated with a reduced risk of neurodevelopmental delay in 3-month-old infants (crude model: RR=0.988, 95%CI:
8.Prevalence, influencing factors, and fibrosis risk stratification of metabolic dysfunction-associated fatty liver disease in the health check-up population in Beijing, China
Haiqing GUO ; Mingliang LI ; Feng LIU ; Jing ZHANG
Journal of Clinical Hepatology 2025;41(4):643-649
ObjectiveTo identify the patients with metabolic dysfunction-associated fatty liver disease (MAFLD) among the health check-up population, and to perform stratified management of patients with the low, medium, and high risk of advanced fibrosis based on noninvasive fibrosis scores. MethodsA cross-sectional study was conducted among 3 125 individuals who underwent physical examination in Beijing Physical Examination Center from December 2017 to December 2019, and they were divided into MAFLD group with 1 068 individuals and non-MAFLD group with 2 057 individuals. According to BMI, the MAFLD group was further divided into lean MAFLD group (125 individuals with BMI<24 kg/m2) and non-lean MAFLD group (943 individuals with BMI≥24 kg/m2). Indicators including demographic data, past history, laboratory examination, and liver ultrasound were compared between groups. Fibrosis-4 (FIB-4) score, NAFLD fibrosis score (NFS), aspartate aminotransferase-to-platelet ratio index (APRI), and BARD score were calculated for the patients in the MAFLD group to assess the risk of advanced fibrosis. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. A logistic regression analysis was used to investigate the influence of each indicator in MAFLD. ResultsCompared with the non-MAFLD group, the MAFLD group had significantly higher age (Z=-9.758, P<0.05), proportion of male patients (χ2=137.555, P<0.05), and levels of body weight (Z=-27.987, P<0.05), BMI (Z=-32.714, P<0.05), waist circumference (Z=-31.805, P<0.05), hip circumference (Z=-26.342, P<0.05), waist-hip ratio (Z=-28.554, P<0.05), alanine aminotransferase (ALT) (Z=-25.820, P<0.05), aspartate aminotransferase (AST) (Z=-16.894, P<0.05), gamma-glutamyl transpeptidase (GGT) (Z=-25.069, P<0.05), alkaline phosphatase (Z=-12.533, P<0.05), triglyceride (Z=-27.559), total cholesterol (Z=-7.833, P<0.05), low-density lipoprotein cholesterol (LDL-C) (Z=-8.222, P<0.05), and uric acid (UA) (Z=-20.024, P<0.05), as well as a significantly higher proportion of patients with metabolic syndrome (MetS) (χ2=578.220, P<0.05), significantly higher prevalence rates of hypertension (χ2=241.694, P<0.05), type 2 diabetes (χ2=796.484, P<0.05), and dyslipidemia (χ2=369.843, P<0.05), and a significant reduction in high-density lipoprotein cholesterol (HDL-C) (Z=23.153, P<0.001). The multivariate logistic regression analysis showed that male sex (odds ratio [OR]=1.45, 95% confidence interval [CI]: 1.203 — 1.737), ALT (OR=1.05, 95%CI: 1.046 — 1.062), LDL-C (OR=1.23, 95%CI: 1.102 — 1.373), and comorbidity with MetS (OR=5.97, 95%CI: 4.876 — 7.316) were independently associated with MAFLD. Compared with the non-lean MAFLD group, the lean MAFLD group had significantly higher age (Z=3.736, P<0.05) and HDL-C (Z=2.679, P<0.05) and significant reductions in the proportion of male patients (χ2=28.970, P<0.05), body weight (Z=-14.230, P<0.05), BMI (Z=-18.188, P<0.05), waist circumference (Z=-13.451, P<0.05), hip circumference (Z=-13.317, P<0.05), ALT (Z=-4.519, P<0.05), AST (Z=-2.258, P<0.05), GGT (Z=-4.592, P<0.05), UA (Z=-4.415, P<0.05), the proportion of patients with moderate or severe fatty liver disease or MetS (χ2=42.564, P<0.05), and the prevalence rates of hypertension (χ2=12.057, P<0.05) and type 2 diabetes (χ2=3.174, P<0.05). Among the patients with MAFLD, 10 patients (0.9%) had an FIB-4 score of >2.67, 4 patients (0.4%) had an NFS score of >0.676, 8 patients (0.7%) had an APRI of >1, and 551 patients (51.6%) had a BARD score of ≥2. ConclusionThere is a relatively high prevalence rate of MAFLD among the health check-up population in Beijing, but with a relatively low number of patients with a high risk of advanced fibrosis, and such patients need to be referred to specialized hospitals for liver diseases.
9.Mechanism of Tangbikang Dry Paste in Prevention and Treatment of Type 2 Diabetic Peripheral Neuropathy Based on GLO-1/AGE/RAGE Pathway
Lijia WU ; Chengfei ZHANG ; Xiaolei JIA ; Lingling QIN ; Haiyan WANG ; Yukun HUANG ; You WANG ; Xincui BAO ; Jing YANG ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):60-69
ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy (DPN) based on the glyoxalase-1 (GLO-1)/advanced glycation end products (AGE)/receptor for advanced glycation end products (RAGE) pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided, with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin (STZ) to induce a type 2 diabetes mellitus (T2DM) model. Based on blood glucose levels, the rats were randomly assigned to the model group, Tanglin group (13.5 mg·kg-1), metformin group (135 mg·kg-1), and Tangbikang dry paste low-, medium-, and high-dose groups (3, 6, 12 g·kg-1). Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose, body weight, and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention, the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin (HE) staining. The expression of RAGE, AGE, protein kinase C (PKC), and collagen (COL) in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE, PKC, Toll-like receptor (TLR), COL, and GLO-1 was detected using real-time quantitative PCR (Real-time PCR). Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CREA), urea (UREA), interleukin-6 (IL-6), and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the normal group, the model group showed significantly increased fasting blood glucose (P<0.01), decreased body weight and mechanical pain threshold (P<0.01), and elevated serum AST, ALT, CREA, UREA, IL-6, and TNF-α levels (P<0.01). The expression of RAGE, AGE, and PKC in the sciatic nerve was significantly increased (P<0.01), while COL expression was decreased (P<0.01). The mRNA expression of TLR, RAGE, and PKC was upregulated (P<0.01), whereas COL and GLO-1 mRNA levels were downregulated (P<0.01). Histological examination showed irregular nerve morphology, axonal alterations, and myelin degeneration. Compared with the model group, fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced (P<0.05, P<0.01). No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups (P<0.05, P<0.01). Serum IL-6 and TNF-α levels were decreased in all dose groups (P<0.05, P<0.01). The expression of RAGE, AGE, and PKC in the sciatic nerve was reduced (P<0.01), while COL expression was increased (P<0.01). The mRNA expression of TLR, RAGE, and PKC was downregulated (P<0.01), whereas GLO-1 mRNA expression was upregulated (P<0.05, P<0.01). Additionally, COL mRNA expression was significantly increased in the low- and high-dose groups (P<0.01). Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN, and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.
10.Mechanism of Tangbikang Dry Paste in Prevention and Treatment of Type 2 Diabetic Peripheral Neuropathy Based on GLO-1/AGE/RAGE Pathway
Lijia WU ; Chengfei ZHANG ; Xiaolei JIA ; Lingling QIN ; Haiyan WANG ; Yukun HUANG ; You WANG ; Xincui BAO ; Jing YANG ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):60-69
ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy (DPN) based on the glyoxalase-1 (GLO-1)/advanced glycation end products (AGE)/receptor for advanced glycation end products (RAGE) pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided, with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin (STZ) to induce a type 2 diabetes mellitus (T2DM) model. Based on blood glucose levels, the rats were randomly assigned to the model group, Tanglin group (13.5 mg·kg-1), metformin group (135 mg·kg-1), and Tangbikang dry paste low-, medium-, and high-dose groups (3, 6, 12 g·kg-1). Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose, body weight, and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention, the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin (HE) staining. The expression of RAGE, AGE, protein kinase C (PKC), and collagen (COL) in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE, PKC, Toll-like receptor (TLR), COL, and GLO-1 was detected using real-time quantitative PCR (Real-time PCR). Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CREA), urea (UREA), interleukin-6 (IL-6), and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the normal group, the model group showed significantly increased fasting blood glucose (P<0.01), decreased body weight and mechanical pain threshold (P<0.01), and elevated serum AST, ALT, CREA, UREA, IL-6, and TNF-α levels (P<0.01). The expression of RAGE, AGE, and PKC in the sciatic nerve was significantly increased (P<0.01), while COL expression was decreased (P<0.01). The mRNA expression of TLR, RAGE, and PKC was upregulated (P<0.01), whereas COL and GLO-1 mRNA levels were downregulated (P<0.01). Histological examination showed irregular nerve morphology, axonal alterations, and myelin degeneration. Compared with the model group, fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced (P<0.05, P<0.01). No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups (P<0.05, P<0.01). Serum IL-6 and TNF-α levels were decreased in all dose groups (P<0.05, P<0.01). The expression of RAGE, AGE, and PKC in the sciatic nerve was reduced (P<0.01), while COL expression was increased (P<0.01). The mRNA expression of TLR, RAGE, and PKC was downregulated (P<0.01), whereas GLO-1 mRNA expression was upregulated (P<0.05, P<0.01). Additionally, COL mRNA expression was significantly increased in the low- and high-dose groups (P<0.01). Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN, and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

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