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1.
Cryobiology ; : 104979, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39395582

RESUMO

Cryopreservation causes higher reactive oxygen species (ROS) concentrations, leading to oxidative stress and lipid peroxidation damage sperm, and using antioxidants can improve semen quality after freeze-thaw. Natural astaxanthin (ASTA) can be inserted into cell membranes and its antioxidant properties are stronger than other antioxidants. We aimed to investigate the effects of ASTA supplementation in the Beltsville Poultry Semen Extender (BPSE) on post-thaw rooster semen quality and to explore the potential mechanism of rooster semen quality change. The qualifying semen ejaculates collected from 30 adult male Jinghong No.1 laying hen breeder roosters (65wk old) were pooled, divided into four aliquots, and diluted with BPSE having different levels of ASTA (0, 0.5, 1, or 2µg/mL). Treated semen was cryopreserved and kept in liquid nitrogen. The entire experiment was replicated three times independently. Sperm viability, motility, curvilinear velocity, amplitude of lateral head displacement, straightness, plasma membrane integrity, and acrosome integrity were observed highest (P < 0.05) with 1µg/mL ASTA at freeze-thawing. Higher (P < 0.05) antioxidant enzyme (CAT-like, SOD) activities and free radical (·OH, O2.-) scavenging ability, less ROS and malondialdehyde (MDA) concentrations were recorded with the addition of appropriate concentrations of ASTA compared to control. In addition, the levels of mitochondrial membrane potential (MMP), adenosine triphosphate (ATP), and lactate dehydrogenase (LDH) in the 1µg/mL ASTA group improved compared to the control group, and decreased the amount of AIF protein level but increased the Bcl-2 protein level (P < 0:05). Collectively, these results demonstrate that adding ASTA in the BPSE promoted rooster freeze-thaw sperm quality, which may be related to reducing ROS levels, protecting the antioxidant defense system, preventing lipid peroxidation, improving mitochondrial structural and functional integrity, and inhibiting sperm apoptosis.

2.
Acta Pharmacol Sin ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39152295

RESUMO

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder characterized by cognitive impairments. Despite the limited efficacy of current treatments for AD, the 1,2,4-oxadiazole structure has garnered significant attention in medicinal chemistry due to its potential impact on mGluR1 and its association with AD therapy. In this study, a series of novel 1,2,4-oxadiazole derivatives were designed, synthesized, and evaluated for the neuroprotective effects in human neuroblastoma (SH-SY5Y) cells. Among all the derivatives tested, FO-4-15 (5f) existed the lowest cytotoxicity and the highest protective effect against H2O2. Based on these in vitro results, FO-4-15 was administered to 3×Tg mice and significantly improved the cognitive impairments of the AD mice. Pathological analysis showed that FO-4-15 significantly reduced Aß accumulation, Tau hyper-phosphorylation, and synaptic impairments in the 3×Tg mice. Dysfunction of the CaMKIIα/Fos signaling pathway in 3×Tg mice was found to be restored by FO-4-15 and the necessity of the CaMKIIα/Fos for FO-4-15 was subsequently confirmed by the use of a CaMKIIα inhibitor in vitro. Beyond that, mGluR1 was identified to be a potential target of FO-4-15, and the interaction of FO-4-15 and mGluR1 was displayed by Ca2+ flow increase, molecular docking, and interaction energy analysis. The target of FO-4-15 was further confirmed in vitro by JNJ16259685, a nonselective inhibitor of mGluR1. These findings suggest that FO-4-15 may hold promise as a potential treatment for Alzheimer's disease.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(2): 403-410, 2023 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37096512

RESUMO

OBJECTIVE: To investigate the mutational spectrum in young patients with diffuse large B-cell lymphoma (DLBCL) based on next generation sequencing (NGS), and to provide a basis for in-depth understanding of the molecular biological characteristics and accurate prognosis of young DLBCL. METHODS: From March 2009 to March 2021, 68 young DLBCL patients with complete initial diagnosis data from the Department of Hematology, The People's Hospital Xinjiang Uygur Autonomous Region were retrospectively analyzed, and their paraffin-embedded tissues were subjected to targeted sequencing analysis by NGS technology (including 475 Target genes), and the differences in gene mutation profiles and signaling pathways between high-risk patients with aaIPI ≥2 and low-intermediate risk patients with aaIPI <2 were compared. RESULTS: A total of 44 high-frequency mutation genes were detected in 68 young DLBCL patients. By comparing the high-frequency mutation genes in aaIPI high-risk group and low-intermediate risk group, it was found that CARD11 mutation in aaIPI high-risk group was significantly higher than that in low-intermediate risk group (P =0.002), while MGA mutation (P =0.037) only appeared in the aaIPI high-risk group, and SPEN mutation (P =0.004) only appeared in the aaIPI low-intermediate risk group. The high-frequency mutation genes and clinical indicators of the aaIPI high-risk group were included in the survival analysis, and the results showed that TP53 (P =0.009, P =0.027), POU2AF1 (P =0.003, P =0.006) and CCND3 (P =0.040, P =0.014) genes mutations were associated with worse PFS and OS, while B2M was associated with better PFS (P =0.014) and OS (P =0.013). Multivariate COX regression analysis showed that the TP53, POU2AF1 and CCND3 were independent risk factors for PFS(P =0.021,P =0.005,P =0.020) and OS(P =0.042,P =0.010,P =0.013). CONCLUSION: The aaIPI staging combination with molecular biology markers is more conducive to accurately judging the prognosis of young DLBCL patients. TP53, POU2AF1 and CCND3 mutations predict worse survival in the patients with the aaIPI high-risk group.


Assuntos
Linfoma Difuso de Grandes Células B , Humanos , Estudos Retrospectivos , Prognóstico , Linfoma Difuso de Grandes Células B/genética , Biomarcadores , Mutação , Sequenciamento de Nucleotídeos em Larga Escala
4.
Toxicol In Vitro ; 86: 105508, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36375677

RESUMO

PURPOSE: To determine whether di-n-butyl phthalate (DBP) promotes the occurrence of bladder cancer (BCa) and explore the action of DBP acts on BCa cells at the cellular and molecular levels. METHODS: MTT and Transwell assays were used to investigate the tumorigenic actions of DBP on BCa cells. Second-generation sequencing was used to identify differences in gene expression before and after DBP treatment. Differential gene expression was verified by q-PCR and analyzed using bioinformatics. Cells were transfected to overexpress genes of interest and proliferation and migration were measured using MTT and Transwell assays, respectively. RESULTS: DBP treatment stimulated both proliferation and invasion in BCa cells. Second-generation sequencing identified differences in the expression of FOSB, JUND, ATP6V1C2, and RHOQ before and after DBP treatment. FOSB expression was confirmed by q-PCR and bioinformatic analyses. FOSB overexpression increased both proliferation and invasion in BCa cells. CONCLUSION: DBP promoted BCa tumorigenesis by inducing changes in gene expression.


Assuntos
Dibutilftalato , Neoplasias da Bexiga Urinária , Humanos , Dibutilftalato/toxicidade , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Proliferação de Células , Carcinogênese
5.
Dis Model Mech ; 16(5)2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35855640

RESUMO

When pathological hypertrophy progresses to heart failure (HF), the prognosis is often very poor. Therefore, it is crucial to find new and effective intervention targets. Here, myocardium-specific Trim44 knockout rats were generated using CRISPR-Cas9 technology. Cardiac phenotypic observations revealed that Trim44 knockout affected cardiac morphology at baseline. Rats with Trim44 deficiency exhibited resistance to cardiac pathological changes in response to stimulation via isoproterenol (ISO) treatment, including improvement of cardiac remodeling and dysfunction by morphological and functional observations, reduced myocardial fibrosis and reduced expression of molecular markers of cardiac stress. Furthermore, signal transduction validation associated with growth and hypertrophy development in vivo and in vitro demonstrated that Trim44 deficiency inhibited the activation of signaling pathways involved in myocardial hypertrophy, especially response to pathological stress. In conclusion, the present study indicates that Trim44 knockout attenuates ISO-induced pathological cardiac remodeling through blocking the AKT/mTOR/GSK3ß/P70S6K signaling pathway. This is the first study to demonstrate the function and importance of Trim44 in the heart at baseline and under pathological stress. Trim44 could be a novel therapeutic target for prevention of cardiac hypertrophy and HF.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Remodelação Ventricular , Animais , Cardiomegalia/genética , Isoproterenol/metabolismo , Isoproterenol/farmacologia , Isoproterenol/uso terapêutico , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Serina-Treonina Quinases TOR/metabolismo , Remodelação Ventricular/fisiologia
6.
Poult Sci ; 101(11): 102113, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36087443

RESUMO

This study's objective was to investigate the effects of dietary Se (in the form of selenomethionine) on the antioxidant activity and selenoprotein gene expressions in layer breeder roosters. One hundred and eighty, 36-wk-old Jingfen layer breeder roosters were randomly allocated to one of 5 dietary treatments (0, 0.25, 0.5, 1, or 2 mg/kg Se) for 6 wk on a corn-soybean meal-based diet. Antioxidant parameters and selenoprotein gene expressions were assessed at the end of the experiment. The results showed that Se supplementation significantly increased the activity of T-SOD, CAT, GSH-Px, and superoxide anion scavenging ability in plasma (P ≤ 0.05), and activities of T-SOD, CAT, GSH-Px, superoxide anion scavenging ability, and hydroxyl radical scavenging ability in the liver, kidney, and testis (P < 0.05). Moreover, MDA levels were significantly reduced in plasma, liver, kidney, and testis (P < 0.01), compared to the control group. Furthermore, the dietary administration of Se significantly increased TrxR2 and GPx4 mRNA levels in kidney and testis, and ID1 mRNA levels in liver and kidney. Most of the antioxidant parameters and selenoprotein-related gene expressions significantly increased, and MDA significantly decreased at dietary supplementation with 0.5 mg/kg Se. Whereas a higher dose of Se level (1 or 2 mg/kg) inhibited the activities of some of the antioxidant enzymes and selenoprotein-related gene expressions in selected tissues. In conclusion, dietary Se supplementation with 0.5 mg/kg significantly improved roosters' antioxidant status and selenoprotein-related gene expression in liver, kidney, and testis, while higher doses led to inhibit these; dietary Se might increase reproductive performance by enhancing their antioxidant status in roosters.


Assuntos
Selênio , Selenometionina , Animais , Masculino , Selenometionina/metabolismo , Antioxidantes/metabolismo , Galinhas/metabolismo , Ração Animal/análise , Suplementos Nutricionais , Superóxidos/metabolismo , Selenoproteínas/genética , Selenoproteínas/metabolismo , Dieta/veterinária , RNA Mensageiro/metabolismo , Expressão Gênica , Superóxido Dismutase/metabolismo , Selênio/metabolismo
7.
Hepatobiliary Surg Nutr ; 10(5): 661-671, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34760969

RESUMO

IMPORTANCE: Transarterial chemoembolization (TACE) has been associated with a wide range of practice variations for hepatocellular carcinoma (HCC) between the East and the West. This considerable ambiguity may lead to the heterogeneous quality in treatment and have a negative impact on the role of TACE in the overall multidisciplinary HCC treatment system. OBJECTIVE: It may be a good start to establish a guideline worldwide to have this consensus from experts who represent east and west, although it does not cover all aspects of TACE. EVIDENCE REVIEW: An international expert panel on TACE is convened to cluster the expert's opinions and summary a standard consensus. This panel committee consist of leading physicians in TACE on HCC from USA, France, Japan, Singapore, Korea, China, and so on. The first-round face-to-face consensus meeting was held during in Nanjing, China in October 2019. The second-round conference for revision of the consensus was held during the Annual Meeting of Chinese College of Interventionalists in August 2020 by a hybrid format of a Webinar and roundtable meeting. After several on-line revisions, the final manuscript was approved by all members of the panel in June 2021. FINDINGS: The consensus statements were organized into the following categories: patients' selection, performing the procedure, TACE outcomes, repeat TACE, TACE failure/refractory, and TACE-based combination treatments. CONCLUSIONS AND RELEVANCE FOR REVIEWS: More and more evidences have showed the better outcomes with strategy of combined TACE with other local therapies such as ablations. The most-recently developing strategy of combined TACE with PD-1/PD-L1 plus tyrosine kinase inhibitor (TKI) agents has shined a light to the HCC patients, especially to those with high risk of tumor recurrence after treatment or TACE failure/refractory.

8.
BMC Urol ; 21(1): 145, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645421

RESUMO

BACKGROUND: Urinary bladder lymphangioma is a rare and benign lesion that is often causes symptoms related to irritation and urinary tract obstruction. Because a lymphangioma may resemble a true neoplasm of the urinary bladder clinically, the lesion must be removed for accurate histologic diagnosis and to rule out malignancy. CASE PRESENTATION: We present a case of a 40-year-old female who was evaluated for painless gross hematuria. Clinical and diagnostic work up revealed a sharply defined mass involving the wall and bulging into the cavity on the dome of the bladder. Partial cystectomy was performed and histologic findings were compatible with cavernous lymphangioma. The symptom of hematuria relieved after the procedure and the patient was in good status without evidence of recurrence by cystoscopy at follow-up 6 months later. CONCLUSIONS: Lymphangioma of the urinary bladder is treated with surgical excision and seems to have no recurrence once completely resected, but long-time follow-up may be needed.


Assuntos
Linfangioma/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Adulto , Cistectomia , Feminino , Hematúria/etiologia , Humanos , Linfangioma/diagnóstico por imagem , Linfangioma/patologia , Linfangioma/cirurgia , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
9.
Theranostics ; 8(14): 3751-3765, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30083257

RESUMO

Long non-coding RNAs (lncRNAs) have recently been identified as critical regulators in tumor initiation and development. However, the function of lncRNAs in human hepatocellular carcinoma (HCC) remains largely unknown. Our study was designed to explore the biological function and clinical implication of lncRNA MIR22HG in HCC. Methods: We evaluated MIR22HG expression in 52-patient, 145-patient, TCGA, and GSE14520 HCC cohorts. The effects of MIR22HG on HCC were analyzed in terms of proliferation, invasion, and metastasis, both in vitro and in vivo. The mechanism of MIR22HG action was explored through bioinformatics, luciferase reporter, and RNA immunoprecipitation analyses. Results:MIR22HG expression was significantly down-regulated in 4 independent HCC cohorts compared to that in controls. Its low expression was associated with tumor progression and poor prognosis of patients with HCC. Forced expression of MIR22HG in HCC cells significantly suppressed proliferation, invasion, and metastasis in vitro and in vivo. Mechanistically, MIR22HG derived miR-22-3p to target high mobility group box 1 (HMGB1), thereby inactivating HMGB1 downstream pathways. Additionally, MIR22HG directly interacted with HuR and regulated its subcellular localization. MIR22HG competitively bound to human antigen R (HuR), resulting in weakened expression of HuR-stabilized oncogenes, such as ß-catenin. Furthermore, miR-22-3p suppression, HuR or HMGB1 overexpression rescued the inhibitory effects caused by MIR22HG overexpression. Conclusion: Our findings revealed that MIR22HG plays a key role in tumor progression by suppressing the proliferation, invasion, and metastasis of tumor cells, suggesting its potential role as a tumor suppressor and prognostic biomarker in HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Genes Supressores de Tumor , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Animais , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Xenoenxertos , Humanos , Neoplasias Hepáticas/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica/patologia , Transplante de Neoplasias
10.
Poult Sci ; 97(12): 4415-4424, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30085275

RESUMO

The objective of this study consisting of 2 trials was to investigate the antioxidant role of conjugated linoleic acid (CLA) isomers (c9, t11-CLA and t10, c12-CLA) and the underlying mechanism by which they act in modulating redox status in a primary laying hen hepatocyte culture. In trial 1, the cytotoxicity of CLA isomers or linoleic acid (LA) (0, 25, 50, 100, 200, 400, 800 µmol/L) was evaluated by 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay. The concentration of CLA isomers or LA (25, 50, 100 µmol/L) for proper antioxidant activity was evaluated by measuring the antioxidant enzyme activity. In trial 2, there were 5 groups: control group, cells were untreated; H2O2 group, cells were exposed to 4 mmol/L H2O2 for 2 h; c9, t11 or t10, c12 or LA group, cells were treated with c9, t11-CLA or t10, c12-CLA or LA for 24 h and then exposed to 4 mmol/L H2O2 for 2 h. Trial 1 showed that the non-toxic dose range for CLA isomers was 0 to 200 µmol/L. The optimum concentration of c9, t11-CLA and t10, c12-CLA for trial 2 was 100 µmol/L. In trial 2, pretreatment with t10, c12-CLA but not c9, t11-CLA attenuated the increase in reactive oxygen species (ROS) compared to hydrogen peroxide (H2O2) group (P < 0.05). t10, c12-CLA elevated the superoxide dismutase (SOD) and catalase (CAT) activities compared with the H2O2 group (P < 0.05). In addition, t10, c12-CLA up-regulated the mRNA expression of nuclear factor E2-related factor-2 (Nrf2) as well as its target genes, Cu-Zn superoxide dismutase (SOD1) and CAT (P < 0.05). Pretreatment with t10, c12-CLA but not c9, t11-CLA decreased Nrf2 protein expression in the cytoplasm and increased Nrf2 protein expression in the nucleus compared with the H2O2 group (P < 0.05). The results indicate that t10, c12-CLA exhibits a stronger antioxidant capacity than c9, t11-CLA in primary cultured laying hen hepatocytes. t10, c12-CLA increases the activity and mRNA expression of antioxidant enzymes via facilitating nuclear translocation of Nrf2.


Assuntos
Antioxidantes/metabolismo , Galinhas/metabolismo , Ácido Linoleico/metabolismo , Ácidos Linoleicos Conjugados/metabolismo , Ração Animal/análise , Animais , Células Cultivadas , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Feminino , Hepatócitos/metabolismo , Ácido Linoleico/administração & dosagem , Ácidos Linoleicos Conjugados/administração & dosagem
11.
Cancer Commun (Lond) ; 38(1): 23, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29764518

RESUMO

BACKGROUND: Few studies have shown nomograms that may predict disease-specific survival (DSS) probability after curative D2 gastrectomy for advanced gastric cancer (AGC), particularly among Chinese patients. This study sought to develop an elaborative nomogram that predicts long-term DSS for AGC in Chinese patients. METHODS: A retrospective study was conducted on 6753 AGC patients undergoing D2 gastrectomy between January 1, 2000 and December 31, 2012 from three large medical hospitals in China. We assigned patients from Sun Yat-sen University Cancer Center to the training set, and patients from the First Affiliated Hospital of China Medical University and Tianjin Medical University Cancer Hospital to two separate external validation sets. A multivariate survival analysis was performed using Cox proportional hazards regression model in a training set, and a nomogram was constructed. Harrell's C-index was used to evaluate discrimination and calibration plots were used to validate similarities between survival probabilities predicted by the nomogram model and actual survival rates in two validation sets. RESULTS: The multivariate Cox regression model identified age, tumor size, location, Lauren classification, lymphatic/venous invasion, depth of invasion, and metastatic lymph node ratio as covariates associated with survival. In the training set, the nomogram exhibited superior discrimination power compared with the 8th American Joint Committee on Cancer TNM classification (Harrell's C-index, 0.82 vs. 0.74; P < 0.001). In two validation sets, the nomogram's discrimination power was also excellent relative to TNM classification (C-index, 0.83 vs. 0.75 and 0.81 vs. 0.74, respectively; P < 0.001 for both). After calibration, the nomogram produced survival predictions that corresponded closely with actual survival rate. CONCLUSIONS: The established nomogram was able to predict 3-, 5-, and 10-year DSS probabilities for AGC patients. Validation revealed that this nomogram exhibited excellent discrimination and calibration capacity, suggesting its clinical utility.


Assuntos
Gastrectomia/métodos , Nomogramas , Avaliação de Resultados em Cuidados de Saúde/métodos , Neoplasias Gástricas/cirurgia , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida
12.
BMC Urol ; 17(1): 96, 2017 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-29037183

RESUMO

BACKGROUND: Renal artery aneurysm (RAA) is rare and its incidence in the general population remains elusive. There have been few reports on the repair of multiple aneurysms conducted with the Da Vinci robot-assisted surgical platform (Intuitive Surgical Inc., Sunnyvale, CA, USA), especially for those located in renal artery primary bifurcations. CASE PRESENTATION: We report our experience in the surgical management of two expanding right-sided RAAs in a 64-year-old man using a robot-assisted laparoscopic approach. Two aneurysms were located in renal artery primary bifurcations, whose diameter was 1.8 and 1.2 cm. The aneurysms were resected and the renal artery branch reconstructed by in situ arteriorrhaphy. The operation lasted for 2 h and 35 min with a warm ischemia time of 26 min and estimated blood loss of 150 ml. The hospital stay was 6 days. The computed tomography (CT) scan performed 2 months after the surgery showed resolution of the aneurysms. Additionally, split renal function indicated the preservation of right renal function in the follow-up period. CONCLUSIONS: The robot-assisted laparoscopic procedure is a safe and effective surgical technique, which may be considered as an alternative to open surgery for complex multiple RAAs in the future.


Assuntos
Aneurisma/cirurgia , Gerenciamento Clínico , Laparoscopia/métodos , Procedimentos de Cirurgia Plástica/métodos , Artéria Renal/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Aneurisma/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Renal/diagnóstico por imagem , Procedimentos Cirúrgicos Vasculares/métodos
13.
World J Gastroenterol ; 23(19): 3522-3529, 2017 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-28596688

RESUMO

AIM: To determine the feasibility, safety, and oncological outcome of laparoscopic resection of gastric gastrointestinal stromal tumors (GISTs) based on favorable or unfavorable location. METHODS: Our hospital database included 207 patients who underwent laparoscopic removal of gastric GISTs from January 2004 to September 2015. Patient demographics, clinical presentation, surgery, histopathology, postoperative course, and oncological outcomes were reviewed and analyzed. RESULTS: Gastric GIST in favorable locations was present in 81/207 (39.1%) cases, and in unfavorable locations in 126/207 (60.9%) cases. Overall mean tumor size was 3.28 ± 1.82 cm. No conversions occurred, and complete R0 resection was achieved in 207 (100%) cases. There were three incidences of iatrogenic tumor rupture. The feasibility and safety of laparoscopic surgery were comparable in both groups with no statistical difference between unfavorable and favorable location groups, respectively: for operative time: 83.86 ± 44.41 vs 80.77 ± 36.46 min, P = 0.627; conversion rate: 0% vs 0%; estimated blood loss: 27.74 ± 45.2 vs 29.59 ± 41.18 mL, P = 0.780; tumor rupture during surgery: 0.90% vs 2.82%, P = 0.322; or postoperative complications: 3.74% vs 7.04%, P = 0.325. The follow-up period recurrence rate was 1.89% with no significant differences between the two groups (3.03% vs 0%, P = 0.447). Overall 5-year survival rate was 98.76% and survival rates were similar between the two groups: 98.99% vs 98.39%, P = 0.623 (unfavorable vs favorable, respectively). CONCLUSION: The laparoscopic approach for gastric GISTs is safe and feasible with well-accepted oncological surgical outcomes. Strategies for laparoscopic resection should be selected according to the location and size of the tumor. Laparoscopic treatment of gastric GISTs in unfavorable locations should not be restricted in gastrointestinal centers.


Assuntos
Tumores do Estroma Gastrointestinal/cirurgia , Laparoscopia , Adulto , Idoso , Endoscopia , Estudos de Viabilidade , Feminino , Seguimentos , Gastrectomia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Recidiva Local de Neoplasia/cirurgia , Duração da Cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
14.
Clin Sci (Lond) ; 131(5): 381-394, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28082516

RESUMO

High-mobility group box-1 (HMGB1) protein, as one of the well-known damage-associated molecular pattern molecules (DAMPs), is enriched in chronic hepatitis B virus (HBV) infection and has a context-dependent role in autophagy, a highly conserved self-digestive process in response to environmental stress. Recent mouse studies indicate that autophagy is highly active in regulatory T (Treg)-cells. In the present study, we evaluated spontaneous and induced autophagy of peripheral Treg cells from 98 patients with chronic hepatitis B (CHB), by measuring levels of lipidated form of microtubule-associated light chain 3 (LC3-II, marker for closed autophagosomes) and observing autophagic vacuoles (AV) with transmission electron microscope. No significant difference was found in spontaneous autophagy of either Treg or CD4+ naive cells when comparing CHB patients with healthy subjects, apart from CHB-Treg showed significantly higher autophagic activity after activation by anti-CD3-CD28 beads. Besides, incubation of CHB-Treg cells with CHB-serum greatly maintained their autophagic behaviour, which could be significantly diminished by blocking HMGB1 with the neutralizing antibody. Further, we characterized time- and dose-dependent effects by recombinant HMGB1 protein on autophagy of CHB-Treg cells. We also documented a significant up-regulation of HMGB1 and its receptors [toll-like receptor (TLR4), receptor for advanced glycation end-product (RAGE)] in both peripheral and intra-hepatic microenvironments of CHB patients. Moreover, the RAGE-extracellular regulated protein kinases (ERK) axis and rapamycin-sensitive components of mammalian target of rapamycin (mTOR) pathways were demonstrated in vitro to be involved in HMGB1-induced autophagy of Treg cells. Additionally, HMGB1-induced autophagy could maintain cell survival and functional stability of CHB-Treg cells. Our findings could open new perspectives in developing therapeutic strategies to activate specific anti-HBV immunity by diminishing Treg autophagy.


Assuntos
Autofagia , Proteína HMGB1/metabolismo , Hepatite B Crônica/imunologia , Linfócitos T Reguladores/fisiologia , Adulto , Antígenos de Neoplasias/metabolismo , Estudos de Casos e Controles , Feminino , Hepatite B Crônica/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Adulto Jovem
15.
Acta Pharmacol Sin ; 35(9): 1103-10, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25152025

RESUMO

Microparticles are small membrane fragments shed primarily from blood and endothelial cells during either activation or apoptosis. There is mounting evidence suggesting that microparticles perform a large array of biological functions and contribute to various diseases. Of these disease processes, a significant link has been established between microparticles and venous thromboembolism. Advances in research on the role of microparticles in thrombosis have yielded crucial insights into possible mechanisms, diagnoses and therapeutic targets of venous thromboembolism. In this review, we discuss the definition and properties of microparticles and venous thromboembolism, provide a synopsis of the evidence detailing the contributions of microparticles to venous thromboembolism, and propose potential mechanisms, by which venous thromboembolism occurs. Moreover, we illustrate a possible role of microparticles in cancer-related venous thromboembolism.


Assuntos
Micropartículas Derivadas de Células/patologia , Tromboembolia Venosa/patologia , Apoptose/fisiologia , Células Endoteliais/patologia , Humanos , Neoplasias/patologia
16.
Onco Targets Ther ; 7: 907-14, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24940075

RESUMO

BACKGROUND: Some studies have found that the NAD(P)H: quinone oxidoreductase 1 (NQO1) SNP609 is associated with an increased risk for several malignancies. Numerous epidemiological studies have evaluated the association between the NQO1 C609T polymorphism and the risk of prostate cancer. However, the results of these studies have been conflicting. The aim of this study was to provide a more precise estimation of its relationship with prostate cancer using a meta-analysis. METHODS: Electronic searches of several databases were conducted for all publications on the association between the NQO1 C609T polymorphism and prostate cancer before May 2013. The odds ratio (OR) and its 95% confidence interval (CI) were used for statistical analysis. RESULTS: A total of six studies with 717 cases and 1,794 controls were included. No significant association was found between the NQO1 C609T polymorphism and prostate cancer risk in the total population analysis. In subgroup meta-analysis by ethnicity, a positive association was found in an Asian subgroup (T versus C, OR 1.337, 95% CI 1.014-1.763, P=0.040; TT + CT versus CC, OR 1.419, 95% CI 1.053-1.913, P=0.021). However, no significant association in any genetic models was observed in Caucasians. CONCLUSION: This meta-analysis showed that the NQO1 SNP609 T allele might be a risk factor for prostate cancer in Asians. However, this result should be verified by additional population-based studies with large sample sizes.

17.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 38(1): 100-2, 2009 01.
Artigo em Chinês | MEDLINE | ID: mdl-19253436

RESUMO

OBJECTIVE: To evaluate the feasibility and safety of transperitoneal laparoscopic nephrectomy in live-donors. METHODS: Two cases of live-donor underwent laparoscopic nephrectomy in May and August 2008 respectively and both were followed up. RESULT: In two cases the operation time was 130, 10 min; blood loss was 50 ml; warm ischemic time was 30 s and 2 min; the length of artery was 4.0 cm and 3.5 cm; the length of vein was 3.0 cm. The grafted kidneys started to produce urine at 30 s and 10 s after blood supply. Renal function of donor returned to normal after two days. The donors were discharged at 7th day after the operation. Renal function of recipient was normal after 3 days. CONCLUSION: Transperitoneal laparoscopic nephrectomy in live-donor is a safe and effective procedure, which provides kidney with satisfactory blood vessels and ureter for graft.


Assuntos
Transplante de Rim , Laparoscopia , Doadores Vivos , Nefrectomia/métodos , Coleta de Tecidos e Órgãos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peritônio/cirurgia
18.
Zhonghua Zhong Liu Za Zhi ; 29(11): 813-7, 2007 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-18396636

RESUMO

OBJECTIVE: To explore the effects of overexpression of human tissue inhibitors of metalloproteinase-1 (hTIMP-1) on proliferation, invasion, metastasis, angiogenesis, and apoptosis in human hepatocellular carcinoma (HCC) cells in vitro and in vivo. METHODS: Recombinant adenoviral vector containing hTIMP-1 (AdhTIMP-1) was constructed previously. HepG2 cells were infected by AdhTIMP-1 and the changes of cell proliferation and invasion were detected in vitro. The anticancer activity of AdhTIMP-1 was evaluated in BAL B/c mice bearing HCC. Tumor volume and pulmonary metastases were observed. The mechanisms underlying the antitumor effect in vivo were investigated based on detection of microvessel density and apoptosis in tumor tissues. RESULTS: The resultant AdhTIMP-1 was successfully constructed and the expression of hTIMP-1 was detected by Western blot and RT-PCR. AdTIMP-1 could effectively infect HepG2 cells and significantly inhibit the proliferative activity and invasive ability of the tumor cells. Compared with the controls, pre-infection of HepG2 cells by AdhTIMP-1 resulted in a significant inhibition of tumor formation by 75. 8%. A single local injection of AdhTIMP-1 into pre-established tumors significantly reduced the tumor growth rate by 45.4%, tumor-associated angiogenesis index by 47.8%, lung metastases by 70.4%, and showed a 3-fold increase of apoptotic tumor cells. CONCLUSION: Our data indicated that AdhTIMP-1 can significantly attenuate tumor proliferation and invasion, reduce metastasis, inhibit angiogenesis, and induce apoptosis in HCC-bearing mice and may pave the way for further liver cancer gene therapy.


Assuntos
Adenoviridae/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Vetores Genéticos , Humanos , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Neovascularização Patológica/prevenção & controle , Plasmídeos , Distribuição Aleatória , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genética , Transfecção , Carga Tumoral
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