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1.
Biochem Biophys Res Commun ; 540: 42-50, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33445109

RESUMO

Liver sinusoidal endothelial cells (LSECs), which play a very critical role in liver regeneration, function in hypoxic environments, but few studies have elucidated the specific mechanism. As a hypoxia-sensitive gene, Sentrin/SUMO-specific protease 1(SENP1) is upregulated in solid tumors due to hypoxia and promotes tumor proliferation. We speculate that LSECs may upregulate SENP1 in hypoxic environments and that SENP1 may act on downstream genes to allow the cells to adapt to the hypoxic environment. To elucidate the reasons for the survival of LSECs under hypoxia, we designed experiments to explore the possible mechanism. First, we cultured murine LSECs in hypoxic conditions for a certain time (24 h and 72 h), and then, we observed that the proliferation ability of the hypoxia group was higher than that of the normoxia group, and the number of unique fenestrae of the LSECs in the hypoxia group was more than that of the LSECs in the normoxia group. Then, we divided the LSECs into several groups for hypoxic culture for time points (6 h, 12 h, 24 h, 36 h, and 72 h), and we found that the expression of SENP1, HIF-1α and VEGF was significantly upregulated. Then, we silenced SENP1 and HIF-1α with si-SENP1 and si-HIF-1α, respectively. SENP1, HIF-1α and VEGF were significantly downregulated, as determined by RT-PCR, WB and ELISA. Unexpectedly, the proliferation activity of the LSECs decreased and the fenestrae disappeared more in the si-SENP1 and si-HIF-1α groups than in the control group. It is concluded that LSECs cultured under hypoxic conditions may maintain fenestrae and promote proliferation through the SENP1/HIF-1α/VEGF signaling axis, thereby adapting to the hypoxic environment.

2.
Zhongguo Gu Shang ; 33(12): 1142-7, 2020 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-33369322

RESUMO

OBJECTIVE: To analyze the causes of vascular injury occurred in oblique lateral interbody fusion for treating lumbar degenerative diseases, and put forward preventive measures. METHODS: There were 235 patients analyzed from October 2014 to May 2017 in five hospitals, who were treated with oblique lateral interbody fusion with or without posterior pedicle screw fixation. There were 79 males and 156 females with an average age of (61.9±13.5) years old (ranged from 32 to 83 years). There were 7 cases of vascular injury, including 4 cases of segmental vessel injury, 1 case of left common iliac artery injury, 1 case of left common iliac veininjury and 1 case of ovarian vein injury. RESULTS: The follow up time ranged from 6 to 36 months, averagely (15.6±7.5) months. There was no pedicle screw loosen or fracture. The low back pain VAS decreased from preoperative 6.7±2.3 to 1.4±0.8 at the latest follow-up, which was statistically difference(t=7.21, P=0.033). The ODI decreased from preoperative (36.5±7.7)% to (9.4±3.6)% at the latest follow-up, which was statistically difference (t=8.11, P=0.025). CONCLUSION: Oblique lateral interbody fusion technique provides a new method for minimally invasive fusion of lumbar internal fixation. However, it has a risk of vascular injury. In order to effectively prevent the occurrence of vascular injury, the operative indications and careful and meticulous operation should be strictly grasped.


Assuntos
Parafusos Pediculares , Fusão Vertebral , Lesões do Sistema Vascular , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Vértebras Lombares/cirurgia , Região Lombossacral , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Resultado do Tratamento , Lesões do Sistema Vascular/etiologia , Lesões do Sistema Vascular/prevenção & controle , Lesões do Sistema Vascular/cirurgia
3.
Biomed Pharmacother ; 129: 110398, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32603889

RESUMO

Hepatic ischemia reperfusion (I/R) injury (HIRI) HIRI is a complex, multifactorial pathophysiological process and in liver surgery has been known to significantly affect disease prognosis, surgical success rates, and patient survival. Ginsenoside Rgl (Rgl) monomer is one of the main active ingredients of ginseng. Previous studies have demonstrated that Rgl exerts various pharmacological effects through several mechanisms including suppression of apoptosis-related proteins levels, downregulation of inflammatory mediators and as well as antioxidant, which effectively exerts an organ protective effect I/R-induced damage. However, the exact mechanisms of Rg1 on HIRI remain to be elucidated. In the present study, we investigated the protective effect of Rg1 on hepatic ischemia-reperfusion (I/R) injury (HIRI) and explored its underlying molecular mechanism. A rat warm I/R injury model in vivo and an oxygen-glucose deprivation/reperfusion (OGD/R)-treated BRL-3A cell model in vitro were established after pretreating with Rg1(20 mg/kg). The results showed that Rg1 reduced the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). TUNEL staining showed that pretreated with Rg1 inhibited the apoptosis rate compared with the I/R group. Moreover, pretreated with Rg1 significantly reduced the expression of Cyt-C, Caspase-9 and Caspase-3 to inhibit the cell apoptosis. Flow cytometry analysis showed the MMP in the I/R group was significantly increased, whereas pretreated with Rg1 effectively stabilized the MMP compared with the I/R group. in vitro, the proliferation of BRL-3A cells was significantly decreased by the OGD/R treatment, while Rg1 effectively reversed this phenomenon. In addition, western blotting showed that the increase of Cyt-C, Caspase-9 and Caspase-3 was inhibited by H2O2. These observations suggest that Rg1 exerts the protective effect by inhibiting the CypD protein-mediated mitochondrial apoptotic pathway.

4.
Am J Chin Med ; 48(5): 1159-1178, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32668973

RESUMO

Hepatic ischemia-reperfusion (IR) injury remains the major cause of liver damage post-liver surgery or transplantation. Diminishing oxidative stress and inflammatory responses is a powerful channel to reduce the rate of morbidity and mortality. Gastrodin (GSTD), a bioactive compound extracted from the traditional Chinese herbal agent with a long history of clinical application in nervous system diseases, is suggested to possess anti-oxidative effects on liver diseases, such as nonalcoholic fatty liver disease. However, the therapeutic potential of GSTD in liver IR injury remains unclear. In this paper, we performed surgery to set up the 70% hepatic IR injury models in mice after a three-day pretreatment of GSTD. We found the administration of GSTD reduced liver damage, which correlated with lower histological Suzuki's score, lower serum alanine transaminase (AST) and alanine transaminase (ALT) levels, less oxidative stress, and cell apoptosis in a dose-responsive manner, as compared to the parallel control. Meanwhile, we observed a great induction of heme oxygenase-1 (HO-1) and an activation of the p38 mitogen-activated protein kinases/nuclear factor erythroid 2-related factor 2 (p38MAPK/Nrf2) pathway in response to the GSTD pretreatment, while the protective effects upon GSTD diminished in mice with HO-1 heterozygous mutation. In addition, GSTD inhibited IR induced toll-like receptor (TLR) 4, but not TLR2 in a HO-1 dependent manner, leading to a down-regulation of cytokines, such as interleukin (IL)-6 and TNF-[Formula: see text]. Collectively, our findings revealed GSTD attenuated liver IR injury via activation of the HO-1 pathway, providing a novel therapeutic strategy to minimize the IR induced oxidative stress in the process of liver transplantation.


Assuntos
Antioxidantes , Álcoois Benzílicos/administração & dosagem , Álcoois Benzílicos/farmacologia , Glucosídeos/administração & dosagem , Glucosídeos/farmacologia , Fígado , Fator 2 Relacionado a NF-E2/metabolismo , Fitoterapia , Traumatismo por Reperfusão/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Medicamentos de Ervas Chinesas , Heme Oxigenase-1/metabolismo , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Cuidados Pré-Operatórios , Receptor 4 Toll-Like/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
5.
Zhongguo Gu Shang ; 33(4): 337-47, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32351088

RESUMO

OBJECTIVE: To explore the clinical effect of combined fixation and interbody bone grafting through intermuscular approach with different fusion cages in the treatment of single segment lumbar diseases. METHODS: From June 2014 to December 2016, the clinical data of 123 cases of single segment lumbar diseases were analyzed retrospectively, including 44 males and 79 females, aged 22 to 60 years old, with the diseases course of 6 to 84 months. The disease types involved lumbar disc degeneration in 65 cases, lumbar spinal stenosis in 30 cases, MeyerdingⅠslip in 21 cases, giant lumbar disc herniation in 7 cases. Lesions was L3, 4 in 5 cases, L4, 5 in 101 cases, L5S1 in 17 cases. According to the application of different interbody fusion cage, patients were divided into single common cage group, double common cage group and banana type cage group. The operation time, intraoperative hemorrhage, postoperative incision drainage fluid and incision length were observed in three groups; VAS score of lumbar incision and JOA score of preoperative and final follow up were recorded 72 hours after operation;the intervertebral space height, Cobb angle of lumbar coronal and sagittal plane before and after operation, and interbody fusion 12 months after operation were observed by imaging data. RESULTS: There was no significant difference in incision length, operation time, intraoperative bleeding volume, postoperative drainage volume and VAS score of lumbar incision 72 hours after operation among three groups (P>0.05). All cases were followed up for 12 to 36 (23.70±4.52) months. The height of intervertebral space in three groups recovered significantly (P<0.05), at the last follow-up, there were different degrees of loss, the loss degree of single common fusion cage group>banana type fusion cage group>double common fusion cage group. At the last follow-up, the Cobb angle in the coronaland sagittal planes of the three groups were significantly improved (P<0.05). During the follow-up, there were 42 cases of fusion cage subsidence, including 26 cases in the single common cage group, 5 cases in the double common cage group, 11 cases in the banana cage group, the difference was statistically significant (P<0.05). At 12 months after operation, the interbody fusion rate was 83% in the single common cage group, 95% in the double common cage group and 90% in the banana cage group, the interbody fusion rate in the two common cage group and the banana cage group was better than that in the single common cage group. No obvious degeneration was observed in the adjacent segments. At the last follow-up, the JOA scores of the three groups were statistically significant (P<0.05). The incidence of single common fusion cage group was 10%(4 / 42), that of double common fusion cage group was 9%(4 / 43), and that of banana fusion cage group was 10%(4 / 39). There was no significant difference among the three groups. CONCLUSION: Through the intermuscular approach, single pedicle screw and contralateral facet screw were used for fixation, and single common fusion cage, double common fusion cage or banana type fusion cage were used for interbody grafting to treat single segment lumbar disease. Although the application of different fusion cage could not increase the axial strength of fixed segment, the speed of fusion was accelerated by increasing the contact area, and the quality of the fusion cage reduces the settlement of the cage and the loss of the height of the intervertebral space. Therefore, two interbody fusion cages implanted in one side are of positive clinical significance for the fixation of unilateral pedicle screw combined with contralateral facet screw, without prolonging the operation time and increasing the complications.


Assuntos
Degeneração do Disco Intervertebral , Fusão Vertebral , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Degeneração do Disco Intervertebral/cirurgia , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
6.
Cochrane Database Syst Rev ; 3: CD009621, 2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-32157697

RESUMO

BACKGROUND: Postoperative pancreatic fistula is one of the most frequent and potentially life-threatening complications following pancreatic resections. Fibrin sealants have been used in some centers to reduce postoperative pancreatic fistula. However, the use of fibrin sealants during pancreatic surgery is controversial. This is an update of a Cochrane Review last published in 2018. OBJECTIVES: To assess the safety, effectiveness, and potential adverse effects of fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery. SEARCH METHODS: We searched trial registers and the following biomedical databases: the Cochrane Library (2019, Issue 2), MEDLINE (1946 to 13 March2019), Embase (1980 to 11 March 2019), Science Citation Index Expanded (1900 to 13 March 2019), and Chinese Biomedical Literature Database (CBM) (1978 to 13 March 2019). SELECTION CRITERIA: We included all randomised controlled trials that compared fibrin sealant (fibrin glue or fibrin sealant patch) versus control (no fibrin sealant or placebo) in people undergoing pancreatic surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes (or a Peto odds ratio (OR) for very rare outcomes), and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs). MAIN RESULTS: We included 12 studies involving 1604 participants in the review. Application of fibrin sealants to pancreatic stump closure reinforcement after distal pancreatectomy We included seven studies involving 860 participants: 428 were randomised to the fibrin sealant group and 432 to the control group after distal pancreatectomy. Fibrin sealants may lead to little or no difference in postoperative pancreatic fistula (fibrin sealant 19.3%; control 20.1%; RR 0.96, 95% CI 0.68 to 1.35; 755 participants; four studies; low-quality evidence). Fibrin sealants may also lead to little or no difference in postoperative mortality (0.3% versus 0.5%; Peto OR 0.52, 95% CI 0.05 to 5.03; 804 participants; six studies; low-quality evidence), or overall postoperative morbidity (28.5% versus 23.2%; RR 1.23, 95% CI 0.97 to 1.58; 646 participants; three studies; low-quality evidence). We are uncertain whether fibrin sealants reduce reoperation rate (2.0% versus 3.8%; RR 0.51, 95% CI 0.15 to 1.71; 376 participants; two studies; very low-quality evidence) or length of hospital stay (MD 0.99 days, 95% CI -1.83 to 3.82; 371 participants; two studies; very low-quality evidence). The studies did not report serious adverse events, quality of life, or cost effectiveness. Application of fibrin sealants to pancreatic anastomosis reinforcement after pancreaticoduodenectomy We included four studies involving 393 participants: 186 were randomised to the fibrin sealant group and 207 to the control group after pancreaticoduodenectomy. We are uncertain whether fibrin sealants reduce postoperative pancreatic fistula (16.7% versus 11.7%; RR 1.14, 95% CI 0.28 to 4.69; 199 participants; two studies; very low-quality evidence). We are uncertain whether fibrin sealants reduce postoperative mortality (0.5% versus 2.4%; Peto OR 0.26, 95% CI 0.05 to 1.32; 393 participants; four studies; low-quality evidence) or length of hospital stay (MD 0.01 days, 95% CI -3.91 to 3.94; 323 participants; three studies; very low-quality evidence). There is probably little or no difference in overall postoperative morbidity (52.6% versus 50.3%; RR 1.04, 95% CI 0.87 to 1.24; 323 participants; three studies; moderate-quality evidence) between the groups. We are uncertain whether fibrin sealants reduce reoperation rate (5.2% versus 7.7%; RR 0.74, 95% CI 0.33 to 1.66; 323 participants; three studies, very low-quality evidence). The studies did not report serious adverse events, quality of life, or cost effectiveness. Application of fibrin sealants to pancreatic duct occlusion after pancreaticoduodenectomy We included two studies involving 351 participants: 188 were randomised to the fibrin sealant group and 163 to the control group after pancreaticoduodenectomy. Fibrin sealants may lead to little or no difference in postoperative mortality (8.4% versus 6.1%; Peto OR 1.41, 95% CI 0.63 to 3.13; 351 participants; two studies; low-quality evidence) or length of hospital stay (median 16 to 17 days versus 17 days; 351 participants; two studies; low-quality evidence). We are uncertain whether fibrin sealants reduce overall postoperative morbidity (32.0% versus 27.6%; RR 1.16, 95% CI 0.67 to 2.02; 351 participants; two studies; very low-quality evidence), or reoperation rate (13.6% versus 16.0%; RR 0.85, 95% CI 0.52 to 1.41; 351 participants; two studies; very low-quality evidence). Serious adverse events were reported in one study (169 participants; low-quality evidence): more participants developed diabetes mellitus when fibrin sealants were applied to pancreatic duct occlusion, both at three months' follow-up (33.7% fibrin sealant group versus 10.8% control group; 29 participants versus 9 participants) and 12 months' follow-up (33.7% fibrin sealant group versus 14.5% control group; 29 participants versus 12 participants). The studies did not report postoperative pancreatic fistula, quality of life, or cost effectiveness. AUTHORS' CONCLUSIONS: Based on the current available evidence, fibrin sealants may have little or no effect on postoperative pancreatic fistula in people undergoing distal pancreatectomy. The effects of fibrin sealants on the prevention of postoperative pancreatic fistula are uncertain in people undergoing pancreaticoduodenectomy.


Assuntos
Adesivo Tecidual de Fibrina/uso terapêutico , Pâncreas/cirurgia , Fístula Pancreática/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Adesivos Teciduais/uso terapêutico , Adesivo Tecidual de Fibrina/efeitos adversos , Humanos , Tempo de Internação , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Fístula Pancreática/mortalidade , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Reoperação/estatística & dados numéricos
7.
J Invest Surg ; 33(9): 876-883, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30821527

RESUMO

Background: Hepatic ischemia reperfusion injury often leads to increased complications and mortality after surgery. Although ischemic preconditioning is used as a convenient and effective method to protect the liver from warm ischemia reperfusion injury, the optimal protocol is currently unclear. Therefore, in this study, we sought to identify ideal conditions and methods for ischemic preconditioning. Materials and methods: We compared several preconditioning protocols of the ischemia/reperfusion (I/R) cycle in 30 male Sprague-Dawley rats (5 groups, n = 6), including relevant sham and I/R injury (no preconditioning) controls. Experimental group conditions included: (1) ischemia for 5 min/reperfusion for 10 min (ischemic preconditioning 1, IPC-1); (2) ischemia for 5 min/reperfusion for 5 min, repeated three times (IPC-2); and (3) ischemia for 10 min/reperfusion for 10 min (IPC-3). Readouts included transaminase activity levels measured from collected sera, and histopathological changes, liver cell apoptosis, superoxide dismutase (SOD) activity, glutathione (GSH) levels, and malondialdehyde (MDA) levels measured from collected liver tissue segments subjected to warm ischemia (that is from the 70% of the liver mass that had been deprived from blood flow during the ischemia phase). Results: Compared to the I/R control group, the IPC-1, IPC-2, and IPC-3 groups all showed significant decreases in liver transaminase activity levels, alleviation of pathological injury-associated changes, and a decrease in liver cell apoptosis. Moreover, SOD activity and GSH content were increased while MDA content was decreased in the three experimental groups. Compared to the IPC-1 and IPC-3 groups, the changes in the IPC-2 group were the most significant (P < 0.05). Conclusions: Ischemic preconditioning can reduce hepatic warm ischemia reperfusion injury in rats. The IPC-2 protocol, involving ischemia for 5 min and reperfusion for 5 min, repeated three times, provided the optimal protection against hepatic ischemia reperfusion injury among the protocols studied.

8.
Cochrane Database Syst Rev ; 10: CD012959, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31618443

RESUMO

BACKGROUND: Severe acute pancreatitis is associated with high rates of mortality and life-threatening complications. Continuous veno-venous hemofiltration (CVVH) has been used in some centers to reduce mortality and avoid local or systemic complications, however its efficiency and safety is uncertain. OBJECTIVES: To assess the benefits and harms of CVVH in patients suffering from severe acute pancreatitis; to compare the effects of different CVVH techniques; and to evaluate the optimal time for delivery of CVVH. SEARCH METHODS: We searched the Cochrane Library (2019, Issue 8), MEDLINE (1946 to 13 September 2019), Embase (1974 to 13 September 2019), and Science Citation Index Expanded (1982 to 13 September 2019). SELECTION CRITERIA: We included all randomized controlled trials (RCTs) that compared CVVH versus no CVVH in participants with severe acute pancreatitis. We also included RCTs that compared different types of CVVH and different schedules for CVVH in participants with severe acute pancreatitis. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes, and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs). MAIN RESULTS: We included two studies, involving a total of 94 participants, in the review.Continuous veno-venous hemofiltration versus no interventionWe included one study in which 64 participants with severe acute pancreatitis were randomized to undergo CVVH (32 participants) or no intervention (32 participants). There were no deaths in either group (very low-quality evidence). Adverse events, length of stay in the intensive care unit (ICU), length of hospital stay, total hospital cost, and quality of life were not reported in the study.One type of continuous veno-venous hemofiltration versus a different type of continuous veno-venous hemofiltrationWe included one study in which 30 participants with severe acute pancreatitis were randomized to undergo high-volume CVVH (15 participants) or standard CVVH (15 participants). High-volume CVVH may lead to little or no difference in in-hospital mortality rates (20.0% in the high-volume CVVH group versus 33.3% in the standard CVVH group; risk ratio (RR) 0.60, 95% confidence interval (CI) 0.17 to 2.07; 30 participants; 1 study; low-quality evidence). We are uncertain whether high-volume hemofiltration reduces rates of adverse events (13.3% in both groups; RR 1.00, 95% CI 0.16 to 6.20; 30 participants; 1 study; very low-quality evidence). Length of ICU stay, length of hospital stay, total hospital cost, and quality of life were not reported in the study. AUTHORS' CONCLUSIONS: The quality of the current evidence is very low or low. For both comparisons addressed in this review, data are sparse. It is unclear whether CVVH has any effect on mortality or complications in patients with severe acute pancreatitis. It is also unclear whether high-volume CVVH is superior, equivalent or inferior to standard CVVH in patients with severe acute pancreatitis.

9.
Med Sci Monit ; 25: 4877-4884, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31258152

RESUMO

BACKGROUND CD8+ cytotoxic T lymphocytes (CTLs) have been proved to exert crucial roles in immunological rejection. Exosomes (EXOs) secreted by CD4+CD25+ regulatory T (Treg) cells is believed to be deeply involved in immune regulation. Nevertheless, whether immunomodulatory effect of CD4+CD25+ Treg cells on CD8+ CTL depends on EXOs remains unknown and needs to be explored. MATERIAL AND METHODS We purified CD4+CD25+ Treg cells followed by in vitro amplification. EXOs in culture supernatants of Treg cells was separated and identified. The effect of CD4+CD25+ Treg cells and CD4+CD25+ Treg cells-derived EXOs on CD8+ CTL viability, proliferation, cell cycle mRNA, intracellular cytokines, and protein expression were investigated. RESULTS We successfully obtained EXOs from CD4+CD25+ Treg cells. The inhibition effect of EXOs on CD8+ CTL was concentration-dependent. In addition, the inhibition effect of CD4+CD25+ Treg cells could be reversed by GW4869, an EXOs inhibitor. The inhibition effect was associated with the regulation of IFN-γ and perforin. Our in vivo experiments proved that natural CD4+CD25+ Treg cells-released EXOs can prolong liver allograft survival. CONCLUSIONS CD4+CD25+ Treg cells-derived EXOs could become an alternative tool for manipulating the immune system to discover novel underlying immunomodulatory mechanisms.


Assuntos
Exossomos/metabolismo , Linfócitos T Citotóxicos/metabolismo , Linfócitos T Reguladores/metabolismo , Aloenxertos/imunologia , Animais , Antígenos CD4/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Proliferação de Células/fisiologia , Exossomos/imunologia , Fígado/metabolismo , Transplante de Fígado/métodos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Linfócitos T Reguladores/imunologia , Tolerância ao Transplante/imunologia
10.
Liver Transpl ; 25(8): 1220-1232, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31125492

RESUMO

In liver transplant cases, severe hepatic ischemia/reperfusion injury (HIRI) is a strong predictor of adverse liver graft and overall outcomes. During HIRI, high-mobility group box 1 (HMGB1) promotes hepatocellular death and proinflammatory cytokine secretion by toll-like receptor 4 (TLR4). Because salicylates inhibit HMGB1/TLR4 interaction, we hypothesized that salicylates may ameliorate HIRI-induced liver damage by inhibiting HMGB1/TLR4 axis activation. Using a murine model of HIRI, we found that the salicylate acetyl-3-aminoethyl salicylic acid (ac3AESA) reduced serum alanine aminotransferase and aspartate aminotransferase as well as Suzuki scores and apoptotic cell counts after HIRI. Ac3AESA also down-regulated hepatocellular HMGB1 and TLR4 expression, phosphorylated inhibitor of κBα, extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, cleaved caspase 3, and cleaved caspase 1 levels after HIRI. Ac3AESA reduced liver Kupffer cell transcription of proinflammatory mediators tumor necrosis factor α (TNF-α), interleukin (IL) 6, IL1ß, chemokine (C-X-C motif) ligand (CXCL) 1, CXCL2, and CXCL8 after HIRI. Ac3AESA also dose-dependently reduced in vitro release of Kupffer cell TNF-α. Employing a murine orthotopic liver transplantation model, we found daily ac3AESA administration up to day 10 after transplant improved liver graft survival, suppressed allograft damage, and down-regulated HMGB1/TLR4 signaling. These benefits to survival and allograft health were maintained for cold ischemia times of 12 and 18 hours. Notably, TLR4 knockout eliminated all foregoing ac3AESA-induced effects. In conclusion, ac3AESA partially rescues the negative effects of HIRI and prolongs liver graft survival in a TLR4-dependent manner.


Assuntos
Ácidos Aminossalicílicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Transplante de Fígado/efeitos adversos , Disfunção Primária do Enxerto/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Aloenxertos/irrigação sanguínea , Aloenxertos/imunologia , Ácidos Aminossalicílicos/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Sobrevivência de Enxerto , Proteína HMGB1/imunologia , Proteína HMGB1/metabolismo , Humanos , Fígado/irrigação sanguínea , Fígado/imunologia , Masculino , Camundongos , Camundongos Knockout , Disfunção Primária do Enxerto/etiologia , Transdução de Sinais/imunologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismo , Isquemia Quente/efeitos adversos
11.
J Pharm Pharmacol ; 71(6): 937-944, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30663067

RESUMO

OBJECTIVES: The current study aimed to explore whether minimally modified low-density lipoprotein (mmLDL) via tail vein injection upregulates the ETB and α1 receptors in mouse mesenteric arteries by activating the PI3K/Akt pathway. METHODS: The contraction curves of the mesenteric arteries caused by sarafotoxin 6c (S6c, ETB receptor agonist) and phenylephrine (PE, α1 receptor agonist) were measured by a myograph system. Serum oxLDL was detected using enzyme-linked immunosorbent assays. The levels of the ETB receptor, the α1 receptor, PI3K, p-PI3K and p-Akt were detected using real-time polymerase chain reaction and Western blot analyses. KEY FINDINGS: Minimally modified low-density lipoprotein noticeably enhanced the contraction effect curves of S6c and PE, with significantly increased Emax values (P < 0.01), compared to those of the control group. This treatment significantly increased the mRNA expression and protein levels of the ETB and α1 receptors and the protein levels of p-PI3K and p-Akt in the vessel wall (P < 0.01). LY294002 inhibited the effect of mmLDL. CONCLUSIONS: An increase in mmLDL activated the PI3K/Akt pathway, which upregulated the expression of the ETB and α1 receptors and enhanced the ETB and α1- receptor-mediated contractile function.


Assuntos
Lipoproteínas LDL/sangue , Artérias Mesentéricas/metabolismo , Receptor de Endotelina B/genética , Receptores Adrenérgicos alfa 1/genética , Agonistas de Receptores Adrenérgicos alfa 1/farmacologia , Animais , Western Blotting , Ensaio de Imunoadsorção Enzimática , Feminino , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Fenilefrina/farmacologia , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptor de Endotelina B/agonistas , Receptores Adrenérgicos alfa 1/efeitos dos fármacos , Regulação para Cima , Vasoconstritores/farmacologia , Venenos de Víboras/farmacologia
12.
Braz J Med Biol Res ; 51(10): e7439, 2018 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-30156611

RESUMO

Nuclear factor erythroid-related factor 2 (Nrf2) has been implicated in several detoxifying and antioxidant defense processes. Nrf2-mediated heme oxygenase-1 (HO-1) expression was demonstrated to play a key role against oxidative stress. Gastrodin (GSTD) is a well-known active compound isolated from the roots of Rhizoma gastrodiae, a plant used in ancient Chinese traditional medicine. The aim of this work was to investigate whether GSTD could alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells (LSECs). In LSECs exposed to 1 mM H2O2, treatment with GSTD (1, 10, or 50 µM) resulted in higher cell viability than the untreated control. Treated cells maintained a higher Bcl2/Bax ratio and suppressed caspase-9 expression compared with untreated cells, reducing cell apoptosis. GSTD was protective for H2O2-induced oxidative injury by reducing the generation of intracellular reactive oxygen species and malondialdehyde. HO-1 and Nrf2 expressions were synergistically upregulated by GSTD. Inhibition of HO-1 by 10 µM zinc protoporphyrin resulted in less protective effects on cell viability and malondialdehyde reduction by GSTD treatment in H2O2-exposed LSECs. Additionally, phosphorylated p38 in LSECs exposed to H2O2 was elevated by GSTD. Inhibition of p38 phosphorylation by SB203580 did not induce Nrf2 and HO-1 expression after 1 or 10 µM GSTD treatment and the protective effect on cell viability and malondialdehyde reduction in H2O2-exposed LSECs was reduced. The data conclusively demonstrated that GSTD-induced HO-1 and Nrf2 expression is involved in protection of LSECs from H2O2-induced oxidative injury, which may be regulated by p38 phosphorylation.


Assuntos
Álcoois Benzílicos/farmacologia , Células Endoteliais/efeitos dos fármacos , Glucosídeos/farmacologia , Heme Oxigenase-1/metabolismo , Peróxido de Hidrogênio/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fígado/citologia , Fígado/efeitos dos fármacos , Malondialdeído/metabolismo , Camundongos , Modelos Teóricos , Estresse Oxidativo/fisiologia , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/sangue
13.
Cochrane Database Syst Rev ; 6: CD009621, 2018 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-29934987

RESUMO

BACKGROUND: Postoperative pancreatic fistula is one of the most frequent and potentially life-threatening complications following pancreatic resections. Fibrin sealants are introduced to reduce postoperative pancreatic fistula by some surgeons. However, the use of fibrin sealants during pancreatic surgery is controversial. This is an update of a Cochrane Review last published in 2016. OBJECTIVES: To assess the safety, effectiveness, and potential adverse effects of fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery. SEARCH METHODS: We searched trial registers and the following biomedical databases: the Cochrane Library (2018, Issue 4), MEDLINE (1946 to 12 April 2018), Embase (1980 to 12 April 2018), Science Citation Index Expanded (1900 to 12 April 2018), and Chinese Biomedical Literature Database (CBM) (1978 to 12 April 2018). SELECTION CRITERIA: We included all randomized controlled trials that compared fibrin sealant (fibrin glue or fibrin sealant patch) versus control (no fibrin sealant or placebo) in people undergoing pancreatic surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes (or a Peto odds ratio (OR) for very rare outcomes), and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs). MAIN RESULTS: We included 11 studies involving 1462 participants in the review.Application of fibrin sealants to pancreatic stump closure reinforcement after distal pancreatectomyWe included seven studies involving 860 participants: 428 were randomized to the fibrin sealant group and 432 to the control group after distal pancreatectomy. Fibrin sealants may lead to little or no difference in postoperative pancreatic fistula (fibrin sealant 19.3%; control 20.1%; RR 0.96, 95% CI 0.68 to 1.35; 755 participants; four studies; low-quality evidence). Fibrin sealants may also lead to little or no difference in postoperative mortality (0.3% versus 0.5%; Peto OR 0.52, 95% CI 0.05 to 5.03; 804 participants; six studies; low-quality evidence), or overall postoperative morbidity (28.5% versus 23.2%; RR 1.23, 95% CI 0.97 to 1.58; 646 participants; three studies; low-quality evidence). We are uncertain whether fibrin sealants reduce reoperation rate (2.0% versus 3.8%; RR 0.51, 95% CI 0.15 to 1.71; 376 participants; two studies; very low-quality evidence). There is probably little or no difference in length of hospital stay between the groups (12.1 days versus 11.4 days; MD 0.32 days, 95% CI -1.06 to 1.70; 755 participants; four studies; moderate-quality evidence). The studies did not report serious adverse events, quality of life, or cost effectiveness.Application of fibrin sealants to pancreatic anastomosis reinforcement after pancreaticoduodenectomyWe included three studies involving 251 participants: 115 were randomized to the fibrin sealant group and 136 to the control group after pancreaticoduodenectomy. We are uncertain whether fibrin sealants reduce postoperative pancreatic fistula (1.6% versus 6.2%; RR 0.25, 95% CI 0.01 to 5.06; 57 participants; one study; very low-quality evidence). Fibrin sealants may lead to little or no difference in postoperative mortality (0.1% versus 0.7%; Peto OR 0.15, 95% CI 0.00 to 7.76; 251 participants; three studies; low-quality evidence) or length of hospital stay (12.8 days versus 14.8 days; MD -1.58 days, 95% CI -3.96 to 0.81; 181 participants; two studies; low-quality evidence). We are uncertain whether fibrin sealants reduce overall postoperative morbidity (33.7% versus 34.7%; RR 0.97, 95% CI 0.65 to 1.45; 181 participants; two studies; very low-quality evidence), or reoperation rate (7.6% versus 9.2%; RR 0.83, 95% CI 0.33 to 2.11; 181 participants; two studies, very low-quality evidence). The studies did not report serious adverse events, quality of life, or cost effectiveness.Application of fibrin sealants to pancreatic duct occlusion after pancreaticoduodenectomyWe included two studies involving 351 participants: 188 were randomized to the fibrin sealant group and 163 to the control group after pancreaticoduodenectomy. Fibrin sealants may lead to little or no difference in postoperative mortality (8.4% versus 6.1%; Peto OR 1.41, 95% CI 0.63 to 3.13; 351 participants; two studies; low-quality evidence) or length of hospital stay (17.0 days versus 16.5 days; MD 0.58 days, 95% CI -5.74 to 6.89; 351 participants; two studies; low-quality evidence). We are uncertain whether fibrin sealants reduce overall postoperative morbidity (32.0% versus 27.6%; RR 1.16, 95% CI 0.67 to 2.02; 351 participants; two studies; very low-quality evidence), or reoperation rate (13.6% versus 16.0%; RR 0.85, 95% CI 0.52 to 1.41; 351 participants; two studies; very low-quality evidence). Serious adverse events were reported in one study: more participants developed diabetes mellitus when fibrin sealants were applied to pancreatic duct occlusion, both at three months' follow-up (33.7% fibrin sealant group versus 10.8% control group; 29 participants versus 9 participants) and 12 months' follow-up (33.7% fibrin sealant group versus 14.5% control group; 29 participants versus 12 participants). The studies did not report postoperative pancreatic fistula, quality of life, or cost effectiveness. AUTHORS' CONCLUSIONS: Based on the current available evidence, fibrin sealants may have little or no effect on postoperative pancreatic fistula in people undergoing distal pancreatectomy. The effects of fibrin sealants on the prevention of postoperative pancreatic fistula are uncertain in people undergoing pancreaticoduodenectomy.


Assuntos
Adesivo Tecidual de Fibrina/uso terapêutico , Pâncreas/cirurgia , Fístula Pancreática/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Adesivos Teciduais/uso terapêutico , Adesivo Tecidual de Fibrina/efeitos adversos , Humanos , Tempo de Internação , Pancreatectomia/métodos , Complicações Pós-Operatórias/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Reoperação/estatística & dados numéricos
14.
Orthop Surg ; 10(2): 98-106, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29878716

RESUMO

OBJECTIVE: To analyze the early complications and causes of oblique lateral interbody fusion, and put forward preventive measures. METHODS: There were 235 patients (79 males and 156 females) analyzed in our study from October 2014 to May 2017. The average age was 61.9 ± 0.21 years (from 32 to 83 years). Ninety-one cases were treated with oblique lateral interbody fusion (OLIF) alone (OLIF alone group) and 144 with OLIF combined with posterior pedicle screw fixation through the intermuscular space approach (OLIF combined group). In addition, 137/144 cases in the combined group were primarily treated by posterior pedicle screw fixation, while the treatments were postponed in 7 cases. There were 190 cases of single fusion segments, 11 of 2 segments, 21 of 3 segments, and 13 of 4 segments. Intraoperative and postoperative complications were observed. RESULTS: Average follow-up time was 15.6 ± 7.5 months (ranged from 6 to 36 months). Five cases were lost to follow-up (2 cases from the OLIF alone group and 3 cases from the OLIF combined group). There were 7 cases of vascular injury, 22 cases of endplate damage, 2 cases of vertebral body fracture, 11 cases of nerve injury, 18 cases of cage sedimentation or cage transverse shifting, 3 cases of iliac crest pain, 1 case of right psoas major hematoma, 2 cases of incomplete ileus, 1 case of acute heart failure, 1 case of cerebral infarction, 3 case of left lower abdominal pain, 9 cases of transient psoas weakness, 3 cases of transient quadriceps weakness, and 8 cases of reoperation. The complication incidence was 32.34%. Thirty-three cases occurred in the OLIF alone group, with a rate of 36.26%, and 43 cases in the group of OLIF combined posterior pedicle screw fixation, with a rate of 29.86%. Fifty-seven cases occurred in single-segment fusion, with a rate of 30.0% (57/190), 4 cases occurred in two-segment fusion, with a rate of 36.36% (4/11), 9 cases occurred in three-segment fusion, with a rate of 42.86% (9/21), and 6 cases occurred in four-segment fusion, with a rate of 46.15% (6/13). CONCLUSION: In summary, OLIF is a relatively safe and very effective technique for minimally invasive lumbar fusion. Nonetheless, it should be noted that OLIF carries the risk of complications, especially in the early stage of development.


Assuntos
Vértebras Lombares/cirurgia , Fusão Vertebral/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/prevenção & controle , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesões , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Debilidade Muscular/prevenção & controle , Parafusos Pediculares , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Radiografia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/prevenção & controle , Fusão Vertebral/instrumentação , Fusão Vertebral/métodos , Tomografia Computadorizada por Raios X , Traumatismos do Sistema Nervoso/etiologia , Traumatismos do Sistema Nervoso/prevenção & controle , Lesões do Sistema Vascular/etiologia
15.
Clin Ther ; 40(3): 440-449, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29519716

RESUMO

PURPOSE: We designed a prospective, multicenter, randomized, controlled study to assess a 5-month regimen compared with the standard regimen on previously treated patients with pulmonary tuberculosis (TB). METHODS: We enrolled 917 sputum smear-positive patients undergoing additional treatment in 27 major tuberculosis hospitals in China. Patients were randomly assigned to a test group (n = 626)treated with a 5-month regimen of moxifloxacin, pasiniazid, rifabutin, ethambutol, and pyrazinamide or a reference group (n = 291) treated with an 8-month regimen of isoniazid, rifampicin, and streptomycin. All patients with a favorable response were followed up for 5 years after the end of treatment. FINDINGS: Of the study patients, 61 in the test group and 19 in the reference group had multidrug-resistant (MDR) TB. The treatment success rate in the study group was 74.12%, which was significantly higher than the 67.70% in the reference group (P = 0.04), whereas the treatment success rate of patients with MDR-TB was not significantly different between the test and reference groups (70.5% vs 63.1%, P =0.79). The adverse effects rates in the test and reference groups were 7.4% and 3.1%, respectively (P = .01). The difference in the TB recurrence rates between the group arm (9.6%) and the reference group (21.8%) was statistically significant (P < 0.001). IMPLICATIONS: The moxifloxacin, pasiniazid, rifabutin, ethambutol, and pyrazinamide test regimen yielded higher success and lower recurrence rates than the currently recommended isoniazid, rifampicin, and streptomycin regimen, but the rate of adverse effects was higher. ClinicalTrials.gov identifier: NCT02331823.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Antituberculosos/administração & dosagem , China , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Resultado do Tratamento , Adulto Jovem
16.
Phys Rev E ; 97(2-1): 023302, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29548227

RESUMO

In this study, an alternative second-order boundary scheme is proposed under the framework of the convection-diffusion lattice Boltzmann (LB) method for both straight and curved geometries. With the proposed scheme, boundary implementations are developed for the Dirichlet, Neumann and linear Robin conditions in a consistent way. The Chapman-Enskog analysis and the Hermite polynomial expansion technique are first applied to derive the explicit expression for the general distribution function with second-order accuracy. Then, the macroscopic variables involved in the expression for the distribution function is determined by the prescribed macroscopic constraints and the known distribution functions after streaming [see the paragraph after Eq. (29) for the discussions of the "streaming step" in LB method]. After that, the unknown distribution functions are obtained from the derived macroscopic information at the boundary nodes. For straight boundaries, boundary nodes are directly placed at the physical boundary surface, and the present scheme is applied directly. When extending the present scheme to curved geometries, a local curvilinear coordinate system and first-order Taylor expansion are introduced to relate the macroscopic variables at the boundary nodes to the physical constraints at the curved boundary surface. In essence, the unknown distribution functions at the boundary node are derived from the known distribution functions at the same node in accordance with the macroscopic boundary conditions at the surface. Therefore, the advantages of the present boundary implementations are (i) the locality, i.e., no information from neighboring fluid nodes is required; (ii) the consistency, i.e., the physical boundary constraints are directly applied when determining the macroscopic variables at the boundary nodes, thus the three kinds of conditions are realized in a consistent way. It should be noted that the present focus is on two-dimensional cases, and theoretical derivations as well as the numerical validations are performed in the framework of the two-dimensional five-velocity lattice model.

17.
Clin Res Hepatol Gastroenterol ; 42(3): 245-254, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29174380

RESUMO

OBJECTIVE: To investigate the effect of heme oxygenase-1 (HO-1) on the ischemic reperfusion injury (IRI) of bile duct in rat models after liver transplantation. METHODS: 320 SD rats were equally and randomly divided into 5 groups, which were group A receiving injection of 3×108/pfu/ml adenovirus (adv), group B with donor receiving Adv-HO-1 and recipient receiving Adv-HO-1-siRNA, group C with donor and recipient both receiving Adv-HO-1, group D with donor receiving Adv-HO-1-siRNA and recipient receiving Adv-HO-1, and group E with donor and recipient both receiving Adv-HO-1-siRNA at 24h before liver transplantation. Donor liver was stored in UW liquid at 4°C followed by measuring HO-1 level by western blot before transplantation. On d1, d3, d7 and d14, serum and liver was isolated for analysis of liver function, inflammatory cell infiltration by H&E staining, ultrastructure of liver by transmission electron microscopy as well as the expression of HO-1, Bsep, Mrp2 and Ntcp by western blot. RESULTS: Compared with group D and E, group B and C displayed improved liver function as demonstrated by lower level of ALT, AST, LDH, TBIL, ALP and GGT, increased secretion of TBA and PL as well as expression of transporter proteins (Bsep, Mrp2 and Ntcp), reduced inflammatory cells infiltration and liver injury. CONCLUSION: Our study demonstrated that overexpression of HO-1 in donor liver can ameliorate the damage to bile duct and liver, and improved liver function, suggesting HO-1 might be a new therapeutic target in the treatment of IRI after liver transplantation.


Assuntos
Ductos Biliares/irrigação sanguínea , Heme Oxigenase-1/fisiologia , Transplante de Fígado , Complicações Pós-Operatórias/etiologia , Traumatismo por Reperfusão/etiologia , Animais , Masculino , Complicações Pós-Operatórias/enzimologia , Distribuição Aleatória , Ratos , Traumatismo por Reperfusão/enzimologia
18.
Transplantation ; 102(3): 426-432, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29189483

RESUMO

BACKGROUND: Heme oxygenase 1 (HO-1), a heat shock protein, can be involved in the resolution of inflammation by modulating cytokine expression and apoptotic cell death. Based on recent evidence that liver sinusoidal endothelial cells (LSECs) is the critical target in early period of liver ischemia-reperfusion injury (IRI), this study aims to clarify whether overexpression of HO-1 gene provides a protective effect on mice LSECs. METHODS: LSECs were transfected with adenovirus vectors encoding mice HO-1 gene (Ad-HO-1) or green fluorescent protein. Controls were not infected with any vector. LSECs were then treated with hypoxic or normoxic culture. We used low serum culture medium and hypoxia-reoxygenation (H-R) conditions to cause IRI in vitro. The transfection efficiency of HO-1 gene in LSECs, after 48 hours of transfection, and the effect of HO-1 on the model of H-R injury in LSECs were observed. RESULTS: Transfection of LSECs with Ad-HO-1 was at an optimal dose (multiplicity of infection = 80) to markedly express HO-1 mRNA and protein. Groups of overexpressed HO-1 showed lower levels of inflammatory factor mediators IL-6 and TNF-α. Survival rate of the cells after H-R injury was higher and attributed to overexpressed HO-1. In contrast, the control adenovirus expressing the enhanced green fluorescent protein failed to induce HO-1 expression and stimulated cell apoptosis. HO-1 expression was downregulated in all H-R groups compared with normoxia groups, which may be related to the disruption of the LSEC structure. CONCLUSIONS: Upregulation of HO-1 can attenuate H-R injury in LSECs by inhibiting proinflammatory cytokine release and diminishing apoptotic cell death.


Assuntos
Células Endoteliais/patologia , Heme Oxigenase-1/fisiologia , Fígado/irrigação sanguínea , Proteínas de Membrana/fisiologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose , Hipóxia Celular , Citocinas/análise , Heme Oxigenase-1/genética , Fígado/patologia , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL
19.
Braz. j. med. biol. res ; 51(10): e7439, 2018. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-951707

RESUMO

Nuclear factor erythroid-related factor 2 (Nrf2) has been implicated in several detoxifying and antioxidant defense processes. Nrf2-mediated heme oxygenase-1 (HO-1) expression was demonstrated to play a key role against oxidative stress. Gastrodin (GSTD) is a well-known active compound isolated from the roots of Rhizoma gastrodiae, a plant used in ancient Chinese traditional medicine. The aim of this work was to investigate whether GSTD could alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells (LSECs). In LSECs exposed to 1 mM H2O2, treatment with GSTD (1, 10, or 50 µM) resulted in higher cell viability than the untreated control. Treated cells maintained a higher Bcl2/Bax ratio and suppressed caspase-9 expression compared with untreated cells, reducing cell apoptosis. GSTD was protective for H2O2-induced oxidative injury by reducing the generation of intracellular reactive oxygen species and malondialdehyde. HO-1 and Nrf2 expressions were synergistically upregulated by GSTD. Inhibition of HO-1 by 10 µM zinc protoporphyrin resulted in less protective effects on cell viability and malondialdehyde reduction by GSTD treatment in H2O2-exposed LSECs. Additionally, phosphorylated p38 in LSECs exposed to H2O2 was elevated by GSTD. Inhibition of p38 phosphorylation by SB203580 did not induce Nrf2 and HO-1 expression after 1 or 10 µM GSTD treatment and the protective effect on cell viability and malondialdehyde reduction in H2O2-exposed LSECs was reduced. The data conclusively demonstrated that GSTD-induced HO-1 and Nrf2 expression is involved in protection of LSECs from H2O2-induced oxidative injury, which may be regulated by p38 phosphorylation.

20.
Phys Rev E ; 95(4-1): 043312, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28505746

RESUMO

In this study, alternative symmetry boundary implementations for the axisymmetric lattice Boltzmann (LB) method are proposed based on the nonequilibrium extrapolation and the direct extrapolation schemes. The proposed boundary schemes are directly implemented on the symmetry axis, and the postcollision distribution function and the macroscopic variables at the boundary nodes are extrapolated from the inner fluid nodes; thereby, the singularities arising at the symmetry axis (r=0) during the collision and the macroscopic variable calculations are completely avoided. The accuracy of the present schemes is consistent with the well-established axisymmetric LB model. Moreover, in comparison with previous symmetry boundary schemes, the present implementations are slightly more accurate than the symmetry scheme by Guo et al. [Phys. Rev. E 79, 046708 (2009)10.1103/PhysRevE.79.046708] and numerically more stable than the specular reflection-based schemes.

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