1.Akkermansia muciniphila-derived acetate activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis in metabolic-associated fatty liver disease.
Aoxiang ZHUGE ; Shengjie LI ; Shengyi HAN ; Yin YUAN ; Jian SHEN ; Wenrui WU ; Kaicen WANG ; Jiafeng XIA ; Qiangqiang WANG ; Yifeng GU ; Enguo CHEN ; Lanjuan LI
Acta Pharmaceutica Sinica B 2025;15(1):151-167
Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.
2.Automatic segmentation technique combined with neurite orientation dispersion and density imaging for observing volume and microstructure changes of hippocampal subregion in patients with hippocampal sclerosis medial temporal lobe epilepsy
Wenrui YANG ; Xucong WANG ; Jian LI ; Mengnan YAN ; Jinqin LI ; Yanling ZHANG ; Bing CHEN
Chinese Journal of Medical Imaging Technology 2024;40(6):838-842
Objective To explore the value of automatic segmentation technique combined with neurite dispersion and density imaging(NODDI)for displaying volume and microstructure changes of hippocampal subregion in patients with hippocampal sclerosis medial temporal lobe epilepsy(mTLE-HS).Methods MRI data of 33 patients with left mTLE-HS(mTLE-HS group)and 35 healthy adults(control group)were retrospectively analyzed.The hippocampal subregions were automatically segmented using FreeSurfer software,the volume of cornu Ammonis(CA)1,CA2-3,CA4,granulose cell-dentate gyrus(GC-DG)and subiculum were measured,then the NODDI parameters of each subregion were obtained through post-processing.The intra-and inter-groups hippocampal subregion volumes and NODDI parameters were compared,and the correlations of parameters being significantly different with the onset age and disease courses were analyzed.Results The volume of hippocampal subregions in mTLE-HS group were all lower than those in control group(all P<0.05).In mTLE-HS group,the neurite density index(NDI)of left CA1 and CA4 subregions were both lower,while the free-water isotropic volume fraction(fiso)of the left CA1 subregion was higher than those of the right side(all P<0.05).The orientation dispersion index(ODI)of left CA1,CA2-3 and CA4 subregions,as well as NDI of left CA1,CA4 and GC-DG subregions in mTLE-HS group were all lower than those in control group(all P<0.05),while fiso of left CA1,GC-DG and subiculum subregions in mTLE-HS group were all higher than those in control group(all P<0.05).The volume of left hippocampal subregions in patients with mTLE-HS were all moderately positively correlated with the onset age(r=0.540-0.667,all P<0.001)but weakly negatively correlated with disease courses(r=-0.492--0.386,all P<0.05).NDI of left CA4 and GC-DG subregions in patients with mTLE-HS were both weakly negatively correlated with disease courses(r=-0.418,-0.388,both P<0.05).Conclusion Automatic segmentation technique combined with NODDI could be used to display the volume and microstructure changes of mTLE-HS.NDI might be a biomarker of mTLE-HS being sensitive to progressive neuronal damage.
3.Study of hippocampal subregion in patients with temporal lobe epilepsy by neurite orientation dispersion and density imaging
Wenrui YANG ; Xucong WANG ; Jian LI ; Mengnan YAN ; Jinqin LI ; Yanling ZHANG ; Bing CHEN
Journal of Practical Radiology 2024;40(9):1403-1407
Objective To explore the hippocampal(HC)microstructural changes in patients with unilateral temporal lobe epilepsy(TLE)by neurite orientation dispersion and density imaging(NODDI).Methods The NODDI indexes of the whole HC and HC subregions of temporal lobe epilepsy with hippocampal sclerosis(TLE-HS)patients,non-HS patients and healthy controls(control group)were calculated.The differences of NODDI indexes among and within the three groups were compared,and the correlation between the difference indexes and the clinical characteristics of the patients was analyzed.Results A total of 47 patients with TLE(27 cases of TLE-HS,20 cases of non-HS)and 22 cases of healthy controls were enrolled.In the TLE-HS group,the free-water isotropic vol-ume fraction(fiso)values of the HC and granular cell layer of dentate gyrus(GC-DG)subregions of the affected side were signifi-cantly higher than those of the contralateral side;the orientation dispersion index(ODI)values of the CA1 and CA4 subregions were significantly lower than those of the contralateral side;and the neurite density index(NDI)values of the HC,CA1,CA2-3,CA4 and GC-DG subregions of the affected side decreased significantly.There was no significant difference between the affected side and the contralateral side in the non-HS group.The fiso values of the HC and GC-DG subregions of the affected side in the TLE-HS group were significantly higher than those in the control group,the ODI values of the HC CA1 subregions of the affected side in the TLE-HS group were significantly lower than those in the control group and the non-HS group,the NDI values of the HC and subiculum(Sub),CA1,CA4 and GC-DG subregions of the affected side in the TLE-HS group were significantly lower than those in the con-trol group,and the NDI values of the HC and CA1,CA4 and GC-DG subregions of the affected side in the non-HS group were significantly lower than those in the control group.In the TLE-HS group,the NDI value of the HC CA4 subregion of the affected side was negatively correlated with the disease course,but there was no clear correlation between other subregion variables and disease course,onset frequency and duration of single onset.Conclusion NODDI technique has the ability to detect the microstructural changes of HC in patients with TLE,among which NDI is more likely to highlight neuronal damage and fiber reorganization in patients with TLE.
4.Problems and countermeasures of industry-university-research cooperation in Liaoning Province
Yudong WU ; Ji WU ; Wei WU ; Xin LI ; Yu YI ; Yanming LIU ; Shuyin LI ; Yuting KANG ; Wenrui LU ; Weiyun CHEN ; Fu REN ; Kebin XU
Journal of Shenyang Medical College 2024;26(5):542-546
Industry-university-research cooperation is not only the core of technological innovation,but also an important way to enhance industrial competitiveness and achieve high-quality development.Industry-university-research cooperation in Liaoning Province has achieved significant results in promoting technological innovation and economic development,but there are still some problems and challenges.The main problems include insufficient depth of industry-university-research cooperation,scattered innovation resources,lack of long-term stable cooperation mechanisms,as well as talent loss and lack of high-quality innovative talents.Through systematically sorting out the existing models of industry-university-research cooperation,it proposes a series of targeted and operable countermeasures and suggestions.These measures and suggestions provide solid theoretical support for the healthy development of industry-university-research cooperation in Liaoning Province.
5.Background, design, and preliminary implementation of China prospective multicenter birth cohort
Si ZHOU ; Liping GUAN ; Hanbo ZHANG ; Wenzhi YANG ; Qiaoling GENG ; Niya ZHOU ; Wenrui ZHAO ; Jia LI ; Zhiguang ZHAO ; Xi PU ; Dan ZHENG ; Hua JIN ; Fei HOU ; Jie GAO ; Wendi WANG ; Xiaohua WANG ; Aiju LIU ; Luming SUN ; Jing YI ; Zhang MAO ; Zhixu QIU ; Shuzhen WU ; Dongqun HUANG ; Xiaohang CHEN ; Fengxiang WEI ; Lianshuai ZHENG ; Xiao YANG ; Jianguo ZHANG ; Zhongjun LI ; Qingsong LIU ; Leilei WANG ; Lijian ZHAO ; Hongbo QI
Chinese Journal of Perinatal Medicine 2024;27(9):750-755
China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.
6.Establishment and evaluation of a streptozotocin-induced diabetic encephalopathy rat model
Simin CHEN ; Yingjun HU ; Wenrui YAN ; Le JI ; Mengli SHAO ; Ze SUN ; Hongxing ZHENG ; Shanshan QI
Chinese Journal of Tissue Engineering Research 2024;28(2):237-241
BACKGROUND:Animal models of diabetic encephalopathy that have been studied mainly include streptozotocin-induced model,high-sugar and high-fat diet-induced model and spontaneous animal model.Establishing a simple,easy,short-cycle,safe and effective model of diabetic encephalopathy can help to explore the subsequent pathogenesis and screen therapeutic drugs. OBJECTIVE:To further explore and evaluate the method of building diabetic encephalopathy rat models. METHODS:Twenty Sprague-Dawley rats were randomly divided into control(n=10)and model(n=10)groups.Rats in the model group were given a single injection of 45 mg/kg streptozotocin in the left lower abdominal cavity,and those in the control group were given the same amount of citrate buffer.During the experiment,the body mass,feed intake,water intake and blood glucose were measured.After 8 weeks,the glucose tolerance and oxidative stress levels were measured,and the pathological changes of brain tissue and the expression of apoptotic proteins were compared between groups. RESULTS AND CONCLUSION:Compared with the control group,the food intake,water intake,encephalization quotient,blood glucose and area under the blood glucose curve were significantly increased in the model group,while the body mass decreased significantly(P<0.01).Histopathological examination of the brain showed that compared with the control group,the number of surviving nerve cells was significantly reduced in the model group(P<0.01),with more significant pathological damage of nerve cells.Compared with the control group,the activities of serum superoxide dismutase,catalase and glutathione in the model group were significantly decreased(P<0.01),and the content of oxidative malondialdehyde was significantly increased(P<0.05).The expression levels of apoptosis-related proteins Bax and Caspase-3 in brain tissue increased in the model group compared with the control group,while the expression of Bcl-2 decreased(P<0.01).In conclusion,an 8-week injection of 45 mg/kg streptozotocin can cause obvious pathological damage to the brain tissue of diabetic rats,to successfully establish the rat model of diabetic encephalopathy.
7.Advances in application of EEG-fNIRS technology in researches on neuropsychiatric disorders
Chenyang GAO ; Kai WU ; Wenhao LI ; Yi LI ; Zhile JIANG ; Yuxin WANG ; Wenrui CHEN ; Jing ZHOU
Chinese Journal of Medical Physics 2024;41(3):348-355
Currently,electroencephalogram(EEG),functional near-infrared spectroscopy(fNIRS),and functional magnetic resonance imaging have been widely studied and applied to neuropsychiatric disorders.In recent years,the devices which can realize the simultaneous acquisition of EEG and fNIRS has been developed and gradually applied in the studies on neuropsychiatric disorders.The review provides an introduction of the techniques of synchronized detection and data analysis for EEG-fNIRS,summarizes the analysis methods and new findings of the recent studies of stroke,epilepsy,and other neuropsychiatric disorders using EEG-fNIRS,and also discusses the future research directions.
8.Mechanical thrombus aspiration combined with superior mesenteric artery transcatheter thrombolysis in the treatment of portal vein thrombosis
Bin LIU ; Hai FENG ; Xueming CHEN ; Wenrui LI ; Hongzhi YU
International Journal of Surgery 2023;50(3):155-159,F3
Objective:To compare the effectiveness and safety of mechanical thrombus aspiration combined with superior mesenteric artery transcatheter thrombolysis with those of simple superior mesenteric artery transcatheter thrombolysis in the treatment of portal vein-superior mesenteric vein thrombosis.Methods:A retrospective case-control study was used to analyze the clinical data of 27 patients with portal vein thrombosis treated by interventional therapy in Beijing Friendship Hospital Affiliated to Capital Medical University from February 2020 to October 2022. According to different interventional procedures, they were divided into two groups: 13 cases were treated with mechanical thrombus aspiration combined with superior mesenteric artery catheterization thrombolysis (combined treatment group), and 14 cases were treated with superior mesenteric artery catheterization thrombolysis alone (catheterization thrombolysis group). The postoperative and preoperative portal vein thrombus grade, catheterization thrombolysis time, parenteral nutrition time and operation-related complications were observed and compared between the two methods, and the incidence of long-term intestinal necrosis was compared after postoperative follow-up. Measurement data of normal distribution were expressed as mean±standard deviation( ± s), t-test was used for comparison between groups. Counting data were expressed as cases and percentage(%), and comparison between groups was used Chi-square test or Fisher exact probability method. Results:There was significant difference in the grade of portal vein thrombosis between the combined treatment group and the catheterization thrombolysis group( P<0.05). The thrombolytic time of catheterization in the two groups was (2.38±0.74) d and (4.79±1.15) d, respectively, and the time of parenteral nutrition was (4.08±2.87) d and (8.50±3.16) d, respectively. The difference was statistically significant ( P<0.05). There was no significant difference in operation-related complications between the two groups ( P>0.05). There were no severe injury of liver and kidney function in both groups. One patient in each group underwent long-term enterectomy. Conclusions:Mechanical thrombus aspiration combined with superior mesenteric artery thrombolysis is safe and effective in the treatment of portal vein thrombosis. Compared with simple superior mesenteric artery thrombolysis, mechanical thrombus aspiration combined with superior mesenteric artery thrombolysis can increase the rate of thrombus clearance and reduce the time of thrombolysis and parenteral nutrition support.
9.Clinical application of G-iliac? iliac branch device in the treatment of common iliac artery aneurysm
Wenrui LI ; Hai FENG ; Zhiwen ZHANG ; Bin LIU ; Hongzhi YU ; Xiang GAO ; Zhe ZHANG ; Xueming CHEN
International Journal of Surgery 2023;50(7):464-468,C2
Objective:To analyze the safety and efficacy of G-iliac? iliac branch device (IBD) in the treatment of common iliac artery aneurysm.Methods:The clinical data of 7 patients with common iliac artery aneurysm who were treated with G-iliac? IBD and internal iliac artery (IIA) preserved were retrospectively analyzed in the Department of Vascular Surgery, Beijing Friendship Hospital, Capital Medical University from June 2021 to June 2022, and the surgical effects and related complications were analyzed.Results:All 7 patients were male, aged from 57 to 80 years, with an average age of 70.9 years. There were 6 cases of abdominal aortic aneurysm combined with common iliac artery aneurysm and 1 case of simple common iliac artery aneurysm, all of them were successfully applied with G-iliac? IBD to preserve IIA. Cardiogenic shock occurred in 1 patient after the operation. 7 patients were followed up for 3-15 months, with an average of 8 months. During the follow-up period, the iliac artery and IIA stents were all patency, and there was no IBD-related endoleak, stent displacement, buttock claudication, sexual dysfunction, or aortic-related death. The diameter of abdominal aortic aneurysm and common iliac artery aneurysm were stable.Conclusion:For patients with common iliac artery aneurysm, preservation of IIA with G-iliac? IBD is a safe and effective technique with a high technical success rate and IIA patency rate, and has a low complication rate, but the long-term effect still requires more data and longer follow-up data to support.
10.MiR-30e-5p overexpression promotes proliferation and migration of colorectal cancer cells by activating the CXCL12 axis via downregulating PTEN.
Ke WEI ; Jiwen SHI ; Yuhan XIAO ; Wenrui WANG ; Qingling YANG ; Changjie CHEN
Journal of Southern Medical University 2023;43(7):1081-1092
OBJECTIVE:
To investigate the regulatory effects of miR-30e-5p on biological behaviors of colorectal cancer cells and the role of PTEN/CXCL12 axis in mediating these effects.
METHODS:
Bioinformatic analysis was performed to explore the differential expression of miR-30e-5p between colorectal cancer tissues and normal tissues. RT-qPCR was used to detect the differential expression of miR-30e-5p in intestinal epithelial cells and colorectal cancer cells. Bioinformatics and dual luciferase assay were used to predict and validate the targeting relationship between miR-30e-5p and PTEN. Human and murine colorectal cancer cell lines were transfected with miR-30e-5p mimics, miR-30e-5p inhibitor, miR-30e-5p mimics+LV-PTEN, or miR-30e-5p inhibitor + si-PTEN. The changes in biological behaviors of the cells were detected using plate clone formation assay, CCK-8 assay, flow cytometry, scratch healing and Transwell assays. PTEN and CXCL12 expressions in the cancer cells were detected by Western blotting. The effects of miR-30e-5p inhibitor on colorectal carcinogenesis and development were observed in nude mice.
RESULTS:
Bioinformatic analysis showed that miR-30e-5p expression was significantly elevated in colorectal cancer tissues compared with the adjacent tissue (P < 0.01). Higher miR-30e-5p expression was detected in colorectal cancer cell lines than in intestinal epithelial cells (P < 0.01). Dual luciferase assay confirmed the targeting relationship between miR-30e-5p and PTEN (P < 0.05). Transfection with miR-30e-5p mimics significantly enhanced proliferation and metastasis and inhibited apoptosis of the colorectal cancer cells (P < 0.05), and co-transfection with LV-PTEN obviously reversed these changes (P < 0.05). MiR-30e-5p mimics significantly inhibited PTEN expression and enhanced CXCL12 expression in the cancer cells (P < 0.01), and miR-30e-5p inhibitor produced the opposite effect. Transfection with miR-30e-5p inhibitor caused cell cycle arrest in the cancer cells, which was reversed by co-transfection with si-PTEN (P < 0.05). In the in vivo experiments, the colorectal cancer cells transfected with miR-30e-5p inhibitor showed significantly lowered tumorigenesis.
CONCLUSION
Overexpression of miR-30e-5p promotes the malignant behaviors of colorectal cancer cells by downregulating PTEN to activate the CXCL12 axis.
Humans
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Animals
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Mice
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MicroRNAs/metabolism*
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Cell Line, Tumor
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Cell Proliferation/physiology*
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Mice, Nude
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Cell Movement/physiology*
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Colorectal Neoplasms/pathology*
;
Luciferases/metabolism*
;
Gene Expression Regulation, Neoplastic
;
PTEN Phosphohydrolase/metabolism*
;
Chemokine CXCL12/metabolism*

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