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1.
Medicine (Baltimore) ; 102(1): e32586, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607861

RESUMO

The aim of this study was to investigate the clinical features and risk factors of intrahepatic cholestasis of pregnancy (ICP) and its effect on pregnancy outcomes. The data from 300 pregnant women with ICP and 300 pregnant women without ICP admitted from July 2015 to December 2016 at Changsha Maternal and Child Health Hospital were collected. The factors associated with ICP were examined. The family history of ICP, twin pregnancies, number of births, hypertensive disorder of pregnancy (HDP), gestational diabetes, hyperlipidemia, hepatitis virus infection, and in vitro fertilization and embryo transfer, differed significantly between the 2 groups (all P < .05). The multivariable analysis showed that body mass index at delivery, number of births, HDP, gestational diabetes, hyperlipidemia, and hepatitis virus infection were associated with ICP (all P < .05). The incidence of abnormal amniotic fluid and premature births in the ICP group were significantly higher than in the control group (all P < .05). ICP is associated with BMI at delivery, number of births, HDP, gestational diabetes, hyperlipidemia, and hepatitis virus infection. ICP greatly influences pregnancy outcomes.


Assuntos
Colestase Intra-Hepática , Diabetes Gestacional , Hepatite , Pré-Eclâmpsia , Complicações na Gravidez , Viroses , Criança , Gravidez , Feminino , Lactente , Humanos , Diabetes Gestacional/epidemiologia , Estudos Retrospectivos , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Colestase Intra-Hepática/complicações , Colestase Intra-Hepática/epidemiologia , Viroses/complicações , Hepatite/complicações
2.
Emerg Infect Dis ; 29(2): 286-293, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36596569

RESUMO

In March 2022, a 61-year-old woman in France who had received a heart-lung transplant sought treatment with chronic hepatitis mainly characterized by increased liver enzymes. After ruling out common etiologies, we used metagenomic next-generation sequencing to analyze a liver biopsy sample and identified an unknown species of circovirus, tentatively named human circovirus 1 (HCirV-1). We found no other viral or bacterial sequences. HCirV-1 shared 70% amino acid identity with the closest known viral sequences. The viral genome was undetectable in blood samples from 2017-2019, then became detectable at low levels in September 2020 and peaked at very high titers (1010 genome copies/mL) in January 2022. In March 2022, we found >108 genome copies/g or mL in the liver and blood, concomitant with hepatic cytolysis. We detected HCirV-1 transcripts in 2% of hepatocytes, demonstrating viral replication and supporting the role of HCirV-1 in liver damage.


Assuntos
Circovirus , Transplante de Coração-Pulmão , Hepatite A , Hepatite , Feminino , Humanos , Pessoa de Meia-Idade , Circovirus/genética , Genoma Viral
3.
Redox Biol ; 59: 102596, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36610223

RESUMO

Alcoholic (ASH) and nonalcoholic. (NASH).steatohepatitis are advanced.stages.of.fatty.liver.disease.Methionine adenosyltransferase 1A (MAT1A) plays a key role in hepatic methionine metabolism and germline Mat1a deletion in mice promotes NASH. Acid sphingomyelinase (ASMase) triggers hepatocellular apoptosis and liver fibrosis and has been shown to downregulate MAT1A expression in the context of fulminant liver failure. Given the role of ASMase in steatohepatitis development, we investigated the status of ASMase in Mat1a-/- mice and the regulation of ASMase by SAM/SAH. Consistent with its role in NASH, Mat1a-/- mice fed a choline-deficient (CD) diet exhibited macrosteatosis, inflammation, fibrosis and liver injury as well as reduced total and mitochondrial GSH levels. Our data uncovered an increased basal expression and activity of ASMase but not neutral SMase in Mat1a-/- mice, which further increased upon CD feeding. Interestingly, adenovirus-mediated shRNA expression targeting ASMase reduced ASMase activity and protected Mat1a-/- mice against CD diet-induced NASH. Similar results were observed in CD fed Mat1a-/- mice by pharmacological inhibition of ASMase with amitriptyline. Moreover, Mat1a/ASMase double knockout mice were resistant to CD-induced NASH. ASMase knockdown protected wild type mice against NASH induced by feeding a diet deficient in methionine and choline. Furthermore, Mat1a-/- mice developed acute-on-chronic ASH and this outcome was ameliorated by amitriptyline treatment. In vitro data in primary mouse hepatocytes revealed that decreased SAM/SAH ratio increased ASMase mRNA level and activity. MAT1A and ASMase mRNA levels exhibited an inverse correlation in liver samples from patients with ASH and NASH. Thus, disruption of methionine metabolism sensitizes to steatohepatitis by ASMase activation via decreased SAM/SAH. These findings imply that MAT1A deletion and ASMase activation engage in a self-sustained loop of relevance for steatohepatitis.


Assuntos
Hepatite , Metionina , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Amitriptilina/farmacologia , Amitriptilina/metabolismo , Colina , Dieta , Modelos Animais de Doenças , Fígado/metabolismo , Metionina/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Racemetionina/metabolismo , Esfingomielina Fosfodiesterase/genética , Esfingomielina Fosfodiesterase/metabolismo , Hepatite/metabolismo
4.
Mediators Inflamm ; 2023: 3732315, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36654880

RESUMO

LIGHT is a member of the TNF superfamily and a proinflammatory cytokine involved in liver pathogenesis. Many liver diseases involve activation of Toll-like receptor 3 (TLR3), which is activated by double-stranded RNA (dsRNA). However, the involvement of LIGHT in TLR3 implicated liver diseases is not clear. In this study, we investigated the role of LIGHT in TLR3 involved liver pathogenesis by using a mouse model of TLR3 agonist poly(I:C)-induced hepatitis. We found LIGHT expression at both protein and mRNA level in liver tissues is dramatically increased during the course of poly(I:C)-induced liver injury. This induction depends on NF-κB activation as pretreating the mice with a NF-κB inhibitor abrogates LIGHT upregulation. Importantly, blockade of the LIGHT signaling pathway with the recombinant LIGHT receptor HVEM protein ameliorates liver injury in poly(I:C)-induced hepatitis. Conclusions. These results indicate that LIGHT amplification by NF-κB plays a significant role in TLR3 involved hepatitis and points LIGHT to be a potential drug target for liver disease therapy.


Assuntos
Hepatite , NF-kappa B , Receptor 3 Toll-Like , Citocinas , Hepatite/genética , Hepatite/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Poli I-C/farmacologia , Transdução de Sinais , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/metabolismo , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Animais , Camundongos , Modelos Animais de Doenças , Doença Aguda
5.
Int J Mol Sci ; 24(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36675133

RESUMO

Corydalis saxicola Bunting (CSB), whose common name in Chinese is Yanhuanglian, is a herb in the family Papaveraceae. When applied in traditional Chinese medicine, it is used to treat various diseases including hepatitis, abdominal pain, and bleeding haemorrhoids. In addition, Corydalis saxicola Bunting injection (CSBI) is widely used against acute and chronic hepatitis. This review aims to provide up-to-date information on the botanical distribution, description, traditional uses, phytochemistry, pharmacology, and clinical applications of CSB. A comprehensive review was implemented on studies about CSB from several scientific databases, such as SciFinder, Elsevier, Springer, ACS Publications, Baidu Scholar, CNKI, and Wanfang Data. Phytochemical studies showed that 81 chemical constituents have been isolated and identified from CSB, most of which are alkaloids. This situation indicates that these alkaloids would be the main bioactive substances and that they have antitumour, liver protective, antiviral, and antibacterial pharmacological activities. CSBI can not only treat hepatitis and liver cancer but can also be used in combination with other drugs. However, the relationships between the traditional uses and modern pharmacological actions, the action mechanisms, quality standards, and the material basis need to be implemented in the future. Moreover, the pharmacokinetics of CSBI in vivo and the toxicology should be further investigated.


Assuntos
Alcaloides , Corydalis , Medicamentos de Ervas Chinesas , Hepatite , Humanos , Corydalis/química , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Hepatite/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
6.
Medicine (Baltimore) ; 102(4): e32530, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36705361

RESUMO

RATIONALE: Emphysematous hepatitis (EH) is a rare and fulminant gas-forming liver infection. Only 3 patients were successfully treated. Diabetes mellitus and a history of digestive system cancer may predispose individuals to EH. Computed tomography (CT) findings support the diagnosis of EH and monitor progress. PATIENT CONCERNS: A 48-year-old man with diabetes presented with nausea, vomiting (gastric contents) and diarrhea. Laboratory test results revealed elevated levels of inflammatory indicators and abnormal liver function. CT showed a large-scale air collection with some remaining parenchymal debris in the left lobe of the liver. Remarkably, no fluid was observed inside the lesion. DIAGNOSE: The abdominal CT features and laboratory examination results rationalized the diagnosis of EH. INTERVENTIONS AND OUTCOMES: The patient finally recovered from this severe disease through a series of effective treatments, including strict glucose control, sensitive antibiotic therapy, and subsequent percutaneous drainage. LESSONS: EH generally deteriorates rapidly and eventually leads to death. This case will raise awareness of the rare and severe disease, strengthen diagnostic capacities, and provide advice to treat it.


Assuntos
Diabetes Mellitus , Enfisema , Hepatite A , Hepatite , Hepatopatias , Masculino , Humanos , Pessoa de Meia-Idade , Enfisema/diagnóstico por imagem , Enfisema/terapia , Diabetes Mellitus/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Hepatite/tratamento farmacológico , Antibacterianos/uso terapêutico
7.
J Formos Med Assoc ; 122(2): 182-186, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36610889

RESUMO

We present the case of a 6-year-old Taiwanese boy with a fulminant course of COVID-19 manifesting as high fever, acute consciousness changes, and status epilepticus. Brain MRI showed restricted diffusion in the bilateral hemisphere. Electroencephalogram showed diffuse slow waves with few spikes. CSF study was clear without evidence of common pathogens. He received treatment with antiviral agents, corticosteroids, intravenous immunoglobulins, and anti-IL-6 monoclonal antibodies. However, progressive fulminant hepatitis, hyperammonaemia, and disseminated intravascular coagulopathy developed. Rescue therapy with hybrid continuous renal replacement therapy and plasma exchange were performed in the first 11 days. The patient improved and was extubated on the 11th day. After physical therapy, his neurological function improved significantly. The patient was discharged under rehabilitation after 1 month of hospitalization. Viral sequencing confirmed infection with the Omicron BA.2.3 variant, one of the dominant strains in Taiwan and Hong Kong. Whole-exome sequencing revealed heterozygous uncertain significance variants in TICAM-1, RNF 31, and mitochondrial MT-RNR1, which provide additional support for the fulminant course. To the best of our knowledge, this is the first reported case of COVID-19 in a child with a fulminant course of acute encephalitis and hepatitis who successfully recovered by hybrid continuous renal replacement therapy and plasma exchange.


Assuntos
COVID-19 , Encefalite , Hepatite , Masculino , Humanos , Criança , COVID-19/terapia , Antivirais/uso terapêutico , Encefalite/terapia , Troca Plasmática
8.
J Tradit Chin Med ; 43(1): 87-94, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36639999

RESUMO

OBJECTIVE: To investigate the efficacy of Astragaloside IV (AS-IV) on radiation-induced liver inflammation in mice. METHODS: The mice were divided into normal group, dimethyl sulfoxide solvent group, irradiation group (IR), irradiation + AS-IV (20 mg/kg) group (IR+AS-20) and irradiation + AS-IV (40 mg/kg) group (IR+AS-40). One month after intraperitoneal injection of AS-IV, the mice were irradiated with 8Gry Co60γ, the blood was collected for biochemical analysis, and the liver was collected for hematoxylin-eosin staining, immunofluorescence and electron microscopic observation, oxidative stress, and Western blot analysis. RESULTS: The AS-IV treatment significantly ameliorated the pathological morphology of liver and reduced the alanine aminotransferase and aspertate amino-transferase levels in serum induced by radiation; AS-IV treatment also significantly reduced the expression of inflammatory factors tumor necrosis factor alpha and interleukin 6 and antagonized malonaldehyde content and superoxide dismutase activity in liver caused by radiation; in addition, AS-IV treatment can significantly inhibited the positive expression of thioredoxin-interacting protein (TXNIP) and nod-like receptor protein 3 (NLRP3) inflammasome in liver tissue after radiation; The expression of TXNIP, NLRP3 inflammasome, apoptosis-associated speck-like protein containing a CARD, cysteinyl aspartate-specific proteinase 1 and interleukin 1beta in the AS-IV prevention group decreased significantly compared to the radiation group. CONCLUSIONS: These findings suggested that Co60γ radiation can cause structural and functional damage to the liver, which may be related to the NLRP3 mediated inflammatory pathway; AS-IV may play a protective role by inhibiting the TXNIP/NLRP3 inflammasome signaling pathway in the radiation-induced liver injury model.


Assuntos
Hepatite , Inflamassomos , Camundongos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de Sinais , Inflamação/tratamento farmacológico , Tiorredoxinas/genética , Tiorredoxinas/metabolismo
10.
J Am Anim Hosp Assoc ; 59(1): 1-6, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36584317

RESUMO

A 7 yr old castrated male Cavalier King Charles spaniel presented for evaluation of liver enzyme elevations. Abdominal ultrasound revealed a small liver with mixed echogenicity, small hypoechoic nodules, and an irregular surface. Histologic examination and copper quantification of the liver obtained by laparoscopy diagnosed copper-associated hepatitis. One month later the dog developed hyperkeratosis of all four foot pads and ulcerations of feet, legs, and rectum. Punch biopsies confirmed superficial necrolytic dermatitis. After a total of 2 mo of chelation with no changes to medications, skin lesions began to improve, continuing over the following 6 wk to almost complete resolution. At this point the skin lesions returned and had minimal response to four amino acids infusions. The dog was switched from penicillamine to trientine. Zinc acetate was initiated 6 wk after the switch to trientine, and skin improvement was noted soon thereafter. At the time of death, skin lesions were improving and the dog was clinically comfortable. Copper-associated hepatitis should be considered as a possible etiology for superficial necrolytic dermatitis. Treatment of superficial necrolytic dermatitis is often unrewarding, and copper chelation, when copper-associated hepatitis has been confirmed, represents another therapeutic option.


Assuntos
Dermatite , Doenças do Cão , Hepatite , Dermatopatias , Cães , Masculino , Animais , Dermatite/tratamento farmacológico , Dermatite/veterinária , Dermatite/diagnóstico , Cobre , Trientina/uso terapêutico , Doenças do Cão/induzido quimicamente , Doenças do Cão/tratamento farmacológico , Doenças do Cão/diagnóstico , Dermatopatias/veterinária , Hepatite/complicações
11.
Pak J Pharm Sci ; 35(5): 1399-1405, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36451570

RESUMO

Despite of plethora of research on hepatoprotective potential of medicinal plants, there is still need to discover potential plants with hepatoprotective activity. Iris florentina L. is a medicinal plant with traditional claims but ignored investigation regarding its hepatoprotective effects. The current study is aimed to investigate the hepatoprotective potential of I. florentina L. methanolic extract on paracetamol (PCM)-induced liver injury. The phytochemical and HPLC screening was done which showed the presence of potential constituents including flavonoids and phenols. For investigating the hepatoprotective effect of I. florentina L. methanolic extract, rats were given five different treatments for seven consecutive days. The normal control (group 1) was administered with normal saline, group 2 (Diseased) received paracetamol and group 3 (Standard) was given silymarin as reference drug. In group 4 and 5 (Treated), I. florentina L. methanolic extract (250 and 500mg/kg) were administered. Different serum biomarkers and histopathological studies were performed to assess the recovery caused by PCM in comparison to diseased group. The treatment of I. florentina methanolic extract significantly improve the serum biomarkers and restored the hepatic injury towards normal, indicating the hepatoprotective potential. Thus, we can conclude that I. florentina have significantly reversed the damage caused by paracetamol in hepatotoxic rat model due to their potential phytochemical constituents.


Assuntos
Acetaminofen , Hepatite , Ratos , Animais , Acetaminofen/toxicidade , Metanol , Extratos Vegetais/farmacologia
12.
BMC Complement Med Ther ; 22(1): 321, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36464690

RESUMO

BACKGROUND: Diazinon (DZN), a widely used chemical herbicide for controlling agricultural pests, is an important organophosphorus pesticide and an environmental pollutant which induces toxic effects on living organisms during long-term exposure. Thymoquinone (TQ) is a phytochemical bioactive compound with antioxidant and anti-inflammatory properties. We aimed to evaluate the protective effects of TQ against DZN-induced hepatotoxicity through alleviating oxidative stress and enhancing cholinesterase (ChE) enzyme activity. METHODS: Rats were randomly divided into six groups (n = 8); a negative control group receiving corn oil; a group only receiving DZN (20 mg/kg/day); a group treated with TQ (10 mg/kg/day), and three treatment groups as TQ + DZN, receiving different doses of TQ (2.5, 5, and 10 mg/kg/day). All experimental animals were orally treated for 28 consecutive days. The levels of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactic acid dehydrogenase (LDH) were determined. In addition, ChE activity and histopathological changes were evaluated. RESULTS: The results showed that DZN decreased GSH level (p < 0.01) and SOD activity (p < 0.01) in parallel to an increase in MDA level (p < 0.01) and increased the activity of AST, ALT, ALP, and LDH (p < 0.01) in comparison to the negative control group. Our findings demonstrated that TQ administration could diminish hepatotoxicity and reduce oxidative damage in DZN-treated rats, which could be linked to its antioxidant and free radical scavenging properties. It was also observed that TQ 10 mg/kg remarkably increased the activity of acetylcholinesterase, butyrylcholinesterase, and SOD enzymes, elevated GSH, decreased MDA, and reduced pathological alternations of the liver induced by DZN. CONCLUSION: Thymoquinone 10 mg/kg increased the activity of plasma and blood cholinesterases and reduced DZN-induced alternations of the liver. Improvement of butyryl- and acetylcholinesterase activity suggests that maybe TQ supplement could be beneficial as pre-exposure prophylaxis among farm workers spraying pesticides.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Hepatite , Praguicidas , Animais , Ratos , Diazinon/toxicidade , Acetilcolinesterase , Antioxidantes/farmacologia , Butirilcolinesterase , Compostos Organofosforados , Praguicidas/toxicidade , Glutationa , Superóxido Dismutase , Fosfatase Alcalina , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle
13.
BMC Complement Med Ther ; 22(1): 331, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36514062

RESUMO

BACKGROUND: Tacrolimus (FK506) is an immunosuppressive agent and has toxic side effects such as nephrotoxicity, hepatotoxicity, and neurotoxicity. In our study, we aimed to investigate the protective effect of silymarin on renal and hepatic toxicity considered to be tacrolimus related. METHODS: In this 6-week experimental study, 46 eight-week-old healthy male rats were used. The groups comprised the Control (healthy rats, n = 6), Tac (tacrolimus 1 mg/kg, n = 8), silymarin 100 mg/kg (SLI 100 mg/kg n = 8), Tac + SLI 100 (tacrolimus 1 mg/kg + SLI 100 n = 8), SLI 200 (SLI 200 mg/kg n = 8), and Tac + SLI 200 (tacrolimus 1 mg/kg + SLI 200 mg/kg n = 8). After 6 weeks, all rats were sacrificed, and the tissue follow-up procedure was performed for kidney and liver tissues, histopathology, and in situ TUNEL analysis. Blood samples were analyzed for the total antioxidant capacity (TAC), total oxidant capacity (TOC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), albumin, total bilirubin, creatine. RESULTS: Histopathological findings of kidney and liver tissue of rats were determined to increase statistically in Tac group compared to SLI 1 00 and SLI 200 groups (P < 0.05). In addition, the Tac + SLI 100 and Tac + SLI 200 groups were found to be statistically similar to the Control group (P > 0.05). The in situ TUNEL method showed that the tacrolimus increased apoptosis while the silymarin decreased it. TOC levels increased statistically in Tac groups compared to silymarin-treated groups (P < 0.05). Although the TAC level was not statistically significant among the experimental groups (P > 0.05), the lowest was measured in the Tac group. The ALT, AST, GGT, total bilirubin, and creatine values were higher in the Tac group than in the silymarin groups (P < 0.05). There was no statistically significant difference between the groups with regard to the albumin level (P > 0.05). CONCLUSION: In our study, we determined that tacrolimus caused damage to kidney and liver tissue. Histopathological, biochemical and apoptotic findings show that silymarin has a protective effect against nephrotoxicity and hepatotoxicity caused by tacrolimus.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Hepatite , Silimarina , Masculino , Ratos , Animais , Silimarina/farmacologia , Tacrolimo/farmacologia , Creatina/farmacologia , Rim , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Bilirrubina/farmacologia , Albuminas/farmacologia
15.
Gac Med Mex ; 158(5): 328-331, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36572034

RESUMO

At the beginning of 2022, in the United Kingdom, and later in several European countries, a group of pediatric patients who developed acute hepatitis of so far unknown origin was reported. Clinical data include nausea, vomiting, jaundice, and liver failure; some patients require liver transplantation. The affected population is younger than 10 years of age. The probable etiological agent is adenovirus genotype F41, and toxic factors have been ruled out, as well as a relationship with COVID-19. There are several theories to explain this phenomenon, which are being investigated.


A inicios de 2022, en Reino Unido, y posteriormente en varios países europeos, se informó sobre un grupo de pacientes pediátricos que desarrollaron hepatitis aguda de origen desconocido hasta ahora. Los datos clínicos consisten en náusea, vómito, ictericia y falla hepática; algunos pacientes necesitan trasplante hepático. La población afectada es menor a los 10 años. El agente etiológico probable es el adenovirus genotipo F41 y se han descartado factores tóxicos, así como la relación con COVID-19. Existen varias teorías para explicar este fenómeno, las cuales se están investigando.


Assuntos
COVID-19 , Hepatite , Icterícia , Transplante de Fígado , Humanos , Criança , COVID-19/complicações , Hepatite/etiologia , Icterícia/complicações , Doença Aguda
17.
Cell Death Dis ; 13(12): 1031, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36494334

RESUMO

The cell-cell interaction between hepatocytes and Kupffer cells (KCs) is crucial for maintaining liver homeostasis, and the loss of KCs and hepatocytes is known to represent a common pathogenic phenomenon in autoimmune hepatitis. Until now, the mechanisms of cell-cell interaction between hepatocytes and KCs involved in immune-mediated hepatitis remains unclear. Here we dissected the impact of activated mTORC1 on the cell-cell interaction of KCs and hepatocyte in immune-mediated hepatitis. In the liver from patients with AIH and mice administrated with Con-A, mTORC1 was activated in both KCs and hepatocytes. The activated mTORC1 signal in hepatocytes with Con-A challenge caused a markedly production of miR-329-3p. Upregulated miR-329-3p inhibited SGMS1 expression in KCs through paracrine, resulting in the death of KCs. Most of maintained KCs were p-S6 positive and distributed in hepatocyte mTORC1 negative area. The activation of mTORC1 enabled KCs expressed complement factor B (CFB) to enhance the complement alternative system, which produced more complement factors to aggravate liver injury. Our findings remonstrate a heterogeneous role of mTORC1 in specific cell type for maintaining tolerogenic liver environment, and will form the basis for the development of new interventions against immune-mediated hepatitis.


Assuntos
Hepatite , MicroRNAs , Camundongos , Animais , Células de Kupffer/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Hepatócitos/metabolismo , Hepatite/metabolismo , Fígado , Concanavalina A , MicroRNAs/metabolismo
19.
Cells ; 11(24)2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36552746

RESUMO

Bile acid (BA) synthesis from cholesterol by hepatocytes is inhibited by inflammatory cytokines. Whether liver inflammation also affects BA side chain shortening and conjugation was investigated. In human liver cell lines (IHH, HepG2, and HepaRG), agonists of nuclear receptors including the farnesoid X receptor (FXR), liver X receptor (LXR), and peroxisome proliferator-activated receptors (PPARs) did not affect the expression of BA-related peroxisomal enzymes. In contrast, hepatocyte nuclear factor 4α (HNF4α) inhibition down-regulated acyl-CoA oxidase 2 (ACOX2). ACOX2 was repressed by fibroblast growth factor 19 (FGF19), which was prevented by extracellular signal-regulated kinase (ERK) pathway inhibition. These changes were paralleled by altered BA synthesis (HPLC-MS/MS). Cytokines able to down-regulate cholesterol-7α-hydroxylase (CYP7A1) had little effect on peroxisomal enzymes involved in BA synthesis except for ACOX2 and bile acid-CoA:amino acid N-acyltransferase (BAAT), which were down-regulated, mainly by oncostatin M (OSM). This effect was prevented by Janus kinase (JAK) inhibition, which restored BA side chain shortening and conjugation. The binding of OSM to the extracellular matrix accounted for a persistent effect after culture medium replacement. In silico analysis of four databases (n = 201) and a validation cohort (n = 90) revealed an inverse relationship between liver inflammation and ACOX2/BAAT expression which was associated with changes in HNF4α levels. In conclusion, BA side chain shortening and conjugation are inhibited by inflammatory effectors. However, other mechanisms involved in BA homeostasis counterbalance any significant impact on the serum BA profile.


Assuntos
Ácidos e Sais Biliares , Hepatite , Humanos , Espectrometria de Massas em Tandem , Colesterol/metabolismo , Citocinas , Inflamação
20.
Front Public Health ; 10: 1012638, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36504992

RESUMO

The etiology of severe acute hepatitis (SAH) in children is various. We describe the first Chinese case of severe acute hepatitis in a 22-month-old boy with the mild illness of Omicron sub-variant BA.2.38. With the application of Compound Glycyrrhizin Injection (CGI), the patient gradually recovered from acute liver injury (ALI). This case highlights the possibility of severe ALI in children with the non-critical illness of SARS-CoV-2. The management of SAH associated with the pandemic presents challenges for clinicians, and follow-up is in need. The method of differential diagnosis using limited laboratory results is of great value to the clinicians.


Assuntos
COVID-19 , Hepatite , Masculino , Criança , Humanos , Lactente , SARS-CoV-2 , Hepatite/diagnóstico
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