RESUMO
BACKGROUND: Hypernatremic donors was regarded as the expanded criteria donors in liver transplantation. The study was to investigate the effects of donor hypernatremia on the outcomes of liver transplantation and identify the prognostic factors possibly contributing to the poor outcomes. METHODS: Donor serum sodium levels before procurement were categorized as normal sodium (< 155 mmol/L), moderate high sodium (155-170 mmol/L), and severe high sodium (≥ 170 mmol/L). Furthermore, we subdivided the 142 hypernatremic donors (≥ 155 mmol/L) into two subgroups: subgroup A, the exposure time of liver grafts from hypernatremia to reperfusion was < 36 h; and subgroup B, the exposure time was ≥ 36 h. The outcomes included initial graft function, survival rates of grafts and recipients, graft loss and early events within the first year following liver transplantation. RESULTS: There were no significant differences in the 1-year survival rates of grafts and recipients, 1-year graft loss rates and early events among the normal, moderate high and severe high sodium groups. However, the overall survival rates of grafts and recipients in subgroup A were significantly higher than those in subgroup B. Cox model showed that the exposure time (HRâ¯=â¯1.117; 95% CI: 1.053-1.186; Pâ¯<â¯0.001), cold ischemia time (HRâ¯=â¯1.015; 95% CI: 1.006-1.024; P = 0.001) and MELD (HRâ¯=â¯1.061; 95% CI: 1.003-1.121; P = 0.037) were the important prognostic factors contributing to the poor outcomes of recipients with hypernatremic donors. CONCLUSIONS: The level of donor sodium immediately before organ procurement does not have negative effects on the early outcomes following adult liver transplantation. For hypernatremia liver donors, minimization of the exposure time from hypernatremia to reperfusion is critical to prevent graft loss.
Assuntos
Morte Encefálica , Sobrevivência de Enxerto , Hipernatremia/terapia , Transplante de Fígado/métodos , Doadores não Relacionados , Adulto , Feminino , Sobrevivência de Enxerto/fisiologia , Humanos , Hipernatremia/complicações , Fígado/cirurgia , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Obtenção de Tecidos e Órgãos , Transplante Homólogo , Resultado do TratamentoRESUMO
Hepatocellular carcinoma (HCC) is known for its high mortality rate worldwide. Based on intensive studies, microRNA (miRNA) expression functions in tumor suppression. Therefore, we aimed to evaluate the contribution of miR-146a-5p to radiosensitivity in HCC through the activation of the DNA damage repair pathway by binding to replication protein A3 (RPA3). First, the limma package of R was performed to differentially analyze HCC expression chip, and regulative miRNA of RPA3 was predicted. Expression of miR-146a-5p, RPA3, and DNA damage repair pathway-related factors in tissues and cells was determined. The effects of radiotherapy on the expression of miR-146a-5p and RPA3 as well as on cell radiosensitivity, proliferation, cell cycle, and apoptosis were also assessed. The results showed that there exists a close correlation between miR-146a and the radiotherapy effect on HCC progression through regulation of RPA3 and the DNA repair pathway. The positive rate of ATM, pCHK2, and Rad51 in HCC tissues was higher when compared with that of the paracancerous tissues. SMMC-7721 and HepG2 cell proliferation were significantly inhibited following 8 Gy 6Mv dose. MiR-146a-5p restrained the expression of RPA3 and promoted the expression of relative genes associated with the DNA repair pathway. In addition, miR-146a-5p overexpression suppresses cell proliferation and enhances radiosensitivity and cell apoptosis in HCC cells. In conclusion, the present study revealed that miR-146a-5p could lead to the restriction of proliferation and the promotion of radiosensitivity and apoptosis in HCC cells through activation of DNA repair pathway and inhibition of RPA3.
Assuntos
Carcinoma Hepatocelular/genética , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Tolerância a Radiação/genética , Adulto , Idoso , Apoptose/genética , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células HEK293 , Células Hep G2 , Humanos , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/genéticaRESUMO
BACKGROUND: Portal hypertension is one of the most important clinical conditions that cause intraoperative intensive hemorrhage in cirrhotic patients undergoing liver transplantation. Pre-transplant portal decompression may reduce the intraoperative bleeding during liver transplantation. METHODS: Splenic artery trunk embolization (SATE) was performed one month prior to liver transplantation. Platelet count, prealbumin, international normalized ratio, and blood flow in the portal vein and hepatic artery were monitored before and one month after SATE. The measurements above were collected on admission and before surgery in the non-SATE patients, who served as controls. We also recorded the intraoperative blood loss, operating time, required transfusion, post-transplant ascites, and complications within three months after operation in all patients. RESULTS: SATE significantly reduced portal venous blood flow, increased hepatic arterial blood flow, normalized platelet count, and improved prealbumin and international normalized ratio in the patients before liver transplantation. Compared to the non-SATE patients, the pre-transplant SATE significantly decreased the operating time, intraoperative bleeding, post-transplant ascites and severe surgical complications. CONCLUSION: Pre-transplant SATE decreases portal pressure, improves liver function reserve, and reduces the surgical risk of liver transplantation effectively in patients with severe portal hypertension.
Assuntos
Embolização Terapêutica/métodos , Hipertensão Portal/terapia , Transplante de Fígado/efeitos adversos , Cuidados Pré-Operatórios/métodos , Artéria Esplênica , Adulto , Ascite/etiologia , Ascite/prevenção & controle , Biomarcadores/sangue , Coagulação Sanguínea , Velocidade do Fluxo Sanguíneo , Perda Sanguínea Cirúrgica/prevenção & controle , Embolização Terapêutica/efeitos adversos , Feminino , Artéria Hepática/fisiopatologia , Artéria Hepática/cirurgia , Humanos , Hipertensão Portal/diagnóstico , Hipertensão Portal/fisiopatologia , Coeficiente Internacional Normatizado , Circulação Hepática , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Contagem de Plaquetas , Pressão na Veia Porta , Veia Porta/fisiopatologia , Veia Porta/cirurgia , Pré-Albumina/metabolismo , Cuidados Pré-Operatórios/efeitos adversos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: Gene therapy can provide a possible avenue in organ transplantation to treat acute allograft rejection. This study was designed to investigate the effect of adenovirus-mediated human IL-10 (hIL-10) gene transfer on the apoptosis of infiltrating lymphocytes and examine the efficacy of hIL-10 gene transfer in combination with subtherapeutic doses of cyclosporine A (CsA) in a rat liver transplantation model. METHODS: Inbred male DA and LEW rats were used for liver donors and recipients, respectively. The rats were divided into saline, Ad-lacZ, CsA, Ad-hIL-10 and Ad-hIL-10 + CsA groups. Graft survival, histopathological, enzyme-linked immunosorbent assay, reverse transcriptase-polymerase chain reaction and flow cytometry were performed in liver specimens obtained from different time points after transplantation in the 5 groups. RESULTS: Ad-hIL-10 pretreatment inhibited allograft rejection, prolonged the survival of hepatic allografts, and downregulated the expression of IFN-gamma and IL-2 mRNA, with simultaneous upregulation of IL-4 mRNA. In addition, Ad-hIL-10 pretreatment upregulated the expression of Fas mRNA in the isolated graft-infiltrating lymphocytes and induced graft-infiltrating lymphocyte apoptosis. A single subtherapeutic dose of CsA acted synergistically with it. CONCLUSION: hIL-10 gene therapy induced alloreactive lymphocyte apoptosis via Fas/FasL pathway. hIL-10 gene transfection in combination with subtherapeutic doses of CsA facilitates the long-term survival of liver grafts.
Assuntos
Interleucina-10/genética , Transplante de Fígado/imunologia , Transplante de Fígado/patologia , Linfócitos/imunologia , Linfócitos/patologia , Adenoviridae/genética , Animais , Apoptose , Sequência de Bases , Primers do DNA/genética , Terapia Genética , Vetores Genéticos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/terapia , Humanos , Interleucina-10/sangue , Interleucina-10/uso terapêutico , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos Lew , Ratos Endogâmicos , Proteínas Recombinantes/sangue , Proteínas Recombinantes/genética , Proteínas Recombinantes/uso terapêutico , Transfecção , Transplante HomólogoRESUMO
BACKGROUND: Interleukin 10 (IL-10), a Th2 type cytokine, modulates inflammatory responses by inhibiting the production of proinflammatory cytokines. This study was designed to investigate the protective effects of adenovirus-mediated human IL-10 (Ad-hIL-10) gene transfer on protecting grafts from cold ischemia-reperfusion injury following orthotopic liver transplantation in rats. METHODS: Adenoviruses encoding hIL-10 or beta-galactosidase (Ad-lacZ) were injected via the superior mesenteric vein into prospective donor animals. The donor liver was harvested 48 hours after transduction, and stored for 12 hours at 4 degree centigrade in lactated Ringer's solution prior to transplantation. The rats were divided into saline, Ad-lacZ, and Ad-hIL-10 groups. Liver function test, histopathological examination, reverse transcriptase-polymerase chain reaction (RT-PCR), and Western blotting were performed at 24 hours after transplantation in the three groups. RESULTS: Liver function (ALT and AST) was significantly improved, and the Suzuki score was significantly decreased in the Ad-hIL-10 group. The levels of hepatic TNF-alpha, MIP-2, ICAM-1 mRNA, and NF-kappaB protein in the Ad-hIL-10 group were significantly decreased. The expression of hIL-10 mRNA was detected by RT-PCR in Ad-hIL-10-treated grafts but not in controls treated with saline or Ad-lacZ. CONCLUSIONS: Donor pretreatment with Ad-hIL-10 down-regulates the expression of proinflammatory cytokines TNF-alpha, MIP-2, and ICAM-1 mRNA. hIL-10 protects against hepatic cold ischemia-reperfusion injury, at least in part, by suppressing NF-kappaB activation and subsequent expression of proinflammatory mediators.
Assuntos
Adenoviridae/genética , Terapia Genética , Interleucina-10/genética , Isquemia/complicações , Transplante de Fígado/efeitos adversos , Traumatismo por Reperfusão/prevenção & controle , Animais , Vetores Genéticos , Humanos , NF-kappa B/fisiologia , Ratos , Ratos Sprague-Dawley , Transplante HomólogoRESUMO
BACKGROUND: Apoptosis as well as necrosis may play an important role in hepatic ischemia/reperfusion (I/R) injury. Interleukin 10 (IL-10), a Th2 type cytokine, modulates inflammatory responses by inhibiting the production of proinflammatory cytokines. The study focused on cytoprotective and antiapoptotic pathways to assess mechanisms by which gene transduction of human IL-10 (hIL-10) may renders grafts resistant to the cold I/R injury. MATERIALS AND METHODS: Adenoviruses encoding hIL-10 or beta-galactosidase (LacZ) were injected via the superior mesenteric vein into prospective donor animals. The donor liver was harvested 48h after transduction, and stored for 12h at 4 degrees C lactated Ringer's solution prior to being transplanted. Graft survival, liver function, the degree of necrosis and apoptosis, and the molecules of apoptotic networks were assessed. RESULTS: Ad-hIL-10 pretreatment significantly prolonged the survival of liver grafts by improving liver function, preserving hepatocyte integrity and architecture, and depressing intrahepatic apoptosis and necrosis. In addition, Ad-hIL-10 pretreatment diminished the release of cytochrome c from mitochondria into cytoplasm and caspase-3 activity, with simultaneous up-regulated of antioxidant HO-1 and anti-antiapoptotic Bcl-2 molecules. CONCLUSION: Adenoviral gene transfer of hIL-10 ameliorated cold I/R injury by decreasing hepatic necrosis and apoptosis. The underlying mechanism of cytoprotective effects may at least be involved with the inhibition of caspase-3 activity and mitochondrial cytochrome c release, and the up-regulation of antiapoptotic (Bcl-2) and antioxidant (HO-1) molecules.
Assuntos
Temperatura Baixa , Terapia Genética/métodos , Interleucina-10/genética , Transplante de Fígado , Traumatismo por Reperfusão/prevenção & controle , Adenoviridae/genética , Animais , Apoptose/imunologia , Crioprotetores , Citocromos c/metabolismo , Sobrevivência de Enxerto/fisiologia , Hepatócitos/patologia , Hepatócitos/fisiologia , Humanos , Interleucina-10/imunologia , Necrose , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/patologiaRESUMO
BACKGROUND: Congenital extrahepatic portosystemic shunt, also known as Abernethy deformation, is a rare malformation caused by dysplasia in the portal vein system. There are few reports of liver transplantation as a treatment for Abernethy deformation, and our report is the first case in China. This is the second reported case with congenital extrahepatic portosystemic shunt combined with focal nodular hyperplasia and hepatopulmonary treated with liver transplantation. CASE SUMMARY: The patient was a 14-year-old girl, diagnosed preoperatively as type Ib Abernethy deformation, intrahepatic multiple space-occupying lesion, and hepatopulmonary syndrome. The patient recovered well after undergoing classic orthotopic liver transplantation. Liver function, pulmonary function, and portal vein computed tomography angiography imaging were reexamined 20 mo postoperatively, and no abnormality was observed. CONCLUSION: Liver transplantation is an effective treatment for type I Abernethy deformation combined with focal nodular hyperplasia and hepatopulmonary syndrome.
RESUMO
Wernicke encephalopathy (WE) is an acute neurological disorder resulting from vitamin B1 deficiency, which is common in chronic alcoholism and is rare in acute liver failure. So far, there are 2 cases of WE reported after liver transplantation. Here, we report a case of a 45-year-old nonalcoholic male patient who developed psychiatric and neurological disturbance 15 d after receiving orthotopic liver transplantation because of hepatitis B-related cirrhosis and portal hypertension. Brain magnetic resonance imaging (MRI) showed symmetric high-signal intensities in the periaqueductal area. The patient was diagnosed with WE and given intravenous high-dose vitamin B1 immediately. His neurological disturbance resolved in 7 d after receiving the vitamin B1. Brain MRI after 5 mo showed nearly complete recovery. Most WE cases may be misdiagnosed in patients after liver transplantation, and we should pay more attention to its onset.
Assuntos
Doença Hepática Terminal/cirurgia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complexo Vitamínico B/uso terapêutico , Encefalopatia de Wernicke/etiologia , Administração Intravenosa , Encéfalo/diagnóstico por imagem , Humanos , Testes de Função Hepática , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/tratamento farmacológico , Tiamina/uso terapêutico , Deficiência de Tiamina/sangue , Deficiência de Tiamina/diagnóstico , Deficiência de Tiamina/tratamento farmacológico , Deficiência de Tiamina/etiologia , Encefalopatia de Wernicke/sangue , Encefalopatia de Wernicke/diagnóstico , Encefalopatia de Wernicke/tratamento farmacológicoRESUMO
OBJECTIVE: To explore the protective effect of octreotide on liver warm ischemia-reperfusion injury and its possible mechanism. METHODS: Pringle's maneuver liver ischemia-reperfusion models were established. Forty eight male Sprague Daweley rats were randomly divided into a sham operation group (S group, n=16), an ischemia-reperfusion group (I/R group, n=16) and an octreotide preconditioning group (OPC group, n=16). ALT and AST in the serum were measured at 30 min after the ischemia and 120 min after the reperfusion. The histomorphological changes and ultrastructure of hepatocellular were observed by optic and transmission electronic microscope. Hepatic adenine nucleotide levels and energy changes (EC) were determined by high performance liquid chromatography (HPLC). RESULTS: (1) At 30 min after the ischemia and 120 min after the reperfusion, the levels of ALT and AST in the serum of OPC group was lower than those in I/R group, whereas the levels of ATP and EC in the hepatic tissue were higher than those in the I/R group (P<0.01 or P<0.05). Compared with the I/R group, the injury of hepatocellular histomorphology and ultrastructure in the OPC group was abated. (2) At 30, 60, and 120 min after the reperfusion, the levels of ATP and EC in the OPC groups were higher than those in the I/R group. During the ischemia, the levels of ATP and EC in the OPC group dropped more slowly than those in the I/R group, but ATP and EC in the OPC groups rose more quickly than those in the I/R group during the reperfusion. CONCLUSION: Octreotide precondition can improve the hepatocellular energy reserve, and protect the liver from warm ischemia-reperfusion injury. The protective of octreotide on warm ischemia-reperfusion injury may be related to its influence on endocrine secretion.
Assuntos
Fígado/irrigação sanguínea , Octreotida/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Temperatura Alta , Masculino , Octreotida/uso terapêutico , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To study microRNA (miR)-20a expression in hepatocellular carcinoma (HCC) and its effects on the proliferation, migration, and invasion of HepG2. METHODS: The real-time polymerase chain reaction was used to detect the expression of miR-20a in HCC tissue and normal tissue, as well as in HCC cell lines and normal liver cells. miR-20a mimic and miR negative control (NC) were transfected into HepG2 cells. MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay was used to detect cell proliferation. Annexin fluorescein isothiocyanate/propidium iodide assay was run to examine the early apoptosis of cells. Transwell chamber assay was carried out to investigate the cell invasion and migration abilities. RESULTS: miR-20a was lowly expressed both in HCC tissues and HCC cell lines. After transfection of exogenous miR-20 mimics, miR-20a expression in HepG2 cells was significantly increased by 61.29% compared to the blank group (P<0.01). MTT assay showed that the growth of HepG2 cells in the miR-20a mimics group was significantly inhibited, and optical density values during the 36-96 hour time period were dramatically decreased compared to the blank group (P<0.01). Apoptosis rates of the miR-20a mimics group were higher than those of the blank and NC groups (both P<0.01). The number of HCC cells after transfection by miR-20a mimics in the G1 and S phases were 15.88% and 7.89%, respectively, which were lower than in the blank and NC groups (both P<0.05). Transwell assay showed that in the miR-20a mimics group the number of cell migration and invasion were 0.459 and 0.501 times that of the blank group (both P<0.01), and the migration and inhibition rates were 54.1% and 51.4%, respectively. After closing target gene CCND1 in HepG2 cells, the number of cell migration and invasion in the small interfering (si)-CCND1 group were 0.444 and 0.435 times that of the si-NC group (P<0.05); and compared to the si-NC group, the migration and inhibition rates were 55.6% and 56.5%, respectively. CONCLUSION: miR-20a can inhibit the growth, invasion, and migration of HepG2 cells, and is therefore promising as a new molecular target for diagnosis and therapy of HCC.
RESUMO
OBJECTIVE: To investigate the role of Thl7 cells and the cytokine interleukin-17 (IL-17) in acute allograft rejection in mice. METHODS: Mouse models of kidney transplantation were randomly divided into rejection group and isograft group. On the post-operative day (POD) 3 and 7, we tested the serum IL-17 level using enzyme-linked immunosorbent assay and measured the number of Th17 cells in the renal grafts by flow cytometry. The grafts were harvested and fixed in 10% formalin to prepare paraffin sections for routine pathological inspection. RESULTS: Compared to isograft group, the allograft group showed a significantly higher level of serum IL-17 on POD3 and POD7 (P<0.05), and the level of IL-17 is significantly higher on POD7 than on POD3 (P<0.05). The allograft group showed more infiltrating Th17 cells in the grafts on POD3 and POD7 (P<0.05), and the cell number was significantly greater on POD7 (P<0.05). Pathological examination also showed an increased severity of graft rejection with the post-transplantation time. CONCLUSION: Thl7 cells may play an important role in the development of renal graft rejection. IL-17 may serve as a potential specific indicator for predicting allograft rejection.