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1.
Stem Cell Res Ther ; 13(1): 179, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505419

RESUMO

Mesenchymal stem cell (MSC) transplantation, as an alternative strategy to orthotopic liver transplantation, has been evaluated for treating end-stage liver disease. Although the therapeutic mechanism of MSC transplantation remains unclear, accumulating evidence has demonstrated that MSCs can regenerate tissues and self-renew to repair the liver through differentiation into hepatocyte-like cells, immune regulation, and anti-fibrotic mechanisms. Multiple clinical trials have confirmed that MSC transplantation restores liver function and alleviates liver damage. A sufficient number of MSCs must be home to the target tissues after administration for successful application. However, inefficient homing of MSCs after systemic administration is a major limitation in MSC therapy. Here, we review the mechanisms and clinical application status of MSCs in the treatment of liver disease and comprehensively summarize the molecular mechanisms of MSC homing, and various strategies for promoting MSC homing to improve the treatment of liver disease.


Assuntos
Hepatopatias , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Diferenciação Celular , Humanos , Cirrose Hepática/terapia , Hepatopatias/terapia
2.
Front Immunol ; 13: 860661, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371024

RESUMO

MicroRNAs (miRNAs) are endogenous non-coding single-stranded small molecule RNAs consisting of 20-24 nucleotides that are highly conserved in species evolution. Expression of miRNAs is strictly tissue-specific, and it is chronological in fungi and plants, as well as in animals. MiR-223 has been shown to play a key role in innate immunity, and dysregulation of its expression contributes to the pathogenesis of multiple inflammatory diseases, and cancers. In this article the biosynthesis and functions of miR-223 in innate immunity are reviewed, and the role of miR-223 in liver physiopathology and therapeutic prospects are highlighted.


Assuntos
Hepatopatias , MicroRNAs , Neoplasias , Animais , Imunidade Inata , Hepatopatias/genética , Hepatopatias/terapia
3.
Clin Liver Dis ; 26(2): 229-243, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35487607

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder that leads to chronic kidney disease and end-stage kidney disease (ESKD). Polycystic liver disease (PCLD) is the most common extrarenal manifestation of ADPKD. Though isolated PCLD and PCLD due to ADPKD are genetically distinct, they follow a similar clinical course of hepatomegaly from multiple cysts with preserved liver function. Tolvaptan use in ADPKD can slow down the deterioration of renal function and growth of cysts. Somatostatin analogs can slow the growth of polycystic livers but the effect is short-lived. The only curative therapy for PCLD is liver transplantation. Renal transplantation can significantly improve survival in patients with ESKD due to ADPKD.


Assuntos
Cistos , Hepatopatias , Doenças Renais Policísticas , Rim Policístico Autossômico Dominante , Cistos/terapia , Feminino , Humanos , Rim/fisiologia , Hepatopatias/etiologia , Hepatopatias/terapia , Masculino , Doenças Renais Policísticas/terapia , Rim Policístico Autossômico Dominante/terapia
4.
Zhonghua Gan Zang Bing Za Zhi ; 30(3): 233-236, 2022 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-35462476

RESUMO

There are increasing number of clinical studies on the use of stem cells in the treatment of liver diseases. Most studies have shown that stem cells can significantly improve liver function and prolong survival in patients with decompensated cirrhosis and liver failure. However, the current study has high heterogeneity and few mechanistic research data, which cannot answer many key questions about stem cell therapy for liver diseases. This paper reviews the research status of stem cells, in order to clarify the existing problems and challenges, and puts forward some reflections and countermeasures, with hope to promote the clinical application of stem cells in the treatment of liver diseases.


Assuntos
Hepatopatias , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Cirrose Hepática/terapia , Hepatopatias/terapia
5.
Zhonghua Gan Zang Bing Za Zhi ; 30(3): 237-243, 2022 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-35462477

RESUMO

The high incidence of chronic liver disease is a serious threat to public health, and the current comprehensive internal medicine treatment is ineffective. Liver transplantation is limited by the shortage of liver source and post-transplant rejection, and thus unmet the clinical needs. More importantly, cell therapy shows great promise for the treatment of chronic liver disease. Over recent years, domestic and foreign scholars have carried out a variety of cell therapy preclinical and clinical trials for critical liver disease, and achieved certain results, providing new methods for the treatment of chronic liver diseases. This review discusses the cell therapy research status and application progress, various existing problems and challenges, and key issues of mesenchymal stem cells in the treatment of chronic liver diseases.


Assuntos
Hepatopatias , Transplante de Fígado , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Hepatopatias/terapia , Transplante de Fígado/métodos
6.
Zhonghua Gan Zang Bing Za Zhi ; 30(3): 253-263, 2022 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-35462480

RESUMO

In 2015, the Chinese Society of Hepatology and Chinese Society of Gastroenterology issued the consensus on the diagnosis and management of cholestatic liver diseases. In the past years, more data have emerged from clinical practice. Herein, the Autoimmune Liver Disease Group of the Chinese Society of Hepatology organized an expert group to review the evidence and updated the recommendations to formulate the guidelines. There are 22 recommendations on clinical practice of cholestatic liver diseases. The guidelines aim to provide a working reference for the management of cholestatic liver diseases.


Assuntos
Doenças Autoimunes , Colestase , Gastroenterologia , Hepatopatias , Doenças Autoimunes/diagnóstico , Colestase/diagnóstico , Colestase/terapia , Consenso , Humanos , Hepatopatias/diagnóstico , Hepatopatias/terapia
7.
Front Immunol ; 13: 865888, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464407

RESUMO

Various factors, including viral and bacterial infections, autoimmune responses, diabetes, drugs, alcohol abuse, and fat deposition, can damage liver tissue and impair its function. These factors affect the liver tissue and lead to acute and chronic liver damage, and if left untreated, can eventually lead to cirrhosis, fibrosis, and liver carcinoma. The main treatment for these disorders is liver transplantation. Still, given the few tissue donors, problems with tissue rejection, immunosuppression caused by medications taken while receiving tissue, and the high cost of transplantation, liver transplantation have been limited. Therefore, finding alternative treatments that do not have the mentioned problems is significant. Cell therapy is one of the treatments that has received a lot of attention today. Hepatocytes and mesenchymal stromal/stem cells (MSCs) are used in many patients to treat liver-related diseases. In the meantime, the use of mesenchymal stem cells has been studied more than other cells due to their favourable characteristics and has reduced the need for liver transplantation. These cells increase the regeneration and repair of liver tissue through various mechanisms, including migration to the site of liver injury, differentiation into liver cells, production of extracellular vesicles (EVs), secretion of various growth factors, and regulation of the immune system. Notably, cell therapy is not entirely excellent and has problems such as cell rejection, undesirable differentiation, accumulation in unwanted locations, and potential tumorigenesis. Therefore, the application of MSCs derived EVs, including exosomes, can help treat liver disease and prevent its progression. Exosomes can prevent apoptosis and induce proliferation by transferring different cargos to the target cell. In addition, these vesicles have been shown to transport hepatocyte growth factor (HGF) and can promote the hepatocytes'(one of the most important cells in the liver parenchyma) growths.


Assuntos
Vesículas Extracelulares , Hepatopatias , Células-Tronco Mesenquimais , Vesículas Extracelulares/metabolismo , Fibrose , Humanos , Imunomodulação , Hepatopatias/etiologia , Hepatopatias/metabolismo , Hepatopatias/terapia , Células-Tronco Mesenquimais/metabolismo
8.
Front Cell Infect Microbiol ; 12: 774335, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35444959

RESUMO

The liver is directly connected to the intestines through the portal vein, which enables the gut microbiota and gut-derived products to influence liver health. There is accumulating evidence of decreased gut flora diversity and alcohol sensitivity in patients with various chronic liver diseases, including non-alcoholic/alcoholic liver disease, chronic hepatitis virus infection, primary sclerosing cholangitis and liver cirrhosis. Increased intestinal mucosal permeability and decline in barrier function were also found in these patients. Followed by bacteria translocation and endotoxin uptake, these will lead to systemic inflammation. Specific microbiota and microbiota-derived metabolites are altered in various chronic liver diseases studies, but the complex interaction between the gut microbiota and liver is missing. This review article discussed the bidirectional relationship between the gut and the liver, and explained the mechanisms of how the gut microbiota ecosystem alteration affects the pathogenesis of chronic liver diseases. We presented gut-microbiota targeted interventions that could be the new promising method to manage chronic liver diseases.


Assuntos
Microbioma Gastrointestinal , Hepatopatias , Microbiota , Probióticos , Disbiose/microbiologia , Disbiose/terapia , Humanos , Intestinos/microbiologia , Fígado/metabolismo , Hepatopatias/microbiologia , Hepatopatias/terapia
10.
Int J Mol Sci ; 23(5)2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35269830

RESUMO

Drug-induced liver injury (DILI) is one of the leading causes of acute liver injury. Many factors may contribute to the susceptibility of patients to this condition, making DILI a global medical problem that has an impact on public health and the pharmaceutical industry. The use of mesenchymal stem cells (MSCs) has been at the forefront of regenerative medicine therapies for many years, including MSCs for the treatment of liver diseases. However, there is currently a huge gap between these experimental approaches and their application in clinical practice. In this concise review, we focus on the pathophysiology of DILI and highlight new experimental approaches conceived to improve cell-based therapy by the in vitro preconditioning of MSCs and/or the use of cell-free products as treatment for this liver condition. Finally, we discuss the advantages of new approaches, but also the current challenges that must be addressed in order to develop safer and more effective procedures that will allow cell-based therapies to reach clinical practice, enhancing the quality of life and prolonging the survival time of patients with DILI.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Hepatopatias , Células-Tronco Mesenquimais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/terapia , Humanos , Hepatopatias/etiologia , Hepatopatias/terapia , Qualidade de Vida
11.
BMB Rep ; 55(4): 166-174, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35321784

RESUMO

Hepatic macrophages are key immune cells associated with the broad ranges of liver diseases including steatosis, inflammation and fibrosis. Hepatic macrophages interact with other immune cells and orchestrate hepatic immune circumstances. Recently, the heterogenous populations of hepatic macrophages have been discovered termed residential Kupffer cells and monocyte-derived macrophages, and identified their distinct population dynamics during the progression of various liver diseases. Liver injury lead to Kupffer cells activation with induction of inflammatory cytokines and chemokines, which triggers recruitment of inflammatory monocyte-derived macrophages. To understand liver pathology, the functions of different subtypes of liver macrophages should be regarded with different perspectives. In this review, we summarize recent advances in the roles of hepatic macrophages under liver damages and suggest hepatic macrophages as promising therapeutic targets for treating liver diseases. [BMB Reports 2022; 55(4): 166-174].


Assuntos
Macrófagos do Fígado , Hepatopatias , Citocinas , Humanos , Fígado/patologia , Hepatopatias/patologia , Hepatopatias/terapia , Macrófagos/fisiologia
12.
Front Immunol ; 13: 833878, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35309311

RESUMO

Mesenchymal stem cells (MSCs), as the most common cell source for stem cell therapy, play an important role in the modulation of innate and adaptive immune responses and have been widely used in clinical trials to treat autoimmune and inflammatory diseases. Recent experimental and clinical studies have shown that MSC-derived extracellular vesicles (MSC-EVs) can inhibit the activation and proliferation of a variety of proinflammatory cells, such as Th1, Th17 and M1 macrophages, reducing the secretion of proinflammatory cytokines, while promoting the proliferation of anti-inflammatory cells, such as M2 macrophages and Tregs, and increasing the secretion of anti-inflammatory cytokines, thus playing a role in immune regulation and exhibiting immunomodulatory functions. Besides MSC-EVs are more convenient and less immunogenic than MSCs. There is growing interest in the role of MSC-EVs in liver diseases owing to the intrinsic liver tropism of MSC-EVs. In this review, we focus on the immunomodulatory effects of MSC-EVs and summarize the pivotal roles of MSC-EVs as a cell-free therapy in liver diseases, including NAFLD, AIH, acute liver failure, liver fibrosis and hepatic ischemia-reperfusion injury. Moreover, we provide a concise overview of the potential use and limits of MSC-EVs in clinical application.


Assuntos
Vesículas Extracelulares , Hepatopatias , Células-Tronco Mesenquimais , Anti-Inflamatórios , Citocinas , Vesículas Extracelulares/fisiologia , Humanos , Hepatopatias/terapia
13.
Sci Transl Med ; 14(636): eabl9238, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35294257

RESUMO

Prime editing is a highly versatile CRISPR-based genome editing technology that works without DNA double-strand break formation. Despite rapid technological advances, in vivo application for the treatment of genetic diseases remains challenging. Here, we developed a size-reduced SpCas9 prime editor (PE) lacking the RNaseH domain (PE2ΔRnH) and an intein-split construct (PE2 p.1153) for adeno-associated virus-mediated delivery into the liver. Editing efficiencies reached 15% at the Dnmt1 locus and were further elevated to 58% by delivering unsplit PE2ΔRnH via human adenoviral vector 5 (AdV). To provide proof of concept for correcting a genetic liver disease, we used the AdV approach for repairing the disease-causing Pahenu2 mutation in a mouse model of phenylketonuria (PKU) via prime editing. Average correction efficiencies of 11.1% (up to 17.4%) in neonates led to therapeutic reduction of blood phenylalanine, without inducing detectable off-target mutations or prolonged liver inflammation. Although the current in vivo prime editing approach for PKU has limitations for clinical application due to the requirement of high vector doses (7 × 1014 vg/kg) and the induction of immune responses to the vector and the PE, further development of the technology may lead to curative therapies for PKU and other genetic liver diseases.


Assuntos
Hepatopatias , Fenilcetonúrias , Animais , Dependovirus/genética , Dependovirus/metabolismo , Edição de Genes , Hepatopatias/genética , Hepatopatias/terapia , Camundongos , Fenilcetonúrias/genética , Fenilcetonúrias/terapia
14.
World J Gastroenterol ; 28(8): 775-793, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35317103

RESUMO

Diabetes mellitus (DM) is common in liver cirrhosis (LC). The pathophysiological association is bidirectional. DM is a risk factor of LC and LC is a diabetogenic condition. In the recent years, research on different aspects of the association DM and LC has been intensified. Nevertheless, it has been insufficient and still exist many gaps. The aims of this review are: (1) To discuss the latest understandings of the association of DM and LC in order to identify the strategies of early diagnosis; (2) To evaluate the impact of DM on outcomes of LC patients; and (3) To select the most adequate management benefiting the two conditions. Literature searches were conducted using PubMed, Ovid and Scopus engines for DM and LC, diagnosis, outcomes and management. The authors also provided insight from their own published experience. Based on the published studies, two types of DM associated with LC have emerged: Type 2 DM (T2DM) and hepatogenous diabetes (HD). High-quality evidences have determined that T2DM or HD significantly increase complications and death pre and post-liver transplantation. HD has been poorly studied and has not been recognized as a complication of LC. The management of DM in LC patients continues to be difficult and should be based on drug pharmacokinetics and the degree of liver failure. In conclusion, the clinical impact of DM in outcomes of LC patients has been the most studied item recently. Nevertheless many gaps still exist particularly in the management. These most important gaps were highlighted in order to propose future lines for research.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatias , Falência Hepática , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/terapia , Hepatopatias/complicações , Hepatopatias/diagnóstico , Hepatopatias/terapia , Falência Hepática/complicações , Fatores de Risco
15.
Cells ; 11(2)2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-35053347

RESUMO

Changes in the structure and function of blood vessels are important factors that play a primary role in regeneration of injured organs. WKYMVm has been reported as a therapeutic factor that promotes the migration and proliferation of angiogenic cells. Additionally, we previously demonstrated that placenta-derived mesenchymal stem cells (PD-MSCs) induce hepatic regeneration in hepatic failure via antifibrotic effects. Therefore, our objectives were to analyze the combination effect of PD-MSCs and WKYMVm in a rat model with bile duct ligation (BDL) and evaluate their therapeutic mechanism. To analyze the anti-fibrotic and angiogenic effects on liver regeneration, it was analyzed using ELISA, qRT-PCR, Western blot, immunofluorescence, and immunohistochemistry. Collagen accumulation was significantly decreased in PD-MSCs with the WKYMVm combination (Tx+WK) group compared with the nontransplantation (NTx) and PD-MSC-transplanted (Tx) group (p < 0.05). Furthermore, the combination of PD-MSCs with WKYMVm significantly promoted hepatic function by increasing hepatocyte proliferation and albumin as well as angiogenesis by activated FPR2 signaling (p < 0.05). The combination therapy of PD-MSCs with WKYMVm could be an efficient treatment in hepatic diseases via vascular remodeling. Therefore, the combination therapy of PD-MSCs with WKYMVm could be a new therapeutic strategy in degenerative medicine.


Assuntos
Hepatopatias/fisiopatologia , Hepatopatias/terapia , Fígado/fisiopatologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Oligopeptídeos/farmacologia , Placenta/citologia , Remodelação Vascular , Animais , Terapia Combinada , Modelos Animais de Doenças , Feminino , Fígado/efeitos dos fármacos , Gravidez , Ratos , Remodelação Vascular/efeitos dos fármacos
16.
Cytotherapy ; 24(4): 376-384, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35086779

RESUMO

The fetal liver is unique because of the coexistence of cells with endodermal and mesenchymal origins, making it a potential source of hepatic and pancreatic regenerative medicine. The liver appears at about the third week of gestation, growing rapidly from the fifth to the 10th week. We define fetal liver from 10 weeks of gestation, when hematopoietic progenitor cells gradually migrate from the aorta-mesonephros-gonad region to colonize the liver. Indeed, the fetal liver may be the most available source of cell therapy for liver disease. We conducted a review of the literature using Medline and EMBASE (up to May 2021) to identify clinical studies in which patients with liver disease had been given fetal liver cell therapy. This literature review highlighted the heterogeneity of cell isolation and selection protocols, which hinders the ability to pool data and perform a meta-analysis. A limitation of the studies analyzed was the scarcity of reports (n = 8) and the extremely small sample sizes (median sample size of treated patients was two), although there was a fairly long follow-up (median 12 months). The weeks after conception ranged from 16 to 34. There were no randomized controlled trials, and therefore no study was stratified as being of good methodological quality. Cryopreservation may help to circumvent the critical logistic issues that hamper the use of fetal liver cell therapy in clinical practice. To help consolidate the role of the fetal liver in regenerative medicine, good preclinical translational studies are necessary, whereas tracing strategies and biopsy-based endpoints are crucial in the clinic, along with well-designed, large, multicenter, randomized controlled trials using clinically applicable primary outcomes and refined imaging assessment.


Assuntos
Hepatopatias , Terapia Baseada em Transplante de Células e Tecidos , Hepatócitos , Humanos , Hepatopatias/terapia , Metanálise como Assunto , Estudos Multicêntricos como Assunto , Resultado do Tratamento
17.
Aliment Pharmacol Ther ; 55(4): 389-400, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35048397

RESUMO

BACKGROUND: Cystic fibrosis-related liver disease (CFLD) is the leading cause of death in cystic fibrosis (CF), after pulmonary disease. To improve identification and management of this condition requires an understanding of the underlying disease mechanism. AIMS: This review summarises the current understanding of CFLD epidemiology, pathology, diagnosis and management. METHODS: Relevant reports on cystic fibrosis liver disease were identified using a literature search and summarised. RESULTS: CFLD is a heterogeneous condition with several different co-existent pathologies, including environmental and genetic factors. Incidence of clinically significant CFLD continues at a linear rate into early adulthood and has been described in up to 25% of CF patients. Diagnosis strategies lack precision and patient risk stratification needs to look beyond Childs-Pugh scoring. Efficacious therapies are lacking and, at present, newer modulator therapies lack data in CFLD and carry an increased risk of hepatotoxicity. Outcomes of liver transplant are comparable to non-CF transplant indications. CONCLUSIONS: The incidence of CFLD increases with age and hence is increasingly important to adult patients with CF. Effective therapies are lacking. For progress to be made a better understanding of pathogenesis and disease detection are required.


Assuntos
Fibrose Cística , Hepatopatias , Transplante de Fígado , Adulto , Criança , Fibrose Cística/complicações , Fibrose Cística/epidemiologia , Fibrose Cística/terapia , Humanos , Incidência , Hepatopatias/complicações , Hepatopatias/epidemiologia , Hepatopatias/terapia , Transplante de Fígado/efeitos adversos
18.
Curr Opin Pediatr ; 34(2): 184-190, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35051980

RESUMO

PURPOSE OF REVIEW: Parenteral nutrition is an integral part of the care of infants in the neonatal ICU. However, prolonged use of parenteral nutrition can be associated with adverse outcomes, most notably parenteral nutrition-associated liver disease, now known as intestinal failure-associated liver disease (IFALD). This review highlights pertinent developments in the epidemiology of IFALD as it pertains to neonates and showcases recent advances in the pathophysiology, treatment, and outcomes of neonates with IFALD. RECENT FINDINGS: The role of intravenous lipid emulsions in the pathogenesis, prevention, and treatment of IFALD remains a target for investigative studies. Recent data continues to support the use of fish-oil based intravenous lipids, but its use is limited due to concerns for essential fatty acid deficiency. Use of soy-based lipids and mixed lipids is not wrought with such concerns as these are often used at greater doses but their use is limited due to higher proinflammatory fatty acid content, increased phytosterols and decreased antioxidants, risk factors for the development of IFALD. SUMMARY: Hepatic complications may limit the use of parenteral nutrition in the neonatal ICU. However, the pathophysiology of IFALD is continuing to be further elucidated and novel targets are being developed for the treatment of IFALD. As noninvasive disease monitoring strategies continue to be developed, early enteral nutrition ameliorates the risk of IFALD and should be considered when possible.


Assuntos
Enteropatias , Hepatopatias , Animais , Emulsões Gordurosas Intravenosas/efeitos adversos , Ácidos Graxos , Óleos de Peixe , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Enteropatias/complicações , Enteropatias/terapia , Hepatopatias/etiologia , Hepatopatias/terapia , Óleo de Soja/efeitos adversos
19.
Int J Biol Sci ; 18(1): 292-300, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34975333

RESUMO

Fibrinogen-like protein 1 (FGL1) is a novel hepatokine that forms part of the fibrinogen superfamily. It is predominantly expressed in the liver under normal physiological conditions. When the liver is injured by external factors, such as chemical drugs and radiation, FGL1 acts as a protective factor to promote the growth of regenerated cells. However, elevated hepatic FGL1 under high fat conditions can cause lipid accumulation and inflammation, which in turn trigger the development of non-alcoholic fatty liver disease, diabetes, and obesity. FGL1 is also involved in the regulation of insulin resistance in adipose tissues and skeletal muscles as a means of communication between the liver and other tissues. In addition, the abnormally changed FGL1 levels in the plasma of cancer patients make it a potential predictor of cancer incidence in clinical practice. FGL1 was recently identified as a major functional ligand of the immune inhibitory receptor, lymphocyte-activation gene 3 (LAG3), thus making it a promising target for cancer immunotherapy except for the classical programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) axis. Despite the potential of FGL1 as a new cancer biomarker and therapeutic target, there are few related studies and much of what has been reported are superficial and lack depth and particularity. Therefore, elucidating the role and underlying mechanisms of FGL1 could be crucial for the development of promising diagnostic and therapeutic strategies for related diseases. Here, we provide a comprehensive review of the cellular mechanisms and clinical prospects of FGL1 in the prevention and treatment of liver diseases, metabolic disorders and cancer, and proffer suggestions for future studies.


Assuntos
Fibrinogênio/metabolismo , Imunoterapia/métodos , Hepatopatias/metabolismo , Doenças Metabólicas/metabolismo , Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Humanos , Hepatopatias/terapia , Doenças Metabólicas/terapia , Neoplasias/terapia
20.
Aliment Pharmacol Ther ; 55(1): 49-63, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34713470

RESUMO

BACKGROUND: Intestinal failure-associated liver disease (IFALD) increases mortality of patients with intestinal failure (IF), but lacks effective prevention or treatment approaches. Bile acids, gut microbiota and the host have close and complex interactions, which play a central role in modulating host immune and metabolic homeostasis. Increasing evidence suggests that derangement of the bile acid-gut microbiota (BA-GM) axis contributes to the development of IFALD. AIMS: To review the BA-GM axis in the pathogenesis and clinical applications of IFALD, and to explore future directions for effective disease management. METHODS: We conducted a literature search on bile acid and gut microbiota in IF and liver diseases. RESULTS: The BA-GM axis demonstrates a unique IF signature manifesting as an increase in primary-to-secondary bile acids ratio, disturbed enterohepatic circulation, blunted bile acid signalling pathways, gut microbial dysbiosis, and altered microbial metabolic outputs. Bile acids and gut microbiota shape the compositional and functional alterations of each other in IF; collaboratively, they promote immune dysfunction and metabolic aberration in the liver. Diagnostic markers and treatments targeting the BA-GM axis showed promising potential in the management of IFALD. CONCLUSIONS: Bile acids and gut microbiota play a central role in the development of IFALD and make attractive biomarkers as well as therapeutic targets. A multitarget, individualised therapy aiming at different parts of the BA-GM axis may provide optimal clinical benefits and requires future investigation.


Assuntos
Microbioma Gastrointestinal , Hepatopatias , Ácidos e Sais Biliares , Humanos , Fígado , Hepatopatias/etiologia , Hepatopatias/terapia
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