Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 31
Filtrar
1.
Medicine (Baltimore) ; 102(47): e36145, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38013302

RESUMO

BACKGROUND: Previous studies have investigated the effectiveness and safety of ultrasound-guided fascia iliaca compartment block (UGFICB) compared to quadratus lumborum block (QLB) for pain management in total hip arthroplasty (THA). However, there is currently a lack of a systematic review specifically addressing this issue. Therefore, the purpose of this study was to conduct a comprehensive analysis and comparison of the efficacy and safety of UGFICB versus QLB for pain management in THA. METHODS: An extensive search was conducted in various electronic databases, including PUBMED, EMBASE, Cochrane Library, Web of Science, Scopus, China Biomedical Literature Service System, and China National Knowledge Infrastructure. This search encompassed all relevant studies published from the inception of these databases until June 30, 2023. The selected outcomes for analysis included moving and resting visual analogue scale (VAS) scores at 12 hours and 24 hours post-surgery, as well as opioids consumption at 24 hours post-surgery. The Cochrane risk-of-bias tool was utilized to assess the risk of bias in the trials included in the analysis. Statistical analysis was conducted using RevMan 5.4 software. RESULTS: A total of 8 trials, involving 656 patients, were included in this study. The results of the meta-analysis showed no significant differences between the 2 modalities in terms of moving VAS scores (mean difference [MD] = 0.17, 95% confidence interval [CI] [-0.79, 1.14], P = .72) and resting VAS scores (MD = 0.04, 95% CI [-0.27, 0.36], P = .78) at 12 hours post-surgery, and moving VAS scores (MD = 0.27, 95% CI [-0.46, 1.01], P = .47) and resting VAS scores (MD = -0.05, 95% CI [-0.45, 0.35], P = .80) at 24 hours post-surgery. However, there was significant differences in opioids consumption at 24 hours post-surgery (MD = 8.98, 95% CI [2.04, 15.93], P = .01) between the 2 groups. CONCLUSION: Based on these findings, the study concludes that UGFICB may be more beneficial than QLB for pain management in THA. However, it is important to interpret these results with caution due to certain limitations.


Assuntos
Artroplastia de Quadril , Manejo da Dor , Humanos , Manejo da Dor/métodos , Artroplastia de Quadril/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Analgésicos Opioides , Fáscia , Ultrassonografia de Intervenção
2.
J Fungi (Basel) ; 8(8)2022 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-36012813

RESUMO

Karst caves are oligotrophic environments that appear to support a high diversity of fungi. Studies of fungi in Thailand's caves are limited. During a 2019 exploration of the mycobiota associated with soil samples from a karst cave, namely, Phu Pha Phet in the Satun UNESCO Global Geopark in Satun Province, southern Thailand, two previously undescribed fungi belonging to Talaromyces (Trichocomaceae, Eurotiales, Eurotiomycetes) were studied using a polyphasic approach combining phenotypic and molecular data. Based on datasets of four loci (ITS, BenA, CaM, and RPB2), phylogenetic trees of the section Trachyspermi were constructed, and two new species-Talaromyces phuphaphetensis sp. nov. and T. satunensis sp. nov.-phylogenetically related to T. subericola, T. resinae, and T. brasiliensis, are described. Detailed descriptions and illustrations of the new species are provided. This study increases the number of cave-dwelling soil fungi discovered in Thailand's Satun UNESCO Global Geopark, which appears to be a unique environment with a high potential for discovering fungal species previously undescribed.

3.
Front Med (Lausanne) ; 9: 828346, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35602511

RESUMO

Background: Uterine cervical neoplasms is widely concerned due to its high incidence rate. Early diagnosis is extremely important for prognosis. The purpose of this article is evaluating the efficacy of Raman spectroscopy in the diagnosis of suspected uterine cervical neoplasms. Methods: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of science up to September 1, 2021. By analyzing the true positive (TP), false positive (FP), true negative (TN) and false negative (FN) of six included study, we evaluated the pooled and grouping sensitivity, specificity, positive, and negative likelihood ratios (LR), and diagnostic odds ratio (DOR), with 95% confidence intervals (CI), based on random effects models. The overall diagnostic accuracy of Raman spectrum was evaluated by SROC curve analysis and AUC. Results: After screening with inclusion and exclusion criteria, a total of six study were included in the study. The pooled sensitivity and specificity was 0.98 (95% Cl, 0.93-0.99) and 0.95 (95% Cl, 0.89-0.98). The total PLR and NLR were 21.05 (95% CI, 8.23-53.86) and 0.03 (95% CI, 0.01-0.07), respectively. And the AUC of the SROC curve which show the overall diagnostic accuracy was 0.99 (0.98-1.00). Conclusion: Through analysis, we confirmed the role of Raman spectroscopy (RS) in the diagnosis of suspected uterine cervical tumors. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021284966].

6.
Neurosurgery ; 86(4): 548-556, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31081882

RESUMO

BACKGROUND: Limited data existed to guide the management of intraspinal neurenteric cysts (ISNECs). OBJECTIVE: To evaluate the risk factors for progression-free survival (PFS), elucidate the radiological features of ISNECs, and propose a treatment protocol. METHODS: From 2003 to 2015, 121 patients with pathologically confirmed ISNECs treated at our institute were included in this study. Pertinent risk factors were evaluated. RESULTS: Gross total resection (GTR) was achieved in 55 (44.6%) patients; 106 (87.6%), 12 (9.9%), and 3 (2.5%) ISNECs were classified as Wilkins A, B, and C, respectively. After a median follow-up duration of 64.2 mo, recurrence occurred in 25 (22.7%) patients, with a median PFS time of 43.1 mo. The actuarial PFS rates at 5 and 10 yr were 73.2% and 66.2%, respectively. The actuarial overall survival rates at 5 and 10 yr were 100% and 97.6%, respectively. Non-GTR (hazard ratio [HR], 5.836; 95% confidence interval [CI], 1.698-20.058; P = .005), Wilkins B/C (HR, 3.129; 95% CI, 1.009-9.702; P = .048), and a history of surgical resection (HR, 3.690; 95% CI, 1.536-8.864; P = .004) were adverse factors. CONCLUSION: GTR and Wilkins A were favorable factors for PFS. If tolerable, GTR alone was advocated as an optimal treatment. Because of the benign nature and favorable prognosis, non-GTR was an alternative if GTR failed. Close follow-up was needed because of the recurrent tendency of ISNEC. Future study with a large cohort is necessary to verify our findings.


Assuntos
Defeitos do Tubo Neural/mortalidade , Defeitos do Tubo Neural/patologia , Defeitos do Tubo Neural/cirurgia , Adolescente , Adulto , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Procedimentos Neurocirúrgicos/métodos , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
7.
Sci Rep ; 9(1): 13239, 2019 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519974

RESUMO

Inflammation and immunoreaction markers were correlated with the survival of patients in many tumors. However, there were no reports investigating the relationships between preoperative hematological markers and the prognosis of medulloblastoma (MB) patients based on the molecular subgroups (WNT, SHH, Group 3, and Group 4). A total 144 MB patients were enrolled in the study. The differences of preoperative hematological markers among molecular subgroups of MB were compared by One-way ANOVA method. Kaplan-Meier method was used to calculate the curves of progression free survival (PFS) and overall survival (OS). The comparison of survival rates in different groups were conducted by the Log-rank test. Multivariate analysis was used to evaluate independent prognostic factors. Increased preoperative NLR (neutrophil-to-lymphocyte ratio, PFS, P = 0.004, OS, P < 0.001) and PLR (platelet-to-lymphocyte ratio, PFS, P = 0.028, OS, P = 0.003) predicted poor prognosis in patients with MB, while preoperative MLR (monocyte-to-lymphocyte ratio), MPV (mean platelet volume), PDW (platelet distribution width), and AGR (albumin-to-globulin ratio) were revealed no predictive value on the prognosis of patients with MB. Furthermore, high preoperative NLR and PLR predicted unfavorable prognosis in childhood MB patients. However, preoperative NLR and PLR were not associated with the prognosis in adult MB patients. Multivariate analysis demonstrated preoperative NLR (PFS, P = 0.029, OS, P = 0.005) and PLR (PFS, P = 0.023, OS, P = 0.005) were the independent prognostic factors in MB patients. Emphatically, the levels of preoperative NLR and PLR in Group 3 MB were significantly higher than those in WNT MB. High preoperative NLR was associated with unfavorable OS in Group 3 (P = 0.032) and Group 4 (P = 0.027) tumors. Similarly, increased preoperative PLR predicted poor PFS (P = 0.012) and OS (P = 0.009) in Group 4 tumors. Preoperative NLR and PLR were the potential prognostic markers for MB patients. Preoperative NLR and PLR were significantly associated with the survival of Group 3 and Group 4 tumors.


Assuntos
Biomarcadores Tumorais/análise , Plaquetas/patologia , Neoplasias Cerebelares/patologia , Linfócitos/patologia , Meduloblastoma/patologia , Cuidados Pré-Operatórios , Adolescente , Adulto , Neoplasias Cerebelares/cirurgia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Meduloblastoma/cirurgia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
8.
Med Sci Monit ; 25: 5312-5320, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31314750

RESUMO

BACKGROUND Osteoporosis is a common osteopathy, resulting in fractures, especially in elder people. Sesamin has many pharmacological effects, including supplying calcium. However, how sesamin might prevent osteoporosis is still under study. MATERIAL AND METHODS Bone marrow stromal cells (BMSCs) extracted from rat femur were induced for osteoblastic differentiation. Cell proliferation, alkaline phosphatase (ALP), osterix (OSX), SRY-box 9 (SOX9), runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), ß-catenin, low density lipoprotein receptor-related protein 5 (LRP5), and glycogen synthase kinase-3ß (GSK-3ß) levels in BMSCs were detected in the presence or absence of sesamin (1 µM or 10 µM). In addition, FH535 (1 µM) was used to silence Wnt/ß-catenin in vitro. Ovariectomized (OVX) rats were established and intragastrically administrated sesamin (80 mg/kg), and then the rat bones were analyzed by micro-computed tomography. Osteocalcin and collagen type I were measured in the rat femurs. RESULTS Sesamin had no influence on BMSC proliferation. Higher sesamin concentration promoted Wnt/ß-catenin activity and enhanced more expressions of ALP, OSX, SOX9, RUNX2, and OCN, gradually and significantly (P<0.05). Silencing Wnt/ß-catenin weakened the enhancement on RUNX2 and OCN expression. Sesamin (80 mg/kg) promoted bone structure in ovariectomized rats, and significantly enhanced osteocalcin and collage type I expression (P<0.05). CONCLUSIONS Sesamin promoted osteoblastic differentiation of rat BMSCs by regulating the Wnt/ß-catenin pathway, and improved rat bone structure. Sesamin could have therapeutic and preventive effects on osteoporosis.


Assuntos
Dioxóis/farmacologia , Lignanas/farmacologia , Osteoblastos/efeitos dos fármacos , Osteoporose/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Osso e Ossos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , China , Colágeno Tipo I/metabolismo , Dioxóis/metabolismo , Feminino , Lignanas/metabolismo , Células-Tronco Mesenquimais , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle , Ovariectomia , Ratos , Ratos Sprague-Dawley , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo
9.
Mol Immunol ; 112: 30-39, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31075560

RESUMO

Traumatic brain injury (TBI) is a major cause of motor and cognitive impairment in young adults. It is associated with high mortality rates and very few effective treatment options. Bisperoxovanadium (pyridine-2-carboxyl) [bpV(pic)] is an commercially available inhibitor of Phosphatase and tensin homolog (PTEN). Previous studies have shown that bpV(pic) has protective effects in central nervous system. However, the role of bpV(pic) in TBI is unclear. In this study we aimed to investigate the neuroprotective role of bpV(pic) in rat TBI model. We found that injection of bpV(pic) significantly reduces brain edema and neurological dysfunction after TBI and this is mediated by AKT pathway. TBI is known to promote the M1 pro-inflammatory phenotype of microglial polarization and this effect is inhibited by bpV(pic) treatment which, instead promotes M2 microglial polarization in vivo and in vitro. We also found evidence of bpV(pic)-regulated neuroinflammation mediated by AKT activation and NF-κB p65 inhibition. BpV(pic) treatment also suppressed microglia in the peri-TBI region. MCP-1 is known to recruit monocytes and macrophages to promote inflammation, we show that bpV(pic) can inhibit TBI-induced up-regulation of MCP-1 via the AKT/NF-κB p65 signaling pathway. Taken together, our findings demonstrate that bpV(pic) plays a neuroprotective role in rat TBI, which may be achieved by inhibiting M1 microglia polarization and MCP-1 expression by modulating AKT/NF-κB p65 signaling pathway.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Quimiocina CCL2/metabolismo , Microglia/efeitos dos fármacos , Neuroproteção/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Microglia/metabolismo , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , NF-kappa B/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley
11.
J Alzheimers Dis ; 66(3): 1001-1014, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30372676

RESUMO

DJ-1 (also called PARK7) is a multifunctional redox-sensitive protein that is protective against oxidative stress-induced cell death. TAR DNA-binding protein 43 (TDP-43) is a major protein component of pathological inclusions in amyotrophic lateral sclerosis and frontotemporal dementia. Reducing aberrant aggregation of TDP-43 is a potential approach to prevent cell death. To investigate whether DJ-1 might inhibit TDP-43 aggregation to exert a protective effect in oxidative stress-induced injury, we tested the protein level and subcellular localization of TDP-43 and DJ-1 in SH-SY5Y cells transfected with wild-type DJ-1, DJ-1 mutant (L166P) cDNA, or DJ-1 siRNA. We show that oxidative stress induced by paraquat leads to the formation of cytosolic TDP-43 aggregation in SH-SY5Y cells. DJ-1 overexpression decreases paraquat-induced cytoplasmic accumulation of TDP-43 in SH-SY5Y cells and protects against paraquat-induced cell death. Transfection of DJ-1 L166P mutant or DJ-1 siRNA leads to increased cytosolic aggregation of TDP-43 in paraquat-treated SH-SY5Y cells and promotes cell death. These data suggest that DJ-1 may protect against oxidative stress-induced cell death through the suppression of cytoplasmic TDP-43 aggregation.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Neurônios/metabolismo , Estresse Oxidativo/fisiologia , Proteína Desglicase DJ-1/genética , Esclerose Lateral Amiotrófica/metabolismo , Linhagem Celular Tumoral , Humanos , Neurônios/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Paraquat/farmacologia , Fosforilação , Proteína Desglicase DJ-1/metabolismo
12.
Neurochem Res ; 43(7): 1424-1438, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29882124

RESUMO

Bisperoxovanadium (pyridine-2-carboxyl) [bpV(pic)] is a commercially available PTEN inhibitor. Previous studies from us and others have shown that bpV(pic) confers neuroprotection in cerebral ischemia injury. We set up to determine whether ERK 1/2 activation plays a role in bpV(pic)-induced neuroprotective effect in cerebral ischemia injury. We found that the phosphorylation levels of Akt (p-AKT) and ERK1/2 (p-ERK 1/2) were down-regulated after cerebral ischemia-reperfusion injury. The injection of bpV(pic) after injury not only increased the level of p-AKT but also the level of p-ERK 1/2. While the inhibition of PTEN mediated the up-regulatation of p-AKT and p-ERK 1/2 by bpV(pic). Interestingly, the ERK 1/2 activation induced by bpV(pic) was also independent of the inhibition of PTEN. Our results indicate that bpV(pic) protects against OGD-induced neuronal death and promotes the functional recovery of stroke animals through PTEN inhibition and ERK 1/2 activation, respectively. This study suggests that the effect of bpV(pic) on ERK 1/2 signaling should be considered while using bpV(pic) as a PTEN inhibitor.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Compostos de Vanádio/farmacologia , Animais , Modelos Animais de Doenças , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos
13.
Cancer Med ; 7(7): 2848-2859, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29777576

RESUMO

Glioblastoma (GBM) is the most aggressive glioma in the brain. Recurrence of GBM is almost inevitable within a short term after tumor resection. In a retrospective study of 386 cases of GBM collected between 2013 and 2016, we found that recurrence of GBM mainly occurs in the deep brain regions, including the basal ganglia, thalamus, and corpus callosum. But the mechanism underlying this phenomenon is not clear. Previous studies suggest that neuroligin-3 (NLGN3) is necessary for GBM growth. Our results show that the levels of NLGN3 in the cortex are higher than those in the deep regions in a normal human brain, and similar patterns are also found in a normal mouse brain. In contrast, NLGN3 levels in the deep brain regions of GBM patients are high. We also show that an increase in NLGN3 concentration promotes the growth of U251 cells and U87-MG cells. Respective use of the cortex neuron culture medium (C-NCM) and basal ganglia neuron culture medium (BG-NCM) with DMEM to cultivate U251, U87-MG and GBM cells isolated from patients, we found that these cells grew faster after treatment with C-NCM and BG-NCM in which the cells treated with C-NCM grew faster than the ones treated with BG-NCM group. Inhibition of NLGN3 release by ADAM10i prevents NCM-induced cell growth. Together, this study suggests that increased levels of NLGN3 in the deep brain region under the GBM pathological circumstances may contribute to GBM recurrence in the basal ganglia, thalamus, and corpus callosum.

14.
Biochem Biophys Res Commun ; 501(1): 85-91, 2018 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-29698679

RESUMO

Glycine has been shown to protect against ischemic stroke through various mechanisms. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) which antagonize Akt-dependent cell survival has been linked to neuronal damage. However, whether glycine has a neuroprotective property in intracerebral hemorrhage (ICH) was unknown. This study aimed to determine the protective effect of glycine in rats ICH. Adult male Sprague-Dawley (SD) rats were subjected to left striatum infusion of autologous blood. ICH animals received glycine (0.2-3 mg/kg, icv) at 1 h after ICH with or without pre-injection of Akt Inhibitor IV (100 µM, 2 µl, icv) 0.5 h prior to glycine treatment. Our results showed that in the perihematomal area PTEN was up-regulated in the early stage after ICH. However, glycine treatment decreased PTEN protein level and increased the phosphorylation level of AKT (p-AKT) in the perihematomal area. With the administration of glycine, neuronal death was significantly reduced and Evans blue leakage was alleviated as well as the brain edema after ICH. Moreover, hematoma volume was decreased and neurobehavioral outcome was improved. Nevertheless, Akt Inhibitor IV abolished the neuroprotective effects of glycine after ICH. Together, our findings demonstrate, for the first time, the protective role of glycine on ICH rats, and suggest that the neuroprotective effect of glycine was mediated through PTEN/Akt signal pathway.


Assuntos
Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/metabolismo , Glicina/farmacologia , Neuroproteção/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Benzimidazóis/farmacologia , Benzotiazóis/farmacologia , Edema Encefálico/tratamento farmacológico , Edema Encefálico/metabolismo , Edema Encefálico/patologia , Morte Celular/efeitos dos fármacos , Hemorragia Cerebral/patologia , Modelos Animais de Doenças , Masculino , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , PTEN Fosfo-Hidrolase/antagonistas & inibidores , Fosforilação , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
15.
Curr Opin Chem Biol ; 43: 30-36, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29136524

RESUMO

Transition metal compounds are a rich source for anticancer drug development. Judicious application of coordination ligands is a critical success factor in the design of effective anti-tumor compounds. N-heterocyclic carbenes (NHC) are stable ligands that have strong donor strengths in stabilizing metal ions and versatility in structural modifications to provide diverse scaffolds for biological molecular targeting. Remarkable advances have been achieved in the development of metal NHC complexes as anticancer as well as theranostic agents. NHC complexes of gold, platinum and palladium have been designed to elicit potent cancer cell cytotoxicity, effective anti-tumor activities in animal models as well as selective binding to molecular targets (e.g. protein thiols, DNA G-quadraplexes, mismatched DNA). The mechanisms of action of some of these complexes have been elucidated.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Ouro/química , Compostos Heterocíclicos/química , Metano/análogos & derivados , Paládio/química , Platina/química , Animais , Modelos Animais de Doenças , Humanos , Ligantes , Metano/química , Sondas Moleculares/química , Compostos de Sulfidrila/química , Nanomedicina Teranóstica
16.
Br J Pharmacol ; 174(8): 641-656, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28127755

RESUMO

BACKGROUND AND PURPOSE: We and others have shown that inhibiting phosphatase and tensin homolog deleted on chromosome 10 (PTEN) or activating ERK1/2 confer neuroprotection. As bisperoxovanadium compounds are well-established inhibitors of PTEN, we designed bisperoxovandium (pyridin-2-squaramide) [bpV(pis)] and determined whether and how bpV(pis) exerts a neuroprotective effect in cerebral ischaemia-reperfusion injury. EXPERIMENTAL APPROACH: Malachite green-based phosphatase assay was used to measure PTEN activity. A western blot assay was used to measure the phosphorylation level of Akt and ERK1/2 (p-Akt and p-ERK1/2). Oxygen-glucose deprivation (OGD) was used to injure cultured cortical neurons. Cell death and viability were assessed by LDH and MTT assays. To verify the effects of bpV(pis) in vivo, Sprague-Dawley rats were subjected to middle cerebral artery occlusion, and brain infarct volume was measured and neurological function tests performed. KEY RESULTS: bpV(pis) inhibited PTEN activity and increased p-Akt in SH-SY5Y cells but not in PTEN-deleted U251 cells. bpV(pis) also elevated p-ERK1/2 in both SH-SY5Y and U251 cells. These data indicate that bpV(pis) enhances Akt activation through PTEN inhibition but increases ERK1/2 activation independently of PTEN signalling. bpV(pis) prevented OGD-induced neuronal death in vitro and reduced brain infarct volume and promoted functional recovery in stroke animals. This neuroprotective effect of bpV(pis) was blocked by inhibiting Akt and/or ERK1/2. CONCLUSIONS AND IMPLICATIONS: bpV(pis) confers neuroprotection in OGD-induced injury in vitro and in cerebral ischaemia in vivo by suppressing PTEN and activating ERK1/2. Thus, bpV(pis) is a bi-target neuroprotectant that may be developed as a drug candidate for stroke treatment.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fármacos Neuroprotetores/farmacologia , PTEN Fosfo-Hidrolase/metabolismo , Compostos de Vanádio/farmacologia , Animais , Isquemia Encefálica/patologia , Morte Celular/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Glucose/metabolismo , Humanos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Oxigênio/metabolismo , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Compostos de Vanádio/síntese química , Compostos de Vanádio/química
17.
BMC Gastroenterol ; 16(1): 57, 2016 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-27255554

RESUMO

BACKGROUND: Hexokinase-2 (HK2) and Beta2-adrenergic receptor (Beta2AR) are overexpressed in hepatocellular carcinoma (HCC) tissues and associated with poor prognosis. However, the synergistic effect of HK2 and Beta2AR in HCC prognosis is not elucidated. The present study aims to investigate the association between HK2 and Beta2AR expressions in HCC tissues, and to evaluate the synergistic effect of HK2 and Beta2AR in HCC prognosis. METHODS: Immunohistochemistry of HK2 and Beta2AR was performed on 155 paraffin embedded HCC samples retrieved from the archives of pathology department. Corresponding clinical data and prognostic data were collected through searching medical record systems, death registration systems and interviews with patient families. Spearman correlation test was performed to evaluate the association between HK2 and Beta2AR expression. Kaplan-Meier survival curves and Cox regressions were employed to evaluate HK2 and Beta2AR expression in HCC prognosis, respectively and synergistically. RESULTS: 109 of 155 HCC patients reached the death point, the survival time of HCC patients was 46.23 ± 31.01 months after curative surgical resections of HCC. Kaplan-Meier survival analysis showed that large tumor size (more than 5 cm) (hazard ratio (HR) = 8.42, 95 % confidence interval (CI) = 3.81-18.59, P < 0.0001), advanced TNM stage (III and IV stages) (HR = 2.09, 95%CI = 1.21-3.62, P < 0.001) and AFP more than 20 µg/L (HR = 1.49, 95%CI = 1.02-2.18, P = 0.0302) were predictors for poor prognosis. HK2 and Beta2AR positive expression was detected in 66 (42.58) and 122 (78.71 %) HCC samples respectively. In univariate analysis, HK2(+) (HR = 2.70, 95%CI = 1.76-4.15, P < 0.0001) and Beta2AR(+) (HR = 4.61, 96%CI = 3.14-6.76, P < 0.0001) were associated with poor prognosis. In multivariate analysis, HK2(+) (P < 0.0001) and Beta2AR(+) (P < 0.0001) were also associated with poor prognosis. HK2(+)/Beta2AR(+) in HCC samples had poorer prognosis compared with HK2(-)/Beta2AR(-) in both univariate analysis (HR = 4.69, 95%CI = 2.91-7.57, P < 0.0001) and multivariate analysis (P < 0.0001). HK2(+)/Beta2AR(+) in HCC samples had poorer prognosis compared with HK2(-)/Beta2AR(+) in both univariate analysis (HR = 1.76, 95%CI = 1.17-2.64, P = 0.003) and multivariate analysis (P = 0.004). CONCLUSION: HK2 and Beta2AR play important roles in HCC progression. HK2 and Beta2AR expression in HCC is correlated positively. Beta2AR may increase HCC invasion and metastasis in collaboration with HK2. HK2 and Beta2AR can predict HCC prognosis both independently and synergistically.


Assuntos
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/cirurgia , Hexoquinase/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/cirurgia , Receptores Adrenérgicos beta 2/metabolismo , Carcinoma Hepatocelular/mortalidade , Sinergismo Farmacológico , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico
18.
Mol Brain ; 9(1): 59, 2016 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-27230112

RESUMO

BACKGROUND: Glycine is known to protect against neuronal death. However, the underlying mechanism remains to be elucidated. The microRNA-301a is involved in both biological and pathological processes. But it is not known whether microRNA-301a has a neuroprotective property. In this study, we aimed to determine whether glycine-induced neuroprotection requires microRNA-301a-dependent signaling. RESULTS: We provided the first evidence that glycine increased the expression of microRNA-301a in cultured rat cortical neurons and protected against cortical neuronal death through up-regulation of microRNA-301a after oxygen-glucose deprivation. MicroRNA-301a directly bound the predicted 3'UTR target sites of PTEN and reduced PTEN expression in cortical neurons. We revealed that PTEN down-regulation by microRNA-301a mediated glycine-induced neuroprotective effect following oxygen-glucose deprivation. CONCLUSIONS: Our results suggest that 1) microRNA-301a is neuroprotective in oxygen-glucose deprivation-induced neuronal injury; 2) glycine is an upstream regulator of microRNA-301a; 3) glycine confers neuroprotection through microRNA-301a/PTEN signal pathway.


Assuntos
Glicina/farmacologia , MicroRNAs/metabolismo , Neuroproteção/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regiões 3' não Traduzidas/genética , Animais , Sequência de Bases , Córtex Cerebral/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/deficiência , MicroRNAs/genética , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Análise de Sequência com Séries de Oligonucleotídeos , Oxigênio , PTEN Fosfo-Hidrolase/genética , Ratos Sprague-Dawley , Transdução de Sinais/genética
19.
Oncol Lett ; 11(2): 1057-1060, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26893690

RESUMO

Solitary fibrous tumors (SFTs) are uncommon, with the pleura as a site of predilection. Central nervous system SFTs, particularly intracranial SFTs, are extremely rare. The lesions are generally benign and localized, and surgery is the main therapeutic solution. The current study reports the cases of a patient who presented with right haunch pain, right leg weakness and paresthesias for several months, and a patient with a history of unexpected loss of consciousness. Magnetic resonance imaging revealed the presence of lesions, with a spindle cell morphology evident on pathological examination. The immunohistochemical examination demonstrated a strong immunoreaction for cluster of differentiation 34, which supported the diagnosis of an SFT. Following a near-total resection, the patients had a good neural prognosis. The present study also provides a literature review, discussing the imageological and pathological characteristics of SFT, and the diagnostic methods that aid in distinguishing the entity from other spindle-cell central nervous system tumors.

20.
Chemistry ; 21(51): 18534-8, 2015 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-26459298

RESUMO

A dinuclear gold(I) pyrrolidinedithiocarbamato complex (1) with a bidentate carbene ligand has been constructed and shows potent in vitro cytotoxic activities towards cisplatin-resistant ovarian cancer cells A2780cis. Its rigid scaffold enables a zinc(II)-based metal-organic framework (Zn-MOF) to be used as a carrier in facilitating the uptake and release of 1 in solutions. Instead of using a conventional dialysis approach for the drug-release testing, in this study, a set of transwell assay-based experiments have been designed and employed to examine the cytotoxic and antimigratory activities of 1@Zn-MOF towards A2780cis.


Assuntos
Cisplatino/química , Compostos de Ouro/química , Compostos de Ouro/toxicidade , Ouro/química , Neoplasias Ovarianas/química , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Tiocarbamatos/química , Zinco/química , Linhagem Celular , Feminino , Humanos , Ligantes , Estrutura Molecular
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA