1.Effects and mechanism of knocking down lncRNA H19 to inhibit lipid accumulation in human THP-1 cells-derived macrophages.
Xuemei WANG ; Yue CHE ; Jieying WANG ; Ke MEN
Chinese Journal of Cellular and Molecular Immunology 2023;39(10):884-890
Objective To investigate the effects of long noncoding RNA H19 on lipid accumulation of macrophages under high fat stress and its mechanism. Methods Human THP-1 cells-derived macrophages were incubated with ox-LDL, and the effects of H19 siRNA intervention on lipid accumulation was observed. The THP-1 cells were divided into control group (conventional culture), ox-LDL group, siRNA negative control (NC siRNA) combined with ox-LDL treatment group, and H19 siRNA combined with ox-LDL treatment group. Oil red O staining was used to determine the lipid accumulation in cells, and cholesterol concentration was analyzed by enzymatic method; ATP assay kit for detecting celluar ATP content; colorimetry was used to detect the levels of oxidative stress indicators and ELISA was used to detect the levels of monocyte chemoattractant protein-1 (MCP-1) in the cell supernatant. Western blot analysis was used to detect the protein expression of ATP binding cassette transporter A1 (ABCA1), peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and nuclear factor κB p-p65 (NF-κB p-p65). Results Knockdown H19 significantly inhibited intracellular lipid accumulation, decreased total cholesterol (TC) and cholesterol ester (CE) content, and decreased CE/TC ratio. Knockdown H19 significantly alleviated cell damage including an increase in ATP content, a decrease in oxidative stress levels and a decrease in MCP-1 levels, which caused by high-fat stress. H19 siRNA upregulated expression of ABCA1, PPARα and PGC-1α in THP-1 derived macrophages, downregulated NF-κB signal pathway. Conclusion Knockdown H19 upregulates PGC-1α expression in THP-1 cells and downregulates NF-κB pathway, which promotes cholesterol reverse transport, reduces inflammatory reaction and inhibits lipid accumulation.
Humans
;
Adenosine Triphosphate
;
Cholesterol
;
NF-kappa B
;
PPAR alpha
;
RNA, Long Noncoding/genetics*
;
RNA, Small Interfering/genetics*
;
THP-1 Cells
;
Macrophages/metabolism*
;
Lipid Metabolism
2.CiteSpace-based visualization analysis of domestic and foreign researches on post-traumatic stress disorder in recent five years
Zhong HUANG ; Jun HU ; Ke HUANG ; Peng CHE
Sichuan Mental Health 2023;36(1):39-47
ObjectiveTo understand the research status of post-traumatic stress disorder (PTSD) at home and abroad in recent five years, and to grasp the research frontiers and hot spots in this field. MethodsTwo electronic databases, Web of Science and China National Knowledge Infrastructure (CNKI), were retrieved for the literature published from January 1, 2017 to December 31, 2021. A total of 8 505 literatures were included, then the visualization analysis of the number of publications, authors, countries, institutions and keywords was conducted based on Microsoft Excel and CiteSpace software. Results① The number of publications in domestic and foreign showed an increasing trend in recent five years. ② In foreign literature, the top five countries in terms of the number of publications were the United States, the United Kingdom, China, Australia and Canada, with Canada having the highest centrality (0.18). ③ Both domestic and foreign research institutions were dominated by universities. ④ In terms of the number of articles published, the top three foreign scholars were Bryant RA, Ressler KJ and Greenberg N, and the top three Chinese scholars were Wu Xinchun, Li Yuefeng, Yan Xingke and Zhang Guiqing (tied for the third place). Compared with foreign authors, the number of articles published by Chinese scholars was relatively small. ⑤ In terms of research keywords, PTSD and depression were of more concern in both domestic and foreign. ConclusionIn recent five years, PTSD has been a hot topic at home and abroad, with both domestic and international studies focusing on PTSD and depression, and strengthening international exchanges may help promote progress in the field of PTSD research.
3.Glutathione S-transferase genetic polymorphisms and fluoride-induced reproductive toxicity in men with idiopathic infertility.
Jun HE ; Yi MU ; Miao LIU ; Bang-Wei CHE ; Wen-Jun ZHANG ; Ke-Hang CHEN ; Kai-Fa TANG
Asian Journal of Andrology 2023;25(3):404-409
Male infertility caused by idiopathic oligoasthenospermia (OAT) is known as idiopathic male infertility. Glutathione S-transferase (GST) and fluoride may play important roles in idiopathic male infertility, but their effects are still unknown. Our study examined the relationship between GST polymorphisms and fluoride-induced toxicity in idiopathic male infertility and determined the underlying mechanism. Sperm, blood, and urine samples were collected from 560 males. Fluoride levels were measured by a highly selective electrode method, and GST genotypes were identified using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Semen parameters, DNA fragmentation index (DFI), mitochondrial membrane potential (MMP), and oxidative stress (OS) biomarkers were statistically assessed at the P < 0.05 level. Compared with healthy fertile group, semen parameters, fluoride levels, OS biomarkers, sex hormone levels, and MMP and DFI levels were lower in the idiopathic male infertility group. For glutathione S-transferase M1 (GSTM1[-]) and glutathione S-transferase T1 (GSTT1[-]) or glutathione S-transferase P1 (GSTP1) mutant genotypes, levels of semen fluoride, OS, MMP, and DFI were considerably higher, and the mean levels of sperm parameters and testosterone were statistically significant in GSTM1(+), GSTT1(+), and GSTP1 wild-type genotypes. Both semen and blood fluoride levels were associated with oxidative stress in idiopathic male infertility patients. Elevated fluoride in semen with the genotypes listed above was linked to reproductive quality in idiopathic male infertility patients. In conclusion, GST polymorphisms and fluorine may have an indicative relationship between reproductive quality and sex hormone levels, and OS participates in the development of idiopathic male infertility.
Humans
;
Male
;
Fluorides/adverse effects*
;
Semen
;
Polymorphism, Genetic
;
Glutathione Transferase/genetics*
;
Glutathione S-Transferase pi/genetics*
;
Infertility, Male/genetics*
;
Genotype
;
Biomarkers
;
Genetic Predisposition to Disease
;
Case-Control Studies
4.Hepatic COX1 loss leads to impaired autophagic flux and exacerbates nonalcoholic steatohepatitis.
Qian YU ; Chang LI ; Qinghui NIU ; Jigang WANG ; Zhaodi CHE ; Ke LEI ; He REN ; Boyi MA ; Yixing REN ; Pingping LUO ; Zhuming FAN ; Huan ZHANG ; Zhaohui LIU ; George L TIPOE ; Jia XIAO
Acta Pharmaceutica Sinica B 2023;13(6):2628-2644
The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.
5.Influence of visceral lipids obesity on the early postoperative complications after radical gastrectomy.
Guang Lin QIU ; Xiao Wen LI ; Hai Jiang WANG ; Pan Xing WANG ; Jia Huang LIU ; Meng Ke ZHU ; Xin Hua LIAO ; Lin FAN ; Xiang Ming CHE
Chinese Journal of Gastrointestinal Surgery 2022;25(7):596-603
Objective: To investigate the effect of visceral fat area (VFA) on the surgical efficacy and early postoperative complications of radical gastrectomy for gastric cancer. Methods: A retrospective cohort study method was used. Clinicopathological data and preoperative imaging data of 195 patients who underwent D2 radical gastric cancer surgery at the First Affiliated Hospital of Xi'an Jiaotong University from January 2014 to December 2017 were analyzed retrospectively. Inclusion criteria: (1) complete clinicopathological and imaging data; (2) malignant gastric tumor diagnosed by preoperative pathology, and gastric cancer confirmed by postoperative pathology; (3) no preoperative complications such as bleeding, obstruction or perforation, and no distant metastasis. Those who had a history of abdominal surgery, concurrent malignant tumors, poor basic conditions, emergency surgery, palliative resection, and preoperative neoadjuvant therapy were excluded. The VFA was calculated by software and VFA ≥ 100 cm2 was defined as visceral obesity according to the Japan Obesity Association criteria . The patients were divided into high VFA (VFA-H, VFA≥100 cm2, n=96) group and low VFA (VFA-L, VFA<100 cm2, n=99) group . The clinicopathological characteristics, surgical outcomes and early postoperative complications were compared between the two groups. Univariate and multivariate Logistic regression models were used to analyze the risk factors of early complications. Receiver operating characteristic (ROC) curve was used to analyze predictive values of VFA for early complications. Pearson's χ2 test was used to analyze the correlation between BMI and VFA. Results: There were no significant differences in terms of gender, age, American Society of Anesthesiologists physical status classification, preoperative comorbidities, preoperative anemia, tumor TNM staging, N staging, T staging and tumor differentiation, surgical method, extent of resection, and tumor location between the VFA-L group and the VFA-H group (all P>0.05). However, patients in the VFA-H group had higher BMI, larger tumor, lower rate of hypoalbuminemia and greater subcutaneous fat area (SFA) (all P<0.05). The VFA-H group presented significantly longer operation time and significantly less number of harvested lymph nodes as compared to the VFA-L group (both P<0.05). However, there were no significant differences in intraoperative blood loss, conversion to laparotomy and postoperative hospital stay (all P>0.05). Complications of Clavien-Dindo grade II and above within 30 days after operation were mainly anastomosis-related complications (leakage, bleeding, infection and stricture), intestinal obstruction and incision infection. The VFA-H group had a higher morbidity of early complications compared to the VFA-L group [24.0% (23/96) vs 10.1% (10/99), χ2=6.657, P=0.010], and the rates of anastomotic complications and incision infection were also higher in the VFA group [10.4% (10/96) vs. 3.0% (3/99), χ2=4.274, P=0.039; 7.3% (7/96) vs. 1.0% (1/99), P=0.033]. Multivariate logistic analysis showed that high BMI (OR=3.688, 95%CI: 1.685-8.072, P=0.001) and high VFA (OR=2.526, 95%CI: 1.148-5.559,P=0.021) were independent risk factors for early complications. The area under the ROC curve (AUC) of VFA for predicting early complications was 0.645, which was higher than that of body weight (0.591), BMI (0.624) and SFA (0.626). Correlation analysis indicated that there was a significantly positive correlation between BMI and VFA (r=0.640, P<0.001). Conclusion: VFA ≥ 100 cm2 is an independent risk factor for early complications after radical gastrectomy for gastric cancer.It can better predict the occurrence of above early postoperative complications.
Gastrectomy/methods*
;
Humans
;
Laparoscopy/methods*
;
Lipids
;
Obesity/surgery*
;
Obesity, Abdominal/surgery*
;
Postoperative Complications/epidemiology*
;
Retrospective Studies
;
Stomach Neoplasms/pathology*
6.Kang-Ai Injection Inhibits Gastric Cancer Cells Proliferation through IL-6/STAT3 Pathway.
Chun-Lei ZHENG ; Ke-Zuo HOU ; An-Qi WANG ; Wan-Xia FANG ; Shi-Tong YU ; Jin-E LIANG ; Hai-Yan QI ; Xiu-Juan QU ; Yun-Peng LIU ; Xiao-Fang CHE
Chinese journal of integrative medicine 2022;28(6):524-530
OBJECTIVE:
To explore the mechanisms underlying the proliferative inhibition of Chinese herbal medicine Kang-Ai injection (KAI) in gastric cancer cells.
METHODS:
Gastric cancer cell lines MGC803 and BGC823 were treated by 0, 0.3%, 1%, 3% and 10% KAI for 24, 48 and 72 h, respectively. The cell proliferation was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The apoptosis and cell cycle were evaluated by flow cytometry. Interleukin (IL)-6 mRNA and protein expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immune sorbent assay (ELISA), respectively. The protein expression levels of cyclin A, cyclin E, cyclin B1, cyclin D1, p21, retinoblastoma (RB), protein kinase B (AKT), extracellular regulated protein kinases (ERK), signal transducer and activator of transcription (STAT) 1 and STAT3 were detected by Western blot.
RESULTS:
KAI inhibited the proliferation of MGC803 and BGC823 gastric cancer cells in dose- and time-dependent manner. After treated with KAI for 48 h, the proportion of G1 phase was increased, expression level of cyclin D1 and phosphorylation-RB were down-regulated, whereas the expression of p21 was up-regulated (all P<0.01). Furthermore, 48-h treatment with KAI decreased the phosphorylation level of STAT3, inhibited the mRNA and protein expressions of IL-6 (all P<0.01). IL-6 at dose of 10 ng/mL significantly attenuated the proliferative effect of both 3% and 10% KAI, and recovered KAI-inhibited STAT3 phosphorylation and cyclin D1 expression level (all P<0.01).
CONCLUSION
KAI exerted an anti-proliferative function by inhibiting IL-6/STAT3 signaling pathway followed by the induction of G1 phase arrest in gastric cancer cells.
Apoptosis
;
Cell Line, Tumor
;
Cell Proliferation
;
Cyclin D1/pharmacology*
;
Humans
;
Interleukin-6/metabolism*
;
RNA, Messenger/metabolism*
;
STAT3 Transcription Factor/metabolism*
;
Stomach Neoplasms/genetics*
7.Efficacy of laparoscopic proximal gastrectomy with double-tract reconstruction versus laparoscopic total gastrectomy with Roux-en-Y reconstruction for early upper gastric cancer.
Guang Lin QIU ; Chao WEI ; Meng Ke ZHU ; Shao Ning HAN ; Xiao Wen LI ; Hai Jiang WANG ; Pan Xing WANG ; Jia Huang LIU ; Hua You ZHOU ; Xin Hua LIAO ; Xiang Ming CHE ; Lin FAN
Chinese Journal of Gastrointestinal Surgery 2022;25(5):412-420
Objective: To compare clinical efficacy between laparoscopic radical proximal gastrectomy with double-tract reconstruction (LPG-DTR) and laparoscopic radical total gastrectomy with Roux-en-Y reconstruction (LTG-RY) in patients with early upper gastric cancer, and to provide a reference for the selection of surgical methods in early upper gastric cancer. Methods: A retrospective cohort study method was carried out. Clinical data of 80 patients with early upper gastric cancer who underwent LPG-DTR or LTG-RY by the same surgical team at the Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2021 were retrospectively analyzed. Patients were divided into the DTR group (32 cases) and R-Y group (48 cases) according to surgical procedures and digestive tract reconstruction methods. Surgical and pathological characteristics, postoperative complications (short-term complications within 30 days after surgery and long-term complications after postoperative 30 days), survival time and nutritinal status were compared between the two groups. For nutritional status, reduction rate was used to represent the changes in total protein, albumin, total cholesterol, body mass, hemoglobin and vitamin B12 levels at postoperative 1-year and 2-year. Non-normally distributed continuous data were presented as median (interquartile range), and the Mann-Whitney U test was used for comparison between groups. The χ(2) test or Fisher's exact test was used for comparison of data between groups. The Mann-Whitney U test was used to compare the ranked data between groups. The survival rate was calculated by Kaplan-Meier method categorical, and compared by using the log-rank test. Results: There were no statistically significant differences in baseline data betweeen the two groups, except that patients in the R-Y group were oldere and had larger tumor. Patients of both groups successfully completed the operation without conversion to laparotomy, combined organ resection, or perioperative death. There were no significant differences in the distance from proximal resection margin to superior margin of tumor, postoperative hospital stay, time to flatus and food-taking, hospitalization cost, short- and long-term complications between the two groups (all P>0.05). Compared with the R-Y group, the DTR group had shorter distal margins [(3.2±0.5) cm vs. (11.7±2.0) cm, t=-23.033, P<0.001], longer surgery time [232.5 (63.7) minutes vs. 185.0 (63.0) minutes, Z=-3.238, P=0.001], longer anastomosis time [62.5 (17.5) minutes vs. 40.0 (10.0) minutes, Z=-6.321, P<0.001], less intraoperative blood loss [(138.1±51.6) ml vs. (184.3±62.1) ml, t=-3.477, P=0.001], with significant differences (all P<0.05). The median follow-up of the whole group was 18 months, and the 2-year cancer-specific survival rate was 97.5%, with 100% in the DTR group and 95.8% in the R-Y group (P=0.373). Compared with R-Y group at postoperative 1 year, the reduction rate of weight, hemoglobin and vitamin B12 were lower in DTR group with significant differences (all P<0.05); at postoperative 2-year, the reduction rate of vitamin B12 was still lower with significant differences (P<0.001), but the reduction rates of total protein, albumin, total cholesterol, body weight and hemoglobin were similar between the two groups (all P>0.05). Conclusions: LPG-DTR is safe and feasible in the treatment of early upper gastric cancer. The short-term postoperative nutritional status and long-term vitamin B12 levels of patients undergoing LPG-DTR are superior to those undergoing LTG-RY.
Albumins
;
Anastomosis, Roux-en-Y/adverse effects*
;
Cholesterol
;
Gastrectomy/methods*
;
Hemoglobins
;
Humans
;
Laparoscopy/methods*
;
Postoperative Complications/etiology*
;
Retrospective Studies
;
Stomach Neoplasms/pathology*
;
Treatment Outcome
;
Vitamin B 12
8.Methodological quality assessment of systematic reviews or Meta-analyses of intervention randomized controlled trials published in the Sichuan Mental Health
Peng CHE ; Jun HU ; Xueli TANG ; Ke HUANG ; Linguo LI ; Chunyan YIN
Sichuan Mental Health 2022;35(2):188-193
ObjectiveTo evaluate the methodological quality of systematic review / Meta analysis (SR/MA) of intervention randomized controlled trial (RCT) published in the Sichuan Mental Health. MethodsThe literature databases such as Wanfang Data, China National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodical (VIP) and Chinese Biomedical Literature Database (CBM) were searched for the SRs/MAs of intervention RCTs published in the Sichuan Mental Health from the initial issue to the issue published on 31 June 2021. Then the methodological quality of eligible SRs/MAs were assessed using A Measurement Tool to Assess systematic Reviews 2 (AMSTAR 2). ResultsThe literature search yielded 24 full-text articles, and the mean AMSTAR 2 score of the included SRs/MAs was (5.21±3.63) with a range from 1 to 11. The total AMSTAR 2 score for SRs/MAs showed difference in terms of the publication date prior to or later than the publication of AMSTAR-2 tool (t=-5.499), number of authors ≤ 2 or ≥ 3 (t=-6.736), with or without funding support (t=3.329) and author unit nature (F=7.827), with statistical significance (P<0.01). All selected studies had deficiencies on explicit statement of a priori design and registrations, list of excluded studies and reasons for exclusion, sources of funding for the research in systematic review, potential conflicts of interest statement, and funding information of the systematic review. ConclusionThe methodological quality of SRs/MAs of intervention RCTs published in the Sichuan Mental Health varies widely, After the release of AMSTAR 2, the methodological quality has improved, but the report still needs to be further standardized to provide high-quality evidence-based evidence.
10.Expression of cyclophilin A in oral squamous cell carcinoma and its effect on cell proliferation and invasion.
Xiao-Yang XIA ; Fei FANG ; Yan LIU ; Chao CHE ; Jin-Juan KE ; Sheng-Jun JIANG
West China Journal of Stomatology 2021;39(2):164-169
OBJECTIVES:
To investigate the expression of cyclophilin A (CyPA) in oral squamous cell carcinoma (OSCC) and explore the effect of downregulating the expression of CyPA gene on the proliferation and invasion of SCC-25 cells.
METHODS:
A total of 77 cases of patients with OSCC were selected. The expression levels of CyPA proteins in OSCC and adjacent normal tissues were evaluated. SCC-25 cells were cultured and divided into the CyPA interference sequence group, negative control group, and blank group. The expression levels of CyPA mRNA and protein in cells were detected by using real-time fluorescent quantitative polymerase chain reaction and Western blot, respectively. Cell proliferation was detected by using methyl thiazolyl tetrazolium and plate colony formation assays. Cell invasion was detected by using Transwell assay.
RESULTS:
The positive expression rate of CyPA protein in OSCC tissues was 76.62%, which was higher than that in adjacent tissues (
CONCLUSIONS
The CyPA protein is highly expressed in OSCC tissues, and the downregulation of CyPA gene expression in SCC-25 cells can reduce cell proliferation and inhibit cell invasion.
Carcinoma, Squamous Cell/genetics*
;
Cell Line, Tumor
;
Cell Movement
;
Cell Proliferation
;
Cyclophilin A/genetics*
;
Gene Expression Regulation, Neoplastic
;
Head and Neck Neoplasms
;
Humans
;
Mouth Neoplasms/genetics*
;
Squamous Cell Carcinoma of Head and Neck

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