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Probiotics as a complementary therapeutic approach in nonalcoholic fatty liver disease

World Journal of Hepatology 2015年第3期7卷 559-565页

作者： Silvia Marinho Ferolla Geyza Nogueira de Almeida Armiliato claudia alves couto Teresa Cristina Abreu Ferrari Departamento de Clinica Medica Centro de Pos-Graduacao Faculdade de Medicina Universidade Federal de Minas Gerais 30130-100 Belo Horizonte Minas Gerais Brazil

Nonalcoholic fatty liver disease(NAFLD) is currently recognized as one of the most common causes of chronic liver disease. It involves a spectrum of conditionsthat include pure steatosis without inflammation, steatohepatitis, fibrosis and cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance that determines lipid accumulation in the hepatocytes and, thus, oxidative stress, which is followed by inflammatory response. However, NAFLD pathogenesis is still largely unknown and has been extensively investigated. Although life style modification with the aim of losing weight has been advocated to treat this disorder, its effectiveness is limited; additionally, there is no specific pharmacologic treatment until nowadays. Recent evidence suggests that the gut microbiota may play a role in the development of insulin resistance, hepatic steatosis, necroinflammation and fibrosis. Differences in gut microbiota between NAFLD patients and lean individuals as well as presence of small intestinal bacterial overgrowth in NAFLD subjects have been demonstrated. Furthermore, some data indicate that the immunoregulatory effects of probiotics may be beneficial in NAFLD treatment as they modulate the intestinal microbiota; improve epithelial barrier function and strengthen the intestinal wall decreasing its permeability; reduce bacterial translocation and endotoxemia; improve intestinal inflammation; and reduce oxidative and inflammatory liver damage. In this article, we review the clinical trials on the use of probiotics in the treatment of NAFLD and discuss the effects of these agents and their efficacy as an emerging therapeutic resource to treat NAFLD patients.

关键词： Fatty liver Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Probiotic Intestinal microbiota

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PNPLA3 and TM6SF2 polymorphisms in Brazilian patients with nonalcoholic fatty liver disease

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World Journal of Hepatology 2020年第10期12卷 792-806页

作者： Quelson Coelho Lisboa Mateus Jorge Nardelli Patrícia de Araújo Pereira Débora Marques Miranda Stephanie Nunes Ribeiro Raissa Soares Neves Costa Camila Azevedo Versiani Paula Vieira Teixeira Vidigal Teresa Cristina de Abreu Ferrari claudia alves couto Departament de Clínica Médica Faculty of MedicineUniversidade Federal de Minas GeraisBelo Horizonte 30130100Brazil

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is becoming the most common chronic liver disease worldwide,with significant morbidity associated with nonalcoholic steatohepatitis(NASH).Genome-wide association studies demonstrated that the variants rs738409 C/G in the PNPLA3 and rs58542926 C/T in the TM6SF2 genes are determinants of inter-individual and ethnicity-related differences in hepatic fat content and NAFLD *** To investigate PNPLA3 and TM6SF2 genotype frequency and their association with NAFLD development and progression in Brazilian *** This cross-sectional case-control study enrolled 285 individuals from the Gastroenterology and Hepatology clinics at a university hospital in *** case patients(n=148)were confirmed to have NAFLD by the identification of hepatic steatosis on ultrasonography and exclusion of other causes of liver *** to the clinical protocol,patients underwent liver biopsy when at high risk for NASH and/or advanced fibrosis(n=65).Steatohepatitis was confirmed in 54 *** who did not have biopsy indication or NASH on histology were considered to have simple steatosis(n=94).The control group(n=137)was selected among patients that attended the Intestinal Disease clinic and was composed of subjects without abnormalities on abdominal ultrasonography and normal liver biochemical *** individuals underwent PNPLA3 and TM6SF2 genotype *** PNPLA3 CC,CG and GG genotype frequencies were 37%,44%and 19%,respectively,in NAFLD patients and were 58%,31%and 10%in controls(P<0.001).In a model adjusted for gender,age,body mass index and type 2 diabetes mellitus,the G allele increased the chance of NAFLD(OR=1.69,95%CI:1.21-2.36,P=0.002)and NASH(OR=3.50,95%CI:1.84-6.64,P<0.001).The chance of NASH was even higher with GG homozygosis(OR=5.53,95%CI:2.04-14.92,P=0.001).No association was found between G allele and the features of metabolic *** histological assessment,PNPLA3 genoty

关键词： Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Genetic variation Single nucleotide polymorphism Genotype Brazil Fibrosis

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Osteoblasts are inherently programmed to repel sensory innervation

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Bone Research 2020年第3期8卷 343-355页

作者： Luis Leitao Estrela Neto Francisco Conceicao Ana Monteiro Marina couto Cecilia Jalves Daniela MSousa Meriem Lamghari Instituto de Investigacao e Inovacao em Saude(i3S) Universidade do Porto4200-135 PortoPortugal Instituto de Engenharia Biomedica(INEB) Universidade do Porto4200-135 PortoPortugal Instituto de Ciencias Biomedicas Abel Salazar(ICBAS) Universidade do Porto4050-313 PortoPortugal

Tissue innervation is a complex process controlled by the expression profile of signaling molecules secreted by tissue-resident cells that dictate the growth and guidance of *** innervation is part of the neuronal network of the bone tissue with a defined spatiotemporal occurrence during bone ***,the current understanding of the mechanisms regulating the map of sensory innervation in the bone tissue is still ***,we demonstrated that differentiation of human mesenchymal stem cells to osteoblasts leads to a marked impairment of their ability to promote axonal growth,evidenced under sensory neurons and osteoblastic-lineage cells *** mechanisms by which osteoblast lineage cells provide this nonpermissive environment for axons include paracrine-induced repulsion and loss of neurotrophic factors *** identified a drastic reduction of NGF and BDNF production and stimulation of Sema3A,Wnt4;and Shh expression culminating at late stage of OB *** noted a correlation between Shh expression profile,OB differentiation stages,and OB-mediated axonal *** of Shh activity and signaling reversed the repulsive action of osteoblasts on sensory ***,to strengthen our model,we localized the expression of Shh by osteoblasts in bone ***,our findings provide evidence that the signaling profile associated with osteoblast phenotype differentiating program can regulate the patterning of sensory innervation,and highlight osteoblast-derived Shh as an essential player in this cue-induced regulation.

关键词： stimulation innervation reversed

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