1.Mechanism of Yueju Wan in Treatment of Functional Dyspepsia Based on Regulation of 5-HT Signaling Pathway
Haoran SHEN ; Yaru GU ; Muqing ZHANG ; Zhikuo DONG ; Xingxing GAO ; Dantong LI ; Ying GU ; Yixin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):20-28
ObjectiveTo investigate the effects of Yueju Wan on the 5-hydroxytryptamine (5-HT) signaling pathway in rats with functional dyspepsia (FD) and to explore its therapeutic mechanism in the treatment of FD. MethodsSixty Sprague-Dawley (SD) rats were randomly divided into a normal group, model group, mosapride group (1.575 mg·kg-1), and Yueju Wan low-, medium-, and high-dose groups (0.735, 1.47, and 2.94 g·kg-1, respectively). The FD rat model was established using GUO's tail-clamping stimulation combined with irregular feeding. After 14 days of modeling, rats were administered the corresponding drugs by gavage for 28 days. After treatment, gastric emptying rate and small intestinal propulsion rate were measured. Serum levels of 5-HT, tryptophan hydroxylase (TPH), and substance P (SP) were detected by enzyme-linked immunosorbent assay (ELISA), and acetylcholine (ACh) levels were determined by chemical methods. Histopathological changes in the gastric antrum were observed using hematoxylin-eosin (HE) staining. Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to assess the mRNA and protein expression levels of 5-hydroxytryptamine 4 receptor (5-HT4R), SP, and acetylcholinesterase (AChE) in colon tissue, as well as 5-hydroxytryptamine 3 receptor (5-HT3R), SP, and AChE in hypothalamic tissue. Immunohistochemistry (IHC) was used to examine the expression of 5-HT and 5-HT4R in the colon and 5-HT and 5-HT3R in the hypothalamus. ResultsCompared with the normal group, the gastric emptying rate and small intestinal propulsion rate in the model group were significantly decreased (P<0.01). Serum levels of 5-HT, SP, ACh, and TPH were significantly reduced (P<0.01). Histopathological examination revealed irregular arrangement of glands in the gastric antrum, slight mucosal atrophy, and mild inflammatory cell infiltration. The mRNA and protein expression levels of 5-HT4R, SP, and AChE in colon tissue, as well as 5-HT3R, SP, and AChE in hypothalamic tissue, were significantly decreased (P<0.01), and 5-HT protein expression in both the colon and hypothalamus was also significantly reduced (P<0.01). Compared with the model group, all Yueju Wan groups showed significantly increased gastric emptying rate and small intestinal propulsion rate (P<0.01). The glands in the gastric antrum were more regularly arranged, with no inflammatory cell infiltration observed. Serum levels of 5-HT, SP, ACh, and TPH were significantly increased (P<0.01). The mRNA and protein expression levels of 5-HT4R, SP, and AChE in colon tissue and 5-HT3R, SP, and AChE in hypothalamic tissue were significantly upregulated (P<0.05, P<0.01), and 5-HT protein expression in both the colon and hypothalamus was significantly increased (P<0.01). ConclusionYueju Wan has preventive and therapeutic effects on FD, and its mechanism may be related to regulation of the 5-HT signaling pathway, promotion of brain-gut peptide secretion, and enhancement of gastric motility.
2.Adiponectin alleviates high glucose-induced retinal angiogenesis by inhibiting NLRP3 inflammasome
Yong ZHANG ; Xiaodi WANG ; Yixin ZHANG ; Guomin YAO
International Eye Science 2026;26(5):732-737
AIM: To explore the effect of adiponectin(ADPN)on angiogenesis of human retinal microvascular endothelial cells(hRMECs)in high glucose(HG)environment and role of NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome.METHODS: The hRMECs were divided into six groups, including control group(without treatment), HG group: incubated with D-glucose, ADPN group: pretreatment with ADPN and then incubated with D-glucose, CY-09 group: pretreatment with CY-09(an NLRP3 inhibitor)and then incubated with D-glucose, Nigericin group: pretreatment with nigericin(an NLRP3 activator)and then incubated with D-glucose, Nigericin+ADPN group: pretreatment with nigericin and ADPN and then incubated with D-glucose. NLRP3 level was detected using Western blot analysis. hRMECs migration was measured using scratch wound healing assay. The tube formation of hRMECs was detected using Matrigel.RESULTS: The NLRP3 expression in hRMECs cultured in an HG environment was significantly increased(P<0.01), while ADPN and CY-09 reduced the elevated NLRP3(both P<0.05 vs HG group). Nigericin significantly increased NLRP3 levels(P<0.01 vs control group)which was reversed by ADPN(P=0.032 vs Nigericin group). hRMECs migration ability(P<0.001), and total master segments length and number of meshes increased in HG group(P<0.001)while decreased in ADPN and CY-09 groups(all P<0.01 vs HG group). The hRMECs migration ability and tube formation(total master segments length and number of meshes)in HG environment were significantly increased by nigericin(P=0.003), while ADPN inversed the change. CONCLUSION: ADPN alleviates the migration and angiogenesis of hRMECs under HG conditions.
3.Syndrome Differentiation and Treatment Mechanisms of Inflammatory Injury in Diabetic Cardiomypathy from Theory of "Gaozhuo"
Xiaoyue WANG ; Yunfeng YU ; Xiangning HUANG ; Yixin XIANG ; Sihao ZHANG ; Qin XIANG ; Rong YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):235-244
Diabetic cardiomyopathy (DCM) is one of the most common complications of diabetes mellitus and is a major threat to global health. As a key mechanism in the occurrence and progression of DCM, the inflammatory response persists throughout the entire course of the DCM. The Gaozhuo theory suggests that the basic pathogenesis of inflammatory injury in DCM is the Qi deficiency of spleen and kidney and Gaozhuo invasion, and divides the pathological process into three phases: Gaozhuo invasion, turbid heat damage to the channels, and turbid blood stasis and heat junction. Among them, the Qi deficiency of spleen and kidney and the endogenous formation of Gaozhuo represent the process of inflammatory factor formation induced by glucose metabolism disorders. Turbid heat damage to the channels refers to the process of myocardial inflammatory injury mediated by inflammatory factors, and turbid blood stasis and heat junction are the process of myocardial injury developing toward myocardial fibrosis and ventricular remodeling. As the disease continues to progress, it eventually develops into a depletion of the heart Yang, leading to the ultimate regression of heart failure. According to the theory of Gaozhuo, traditional Chinese medicine (TCM) should regulate inflammatory injury in DCM by strengthening the spleen and tonifying the kidney to address the root cause, and resolving dampness and lowering turbidity to treat the symptoms. If the turbidity has been stored for a long time and turns into heat, strengthening the spleen and tonifying the kidney, and clearing heat and resolving turbidity should be the therapy. If the turbidity, stasis, and heat are knotted in the heart and collaterals, strengthening the spleen and tonifying the kidney, and resolving stasis and lowering turbidity should be the therapy. TCM compounds and monomers can regulate the inflammatory response in DCM. TCM compounds can be divided into the categories for benefiting Qi to resolve turbidity, benefiting Qi and clearing heat to resolve turbidity, and benefiting Qi and activating blood to reduce turbidity. The compounds can inhibit upstream signals of inflammation and expression of inflammatory factors, improve the inflammatory damage to myocardium and blood vessels, myocardial fibrosis, and cardiac systole and diastole, and thus slow down the onset and progression of DCM.
4.Prevalence and associated factors of short video addiction among nursing students in higher vocational colleges
YAN Menghua, LU Yixin, WANG Meili, ZHANG Zhenxiang, MEI Yongxia, CHANG Xiaofang, XIANG Xu
Chinese Journal of School Health 2026;47(5):700-703
Objective:
To understand the current status of short video addiction among vocational nursing students in higher vocational colleges (hereinafter referred to as "nursing students") and its related factors, so as to provide a reference for formulating online education programs in colleges.
Methods:
From March to May 2025, a stratified random sample of 2 223 nursing students from four vocational colleges in Henan Province was selected. Short Video Addiction Scale for College Students, Short form Egna Minnen av Barndoms Uppfostran for Chinese, Peer Rejection Scale, and University of California at Los Angels Loneliness Scale were used for investigation. Chi square test and multivariate Logistic regression analysis were used to explore the related factors of short video addiction among nursing students.
Results:
The detection rate of short video addiction of higher vocational nursing students was 26.95%, and the scores for avoidance, loss of control, inefficiency and withdrawal were (8.05±2.97) (10.24±3.09) (4.99±1.88) and (11.97±4.10), respectively. Multivariate Logistic regression analysis showed that sophomore year 2 ( OR=1.83, 95%CI =1.39-2.40), higher maternal education level (secondary school/vocational college: OR =1.34, 95% CI =1.06-1.68; college/undergraduate: OR =1.38, 95% CI =1.05-1.82), paternal overprotection ( OR=1.59, 95%CI =1.27-2.00), high peer rejection ( OR=1.40, 95%CI =1.19-1.66), and strong loneliness ( OR=1.57, 95%CI =1.07-2.28) were associated with a higher risk of short video addiction among nursing students (all P <0.05). Paternal affectionate and warm rearing style ( OR=0.82, 95%CI = 0.71- 0.95) was associated with a lower risk of short video addiction ( P <0.05).
Conclusions
The detection rate of short video addiction among nursing students is relatively high. Short video addiction is related to the nursing students grade, maternal education level, paternal overprotection and affectionate rearing style, peer rejection, and loneliness.
5.Mechanism of Zuogui Wan in Improving Nephrotic Syndrome in Rats Based on Regulating Gut Microbiota
Xinyu HU ; Tubei ZHANG ; Yixin HU ; Rui WANG ; Zhili XIONG ; Yan CAI ; Xuerong ZHANG ; Linqun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(19):32-41
ObjectiveTo investigate the protective effects of Zuogui Wan (ZGW) decoction on nephrotic syndrome (NS) through the regulation of gut microbiota. MethodsThirty male Sprague-Dawley (SD) rats were randomly divided into five groups, with 6 rats in each group: The control group, model group, low-dose group, medium-dose group, and high-dose group. The NS rat model was induced by tail vein injection of 6.5 mg·kg-1 doxorubicin. After successful modeling, the control and model groups were gavaged with normal saline (10 mL·kg-1) twice daily, while the low- (50 mg·kg-1), medium- (100 mg·kg-1), and high-dose (200 mg·kg-1) groups were gavaged with ZGW (10 mL·kg-1) twice daily. All rats were administered at fixed intervals daily for 8 consecutive weeks. The therapeutic effects of ZGW on NS in rats were observed, and the optimal dose was screened. Renal and intestinal pathological changes in rats were examined. Fecal samples were collected, and 16S rDNA sequencing technology was used to detect the diversity and abundance of gut microbiota in each group. ResultsCompared with the control group, 24-hour urinary protein, serum creatinine, urea nitrogen, and cholesterol levels significantly increased in the model group (P<0.01), while serum albumin levels decreased (P<0.01). These changes were ameliorated in the treatment groups (P<0.05, P<0.01). Renal pathology revealed intact and orderly arranged glomeruli and renal tubules in the control group. In the model group, glomerular atrophy, widened mesangial areas, podocyte swelling, disordered renal tubular arrangement, and numerous casts were observed. Varying degrees of glomerular atrophy and disordered renal tubular arrangement were seen in the treatment groups. Specific protein assays revealed increased serum levels of kidney injury molecule-1(KIM-1) and α1-microglobulin (P<0.01), and significantly decreased levels of E-cadherin, Podocin, and Nephrin in renal tissues (P<0.01), along with a significant increase in transforming growth factor-β(TGF-β) (P<0.01) in the model group. In the treatment groups, serum KIM-1 and α1-microglobulin levels decreased, E-cadherin levels significantly increased (P<0.01), and TGF-β levels significantly decreased (P<0.01). Podocin and Nephrin levels increased in the high-dose group (P<0.05). Additionally, intestinal mucosal atrophy, epithelial cell edema, decreased goblet cells, and multiple inflammatory infiltrations were observed in the model group. The sequencing results of gut microbiota demonstrate that ZGW can significantly ameliorate intestinal dysbiosis in rats, restore the abundance of beneficial bacteria, and exert a profound influence on the compositional profile of gut microbiota. ConclusionZGW can alleviate renal injury in rats with nephrotic syndrome by improving gut microbiota and protecting the intestinal barrier.
6.Contralateral posteromedial thigh flap for salvage breast reconstruction with adductor magnus perforator flap failure
Dajiang SONG ; Tianyi ZHANG ; Zan LI ; Yixin ZHANG
Chinese Journal of Plastic Surgery 2025;41(6):577-582
Objective:To summarize the technical experience of using a contralateral free gracilis myocutaneous flap combined with an adductor magnus perforator flap for salvaging failure of breast reconstruction after transplantation with the free adductor magnus perforator flap.Methods:A retrospective analysis was conducted on patients with breast cancer who received contralateral posteromedial thigh flap (gracilis myocutaneous flap combined with adductor magnus perforator flap) transplantation for immediate unilateral breast reconstruction developed vascular crisis and caused flap necrosis at the Department of Oncology Plastic Surgery, Hunan Cancer Hospital, between December 2016 to December 2022. All patients with early-stage breast cancer received modified radical mastectomy. All patients were selected to undergo the immediate breast reconstruction surgery with unilateral free adductor magnus perforator flap transplantation. The proximal end of internal mammary vessels were used as the recipient vessels in all cases. After the emergency exploration confirmed the necrosis of the flap, a contralateral free gracilis myocutaneous flap combined with adductor magnus perforator flap were immediately harvested for salvage breast reconstruction. The vascular pedicle of the gracilis muscular branch and the adductor magnus perforator branch were anastomosed with the proximal and distal ends of the internal mammary vessels, respectively. Postoperative patient monitoring was conducted intensively, with follow-up assessments focusing on breast contour and donor site recovery.Results:A total of 5 patients were included, aged 26 to 42 years, with an average of (31.5±1.8) years. All salvaged breast reconstruction surgeries were successful, the salvaged flap measured 15.0 cm×6.0 cm×4.0 cm-17.0 cm×7.5 cm×5.5 cm. All the transplanted flaps survived after the operation, with satisfactory breast contour, good flap elasticity, and no contracture or deformation. The donor sites of both thigh flaps healed well, leaving only linear scars and no significant functional impairment to the lower limbs. Follow-up ranged from 9 to 24 months, with an average of 15.7 months. The breast shape was satisfactory, and there was no recurrence of breast cancer.Conclusion:The donor site morbidity of the posteromedial thigh flap is relatively small. When unilateral flap transplantation fails, immediate transfer of the contralateral flap can be chosen for salvage reconstruction. This approach ensures symmetrical donor site outcomes and is generally well-accepted by patients.
7.Feature of Cardiovascular-kidney-metabolic Syndrome Among Ethnic Minorities in Yunnan,China
Nuerguli TUERDI ; Xue CAO ; Yujie ZHANG ; Zixuan DONG ; Weiping LI ; Fan LI ; Xin WANG ; Congyi ZHENG ; Yixin TIAN ; Chenye CHANG ; Xuyan PEI ; Qinglan JIA ; Jialu YANG ; Zengwu WANG
Chinese Circulation Journal 2025;40(10):1022-1029
Objectives:To investigate the epidemiological characteristics and ethnic differences of cardiovascular-kidney-metabolic syndrome(CKM)among the Hani,Dai,Bai,and Lisu populations in Yunnan Province,and to provide evidence for developing effective prevention and control strategies for CKM.Methods:A cross-sectional survey was conducted among four ethnic minority groups.A total of 3 906 permanent residents aged 18 years and older were enrolled using a multistage cluster random sampling method.CKM stages(0-4)were defined based on the 2023 American Heart Association criteria,stages 3-4 were classified as advanced CKM.Descriptive statistics and chi-square tests were used to compare the prevalence of CKM stages across ethnic groups.Modified Poisson regression was applied to estimate relative risk(RR)and 95%confidence intervals(CI)for factors associated with advanced CKM.Results:The prevalence rates of CKM stage 1 and above among the Hani,Dai,Bai and Lisu ethnic groups were 80.1%,87.3%,84.8%and 67.8%,respectively.The prevalence of CKM was generally higher in males than in females,and the prevalence of CKM increased significantly with age.The Dai ethnic group had the highest prevalence of advanced CKM(24.7%,95%CI:22.1%-27.4%),while the Lisu ethnic group had the lowest prevalence of advanced CKM(13.7%,95%CI:11.5%-15.9%).Modified Poisson regression analysis showed that older age and higher body mass index were common risk factors for advanced CKM across all four ethnic groups.Additionally,except for the Lisu ethnic group,the other three ethnic groups had specific individual risk factors:among the Hani ethnic group,low educational attainment(RR=2.18,95%CI:1.12-4.25)and low income(RR=1.47,95%CI:1.00-2.18)were the primary risk factors of CKM.Among the Dai ethnic group,smoking(RR=1.60,95%CI:1.07-2.37)and a family history of cardiovascular disease(RR=1.61,95%CI:1.14-2.27)are the primary risk factors of CKM.Among the Bai ethnic group,male gender(RR=0.48,95%CI:0.29-0.79)was the primary risk factor of CKM.Conclusions:The prevalence of CKM stage 1 or higher is relatively high among the four minority ethnic groups in Yunnan province.There are significant differences in staging characteristics and primary risk factors across ethnic groups,necessitating the development of stratified,differentiated intervention strategies to achieve precise prevention and control and ethnic health equity in terms of CKM.
8.Effects and mechanisms of capsaicin on full-thickness skin defects in diabetic mice
Hao MA ; Peiru MIN ; Yixin ZHANG ; Liuhanghang CHENG
Chinese Journal of Burns 2025;41(7):645-654
Objective:To investigate the effects and mechanisms of capsaicin on full-thickness skin defects in diabetic mice.Methods:This study was an experimental study. Thirty-six male db/db mice aged 6-8 weeks were taken. Circular full-thickness skin defect wounds (6 mm in diameter) were created on their backs. According to the random number table method (grouping method same below), the mice were divided into control group, low-concentration capsaicin group, and high-concentration capsaicin group injected with normal saline, 10 μmol/L capsaicin solution, and 20 μmol/L capsaicin solution, respectively ( n=12). Immediately after modeling and on day 2, 30 μL of the corresponding solution was injected locally into the wounds. At 4, 8, and 12 days after injury, wound healing status was observed grossly and the percentage of residual wound area was calculated. At 12 days after injury, the proportions of inflammatory cell, collagen fiber, and CD31-positive expression areas in the wound of mice were observed and detected respectively using hematoxylin and eosin staining, Masson staining, and immunohistochemical staining, and the protein expression of transient receptor potential vanilloid type 1 (TRPV1) in the wound tissue of mice was detected using Western blotting. Human primary fibroblasts were prepared from normal skin tissue obtained from 5 patients (2 male and 3 female patients, aged 20-45 years) who were admitted to the Department of Plastic and Reconstructive Surgery of Shanghai Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine in October 2024. Cells in the logarithmic growth phase (passages 2-5) were used for subsequent experiments. Cells were divided into control group and high-concentration capsaicin group, cultured in complete media without or with 20 μmol/L capsaicin, respectively. After 24 hours of culture, differentially expressed genes (DEGs) between two groups were identified using the DESeq2 R package, followed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The cells were divided into control group, low-concentration capsaicin group, and high-concentration capsaicin group, which were cultured in complete media without capsaicin, and with 10 μmol/L capsaicin, and with 20 μmol/L capsaicin, respectively. After 48 hours of culture, cell apoptosis status was assessed using flow cytometer. The protein expression levels of protein kinase B (Akt), phosphorylated Akt (p-Akt), mammalian target of rapamycin (mTOR), and phosphorylated mTOR (p-mTOR) in cells were detected by Western blotting, and the p-Akt/Akt and p-mTOR/mTOR ratios were calculated. At 12 days after injury, the protein expression levels of Akt, p-Akt, mTOR, and p-mTOR in the wounds of diabetic mice in both control group and high-concentration capsaicin group were detected by Western blotting, and the p-Akt/Akt and p-mTOR/mTOR ratios were calculated. All animal experiments used a sample size of 6, and all cellular experiments used 3. Results:At 4 days after injury, the wounds of three groups of diabetic mice began to heal gradually, and the percentages of residual wound area of mice in both low-concentration capsaicin group and high-concentration capsaicin group were significantly lower than that in control group (with t values of 2.31 and 2.87, respectively, P<0.05). At 8 days after injury, the percentages of residual wound area of mice in both low-concentration capsaicin group and high-concentration capsaicin group were significantly lower than that in control group (with t values of 2.55 and 5.38, respectively, P<0.05). At 12 days after injury, the percentages of residual wound area of mice in both low-concentration capsaicin group and high-concentration capsaicin group remained significantly lower than that in control group (with t values of 3.31 and 6.24, respectively, P<0.05), with the high-concentration capsaicin group showing a significantly greater reduction compared to that in low-concentration capsaicin group ( t=3.42, P<0.05). At 12 days after injury, the proportion of inflammatory cell area in the wound of mice in high-concentration capsaicin group was (6.2±1.8)%, significantly lower than (15.5±3.0)% in control group ( t=6.45, P<0.05). The proportion of collagen fiber area, proportion of CD31-positive expression area, and protein expression of TRPV1 in the wound of mice in high-concentration capsaicin group were significantly higher compared with those in control group (with t values of 5.48, 7.11, and 15.41, respectively, P<0.05). After 24 hours of culture, 51 DEGs with significantly differential expression were detected in high-concentration capsaicin group of cells compared with those in control group ( P<0.05), with 31 upregulated and 20 downregulated genes. GO analysis showed that the significantly upregulated and significantly downregulated DEGs mainly participated in biological processes such as extracellular matrix (ECM) polymerization, extracellular structure organization, collagen metabolic process regulation, and ECM component secretion regulation. KEGG analysis showed that the significantly upregulated and significantly downregulated DEGs mainly participated in cell apoptosis-related pathways such as the phosphatidylinositol 3-kinase/Akt pathway and tumor necrosis factor signaling pathway. After 48 hours of culture, the cell apoptosis rates in both low-concentration capsaicin group and high-concentration capsaicin group were significantly lower than that in control group (with t values of 6.38 and 9.09, respectively, P<0.05). The p-mTOR/mTOR ratio in cells in low-concentration capsaicin group was significantly higher than that in control group ( t=2.74, P<0.05). The p-Akt/Akt and p-mTOR/mTOR ratios in cells in high-concentration capsaicin group were significantly higher than those in control group (with t values of 4.43 and 3.33, respectively, P<0.05). At 12 days after injury, the p-Akt/Akt and p-mTOR/mTOR ratios in wounds of diabetic mice in high-concentration capsaicin group were 0.470±0.044 and 0.549±0.106, respectively, which were significantly higher than 0.189±0.058 and 0.241±0.120 in control group (with t values of 6.67 and 3.36, respectively, P<0.05). Conclusions:Capsaicin can promote the healing of full-thickness skin defect wounds in diabetic mice by activating the Akt/mTOR signaling pathway in fibroblasts, thereby inhibiting apoptosis.
9.Mechanism of Xielitang Against Ulcerative Colitis in Mice Based on "Intestinal Flora-bile Acid" Axis
Xiaotian WANG ; Yaning BIAO ; Yixin ZHANG ; Jian CHEN ; Ya GAO ; Yufang ZHANG ; Muqing ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):30-38
ObjectiveTo investigate the protective effect of Xielitang on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice and its possible mechanism. MethodsDSS was used to establish UC model. Sixty mice were randomly divided into a normal group, a model group, a sulfasalazine group (0.6 g·kg-1), and low-, medium-, and high-dose Xielitang groups (1.67, 3.34, 6.68 g·kg-1). After treatment for 42 d, the colon length was recorded, and the disease activity index (DAI) score was calculated. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10). Hematoxylin-eosin (HE) staining was used to observe the pathomorphological changes of colon. Western blot was used to detect the protein expression of farnesoid X receptor (FXR), small heterodimer partner (SHP), liver receptor homolog-1 (LRH-1), cholesterol 7α-hydroxylase (CYP7A1), and fibroblast growth factor receptor 4 (FGFR4) in liver and FXR, sodium-dependent bile acid transporter (ASBT), and fibroblast growth factor 15 (FGF15) in ileum. 16S rRNA sequencing was used to analyze the intestinal flora. Moreover, ultra-high performance liquid chromatography–tandem mass spectrometry was used to detect the bile acid content. ResultsCompared with the normal group, the model group showed significantly decreased colon length, IL-10 content, α-diversity index, abundance of Firmicutes and Lactobacillus, and content of deoxycholic acid (DCA) and lithocholic acid (LCA) (P<0.01), significantly increased DAI score, IL-6 and TNF-α content, abundance of Bacteroidetes, and the content of cholic acid (CA), chenodeoxycholic acid (CDCA), and taurocholic acid (TCA) (P<0.05, P<0.01), significantly down-regulated protein expression of FXR, SHP, and FGFR4 in liver and FXR, ASBT, and FGF15 in ileum (P<0.01), and significantly up-regulated protein expression of LRH-1 and CYP7A1 in liver (P<0.01). In addition, the structure of colonic mucosa was destroyed, and inflammatory cells infiltrated in the model group. Compared with the model group, Xielitang could significantly increase the colon length, IL-10 content, α-diversity index, the abundance of Firmicutes and Lactobacillus, and DCA and LCA content (P<0.05, P<0.01), decrease DAI score, abundance of Bacteroidetes, and the content of IL-6, TNF-α, CA, CDCA, and TCA (P<0.01), up-regulate the protein expression of FXR, SHP, and FGFR4 in liver and FXR, ASBT, and FGF15 in ileum (P<0.01), and down-regulate the protein expression of LRH-1 and CYP7A1 in liver (P<0.01). The pathological damage of colonic mucosa was obviously alleviated. ConclusionXielitang protects against UC probably by regulating the "intestinal microbiota-bile acid" axis, regulating intestinal flora imbalance, and maintaining bile acid homeostasis.
10.VDAC1 activates the PI3K/AKT/mTOR pathway to promote epithelial-mesenchymal transition and cell proliferation in lung adenocarcinoma
Yingru XING ; Ying ZHANG ; Yixin SU ; Yafeng LIU ; Jiawei ZHOU ; Feng ZHAO
Chinese Journal of Preventive Medicine 2025;59(3):317-327
Objective:To explore the regulatory mechanism of voltage-dependent anion channel 1(VDAC1) on the proliferation, migration and invasion of lung adenocarcinoma(LUAD) cells.Methods:This study employed a combination of bioinformatics and experimental validation methods, conducting bioinformatics analysis and cytological experimental validation in the central laboratory of the School of Medicine, Anhui University of Science and Technology from February 2023 to August 2024.Clinical histological specimen validation was performed using immunohistochemistry, and a retrospective analysis was conducted on 5 cases of lung adenocarcinoma and adjacent samples from Huai′an First People′s Hospital affiliated with Nanjing Medical University. The TCGA network database was analyzed for the expression pattern, prognostic value, and functional enrichment of VDAC1 in LUAD. A549 cells with VDAC1 knockdown and H1650 cells with VDAC1 overexpression were established through lentiviral transfection. The expression difference of VDAC1 protein in LUAD and adjacent tissue specimens was detected by immunohistochemistry.The effects of VDAC1 on the proliferation, migration, and invasion capabilities were explored through CCK8 assay, scratch healing assay, and Transwell assay.The activation levels of epithelial-mesenchymal transition (EMT) marker proteins, cell cycle-dependent kinases, and molecules in the PI3K/AKT/mTOR signaling pathway were detected by Western blot.Results:Bioinformatics analysis revealed that VDAC1 was highly expressed in LUAD cells ( P<0.000 1) and was an independent risk factor for LUAD ( P<0.000 1). Functional enrichment analysis showed significant enrichment of the PI3K/AKT/mTOR, G2M checkpoint, and P53 signaling pathways ( P<0.001). Compared to adjacent control tissues, the expression level of VDAC1 protein is higher in lung adenocarcinoma tissues.Overexpression of VDAC1 promoted the proliferation ( P<0.000 1), migration, and invasion( P<0.01) of H1650 cells, while knockdown of VDAC1 inhibited the proliferation ( P<0.000 1), migration, and invasion ( P<0.05) of A549 cells.Western Blot experiments showed that compared to the control group, the expression levels of vimentin (1.10±0.11 vs 2.39±0.15, P<0.001), N-cadherin (0.94±0.12 vs 2.72±0.06, P<0.001), CDK1 (0.93±0.04 vs 1.53±0.03, P<0.000 1), CDK2 (1.04±0.13 vs 2.29±0.06, P<0.001), CDK4 (0.90±0.03 vs 2.00±0.11, P<0.01), p-PI3K (1.08±0.13 vs 1.85±0.12, P<0.01), and p-AKT (1.03±0.11 vs 1.69±0.06, P<0.001) were increased in H1650 cells overexpressing VDAC1, while E-cadherin expression decreased (2.18±0.14 vs 0.997±0.11, P<0.001).In contrast, in A549 cells with VDAC1 knockdown, the expression levels of vimentin (1.70±0.26 vs 0.97±0.09, P<0.05), N-cadherin (1.98±0.25 vs 1.03±0.06, P<0.05), CDK1 (1.13±0.03 vs 0.95±0.02, P<0.01), CDK2 (2.29±0.12 vs 0.92±0.10, P<0.001), CDK4 (1.71±0.096 vs 1.12±0.11, P<0.01), p-PI3K (1.67±0.09 vs 0.97±0.03, P<0.001), and p-AKT (1.53±0.04 vs 1.02±0.03, P<0.000 1) decreased, while E-cadherin expression increased (1.04±0.04 vs 1.85±0.26, P<0.05). Conclusions:VDAC1 may promote the proliferation, migration, and invasion of LUAD cells by activating EMT and cyclin-dependent kinases through the PI3K/AKT/mTOR pathway.


Result Analysis
Print
Save
E-mail