Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 32
Filter
1.
Int J Biol Sci ; 20(7): 2763-2778, 2024.
Article in English | MEDLINE | ID: mdl-38725845

ABSTRACT

Dysregulation of the aldehyde dehydrogenase (ALDH) family has been implicated in various pathological conditions, including cancer. However, a systematic evaluation of ALDH alterations and their therapeutic relevance in hepatocellular carcinoma (HCC) remains lacking. Herein, we found that 15 of 19 ALDHs were transcriptionally dysregulated in HCC tissues compared to normal liver tissues. A four gene signature, including ALDH2, ALDH5A1, ALDH6A1, and ALDH8A1, robustly predicted prognosis and defined a high-risk subgroup exhibiting immunosuppressive features like regulatory T cell (Tregs) infiltration. Single-cell profiling revealed selective overexpression of tumor necrosis factor receptor superfamily member 18 (TNFRSF18) on Tregs, upregulated in high-risk HCC patients. We identified ALDH2 as a tumor suppressor in HCC, with three novel phosphorylation sites mediated by protein kinase C zeta that enhanced enzymatic activity. Mechanistically, ALDH2 suppressed Tregs differentiation by inhibiting ß-catenin/TGF-ß1 signaling in HCC. Collectively, our integrated multi-omics analysis defines an ALDH-Tregs-TNFRSF18 axis that contributes to HCC pathogenesis and represents potential therapeutic targets for this aggressive malignancy.


Subject(s)
Aldehyde Dehydrogenase, Mitochondrial , Carcinoma, Hepatocellular , Liver Neoplasms , T-Lymphocytes, Regulatory , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/immunology , Liver Neoplasms/genetics , Humans , Aldehyde Dehydrogenase, Mitochondrial/metabolism , Aldehyde Dehydrogenase, Mitochondrial/genetics , T-Lymphocytes, Regulatory/metabolism , T-Lymphocytes, Regulatory/immunology , Tumor Microenvironment , Aldehyde Dehydrogenase/metabolism , Aldehyde Dehydrogenase/genetics , Animals , Cell Line, Tumor , Male , Mice , Multiomics
2.
Cancer Cell Int ; 24(1): 13, 2024 Jan 06.
Article in English | MEDLINE | ID: mdl-38184573

ABSTRACT

Gastric cancer remains a leading cause of cancer-related death worldwide, largely due to inadequate screening methods, late diagnosis, and limited treatment options. Liquid biopsy has emerged as a promising non-invasive approach for cancer screening and prognosis by detecting circulating tumor components like circulating tumor DNA (ctDNA) in the blood. Numerous gastric cancer-specific ctDNA biomarkers have now been identified. CtDNA analysis provides insight into genetic and epigenetic alterations in tumors, holding promise for predicting treatment response and prognosis in gastric cancer patients. This review summarizes current research on ctDNA biology and detection technologies, while highlighting clinical applications of ctDNA for gastric cancer diagnosis, prognosis, and guiding treatment decisions. Current challenges and future perspectives for ctDNA analysis are also discussed.

3.
Inflammopharmacology ; 31(1): 423-438, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36534240

ABSTRACT

OBJECTIVES: To explore the anti-inflammatory effect and the potential mechanism of dexmedetomidine in ARDS/ALI. MATERIALS AND METHODS: C57BL/6 mice and EL-4 cells were used in this research. The ALI model was established by CLP. The level of inflammatory cytokines in the lung and blood, the severity of lung injury, the expression of Foxp3, and the proportion of Tregs were detected before and after dexmedetomidine treatment. The expression of the AMPK/SIRT1 after dexmedetomidine treatment was detected in vivo and in vitro. After blocking the AMPK/SIRT1 pathway or depleting Tregs in vivo, the level of the inflammatory response, tissue injury, and Tregs differentiation were detected again to clarify the effect of dexmedetomidine. RESULTS: Dexmedetomidine significantly reduced systemic inflammation and lung injury in CLP mice. Dexmedetomidine enhanced the Foxp3 expression in the lungs and the frequency of Tregs in the spleen. Dexmedetomidine up-regulated the protein expression of p-AMPK and SIRT1 in lungs and EL-4 cells and facilitated the differentiation of naïve CD4+ T cells into Tregs in vitro. Meanwhile, DEX also increased the expression of Helios in Treg cells. CONCLUSIONS: DEX could improve ARDS/ALI by facilitating the differentiation of Tregs from naïve CD4+ T cells via activating the AMPK/SIRT1 pathway.


Subject(s)
Acute Lung Injury , Dexmedetomidine , Respiratory Distress Syndrome , Mice , Animals , AMP-Activated Protein Kinases/metabolism , Dexmedetomidine/pharmacology , Sirtuin 1/metabolism , Mice, Inbred C57BL , Acute Lung Injury/metabolism , Lung , Cell Differentiation , Forkhead Transcription Factors/metabolism
4.
Exp Hematol Oncol ; 11(1): 92, 2022 Nov 08.
Article in English | MEDLINE | ID: mdl-36348379

ABSTRACT

BACKGROUND: Though circular RNAs (circRNAs) are the key regulators in tumor carcinogenesis, they remain largely unexplored in hepatocellular carcinoma (HCC). METHODS: The expression of RanGAP1-derived circRNAs (circ_0063531, circ_0063534, circ_0063513, circ_0063518, circ_0063507, circ_0063723) were evaluated in eight paired HCC and normal tissues, and the correlation between circRanGAP1 (circ_0063531) expression and clinicopathological characteristics in 40 HCC patients was determined. The association between miR-27b-3p and circRanGAP1 or NRAS was predicted using bioinformatics analysis. The expression of circRanGAP1, miR-27b-3p, and NRAS were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The potential oncogenic role of circ-RanGAP1 was assessed using CCK-8, colony formation, transwell assays in vitro, subcutaneous tumor mouse model, vein tail metastatic model, and orthotopically implanted intrahepatic HCC model in vivo. Luciferase reporter and RNA immunoprecipitation (RIP) assays were used to explore the binding site between miR-27b-3p and circ-RanGAP1 or NRAS. Protein expression was detected using western blotting. The localization of miR-27b-3p and circ-RanGAP1 was investigated using fluorescence in situ hybridization (FISH). The level of immune infiltration was assessed by bioinformatics analysis, flow cytometry, and orthotopically implanted intrahepatic HCC models. RESULTS: Here, we found elevated circRanGAP1 in the cells and clinical tissues of patients with HCC. Increased circRanGAP1 levels are associated with enlarged tumors and the advanced stage of TNM. CircRanGAP1 promotes the growth, migration, and HCC cell invasion, concurrently with the growth and metastasis of tumors in-vivo. Moreover, circRanGAP1 is mainly located inside the cytoplasm. Mechanistically, circRanGAP1 as an oncogene promotes HCC progression by miR-27b-3p/NRAS/ERK axis, furthermore, affects the infiltration level of tumor-associated macrophages probably by sponging miR-27b-3p. Immune infiltration analysis shows that NRAS is positively correlated with the levels of CD68+ tumor-associated macrophages in HCC samples and that NRAS and CD68 are related to the poor outcome of HCC. CONCLUSION: These results reveal that circRanGAP1 is a HCC oncogene that function by the miR-27b-3p/NRAS/ERK axis and regulates the infiltration levels of tumor-associated macrophages by sponging miR-27b-3p. Therefore, circRANGAP1/ NRAS axis may be an important potential treatment target against HCC.

5.
Front Pharmacol ; 13: 952482, 2022.
Article in English | MEDLINE | ID: mdl-36071851

ABSTRACT

Sorafenib resistance is often developed and impedes the benefits of clinical therapy in hepatocellular carcinoma (HCC) patients. However, the relationship between sorafenib resistance and tumor immune environment and adjuvant drugs for sorafenib-resistant HCC are not systemically identified. This study first analyzed the expression profiles of sorafenib-resistant HCC cells to explore immune cell infiltration levels and differentially expressed immune-related genes (DEIRGs). The prognostic value of DEIRGs was analyzed using Cox regression and Kaplan-Meier analysis based on The Cancer Genome Atlas. The primary immune cells infiltrated in sorafenib-resistant HCC mice were explored using flow cytometry (FCM). Finally, small-molecule drugs for sorafenib-resistant HCC treatment were screened and validated by experiments. The CIBERSORT algorithm and mice model showed that macrophages and neutrophils are highly infiltrated, while CD8+ T cells are downregulated in sorafenib-resistant HCC. Totally, 34 DEIRGs were obtained from sorafenib-resistant and control groups, which were highly enriched in immune-associated biological processes and pathways. NR6A1, CXCL5, C3, and TGFB1 were further identified as prognostic markers for HCC patients. Finally, nalidixic acid was identified as a promising antagonist for sorafenib-resistant HCC treatment. Collectively, our study reveals the tumor immune microenvironment changes and explores a promising adjuvant drug to overcome sorafenib resistance in HCC.

6.
J Transl Med ; 20(1): 379, 2022 08 29.
Article in English | MEDLINE | ID: mdl-36038907

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most malignant tumors to threaten human life, and the survival rate remains low due to delayed diagnosis. Meanwhile, lncRNAs have great potential for application in tumor prognosis, therefore relevant research in hepatocellular carcinoma is indispensable. METHODS: Based on the EZH2 expression, the differentially expressed lncRNAs DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) were identified in hepatocellular carcinoma by using the TCGA database. Bioinformatics technology was utilized to determine the effect of key genes in HCC progression. The methylation and immune infiltration analyses were performed to explore the underlying function of hub genes. Finally, cellular function experiments were performed to investigate the association between identified genes and biological phenotypes in HCC. RESULTS: lncRNA-AC079061.1, hsa-miR-765, and VIPR1 were identified as independent factors that affect the prognosis of hepatocellular carcinoma. The immune infiltration analyses revealed that lncRNA-AC079061.1 can alter the immune microenvironment and thus inhibit the development of HCC by regulating the expression of an immune-related gene (VIPR1). Methylation analyses demonstrated that VIPR1 expression is negatively related to the methylation level in HCC. Experimental results suggested that lncRNA-AC079061.1 and VIPR1 were frequently downregulated in HCC cells, while hsa-miR-765 was significantly upregulated. Moreover, the lncRNA-AC079061.1/VIPR1 axis suppressed the proliferation and invasion of HCC cells. CONCLUSION: The present study identified the lncRNA-AC079061.1/VIPR1 axis as a novel biomarker that inhibited the proliferation and invasion of hepatocellular carcinoma, affecting the ultimate disease outcome.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , RNA, Long Noncoding , Carcinoma, Hepatocellular/pathology , Computational Biology , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Receptors, Vasoactive Intestinal Polypeptide, Type I/genetics , Receptors, Vasoactive Intestinal Polypeptide, Type I/metabolism , Tumor Microenvironment
7.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-965133

ABSTRACT

@#Abstract: - ( ) , Work related musculoskeletal disorders WMSDs are common occupational diseases in construction workers which have a high prevalence rate and involve a large number of construction workers. WMSDs affect daily work and quality of life of , patients leading to absenteeism and burden. The main body parts of construction workers suffering from WMSDs are lower back/ , , , , , waist neck shoulder knee elbow and hand/wrist and most of the patients are complicated in multiple sites. The prevalence , of WMSDs varies by site with the lower back/waist being the most common sites. The influencing factors of WMSDs in ( , , , , , construction workers mainly include individual factors age years of work gender smoking status sleep habits physical , ), ( , , , fitness and physical exercise etc. occupational factors work load job type working posture work organization and , ) management working environment and social psychological factors. The incidence of WMSDs is the result of multiple factors. , , Therefore tertiary prevention is the key to the prevention and control of WMSDs especially the etiological prevention. Chinese , construction industry is in the period of rapid development and the demand of construction workers is large. It is urgent to carry out epidemiological and intervention studies on WMSDs for construction workers to guide the formulation of relevant guidelines and measures for prevention and control of WMSDs.

8.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-965132

ABSTRACT

@#Abstract: - ( ) , Work related musculoskeletal disorders WMSDs are common occupational diseases in construction workers which have a high prevalence rate and involve a large number of construction workers. WMSDs affect daily work and quality of life of , patients leading to absenteeism and burden. The main body parts of construction workers suffering from WMSDs are lower back/ , , , , , waist neck shoulder knee elbow and hand/wrist and most of the patients are complicated in multiple sites. The prevalence , of WMSDs varies by site with the lower back/waist being the most common sites. The influencing factors of WMSDs in ( , , , , , construction workers mainly include individual factors age years of work gender smoking status sleep habits physical , ), ( , , , fitness and physical exercise etc. occupational factors work load job type working posture work organization and , ) management working environment and social psychological factors. The incidence of WMSDs is the result of multiple factors. , , Therefore tertiary prevention is the key to the prevention and control of WMSDs especially the etiological prevention. Chinese , construction industry is in the period of rapid development and the demand of construction workers is large. It is urgent to carry out epidemiological and intervention studies on WMSDs for construction workers to guide the formulation of relevant guidelines and measures for prevention and control of WMSDs.

9.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-965131

ABSTRACT

@#Abstract: - ( ) , Work related musculoskeletal disorders WMSDs are common occupational diseases in construction workers which have a high prevalence rate and involve a large number of construction workers. WMSDs affect daily work and quality of life of , patients leading to absenteeism and burden. The main body parts of construction workers suffering from WMSDs are lower back/ , , , , , waist neck shoulder knee elbow and hand/wrist and most of the patients are complicated in multiple sites. The prevalence , of WMSDs varies by site with the lower back/waist being the most common sites. The influencing factors of WMSDs in ( , , , , , construction workers mainly include individual factors age years of work gender smoking status sleep habits physical , ), ( , , , fitness and physical exercise etc. occupational factors work load job type working posture work organization and , ) management working environment and social psychological factors. The incidence of WMSDs is the result of multiple factors. , , Therefore tertiary prevention is the key to the prevention and control of WMSDs especially the etiological prevention. Chinese , construction industry is in the period of rapid development and the demand of construction workers is large. It is urgent to carry out epidemiological and intervention studies on WMSDs for construction workers to guide the formulation of relevant guidelines and measures for prevention and control of WMSDs.

10.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-965130

ABSTRACT

@#Abstract: - ( ) , Work related musculoskeletal disorders WMSDs are common occupational diseases in construction workers which have a high prevalence rate and involve a large number of construction workers. WMSDs affect daily work and quality of life of , patients leading to absenteeism and burden. The main body parts of construction workers suffering from WMSDs are lower back/ , , , , , waist neck shoulder knee elbow and hand/wrist and most of the patients are complicated in multiple sites. The prevalence , of WMSDs varies by site with the lower back/waist being the most common sites. The influencing factors of WMSDs in ( , , , , , construction workers mainly include individual factors age years of work gender smoking status sleep habits physical , ), ( , , , fitness and physical exercise etc. occupational factors work load job type working posture work organization and , ) management working environment and social psychological factors. The incidence of WMSDs is the result of multiple factors. , , Therefore tertiary prevention is the key to the prevention and control of WMSDs especially the etiological prevention. Chinese , construction industry is in the period of rapid development and the demand of construction workers is large. It is urgent to carry out epidemiological and intervention studies on WMSDs for construction workers to guide the formulation of relevant guidelines and measures for prevention and control of WMSDs.

11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-976140

ABSTRACT

@#Objective To analyze the physical agent detection ability of occupational health technical service institutions in Methods Guangdong Province. A total of 92 institutions in Guangdong Province that participated in the inter laboratory comparison of physical agents organized in 2020 were taken as the research subjects using purposive sampling method. The , Results certified physical factor items number of measuring instruments and measurement standards were investigated. The , , certification and accreditation project on physical agents in 92 institutions with certification and accreditation rate >80.0% , , , - were noise high temperature ultraviolet radiation hand transmitted vibration and illumination. The certification approval rates , , , , of power frequency magnetic field 1 Hz to 100 kHz electric field 1 Hz to 100 kHz magnetic field laser radiation physical , - < ( ) labor intensity and whole body vibration were 60.0%. The certification and accreditation rate of noise 98.9% was the , ( ) (P< ) , highest and that of the physical labor intensity 3.3% was the lowest 0.01 . As for the number of measuring instruments ( ) the number of noise measuring instruments accounted for the highest proportion 52.6% in 92 institutions. The number of , (P< ) measuring instruments from the most to the least was grade A grade B and unqualified institutions 0.01 . The number of - (P< ) measuring instruments in private institutions was greater than that in non private institutions 0.01 . In the measurement , , standards some institutions that have certified power frequency electric field power frequency magnetic field and microclimate , - projects still used the abandoned standard. Some institutions that have certified microclimate illuminance and whole body Conclusion , vibration used the wrong measurement standards. Among the physical agents the certification and accreditation , rate of noise is the highest and the number of noise related measuring instruments is the largest. The qualified institutions and private institutions have greater number of certification and accreditation projects on physical agents and measuring instruments.

12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-976116

ABSTRACT

@#Objective - ( ) To analyze the occurrence pattern of work related musculoskeletal disorders WMSDs among workers Methods in a shipyard based on latent category model. A total of 446 workers from a shipyard in Guangdong Province were selected as the research subjects using convenience sampling method. The prevalence of WMSDs in the past year was , investigated using China Musculoskeletal Questionnaire and the occurrence patterns of WMSDs were analyzed by latent class. Results ( ) The prevalence of WMSDs in the past year was 71.1% 317/446 . The prevalence of WMSDs in single site was 24.4% ( ), ( ) - 109/446 and was 46.6% 208/446 in multiple sites. The prevalence of WMSDs in multiple sites was 3.9 17.3 times higher than that in single site. The fitting results of latent class model showed that the model with three latent classes was the best - ( ), model. The three potential categories of WMSDs occurrence patterns in the study subjects were the all site group 28 patients ( ), ( ), , the neck and lower back/waistgroup 153 patients and the few or no site group 265 patients accounting for 6.3% 34.3% , Conclusion and 59.4% respectively. WMSDs of shipyard workers have obvious category characteristics. Latent class analysis can be used to explore the occurrence pattern of WMSDs in shipyard workers.

13.
Cell Cycle ; 20(22): 2402-2412, 2021 11.
Article in English | MEDLINE | ID: mdl-34606419

ABSTRACT

Multiple myeloma (MM) remains an incurable hematological malignancy characterized by proliferation and accumulation of plasma cells in the bone marrow. Innovative and effective therapeutic approaches that are able to improve the outcome and the survival of MM sufferers, especially the identification of novel natural compounds and investigation of their anti-MM mechanisms, are needed. Here, we investigated the effects and the potential mechanisms against MM of forskolin, a diterpene derived from the medicinal plant Coleus forskohlii, in MM cell line MM.1S. CCK-8 assay showed that forskolin significantly inhibited MM.1S cells viability in a time- and dose-dependent manner. Furthermore, we demonstrated that forskolin induced G2/M phase arrest with a remarkable increase of p-cdc25c, p-cdc2, and a decrease of cyclin B1, indicating the suppression of cdc25C/cdc2/cyclin B pathway. Moreover, we found that forskolin induced mitochondrion-dependent apoptosis which was accompanied by the increase of pro-apoptotic proteins Bax, Bad, Bim and Bid, the decrease of anti-apoptotic proteins Bcl-2 and Bcl-xl, the changes of the mitochondrial membrane potential (MMP) and increase of cleaved caspase-9, cleaved caspase-3 and cleaved PARP. Of note, we demonstrated that forskolin induced a decrease of p-C-Raf, p-MEK, p-ERK1/2 and p-p90Rsk, and an increase of p-PERK, p-eIF2α and CHOP, which indicated that the inhibition of Raf/MEK/ERK pathway and activation of PERK/eIF2α/CHOP pathway were involved, at least partially, in forskolin-induced MM.1S cells apoptosis. These findings confirm the anti-MM action of forskolin and extend the understanding of its anti-MM mechanism in MM.1S cells, as well as reinforcing the evidence for forskolin as a natural chemotherapeutic compound against MM.


Subject(s)
Apoptosis , Colforsin , G2 Phase Cell Cycle Checkpoints , Cell Line, Tumor , Colforsin/pharmacology , Cyclin B1/metabolism , Eukaryotic Initiation Factor-2/metabolism , Humans , Mitochondria/metabolism , Mitogen-Activated Protein Kinase Kinases/metabolism
14.
Int Immunopharmacol ; 99: 107914, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34246059

ABSTRACT

OBJECTIVES: Acute respiratory distress syndrome (ARDS) is characterized by an excessive pulmonary inflammatory response. Pyroptosis is a newly form of programmed inflammatory cell death that is triggered by inflammatory caspases. Studies have shown that Luteolin has powerful anti-inflammation effects through activating the function of regulatory T cells (Tregs). The study aimed at investigating the effects of Luteolin on CLP-induced ALI. METHODS: In our study, we employed the mouse cecal ligation and puncture (CLP) model to explore whether Luteolin contributed to alleviated lung injury in vivo. H&E staining and wet/dry (W/D) weight ratios were used to evaluate the severity of lung injury. The serum and BALF of cytokines were assessed by ELISA. The number of neutrophils in the BALF was counted. Immunohistochemistry of IL-10 and MPO in lung tissue was detected. The ROS level in lung was tested by ROS Assay Kit and expression of Gpx4 in lung tissue was detected by qRT-PCR and Western blotting. The regulatory T cells (Treg) population was analyzed in spleen and Peripheral blood mononuclear cells (PBMCs). The levels of caspase-11 protein, caspase-1 protein, GSDMD protein, IL-1α and IL-1ß protein in the lung tissue was evaluated by Western blotting. RESULTS: We found Luteolin significantly inhibits inflammation and attenuated CLP-induced lung injury in vivo, and the levels of, caspase-11, caspase-1, GSDMD, IL-1α and IL-1ß protein in the lungs of CLP mice decreased significantly after pretreatment with Luteolin. Furthermore, the results showed that Luteolin could increase Treg frequencies and IL-10 levels in serum and BALF of CLP mice. It is noteworthy that depleting Tregs reverse Luteolin ameliorated lung injury, and IL-10 neutralizing antibodies treatment aggravated lung pyroptosis. CONCLUSIONS: Our study illustrated that Luteolin contributed to alleviated lung injury, and attenuated caspase-11-dependent pyroptosis in the lung tissue of the CLP-induced ALI mouse model. The mechanisms could be related to regulating the frequency of Tregs and the levels of Treg derived IL-10. Treg cells were show to produce IL-10 and could alleviating caspase-11-dependent lung pyroptosis.


Subject(s)
Acute Lung Injury/drug therapy , Anti-Inflammatory Agents/therapeutic use , Luteolin/therapeutic use , Sepsis/drug therapy , Acute Lung Injury/etiology , Acute Lung Injury/immunology , Acute Lung Injury/pathology , Animals , Anti-Inflammatory Agents/pharmacology , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Caspases, Initiator/immunology , Interleukin-10/immunology , Leukocyte Count , Lung/drug effects , Lung/immunology , Lung/pathology , Luteolin/pharmacology , Male , Mice, Inbred C57BL , Neutrophils/drug effects , Neutrophils/immunology , Pyroptosis/drug effects , Sepsis/complications , Sepsis/immunology , Sepsis/pathology , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology
15.
Drug Des Devel Ther ; 13: 2249-2270, 2019.
Article in English | MEDLINE | ID: mdl-31308634

ABSTRACT

Background: It is reported that various diseases such as non-alcoholic fatty liver disease (NAFLD) are associated with imbalance of microbiome. And FXR has been well investigated in liver diseases. Purpose: The objective of this study was to identify the role of farnesoid X receptor agonist obeticholic acid via targeting gut microbiota in NAFLD. Patients and methods: Male C57BL/6 mice were fed either a normal-chow diet or a high-fat diet (HFD). Obeticholic acid(30mg/(kg·d)) and/or a combination of antibiotics were administered orally by gavage to mice for 12 weeks. Gut microbiota profiles were established through 16S rRNA amplicon sequencing. The effects of obeticholic acid on liver inflammation, the gut barrier, endotoxemia, gut microbiome and composition of the bile acid were also investigated. Results: Obeticholic acid treatment can significantly improve obesity, circulation metabolism disorders, liver inflammation and fibrosis, and intestinal barrier damage caused by HFD. Removal of normal commensal bacteria can weaken the effect of obeticholic acid. The gut microbial structure was changed, and abundance of Blautia was increased significantly after treated with obeticholic acid. After obeticholic acid treatment, the concentration of taurine-bound bile acid caused by HFD was reduced in the liver. Conclusion: Taken together, these data suggest that obeticholic acid has aprotective effect on NAFLD via changing the components of gut microbiota, specifically increasing the abundance of Blautia.


Subject(s)
Chenodeoxycholic Acid/analogs & derivatives , Gastrointestinal Microbiome/drug effects , Non-alcoholic Fatty Liver Disease/prevention & control , Protective Agents/pharmacology , Receptors, Cytoplasmic and Nuclear/agonists , Animals , Bile Acids and Salts/antagonists & inhibitors , Bile Acids and Salts/biosynthesis , Chenodeoxycholic Acid/chemistry , Chenodeoxycholic Acid/pharmacology , Male , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/microbiology , Protective Agents/chemistry
16.
BMC Cancer ; 18(1): 415, 2018 04 13.
Article in English | MEDLINE | ID: mdl-29653559

ABSTRACT

BACKGROUND: Many novel diagnostic biomarkers have been developed for gastric cancer (GC) recently. We chose two methods with high diagnostic value, the detection of serum microRNAs and metabolomics based on gas chromatography/mass spectrometry (GC/MS), and aimed to establish appropriate models. METHODS: We reviewed the diagnostic accuracies of all microRNAs identified by previous diagnostic tests. Then appropriate microRNAs and their combinations were validated the diagnostic value. We included 80 patients with GC and 82 healthy controls (HCs) and detected the expression of the microRNAs. GC/MS analysis was conducted, and we used three multivariate statistical analyses to establish diagnostic models. The concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were detected for comparison with the novel models. RESULTS: Sixty-seven published studies and 70 microRNAs were finally included in the systematic review. MiR-18a, miR-19a, miR-21, miR-92a, miR-199a and miR-421 were chosen to further validate their diagnostic efficiencies. Five of those microRNAs in GC patients had significantly different expression. The combination of miR-19a and miR-92a had the highest area under the curve (AUC) at 0.850 with a sensitivity of 91.3% and a specificity of 61.0%. The GC/MS analysis performed an excellent diagnostic value and the AUC reached 1.0. CONCLUSION: There is a good potential for microRNAs and GC/MS analysis as new diagnostic methods in view of their high diagnostic value compared with traditional biomarkers.


Subject(s)
Biomarkers, Tumor , Circulating MicroRNA , Metabolomics , MicroRNAs/genetics , Stomach Neoplasms/diagnosis , Stomach Neoplasms/genetics , Case-Control Studies , Circulating MicroRNA/blood , Female , Gas Chromatography-Mass Spectrometry , Gene Expression , Humans , Male , Metabolomics/methods , MicroRNAs/blood , Neoplasm Grading , Neoplasm Staging , Publication Bias , Sensitivity and Specificity , Stomach Neoplasms/blood
17.
Article in English | MEDLINE | ID: mdl-29333184

ABSTRACT

OBJECTIVES: To evaluate the efficacy and safety of Bushen Huoxue prescription (BSHXP) for endometriosis. METHODS: A meta-analysis was performed, and studies were searched from the seven databases from the date of database establishment to April 30, 2017. Randomized controlled trials (RCTs) that explored the efficacy and safety of BSHXP for patients with endometriosis were included. Two assessors independently reviewed each trial. The Cochrane Risk of Bias assessment tool was used for quality assessment. RESULTS: In the 13 included studies, the total effectiveness rates of BSHXP were higher than those of Western medicine (RR, 1.55; 95% CI, 1.03-2.32; P = 0.04), but the dysmenorrhea alleviation rates of the two treatments did not significantly differ (RR, 1.28; 95% CI, 0.70-2.34; P = 0.42). The pregnancy rates of BSHXP were also higher than those of hormone therapy (RR, 1.99; 95% CI, 1.17-3.39; P = 0.01). However, whether BSHXP is more effective than Western medicine in diminishing endometriotic cyst remains unknown. CONCLUSIONS: Our study provides evidence that BSHXP is effective and safe for endometriosis, but this evidence is inconclusive because of the low methodological quality of the included RCTs. Our findings suggest that BSHXP is an alternative drug for endometriosis, but it should be further examined in future clinical research.

18.
J Biomed Sci ; 23(1): 71, 2016 Oct 12.
Article in English | MEDLINE | ID: mdl-27733149

ABSTRACT

BACKGROUND: The mechanism of Nova1's role in hepatocellular carcinoma has not been delineated. Also its interaction with GABAA receptor γ2 in HCC is unveiled. This study is aimed to make it clear the distribution, prognostic value of GABAARγ2 in human hepatocellular carcinoma. And its role in HCC tumorigenesis under the regulation of its alternative splicing factor Nova1. METHODS: Immunohistochemistry staining was used to investigate the distribution and clinical significance of GABAARγ2 protein expression in hepatocellular carcinoma. In vivo tumorigenticity test was conducted in nude mice by regulation the expression of Nova1. Later, western blot and co-immunoprecipitation were carried out to verify the interaction between Nova1 and GABAARγ2 in HCC tissue. RESULTS: Immunohistochemical staining showed GABAARγ2 expression in HCC. Survival analysis showed intratumoral GABAARγ2 was an independent prognostic factor for overall survival (OS) and disease free survival (DFS). Up-regulation of Nova1 expression promotes subcutaneous HCC growth in nude mice and western blot showed the ectopic expression of Nova-1 restro-regulates the expression of GABAARγ2 and GABA. Protein level interaction of GABAARγ2 and Nova-1 was evidenced by co-immunoprecipitation. CONCLUSIONS: Nova1 interacts with GABAARγ2 not only in CNS but also in HCC. Nova1's potential mechanism as an oncogene may due to its interaction with GABAA Rγ2. A better understanding of the mechanism of Nova1 for HCC progression provides a novel target for an optimal immunotherapy against this fatal malignancy.


Subject(s)
Carcinogenesis , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , Oncogenes , RNA-Binding Proteins/genetics , Receptors, GABA-A/genetics , Animals , Carcinoma, Hepatocellular/diagnosis , Cell Line, Tumor , Humans , Liver Neoplasms/diagnosis , Mice , Mice, Inbred BALB C , Mice, Nude , Neuro-Oncological Ventral Antigen , Organ Specificity , Prognosis , RNA-Binding Proteins/metabolism , Receptors, GABA-A/metabolism
19.
World J Gastroenterol ; 21(7): 2229-35, 2015 Feb 21.
Article in English | MEDLINE | ID: mdl-25717263

ABSTRACT

Intrahepatic arterioportal fistula (IAPF) can be caused by many secondary factors. We report four cases of portal hypertension that were eventually determined to be caused by congenital hepatic arterioportal fistula. The clinical manifestations included ascites, variceal hemorrhage and hepatic encephalopathy. Computed tomography scans from all of the patients revealed the early enhancement of the portal branches in the hepatic arterial phase. All patients were diagnosed using digital subtraction angiography (DSA). DSA before embolization revealed an arteriovenous fistula with immediate filling of the portal venous radicles. All four patients were treated with interventional embolization. The four patients remained in good condition throughout follow-up and at the time of publication. IAPF is frequently misdiagnosed due to its rarity; therefore, clinicians should consider IAPF as a potential cause of non-cirrhotic portal hypertension.


Subject(s)
Arteriovenous Fistula/complications , Hepatic Artery/abnormalities , Hypertension, Portal/etiology , Portal Vein/abnormalities , Adult , Aged , Aged, 80 and over , Angiography, Digital Subtraction , Arteriovenous Fistula/diagnosis , Arteriovenous Fistula/therapy , Embolization, Therapeutic , Female , Hepatic Artery/diagnostic imaging , Humans , Hypertension, Portal/diagnosis , Hypertension, Portal/physiopathology , Hypertension, Portal/therapy , Male , Phlebography/methods , Portal Pressure , Portal Vein/diagnostic imaging , Portal Vein/physiopathology , Tomography, X-Ray Computed , Treatment Outcome
20.
Chin J Integr Med ; 21(9): 697-702, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25579196

ABSTRACT

OBJECTIVE: To evaluate the effects of wrist-ankle acupuncture combined with ginger moxibustion against gastrointestinal tract reactions (nausea, vomiting, and constipation) to chemotherapy in cancer patients. METHODS: A total of 60 patients with gynecological tumors treated by chemotherapy were randomly divided into two groups. The treatment group (30 cases) underwent wrist-ankle acupuncture and ginger moxibustion, whereas tropisetron hydrochloride and dexamethasone were intravenously administered to the control group (30 cases) during chemotherapy. RESULTS: The frequency of nausea in the treatment group was significantly less than that of the control group from the 2nd to the 5th day of chemotherapy (P<0.01). The anti-emetic effect in the treatment group was significantly better than that in the control group on the 3rd day of therapy (P<0.05). The incidence rate of constipation was significantly lower in the treatment group than that in the control group (P<0.01). Furthermore, the cost of therapy for the treatment group was significantly lower than that of the control group (P<0.01). Only 1 patient manifested a post-acupuncture side effect in the form of subcutaneous blood stasis. CONCLUSION: Wrist-ankle acupuncture combined with ginger moxibustion could prevent gastrointestinal tract reactions to chemotherapy in cancer patients. In addition, the proposed method had fewer side effects, lower cost, and less risk.


Subject(s)
Acupuncture Therapy , Ankle/physiology , Antineoplastic Agents/adverse effects , Gastrointestinal Diseases/prevention & control , Moxibustion , Wrist/physiology , Zingiber officinale/chemistry , Acupuncture Therapy/adverse effects , Constipation/etiology , Constipation/therapy , Female , Gastrointestinal Diseases/chemically induced , Humans , Male , Middle Aged , Moxibustion/adverse effects , Nausea/chemically induced , Nausea/therapy , Vomiting/etiology , Vomiting/therapy
SELECTION OF CITATIONS
SEARCH DETAIL
...