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1.
Clin Res Hepatol Gastroenterol ; 45(4): 101529, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33268035

ABSTRACT

BACKGROUND AND AIM: Achalasia patients usually present lower esophageal sphincter thickening, which can impact the expansibility of cardia. We aimed to investigate the effect of cardiac muscularis propria (MP) on perioperative adverse events (AEs) and treatment outcomes of patients treated with peroral endoscopic myotomy (POEM). METHODS: We retrospectively reviewed 114 patients with achalasia undergoing pre-POEM endoscopic ultrasonography (EUS) between May 2013 and November 2019. Cardiac MP thickness was measured using EUS. POEM failure was defined as Eckardt score >3. Risk factors for perioperative AEs and POEM failure were identified. RESULTS: Patients were divided into the thin (n = 52) and the thick group (n = 62) based on the median of cardiac MP thickness (3.0 mm). Perioperative AEs rate of the thin group seemed to be slightly higher than that of the thick group (11.5% vs. 4.8%, P = 0.30). During a median follow-up of 30 months (range 1-77), 100 patients completed follow-up, 16 (16%) of which occurred clinical failure. The clinical outcomes of patients in the thin group were significantly poorer than those patients in the thick group (P = 0.006). Cardiac MP thickness was an independent risk factor for POEM failure (hazard ratio 3.9, P = 0.02; Cox regression), but not the risk factor for perioperative AEs (odds ratio 2.6, P = 0.2; logistic regression). CONCLUSION: Cardiac MP thickness could be a novel predictive factor for POEM failure in patients with achalasia.


Subject(s)
Esophageal Achalasia , Myotomy , Natural Orifice Endoscopic Surgery , Esophageal Achalasia/surgery , Esophageal Sphincter, Lower , Humans , Retrospective Studies
2.
Sci Rep ; 6: 36436, 2016 11 07.
Article in English | MEDLINE | ID: mdl-27819314

ABSTRACT

IL-22 ameliorates liver fibrosis by inhibiting hepatic stellate cells (HSC), and loss of miR-200a is associated with the development of liver fibrosis. The study aimed to investigate the interplay between IL-22 and miR-200a in regulating liver fibrosis in vivo and in vitro. We observed that IL-22 significantly reduced the proliferation of HSC and increased the expression of p-STAT3. ß-catenin was identified as a target gene of miR-200a by luciferase reporter assay, and upregulation of miR-200a significantly attenuated the proliferation of HSC and reduced ß-catenin expression. IL-22 treatment increased expression of miR-200a and decreased expression of ß-catenin in HSC. The expression of p-STAT3 and miR-200a was elevated while ß-catenin was decreased in fibrotic rat liver after IL-22 treatment. Expression levels of ß-catenin and p-STAT3 were inversely correlated in fibrotic rat liver and HSC. Upregulation of ß-catenin suppressed expression of p-STAT3 in HSC. We concluded that IL-22 inhibits HSC activation and ameliorates liver fibrosis through enhancing expression of miR-200a and reducing expression of ß-catenin, suggesting there may be a crosstalk between IL-22/STAT3 and ß-catenin pathway.


Subject(s)
Armadillo Domain Proteins/metabolism , Interleukins/therapeutic use , Liver Cirrhosis/prevention & control , MicroRNAs/metabolism , Nerve Tissue Proteins/metabolism , Actins/analysis , Animals , Antagomirs/metabolism , Apoptosis/drug effects , Armadillo Domain Proteins/antagonists & inhibitors , Armadillo Domain Proteins/genetics , Cell Line , Cell Proliferation/drug effects , Collagen Type I/analysis , Hepatic Stellate Cells/cytology , Hepatic Stellate Cells/metabolism , Interleukins/genetics , Interleukins/metabolism , Interleukins/pharmacology , Liver Cirrhosis/pathology , Male , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , Nerve Tissue Proteins/antagonists & inhibitors , Nerve Tissue Proteins/genetics , Rats , Rats, Sprague-Dawley , Recombinant Proteins/biosynthesis , Recombinant Proteins/isolation & purification , Recombinant Proteins/pharmacology , Recombinant Proteins/therapeutic use , STAT3 Transcription Factor/metabolism , Sequence Alignment , Transforming Growth Factor beta1/pharmacology , Up-Regulation/drug effects , Interleukin-22
3.
Sci Rep ; 6: 18694, 2016 Jan 05.
Article in English | MEDLINE | ID: mdl-26728971

ABSTRACT

T helper 9 (Th9) cells, a recently recognized Th cell subset, are involved in autoimmune diseases. We aimed to investigate the role of Th9/interleukin-9 (IL-9) in the pathogenesis of hepatic fibrosis. Th9 and Th17 cells were quantified in chronic hepatitis B (CHB) patients with hepatic fibrosis, HBV-associated liver cirrhosis (LC) patients and healthy controls (HC). The percentages of Th9 and Th17 cells, concentrations of IL-9 and IL-17, as well as expression of IL-17, TNF-α, IL-6, IL-4, IL-21, TGF-ß1 and IFN-γ were significantly increased in plasma of CHB and LC patients compared with those in HC. Splenic Th9 and Th17 cells, plasma concentrations and liver expression of IL-9 and IL-17A were significantly elevated in mice with hepatic fibrosis compared with controls. Neutralization of IL-9 in mice ameliorated hepatic fibrosis, attenuated the activation of hepatic stellate cells, reduced frequencies of Th9, Th17 and Th1 cells in spleen, and suppressed expression of IL-9, IL-17A, IFN-γ, TGF-ß1, IL-6, IL-4 and TNF-α in plasma and liver respectively. Our data suggest a deleterious role of Th9/IL-9 in increasing hepatic fibrosis and exacerbating disease endpoints, indicating that Th9/IL9 based immunotherapy may be a promising approach for treating hepatic fibrosis.


Subject(s)
Interleukin-9/metabolism , Liver Cirrhosis/etiology , Liver Cirrhosis/metabolism , T-Lymphocyte Subsets , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Helper-Inducer/metabolism , Adolescent , Adult , Aged , Animals , Antibodies, Monoclonal/pharmacology , Antibodies, Neutralizing/pharmacology , Case-Control Studies , Cytokines/metabolism , Disease Models, Animal , Female , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/metabolism , Humans , Immunophenotyping , Interleukin-17/antagonists & inhibitors , Interleukin-17/blood , Interleukin-17/genetics , Interleukin-17/metabolism , Interleukin-9/antagonists & inhibitors , Interleukin-9/blood , Interleukin-9/genetics , Liver Cirrhosis/pathology , Lymphocyte Count , Male , Mice , Middle Aged , RNA, Messenger/genetics , Spleen/immunology , Spleen/metabolism , Spleen/pathology , Th17 Cells/immunology , Th17 Cells/metabolism , Young Adult
4.
World J Gastroenterol ; 21(5): 1531-45, 2015 Feb 07.
Article in English | MEDLINE | ID: mdl-25663772

ABSTRACT

AIM: To investigate the effect of interleukin (IL)-22 on hepatic fibrosis in mice and the possible mechanism involved. METHODS: Liver fibrosis was induced in male BALB/c mice by CCl4. Recombinant IL-22 (rmIL-22) was administered intraperitoneally in CCl4-treated mice. Fibrosis was assessed by histology and Masson staining. The activation of hepatic stellate cells (HSCs) was investigated by analysis of α-smooth muscle actin expression. The frequencies of T helper (Th) 22 cells, Th17 cells and Th1 cells, the expression of inflammatory cytokines [IL-22, IL-17A, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-6, IL-1ß] and transcription factors [aryl hydrocarbon receptor (AHR), RAR-related orphan receptor (RORγt), T-bet] mRNA in the liver were investigated. In addition, the plasma levels of IL-22, IL-17A, IFN-γ, TNF-α, IL-6 and IL-1ß were evaluated. RESULTS: Significant elevations in circulating Th22 cells, Th17 cells, Th1 cells, IL-22, IL-17A, and IFN-γ were observed in the hepatic fibrosis group compared with the control group (P < 0.01). Treatment with rmIL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis, which was confirmed by lower hepatic fibrosis pathological scores (P < 0.01). RmIL-22 decreased the frequencies of Th22 cells (6.71% ± 0.97% vs 8.09% ± 0.74%, P < 0.01), Th17 cells (4.34% ± 0.37% vs 5.71% ± 0.24%, P < 0.01), Th1 cells (3.09% ± 0.49% vs 4.91% ± 0.73%, P < 0.01), and the levels of IL-22 (56.23 ± 3.08 vs 70.29 ± 3.01, P < 0.01), IL-17A (30.74 ± 2.77 vs 45.68 ± 2.71, P < 0.01), and IFN-γ (74.78 ± 2.61 vs 124.89 ± 2.82, P < 0.01). Down-regulation of IL-22, IL-17A, IFN-γ, TNF-α, IL-6, IL-1ß, AHR RORγt, and T-bet gene expression in the liver was observed in the rmIL-22 group (P < 0.01). CONCLUSION: The frequencies of Th22, Th17 and Th1 cells are elevated in hepatic fibrosis. RmIL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines, thereby ameliorating liver fibrogenesis.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Cytokines/metabolism , Hepatic Stellate Cells/drug effects , Inflammation Mediators/metabolism , Interleukins/pharmacology , Liver Cirrhosis, Experimental/prevention & control , Liver/drug effects , Animals , Carbon Tetrachloride , Cytokines/genetics , Cytokines/immunology , Hepatic Stellate Cells/immunology , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/pathology , Inflammation Mediators/immunology , Liver/immunology , Liver/metabolism , Liver/pathology , Liver Cirrhosis, Experimental/chemically induced , Liver Cirrhosis, Experimental/genetics , Liver Cirrhosis, Experimental/immunology , Liver Cirrhosis, Experimental/metabolism , Liver Cirrhosis, Experimental/pathology , Male , Mice, Inbred BALB C , RNA, Messenger/metabolism , Recombinant Proteins/pharmacology , Severity of Illness Index , Signal Transduction/drug effects , Th1 Cells/drug effects , Th1 Cells/immunology , Th1 Cells/metabolism , Th17 Cells/drug effects , Th17 Cells/immunology , Th17 Cells/metabolism , Time Factors , Interleukin-22
5.
World J Gastroenterol ; 19(48): 9472-80, 2013 Dec 28.
Article in English | MEDLINE | ID: mdl-24409078

ABSTRACT

AIM: To clarify the current understanding of the association between interleukin-10 (IL-10) polymorphisms and the risk of irritable bowel syndrome (IBS). METHODS: We searched for studies in any language recorded in PubMed, Embase and Cochrane library before August 2013. The associations under allele contrast model, codominant model, dominant model, and recessive model were analyzed. The strengths of the association between IL-10 polymorphisms and IBS risk were estimated using odds ratios (OR) with 95% confidence interval (CI). Fixed effects model was used to pool the result if the test of heterogeneity was not significant, otherwise the random-effect model was selected. RESULTS: Eight case-control studies analyzing three single-nucleotide polymorphisms rs1800870 (-1082 A/G), rs1800871 (-819C/T), and rs1800872 (-592A/C) of the IL-10 gene, which involved 928 cases and 1363 controls, were eligible for our analysis. The results showed that rs1800870 polymorphisms were associated with a decreased risk of IBS (GG+GA vs AA: OR = 0.80, 95%CI: 0.66-0.96), (AA+GA vs GG: OR = 0.68, 95%CI: 0.52-0.90). Subgroup analysis revealed such association only existed in Caucasian ethnicity (AA+GA vs GG, OR = 0.70, 95%CI: 0.55-0.89). The rs1800872 polymorphisms were associated with an increased risk of IBS in Asian ethnicity (CC vs GG: OR = 1.29, 95%CI: 1.01-1.16). There were no associations between rs1800871 polymorphisms and the IBS risk. CONCLUSION: The results suggest that IL-10 rs1800870 confers susceptibility to the risk of IBS in Caucasian ethnicity, and the rs1800872 may associate with IBS risk in Asians. However, no significant associations are found between rs1800871 and IBS risk.


Subject(s)
Interleukin-10/genetics , Irritable Bowel Syndrome/genetics , Polymorphism, Single Nucleotide , Asian People/genetics , Genetic Predisposition to Disease , Humans , Irritable Bowel Syndrome/ethnology , Irritable Bowel Syndrome/immunology , Odds Ratio , Phenotype , Risk Factors , White People/genetics
6.
Zhonghua Yi Xue Za Zhi ; 91(23): 1613-6, 2011 Jun 21.
Article in Chinese | MEDLINE | ID: mdl-21914394

ABSTRACT

OBJECTIVE: To evaluate the effects of PRL-3 siRNA (small interfering RNA) on the migration of endometriotic stromal cells. METHODS: Primary endometriotic stromal cells were cultured in vitro. Then PRL-3 (phosphatase of regenerating liver-3) siRNA was transfected to silence the PRL-3 gene. And the PRL-3 protein expression was analyzed by Western blot. The changes of cell migration were detected by cell pseudopod formation, scratch test and transwell cell migration test. RESULTS: The expression of PRL-3 protein significantly decreased in the experimental group versus two other control groups (P < 0.05). The formation of cell pseudopod was much less in experimental group than that in control groups. Within the same time, the number of migration cells was 0.87 ± 0.21 in experimental group. It was less than 1.75 ± 0.28 in blank control group and 1.63 ± 0.39 in negative control group (P < 0.05). CONCLUSION: PRL-3 siRNA can down-regulate the PRL-3 gene and decrease the migratory capacity of endometriotic stromal cells. And PRL-3 may be a promising target in the therapeutics of endometriosis.


Subject(s)
Endometrium/cytology , Neoplasm Proteins/genetics , Protein Tyrosine Phosphatases/genetics , RNA, Small Interfering/genetics , Stromal Cells/metabolism , Adult , Cell Movement , Cells, Cultured , Endometriosis/genetics , Endometriosis/metabolism , Endometrium/metabolism , Female , Humans , Middle Aged , Stromal Cells/cytology , Transfection , Young Adult
7.
Zhonghua Yi Xue Za Zhi ; 88(15): 1032-5, 2008 Apr 15.
Article in Chinese | MEDLINE | ID: mdl-18754435

ABSTRACT

OBJECTIVE: To evaluate the association between the susceptibility of endometriosis (EMS) and the gene polymorphism of tumor necrosis factor (TNF) in Chinese Han population. METHODS: Peripheral blood samples were collected from 76 EMS patients and 87 normal controls. PCR-RFLP was used to detect the single base change polymorphism in both TNFalpha gene and TNFbeta gene. RESULTS: The allele frequencies of the TNFalpha polymorphism were 0.9474 and 0.9253 in the EMS patients and the control group respectively, and the TNFbeta polymorphism were 0.0526 and 0.0747 respectively. The allele frequencies of the TNFbeta1 polymorphism were 0.4605 and 0.5115 in the EMS patients and the control group, and the TNFbeta2 polymorphism were 0.5395 and 0.4885. No difference in the gene and genotype frequencies of TNFalpha and TNFbeta was noted in the EMS patients and normal controls (all P > 0.05). CONCLUSION: TNF gene polymorphism has no effect on EMS in Chinese Han population. Ethnic difference may exist in TNF allele frequency.


Subject(s)
Endometriosis/genetics , Polymorphism, Genetic , Tumor Necrosis Factor-alpha/genetics , Adult , Alleles , Asian People/genetics , China , Endometriosis/ethnology , Endometriosis/pathology , Female , Gene Frequency , Genotype , Humans , Middle Aged , Young Adult
8.
Zhonghua Yi Xue Za Zhi ; 86(45): 3190-2, 2006 Dec 05.
Article in Chinese | MEDLINE | ID: mdl-17313784

ABSTRACT

OBJECTIVE: To investigate the changes and of serum cardiotrophin I (cTN I) and cystatin C in preeclampsia clinical significance thereof. METHODS: Peripheral blood samples were collected from 40 women with preeclampsia, aged 29 (18 - 39), with the medium gestational age of 35 weeks, and 40 age- and gestational age-matched controls. Serum cTN I and cystatin C were determined with ELISA and serum levels of creatinine kinase, creatinine, and uric acid were assayed by automatic biochemical analyzer. Comparison was made between the 2 groups. RESULTS: The serum cTn I of the preeclampsia group was 0.59 microg/L +/- 0.42 microg/L, significantly higher than that of the control group (0.09 microg/L +/- 0.22 microg/L P < 0.001), and the serum cystatin C of the preeclampsia group was 1.64 mg/L +/- 0.47 mg/L, significantly higher than that of the control group (1.08 mg/L +/- 0.19 mg/L, P < 0.001). And the serum cardiotrophin I and cystatin C concentrations of the patients with severe preeclampsia were 0.66 microg/L +/- 0.40 microg/L and 1.72 mg/L +/- 0.46 mg/L respectively, both significantly higher than those of the patients with mild preeclampsia (0.17 microg/L +/- 0.26 microg/L and 1.21 mg/L +/- 0.37 mg/L respectively, P < 0.001 and 0.05 respectively). CONCLUSION: Serum cTn I and cystatin C levels are elevated in preeclampsia and the elevation is associated with the severity of preeclampsia, suggesting that serum concentrations of cTn I and cystatin C are useful markers in the early diagnosis of cardiac and renal injury in patients of preeclampsia.


Subject(s)
Cystatins/blood , Pre-Eclampsia/blood , Troponin I/blood , Adolescent , Adult , Analysis of Variance , Case-Control Studies , Creatine/blood , Creatine Kinase/blood , Cystatin C , Female , Humans , Pregnancy , Pregnancy Trimester, Third/blood , Uric Acid/blood
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