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1.
J Biosci Bioeng ; 131(1): 107-113, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32948422

RESUMO

Liver transplantation plays an important role in the medical field. To improve the quality of a donor liver, there is a need to establish a preservation system to prevent damage and maintain liver function. In response to this demand, machine perfusion (MP) has been proposed as a new liver preservation method instead of the conventional static cold storage. There is controversy about the optimal MP temperature of the donor liver. Since the oxygen consumption of the liver differs depending on the temperature, construction of a system that satisfies the oxygen demand of the liver is crucial for optimizing the preservation temperature. In this study, an MP system, which satisfies the oxygen demand of liver at each temperature, was constructed using an index of oxygen supply; the overall volumetric oxygen transfer coefficient, the amount of oxygen retention of perfusate and oxygen saturation. Both subnormothermic MP (SNMP, 20-25 °C) and normothermic MP (NMP, 37 °C) could maintain liver viability at a high level (94%). However, lactate metabolism of the liver during NMP was more active than that during SNMP. Furthermore, the ammonia metabolism of liver after NMP was superior to that after SNMP. Hence, NMP, which maintains the metabolic activity of the liver, is more suitable for preservation of the donor liver than SNMP, which suppresses the metabolic activity. In summary, normothermia is the optimal temperature for liver preservation, and we succeeded in constructing an NMP system that could suppress liver damage and maintain function.


Assuntos
Fígado/fisiologia , Oxigênio/metabolismo , Perfusão/métodos , Temperatura , Humanos , Fígado/metabolismo , Transplante de Fígado , Doadores Vivos
2.
Nat Commun ; 11(1): 5785, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-33214549

RESUMO

The liver plays a central role in metabolism, protein synthesis and detoxification. It possesses unique regenerative capacity upon injury. While many factors regulating cellular proliferation during liver repair have been identified, the mechanisms by which the injured liver maintains vital functions prior to tissue recovery are unknown. Here, we identify a new phase of functional compensation following acute liver injury that occurs prior to cellular proliferation. By coupling single-cell RNA-seq with in situ transcriptional analyses in two independent murine liver injury models, we discover adaptive reprogramming to ensure expression of both injury response and core liver function genes dependent on macrophage-derived WNT/ß-catenin signaling. Interestingly, transcriptional compensation is most prominent in non-proliferating cells, clearly delineating two temporally distinct phases of liver recovery. Overall, our work describes a mechanism by which the liver maintains essential physiological functions prior to cellular reconstitution and characterizes macrophage-derived WNT signals required for this compensation.


Assuntos
Regeneração Hepática/fisiologia , Fígado/lesões , Fígado/fisiologia , Acetaminofen/toxicidade , Animais , Ciclo Celular , Proliferação de Células , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Hepatectomia/efeitos adversos , Hepatócitos/citologia , Hepatócitos/metabolismo , Hepatócitos/fisiologia , Fígado/patologia , Regeneração Hepática/genética , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Via de Sinalização Wnt , beta Catenina/genética , beta Catenina/metabolismo
3.
Front Cell Infect Microbiol ; 10: 560899, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33117727

RESUMO

Background: Coronavirus disease (COVID-19) is a current global public health emergency. However, current research on the blood test results of pregnant women with COVID-19 is insufficient. Methods: A case-control study was carried out based on clinical blood test results. Pregnant COVID-19 patients, pregnant COVID-19 patients with diabetes, and pregnant COVID-19 patients with hypertension, were assessed in this study. Also, 120 controls were matched by age, parity, fetus number, and presence of chronic disease. T-tests, Chi-square tests, Wilcoxon signed-rank tests, and Kruskal-Wallis tests were used to compare data from the blood tests and liver function indices among the selected groups. Results: Between January 24 and March 14, 2020, 60 pregnant COVID-19 patients delivered at the Maternal and Child Health Hospital of Hubei Province. The average maternal age of pregnant COVID-19 patients was 30.97 years and the mean gestational period was 37.87 weeks. 71.67% (43/60) of pregnant COVID-19 patients gave birth by cesarean delivery. In total, 21.67% (13/60) were diagnosed with diabetes and 18.33% (11/60) were diagnosed with hypertension during pregnancy. Compared to controls, pregnant COVID-19 patients showed significantly lower numbers of blood lymphocytes and higher numbers of neutrophils, as well as higher levels of C-reactive protein and total bilirubin. Among the three groups, pregnant COVID-19 patients with diabetes had significantly higher levels of neutrophils and lower levels of total protein. Aspartate transaminase levels were higher in pregnant COVID-19 patients with hypertension than in pregnant COVID-19 patients with no comorbidities and controls with hypertension. Interpretations: Blood and liver function indices indicate that chronic complications, including hypertension and diabetes, could increase the risk of inflammation and liver injury in pregnant COVID-19 patients.


Assuntos
Infecções por Coronavirus/fisiopatologia , Diabetes Mellitus/diagnóstico , Hipertensão/diagnóstico , Pneumonia Viral/fisiopatologia , Complicações Infecciosas na Gravidez/virologia , Adulto , Aspartato Aminotransferases/sangue , Betacoronavirus , Bilirrubina/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , Cesárea/estatística & dados numéricos , Diabetes Mellitus/sangue , Feminino , Humanos , Hipertensão/sangue , Fígado/fisiologia , Testes de Função Hepática , Contagem de Linfócitos , Linfócitos/citologia , Neutrófilos/citologia , Pandemias , Gravidez
4.
Zhonghua Wai Ke Za Zhi ; 58(11): 835-840, 2020 Nov 01.
Artigo em Chinês | MEDLINE | ID: mdl-33120445

RESUMO

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can speed up the regeneration of future liver remnant (FLR) in short period of time, and offer a chance for surgical resection for patients without sufficient FLR. However, ALPPS still remains controversy due to its high perioperative morbidity and mortality, as well as the uncertain long-term oncological benefits. How to solve these problems is the key to ensure the safety of surgery.This article focus on the indication selection, liver function reserve evaluation and timing to perform the second stage surgery, surgical mode evolution and comparison with portal venous embolization/portal venous ligation+two-stage hepatectomy.


Assuntos
Hepatectomia , Neoplasias Hepáticas , Fígado/cirurgia , Veia Porta/cirurgia , Embolização Terapêutica , Hepatectomia/métodos , Humanos , Ligadura , Fígado/anatomia & histologia , Fígado/fisiologia , Neoplasias Hepáticas/cirurgia , Regeneração Hepática , Resultado do Tratamento
5.
PLoS One ; 15(10): e0239743, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33002028

RESUMO

PURPOSE: The purpose of this study was to investigate whether the cardiac motion artifact that regularly appears in diffusion-weighted imaging of the left liver lobe might be reduced by acquiring images in inspiration, when the coupling between heart and liver might be minimal. MATERIALS AND METHODS: 43 patients with known or suspected focal liver lesions were examined at 1.5 T with breath hold acquisition, once in inspiration and once in expiration. Data were acquired with a diffusion-weighted echo planar imaging sequence and two b-values (b50 = 50 s/mm² and b800 = 800 s/mm²). The severity of the cardiac motion artifact in the left liver lobe was rated by two experienced radiologists for both b-values with a 5 point Likert scale. Additionally, the normalized signal S(b800)/S(b50) in the left liver lobe was computed. The Wilcoxon signed-rank test was used comparing the scores of the two readers obtained in inspiration and expiration, and to compare the normalized signal in inspiration and expiration. RESULTS: The normalized signal in inspiration was slightly higher than in expiration (0.349±0.077 vs 0.336±0.058), which would indicate a slight reduction of the cardiac motion artifact, but this difference was not significant (p = 0.24). In the qualitative evaluation, the readers did not observe a significant difference for b50 (reader 1: p = 0.61; reader 2: p = 0.18). For b800, reader 1 observed a significant difference of small effect size favouring expiration (p = 0.03 with a difference of mean Likert scores of 0.27), while reader 2 observed no significant difference (p = 0.62). CONCLUSION: Acquiring the data in inspiration does not lead to a markedly reduced cardiac motion artifact in diffusion-weighted imaging of the left liver lobe and is in this regard not to be preferred over acquiring the data in expiration.


Assuntos
Coração/fisiologia , Fígado/diagnóstico por imagem , Respiração , Adulto , Idoso , Idoso de 80 Anos ou mais , Artefatos , Suspensão da Respiração , Imagem de Difusão por Ressonância Magnética , Expiração , Feminino , Humanos , Fígado/anatomia & histologia , Fígado/fisiologia , Hepatopatias/diagnóstico por imagem , Hepatopatias/patologia , Hepatopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
PLoS One ; 15(9): e0238115, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915812

RESUMO

This work provides an in-depth computational performance study of the parallel finite-difference time-domain (FDTD) method. The parallelization is done at various levels including: shared- (OpenMP) and distributed- (MPI) memory paradigms and vectorization on three different architectures: Intel's Knights Landing, Skylake and ARM's Cavium ThunderX2. This study contributes to prove, in a systematic manner, the well-established claim within the Computational Electromagnetic community, that the main factor limiting FDTD performance, in realistic problems, is the memory bandwidth. Consequently a memory bandwidth threshold can be assessed depending on the problem size in order to attain optimal performance. Finally, the results of this study have been used to optimize the workload balancing of simulation of a bioelectromagnetic problem consisting in the exposure of a human model to a reverberation chamber-like environment.


Assuntos
Algoritmos , Campos Eletromagnéticos , Osso e Ossos/fisiologia , Dispositivos de Armazenamento em Computador , Sistemas Computacionais , Humanos , Rim/fisiologia , Fígado/fisiologia , Modelos Teóricos , Software
7.
Int J Nanomedicine ; 15: 6519-6529, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32943866

RESUMO

Background: Understanding the biocompatibility and biointeractions of nano-carbon quantum dots (nano-CQDs) in vitro and in vivo is important for assessing their potential risk to human health. In the previous research, the physical properties of CQDs synthesized by the laser ablation in liquid (LAL) method were analyzed in detail; however, possible bioapplications were not considered. Materials and Methods: CQDs were prepared by LAL and characterized by atomic force microscopy, fluorescence lifetime, absorption spectrum, Fourier-transform infrared spectroscopy, and dynamic light scattering. Their biocompatibility was evaluated in vitro using assays for cytotoxicity, apoptosis, and biodistribution and in vivo using immunotoxicity and the relative expression of genes. Cells were measured in vitro using fluorescence-lifetime imaging microscopy to analyze the biointeractions between CQDs and intracellular proteins. Results: There were no significant differences in biocompatibility between the CQDs and the negative control. The intracellular interactions had no impact on the optical imaging of CQDs upon intake by cells. Optical imaging of zebrafish showed the green fluorescence was well dispersed. Conclusion: We have demonstrated that the CQDs have an excellent biocompatibility and can be used as efficient optical nanoprobes for cell tracking and biomedical labeling except for L929 and PC-3M cells.


Assuntos
Pontos Quânticos/química , Pontos Quânticos/toxicidade , Animais , Antígenos CD/sangue , Apoptose/efeitos dos fármacos , Carbono/química , Difusão Dinâmica da Luz , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Fígado/efeitos dos fármacos , Fígado/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Imagem Óptica , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Distribuição Tecidual , Testes de Toxicidade , Peixe-Zebra
8.
Mol Cell ; 79(4): 660-676.e8, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32755593

RESUMO

Specific combinations of two transcription factors (Hnf4α plus Foxa1, Foxa2, or Foxa3) can induce direct conversion of mouse fibroblasts into hepatocyte-like cells. However, the molecular mechanisms underlying hepatic reprogramming are largely unknown. Here, we show that the Foxa protein family members and Hnf4α sequentially and cooperatively bind to chromatin to activate liver-specific gene expression. Although all Foxa proteins bind to and open regions of closed chromatin as pioneer factors, Foxa3 has the unique potential of transferring from the distal to proximal regions of the transcription start site of target genes, binding RNA polymerase II, and co-traversing target genes. These distinctive characteristics of Foxa3 are essential for inducing the hepatic fate in fibroblasts. Similar functional coupling of transcription factors to RNA polymerase II may occur in other contexts whereby transcriptional activation can induce cell differentiation.


Assuntos
Fator 3-gama Nuclear de Hepatócito/metabolismo , Fator 4 Nuclear de Hepatócito/metabolismo , Fígado/citologia , Fígado/fisiologia , Ativação Transcricional , Animais , Sítios de Ligação , Células Cultivadas , Reprogramação Celular/fisiologia , Cromatina/metabolismo , DNA Polimerase II/genética , DNA Polimerase II/metabolismo , Fibroblastos/citologia , Fibroblastos/fisiologia , Regulação da Expressão Gênica , Fator 3-gama Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/genética , Camundongos Endogâmicos C57BL , Domínios Proteicos , Sítio de Iniciação de Transcrição
9.
PLoS One ; 15(8): e0236438, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790680

RESUMO

The life cycle of European eel (Anguilla anguilla), a catadromous species, is complex and enigmatic. In nature, during the silvering process prior to their long spawning migration, reproductive development is arrested, and they cease feeding. In studies of reproduction using hormonal induction, eels are equivalently not feed. Therefore, in female eels that undergo vitellogenesis, the liver plays different, essential roles being involved both in vitellogenins synthesis and in reallocating resources for the maintenance of vital functions, performing the transoceanic reproductive migration and completing reproductive development. The present work aimed at unravelling the major transcriptomic changes that occur in the liver during induced vitellogenesis in female eels. mRNA-Seq data from 16 animals (eight before induced vitellogenesis and eight after nine weeks of hormonal treatment) were generated and differential expression analysis was performed comparing the two groups. This analysis detected 1,328 upregulated and 1,490 downregulated transcripts. Overrepresentation analysis of the upregulated genes included biological processes related to biosynthesis, response to estrogens, mitochondrial activity and localization, while downregulated genes were enriched in processes related to morphogenesis and development of several organs and tissues, including liver and immune system. Among key genes, the upregulated ones included vitellogenin genes (VTG1 and VTG2) that are central in vitellogenesis, together with ESR1 and two novel genes not previously investigated in European eel (LMAN1 and NUPR1), which have been linked with reproduction in other species. Moreover, several upregulated genes, such as CYC1, ELOVL5, KARS and ACSS1, are involved in the management of the effect of fasting and NOTCH, VEGFA and NCOR are linked with development, autophagy and liver maintenance in other species. These results increase the understanding of the molecular changes that occur in the liver during vitellogenesis in this complex and distinctive fish species, bringing new insights on European eel reproduction and broodstock management.


Assuntos
Anguilla/fisiologia , Transcriptoma , Vitelogênese , Anguilla/genética , Animais , Feminino , Fígado/fisiologia , RNA-Seq , Reprodução
10.
Ecotoxicol Environ Saf ; 204: 111051, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32763565

RESUMO

The present study was performed to determine the effect of waterborne cadmium (Cd) exposure on oxidative stress, autophagy and mitochondrial dysfunction, and to explore the mechanism of Cd-induced liver damage in freshwater teleost Procypris merus. To this end, P. merus were exposed to waterborne 0, 0.25 and 0.5 mg/L Cd for 30 days (equal to 0, 2.22 and 4.45 µmol Cd/l). The waterborne Cd exposure significantly increased hepatic Cd accumulation and impaired histological structure of the liver of P. merus. both low and high-dose waterborne Cd exposure induced oxidative stress in the liver of P. merus, through increases Malondialdehyde (MDA) and reactive oxide species (ROS) accumulation in the liver. The Cd-induced oxidative stress in liver may result from reduction of enzyme activities (superoxide dismutases (SOD), catalases (CAT), GSH-S-transferases (GST)) and transcriptional expression of antioxidant related genes (gpx1, gpx2, cata, gsta1, sod1). Furthermore, the present study showed that waterborne Cd exposure decreased the transcriptional factor (nrf2) expression, which might lead to the down-regulation of antioxidant gene expression. Transmission electron microscopy (TEM) observations demonstrated that waterborne Cd exposure induced autophagy in the liver of P. merus. Gene expression analysis showed that waterborne Cd exposure also induced mRNA expression of a set of genes (beclin1, ulk1, atg5, lc3a, atg4b, atg9a, and p62) involved in the autophagy process, indicating that the influence of Cd on autophagy involved transcription regulation of autophagy gene expression. Waterborne Cd exposure induced a sharp decrease in ATP content in the liver of P. merus. In addition, the expression of mitochondrial function genes (sdha, cox4i1, cox1, atp5f1, and mt-cyb) are significantly decreased in the liver of P. merus in Cd treated groups, manifesting the suppression of Cd on mitochondrial energy metabolism. Taken together, our experiments demonstrate that waterborne Cd exposure induced oxidative stress, autophagy and mitochondrial dysfunction in the liver of P. merus. These results may contribute to the understanding of mechanisms that hepatotoxicity of Cd in teleost.


Assuntos
Antioxidantes/fisiologia , Autofagia/efeitos dos fármacos , Cádmio/toxicidade , Cyprinidae/fisiologia , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Relação Dose-Resposta a Droga , Fígado/fisiologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Distribuição Aleatória
11.
Science ; 369(6509): 1388-1394, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32732282

RESUMO

Most cells of the body contain molecular clocks, but the requirement of peripheral clocks for rhythmicity and their effects on physiology are not well understood. We show that deletion of core clock components REV-ERBα and REV-ERBß in adult mouse hepatocytes disrupts diurnal rhythms of a subset of liver genes and alters the diurnal rhythm of de novo lipogenesis. Liver function is also influenced by nonhepatocytic cells, and the loss of hepatocyte REV-ERBs remodels the rhythmic transcriptomes and metabolomes of multiple cell types within the liver. Finally, alteration of food availability demonstrates the hierarchy of the cell-intrinsic hepatocyte clock mechanism and the feeding environment. Together, these studies reveal previously unsuspected roles of the hepatocyte clock in the physiological coordination of nutritional signals and cell-cell communication controlling rhythmic metabolism.


Assuntos
Relógios Circadianos/genética , Ritmo Circadiano/genética , Comportamento Alimentar , Regulação da Expressão Gênica , Hepatócitos/fisiologia , Fígado/fisiologia , Animais , Comunicação Celular , Deleção de Genes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Receptores Citoplasmáticos e Nucleares/genética , Proteínas Repressoras/genética
12.
Aliment Pharmacol Ther ; 52(4): 619-636, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32638417

RESUMO

BACKGROUND: Patients with non-alcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease, are at higher risk of cardiovascular disease (CVD) and associated mortality. Therefore, it is important to understand how new therapies for non-alcoholic steatohepatitis (NASH) may impact CVD risk factors in these patients. AIMS: To summarise the effects of drug therapies on lipid and lipoprotein levels in patients with NASH and provide insight into the potential mechanisms for the observed changes. METHODS: PubMed searches of the literature were performed and results were compiled. RESULTS: Recent clinical trials have highlighted the safety and efficacy of drug candidates for the treatment of NASH. Several agents have shown improvements in the histological features of NASH and liver function. Pioglitazone, a drug that is currently available for type 2 diabetes and may be useful for NASH, exhibits beneficial effects on lipids. However, agents such as farnesoid X receptor agonists, which are in development for NASH, may adversely affect circulating lipids and lipoproteins. CONCLUSIONS: NASH is a multi-system disease with a disproportionate CVD burden. Current and future drugs for NASH have had variable impact on the atherogenic risk profile. Potential co-administration of a statin may help mitigate the negative impact of some of these therapies on lipid and lipoprotein levels.


Assuntos
Aterosclerose/etiologia , Hipolipemiantes/uso terapêutico , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Aterosclerose/epidemiologia , Aterosclerose/prevenção & controle , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Desenvolvimento de Medicamentos/métodos , Desenvolvimento de Medicamentos/tendências , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/fisiologia , Testes de Função Hepática , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Pioglitazona/uso terapêutico , Fatores de Risco
13.
Medicine (Baltimore) ; 99(27): e20749, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629651

RESUMO

Dimethylformamide (DMF) is widely used as a solvent in the production of synthetic leather. Previous studies have focused on workers exposed to DMF in leather factories; however, little attention has been paid to the general population. This study was conducted to examine the effects of DMF exposure on elderly residents living near synthetic leather factories. A total of 962 subjects over 60 years of age in proximity to these factories (monitoring points) were enrolled as the exposure group, and 1924 permanent residents living distant from the factories were enrolled as the control group. The exposure group was divided into 3 groups according to their distance from the monitoring points. Physical examination, routine blood tests, and liver and renal function data were collected, and the DMF concentration in the air was analyzed by gas chromatography-mass spectroscopy. The prevalence of abnormal heart rhythm, electrocardiogram and B-mode ultrasound results in the exposure group was significantly greater than in the control group. Aspartate transaminase (AST), alanine transaminase (ALT), and blood urea nitrogen (BUN) levels in the exposure group also were higher than those in the control group (P < .01). There was an effect of distance from leather factories on liver and kidney dysfunction in the 3 exposure groups. Compared with the exposure group at >3 km distance from the source, the prevalence of increased AST, ALT, and BUN in the exposure group at <1 km was significantly greater (P < .001). It was concluded that DMF exposure was related to an increased risk of a cardiac injury and liver and kidney dysfunction.


Assuntos
Dimetilformamida/efeitos adversos , Exposição Ambiental/efeitos adversos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Nitrogênio da Ureia Sanguínea , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Rim/fisiologia , Fígado/fisiologia , Masculino , Pessoa de Meia-Idade , Curtume
14.
Nat Commun ; 11(1): 2939, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546694

RESUMO

There is a limited access to liver transplantation, however, many organs are discarded based on subjective assessment only. Here we report the VITTAL clinical trial (ClinicalTrials.gov number NCT02740608) outcomes, using normothermic machine perfusion (NMP) to objectively assess livers discarded by all UK centres meeting specific high-risk criteria. Thirty-one livers were enroled and assessed by viability criteria based on the lactate clearance to levels ≤2.5 mmol/L within 4 h. The viability was achieved by 22 (71%) organs, that were transplanted after a median preservation time of 18 h, with 100% 90-day survival. During the median follow up of 542 days, 4 (18%) patients developed biliary strictures requiring re-transplantation. This trial demonstrates that viability testing with NMP is feasible and in this study enabled successful transplantation of 71% of discarded livers, with 100% 90-day patient and graft survival; it does not seem to prevent non-anastomotic biliary strictures in livers donated after circulatory death with prolonged warm ischaemia.


Assuntos
Sobrevivência de Enxerto/fisiologia , Testes de Função Hepática/métodos , Transplante de Fígado/métodos , Fígado/fisiologia , Preservação de Órgãos/métodos , Doadores de Tecidos/estatística & dados numéricos , Idoso , Feminino , Humanos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados não Aleatórios como Assunto , Preservação de Órgãos/estatística & dados numéricos , Perfusão/métodos , Estudos Prospectivos , Análise de Sobrevida , Temperatura , Fatores de Tempo , Coleta de Tecidos e Órgãos/métodos , Coleta de Tecidos e Órgãos/estatística & dados numéricos
15.
J Sports Med Phys Fitness ; 60(7): 1034-1039, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32597619

RESUMO

BACKGROUND: Creatine represents a natural supplement and ergogenic aid for sport performance, but there are several concerns regarding its safety for health. The present double-blind placebo-controlled study evaluated the effect of creatine monohydrate supplementation on a panel of blood and urine health indicators in resistance training practitioners. METHODS: Eighteen males performing resistance training three times per week were supplemented with 0.3 g/kg per day creatine monohydrate for 7 days and compared with matched controls supplemented with dextrosol. Blood and urine samples were collected pre- and 30 days post-supplementation to evaluate 41 biochemical parameters and renal function. RESULTS: Creatine monohydrate supplementation did not cause adverse events and, as expected, promoted an increase of the performance and body weight. No modification of red blood cells parameters, white blood cells profile, blood lipid profile, metabolic and urine markers, hepatic and renal function were observed in the supplemented group. CONCLUSIONS: Despite the expected weight increase, the creatine monohydrate supplementation is safe for health and no detrimental effects on different organs and physiological systems were observed in our cohort of volunteers.


Assuntos
Desempenho Atlético/fisiologia , Creatina/administração & dosagem , Creatina/efeitos adversos , Suplementos Nutricionais , Substâncias para Melhoria do Desempenho/administração & dosagem , Substâncias para Melhoria do Desempenho/efeitos adversos , Treinamento de Resistência , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Método Duplo-Cego , Testes Hematológicos , Humanos , Rim/fisiologia , Contagem de Leucócitos , Lipídeos/sangue , Fígado/fisiologia , Masculino , Músculo Esquelético/metabolismo , Ganho de Peso , Adulto Jovem
16.
Nat Rev Gastroenterol Hepatol ; 17(8): 457-472, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32483353

RESUMO

Liver disease is a major global health-care problem, affecting an estimated 844 million people worldwide. Despite this substantial burden, therapeutic options for liver disease remain limited, in part owing to a paucity of detailed analyses defining the cellular and molecular mechanisms that drive these conditions in humans. Single-cell transcriptomic technologies are transforming our understanding of cellular diversity and function in health and disease. In this Review, we discuss how these technologies have been applied in hepatology, advancing our understanding of cellular heterogeneity and providing novel insights into fundamental liver biology such as the metabolic zonation of hepatocytes, endothelial cells and hepatic stellate cells, and the cellular mechanisms underpinning liver regeneration. Application of these methodologies is also uncovering critical pathophysiological changes driving disease states such as hepatic fibrosis, where distinct populations of macrophages, endothelial cells and mesenchymal cells reside within a spatially distinct fibrotic niche and interact to promote scar formation. In addition, single-cell approaches are starting to dissect key cellular and molecular functions in liver cancer. In the near future, new techniques such as spatial transcriptomics and multiomic approaches will further deepen our understanding of disease pathogenesis, enabling the identification of novel therapeutic targets for patients across the spectrum of liver diseases.


Assuntos
Perfilação da Expressão Gênica , Hepatopatias/genética , Fígado/metabolismo , Análise de Célula Única , Células Endoteliais/metabolismo , Células Endoteliais/fisiologia , Fibroblastos/metabolismo , Fibroblastos/fisiologia , Gastroenterologia , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/fisiologia , Hepatócitos/metabolismo , Hepatócitos/fisiologia , Humanos , Inflamação/imunologia , Macrófagos do Fígado/imunologia , Fígado/citologia , Fígado/imunologia , Fígado/fisiologia , Cirrose Hepática/genética , Cirrose Hepática/imunologia , Cirrose Hepática/metabolismo , Hepatopatias/imunologia , Hepatopatias/metabolismo , Macrófagos/imunologia , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/fisiologia , Regeneração , Análise de Sequência de RNA
17.
PLoS One ; 15(6): e0232371, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555707

RESUMO

Sarcopenia has been associated with lower overall survival in patients with cirrhosis and hepatocellular carcinoma (HCC) undergoing surgical resection, TACE, TARE, or transplantation. This monocentric study evaluated the prognostic significance of sarcopenia in patients affected by HCC who received bland transarterial embolization (TAE) therapy, by analyzing its impact on survival and treatment-related complications. All consecutive patients who underwent the 1st TAE between March 1st 2011 and July 1st 2019 in our Institution were retrospectively studied. To evaluate sarcopenia, the skeletal muscle index (SMI) was calculated by normalizing the cross-sectional muscle area at the level of L3 on an abdominal CT scan prior to embolization (cm2) by patient height (m2). SMI cut-off values for sarcopenia were considered ≤ 39 cm2/m2 for women and ≤55 cm2/m2 for men. Data about age, gender, body mass index (BMI), underlying liver disease, liver function, MELD score, Child-Pugh score, multifocal disease, performance status, previous interventions, length of stay (LOS), complications after the procedure, readmission rate within 30 days, survival time from TAE and total number and type of TAE received following the first procedure were collected. From 2011 to 2019, 142 consecutive patients underwent 305 TAEs. Observation time ranged from 1.4 to 100.5 months (median 20.1 SD = 22). Sarcopenia at baseline was present in 121 (85%) patients. Overall 87 (61.2%) patients died during follow-up with survival rates at 1-, 2-, 3-, 4-, and 5-year of 71%, 41%, 22%, 16% and 11% respectively. After multivariate analysis sarcopenia (HR = 2.22, p = 0.046), previous ablation/resection (HR = 0.51, p = 0.005) and multifocal disease (HR = 1.84, p = 0.02) were associated with reduced survival. Sarcopenia did not influence the safety of TAE in terms of LOS (2 days vs 1.5 days, p = 0.2), early complications rate (8% vs 5%, p = 0.5) and readmission rate within 30 days (7% vs 5%, p = 0.74). Sarcopenia, estimated by the L3SMI method, is an emerging prognostic factor in patients with HCC undergoing bland TAE therapy as it is associated with increased mortality, without impairing the safety of the locoregional treatment. Measures to ameliorate the SMI, such as nutritional support and physical exercise, should be evaluated in clinical trials for HCC patients receiving liver embolization to determine their impact on overall survival.


Assuntos
Carcinoma Hepatocelular/terapia , Embolização Terapêutica , Neoplasias Hepáticas/terapia , Sarcopenia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Embolização Terapêutica/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Tempo de Internação , Fígado/patologia , Fígado/fisiologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Sarcopenia/etiologia , Índice de Gravidade de Doença
18.
Khirurgiia (Mosk) ; (4): 47-52, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32352668

RESUMO

The researches devoted to postoperative liver regeneration and influence in this process were analyzed. Liver injury is followed by hypertrophy of residual liver parenchyma. The use of various cytokines is perspective for activation, acceleration and inhibition of liver recovery. Cellular technologies in the treatment of liver diseases can affect its repair. Moreover, these methods could make unnecessary resection and transplantation of liver in certain cases. It is generally accepted that the main effect of multipotent stromal cells (MSC) in liver failure is associated with their differentiation to the cellular elements of this organ. At the same time, recent reports revealed that MSC injection to the liver is followed by their quick death, dissemination to other organs and tissues or even elimination from the organism. Regeneration of non-parenchymal structures (vascular network and bile ducts) should be considered in addition to functional recovery of liver parenchyma after resection. Clarification of indications and contraindications for MSC therapy, as well as prevention of possible complications associated with cellular technologies are required.


Assuntos
Hepatectomia , Hepatopatias/fisiopatologia , Hepatopatias/cirurgia , Regeneração Hepática/fisiologia , Fígado/fisiologia , Humanos , Recuperação de Função Fisiológica
19.
Poult Sci ; 99(5): 2616-2623, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32359597

RESUMO

The effects of coextruded full-fat flaxseed and pulses (FFF; 1:1 wt/wt) mixture on n-3 polyunsaturated fatty acids (PUFA) enrichment in egg yolk, hepatic attributes, apparent retention (AR) of components, and ceca metabolites were evaluated in broiler breeder hens. The diets were as follows: 1) corn-soybean control, 2) control diet plus 18% FFF (FFF-), and 3) FFF plus enzyme supplement (FFF+) containing galactanase, protease, mannanase, glucanase, xylanase, amylase, and cellulase activities. Twenty-six-week-old Cobb 500 broiler breeder hens were allocated to 30 identical cages (2 hens/cage) and given 1-week adaptation period. The 3 diets were assigned to 10 replicate cages based on postadaptation BW and fed based on breeder curve for 30 D. Excreta samples were collected from day 24 to 27 for determination of AR of components, and eggs were collected from day 28 to 30 for yolk polyunsaturated fatty acids analyses. On day 30, birds were weighed, killed via cervical dislocation, liver weighed, and stored for fat analyses. Ceca digesta samples were taken for concentration of short-chain fatty acids. Liver and yolk weights as well as total yolk FA were not influenced by diets (P > 0.05). Control birds had lower yolk concentration of α-linolenic acid than birds fed either FFF- or FFF+ (P < 0.01) corresponding to 7.5, 36.8, and 37.3 mg/g for the control, FFF-, and FFF+, respectively. Control birds also exhibited lower yolk concentration of docosahexaenoic acid (P < 0.01). Control birds had higher hepatic concentration of crude fat and apparent retention of dry matter and crude protein compared with either the FFF- or FFF+ birds (P < 0.05). Birds fed FFF- diet had lower ceca digesta concentration of lactic acid than control and FFF+ (P < 0.05) birds. Results showed broiler breeder hens enriched egg yolk with n-3 polyunsaturated fatty acids without effects on the liver while the supplemental enzyme did not improve the utilization of FFF.


Assuntos
Galinhas/fisiologia , Gema de Ovo/efeitos dos fármacos , Enzimas/metabolismo , Fabaceae/química , Linho/química , Ração Animal/análise , Animais , Ceco/metabolismo , Dieta/veterinária , Suplementos Nutricionais/análise , Digestão/efeitos dos fármacos , Gema de Ovo/fisiologia , Enzimas/administração & dosagem , Ácidos Graxos Ômega-3/metabolismo , Feminino , Fígado/efeitos dos fármacos , Fígado/fisiologia , Distribuição Aleatória
20.
Nat Commun ; 11(1): 2461, 2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32424153

RESUMO

It is well established that pluripotent stem cells in fetal and postnatal liver (LPCs) can differentiate into both hepatocytes and cholangiocytes. However, the signaling pathways implicated in the differentiation of LPCs are still incompletely understood. Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is known to be involved in osteoblast and myeloid differentiation, but its role in lineage commitment in the liver has not been investigated. Here we show that during development and upon regeneration TFEB drives the differentiation status of murine LPCs into the progenitor/cholangiocyte lineage while inhibiting hepatocyte differentiation. Genetic interaction studies show that Sox9, a marker of precursor and biliary cells, is a direct transcriptional target of TFEB and a primary mediator of its effects on liver cell fate. In summary, our findings identify an unexplored pathway that controls liver cell lineage commitment and whose dysregulation may play a role in biliary cancer.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Linhagem da Célula , Fígado/citologia , Fígado/fisiologia , Regeneração/fisiologia , Animais , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares/metabolismo , Diferenciação Celular , Proliferação de Células , Colangiocarcinoma/patologia , Regulação para Baixo/genética , Hepatócitos/citologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Biológicos , Fenótipo , Regiões Promotoras Genéticas/genética , Ligação Proteica , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Esferoides Celulares/citologia , Células-Tronco/citologia , Células-Tronco/metabolismo , Regulação para Cima/genética
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