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1.
Gene ; 806: 145935, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34478821

RESUMO

Soluble molecules of programmed death ligand 1 (sPD-L1) are known to modulate T-cell depletion, an important mechanism of hepatitis B virus (HBV) persistence and liver disease progression. In addition, PD-L1 polymorphisms in the 3'-UTR can influence PD-L1 expression and have been associated with cancer risk, although not definitively. The purpose of this study was to investigate the association of PD-L1 polymorphisms and circulating levels of sPD-L1 in HBV infection and live disease progression. In this study, five hundred fifty-one HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n = 186), liver cirrhosis (LC, n = 142) and hepatocellular carcinoma (HCC, n = 223) and 240 healthy individuals (HC) were enrolled. PD-L1 polymorphisms (rs2297136 and rs4143815) were genotyped by in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of PD-L1 polymorphisms with HBV infection as well as with progression of related liver diseases. Plasma sPD-L1 levels were quantified by ELISA assays. The PD-L1 rs2297136 AA genotype was associated with HBV infection susceptibility (HBV vs. HC: OR = 1.6; 95%CI = 1.1-2.3; p = 0.0087) and disease progression (LC vs. CHB: OR = 1.8; 95%CI = 1.1-2.9; p = 0.018). Whereas, the rs2297136 GG genotype was a protective factor for HCC development. Plasma sPD-L1 levels were significantly high in HBV patients (p < 0.0001) and higher in the LC followed by CHB and HCC groups. High sPD-L1 levels correlated with increased liver enzymes and with advanced liver disease progression (Child-pugh C > B > A, p < 0.0001) and BCLC classification (BCLC D > C > B > A, p = 0.031). We could, for the first time, conclude that PD-L1 rs2297136 polymorphism and plasma sPD-L1 protein levels associate with HBV infection and HBV-related liver disease progression.


Assuntos
Antígeno B7-H1/genética , Carcinoma Hepatocelular/genética , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Polimorfismo Genético , Regiões 3' não Traduzidas , Adulto , Idoso , Antígeno B7-H1/sangue , Biomarcadores/sangue , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Expressão Gênica , Predisposição Genética para Doença , Vírus da Hepatite B/crescimento & desenvolvimento , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/virologia , Humanos , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes
2.
Infectio ; 25(4): 250-255, oct.-dic. 2021. tab
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1286718

RESUMO

Resumen Introducción: Las alteraciones de la bioquímica hepática son frecuentes en los pacientes con infección por VIH, la etiología es variada, la esteatosis hepática es frecuente con una prevalencia estimada del 60% Objetivos: Caracterizar las alteraciones hepáticas en una serie de pacientes con infección por VIH en un centro de investigación de Bogotá Colombia durante el periodo 2009 - 2019. Materiales y Métodos: Estudio descriptivo, retrospectivo, observacional de pacientes con infección por VIH que asistieron a un centro de investigación durante los años 2009-2019. Resultados: 94% fueron hombres y 6% mujeres con edad promedio de 44 años, 92,5% de los pacientes presentaba uso de terapia antiretroviral. Las principales hepatopatías fueron la coinfección VIH-Hepatitis C y el hígado graso en iguales porcentajes, 31,3%. El promedio del indice HOMA fue de 2,58. Discusión: Las enfermedades hepáticas son una causa importante de morbimortalidad en pacientes con infección por VIH, las coinfecciones virales y el hígado graso pueden ser muy frecuentes en nuestro medio a diferencia de otros estudios Conclusiones: Este es el primer estudio a nivel local en describir las alteraciones hepáticas en pacientes con VIH, las comorbilidades no SIDA, juegan un papel importante dentro de la enfermedad. La hepatitis C continúa siendo una coinfección frecuente en la población VIH.


Abstract Introduction: Alterations in liver biochemistry are frequent in patients with HIV infection, the etiology is varied and includes multiple causes, liver steatosis is one of the most frequent with an estimated prevalence of 60% after the appearance of antiretroviral treatment Objectives: To characterize liver disorders in a series of patients with HIV infection at a research center in Bogotá Colombia during the period 2009-2019. Materials and Methods: Descriptive, retrospective, observational study of patients with HIV infection who attended a disease research center during the years 2009-2019. Results: 67 clinical histories were reviewed, 94% were men and 6% women with an average age of 44 years, 92.5% of the patients had use of anti-retroviral therapy and the diagnosis of HIV was known 11.7 years ago on average. The main liver diseases were HIV-Hepatitis C coinfection and fatty liver in equal percentages, 31.3%. The average HOMA index was 2.58. Discussion: Liver diseases are an important cause of morbidity and mortality in patients with HIV infection. Viral coinfections and fatty liver can be very frequent in our setting, unlike other studies. Conclusions: This is the first study locally to describe the liver disorders in patients with HIV, non-AIDS comorbidities, including fatty liver, play an important role in the disease and could behave like the general population. Hepatitis C continues to be a frequent coinfection in the HIV population.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Infecções por HIV , Hepatopatias , Terapêutica , Prevalência , Síndrome de Imunodeficiência Adquirida , Hepatite C , Colômbia , Fígado Gorduroso , Fígado
3.
J Agric Food Chem ; 69(36): 10572-10580, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34490775

RESUMO

Bile acids are being increasingly investigated in humans and laboratory animals as markers for various diseases in addition to their important functions, such as promoting the emulsification in fat digestion and preventing gallstone formation. In humans and animals, primary bile acids are formed from cholesterol in the liver, converted in the intestine into various secondary bile acids by the intestinal microbiota and reabsorbed in the terminal ileum, and partially returned to the liver. A universal high-throughput workflow, including a simple workup, was applied as a tool for bile acid analysis in animal studies. The complex bile acid profiles in various tissues, organs, and body fluids from different animals were mapped using a newly developed comprehensive liquid chromatography-tandem mass spectrometry method. The method can also be used in screening food to obtain information about the nutritional content of bile acids. This could be relevant to investigations on various animal diseases and on the bioavailability of bile acids that pass through the gastric tract.


Assuntos
Ácidos e Sais Biliares , Líquidos Corporais , Animais , Cromatografia Líquida , Humanos , Fígado , Espectrometria de Massas em Tandem
4.
Virulence ; 12(1): 2430-2442, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34517779

RESUMO

Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is currently causing a worldwide threat with its unusually high transmission rates and rapid evolution into diverse strains. Unlike typical respiratory viruses, SARS-CoV-2 frequently causes systemic infection by breaking the boundaries of the respiratory systems. The development of animal models recapitulating the clinical manifestations of COVID-19 is of utmost importance not only for the development of vaccines and antivirals but also for understanding the pathogenesis. However, there has not been developed an animal model for systemic infection of SARS-CoV-2 representing most aspects of the clinical manifestations of COVID-19 with systemic symptoms. Here we report that a Roborovski hamster strain SH101, a laboratory inbred hamster strain of P. roborovskii, displayed most symptoms of systemic infection upon SARS-CoV-2 infection as in the case of the human counterpart, unlike current COVID-19 animal models. Roborovski hamster strain SH101 post-infection of SARS-CoV-2 represented most clinical symptoms of COVID-19 such as snuffling, labored breathing, dyspnea, cough, hunched posture, progressive weight loss, ruffled fur, and high fever following shaking chills. Histological examinations also revealed initial right-predominated pneumonia as well as slight organ damages in the brain and liver, manifesting systemic COVID-19 cases. Considering the merit of a small animal as well as its clinical manifestations of SARS-CoV-2 infection in human, this hamster model seems to provide an ideal tool to investigate COVID-19.


Assuntos
COVID-19 , Cricetinae/classificação , Modelos Animais de Doenças , SARS-CoV-2 , Animais , Temperatura Corporal , Encéfalo/patologia , COVID-19/patologia , COVID-19/fisiopatologia , Feminino , Fígado/patologia , Pulmão/patologia , Masculino , Mesocricetus , Camundongos , Camundongos Transgênicos
5.
Zhonghua Bing Li Xue Za Zhi ; 50(9): 1029-1033, 2021 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-34496494

RESUMO

Objective: To investigate the clinicopathological features of hepatic vascular tumors in children. Methods The clinical characteristics, histology and immunohistochemical staining results were summarized and analyzed in 22 cases of hepatic vascular tumors in children at Guangzhou Women and Children's Medical Center from September 2007 to November 2020. Results: The 22 patients aged from 1.0 month to 2.5 years (mean age 9 months). There were 10 males and 12 females. Five cases were found in premature and had low birth weight infants; three cases were discovered in the antenatal period; one patient also had cutanous hemangioma; six patients had associated anemia; Kasabach-Merritt phenomenon was not seen in any patient. CT examination showed 17 tumors were solitary and five were multifocal lesions. Macroscopically, the tumors size ranged from was 0.6 cm to 11.0 cm; the cut surface was solid, gray red and brown in color, and in six cases there were hemorrhage and necrosis in the central area. Microscopically,15 cases of solitary congenital hepatic hemangiomas showed characteristic necrosis in the central area, with loose fibrous tissues at periphery. Proliferation of capillaries, residual bile ducts between the vascular lumens, and dilated thrombosed vascular channels were seen, and contained extramedullary hematopoietic foci and calcification. Five cases of multiple hepatic infantile hemangiomas showed capillaries of different sizes composing of plump endothelium and pericytes and were arranged in lobular or diffuse patterns. Two cases of cavernous hemangioma (venous malformation) consisted of dilated thin-walled blood vessels with branch-like pattern lined with flat endothelial cells. Immunohistochemically, all 22 case expressed vascular endothelial markers CD31 and CD34, but D2-40 was negative. Glut1 was positive in five cases of multiple hepatic infantile hemangiomas, and the other cases were negative. Conclusion: Hepatic vascular tumors in children are rare, and their classification is different from that of adults. It is of great significance to make clear pathologic diagnosis.


Assuntos
Hemangioma , Síndrome de Kasabach-Merritt , Neoplasias Vasculares , Criança , Células Endoteliais , Feminino , Humanos , Lactente , Fígado , Masculino , Gravidez
6.
World J Gastroenterol ; 27(30): 4999-5018, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34497431

RESUMO

Metabolic associated fatty liver disease (MAFLD), formerly named "nonalcoholic fatty liver disease" occurs in about one-third of the general population of developed countries worldwide and behaves as a major morbidity and mortality risk factor for major causes of death, such as cardiovascular, digestive, metabolic, neoplastic and neuro-degenerative diseases. However, progression of MAFLD and its associated systemic complications occur almost invariably in patients who experience the additional burden of intrahepatic and/or systemic inflammation, which acts as disease accelerator. Our review is focused on the new knowledge about the brain-gut-liver axis in the context of metabolic dysregulations associated with fatty liver, where insulin resistance has been assumed to play an important role. Special emphasis has been given to digital imaging studies and in particular to positron emission tomography, as it represents a unique opportunity for the noninvasive in vivo study of tissue metabolism. An exhaustive revision of targeted animal models is also provided in order to clarify what the available preclinical evidence suggests for the causal interactions between fatty liver, dysregulated endogenous glucose production and insulin resistance.


Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Animais , Encéfalo/diagnóstico por imagem , Glucose , Humanos , Fígado/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem
7.
Chirurgia (Bucur) ; 116(4): 387-398, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34498560

RESUMO

Hepatectomy is the only potentially curative treatment of hepatic tumors, but remains challenging in case of multiple, bilobar lesions and those located in the vicinity of the hepatic hilum and hepatic veins. Regenerative liver surgery utilizes the unique ability of the liver to re-grow after tissue loss and vascular deprivation. All concepts subsumed under this term aim to increase the resectability of hepatic tumors by stimulating growth of future liver remnant. Many of these techniques have evolved over the last decades. ALPPS (associated liver partition and portal vein ligation for staged hepatectomy) is an advanced technique combining portal vein ligation and parenchymal transection which gave rise to many variants, all with the common goal of extending resectability. This article reviews techniques currently available for regenerative liver surgery focusing on ALPPS, its mechanisms of liver regeneration, indications, advantages, drawbacks, results and future perspectives.


Assuntos
Neoplasias Hepáticas , Regeneração Hepática , Hepatectomia , Humanos , Ligadura , Fígado/cirurgia , Neoplasias Hepáticas/cirurgia , Veia Porta/cirurgia , Resultado do Tratamento
8.
Chirurgia (Bucur) ; 116(4): 438-450, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34498563

RESUMO

BACKGROUND AIMS: The emergence of tyrosine kinase inhibitors, radically altered the management of GISTs and sparked controversy regarding the role of hepatic resection for metastatic tumors. This study aims to identify whether there is improvement in the overall survival of patients with gastrointestinal liver metastases, undergoing hepatic resection in the context of multimodal treatment strategy, as to those approached only by systemic therapy. Methods: Using a retrospective database, we identified 57 patients treated at our center over a 12-year period: Group A (n=31) underwent hepatic resection alongside systemic therapies, and B (n=26) only systemic therapies. In order to obtain a more robust sample, needed for the survival analysis, we performed a propensity score matching and a bootstrapping selection with Jackknife correction for errors; thus, we created an extended sample of 1000 virtual patients. Results: The overall survival measured in all patients was 47 months (95%CI:34-60); significantly higher for group A (56 months, 95%CI:37-75) compared to group B (38 months, 95%CI:19-56), (p=0.007, Log Rank test). Multivariate analysis identified one risk factor: the presence synchronous liver metastases upon diagnosis of primary. Conclusions: Liver resection following TKI therapy is the current mainstay of treatment strategy for potential cure and prolonged survival, in appropriately selected patients evaluated in an multidisciplinary tumor board.


Assuntos
Tumores do Estroma Gastrointestinal , Neoplasias Hepáticas , Tumores do Estroma Gastrointestinal/cirurgia , Hepatectomia , Humanos , Fígado , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
9.
Chirurgia (Bucur) ; 116(4): 451-465, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34498564

RESUMO

Background: The need to maximize the use of donor organs and the issue of ischemia-reperfusion injury led to the use of thermoregulated oxygenated machine perfusion that improves the function of liver graft prior to transplantation. Among these methods, the HOPE (hypothermic oxygenated perfusion) protocol shows significant benefits. The aim of the paper is to analyze the early experience in using such procedure in a high-volume liver transplantation center. Methods: Normal liver grafts with cold ischemia time â?¥6 hours, marginal grafts and discarded (beyond ECD criteria) grafts were perfused using HOPE. Our selection criteria for dual HOPE (hepatic artery and portal perfusion) were steatosis, at least 3 associated ECD criteria, and discarded grafts. The main criteria to establish graft improvement were the progressive increase of arterial and portal flows, with lactate under 3 mmol/L or, even if over this value, with a decreasing trend during perfusion. Results: Whole liver grafts harvested from 28 donors between February 2016 and June 2021 benefitted from HOPE: 9 otherwise discarded grafts were assessed and considered not fit for transplantation, while the other 19 were ECD or standard grafts that were subsequently transplanted. Dual HOPE was used in 8 out of the 19 procedures (42.1%). We obtained a significant increase of arterial and portal flow (p=0.005 and p=0.001, respectively). In recipients, significant improvement of AST, ALT, INR and lactate values were recorded (p 0.001, p 0.001, p 0.001, and p=0.05, respectively). The rate of major postoperative complications (Dindo-Clavien grade 3) after LT was 26.3%, while the rate of early graft dysfunction was 15.8%. No PRS or acute rejection was recorded. The postoperative mortality rate was 15.8%. After a median follow-up of 9.3 months (range 2-44), the late major complication rate was 15.8%, without mortality. Conclusion: Machine perfusion is nowadays part of current clinical practice. This way, marginal liver grafts (DCD, ECD-DBD) may be safely used for transplantation improving the outcome, thus effectively enhance the use of a persistent scarce pool of donors. For best results, we believe that both techniques of HOPE (mono and dual HOPE) should be used based on specific selection criteria.


Assuntos
Transplante de Fígado , Sobrevivência de Enxerto , Humanos , Fígado/cirurgia , Preservação de Órgãos , Perfusão , Doadores de Tecidos , Resultado do Tratamento
10.
Chirurgia (Bucur) ; 116(4): 409-423, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34498568

RESUMO

Introduction: Presentation of the first experience of a liver surgery center in applying an innovative procedure - ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) for massive liver tumors. This medod has been performed in the surgery clinic 2 since 2018 in patients with massive primary or metastatic liver tumors, whose future residual liver volume is considered too small to perform curative liver resection safely. Until recently, these conditions assigned large tumors occupying more than 75-90% of the liver to the group of unresectable tumors. Prospectively, the ALPPS procedure was evaluated to convert unresectable liver tumors due to the small residual liver volume into resectable ones. Literature data were systematically reviewed using PubMed, Scopus, Google Scholar. Materials and methods: Since June 2018, 18 ALPPS procedures were performed in patients aged 62 +-8 years. Indications for surgical resection were liver metastases of colorectal cancer in 7 cases, perihilar cholangiocarcinoma in 4 cases, hepatocellular carcinoma in 6 cases, and GIST metastases 1 case. From the literature data we analyzed articles from 2014 to 2019. Results: Residual liver volume was calculated on CT angiography using the program included in the Siemens machine software and was 252 +- 115 ml (19.4 +- 6.2%) before ALPPS-1 and 542 +- 165 ml (30.7 +- 6.5%) before ALLPS-2 (P 0.001). The increase in residual liver volume between the two procedures was 60.4 +- 38% (range: 31-110%, P 0.001). The mean time between the first and second procedure was 9.4 +- 2.3 days. Average hospital stay was 28.4 +- 9.2 days. Postoperative morbidity 34.8%, mortality 0. Survival at 18 months was 100%. Conclusion: The ALPPS technique allows us to increase the resectability rate in patients with initially unresectable liver tumors with favorable postoperative outcomes. Careful selection of patients for a major complex procedure such as ALPPS allowed us to avoid postoperative mortality. Liver cirrhosis, cholestasis, and intraoperative hemorrhage are major factors for the development of postoperative morbidity.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias Hepáticas , Neoplasias dos Ductos Biliares/cirurgia , Hepatectomia , Humanos , Ligadura , Fígado , Neoplasias Hepáticas/cirurgia , Veia Porta/cirurgia , Resultado do Tratamento
11.
Chirurgia (Bucur) ; 116(4): 431-437, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34498569

RESUMO

As laparoscopic approach becomes increasingly routine for liver resections, several centers have also adopted the robotic approach for its many purported benefits of magnified steady views, intuitive instrument articulation, and tremor filtration amongst others. In this article we highlight the technical considerations specific to robotic-assisted laparoscopic liver resections for the da Vinci robotic Xi Surgical System.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Hepatectomia , Humanos , Fígado , Resultado do Tratamento
12.
Chirurgia (Bucur) ; 116(4): 503-505, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34498574

RESUMO

We present the case of a 72-year-old patient with multiple cardiovascular comorbidities, hospitalized in our center for a liver tumor, impossible to biopsy percutaneously. CT examination detected a tumor formation with radiological features of cholangiocarcinoma, located in the upper part of segment I, extending to segments VII, VIII, IV superior and II, invading the right and middle hepatic vein, adherent to the left hepatic vein and to the retrohepatic inferior vena cava. Worth mentioning is the existence of 2 accessory lower right hepatic veins, which allowed us to perform a superior transverse non-anatomical ultrasound resection of the upper I, VII, VIII, IV and II segments, which also involved the right and middle hepatic veins, preserving the left hepatic vein, by detaching the tumor from it, but also from the retrohepatic inferior vena cava. Although the literature still debates the R1 vascular resection for cholangiocarcinoma, we decided to adopt this approach on the hepatic veins. Of note, we consider this policy not applicable for the portal pedicles. By adopting this strategy, the venous drainage of the remaining left hemiliver was ensured by the hepatic vein, and of the right one by the accessory veins. Although resecting tumors located at the hepato-caval confluence involving all hepatic veins is technically difficult, we consider it feasible especially when intraoperative ultrasound is used. (video article https://www.revistachirurgia.ro/pdfs/video/Ultrasound-Guided-Liver-Resection-Tumor-2282.mp4).


Assuntos
Hepatectomia , Neoplasias Hepáticas , Idoso , Veias Hepáticas/diagnóstico por imagem , Veias Hepáticas/cirurgia , Humanos , Fígado , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Resultado do Tratamento , Ultrassonografia de Intervenção , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/cirurgia
13.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(4): 536-544, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34494523

RESUMO

Objective To obtain the metabolome profiles in liver and serum of mice during normal aging. Methods The liver and serum samples of ten 2-month-old mice and ten 18-month-old C57BL/6J mice under physiological conditions were collected.Metabolites were identified and quantified by liquid chromatography-tandem mass spectrometry.The overall assessment,differential screening,and functional analysis were performed with the filtered high-quality data. Results In the negative-ion mode and positive-ion mode,242 and 399 metabolites were identified in the liver and 265 and 230 in serum,respectively.The difference of metabolome between young and old mice was moderate.The upregulated metabolites identified in aging liver were related to the metabolism of riboflavin,glucose,and arachidonic acid,while the downregulated ones were associated with the metabolism of pyrimidine,purine,glycerophospholipid,glutathione,and nicotinamide.Altered metabolites in serum during aging were involved in a variety of nucleic acid metabolism-related pathways,such as pyrimidine metabolism,purine metabolism,one carbon pool by folate,and amino sugar and nucleotide sugar metabolism. Conclusions The metabolome profiles of mouse liver and serum both revealed dysregulated nucleic acid metabolism pathways during normal aging.This study provides metabolome data for further research on aging-associated mechanism and may support the discovery of intervention methods for aging.


Assuntos
Metaboloma , Metabolômica , Envelhecimento , Animais , Fígado , Camundongos , Camundongos Endogâmicos C57BL
14.
Int J Mol Sci ; 22(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34502454

RESUMO

COVID-19 is a global threat that has spread since the end of 2019, causing severe clinical sequelae and deaths, in the context of a world pandemic. The infection of the highly pathogenetic and infectious SARS-CoV-2 coronavirus has been proven to exert systemic effects impacting the metabolism. Yet, the metabolic pathways involved in the pathophysiology and progression of COVID-19 are still unclear. Here, we present the results of a mass spectrometry-based targeted metabolomic analysis on a cohort of 52 hospitalized COVID-19 patients, classified according to disease severity as mild, moderate, and severe. Our analysis defines a clear signature of COVID-19 that includes increased serum levels of lactic acid in all the forms of the disease. Pathway analysis revealed dysregulation of energy production and amino acid metabolism. Globally, the variations found in the serum metabolome of COVID-19 patients may reflect a more complex systemic perturbation induced by SARS-CoV-2, possibly affecting carbon and nitrogen liver metabolism.


Assuntos
Biomarcadores/sangue , Carbono/metabolismo , Fígado/metabolismo , Metaboloma , Nitrogênio/metabolismo , Aminoácidos/metabolismo , COVID-19/sangue , COVID-19/patologia , COVID-19/virologia , Citocinas/sangue , Análise Discriminante , Humanos , Análise dos Mínimos Quadrados , Redes e Vias Metabólicas/genética , Metabolômica/métodos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
16.
Nat Commun ; 12(1): 5204, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471136

RESUMO

Secretory proteins are an essential component of interorgan communication networks that regulate animal physiology. Current approaches for identifying secretory proteins from specific cell and tissue types are largely limited to in vitro or ex vivo models which often fail to recapitulate in vivo biology. As such, there is mounting interest in developing in vivo analytical tools that can provide accurate information on the origin, identity, and spatiotemporal dynamics of secretory proteins. Here, we describe iSLET (in situ Secretory protein Labeling via ER-anchored TurboID) which selectively labels proteins that transit through the classical secretory pathway via catalytic actions of Sec61b-TurboID, a proximity labeling enzyme anchored in the ER lumen. To validate iSLET in a whole-body system, we express iSLET in the mouse liver and demonstrate efficient labeling of liver secretory proteins which could be tracked and identified within circulating blood plasma. Furthermore, proteomic analysis of the labeled liver secretome enriched from liver iSLET mouse plasma is highly consistent with previous reports of liver secretory protein profiles. Taken together, iSLET is a versatile and powerful tool for studying spatiotemporal dynamics of secretory proteins, a valuable class of biomarkers and therapeutic targets.


Assuntos
Retículo Endoplasmático/metabolismo , Canais de Translocação SEC/metabolismo , Via Secretória/fisiologia , Animais , Células HEK293 , Células HeLa , Células Hep G2 , Humanos , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos C57BL , Células NIH 3T3 , Proteoma/metabolismo , Proteômica
17.
Sci Rep ; 11(1): 17810, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34497279

RESUMO

Transporters in the human liver play a major role in the clearance of endo- and xenobiotics. Apical (canalicular) transporters extrude compounds to the bile, while basolateral hepatocyte transporters promote the uptake of, or expel, various compounds from/into the venous blood stream. In the present work we have examined the in vitro interactions of some key repurposed drugs advocated to treat COVID-19 (lopinavir, ritonavir, ivermectin, remdesivir and favipiravir), with the key drug transporters of hepatocytes. These transporters included ABCB11/BSEP, ABCC2/MRP2, and SLC47A1/MATE1 in the canalicular membrane, as well as ABCC3/MRP3, ABCC4/MRP4, SLC22A1/OCT1, SLCO1B1/OATP1B1, SLCO1B3/OATP1B3, and SLC10A1/NTCP, residing in the basolateral membrane. Lopinavir and ritonavir in low micromolar concentrations inhibited BSEP and MATE1 exporters, as well as OATP1B1/1B3 uptake transporters. Ritonavir had a similar inhibitory pattern, also inhibiting OCT1. Remdesivir strongly inhibited MRP4, OATP1B1/1B3, MATE1 and OCT1. Favipiravir had no significant effect on any of these transporters. Since both general drug metabolism and drug-induced liver toxicity are strongly dependent on the functioning of these transporters, the various interactions reported here may have important clinical relevance in the drug treatment of this viral disease and the existing co-morbidities.


Assuntos
Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/metabolismo , Antivirais/farmacologia , Transportador 1 de Ânion Orgânico Específico do Fígado/metabolismo , Fígado/efeitos dos fármacos , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/química , Monofosfato de Adenosina/metabolismo , Monofosfato de Adenosina/farmacologia , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/química , Alanina/metabolismo , Alanina/farmacologia , Alanina/uso terapêutico , Antivirais/química , Antivirais/metabolismo , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Comorbidade , Reposicionamento de Medicamentos , Humanos , Fígado/metabolismo , Fígado/patologia , Transportador 1 de Ânion Orgânico Específico do Fígado/antagonistas & inibidores , Lopinavir/química , Lopinavir/metabolismo , Lopinavir/farmacologia , Lopinavir/uso terapêutico , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Ritonavir/química , Ritonavir/metabolismo , Ritonavir/farmacologia , Ritonavir/uso terapêutico , SARS-CoV-2/isolamento & purificação , Especificidade por Substrato
18.
Acta Biomed ; 92(S5): e2021405, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34505844

RESUMO

BACKGROUND AND AIM: Intraabdominal hemorrhage secondary to liver and kidney injury is a major cause of morbidity and mortality. Endovascular arterial embolization is an established interventional radiology technique used to treat active bleeding, and its role in managing abdominal hemorrhages is growing, given the increasing trend for conservative treatment. Our study aims to retrospectively evaluate the technical and clinical results and the possible complications of arterial embolization procedures performed in emergency, in post-traumatic, iatrogenic, and pathological hepatic and renal bleedings. METHODS: We performed a ten-year, single-center retrospective survey (from January 2010 to December 2019) of all patients treated in emergency by intra-arterial embolization of liver and kidney bleeding. Preliminary CT angiography studies were evaluated, as well as the angiographic findings. Materials used, procedural data, and clinical outcomes, including complications, were recorded. RESULTS: The diagnostic angiography showed a single source of bleeding in 20 cases (66.7%), two bleeding vessels in 4 cases (13.3%), and multiple hemorrhagic sources in 6 cases (20%). All bleeding sources were successfully embolized; in 12 patients (40%), complete embolization was achieved with coils and 18 patients (60%) with hemostatic sponges. In one case, a second embolization procedure was performed for the persistence of hemodynamic instability. No major post-procedural complications were recorded. The mean procedure duration was 65.1 minutes. CONCLUSIONS: Based on our experience and literature data, the treatment of endovascular embolization in acute abdominal bleeding of hepatic and renal origin represents the treatment of choice, as it can provide complete therapeutic success in hemodynamically stable patients. (www.actabiomedica.it).


Assuntos
Embolização Terapêutica , Radiologia Intervencionista , Hemorragia/diagnóstico por imagem , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Fígado , Estudos Retrospectivos , Resultado do Tratamento
20.
World J Surg Oncol ; 19(1): 276, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526025

RESUMO

BACKGROUND: Skin autofluorescence (SAF) reflects accumulation of advanced glycation end-products (AGEs). The aim of this study was to evaluate predictive usefulness of SAF measurement in prediction of acute kidney injury (AKI) after liver resection. METHODS: This prospective observational study included 130 patients undergoing liver resection. The primary outcome measure was AKI. SAF was measured preoperatively and expressed in arbitrary units (AU). RESULTS: AKI was observed in 32 of 130 patients (24.6%). SAF independently predicted AKI (p = 0.047), along with extent of resection (p = 0.019) and operative time (p = 0.046). Optimal cut-off for SAF in prediction of AKI was 2.7 AU (area under the curve [AUC] 0.611), with AKI rates of 38.7% and 20.2% in patients with high and low SAF, respectively (p = 0.037). Score based on 3 independent predictors (SAF, extent of resection, and operative time) well stratified the risk of AKI (AUC 0.756), with positive and negative predictive values of 59.3% and 84.0%, respectively. In particular, SAF predicted AKI in patients undergoing major and prolonged resections (p = 0.010, AUC 0.733) with positive and negative predictive values of 81.8%, and 62.5%, respectively. CONCLUSIONS: AGEs accumulation negatively affects renal function in patients undergoing liver resection. SAF measurement may be used to predict AKI after liver resection, particularly in high-risk patients.


Assuntos
Injúria Renal Aguda , Produtos Finais de Glicação Avançada , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Biomarcadores , Humanos , Fígado , Prognóstico , Pele
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