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1.
Oxid Med Cell Longev ; 2022: 5121496, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36187337

RESUMEN

Background: Fecal microbiota transplantation (FMT) has been found to be effective in irritable bowel syndrome with predominant diarrhea (IBS-D). We conducted this study to determine the impact of a low FODMAP diet (LFD) on the gut microbiota and the efficacy of FMT in the treatment of IBS-D. Methods: A retrospective analysis of a single-arm open-label prospective study was conducted to investigate the impact of FMT alone (n = 40) and FMT+LFD (n = 40) in refractory IBS-D. The IBS-quality of life (QOL), IBS-severity scoring system (SSS), gastrointestinal symptom rating scale (GSRS), Hamilton anxiety scale (HAMA), and Hamilton depression scale (HAMD) were used to evaluate the efficacy, and partial 16S rDNA amplicon sequencing was used to profile the microbiota. Results: The response rates were higher in the FMT+LFD group than in the FMT group (1 mo, 3 mo, 6 mo: 70.0% vs. 55.0%, 67.5% vs. 57.5%, 62.5% vs. 27.5%, respectively). The FMT+LFD group showed significantly better improvement in IBS-QOL at 1, 3, and 6 months; IBS-SSS at 6 months; and GSRS at 1 month compared to FMT alone. Changes in HAMA and HAMD were similar in the two groups. The LFD significantly upregulated the FMT-induced microbial diversity (OTUs: 666 vs. 574, Adonis: P = 0.02) and significantly strengthened the upregulation of Bacteroides, Alistipes, and Ruminococcaceae_UCG-002 and the downregulation of Bifidobacterium. Conclusion: An LFD enhanced the efficacy of FMT, increased the gut microbial diversity after FMT, and strengthened the inhibitory effect of FMT on conditional pathogens.


Asunto(s)
Enfermedades Gastrointestinales , Síndrome del Colon Irritable , ADN Ribosómico , Diarrea/terapia , Dieta , Trasplante de Microbiota Fecal , Heces/microbiología , Humanos , Síndrome del Colon Irritable/terapia , Estudios Prospectivos , Calidad de Vida , Estudios Retrospectivos
2.
Front Psychiatry ; 13: 695481, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35370847

RESUMEN

Asperger syndrome (AS) is a chronic neurodevelopmental disorder. Although all of the clinically diagnosed cases display normal intelligence and speech functions, barriers in social interaction and communication seriously affect mental health and psychological function. In addition to traditional psychological/behavioral training and symptomatic medication, in-depth studies of intestinal microbiota and mental health have indicated that probiotics (e.g., Lactobacillus rhamnosus) can effectively reduce the occurrence of AS. Fecal microbiota transplantation (FMT) is a type of biological therapy that involves the transplant of intestinal microbiota from healthy donors into the patient's gastrointestinal tract to improve the gut microenvironment. In this case report, we describe the first case of adult AS treated with FMT. The patient suffered from diarrhea-predominant irritable bowel syndrome for 6 years with symptoms of diarrhea and abdominal pain. After three rounds of FMT, the diarrhea and abdominal pain were significantly improved. Moreover, the symptoms of AS were also significantly ameliorated. We found that FMT changed the structure of the intestinal microbiota as well as the patient's serum metabolites, and these changes were consistent with the patient's symptoms. The metabolites may affect signaling pathways, as revealed by Kyoto Encyclopedia of Genes and Genomes enrichment analysis. The changes in microbial metabolites following FMT may affect other regions (e.g., the nervous system) via the circulatory system, such that the bacteria-gut-blood-brain axis may be the means through which FMT mitigates AS.

3.
J Clin Transl Hepatol ; 9(5): 607-614, 2021 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-34722175

RESUMEN

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic disorders. This study aimed to explore the role of metabolic disorders in screening advanced fibrosis in NAFLD patients. METHODS: A total of 246 histologically-proven NAFLD patients were enrolled across 14 centers. We compared the severity of fibrosis in patients with different components of metabolic disorders. Based on standard noninvasive tests and metabolic disorders, we developed new algorithms to identify advanced fibrosis. RESULTS: Metabolic syndrome (MetS) was frequent in NAFLD patients (133/246, 54%). Patients with MetS had a higher proportion of significant fibrosis (p=0.014) and higher LSM values (9.2 kPa, vs. 7.4 kPa, p=0.002) than those without MetS. Patients with more metabolic disorders had higher fibrosis stages (p=0.017). Reduced high-density lipoprotein cholesterol (odds ratio [OR]: 2.241, 95% confidence interval [CI]: 1.004-5.002, p=0.049) and raised fasting glucose (OR: 4.500, 95% CI: 2.083-9.725, p<0.001) were significantly associated with advanced fibrosis. Using these two metabolic disorders as a screening tool, a sensitivity, specificity and accuracy of 92%, 81% and 83% was achieved, respectively. With the new algorithms combining metabolic disorders with noninvasive measurements, the number of patients requiring liver biopsy was reduced, especially in combination with the Fibrosis-4 score and metabolic disorders (36% to 17%, p<0.001). In addition, this stepwise algorithm could achieve a high accuracy (85%) and high negative predictive value (93%). CONCLUSIONS: Metabolic disorders should be taken into consideration in the diagnosis of advanced fibrosis. With further validation and investigation, new algorithms could be recommended in primary care units to spare patients from unnecessary referral and liver biopsies.

4.
BMC Cancer ; 21(1): 1170, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34724907

RESUMEN

BACKGROUND: The prognosis of patients with gastrointestinal stromal tumors (GISTs) is generally evaluated at the time of diagnosis but does not reflect the survival dynamics of patients in the future. Therefore, the purpose of this article was to evaluate the conditional survival (CS) of Chinese patients with GISTs after radical resection. METHODS: This retrospective study included 451 patients who underwent radical surgery for GISTs. A Cox proportional hazard model was used to evaluate the prognostic factors of disease-free survival (DFS). The 3-year conditional DFS (CDFS3) of patients who survived for x years was expressed as CDFS3=DFS(x + 3)/DFS(x). RESULTS: The traditional 3-year DFS rate decreased gradually from 94.0% at 3 years to 77.3% at 7 years, while the CDFS3 rate increased from 94.0 to 95.2% over the survival time of the patients. In addition, classic clinicopathological prognostic factors had different effects on CDFS3, with changes observed in survival time, but these effects were only slight or moderate (|d|<0.5). Although multivariate analysis showed that age, sex, mitotic index and tumor rupture were independent risk factors for DFS at baseline, all adverse prognostic factors, except for the mitotic index, lost their predictive significance at 5 years after operation. When the Modified NIH criteria were included, the risk staging was found to be an independent risk factor for recurrence or death. Time-dependent Cox regression analysis showed that the modified NIH criteria independently affected the recurrence or death of GIST patients within 2 years after operation. CONCLUSION: CS provides detailed dynamic survival information about Chinese patients with primary resected GISTs. The mitotic index is of great clinical significance for the monitoring and follow-up of patient populations with a high risk of tumor recurrence or death until 5 years after surgery.


Asunto(s)
Tumores del Estroma Gastrointestinal/mortalidad , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , China/epidemiología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Masculino , Persona de Mediana Edad , Índice Mitótico , Análisis Multivariante , Recurrencia Local de Neoplasia/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores Sexuales , Factores de Tiempo , Carga Tumoral , Adulto Joven
5.
BMC Microbiol ; 21(1): 279, 2021 10 16.
Artículo en Inglés | MEDLINE | ID: mdl-34654370

RESUMEN

BACKGROUND: Dextran sulfate sodium (DSS) replicates ulcerative colitis (UC)-like colitis in murine models. However, the microbial characteristics of DSS-triggered colitis require further clarification. To analyze the changes in gut microbiota associated with DSS-induced acute and chronic colitis. METHODS: Acute colitis was induced in mice by administering 3% DSS for 1 week in the drinking water, and chronic colitis was induced by supplementing drinking water with 2.5% DSS every other week for 5 weeks. Control groups received the same drinking water without DSS supplementation. The histopathological score and length of the colons, and disease activity index (DAI) were evaluated to confirm the presence of experimental colitis. Intestinal microbiota was profiled by 16S rDNA sequencing of cecal content. RESULTS: Mice with both acute and chronic DSS-triggered colitis had significantly higher DAI and colon histopathological scores in contrast to the control groups (P < 0.0001, P < 0.0001), and the colon was remarkably shortened (P < 0.0001, P < 0.0001). The gut microbiota α-diversity was partly downregulated in both acute and chronic colitis groups in contrast to their respective control groups (Pielou index P = 0.0022, P = 0.0649; Shannon index P = 0.0022, P = 0.0931). The reduction in the Pielou and Shannon indices were more obvious in mice with acute colitis (P = 0.0022, P = 0.0043). The relative abundance of Bacteroides and Turicibacter was increased (all P < 0.05), while that of Lachnospiraceae, Ruminococcaceae, Ruminiclostridium, Rikenella, Alistipes, Alloprevotella, and Butyricicoccus was significantly decreased after acute DSS induction (all P < 0.05). The relative abundance of Bacteroides, Akkermansia, Helicobacter, Parabacteroides, Erysipelatoclostridium, Turicibacter and Romboutsia was also markedly increased (all P < 0.05), and that of Lachnospiraceae_NK4A136_group, Alistipes, Enterorhabdus, Prevotellaceae_UCG-001, Butyricicoccus, Ruminiclostridium_6, Muribaculum, Ruminococcaceae_NK4A214_group, Family_XIII_UCG-001 and Flavonifractor was significantly decreased after chronic DSS induction (all P < 0.05). CONCLUSION: DSS-induced acute and chronic colitis demonstrated similar symptoms and histopathological changes. The changes in the gut microbiota of the acute colitis model were closer to that observed in UC. The acute colitis model had greater abundance of SCFAs-producing bacteria and lower α-diversity compared to the chronic colitis model.


Asunto(s)
Biodiversidad , Colitis/inducido químicamente , Colitis/microbiología , Sulfato de Dextran , Microbioma Gastrointestinal/fisiología , Enfermedad Aguda , Animales , Enfermedad Crónica , Colitis/patología , Modelos Animales de Enfermedad , Ratones
7.
Hepatobiliary Pancreat Dis Int ; 20(5): 426-432, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34246549

RESUMEN

BACKGROUND: This study aimed to assess the association between metabolic syndrome (MetS) and severity of nonalcoholic fatty liver disease (NAFLD), and to discuss the pathological relevance of the diagnostic criteria in metabolic (dysfunction) associated fatty liver disease (MAFLD). METHODS: This was a multicenter, cross-sectional study. Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China. Anthropometric and metabolic parameters were collected to assess the pathological relevance. RESULTS: Of 246 enrolled patients with NAFLD, 150 (61.0%) had the comorbidity of MetS. With the increase of metabolic components, the proportions of nonalcoholic steatohepatitis (NASH) and significant fibrosis were notably increased. The comorbid three metabolic components significantly increased the proportion of NASH, and further increase of metabolic components did not increase the proportion of NASH. However, the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis. Among the 246 patients, 239 (97.2%) met the diagnostic criteria of MAFLD. Although non-MAFLD patients had less NASH, they present with similar proportion of significant fibrosis and cirrhosis. In the diagnostic criteria of MAFLD, BMI ≥ 23 kg/m2 was related to NASH (Mantel-Haenszel Common Estimate OR: 2.975; 95% CI: 1.037-8.538; P = 0.043), and T2DM was related to significant fibrosis (Mantel-Haenszel Common Estimate OR: 2.531; 95% CI: 1.388-4.613; P = 0.002). The homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.5 was the most significant factor for NASH (OR: 4.100; 95% CI: 1.772-9.487; P = 0.001) and significant factor for liver fibrosis (OR: 2.947; 95% CI: 1.398-6.210; P = 0.004) after the adjustments of the BMI and diabetes. CONCLUSIONS: Metabolic dysregulations are important risk factors in NAFLD progression. The insulin resistance status may play a predominant role in the progression in MAFLD patients.


Asunto(s)
Resistencia a la Insulina , Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Biopsia , China/epidemiología , Estudios Transversales , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología
8.
Clin Transl Gastroenterol ; 12(4): e00323, 2021 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-33848277

RESUMEN

INTRODUCTION: To evaluate the diagnostic performance of ultrasound attenuation parameter (UAP) and liver stiffness measurement (LSM) by FibroTouch for diagnosis of hepatic steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: We recruited 237 patients undergoing FibroTouch and liver biopsy within 2 weeks. The pathological findings of liver biopsy were scored by Nonalcoholic Steatohepatitis Clinical Research Network, and the diagnostic accuracy of UAP for steatosis and LSM for fibrosis was evaluated by area under the receiver operating characteristic curve (AUROC). The impacts of histological parameters on UAP and LSM were analyzed, and diagnostic performance of FibroTouch UAP and LSM was compared with other noninvasive biomarkers. RESULTS: The success rate of FibroTouch examination was 96.51%. The AUROC of UAP for diagnosis of steatosis ≥S1, ≥S2, and S3 was 0.88, 0.93, and 0.88, and the cutoff values were 244, 269, and 296 dB/m, respectively. The AUROC of LSM for the diagnosis of fibrosis stages ≥F2, ≥F3, and F4 was 0.71, 0.71, and 0.77, and the cutoff values were 9.4, 9.4, and 11 kPa, respectively. Multiple regression analysis showed that LSM was positively correlated with degree of fibrosis and NAFLD activity score. UAP was positively correlated with liver steatosis. The diagnostic performance of UAP for steatosis was significantly superior to that of the hepatic steatosis index. DISCUSSION: FibroTouch has a low failure rate with moderate to high diagnostic performance for discriminating the steatosis degree and fibrosis stage and is suitable for clinical evaluation and monitoring of patients with NAFLD.


Asunto(s)
Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/patología , Hígado/diagnóstico por imagen , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/patología , Ultrasonografía/métodos , Adulto , Área Bajo la Curva , Biomarcadores , Biopsia , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
9.
Front Microbiol ; 12: 658292, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33912150

RESUMEN

Fecal microbiota transplantation (FMT) can inhibit the progression of ulcerative colitis (UC). However, how FMT modulates the gut microbiota and which biomarker is valuable for evaluating the efficacy of FMT have not been clarified. This study aimed to determine the changes in the gut microbiota and their relationship with butyric acid following FMT for UC. Fecal microbiota (FM) was isolated from healthy individuals or mice and transplanted into 12 UC patients or colitis mice induced by dextran sulfate sodium (DSS). Their clinical colitis severities were monitored. Their gut microbiota were analyzed by 16S sequencing and bioinformatics. The levels of fecal short-chain fatty acids (SCFAs) from five UC patients with recurrent symptoms after FMT and individual mice were quantified by liquid chromatography-mass spectrometry (LC-MS). The impact of butyric acid on the abundance and diversity of the gut microbiota was tested in vitro. The effect of the combination of butyric acid-producing bacterium and FMT on the clinical responses of 45 UC patients was retrospectively analyzed. Compared with that in the controls, the FMT significantly increased the abundance of butyric acid-producing bacteria and fecal butyric acid levels in UC patients. The FMT significantly increased the α-diversity, changed gut microbial structure, and elevated fecal butyric acid levels in colitis mice. Anaerobic culture with butyrate significantly increased the α-diversity of the gut microbiota from colitis mice and changed their structure. FMT combination with Clostridium butyricum-containing probiotics significantly prolonged the UC remission in the clinic. Therefore, fecal butyric acid level may be a biomarker for evaluating the efficacy of FMT for UC, and addition of butyrate-producing bacteria may prolong the therapeutic effect of FMT on UC by changing the gut microbiota.

10.
Gastroenterol Res Pract ; 2021: 6699268, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33510784

RESUMEN

Gut dysbacteriosis is closely related to various intestinal and extraintestinal diseases. Fecal microbiota transplantation (FMT) is a biological therapy that entails transferring the gut microbiota from healthy individuals to patients in order to reconstruct the intestinal microflora in the latter. It has been proved to be an effective treatment for recurrent Clostridium difficile infection. Studies show that the gut microbiota plays an important role in the pathophysiology of neurological and psychiatric disorders through the microbiota-gut-brain axis. Therefore, reconstruction of the healthy gut microbiota is a promising new strategy for treating cerebral diseases. We have reviewed the latest research on the role of gut microbiota in different nervous system diseases as well as FMT in the context of its application in neurological, psychiatric, and other nervous system-related diseases (Parkinson's disease, Alzheimer's disease, multiple sclerosis, epilepsy, autism spectrum disorder, bipolar disorder, hepatic encephalopathy, neuropathic pain, etc.).

11.
Appl Microbiol Biotechnol ; 105(4): 1669-1681, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33511441

RESUMEN

The gut microbiota is closely related to host health and disease. However, there are no suitable animal models available at present for exploring its functions. We analyzed the effect of 3 different antibiotic cocktails (ABx) via two administration routes on the composition of murine gut microbiota, as well as on the general physiological and metabolic indices. High-throughput 16S rRNA sequencing showed that ABx treatment altered the gut microbiota community structure, and also caused low-degree inflammation in the colon. In addition, ad libitum administration of antibiotics depleted the gut microbiota more effectively compared to direct oral gavage, especially with 3ABx. The ABx treatment also had a significant impact on renal and liver functions, as indicated by the altered serum levels of creatinine, urea, total triglycerides, and total cholesterol. Finally, Spearman's correlation analysis showed that the predominant bacterial genera resulting from ABx intervention, including Lactobacillus, Roseburia, and Candidatus-Saccharimonas, were negatively correlated with renal function indices. Taken together, different antibiotic combinations and interventions deplete the gut microbiota and induce physiological changes in the host. Our findings provide the basis for developing an adaptive animal model for studying gut microbiota. KEY POINTS: • Ad libitum administration of 3ABx can effectively deplete intestinal microbiota. • ABx treatment may have slight effect on renal and liver function. • The levels of urea and creatinine correlated with the growth of Roseburia.


Asunto(s)
Microbioma Gastrointestinal , Microbiota , Animales , Antibacterianos/farmacología , Lactobacillus , Ratones , ARN Ribosómico 16S/genética
12.
Biomed Res Int ; 2021: 4192451, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33506015

RESUMEN

METHODS: Colitis was induced in mice using 2,4,6-trinitrobenzene-sulfonic acid (TNBS), and mice were subsequently treated with either a PD-1 inhibitor or 5-amino-salicylic acid (ASA) as a positive control. Body weight, disease activity index (DAI), colon length, and tissue damage were evaluated, and the enteric microbiota was profiled using high-throughput 16S rRNA sequencing of fecal samples from the experimental mice. RESULTS: TNBS caused mice to experience IBD-like symptoms, which were attenuated by the PD-1 inhibitor, as indicated by a decrease in DAI scores (p = 0.0002). Furthermore, in this mouse model of IBD, PD-1 inhibition improved the alpha diversity as well as restored the beta diversity of the enteric microbiome. It also significantly enriched the abundance of short-chain fatty acid- (SCFA-) producing bacteria of the Firmicutes (p < 0.05) and Bacteroidetes (p < 0.05) phyla but depopulated Proteobacteria (p < 0.05). CONCLUSION: PD-1 inhibition can partly mitigate TNBS-induced colitis and restore the enteric microbiota by enriching the abundance of SCFA-producing bacteria.


Asunto(s)
Colitis/metabolismo , Colitis/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Sustancias Protectoras/farmacología , Animales , Colitis/inducido químicamente , Colon/efectos de los fármacos , Colon/patología , Modelos Animales de Enfermedad , Inhibidores de Puntos de Control Inmunológico/farmacología , Masculino , Mesalamina/farmacología , Ratones , Ratones Endogámicos BALB C , Ácido Trinitrobencenosulfónico/efectos adversos
13.
Cancer Manag Res ; 12: 11713-11721, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33239911

RESUMEN

BACKGROUND: Preoperative imaging examination is the primary method for diagnosing metastatic gastrointestinal stromal tumor (GIST), but it is associated with a high rate of missed diagnosis. Therefore, it is important to establish an accurate model for predicting occult peritoneal metastasis (PM) of GIST. PATIENTS AND METHODS: GIST patients seen between April 2002 and December 2018 were selected from an institutional database. Using multivariate logistic regression analyses, we created a nomogram to predict occult PM of GIST and validated it with an independent cohort from the same center. The concordance index (C-index), decision curve analysis (DCA) and a clinical impact curve (CIC) were used to evaluate its predictive ability. RESULTS: A total of 522 eligible GIST patients were enrolled in this study and divided into training (n=350) and validation cohorts (n=172). Factors associated with occult PM were included in the model: tumor size (odds ratio [OR] 1.194 95% confidence interval [CI], 1.034-1.378; p=0.016), primary location (OR 7.365 95% CI, 2.192-24.746; p=0.001), tumor capsule (OR 4.282 95% CI, 1.209-15.166; p=0.024), Alb (OR 0.813 95% CI, 0.693-0.954; p=0.011) and FIB (OR 2.322 95% CI, 1.410-3.823; p=0.001). The C-index was 0.951 (95% CI, 0.917-0.985) in the training cohort and 0.946 (95% CI, 0.900-0.992) in the validation cohort. In the training cohort, the prediction model had a sensitivity of 82.8%, a specificity of 93.8%, a positive predictive value of 54.7%, and a negative predictive value of 98.4%; the validation cohort values were 94.7%, 85.0%, 43.9% and 99.2%, respectively. DCA and CIC results showed that the nomogram had clinical value in predicting occult PM in GIST patients. CONCLUSION: Imaging and inflammatory indexes are significantly associated with microscopic metastases of GIST. A nomogram including these factors would have an excellent ability to predict occult PM.

14.
Neuroreport ; 31(9): 663-671, 2020 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-32427716

RESUMEN

Effective therapeutic drugs for prevent or reverse the pathobiology of Alzheimer's disease (AD) have not been developed. Icariin (ICA), a prenylated flavonol glycoside derived from the traditional Chinese herb Epimedium sagittatum, exerts a variety of pharmacological activities and shows promise in the treatment and prevention of AD. This study investigated the neuroprotective effects of ICA in SAMP8 mice model of aspects of early AD and explored potential underlying mechanisms. Our results showed that intragastric administration of ICA could reverse the learning and memory impairment of SAMP8 mice in the Morris water maze. Western blot of hippocampal specimens revealed that ICA down-regulated the expression of BACE1 to reduce the expression of cytotoxic Aß1-42. Furthermore, ICA siginificantly increase the Bcl-2/Bax ratio by increasing the expression of anti-apoptotic protein Bcl-2, and decreasing the expression of pro-apoptotic protein Bax, and thus inhibit neurons apoptosis. These findings indicate that ICA could improve cognitive deficits by reducing the deposition of ß1-42 and inhibition of neurons apoptosis and provide further evidence for the clinical efficacy of ICA in the treatment of AD.


Asunto(s)
Péptidos beta-Amiloides/metabolismo , Apoptosis/efectos de los fármacos , Disfunción Cognitiva/metabolismo , Flavonoides/administración & dosificación , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/administración & dosificación , Animales , Disfunción Cognitiva/prevención & control , Modelos Animales de Enfermedad , Masculino
15.
Arab J Gastroenterol ; 21(3): 162-168, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32451200

RESUMEN

BACKGROUND AND STUDY AIMS: To identify the roles and interaction of farnesoid X receptor (FXR) and peroxisome proliferator activated receptors (PPARs) in Non-alcoholic fatty liver disease (NAFLD) pathogenesis. MATERIAL AND METHODS: 16 C57/BL male FXR knockout (KO) mice and sex- and age-matched C57/BL wild type mice were received either standard rodent chow or high-fat and sucrose diet (Blank control, NAFLD, FXR KO and FXR KO NAFLD) for 8 weeks. After that, all mice were sacrificed. Liver tissues and blood samples were collected for laboratory and RT-PCR examination. RESULTS: NAFLD, FXR KO and FXR KO NAFLD mouse models were successful established. Compared with blank control, FXR and PPAR-α mRNA expression decreased significantly (P < 0.05), PPAR-ß expression increased slightly (P > 0.05), PPAR-γ expression increased significantly in NAFLD (P < 0.05). Slight increased PPAR-α mRNA expression (P > 0.05) and markedly decreased PPAR-ß and PPAR-γ expression (P < 0.05) were found in FXR KO. Compared with FXR KO group, there was a slight increase in PPAR-αand PPAR-ßmRNA expression (P > 0.05) and significant increase in PPAR-γ expression (P < 0.05) in FXR KO NAFLD group. Comparison with NAFLD, PPAR-α mRNA expression increased slightly (P > 0.05), PPAR-ß and PPAR-γ expression decreased significantly (P < 0.05) in FXR KO NAFLD. CONCLUSION: FXR and PPARs interaction may play important roles in NAFLD pathogenesis.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Receptores Citoplasmáticos y Nucleares , Animales , Hígado , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/metabolismo , PPAR alfa/metabolismo
16.
World J Gastroenterol ; 26(16): 1901-1911, 2020 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-32390701

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent metabolic disorder with steadily increasing incidence rates worldwide, especially in the West. There are no drugs available at present to treat NAFLD, and the primary therapeutic options include weight loss and the combination of healthy diet and exercise. Therefore, novel interventions are required that can target the underlying risk factors. Gut microbiota is an "invisible organ" of the human body and vital for normal metabolism and immuno-modulation. The number and diversity of microbes differ across the gastrointestinal tract from the mouth to the anus, and is most abundant in the intestine. Since dysregulated gut microbiota is an underlying pathological factor of NAFLD, it is a viable therapeutic target that can be modulated by antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and microbial metabolites. In this review, we summarize the most recent advances in gut microbiota-targeted therapies against NAFLD in clinical and experimental studies, and critically evaluate novel targets and strategies for treating NAFLD.


Asunto(s)
Disbiosis/terapia , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal/inmunología , Enfermedad del Hígado Graso no Alcohólico/terapia , Probióticos/administración & dosificación , Animales , Antibacterianos/administración & dosificación , Ensayos Clínicos como Asunto , Terapia Combinada/métodos , Modelos Animales de Enfermedad , Disbiosis/complicaciones , Disbiosis/inmunología , Disbiosis/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Enfermedad del Hígado Graso no Alcohólico/inmunología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/microbiología , Prebióticos/administración & dosificación , Simbióticos/administración & dosificación , Resultado del Tratamiento
17.
Exp Ther Med ; 19(4): 2650-2660, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32256746

RESUMEN

Ulcerative colitis (UC) is a complex chronic pathological condition of the gut in which microbiota targeted treatment, such as fecal microbiota transplantation (FMT), has shown an encouraging effect. The aim of the present study was to investigate the efficacy and safety of FMT in patients with mild or moderate UC. A single-center, open-label study was designed, including 47 patients with mild or moderate active UC who received three treatments of fresh FMT via colonic transendoscopic enteral tubing within 1 week. The inflammatory bowel disease questionnaire, partial Mayo scores, colonoscopy, erythrocyte sedimentation rate, C-reactive protein level and procalcitoin values were used to assess the efficacy of FMT and alteration in gut microbiota was detected by 16S ribosomal RNA-sequencing. Before FMT, microbiota Faecalibacterium prausnitzii (F. prausnitzii) levels were significantly decreased in patients with UC compared with healthy donors (P<0.01). At 4 weeks post-FMT, F. prausnitzii levels were significantly increased (P<0.05), and the Mayo score was significantly decreased (1.91±1.07 at baseline vs. 4.02±1.47 at week 4; P<0.001) in patients with UC compared with healthy donors. Steroid-free clinical responses were reported in 37 patients (84.1%), and steroid-free clinical remission was achieved in 31 patients (70.5%) at week 4 post-FMT, however, steroid-free remission was not achieved in any patient. No adverse events were reported in 41 (93.2%) patients after FMT or during the 12-week follow-up. Shannon's diversity index and Chao1 estimator were also improved in patients with UC receiving FMT. In conclusion, the results of the present study suggested that FMT resulted in clinical remission in patients with mild to moderate UC, and that the remission may be associated with significant alterations to the intestinal microbiota of patients with UC. Furthermore, F. prausnitzii may serve as a diagnostic and therapeutic biomarker for the use of FMT in UC.

18.
World J Clin Oncol ; 11(12): 1076-1083, 2020 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-33437669

RESUMEN

BACKGROUND: To investigate the clinicopathological features of endometrial clear cell carcinoma that has invaded the right oviduct with a cooccurring ipsilateral oviduct adenomatoid tumor. CASE SUMMARY: A case of endometrial clear cell carcinoma invading the right oviduct with a cooccurring ipsilateral oviduct adenomatoid tumor was collected and analyzed using pathomorphology and immunohistochemistry. Endometrial clear cell carcinoma cells were distributed in a solid nest, papillary, shoe nail-like, and glandular tube-like distribution. There was infiltrative growth, and tumor cells had clear cytoplasm and obvious nuclear heteromorphism. The cancer tissue was necrotic and mitotic. The cancer tissue invaded the right oviduct. The ipsilateral oviduct also had an adenomatoid tumor. The adenomatoid tumor was arranged in microcapsules lined with flat or cubic cells that were surrounded by smooth muscle tissue. The adenomatoid tumor cells were round in shape. CONCLUSION: Clear cell carcinoma of the endometrium can invade the oviduct and occur simultaneously with tubal adenomatoid tumors. Upon pathological diagnosis, one should pay close attention to distinguishing whether an endometrial clear cell carcinoma is invading the oviduct or whether it is accompanied by an adenomatoid tumor of the oviduct. Immunohistochemistry is helpful to differentiate these two disease entities. Endometrial clear cell carcinomas express Napsin-A and P16 and are negative for estrogen receptor and progesterone receptor. The presence of endometrial clear cell carcinoma does not affect the expression of CK and calretinin in adenomatoid tumors.

19.
J Dig Dis ; 20(8): 401-408, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31070838

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for refractory irritable bowel syndrome (IBS). METHODS: Microbiota suspensions from feces of the donors were injected into the intestines of 30 Chinese patients with refractory IBS. Microbiota composition analysis and genomic DNA extraction of fecal samples obtained from these patients at baseline and 1 month after FMT were performed. Clinical efficacy and safety of FMT were assessed using questionnaires covering four aspects of IBS therapeutic efficacy and assessment of adverse effects during a 6-month follow-up. RESULTS: FMT improved IBS gastrointestinal symptoms and alleviated depression and anxiety, as shown by the improved IBS-QOL, IBS-SSS, GSRS, HAMA and HAMD scores at 1 month and 3 months after FMT. A total adverse event rate of FMT was 6.7% (2/30). Gut microbiota analysis revealed that FMT responders had a significantly higher Shannon diversity index before FMT than non-responders. In addition, analysis of differences in bacterial composition before and after FMT in responders showed specific abundance of the phyla Verrucomincrobia and Euryarchaeota at 1 month after FMT. At the genus level, Methanobrevibacter and Akkermansia were the most abundant fecal microbiota 1 month after FMT compared with those before FMT. CONCLUSIONS: FMT may be an effective and safe therapeutic strategy for treating IBS that achieves a sustained clinical response 3-6 months after the first procedure. Changes in the diversity and dominant flora may contribute to its therapeutic effect.


Asunto(s)
Trasplante de Microbiota Fecal , Heces/microbiología , Microbioma Gastrointestinal , Síndrome del Colon Irritable/microbiología , Síndrome del Colon Irritable/terapia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
20.
Chin Med J (Engl) ; 131(11): 1349-1356, 2018 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-29786050

RESUMEN

BACKGROUND: Increasing evidence has supported the link of intestinal Fusobacterium nucleatum infection to colorectal cancer (CRC). However, the value of F. nucleatum as a biomarker in CRC detection has not been fully defined. In order to reduce the random error and bias of individual research, this meta-analysis aimed to evaluate the diagnostic performance of intestinal F. nucleatum in CRC patients and provide evidence-based data to clinical practice. METHODS: An article search was performed from PubMed, Embase, Cochrane Library, and Web of Science databases up to December 2017, using the following key words: "Fusobacterium nucleatum", "Fusobacterium spp.", "Fn", "colorectal cancer(s)", "colorectal carcinoma(s)", "colorectal neoplasm(s)", and "colorectal tumor(s)". Articles on relationships between F. nucleatum and CRC were selected according to the preestablished inclusion and exclusion criteria. This meta-analysis was performed using STATA 12.0 software, which included mapping of forest plots, heterogeneity tests, meta-regression, subgroup analysis, sensitivity analysis, and publication bias. The sensitivity, specificity, positive likelihood ratio (LR), negative LR, diagnostic odds ratio (DOR), and their corresponding 95% confidence interval (CI) of each eligible study were summarized. RESULTS: Finally, data for 1198 participants (629 CRC and 569 healthy controls) in 10 controlled studies from seven articles were included. The summary receiver operator characteristic curve was mapped. The diagnostic performance of intestinal F. nucleatum infection on CRC was as follows: the area under the curve: 0.86 (95% CI: 0.83-0.89), the pooled sensitivity: 0.81 (95% CI: 0.64-0.91), specificity: 0.77 (95% CI: 0.59-0.89), and DOR: 14.00 (95% CI: 9.00-22.00). CONCLUSION: Intestinal F. nucleatum is a valuable marker for CRC diagnosis.


Asunto(s)
Neoplasias del Colon/microbiología , Neoplasias Colorrectales/microbiología , Fusobacterium nucleatum/fisiología , Intestinos/microbiología , Humanos , Intestinos/patología
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