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1.
BMC Gastroenterol ; 23(1): 245, 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37464298

RESUMO

AIM: To analyze the efficacy and safety of Bifidobacterium quadruple viable tablets combined with mosapride citrate for the treatment of constipation. METHODS: A systematic review was performed on studies published until July 2022 in PubMed, Embase, China National Knowledge Infrastructure, and Wanfang. The efficacy rate, adverse reaction rate, recurrence rate, and clinical symptoms were included in the measured outcomes. RESULTS: The efficacy of Bifidobacterium quadruple viable tablets combined with mosapride citrate in the treatment of constipation was higher than that of mosapride citrate alone (OR = 4.75, 95% CI (3.27, 6.90), Z = 8.19, P < 0.001; I2 = 0.0%, P = 0.645). There was no significant difference in the incidence of adverse reactions between the two groups (OR = 0.97, 95% CI (0.61,1.57), Z = 0.11, P = 0.911; I2 = 0.0%, P = 0.958). The recurrence rate of constipation in patients receiving the combination treatment was lower than that of patients treated with mosapride citrate alone (OR = 0.48, 95%CI (0.31, 0.73), Z = 3.38, P = 0.001; I2 = 29.8%, P = 0.200). CONCLUSIONS: Bifidobacterium quadruple viable tablets combined with mosapride citrate demonstrated efficacy and safety in treating constipation. Probiotics have the potential to positively influence gut health and microbial profiles in patients with functional constipation.


Assuntos
Bifidobacterium , Constipação Intestinal , Humanos , Constipação Intestinal/induzido quimicamente , Benzamidas/uso terapêutico , Comprimidos/uso terapêutico
2.
J Gastroenterol Hepatol ; 38(7): 1072-1082, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36869260

RESUMO

Irritable bowel syndrome (IBS) is a relatively common functional gastrointestinal disease with a disturbance of intestinal bacteria. Bile acids, gut microbiota, and the host have close and complex interactions, which play a central role in modulating host immune and metabolic homeostasis. Recent studies suggested that the bile acid-gut microbiota axis played a key role in the development of IBS patients. In order to investigate the role of bile acids in the pathogenesis of IBS and present potentially relevant clinical implications, we conducted a literature search on intestinal interactions between bile acid and gut microbiota. The intestinal crosstalk between bile acids and gut microbiota shapes the compositional and functional alterations in IBS, manifesting as gut microbial dysbiosis, disturbed bile acid pathway, and alteration of the microbial metabolites. Collaboratively, bile acid conducts the pathogenesis of IBS through the alterations of the farnesoid-X receptor and G protein-coupled receptor. Diagnostic markers and treatments targeting the bile acids and its receptor showed promising potential in the management of IBS. Bile acids and gut microbiota play a key role in the development of IBS and make attractive biomarkers for treatments. Individualized therapy aiming at bile acids and its receptor may provide significant diagnostic and requires further investigation.


Assuntos
Gastroenteropatias , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Microbiota , Humanos , Síndrome do Intestino Irritável/microbiologia , Ácidos e Sais Biliares
3.
World J Surg Oncol ; 20(1): 205, 2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35710558

RESUMO

BACKGROUND: Testicular tumor is one of the common solid tumors in young men. Testicular choriocarcinoma is a non-spermatogonial germ cell tumor, which is the rarest of all testicular cancers. Choriocarcinoma usually shows bleeding at the metastatic site, while gastrointestinal involvement is rare. METHODS: Here, we report a case of testicular choriocarcinoma with gastrointestinal bleeding as the first diagnosis and summarize the similar cases all over the world in recent 20 years. RESULTS: A 28-year-old male was treated with repeated melena for 2 months. No bleeding foci of the stomach, duodenum, colon, and rectum were found in endoscopy, and no bleeding foci of digestive tract was found in selective angiography, but a space occupying lesions of the lung, liver, and upper jejunum were found in chest and abdominal CT. Considering the possibility of a metastatic tumor and the ineffectiveness of medical treatment, the patient was converted to surgical treatment. The postoperative pathology was consistent with testicular choriocarcinoma. The patient received a chemotherapy regimen of paclitaxel, ifosfamide, and cisplatin. At present, the chemotherapy regimen is well tolerated. CONCLUSIONS: The case report confirmed that even if we cannot find the logical relationship between clinical manifestations and genital examination, genital examination should also be part of the patient's systematic examination.


Assuntos
Coriocarcinoma , Neoplasias Embrionárias de Células Germinativas , Segunda Neoplasia Primária , Neoplasias Testiculares , Coriocarcinoma/complicações , Coriocarcinoma/diagnóstico , Coriocarcinoma/cirurgia , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/complicações , Segunda Neoplasia Primária/complicações , Neoplasias Testiculares/complicações , Neoplasias Testiculares/patologia
4.
BMC Gastroenterol ; 21(1): 14, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407171

RESUMO

BACKGROUND: Short-chain fatty acids (SCFAs) and serotonin (5-hydroxytryptamine, 5-HT) may be associated with the pathogenesis of irritable bowel syndrome (IBS). There are some reports of alterations in SCFAs and 5-HT in IBS, but their results are inconsistent. We aimed to perform a meta-analysis to assess alterations in SCFAs and 5-HT in IBS patients and their potential role in the abnormal brain-gut-microbiota (BGM) axis. METHODS: Case-control studies detecting SCFAs and 5-HT in IBS patients were identified from PubMed, Web of Science, Cochrane Library, and Scopus databases to identify relevant articles up to September 2018. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) of SCFAs and 5-HT were calculated by REVIEW MANAGER 5.3 to evaluate the alterations of 5-HT and SCFAs in IBS. RESULTS: Five studies on SCFAs and 5 on 5-HT in IBS patients were included. As compared to healthy controls (HCs), the SMDs of 5-HT in IBS patients was 2.35 (95% CI 0.46-4.24) and the SMDs of total SCFAs, acetic acid, propionic acid, and butyric acid in IBS patients were - 0.01 (95% CI - 0.57-0.55), - 0.04 (95% CI - 0.55-0.47), 0.07 (95% CI - 0.45-0.60), and - 0.00 (95% CI - 0.49-0.49), respectively. CONCLUSIONS: There was an increase in 5-HT in blood of IBS patients, indicating the increased 5-HT in blood may be involved in IBS pathogenesis. However, there were no significant differences in SCFAs in feces between IBS patients and HCs. But the study did not differentiate between subgroups of IBS. These findings might provide insight for future studies of the BGM axis in the pathogenesis of IBS. Mei Luo and Xiaojun Zhuang contributed equally to the writing of this article.


Assuntos
Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Ácidos Graxos , Ácidos Graxos Voláteis , Humanos , Serotonina
5.
BMC Gastroenterol ; 20(1): 187, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32532214

RESUMO

BACKGROUND: Gut microbiota alterations including small intestinal bacterial overgrowth (SIBO) might play a role in pathogenesis of irritable bowel syndrome (IBS). Rifaximin could effectively and safely improve IBS symptoms. The aim of this study was to investigate the effect of rifaximin on Gastrointestinal (GI) symptoms, quality of life (QOL) and SIBO eradication in Chinese IBS-D patients. METHODS: This study included 78 IBS-D patients defined by the Rome IV criteria. Patients received 400 mg rifaximin twice daily for 2 weeks and 10-week follow-up. GI symptoms were assessed at week 0, 2, 4, 8 and 12. QOL and lactulose hydrogen breath test (LHBT) results were estimated at week 0 and 4. RESULTS: All participants showed significant improvements in GI symptom subdomains after rifaximin treatment (all P < 0.05), which could maintain at least 10 weeks of follow-up. Additionally, QOL scores were increased with concomitant improvement of clinical symptoms (all P < 0.05). The 45 rifaximin-responsive patients (57.7%) achieved significantly greater GI-symptom improvement than non-responders (all P < 0.05). No GI symptoms were associated with SIBO (all P > 0.05). SIBO normalization after rifaximin treatment measured by LHBT was found in 44.4% (20/45) of patients with SIBO before treatment. CONCLUSION: A short course (2 weeks) of rifaximin improved GI symptoms and QOL in Chinese IBS-D patients whether they had SIBO or not. However, the efficacy of rifaximin could not be explained by the successful eradication of SIBO. Further studies on the therapeutic mechanisms of rifaximin in IBS are urgently needed.


Assuntos
Síndrome da Alça Cega/tratamento farmacológico , Diarreia/tratamento farmacológico , Fármacos Gastrointestinais/administração & dosagem , Síndrome do Intestino Irritável/tratamento farmacológico , Rifaximina/administração & dosagem , Adulto , Síndrome da Alça Cega/complicações , Síndrome da Alça Cega/microbiologia , Testes Respiratórios/métodos , China , Diarreia/complicações , Diarreia/microbiologia , Esquema de Medicação , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/microbiologia , Lactulose/análise , Masculino , Qualidade de Vida , Resultado do Tratamento
6.
BMC Gastroenterol ; 20(1): 73, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32178625

RESUMO

BACKGROUND: Short-chain fatty acids (SCFAs) alteration have been reported in irritable bowel syndrome (IBS), but the results are conflicting. Our study aims to explore the alteration of SCFAs in patients with diarrhea-predominant IBS (IBS-D) and their potential role in the occurrence and development of IBS. METHODS: We recruited patients with IBS-D defined by Rome IV criteria and age-and-gender matched healthy controls (HCs). A headspace solid-phase microextraction gas chromatography-mass spectrometric (HS-SPME-GC-MS) method was developed for the analysis of acetic, propionic and butyric acid in feces and serum. RESULTS: Compared with HCs, the levels of the serum propionate (2.957 ± 0.157 vs 2.843 ± 0.098 mmol/L, P = 0.012) and butyrate (2.798 ± 0.126 vs 2.697 ± 0.077 mmol/L, P = 0.012) were significantly higher in IBS-D group. No significant differences were found among two groups with regard to the concentration of fecal acetate (4.953 ± 1.065 vs 4.774 ± 1.465 mg/g, P = 0.679), propionate (6.342 ± 1.005 vs 6.282 ± 1.077 mg/g, P = 0.868) and butyrate (2.984 ± 0.512 vs 3.071 ± 0.447 mg/g, P = 0.607). CONCLUSIONS: Metabolites of gut microbiota, the propionic and butyric acid, are increased in patients with IBS-D in serum but not in feces. It suggests that propionic and butyric acid might be associated with the occurrence and development of IBS.


Assuntos
Ácido Butírico/análise , Diarreia/etiologia , Síndrome do Intestino Irritável/complicações , Propionatos/análise , Acetatos/análise , Adulto , Biomarcadores/análise , Estudos de Casos e Controles , Fezes/química , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
J Gastroenterol Hepatol ; 34(8): 1344-1350, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30681185

RESUMO

BACKGROUND AND AIM: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a major cause of gastric mucosal lesions. In China, teprenone is frequently prescribed as a mucoprotective agent, but the literature regarding their efficacy is limited. Our purpose was to address the effects of teprenone on long-term NSAID-associated gastric mucosal lesions. METHODS: This study examined 369 patients taking NSAIDs for at least 12 weeks. Patients without gastroduodenal ulcer and without Helicobacter pylori infection on endoscopy at baseline were randomized to receive either NSAID plus teprenone (150 mg/day) or NSAID only for 12 weeks. Lanza scores were examined using endoscopy before and after treatment, and dyspeptic symptom scores are also analyzed. RESULTS: A total of 158 patients were randomized to the teprenone group (n = 74) or the control group (n = 84) for 12 weeks. Seventy-one of patients in the teprenone group and 79 of patients in the control group were analyzed finally. After treatment, the Lanza scores and dyspeptic symptom scores decreased significantly in the teprenone group while increased in the control group (P < 0.05). The changes of Lanza scores and dyspeptic symptom scores were higher in the teprenone group than in the control group (P < 0.05). For subgroup analysis, the change in Lanza scores and dyspeptic symptom scores improved significantly in the teprenone group receiving long-term low-dose aspirin treatment, as well as in the teprenone group receiving other NSAIDs treatment (P < 0.05). CONCLUSIONS: Teprenone may be an effective treatment choice of gastric mucosal injuries and dyspepsia symptoms in patients who used NSAIDs chronically without H. pylori infection or history of gastroduodenal ulcer.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Antiulcerosos/uso terapêutico , Diterpenos/uso terapêutico , Dispepsia/tratamento farmacológico , Mucosa Gástrica/efeitos dos fármacos , Adulto , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Antiulcerosos/efeitos adversos , Pequim , Diterpenos/efeitos adversos , Esquema de Medicação , Dispepsia/induzido quimicamente , Dispepsia/patologia , Feminino , Mucosa Gástrica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
8.
BMC Gastroenterol ; 17(1): 118, 2017 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-29166876

RESUMO

OBJECTIVE: The anatomy of esophagogastric junction (EGJ) serves as the anti-reflux barrier. The gastroesophageal flap valve (GEFV) is a component of EGJ. The aim of the current study was to assess its correlation with the esophageal acid exposure and the impact on anti-reflux barrier function by using the metrics of EGJ contraction. METHODS: Eighty three patients with typical GERD symptoms were included in the study. Upper endoscopy, high-resolution manometry (HRM) and 24 h multichannel intraluminal impedance-pH (MII-pH) monitoring were performed in all patients. GEFV was determined as four grades during endoscopic examination based on the Hill classification. The esophageal pressure topography (EPT) metrics defined in the updated Chicago Classification were measured by HRM, including integrated relaxation pressure (IRP), EGJ contractile index (EGJ-CI),expiratory EGJ pressure(EGJP-exp) and inspiratory EGJ pressure (EGJP-insp). RESULTS: The GEFV grade III and IV was more commonly found in patients with esophagitits (p < 0.05). The acid exposure time (AET%) and supine AET% were lower in patients with GEFV grade I (p < 0.01). There was weak correlation between AET% and GEFV grades (r = 0.27, p = 0.013). There were more EGJ morphology type III in patients with GEFV grade IV (p < 0.05).There were no significant differences on the values of four HRM metrics among the patients with different GEFV grades (p > 0.05). CONCLUSION: The GEFV grades were associated with acid reflux positively and could be a good reflection of EGJ morphology in HRM. But it had no impact on the four HRM metrics. Our research revealed that GEFV may play an assistant role in the anti-reflux barrier.


Assuntos
Junção Esofagogástrica/patologia , Junção Esofagogástrica/fisiopatologia , Refluxo Gastroesofágico/patologia , Refluxo Gastroesofágico/fisiopatologia , Esofagite Péptica/patologia , Esofagite Péptica/fisiopatologia , Esofagoscopia , Gastroscopia , Azia/etiologia , Humanos , Concentração de Íons de Hidrogênio , Manometria/métodos
9.
J Gastroenterol Hepatol ; 32(1): 28-38, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27300149

RESUMO

BACKGROUND AND AIMS: Alterations of gut microbiota were assumed to be the etiology and pathogenesis of irritable bowel syndrome (IBS) in some studies. However, alterations of gut microbiota in IBS patients had not been systematically assessed with a meta-analysis. We performed a mate-analysis to explore and compare the alterations of gut microbiota in IBS patients from China and other regions around the world. METHODS: Case-control studies detecting gut microbiota in IBS patients were identified through English and Chinese databases. The standardized mean difference (SMD) with 95% confidence interval (CI) of bacterial counts was calculated. RESULTS: Ten studies from China and seven studies from other regions around the world were included in our study. As compared with healthy controls, the SMDs of Bifidobacteria, Lactobacillus, Escherichia Coli, and Enterobacter in Chinese IBS patients were -1.42 (CI: -2.10, -0.75), -0.91 (95% CI: -1.31, -0.52), 0.83 (95% CI: 0.26, 1.40), and 0.57 (95% CI: 0.33, 0.82), respectively. But the SMDs of Bacteroides and Enterococcus were found no significant differences in Chinese IBS patients. However, the SMDs of Bifidobacteria and Bacteroides in IBS patients from other regions were -0.76 (CI: -1.43, -0.09) and 1.17 (CI: 0.00, 2.35), while the SMDs of Lactobacillus, E. Coli, Enterobacter, and Enterococcus were found no significant differences. CONCLUSIONS: There were alterations of gut microbiota in IBS patients, and it implied that alterations of gut microbiota might be involved in the pathogenesis of IBS. However, the species-specific alterations of gut microbiota were different between IBS patients from China and other regions.


Assuntos
Microbioma Gastrointestinal/fisiologia , Síndrome do Intestino Irritável/microbiologia , Carga Bacteriana , Bifidobacterium/isolamento & purificação , Estudos de Casos e Controles , Bases de Dados Bibliográficas , Enterobacter/isolamento & purificação , Escherichia coli/isolamento & purificação , Humanos , Síndrome do Intestino Irritável/etiologia , Lactobacillus/isolamento & purificação
10.
J Gastroenterol Hepatol ; 32(8): 1450-1456, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28084664

RESUMO

BACKGROUND AND AIM: Information on real world treatment experiences of patients with functional bowel disorders is lacking from Asia. This study aimed to describe the medication exposure and treatment satisfaction of patients presenting to gastroenterology clinics across a sampling of Asian cities. METHODS: From March 2011 to October 2013, adult patients presenting to hospital-based gastroenterology outpatient clinics in 11 cities across Asia, who fulfilled screening criteria for any functional gastrointestinal disorder, were asked to complete a validated culturally adapted translation of the Rome III diagnostic questionnaire, a checklist of medications received in the preceding 3 months and questions on treatment satisfaction. RESULTS: A total of 1376 patients (female 755, male 621, 41.36 ± 13.25 years) comprising irritable bowel (621, 45.1%), unspecified functional bowel disorder (372, 27.8%), functional constipation (202, 14.7%), functional bloating (144, 10.5%), and functional diarrhea (56, 4.1%) completed the study. Of 1105 patients with a previous consultation, 509 (46.1%) were dissatisfied with their treatment, with ineffective treatment being the commonest reason. Satisfaction with previous consultation was lowest by diagnosis for functional constipation (29.2%), and the most bothersome symptom was straining (37.5%). Of 1046 patients who had taken medications for their gastrointestinal symptoms in the last 3 months, 793 (75.8%) had received two or more drugs. For irritable bowel syndrome patients, treatment with proton pump inhibitors and antispasmodics was recorded in 57% and 31%, with overlapping epigastric pain and heartburn predicting proton pump inhibitors use. CONCLUSIONS: More attention should be given to treatment gaps with regards to possible under-treatment with antispasmodics in irritable bowel syndrome and to critically evaluating the efficacy of constipation management.


Assuntos
Síndrome do Intestino Irritável/tratamento farmacológico , Parassimpatolíticos/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Ásia/epidemiologia , Povo Asiático , Constipação Intestinal/diagnóstico , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/epidemiologia , Constipação Intestinal/psicologia , Diarreia/diagnóstico , Diarreia/tratamento farmacológico , Diarreia/epidemiologia , Diarreia/psicologia , Quimioterapia Combinada , Feminino , Humanos , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/psicologia , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Inquéritos e Questionários
11.
J Biol Chem ; 290(6): 3793-802, 2015 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-25538235

RESUMO

Metformin is the most widely prescribed oral anti-diabetic agent. Recently, we have shown that low metformin concentrations found in the portal vein suppress glucose production in hepatocytes through activation of AMPK. Moreover, low concentrations of metformin were found to activate AMPK by increasing the phosphorylation of AMPKα at Thr-172. However, the mechanism underlying the increase in AMPKα phosphorylation at Thr-172 and activation by metformin remains unknown. In the current study, we find that low concentrations of metformin promote the formation of the AMPK αßγ complex, resulting in an increase in net phosphorylation of the AMPK α catalytic subunit at Thr-172 by augmenting phosphorylation by LKB1 and antagonizing dephosphorylation by PP2C.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Multimerização Proteica , Animais , Linhagem Celular Tumoral , Células Cultivadas , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Camundongos , Fosforilação , Ligação Proteica , Proteína Fosfatase 2/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Subunidades Proteicas/metabolismo
12.
J Biol Chem ; 289(30): 20435-46, 2014 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-24928508

RESUMO

Metformin is a first-line antidiabetic agent taken by 150 million people across the world every year, yet its mechanism remains only partially understood and controversial. It was proposed that suppression of glucose production in hepatocytes by metformin is AMPK-independent; however, unachievably high concentrations of metformin were employed in these studies. In the current study, we find that metformin, via an AMP-activated protein kinase (AMPK)-dependent mechanism, suppresses glucose production and gluconeogenic gene expression in primary hepatocytes at concentrations found in the portal vein of animals (60-80 µM). Metformin also inhibits gluconeogenic gene expression in the liver of mice administered orally with metformin. Furthermore, the cAMP-PKA pathway negatively regulates AMPK activity through phosphorylation at Ser-485/497 on the α subunit, which in turn reduces net phosphorylation at Thr-172. Because diabetic patients often have hyperglucagonemia, AMPKα phosphorylation at Ser-485/497 is a therapeutic target to improve metformin efficacy.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Gluconeogênese/efeitos dos fármacos , Glucose/biossíntese , Hepatócitos/metabolismo , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Animais , Células Cultivadas , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatócitos/citologia , Camundongos
13.
J Biol Chem ; 289(29): 20039-53, 2014 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-24867958

RESUMO

NHERF1, NHERF2, and NHERF3 belong to the NHERF (Na(+)/H(+) exchanger regulatory factor) family of PSD-95/Discs-large/ZO-1 (PDZ) scaffolding proteins. Individually, each NHERF protein has been shown to be involved in the regulation of multiple receptors or transporters including Na(+)/H(+) exchanger 3 (NHE3). Although NHERF dimerizations have been reported, results have been inconsistent, and the physiological function of NHERF dimerizations is still unknown. The current study semiquantitatively compared the interaction strength among all possible homodimerizations and heterodimerizations of these three NHERF proteins by pulldown and co-immunoprecipitation assays. Both methods showed that NHERF2 and NHERF3 heterodimerize as the strongest interaction among all NHERF dimerizations. In vivo NHERF2/NHERF3 heterodimerization was confirmed by FRET and FRAP (fluorescence recovery after photobleach). NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. The NHERF3-4A mutant is defective in heterodimerization with NHERF2 and does not support the inhibition of NHE3 by carbachol. This suggests a role for NHERF2/NHERF3 heterodimerization in the regulation of NHE3 activity. In addition, both PDZ domains of NHERF2 could be simultaneously occupied by NHERF3 and another ligand such as NHE3, α-actinin-4, and PKCα, promoting formation of NHE3 macrocomplexes. This study suggests that NHERF2/NHERF3 heterodimerization mediates the formation of NHE3 macrocomplexes, which are required for the inhibition of NHE3 activity by carbachol.


Assuntos
Carbacol/farmacologia , Fosfoproteínas/química , Fosfoproteínas/metabolismo , Trocadores de Sódio-Hidrogênio/antagonistas & inibidores , Trocadores de Sódio-Hidrogênio/química , Trocadores de Sódio-Hidrogênio/metabolismo , Substituição de Aminoácidos , Animais , Células CACO-2 , Linhagem Celular , Cricetinae , Recuperação de Fluorescência Após Fotodegradação , Transferência Ressonante de Energia de Fluorescência , Humanos , Complexos Multiproteicos/química , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo , Mutagênese Sítio-Dirigida , Domínios PDZ , Fosfoproteínas/genética , Multimerização Proteica , Coelhos , Ratos , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Trocador 3 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/genética
14.
J Biol Chem ; 289(7): 4326-33, 2014 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-24379407

RESUMO

FOXO1 is an important downstream mediator of the insulin signaling pathway. In the fed state, elevated insulin phosphorylates FOXO1 via AKT, leading to its nuclear exclusion and degradation. A reduction in nuclear FOXO1 levels then leads to suppression of hepatic glucose production. However, the mechanism leading to expression of Foxo1 gene in the fasted state is less clear. We found that Foxo1 mRNA and FOXO1 protein levels of Foxo1 were increased significantly in the liver of mice after 16 h of fasting. Furthermore, dibutyrl cAMP stimulated the expression of Foxo1 at both mRNA and protein level in hepatocytes. Because cAMP-PKA regulates hepatic glucose production through cAMP-response element-binding protein co-activators, we depleted these co-activators using adenoviral shRNAs. Interestingly, only depletion of co-activator P300 resulted in the decrease of Foxo1 mRNA and FOXO1 protein levels. In addition, inhibition of histone acetyltransferase activity of P300 significantly decreased hepatic Foxo1 mRNA and FOXO1 protein levels in fasted mice, as well as fasting blood glucose levels. By characterization of Foxo1 gene promoter, P300 regulates the Foxo1 gene expression through the binding to tandem cAMP-response element sites in the proximal promoter region of Foxo1 gene.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Fatores de Transcrição Forkhead/biossíntese , Regulação da Expressão Gênica/fisiologia , Fígado/metabolismo , Animais , Bucladesina/farmacologia , Linhagem Celular Tumoral , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Jejum/metabolismo , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/citologia , Camundongos
15.
J Gastroenterol Hepatol ; 30(6): 995-1000, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25470082

RESUMO

BACKGROUND AND AIM: It has been reported that small intestinal bacterial overgrowth (SIBO) may lead to false positive diagnoses of lactose malabsorption (LM) in irritable bowel syndrome patients. The aim of this study was to determine the influence of SIBO on lactose hydrogen breath test (HBT) results in these patients. METHODS: Diarrhea-predominant irritable bowel syndrome patients with abnormal lactose HBTs ingested a test meal containing (99m) Tc and lactose. The location of the test meal and the breath levels of hydrogen were recorded simultaneously by scintigraphic scanning and lactose HBT, respectively. The increase in hydrogen concentration was not considered to be caused by SIBO if ≥ 10% of (99m) Tc accumulated in the cecal region at the time or before of abnormal lactose HBT. RESULTS: LM was present in 84% (31/37) of irritable bowel syndrome patients. Twenty of these patients agreed to measurement of oro-cecal transit time. Only three patients (15%) with abnormal lactose HBT might have had SIBO. The median oro-cecal transit time between LM and lactose intolerance patients were 75 min and 45 min, respectively (Z=2.545, P=0.011). CONCLUSIONS: Most of irritable bowel syndrome patients with an abnormal lactose HBT had LM. SIBO had little impact on the interpretation of lactose HBTs. The patients with lactose intolerance had faster small intestinal transit than LM patients.


Assuntos
Testes Respiratórios/métodos , Diarreia/diagnóstico , Diarreia/epidemiologia , Intestino Delgado/microbiologia , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/epidemiologia , Intolerância à Lactose/diagnóstico , Adulto , Ásia/epidemiologia , Diarreia/microbiologia , Diarreia/fisiopatologia , Reações Falso-Positivas , Feminino , Trânsito Gastrointestinal , Humanos , Hidrogênio , Síndrome do Intestino Irritável/microbiologia , Síndrome do Intestino Irritável/fisiopatologia , Lactose , Intolerância à Lactose/epidemiologia , Intolerância à Lactose/microbiologia , Intolerância à Lactose/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Tempo , Adulto Jovem
16.
Front Med (Lausanne) ; 11: 1338206, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660419

RESUMO

Aims: This cohort study aimed to explore the effect of a one-day online continuing medical education (CME) on the improvement of physicians' knowledge and clinical practice on functional dyspepsia (FD). Methods: Physicians were invited to participate in this CME via medical education applications. FD training videos made in advance were sent to participants via a weblink. Before and after training, participants were required to finish the FD knowledge test and provide case information of FD patients. McNemar test, Wilcoxon rank-sum test, Freidman test, Chi-square test, quantile regression, and generalized estimating equations (GEE) were used to perform statistical analysis. Results: There were 397 of 430 (92.33%) physicians finished this CME program. The total score of the FD knowledge test after training was significantly higher compared with before training [488.3 (468.3-510.0) vs. 391.7 (341.7-450.0), p < 0.001]. Particularly, physicians from primary hospitals show more increase in total scores than physicians from secondary and tertiary hospitals. According to the GEE model, receiving this online training was an independent predictor of physicians' choice of upper gastrointestinal endoscopy in patients with FD [OR 1.73, 95%CI (1.09-2.73), p = 0.020], especially in PDS. Also, it was an independent predictor of physicians' choice of acid-suppressive drugs in patients with FD [OR 1.30, 95%CI (1.03-1.63), p = 0.026], especially in EPS and PDS overlapping EPS. Conclusion: This one-day online CME program effectively and conveniently improved physicians' knowledge and clinical practice, providing new ideas for future CME and facilitating precise clinical management of FD patients with different subtypes especially in primary hospitals.

17.
J Gastroenterol Hepatol ; 28(10): 1611-5, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23730912

RESUMO

BACKGROUND AND AIM: Current normative data of high-resolution manometry have been obtained from Western populations, and esophageal motility disorders have been categorized using Chicago classification. However, the utility of high-resolution impedance manometry (HRiM) in the Chinese population has not been evaluated. The study aimed to investigate the normal reference of esophageal motility in healthy volunteers (as defined by Chicago classification) using HRiM. METHODS: Healthy, fasted volunteers underwent HRiM in a supine position with 10 liquid swallows and 10 viscous swallows. Integrated relaxation pressure (IRP), distal contractile integral (DCI), contractile front velocity (CFV), and distal latency were calculated. The interquartile ranges and the 95th percentile range for each metric were obtained. RESULTS: Forty-two healthy volunteers were enrolled with 411 total liquid swallows and 398 viscous swallows available for analysis. A 20.5 mmHg of IRP and a 3195 mmHg·s·cm of DCI as the 95th percentile for liquid swallows were established. Using the reference range defined by Chicago classification, 6.3% (26/411) weak peristalsis and 0.7% (3/411) failed peristalsis for liquid swallows were observed; 12 (28.6%, 12/42) and 2 (4.7%, 2/42) individuals were diagnosed as esophagogastric junction outflow obstruction and weak peristalsis for liquid swallows. Compared with liquid swallows, viscous swallows had a decreased IRP (P = 0.000) and CFV (P = 0.000), and an unchanged DCI (P = 0.211). CONCLUSIONS: HRiM normative data of both liquid and viscous swallows from healthy Chinese volunteers were established. The IRP and CFV were significantly decreased in the viscous swallows compared with those of the liquid swallows.


Assuntos
Deglutição/fisiologia , Esôfago/fisiologia , Motilidade Gastrointestinal , Aumento da Imagem/métodos , Manometria/métodos , Adolescente , Adulto , Idoso , Povo Asiático , Impedância Elétrica , Transtornos da Motilidade Esofágica/diagnóstico , Voluntários Saudáveis , Humanos , Pessoa de Meia-Idade , Valores de Referência , Adulto Jovem
18.
Nutrients ; 15(21)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37960154

RESUMO

Structural changes in the gut microbiota are closely related to the development of functional constipation, and regulating the gut microbiota can improve constipation. Rifaximin is a poorly absorbed antibiotic beneficial for regulating gut microbiota, but few studies have reported its effects on constipation. The purpose of this study was to investigate the effect of rifaximin on loperamide-induced constipation in SD rats. The results showed that rifaximin improved constipation by increasing serum 5-HT, SP, and the mRNA expression of AQP3, AQP8, and reducing the mRNA expression of TLR2 and TLR4. In addition, rifaximin could regulate the gut microbiota of constipated rats, such as increasing the potentially beneficial bacteria Akkermansia muciniphila and Lactobacillus murinus, reducing the Bifidobacterium pseudolongum. According to metabolomics analysis, many serum metabolites, including bile acids and steroids, were changed in constipated rats and were recovered via rifaximin intervention. In conclusion, rifaximin might improve loperamide-induced constipation in rats by increasing serum excitatory neurotransmitters and neuropeptides, modulating water metabolism, and facilitating intestinal inflammation. Muti-Omics analysis results showed that rifaximin has beneficial regulatory effects on the gut microbiota and serum metabolites in constipated rats, which might play critical roles in alleviating constipation. This study suggests that rifaximin might be a potential strategy for treating constipation.


Assuntos
Microbioma Gastrointestinal , Loperamida , Ratos , Animais , Loperamida/efeitos adversos , Rifaximina/efeitos adversos , Ratos Sprague-Dawley , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico , RNA Mensageiro
19.
Nutrients ; 15(17)2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37686889

RESUMO

Irritable bowel syndrome (IBS) is a common gastrointestinal disease. The efficacy of different probiotics in treating IBS remains controversial. This network meta-analysis aimed to compare and rank the outcome-specific efficacy of different probiotic strains or combinations in adults with IBS. We searched the literature up to June 2023. Randomized controlled trials (RCTs) that evaluated the efficacy of probiotics in IBS were included. A frequentist framework was used to perform this study. In total, 9253 participants from 81 RCTs were included in the study. Four probiotic strains and five mixtures were significantly superior to placebo in improving IBS Symptom Severity Scale, among which Lactobacillus acidophilus DDS-1 ranked first (surface under the cumulative ranking, SUCRA, 92.9%). A mixture containing five probiotics (SUCRA, 100%) ranked first in improving the IBS-Quality of life. Bacillus coagulans MTCC 5856 (SUCRA, 96.9%) and Bacillus coagulans Unique IS2 (SUCRA, 92.6%) were among the most effective probiotics for improving abdominal pain. Three probiotic strains and two mixtures were effective in alleviating abdominal bloating. Four probiotic strains and a mixture were significantly superior to placebo in reducing the bowel movement frequency in diarrhea-predominant IBS (IBS-D). Bacillus coagulans MTCC 5856 (SUCRA, 99.6%) and Saccharomyces cerevisiae CNCM I-3856 (SUCRA, 89.7%) were among the most effective probiotics for improving the Bristol stool form scale of IBS-D. Only some probiotics are effective for particular outcomes in IBS patients. This study provided the first ranking of outcome-specific efficacy of different probiotic strains and combinations in IBS. Further studies are needed to confirm these results.


Assuntos
Bacillus coagulans , Síndrome do Intestino Irritável , Probióticos , Adulto , Humanos , Síndrome do Intestino Irritável/terapia , Metanálise em Rede , Dor Abdominal/terapia , Probióticos/uso terapêutico , Saccharomyces cerevisiae
20.
J Health Popul Nutr ; 41(1): 21, 2022 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-35578355

RESUMO

OBJECTIVE: Gut microbiota might play a crucial role in the pathogenesis of irritable bowel syndrome (IBS), and probiotics supplement may be an effective treatment option. This study aims to explore the therapeutic effects of Golden bifid on the diarrhea-predominant IBS (IBS-D). METHODS: Twenty-one consecutive IBS-D patients were recruited based on Rome IV criteria. All patients took 2000 mg Golden bifid triple daily for 4 weeks. Gastrointestinal (GI) symptoms, psychological symptoms, small intestine bacterial overgrowth (SIBO) and fecal microbiota characteristics were evaluated in IBS-D patients before and after treatment. RESULTS: After 4-week treatment of Golden bifid, the GI symptoms such as abdominal pain (2.90 ± 1.04 vs. 1.90 ± 1.26, P = 0.002), abdominal distension (2.00 ± 1.34 vs. 1.29 ± 1.31, P = 0.007), diarrhea (3.24 ± 1.37 vs. 1.81 ± 1.21, P = 0.001), defecatory urgency (3.48 ± 1.03 vs. 2.33 ± 1.35, P = 0.000) and incomplete evacuation (2.71 ± 1.15 vs. 1.76 ± 1.26, P = 0.003) were significantly alleviated in IBS-D patients. The Self-Rating Depression Scale (SDS) decreased significantly (46.19 ± 11.36 vs. 43.33 ± 9.65, P = 0.041), and SIBO could be eradicated in 25% (4/16) of IBS-D patients with SIBO. Meanwhile, the abundance of Unclassified Lachnospiraceae and Dorea in genus level and Unclassified Lachnospiraceae, Bacterium Dorea, Bacterium Butyricicoccus and Dorea formicigenerans ATCC 27755 in species level were increased in fecal microbiota (P < 0.05). CONCLUSIONS: Golden bifid could improve most of GI symptoms and depressive symptoms in IBS-D patients and eradicate a small proportion of SIBO in those IBS-D patients with SIBO. What's more, Golden bifid could also modulate the fecal microbiota in IBS-D patients, which implied that the Golden bifid might improve IBS-D via microbiota modulation.


Assuntos
Infecções Bacterianas , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Diarreia/etiologia , Diarreia/terapia , Fezes/microbiologia , Humanos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/terapia
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