1.Effect of amino acid metabolic reprogramming on immune microenvironment of hepatocellular carcinoma
Xiaoli LIU ; Qinwen TAN ; Jian XU ; Huanling CHEN ; Jie YU ; Lu LU ; Mingkan DAI ; Jingjing HUANG ; Hongna HUANG ; Dewen MAO
Journal of Clinical Hepatology 2024;40(12):2531-2537
Tumor immune microenvironment is a local external tumor environment composed of tumor immune cells and the cytokines secreted by these cells, and it plays a regulatory role in the development and progression of tumors. In the treatment of hepatocellular carcinoma, amino acid metabolism and its reprogramming of proliferating cell metabolism have attracted more and more attention, showing potential in regulating the tumor immune microenvironment. Although amino acid metabolic reprogramming is regarded as a novel approach for tumor therapy, its specific mechanism remains unclear in the regulation of tumor immunity in hepatocellular carcinoma. This article discusses the mechanism of action of amino acid metabolism in the tumor immune microenvironment of hepatocellular carcinoma and its application prospect in clinical practice, in order to provide new ideas for immunotherapy for liver cancer.
2.Analysis of core functional components in Yinchenhao Decoction and their pathways for treating liver fibrosis
Xingmei CHEN ; Qinwen LIU ; Yi LI ; Xiaoyu ZHONG ; Qiling FAN ; Ke MA ; Liuting LUO ; Daogang GUAN ; Zhibo ZHU
Journal of Southern Medical University 2024;44(8):1508-1517
Objective To analyze the core functional component groups(CFCG)in Yinchenhao Decoction(YCHD)and their possible pathways for treating hepatic fibrosis based on network pharmacology.Methods PPI data were extracted from DisGeNET,Genecards,CMGRN and PTHGRN to construct a weighted network using Cytoscape 3.9.1.The data of the chemical components in YCHD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the potential active components and targets were selected using PreADMET Web server and SwissTargetPrediction.A fusion model was constructed to obtain the functional effect space and evaluate the effective proteins to identify the CFCG followed by GO and KEGG pathway enrichment analyses for all the targets.In cultured human hepatic stellate cells(LX-2 cells),the cytotoxicity of different compounds in YCHD was tested using CCK-8 assay;the effects of these compounds on collagen α1(Col1a1)mRNA expression and the pathways in 20 ng/mL TGF-β1-stimulated cells were analyzed using RT-qPCR and Western blotting.Results A total of 1005 pathogenic genes,226 potential active components and 1529 potential targets in YCHD and 52 potential targets of CFCG were obtained.Benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid were selected for CCK-8 verification,and they all showed minimal cytotoxicity below the concentration of 200 μmol/L.Clorius,polydatin,lauric acid and ferulic acid all effectively inhibited TGF-β1-induced LX-2 cell activation.At the concentration of 200 μmol/L,all these 4 components inhibited PI3K,p-PI3K,AKT,p-AKT,ERK,p-ERK,P38 MAPK and p-P38 MAPK expressions in TGF-β1-induced LX-2 cells.Conclusion The therapeutic effect of YCHD on hepatic fibrosis is probably mediated by its core functional components including benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid,which inhibit the PI3K-AKT and MAPK pathways in hepatic stellate cells.
3.Analysis of core functional components in Yinchenhao Decoction and their pathways for treating liver fibrosis
Xingmei CHEN ; Qinwen LIU ; Yi LI ; Xiaoyu ZHONG ; Qiling FAN ; Ke MA ; Liuting LUO ; Daogang GUAN ; Zhibo ZHU
Journal of Southern Medical University 2024;44(8):1508-1517
Objective To analyze the core functional component groups(CFCG)in Yinchenhao Decoction(YCHD)and their possible pathways for treating hepatic fibrosis based on network pharmacology.Methods PPI data were extracted from DisGeNET,Genecards,CMGRN and PTHGRN to construct a weighted network using Cytoscape 3.9.1.The data of the chemical components in YCHD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the potential active components and targets were selected using PreADMET Web server and SwissTargetPrediction.A fusion model was constructed to obtain the functional effect space and evaluate the effective proteins to identify the CFCG followed by GO and KEGG pathway enrichment analyses for all the targets.In cultured human hepatic stellate cells(LX-2 cells),the cytotoxicity of different compounds in YCHD was tested using CCK-8 assay;the effects of these compounds on collagen α1(Col1a1)mRNA expression and the pathways in 20 ng/mL TGF-β1-stimulated cells were analyzed using RT-qPCR and Western blotting.Results A total of 1005 pathogenic genes,226 potential active components and 1529 potential targets in YCHD and 52 potential targets of CFCG were obtained.Benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid were selected for CCK-8 verification,and they all showed minimal cytotoxicity below the concentration of 200 μmol/L.Clorius,polydatin,lauric acid and ferulic acid all effectively inhibited TGF-β1-induced LX-2 cell activation.At the concentration of 200 μmol/L,all these 4 components inhibited PI3K,p-PI3K,AKT,p-AKT,ERK,p-ERK,P38 MAPK and p-P38 MAPK expressions in TGF-β1-induced LX-2 cells.Conclusion The therapeutic effect of YCHD on hepatic fibrosis is probably mediated by its core functional components including benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid,which inhibit the PI3K-AKT and MAPK pathways in hepatic stellate cells.
4.The microbiota-gut-brain axis and neurodevelopmental disorders.
Qinwen WANG ; Qianyue YANG ; Xingyin LIU
Protein & Cell 2023;14(10):762-775
The gut microbiota has been found to interact with the brain through the microbiota-gut-brain axis, regulating various physiological processes. In recent years, the impacts of the gut microbiota on neurodevelopment through this axis have been increasingly appreciated. The gut microbiota is commonly considered to regulate neurodevelopment through three pathways, the immune pathway, the neuronal pathway, and the endocrine/systemic pathway, with overlaps and crosstalks in between. Accumulating studies have identified the role of the microbiota-gut-brain axis in neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity disorder, and Rett Syndrome. Numerous researchers have examined the physiological and pathophysiological mechanisms influenced by the gut microbiota in neurodevelopmental disorders (NDDs). This review aims to provide a comprehensive overview of advancements in research pertaining to the microbiota-gut-brain axis in NDDs. Furthermore, we analyzed both the current state of research progress and discuss future perspectives in this field.
Humans
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Brain-Gut Axis
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Autism Spectrum Disorder/metabolism*
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Brain/metabolism*
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Gastrointestinal Microbiome
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Neurodevelopmental Disorders/metabolism*
5.Investigation and analysis of smoking behaviour of civil servants in Minhang District, Shanghai
Weiqing GUO ; Keying DING ; Jian WANG ; Hui CHEN ; Jing LUAN ; Zhilian LIU ; Tao LIU ; Jiajie WU ; Qinwen YANG
Journal of Environmental and Occupational Medicine 2022;39(1):47-52
Background The tobacco epidemic as one of the most serious public health problems in the world contributes great harm to human health. It is urgent to develop tobacco control strategy. Civil servants' behaviors as a role model for society have a great influence on the rest of society. Thus, it is important to promote tobacco control program on helping civil servants to quit smoking. Objective To understand the smoking and second-hand smoking exposures status, the awareness of knowledge of tobacco hazards, and the attitudes to tobacco control policies of civil servants in Minhang District, Shanghai. Furthermore, to explore the related strategies and measures for tobacco control, to provide a basis for the development and revision of relevant intervention measures and policies. Methods A total of 20 government agencies with newly installed smoking-free programs from 10 subdistricts and towns in Minhang District, including Xinzhuang, Wujing, Maqiao, Qibao, Meilong, Hongqiao, Zhuanqiao, Jiangchuan, Gumei, and Xinhong were selected as study sites.A questionnaire survey was conducted to investigate all civil servants (n=801) of selected agencies. The questionnaire included general characteristics, smoking and second-hand smoking exposure status, knowledge of tobacco hazard, and attitudes to tobacco control policies. Results A total of 794 civil servants returned valid questionnaires. The awareness rate of tobacco hazards in the smoking group was lower than that in the non-smoking group (P<0.05). Relatively high smoking rates were reported in those being male (17.08%), age ≥51 years old (25.61%), divorced or widowed (12.50%), technical secondary school or below education level (22.81%), having more than 10 years of working years (11.57%), being willing to dissuade indoor smoking (24.54%), having no punishment or warning measures for violation of smoking regulations in workplaces (18.37%), and having no dedicated smoking spot at home (15.38%). The results of multiple logistic regression analysis showed that age 31-40 years old (OR=3.446, 95%CI: 1.236-9.609) and to avoid confronting indoor smoking (OR=3.686, 95%CI: 1.041-13.049) were risk factors for smoking in civil servants. Conclusion Civil servants aged 31-40 years old who deliberately avoid confronting indoor smoking behaviors are the key intervention population of smoking control in Minhang District, Shanghai.
6.Preliminary study on the polymorphisms of some related genes and the methylation levels of BAX and ApoE genes in Alzheimer′s disease
Wei CHEN ; Xiaohui ZHOU ; Yali DUAN ; Ting ZOU ; Shiwei DUAN ; Qinwen WANG ; Guili LIU ; Xiuru YING
Chinese Journal of Neurology 2021;54(11):1119-1127
Objective:To preliminarily explore the association between single nucleotide polymorphisms (SNP) of five candidate genes (APH1B, PRNP, HMGCR, SIRT1, ApoE) and Alzheimer′s disease (AD), and to analyze the methylation levels of BAX and ApoE promoters on the pathogenesis of AD.Methods:Seventeen cases who were admitted to the Department of Geriatrics of the First Affiliated Hospital of Xinjiang Medical University from 2014 to 2015 and diagnosed as likely to be AD by geriatrician and neurologists according to the AD diagnostic criteria in 4th Revised Edition of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association served AD group, with an age of (75.65±5.86) years, and 34 non-AD patients with matching baseline data such as age, gender, ethnicity, and education status among patients hospitalized during the same period were selected as control group, with an age of (77.59±7.41) years. Sanger sequencing method was used for SNP typing of candidate genes. Methylation-specific polymerase chain reaction was used to determine the DNA methylation level.Results:The distribution of ApoE ε4 allele was statistically different between the AD group and the control group (χ 2=9.718, P=0.002). Candidate genes (SIRT1 rs7895833, APH1B rs1047552, PRNP rs1799990, HMGCR rs3846662) SNP locus genotypes and alleles had no statistically significant differences in the distribution between the AD group and the control group ( P>0.05). After stratification according to whether they carried ApoE ε4, no statistically significant difference was found between the two groups ( P>0.05). The BAX promoter methylation level of the AD group (0.045±0.025) was lower than that of the control group (0.061±0.028) ( t=-2.078, P=0.045). After gender stratification, the BAX methylation level of the female AD group (0.044±0.021) was lower than that of the control group (0.065±0.275) ( t=-2.230, P=0.045). There was no statistically significant difference in the methylation level of ApoE promoter between the AD group and the control group ( P>0.05). After stratification according to whether they carry ApoE ε4 or not, the methylation level of AD patients with ApoE ε4 allele (1.553±0.291) was higher than that of non-carriers (1.221±0.261) ( t=2.480, P=0.025). Conclusions:ApoE ε4 allele may be a risk factor for the onset of AD. BAX promoter hypomethylation contributes to AD in the elderly in Xinjiang, especially in female. ApoE ε4 allele may cause AD through the interaction with ApoE methylation.
7.Two Arbuscular Mycorrhizal Fungi Alleviates Drought Stress and Improves Plant Growth inCinnamomum migao Seedlings
Xiaofeng LIAO ; Jingzhong CHEN ; Ruiting GUAN ; Jiming LIU ; Qinwen SUN
Mycobiology 2021;49(4):396-405
Cinnamomum migao plants often face different degrees of drought in karst habitats, which can lead to plants’ death, especially in the seedling stage. Widespread of arbuscular mycorrhizal (AM) fungi in karst soils have the potential to address this drought, which is a threat to C. migao seedlings. We inoculated C. migao seedlings with spores from Glomus lamellosum and Glomus etunicatum, two AM fungi widely distributed in karst soils, to observe seedling growth response after simulated drought. Our results showed that 40 g of G. lamellosum and G. etunicatum significantly promoted the growth of C. migao seedlings, 120 days after inoculation. Following a 15-day drought treatment, root colonization of the seedlings with G. lamellosum or G. etunicatum had lower the accumulation of malondialdehyde (MDA) and increased the accumulation of enzymes and osmotic substances in the seedlings. The relative water content in different organs (roots, stems, and leaves) of the drought-stressed seedlings was higher in plants with G. lamellosum or G. etunicatum than in plants without AM fungi colonization. Our results showed that inoculation with AM fungi was an effective means to improve the drought resistance of C. migao seedlings.
8.Two Arbuscular Mycorrhizal Fungi Alleviates Drought Stress and Improves Plant Growth inCinnamomum migao Seedlings
Xiaofeng LIAO ; Jingzhong CHEN ; Ruiting GUAN ; Jiming LIU ; Qinwen SUN
Mycobiology 2021;49(4):396-405
Cinnamomum migao plants often face different degrees of drought in karst habitats, which can lead to plants’ death, especially in the seedling stage. Widespread of arbuscular mycorrhizal (AM) fungi in karst soils have the potential to address this drought, which is a threat to C. migao seedlings. We inoculated C. migao seedlings with spores from Glomus lamellosum and Glomus etunicatum, two AM fungi widely distributed in karst soils, to observe seedling growth response after simulated drought. Our results showed that 40 g of G. lamellosum and G. etunicatum significantly promoted the growth of C. migao seedlings, 120 days after inoculation. Following a 15-day drought treatment, root colonization of the seedlings with G. lamellosum or G. etunicatum had lower the accumulation of malondialdehyde (MDA) and increased the accumulation of enzymes and osmotic substances in the seedlings. The relative water content in different organs (roots, stems, and leaves) of the drought-stressed seedlings was higher in plants with G. lamellosum or G. etunicatum than in plants without AM fungi colonization. Our results showed that inoculation with AM fungi was an effective means to improve the drought resistance of C. migao seedlings.
9.A clinical analysis of idiopathic hypertrophic cranial pachymeningitis with a nodular space-occupying effect
Hailing ZHANG ; Qinwen DONG ; Bin XIONG ; Dongdong SONG ; Jianguo LIU ; Xiaokun QI
Chinese Journal of Internal Medicine 2014;53(2):127-130
Objective To explore the clinical features,neuroimaging and histopathological findings in patients with idiopathic hypertrophic cranial pachymeningitis (IHCP) with a nodular space occupying effect.Methods Four IHCP cases with a nodular space occupying effect diagnosed in our hospital were retrospectively studied.Results All the 4 patients were men with a mean onset age of 40.25 (33 ~ 50) years old.They all had long disease duration and relapses.The common symptoms of IHCP were chronic headache,multiple cranial nerve palsies and epileptic seizures.CT and MRI of the brain revealed prominent dural partial thickening,which indicated a mass or nodular space occupying effect that mimicked intracranial tumour-like meningioma.The histopathological findings of dura in 2 cases revealed connective tissue proliferation,scattered neutrophile granulocytes and plasmacytes infiltration.Combination therapy of corticosteroid or/and immunosuppressive drugs was effective for the IHCP patients.Conclusions IHCP patients with a nodular space occupying effect usually onset with chronic headache and are often recurrent.The combination therapy of corticosteroid or/and immunosuppressive drugs is effective.The image of the brain presents prominent dural partial thickening,indicating a mass or nodular space occupying effect,which often lead to confusion with intracranial tumours or granulomatosis.
10.Six cases of deep cerebral veins thrombosis
Hailing ZHANG ; Qinwen DONG ; Jianguo LIU ; Yuhong MENG ; Xiaokun QI
Chinese Journal of Neurology 2013;46(12):810-815
Objective To analyse the clinical features,imaging characteristics diversity of deep cerebral veins thrombosis (DCVT).Methods From 2004 to 2013,6 patients diagnosed as DCVT were recorded and a retrospective review of the cases were undertaken for the purpose of this analysis.Results Among the 6 patients with DCVT,4 were male and 2 were female,aged from 28 to 69 years old.The disease duration of 4 cases ranged from 2 to 7 days,remnants were 20 days and 3 months respectively.The first symptoms of 4 cases were headache,1 was feeblemindedness,and the other was hemiplegia.The secondary symptoms were disturbance of consciousness,apathy,diplopia and non-infectious fever.Non-contrast computed tomography showed low signal in the bilateral thalamus in four patients,high signal in the transverse sinus and straight sinus in one patient and high signal in torcular in one patient.Abnormal signal was found in bilateral thalamus on magnetic resonance imaging in all patients and some of them had abnormal signal in the mesencephalon or basal ganglia.The patients were definitely diagnosed as DCVT by magnetic resonance venography (MRV) or digital subtraction angiography (DSA).Among them,2 patients were confirmed by brain biopsy.Four patients were followed up with good outcome and 2 were lost to follow-up.Conclusions The clinical manifestations of DCVT are not specific.For acute-onset DCVT patients,the first symptoms are always headache and vomiting,while the main symptoms are declined cognition and slow reaction for chronic-onset ones.Along with the progress,the main symptoms of DCVT are disturbance of consciousness,psychiatric symptoms and intracranial hypertension.Changes in the bilateral thalamus and basal ganglia are especially main characteristics which are easily misdiagnosed as brain tumor according to the images.DCVT can be definitely diagnosed by no signal of deep cerebral veins on MRV or DSA.

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