Most Down Articles

Published in last 1 year | In last 2 years| In last 3 years| All| Most Downloaded in Recent Month | Most Downloaded in Recent Year|

In last 3 years

Please wait a minute...


For Selected: Download Citations EndNote Ris BibTeX Toggle Thumbnails

Select

ARL67156, a small-molecule CD39 inhibitor, enhances natural killer cell cytotoxicity against gastric cancer cells in vitro and in nude mice GONG Ying, AIMAITI Ailifeire, HE Zongzhong Journal of Southern Medical University    2023, 43 (12): 2006-2014.   DOI: 10.12122/j.issn.1673-4254.2023.12.03 Abstract （270）   HTML （39）    PDF（pc） （2268KB）（2995）       Knowledge map    Save Objective To investigate the effect of ARL67156, a small-molecule inhibitor of CD39, on cytotoxicity of natural killer (NK) cells against gastric cancer cells. Methods Human peripheral blood-derived primary NK cells isolated and purified using a magnetic bead antibody method were treated with 100 μmol/L ARL67156 for 24 h, and the signaling pathway of NK cell activation was detected by Western blotting. The level of interferon-γ (IFN-γ) in the supernatant of NK cells co-cultured with gastric cancer cells was detected using ELISA, and NK cell CD107a degranulation was measured with flow cytometry. The cytotoxicity of NK cells against co-cultured gastric cancer cells was evaluated using flow cytometry. In a nude mouse model bearing subcutaneous gastric cancer xenografts, the therapeutic effect of intravenous transfusion of NK cells and intraperitoneal injection of ARL67156 was assessed by measuring the changes in tumor volume. Results (25.97±5.69) % of peripheral blood NK cells from healthy individuals positive for CD39 expression. Treatment with ARL67156 significantly upregulated the activation molecules including NKG2D, DAP10, CD57, and CD16 and reduced the expressions of the inhibitory receptors TIGIT and KIR, thereby promoting the secretion of IFN-γ and CD107a degranulation in NK cells (P<0.05). In both the in vitro and in vivo experiments, ARL67156 significantly enhanced the cytotoxicity of NK cells against gastric cancer cells (P<0.05). Conclusion ARL67156 activates NK cells through the vav1-Syk signaling pathway to enhance their cytotoxicity against gastric cancer cells, which may serve as a new strategy for NK cell immunotherapy for gastric cancer. Related Articles | Metrics | Comments（0）

Select

Fucoxanthin regulates Nrf2/Keap1 signaling to alleviate myocardial hypertrophy in diabetic rats ZHENG Dongxiao, CHEN Linlin, WEI Qihui, ZHU Ziran, LIU Zilue, JIN Lin, YANG Guanyu, XIE Xi Journal of Southern Medical University    2022, 42 (5): 752-759.   DOI: 10.12122/j.issn.1673-4254.2022.05.18 Abstract （739）   HTML （33）    PDF（pc） （3710KB）（2443）       Knowledge map    Save Objective To investigate the protective effect of fucoxanthin (FX) against diabetic cardiomyopathy and explore the underlying mechanism. Methods Rat models of diabetes mellitus (DM) induced by intraperitoneal injection of streptozotocin (60 mg/kg) were randomized into DM model group, fucoxanthin treatment (DM+FX) group and metformin treatment (DM+Met) group, and normal rats with normal feeding served as the control group. In the two treatment groups, fucoxanthin and metformin were administered after modeling by gavage at the daily dose of 200 mg/kg and 230 mg/kg, respectively for 12 weeks, and the rats in the DM model group were given saline only. HE staining was used to examine the area of cardiac myocyte hypertrophy in each group. The expression levels of fibrotic proteins TGF-β1 and FN proteins in rat hearts were detected with Western blotting. In the cell experiment, the effect of 1 μmol/L FX on H9C2 cell hypertrophy induced by exposure to high glucose (HG, 45 mmol/L) was evaluated using FITC-labeled phalloidin. The mRNA expression levels of the hypertrophic factors ANP, BNP and β-MHC in H9C2 cells were detected using qRT-PCR. The protein expressions of Nrf2, Keap1, HO-1 and SOD1 proteins in rat heart tissues and H9C2 cells were determined using Western blotting. The DCFH-DA probe was used to detect the intracellular production of reactive oxygen species (ROS). Results In the diabetic rats, fucoxanthin treatment obviously alleviated cardiomyocyte hypertrophy and myocardial fibrosis, increased the protein expressions of Nrf2 and HO-1, and decreased the protein expressions of Keap1 in the heart tissue (P<0.05). In H9C2 cells with HG exposure, fucoxanthin significantly inhibited the enlargement of cell surface area, lowered the mRNA expression levels of ANP, BNP and β-MHC (P<0.05), promoted Nrf2 translocation from the cytoplasm to the nucleus, and up-regulated the protein expressions its downstream targets SOD1 and HO-1 (P<0.05) to enhance cellular antioxidant capacity and reduce intracellular ROS production. Conclusion Fucoxanthin possesses strong inhibitory activities against diabetic cardiomyocyte hypertrophy and myocardial fibrosis and is capable of up-regulating Nrf2 signaling to promote the expression of its downstream antioxidant proteins SOD1 and HO-1 to reduce the level of ROS. Related Articles | Metrics | Comments（0）

Select

Linagliptin improves diabetic kidney disease in rats by promoting mitochondrial biogenesis through the AMPK/PGC-1α/TFAM pathway WAN Lu, QIAN Yuchi, NI Wenjing, LU Yuxin, LI Wei, PAN Yan, CHEN Weidong Journal of Southern Medical University    2023, 43 (12): 2053-2060.   DOI: 10.12122/j.issn.1673-4254.2023.12.09 Abstract （467）   HTML （24）    PDF（pc） （5421KB）（2377）       Knowledge map    Save Objective To investigate whether linagliptin improves diabetic kidney disease (DKD) by promoting mitochondrial biosynthesis via activating adenosine monophosphate activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1α/mitochondrial transcription factor A (AMPK/PGC-1α/TFAM) pathway. Methods With 6 male SD rats feeding normal chow as the control group, 16 SD rat models of DKD induced by intraperitoneal injection of 45 mg/kg STZ and high-fat and high-glucose feeding for 4 weeks were randomized into DKD model group and linagliptin treatment group. The rats in the latter two groups were subjected to daily intragastric administration of vehicle or 5 mg/kg linagliptin (dissolved in 5 g/L sodium carboxymethylcellulose, final concentration of 2 mg/mL) for 12 weeks with further high-fat and high- glucose feeding. After the treatments, the rats were sacrificed and blood samples from the abdominal aorta and kidney tissues were collected for testing blood glucose, liver function and lipid metabolism; HE, PAS, Masson, Sirius red staining and electron microscopy were used to observe renal tissue damage. Renal expressions of transforming growth factor β1 (TGF-β1), fibronectin (FN) and collagen I (Col I) were detected by immunohistochemistry, and the changes in membrane potential (ΔψM) and ATP enzyme content were analyzed to assess mitochondrial damage; The expressions of AMPK/PGC-1α/TFAM pathway proteins were detected using Western blotting. Results Compared with DKD model rats, the rats receiving linagliptin treatment showed significantly decreased blood glucose level (P<0.01) and improved proteinuria (P<0.05) with obviously alleviated renal ultrastructural damage and fibrosis, increased ATPase content and ΔψM (P<0.0001), and enhanced renal expressions of P-AMPK/AMPK, PGC-1α and TFAM (P<0.05). Conclusions Linagliptin improves proteinuria and renal fibrosis in rat models of DKD possibly by activating the AMPK/PGC-1α/TFAM pathway to promote mitochondrial biosynthesis. Related Articles | Metrics | Comments（0）

Select

Hmga2 knockdown enhances osteogenic differentiation of adipose-derived mesenchymal stem cells and accelerates bone defect healing in mice Zhiyong KE, Zicheng HUANG, Ruolin HE, Qian ZHANG, Sixu CHEN, Zhong-Kai CUI, Jing DING Journal of Southern Medical University    2024, 44 (7): 1227-1235.   DOI: 10.12122/j.issn.1673-4254.2024.07.02 Abstract （356）   HTML （813）    PDF（pc） （5574KB）（2263）       Knowledge map    Save Objective To investigate the role of high-mobility group AT-hook 2 (HMGA2) in osteogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs) and the effect of Hmga2 knockdown for promoting bone defect repair. Methods Bioinformatics studies using the GEO database and Rstudio software identified HMGA2 as a key factor in adipogenic-osteogenic differentiation balance of ADSCs. The protein-protein interaction network of HMGA2 in osteogenic differentiation was mapped using String and visualized with Cytoscape to predict the downstream targets of HMGA2. Primary mouse ADSCs (mADSCs) were transfected with Hmga2 siRNA, and the changes in osteogenic differentiation of the cells were evaluated using alkaline phosphatase staining and Alizarin red S staining. The expressions of osteogenic markers Runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcein (OCN) in the transfected cells were detected using RT-qPCR and Western blotting. In a mouse model of critical-sized calvarial defects, mADSCs with Hmga2-knockdown were transplanted into the defect, and bone repair was evaluated 6 weeks later using micro-CT scanning and histological staining. Results GEO database analysis showed that HMGA2 expression was upregulated during adipogenic differentiation of ADSCs. Protein-protein interaction network analysis suggested that the potential HMGA2 targets in osteogenic differentiation of ADSCs included SMAD7, CDH1, CDH2, SNAI1, SMAD9, IGF2BP3, and ALDH1A1. In mADSCs, Hmga2 knockdown significantly upregulated the expressions of RUNX2, OPN, and OCN and increased cellular alkaline phosphatase activity and calcium deposition. In a critical-sized calvarial defect model, transplantation of mADSCswith Hmga2 knockdown significantly promoted new bone formation. Conclusion HMGA2 is a crucial regulator of osteogenic differentiation in ADSCs, and Hmga2 knockdown significantly promotes osteogenic differentiation of ADSCs and accelerates ADSCs-mediated bone defect repair in mice. Table and Figures | Reference | Related Articles | Metrics | Comments（0）

Select

Therapeutic mechanism of Guizhi Gancao Decoction for heart failure: a network pharmacology-based analysis ZHAO Yuxi, ZHAO Xu, ZHU Qingnan, ZHU Bingrui, ZHANG Zhenbin, CHEN Jing Journal of Southern Medical University    2023, 43 (5): 772-782.   DOI: 10.12122/j.issn.1673-4254.2023.05.13 Abstract （517）   HTML （24）    PDF（pc） （6144KB）（2205）       Knowledge map    Save Objective To predict the targets and pathways in the therapeutic mechanism of Guizhi Gancao Decoction (GZGCD) against heart failure (HF) based on network pharmacology. Methods The chemical components of GZGCD were analyzed using the databases including TCMSP, TCMID and TCM@Taiwan, and the potential targets of GZGCD were predicted using the SwissTargetPrediction database. The targets of HF were obtained using the databases including DisGeNET, Drugbank and TTD. The intersection targets of GZGCD and HF were identified using VENNY. Uniport database was used to convert the information, and the components- targets-disease network was constructed using Cytoscape software. The Bisogene plug-in, Merge plug-in, and CytoNCA plug-in in Cytoscape software were used for protein-protein interaction (PPI) analysis to acquire the core targets. Metascape database was used for GO and KEGG analysis. The results of network pharmacology analysis were verified with Western blot analysis. Three factors (PKCα, ERK1/2 and BCL2) were screened according to the degree value of network pharmacology results and the degree of correlation with heart failure process. The pentobarbtal sodium was dissolvein H9C2 cells treated with serum- free high glucose medium to simulate the ischemic anoxic environment of heart failure. The total proteins of myocardial cells were extracted. The protein contents of PKCα, ERK1/2 and BCL2 were determined. Results We identified a total of 190 intersection targets between GZGCD and HF using Venny database, involving mainly the circulatory system process, cellular response to nitrogen compounds, cation homeostasis, and regulation of the MAPK cascade. These potential targets were also involved in 38 pathways, including the regulatory pathways in cancer, calcium signal pathway, cGMP-PKG signal pathway, and cAMP signal pathway. Western blot analysis showed that in an in vitro H9C2 cell model of HF, treatment with GZGCD downregulated PKCα and ERK1/2 expressions and upregulated BCL2 expression. Conclusion The therapeutic mechanism of GZGCD for HF involves multiple targets including PRKCA, PRKCB, MAPK1, MAPK3, and MAPK8 and multiple pathways including the regulatory pathway in cancer and the calcium signaling pathway Related Articles | Metrics | Comments（0）

Select

Integrated analysis of serum untargeted metabolomics and targeted bile acid metabolomics for identification of diagnostic biomarkers for colorectal cancer WANG Xuancheng, ZHU Yifan, ZHOU Hailin, HUANG Zongsheng, CHEN Hongwei, ZHANG Jiahao, YANG Shanyi, CHEN Guanghui, ZHANG Qisong Journal of Southern Medical University    2023, 43 (3): 443-453.   DOI: 10.12122/j.issn.1673-4254.2023.03.15 Abstract （391）   HTML （44）    PDF（pc） （3247KB）（2085）       Knowledge map    Save Objective To identify potential diagnostic biomarkers of colorectal cancer (CRC) using serum metabolomic technology for minimally invasive and efficient screening for CRC. Methods Serum samples from 79 healthy individuals and 82 CRC patients were analyzed by metabolomics using ultra-high-performance liquid chromatography-tandem high-resolution mass spectrometry (UHPLC-HRMS). The differential metabolites between the two groups were analyzed using principal component analysis and orthogonal partial least squares discriminant analysis (OPLS- DA). Receiver operating characteristic curve (ROC) analysis was performed to identify the differential metabolites with good diagnostic performance (AUC>0.80) for CRC, and targeted bile acid metabolomics was used to verify the selected bile acids as biomarkers. Results Serum metabolic profiles differed significantly between the healthy individuals and CRC patients, and a total of 82 differential metabolites (mostly fatty acids and glycerophospholipids) were selected. ROC analysis identified 10 differential metabolites, including adenine, bilirubin, ACar 12:0, ACar 10:1, ACar 9:0, PC 18:2e, deoxycholic acid, chenodeoxycholic acid, ACar 14:1 and palmitoylcarnitine. One of these metabolites was significantly up-regulated and 9 were down-regulated in the serum of CRC patients (P<0.05). Multivariate ROC analysis with support vector machine algorithm showed that the biomarker panel consisting of 7 differential metabolites had an AUC of 0.94 for CRC diagnosis. The results of targeted bile acid metabolomics were consistent with those of untargeted metabolomics. The serum levels of deoxycholic acid and chenodeoxycholic acid were significantly down-regulated in patients with CRC as compared with the healthy individuals (P<0.05). Conclusion Metabolic disorders of fatty acids and glycerophospholipids are closely related wigh tumorigenesis of CRC. Ten differential metabolites show good performance for CRC diagnosis, and the panel consisting 7 of these metabolites has important diagnostic value for CRC. Deoxycholic acid and chenodeoxycholic acid may serve as potential diagnostic biomarkers of CRC. Related Articles | Metrics | Comments（0）

Select

Ultrasound-guided stellate ganglion block improves sleep quality in elderly patients early after thoracoscopic surgery for lung cancer: a randomized controlled study GU Cuifang, ZHAI Mingjian, LÜ Aijun, LIU Lu, HU Huan, LIU Xi, LI Xuan, CHENG Xiangyang Journal of Southern Medical University    2022, 42 (12): 1807-1814.   DOI: 10.12122/j.issn.1673-4254.2022.12.08 Abstract （489）   HTML （30）    PDF（pc） （1443KB）（1964）       Knowledge map    Save Objective To investigate the effects of ultrasound-guided stellate ganglion block (SGB) on sleep quality in elderly patients with lung cancer early after thoracoscopic surgery. Methods A total of 86 patients with lung cancer (ASA class I-III, aged 60-80 years) undergoing elective thoracoscopic surgery were randomized into stellate ganglion block (SGB) group (n=43) and control group (n=43) to receive ultrasound-guided right SGB with 7 mL of 0.5% ropivacaine at the C6-7 level and injection of 7 mL saline at the same site 30 min before anesthesia induction, respectively. On the day before surgery and the first two days after the surgery, sleep duration, sleep efficiency index (SEI) and N3 sleep stage of the patients were monitored using a BIS-Vista monitor, and Athens Insomnia Scale (AIS) scores were recorded. The plasma levels of norepinephrine and cortisol of the patients were measured before SGB (T1), at 5 min after extubation (T2) and at 6:00 on the first morning after the surgery (T4). Urine levels of 6-hydroxysulfate melatonin (6-HMS) were measured at 6:00 in the morning for 3 consecutive days starting on the day of surgery (T3, T4 and T5, respectively). VAS score, incidences of postoperative delirium and depression, sufentanil consumption after surgery, and discharge time of the patients were recorded. Results Thirty-six patients in SGB group and 35 in the control group were analyzed. In both groups, most of the patients had insomnia after surgery, but compared with those in the control group, the patients in SGB group had significantly longer sleep duration (P<0.05) with a higher sleep efficiency index (P<0.05) and a longer sleep time in N3 stage (P<0.05) on the first two nights after surgery. The mean postoperative AIS score and incidence of insomnia were significantly lower in SGB group than in the control group (P<0.05). Compared with the control group, SGB group showed significantly lower plasma levels of norepinephrine and cortisol at T2 and T4 (P<0.05), a higher urine level of 6-HMS at T5 (P<0.05), and a shorter discharge time after the surgery (P<0.05). The VAS scores, postoperative incidences of delirium and depression, or postoperative sufentanil consumption did not differ significantly between the two groups. Conclusion Ultrasound-guided SGB improves objective and subjective sleep quality in elderly patients early after thoracoscopic surgery for lung cancer to alleviate stress responses and sleep disorders, reduce postoperative hospital stay, and accelerate postoperative recovery of the patients. Related Articles | Metrics | Comments（0）

Select

FNDC1 is highly expressed in lung adenocarcinoma and closely related with poor prognosis HONG Haining, ZHU Haonan, LI Chao, ZANG Chao, SANG Haiwei, CHEN Liwei, WANG Ansheng Journal of Southern Medical University    2022, 42 (8): 1182-1190.   DOI: 10.12122/j.issn.1673-4254.2022.08.10 Abstract （1686）   HTML （58）    PDF（pc） （1853KB）（1766）       Knowledge map    Save Objective To explore the expression of fibronectin type III domain containing 1 (FNDC1) protein in lung adenocarcinoma and its prognostic significance. Methods The expression of FNDC1 in lung adenocarcinoma was predicted by analysis of data from GEO database and GEPIA, and the results were verified by immunohistochemical staining in 92 pairs of clinical specimens of lung adenocarcinoma and adjacent tissues. We further analyzed the correlation of FNDC1 expression with the clinicopathological features of the patients, and evaluated its prognostic value using Cox survival analysis. Results Analysis of the data form GEO database and GEPIA showed a significantly higher expression level of FNDC1 in lung adenocarcinoma than in matched normal tissues (P<0.05). Kaplan-Meier survival analysis suggested that a high expression of FNDC1 protein was associated with a significantly shorter overall survival time of the patients (P<0.05). Immunohistochemistry of the clinical specimens also showed a significantly higher protein expression of FNDC1 in lung adenocarcinoma tissues than in paired adjacent tissues (P<0.001). A high expression of FNDC1 protein was significantly correlated with advanced clinical stage, T stage and N stage (P<0.05). Cox univariate and multivariate regression survival analysis indicated that an increased expression of FNDC1 was an independent risk factor for poor prognosis of the patients with lung adenocarcinoma (P<0.05). Conclusion FNDC1 protein is highly expressed in patients with lung adenocarcinoma and in closely related with the occurrence, progression and prognosis of the tumor, suggesting the value of FNDC1 protein as a potential biomarker for assessment of the survival and prognosis of patients with lung adenocarcinoma. Related Articles | Metrics | Comments（0）

Select

Hsa-miR-148a-3p promotes malignant behavior of breast cancer cells by downregulating DUSP1 XU Jiaming, LIN Long, CHEN Qionghui, LI Lan Journal of Southern Medical University    2023, 43 (9): 1515-1524.   DOI: 10.12122/j.issn.1673-4254.2023.09.09 Abstract （199）   HTML （23）    PDF（pc） （5214KB）（1660）       Knowledge map    Save Objective To investigate the role of Hsa-miR-148a-3p in regulating biological behaviors of breast cancer cells and explore the mechanism. Methods TCGA database was used to identify the differential miRNAs and mRNAs in breast cancer, and the protein-protein interaction (PPI) network was constructed using String and Cytoscape to screen the top 10 hub genes and construct the miRNA-TOP10hub network. RT-qPCR was used to detect the expressions of Hsa-miR-148a-3p and DUSP1 in breast cancer tissues and cell lines. The effects of Hsa-miR-148a-3p mimic and inhibitor on proliferation, migration, invasion and apoptosis of MCF-7 cells were analyzed, and luciferase reporter gene experiment was performed to verify the binding of Hsa-miR-148a-3p to DUSP1. The effect of Hsa-miR-148a-3p overexpression on breast cancer cell xenograft growth was evaluated in nude mice. Kaplan-Meier survival curve analysis was used to analyze the survival of the tumor-bearing mice, and the expression level of DUSP1 in the xenografts was detected using immunohistochemistry. Results A total of 54 differential miRNAs and 799 differential mRNAs were identified in breast cancer; 3716 target genes were intersected with the differential mRNA, resulting in 150 intersected genes. The top 10 hub genes were downregulated in breast cancer tissues in the PPI network. Double luciferase reporter gene experiment confirmed that Hsa-miR-148a-3p was capable of binding to DUSP1. Hsa-miR-148a-3p was up-regulated and DUSP1 was down-regulated significantly in breast cancer tissues and cells (P<0.01). In breast cancer cells, Hsa-miR-148a- 3p mimic strongly promoted cell proliferation, migration and invasion and inhibited cell apoptosis (P<0.01). Hsa-miR-148a-3p overexpression obviously promoted xenograft growth in nude mice (P<0.01), shortened survival time of the mice (P<0.01), and reduced the expression of DUSP1 in the xenografts (P<0.01). Conclusion Hsa-miR-148a-3p promotes malignant behavior of breast cancer cells by inhibiting the expression of DUSP1. Related Articles | Metrics | Comments（0）

Select

Erchen Decoction improves iron homeostasis in mice with non-alcoholic fatty liver disease by regulating iron transport capacity in the spleen DENG Guanghui, JIA Hui, LI Yunjia, LI Junjie, WU Chaofeng, SHI Hao, QIN Mengchen, ZHAO Jiamin, LIU Chang, LIAO Yuxin, GAO Lei Journal of Southern Medical University    2023, 43 (8): 1287-1296.   DOI: 10.12122/j.issn.1673-4254.2023.08.04 Abstract （592）   HTML （23）    PDF（pc） （3455KB）（1603）       Knowledge map    Save Objective To investigate the effect of Erchen Decoction on iron homeostasis in mice with nonalcoholic fatty liver disease (NAFLD) and its mechanism for regulating iron transport in spleen cells. Methods Thirty male C57BL/6J mice were given a high-fat diet for 12 weeks and randomized (n=6) at the 7th week for gavage (3 times a week) of drinking water (NAFLD model group), Erchen Decoction at low, medium and high doses (7.5, 15, and 30g/kg, respectively), or polyene phosphatidyl choline (PPC; 9.12 mg/kg), with another 6 mice with low-fat and low-sugar feeding as the control group. The active components of Erchen Decoction were determined by HPLC-MS. Lipid accumulation in the liver was evaluated by HE staining and Nile red staining. Prussian blue staining was used to observe iron content in the spleen. The iron ion content in the liver tissue was detected using a detection kit. The expressions of ferroportin1 (Fpn1), transferrin receptor (TfR), Steap3, HO-1, Ter-119, CD163 and CD68 were detected using Western blotting, immunohistochemistry and immunofluorescence staining. Results Medium- and high-dose Erchen Decoction partially reversed the increase of lipid accumulation in the liver of NAFLD mice and showed better lipid-lowering effect than PPC. The NAFLD mice showed significantly decreased iron ion content in the spleen with increased hepatic and serum iron contents (P<0.05), decreased TfR protein expression (P<0.05), and increased Fpn1 and Steap3 protein expressions (P<0.05), and these changes were significantly improved by the drug interventions. Erchen Decoction also improved the function of CD163 macrophages in the spleen of NAFLD mice by up-regulating the expression of HO-1 (P<0.05). Conclusion Erchen Decoction can alleviate high- fat diet-induced iron metabolism disorder by improving the iron ion transport ability of the spleen cells to delay the progression of NAFLD. Related Articles | Metrics | Comments（0）

Select

Huangqi Sijunzi decoction for treating cancer-related fatigue in breast cancer patients: a randomized trial and network pharmacology study CUI Yixin, MI Jiwei, FENG Yu, LI Lingsheng, WANG Yujia, HU Jian, WANG Haiming Journal of Southern Medical University    2022, 42 (5): 649-657.   DOI: 10.12122/j.issn.1673-4254.2022.05.04 Abstract （1044）   HTML （30）    PDF（pc） （6179KB）（1592）       Knowledge map    Save Objective To evaluate the clinical efficacy of Huangqi Sijunzi decoction (HQSJZD) for treating cancer-related fatigue (CRF) of spleen and stomach Qi deficiency type after chemotherapy in patients with breast cancer. Methods A total of 94 breast cancer patients who developed CRF of spleen and stomach Qi deficiency type after chemotherapy were randomized into chemotherapy group (n=47) and traditional Chinese medicine (TCM) + chemotherapy group (n=47). The patients in chemotherapy group received the AC or EC regimen and non-drug interventions including psychological counseling, and those in TCM + chemotherapy group received oral administration of HQSJZD in addition to chemotherapy for 21 days as a treatment cycle, after which improvement of fatigue was assessed using Modified Piper Fatigue Scale. The active ingredients and targets of HQSJZD were screened using the TCM System Pharmacology Analysis Platform (TCMSP); the CRF- and breast cancer-related disease targets were retrieved based on data from the GeneCards, NCBI gene and OMIM databases to construct the component-target network and the protein-protein interaction (PPI) network. GO functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes KEGG pathway enrichment analysis of the target genes were performed to construct the component-disease-pathway- target biological network. The binding strength of the major drug ingredients and CRF key targets were predicted using AutoDock software. Results The scores for somatic fatigue, emotional fatigue and cognitive fatigue, along with the overall fatigue score, showed more significant improvements in TCM+chemotherapy group than in chemotherapy group (P<0.001), and the response rate reached 89.4% in the combined treatment group. We identified 250 targets for HQSJZD, 2653 CRF-related genes, 15 329 breast cancer-related genes and 161 prescription-disease intersected targets, from which topological analysis identified 66 potential key targets. GO and KEGG enrichment analyses predicted multiple pathways related with the disease. Molecular docking results suggested that the core ingredients of HQSJZD showed high affinities to the key targets AKT1, CASP3, IL6, JUN and VEGFA, among which AKT1 might be the most important target for HQSJZD to treat CRF. Conclusion HQSJZD can obviously improve CRF symptoms in breast cancer patients possibly by regulating multiple signaling pathways including PI3K-Akt through AKT1. Related Articles | Metrics | Comments（0）

Select

Berberine inhibits erastin-induced ferroptosis of mouse hippocampal neuronal cells possibly by activating the Nrf2-HO-1/GPX4 pathway HUANG Qingyang, JI Dongdong, TIAN Xiuyun, MA Linyan, SUN Xiaojin Journal of Southern Medical University    2022, 42 (6): 937-943.   DOI: 10.12122/j.issn.1673-4254.2022.06.19 Abstract （1575）   HTML （39）    PDF（pc） （1245KB）（1528）       Knowledge map    Save Objective To explore the mechanism by which berberine inhibits ferroptosis of mouse hippocampal neuronal cells (HT22). Methods Cultured HT22 cells were pretreated with 30 or 60 μmol/L berberine for 2 h before exposure to 0.5 μmol/L erastin for 8 h, and the cell proliferation, intracellular ferric iron level, changes in intracellular reactive oxygen species (ROS) and cell apoptosis were detected using CCK-8, Fe2 + fluorescent probe, fluorescent dye (DAPI) and fluorescent probe (H2DCFH-DA). RT-qPCR and Western blotting were used to detect the mRNA and protein expressions of Nrf2, HO-1 and GPX4 in the cells. We further tested the effects of treatments with 2 μmol/L ML385 (a Nrf2 inhibitor), 60 μmol/L berberine and erastin in the cells to explore the protective mechanism of berberine against erastin-induced ferroptosis in the neuronal cells. Results Treatment with 0.5 μmol/L erastin significantly lowered the viability of HT22 cells (P<0.05) and increased the production of ROS, cell apoptosis rate and ferric iron level (P<0.05). Pretreatment with 30 and 60 μmol/L berberine both significantly increased the vitality of erastin-exposed cells (P<0.05) and lowered the levels of intracellular ROS and ferric iron content (P<0.05). RT-qPCR and Western blotting showed that berberine obviously promoted the expressions of Nrf2, HO-1 and GPX4 in the cells (P<0.05), and treatment with ML385 significantly inhibited the Nrf2-HO-1/GPX4 pathway, increased intracellular ROS and ferric iron contents and mitigated the protective effect of berberine against erastin-induced ferroptosis (P<0.05). Conclusion Berberine can inhibit erastin-induced ferroptosis in HT22 cells possibly by activating the Nrf2-HO-1/GPX4 pathway. Related Articles | Metrics | Comments（0）

Select

Exploring the therapeutic mechanism of Liuwei Suanzao decoction for perimenopausal insomnia based on network pharmacology and animal experiments ZHANG Qian, ZHANG Meikui, LIU Yinglu, WANG Yan, LV Feifei, WANG Yuguo Journal of Southern Medical University    2023, 43 (9): 1536-1547.   DOI: 10.12122/j.issn.1673-4254.2023.09.11 Abstract （342）   HTML （38）    PDF（pc） （3884KB）（1526）       Knowledge map    Save Objective To explore the therapeutic mechanism of Liuwei Suanzao decoction (LWSZD) for perimenopausal insomnia (PI) based on network pharmacology. Methods TCMSP and Batman-TCM databases were searched for the active ingredients and targets of LWSZD and a herb- active ingredient-target network was constructed, and the disease targets were obtained from the OMIM, Genecards and Gene databases. The common targets were imported into STRING database and Cytoscape software to screen the core therapeutic targets, and GO enrichment and KEGG pathway analyses were performed using DAVID database. Molecular docking of the main active ingredients of LWSZD and the core targets was conducted using AutoDock, and the results were verified by observing the therapeutic effects of LWSZD and zolpidem in a rat model of PI induced by bilateral ovariectomy and intraperitoneal p-chlorophenylalanine injection. Results A total of 99 active ingredients, 389 drug targets, 187 PI-related targets, and 15 drug-PI common targets were screened. The core active ingredients were armepavine, sanjoinenine and mairin, and the core targets included ESR1, SIRT1, SERPINE1, COMT and CCL2, which were involved in the positive regulation of transcription from RNA polymerase II promoter, signal transduction, response to drug and positive regulation of transcription and in the pathways of dopaminergic synapses, tyrosine metabolism and tryptophan metabolism. Molecular docking results showed that LWSZD had a strong binding with ESR1, SIRT1 and SERPINE1 and was comparable to zolpidem. In the rat models of PI, treatment with LWSZD effectively alleviated the symptoms of insomnia (P<0.01), improved the levels of estrogen and other HPO axis-related hormones (P<0.05), and promoted the mRNA and protein expressions of ESR1 and SIRT1 in the hypothalamus tissues (P<0.01). Conclusion The active ingredients armepavine, sanjoinenine and mairin in LWSZD may synergistically regulate the expressions of ESR1, SIRT1 and SERPINE1 to improve PI in rats. Related Articles | Metrics | Comments（0）

Select

Advances in diagnosis and treatment of familial hypercholesterolemia ZHENG Hua, JIANG Sijie, LIN Lilong Journal of Southern Medical University    2023, 43 (1): 153-156.   DOI: 10.12122/j.issn.1673-4254.2023.01.22 Abstract （549）   HTML （77）    PDF（pc） （880KB）（1515）       Knowledge map    Save : Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease caused by abnormal lipoprotein metabolism. Patients with FH have a significantly increased risk of coronary artery disease (CAD) due to long-term exposure to high levels of low-density lipoprotein (LDL). The diagnosis of FH relies heavily on gene detection, and examination of LDL receptor (LDLR) function is of great significance in its treatment. This review summarizes the current advances in the screening, diagnosis, and treatment of FH and functional analysis of LDLR gene mutations. Related Articles | Metrics | Comments（0）

Select

Changes in percentage of GATA3+ regulatory T cells and their pathogenic roles in allergic rhinitis SUN Liu, JIAO Woer, KONG Yonggang, YANG Changliang, XU Shan, QIAO Yuelong, CHEN Shiming Journal of Southern Medical University    2023, 43 (2): 280-286.   DOI: 10.12122/j.issn.1673-4254.2023.02.17 Abstract （458）   HTML （22）    PDF（pc） （1903KB）（1474）       Knowledge map    Save Objective To investigate the changes in percentage of GATA3 + regulatory T (Treg) cells in patients with allergic rhinitis (AR) and mouse models. Methods The nasal mucosa specimens were obtained from 6 AR patients and 6 control patients for detection of nasal mucosal inflammation. Peripheral blood mononuclear cells (PBMC) were collected from 12 AP patients and 12 control patients to determine the percentages of Treg cells and GATA3+ Treg cells. In a C57BL/6 mouse model of AR, the AR symptom score, peripheral blood OVA-sIgE level, and nasal mucosal inflammation were assessed, and the spleen of mice was collected for detecting the percentages of Treg cells and GATA3+ Treg cells and the expressions of Th2 cytokines. Results Compared with the control patients, AR patients showed significantly increased eosinophil infiltration and goblet cell proliferation in the nasal mucosa (P<0.01) and decreased percentages of Treg cells and GATA3+ Treg cells (P<0.05). The mouse models of AR also had more obvious allergic symptoms, significantly increased OVA-sIgE level in peripheral blood, eosinophil infiltration and goblet cell hyperplasia (P<0.01), markedly lowered percentages of Treg cells and GATA3 + Treg cells in the spleen (P<0.01), and increased expressions of IL-4, IL-6 and IL-10 (P<0.05). Conclusion The percentage of GATA3+ Treg cells is decreased in AR patients and mouse models. GATA3 + Treg cells possibly participate in Th2 cell immune response, both of which are involved in the occurrence and progression of AR, suggesting the potential of GATA3 + Treg cells as a new therapeutic target for AR. Related Articles | Metrics | Comments（0）

Select

METTL3 inhibitor STM2457 improves metabolic dysfunction-associated fatty liver disease by regulating mitochondrial function in mice GAO Yinan, WANG Peijun, LU Sumei, MA Wanshan Journal of Southern Medical University    2023, 43 (10): 1689-1696.   DOI: 10.12122/j.issn.1673-4254.2023.10.06 Abstract （521）   HTML （23）    PDF（pc） （4948KB）（1442）       Knowledge map    Save Objective To investigate the effect of methyltransferase-like 3 (METTL3) inhibitor STM2457 in metabolic dysfunction-associated fatty liver disease (MAFLD). Methods C57BL/6J mouse models of MAFLD induced by high-fat diet feeding for 16 weeks were treated with intraperitoneal injections of STM2457 (50 mg/kg) for 2 weeks. The changes in m6A modification level in the liver tissue of the mice were determined with dot-blot hybridization, and the hepatic levels of triglyceride (TG), alanine aminotransferase (ALT) and glutathione aminotransferase (AST) were detected. The histological changes of the liver and changes in insulin resistance and metabolic profile of the mice were evaluated using HE staining, insulin tolerance tests and metabolic cages; transmission electron microscopy (TEM) was employed to examine the changes in mitochondrial morphology. In a HepG2 cell model of steatosis induced by treatment with sodium oleate/sodium palmitate for 48 h, the protective effect of STM2457 (1 μmol/L) on mitochondrial function was assessed by measuring mitochondrial membrane potential using a fluorescence probe (JC-1). Results The mouse models of MAFLD showed significant elevation of m6A modification level in the liver tissues and obviously upregulated mRNA expression of METT3 (P<0.05). Treatment with STM2457 significantly reduced body weight and liver lipid deposition and m6A modification levels, increased glucose tolerance and insulin sensitivity, lowered hepatic TG and serum ALT and AST levels, and increased respiratory entropy (RQ) in the mouse models (all P<0.05). HepG2 cells with steatosis exhibited obvious mitochondrial swelling with decreased mitochondrial membrane potential, but the STM2457-treated cells maintained a normal mitochondrial morphology with a higher membrane potential (P<0.05). Conclusion The METTL3 inhibitor STM2457 improves MAFLD by reducing high-fat diet-induced mitochondrial damage in mice. Related Articles | Metrics | Comments（0）

Select

Therapeutic mechanism of Shenbing Decoction III for renal fibrosis in chronic kidney disease: a study with network pharmacology, molecular docking and validation in rats LUO Guanfeng, LIU Huaxi, XIE Bei, DENG Yijian, XIE Penghui, ZHAO Xiaoshan, SUN Xiaomin Journal of Southern Medical University    2023, 43 (6): 924-934.   DOI: 10.12122/j.issn.1673-4254.2023.06.07 Abstract （1291）   HTML （18）    PDF（pc） （4146KB）（1441）       Knowledge map    Save Objective To observe the effect of Shenbing Decoction III for improving renal function and pathology in rats with 5/6 nephrectomy and analyze its therapeutic mechanism for renal fibrosis in chronic kidney disease using network pharmacology combined with molecular docking. Methods Forty male SD rats were randomized into two groups to receive two-staged 5/6 nephrectomy (n=30) or sham operation (n=10), and 2 weeks after the final operation, serum creatinine level of the rats was measured. The rats with nephrectomy were further randomized into Shenbing Decoction III group, losartan group and model group for daily treatment with the corresponding drugs via gavage starting at 1 week after 5/6 nephrectomy. After 16 weeks of treatment, serum creatinine and urea nitrogen levels of the rats were measured, and HE staining and Western blotting were used to examine the changes in renal pathology and fibrosis-related factors. Network pharmacology combined with molecular docking study was performed to explore the therapeutic mechanism Shenbing Decoction III against renal fibrosis in chronic kidney disease, and Western blotting was used to verify the expressions of the core targets. Results Compared with those in the model group, the rats receiving 5/6 nephrectomy and Shenbing Decoction III treatment showed significantly reduced serum creatinine and urea nitrogen levels, lessened renal pathologies, and improvement of the changes in epithelial mesenchymal transition-related proteins. Network pharmacological analysis showed that the main active ingredients of Shenbing Decoction III were acacetin, apigenin, eupatilin, quercetin, kaempferol and luteolin, and the key targets included STAT3, SRC, CTNNB1, PIK3R1 and AKT1. Molecular docking study revealed that the active ingredients of Shenbing Decoction III had good binding activity to the key targets. Western blotting showed that in rats with 5/6 nephrectomy, treatment with Shenbing Decoction III obviously restored the protein expression of STAT3, PI3K, and AKT in renal tissue. Conclusion Shenbing Decoction III can reduce renal injury induced by 5/6 nephrectomy in rats, and its therapeutic effects are mediated possibly by its main pharmacologically active ingredients that alleviate renal fibrosis via modulating multiple targets including STAT3, PIK3R1, and AKT1. Related Articles | Metrics | Comments（0）

Select

Indirubin relieves inflammatory injury of chondrocytes in a mouse model of osteoarthritis CHEN Xin, QI Xiuchun, CAO Yujing, LI Yang, LI Haoliang, WANG Qianjin, AI Jinwei Journal of Southern Medical University    2022, 42 (9): 1381-1388.   DOI: 10.12122/j.issn.1673-4254.2022.09.15 Abstract （1073）   HTML （40）    PDF（pc） （1826KB）（1429）       Knowledge map    Save Objective To investigate the effect of indirubin for relieving joint inflammation and injury in a rat model of osteoarthritis. Methods Articular cartilage chondrocytes were isolated from adult rat knee joint and cultured in the presence of interleukin-1β (IL-1β) and 0.1, 0.5, 1.0, or 2.0 μmol/L indirubin. The cells were transfected with NPAS2 siRNA or a non-specific siRNA, and the cell proliferation and apoptosis were evaluated using tetramethylthiazole blue staining and flow cytometry. The protein expression levels of Bax, Bcl-2, ACAN, COL2A1, MMP-13 and NPAS2 were detected with Western blotting, and the levels of NO, PGE2 and TNF-α in the culture supernatant were determined with ELISA. The mRNA expression levels of NPAS2, ACAN, COL2A1 and MMP-13 were detected using fluorescence quantitative PCR. In a C57BL/6 mouse model of osteoarthritis, the effect of indirubin on BAX, Bcl-2, ACAN and MMP-13 protein expressions in the bone and joint tissues were evaluated with Western blotting. Results Treatment with 0.1 μmol/L indirubin produced no significant changes in chondrocyte proliferation, apoptosis, caspase-3 activity, or BAX and Bcl-2 protein expressions. At higher doses (0.5, 1.0 and 2.0 μmol/L), indirubin significantly promoted cell proliferation, increased Bcl- 2 protein expression, and lowered cell apoptosis rate, caspase-3 activity and Bax protein expression (P<0.05). Indirubin treatment at 0.5 μmol/L up-regulated the protein and mRNA expressions of NPAS2, ACAN and COL2A1, and down-regulated the expressions of MMP-13, NO, PGE2 and TNF-α (P<0.05). Interference of NPAS2 expression significantly attenuated the protective effect of 0.5 μmol/L indirubin against IL-1β-induced chondrocyte injury. The mouse model of osteoarthritis showed obviously increased protein levels of BAX and MMP-13 (P< 0.01) and decreased levels of Bcl-2 (P<0.05) and ACAN (P<0.01) in the knee joint, and indirubin treatment of the mouse models significantly inhibited the increase of BAX and MMP-13 protein expressions (P<0.01) and up-regulated the protein expressions of Bcl-2 and ACAN (P<0.05). Conclusion Indirubin has a protective effect on osteoarthritis tissue and alleviates inflammation and damage of osteoarthritis chondrocytes possibly through NPAS2. Related Articles | Metrics | Comments（0）

Select

Cold stress reduces lifespan and mobility of C. elegans by mediating lipid metabolism disorder and abnormal stress response SHI Hao, ZHANG Chao, ZHAO Jiamin, LI Yiwen, LI Yunjia, LI Junjie, ZENG Zhiyun, GAO Lei Journal of Southern Medical University    2022, 42 (8): 1159-1165.   DOI: 10.12122/j.issn.1673-4254.2022.08.07 Abstract （2099）   HTML （54）    PDF（pc） （1178KB）（1426）       Knowledge map    Save Objective To investigate the changes of lipid metabolism and stress response of adult C. elegans exposed to non-freezing low temperature and explore the possible mechanism. Methods The survival rate and activity of adult C. elegans cultured at 20 ℃ or 4 ℃ were observed. Lipid metabolism of the cultured adult C. elegans was evaluated using oil red O staining and by detecting the expressions of the genes related with lipid metabolism. The effects of low temperature exposure on stress level of adult C. elegans were evaluated using mitochondrial fluorescence staining and by detecting the expression levels of stress-related genes and antioxidant genes at both the mRNA and protein levels. Results The lifespan and activity of adult C. elegans exposed to low temperature were significantly reduced with decreased lipid accumulation (P<0.05) and decreased expressions of genes related with fatty acid synthesis and metabolism (fat-5, fat-6, fat-7, fasn-1, nhr-49, acs-2 and aco-1; P<0.01). Cold stress significantly increased the expressions of heat shock proteins hsp-70 and hsp16.2 (P<0.05) but lowered the number of mitochondria (P<0.0001) and the expressions of atfs-1, sod-2, sod-3 and gpx-1 (P<0.05). Knockout of fat-5, nhr-49 or both fat-5 and fat-6 obviously enhanced the sensitivity of C. elegans to cold stress as shown by further reduced activity (P<0.05) and reduced survival rate at 24 h (P<0.0001) under cold stress. Conclusion Exposure to a low temperature at 4 ℃ results in lowered lipid metabolism of adult C. elegans accompanied by a decreased mitochondrial number and quality control ability, which triggers high expressions of stress-related genes and causes reduction of antioxidant capacity, thus callsing lowered activity and reduced lifespan of C. elegans. Related Articles | Metrics | Comments（0）

Select

Nur77 promotes invasion and migration of gastric cancer cells through the NF-κB/IL-6 pathway LI Wei, SHI Yongkang, GUO Yuhua, TIAN Shengwang Journal of Southern Medical University    2022, 42 (9): 1410-1417.   DOI: 10.12122/j.issn.1673-4254.2022.09.19 Abstract （1178）   HTML （41）    PDF（pc） （2517KB）（1417）       Knowledge map    Save Objective To analyze the association of Nur77 with overall survival of gastric cancer patients and investigate the role of Nur77 in invasion and migration of gastric cancer cells. Methods Oncomine database was used to analyze the expression of Nur77 in gastric cancer and gastric mucosa tissues, and the distribution characteristics of Nur77 protein between gastric cancer and normal tissues were compared using Human Protein Atlas. GEPIA2 was used to analyze the relationship of Nur77 expression and the patients' survival. The expression of Nur77 in gastric cancer cell lines GES-1, AGS and MKN-45 were detected by Western blotting. The regulatory interactions between IL-6 and Nur77 were verified by transfecting the cells with specific Nur-77 siRNA and Nur-77-overexpressing plasmid. The changes in migration ability of the cells following Nur-77 knockdown were assessed with scratch assay. The effect of Nur-77 overexpression or IL-6 knockdown, or their combination, on migration and invasion of the gastric cancer cells were examined using Transwell assay. The effect of Nur77 expression level on NF-κB/IL-6 pathway activation was analyzed using Western blotting. Results Oncomine database showed that gastric cancer tissues expressed a significantly higher level of Nur77 mRNA than normal tissues (P<0.05). Nur77 expression was detected mostly in the nucleus, and a high Nur77 expression was associated with a poor survival outcome of the patients (P<0.05). In gastric cancer cells, the high expression of Nur77 participated in the regulation of IL-6. Nur77 silencing significantly lowered the migration ability of the cells (P<0.05), and IL-6 silencing significantly attenuated the enhanced migration caused by Nur77 overexpression (P<0.05). Nur77 participates in the activation of NF-κB/IL-6 signaling pathway by regulating the expression of p-p65, p65, p- Stat3 and Stat3. Conclusion A high Nur77 expression is strongly correlated with a poor prognosis of gastric cancer patients. Nur77 promotes the invasion and migration of gastric cancer cells possibly by regulating the NF-κB/IL-6 signaling pathway. Related Articles | Metrics | Comments（0）