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1.
Bioorg Chem ; 142: 106925, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37890213

RESUMO

Thirty new tricyclicmatrinic derivatives were successively synthesized and evaluated for their inhibitory activity on the accumulation of triglycerides (TG) in AML12 cells, using 12 N-m-trifluoromethylbenzenesulfonyl matrine (1) as the hit compound. Among the analogues, compound 7n possessing 11-trimethylbutylamine quaternary exerted the highest in vitro TG-lowering potency, as well as a good safety profile. 7n significantly attenuated the hepatic injury and steatosis, and ameliorated dyslipidemia and dysglycemia in the mice with non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet. Primary mechanism study revealed that upregulation of peroxisome proliferator-activated receptors α (PPARα)-carnitine palmitoyltransferase 1A (CPT1A) pathway mediated the efficacy of 7n. Our study provides powerful information for developing this kind of compound into a new class of anti-NAFLD candidates, and compound 7n is worthy of further investigation as an ideal lead compound.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Matrinas , Triglicerídeos/metabolismo , Fígado/metabolismo , PPAR alfa/metabolismo , Camundongos Endogâmicos C57BL
2.
Vet Res ; 54(1): 86, 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37784173

RESUMO

C-type lectin (CTL) is a protein that binds to saccharides and plays an important role in parasite adhesion, host cell invasion and immune evasion. Previous studies showed that recombinant T. spiralis C-type lectin (rTsCTL) promotes larval invasion of intestinal epithelium cells (IEC), whereas anti-rTsCTL antibodies inhibits larval invasion. Syndecan-1 (SDC-1) is a member of the heparan sulfate proteoglycan family which is mainly expressed on the surface of IEC and in extracellular matrices where they interact with a plethora of ligands. SDC-1 has a principal role in maintaining cell morphogenesis, establishing cell-cell adhesions, and regulating the gut mucosal barrier. The aim of this study was to investigate whether rTsCTL binds to SDC-1 on IEC, and the binding of rTsCTL with SDC-1 promotes larval invasion and its mechanism. IFA results show that rTsCTL and SDC-1 co-localized on Caco-2 cell membrane. GST pull-down and Co-IP verified the direct interaction between rTsCTL and SDC-1 on Caco-2 cells. qPCR and Western blotting revealed that rTsCTL binding to SDC-1 increased the expression of SDC-1 and claudin-2, and reduced the expression of occludin and claudin-1 in Caco-2 cells incubated with rTsCTL via the STAT3 pathway. ß-Xyloside (a syndecan-1 synthesis inhibitor) and Stattic (a STAT3 inhibitor) significantly inhibited rTsCTL binding to syndecan-1 in Caco-2 cells and activation of the STAT3 pathway, abrogated the effects of rTsCTL on the expression of gut tight junctions, and impeded larval invasion. The results demonstrate that binding of rTsCTL to SDC-1 on Caco-2 cells activated the STAT3 pathway, decreased gut tight junction expression, damaged the integrity of the gut epithelial barrier, and mediated T. spiralis invasion of the gut mucosa. TsCTL might be regarded as a candidate vaccine target against T. spiralis invasion and infection.


Assuntos
Trichinella spiralis , Triquinelose , Animais , Camundongos , Humanos , Trichinella spiralis/fisiologia , Triquinelose/parasitologia , Triquinelose/veterinária , Larva/fisiologia , Células CACO-2 , Sindecana-1/genética , Sindecana-1/metabolismo , Mucosa Intestinal/metabolismo , Células Epiteliais/metabolismo , Camundongos Endogâmicos BALB C
3.
Planta Med ; 88(11): 881-890, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34359084

RESUMO

The root Rhynchosia volubilis was widely used for contraception in folk medicine, although its molecular mechanism on antifertility has not yet been revealed. In human sperm, it was reported that the cation channel of sperm, an indispensable cation channel for the fertilization process, could be regulated by various steroid-like compounds in plants. Interestingly, these nonphysiological ligands would also disturb the activation of the cation channel of sperm induced by progesterone. Therefore, this study aimed to explore whether the compounds in R. volubilis affect the physiological regulation of the cation channel of sperm. The bioguided isolation of the whole herb of R. volubilis has resulted in the novel discovery of five new prenylated isoflavonoids, rhynchones A - E (1:  - 5: ), a new natural product, 5'-O-methylphaseolinisoflavan (6: ) (1H and 13C NMR data, Supporting Information), together with twelve known compounds (7:  - 18: ). Their structures were established by extensive spectroscopic analyses and drawing a comparison with literature data, while their absolute configurations were determined by electronic circular dichroism calculations. The experiments of intracellular Ca2+ signals and patch clamping recordings showed that rhynchone A (1: ) significantly reduced cation channel of sperm activation by competing with progesterone. In conclusion, our findings indicat that rhynchone A might act as a contraceptive compound by impairing the activation of the cation channel of sperm and thus prevent fertilization.


Assuntos
Progesterona , Motilidade dos Espermatozoides , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Sinalização do Cálcio , Humanos , Masculino , Progesterona/análise , Progesterona/metabolismo , Progesterona/farmacologia , Sementes , Espermatozoides/química , Espermatozoides/metabolismo
4.
Bioorg Chem ; 117: 105432, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34678602

RESUMO

Twenty-nine 12 N-substituted aloperine derivatives were synthesized and screened for suppression on PD-L1 expression in H460 cells, as a continuation of our work. Systematic structural modifications led to the identification of compound 6b as the most active PD-L1 modulator. Compound 6b could significantly down-regulate both constitutive and inductive PD-L1 expression in NSCLC cells, and successively enhance the cytotoxicity of co-cultured T cells against tumor cells at the concentration of 20 µM. Also, it exhibited a moderate in vivo anticancer efficacy against Lewis tumor xenograft with a stable PK and safety profile. The mechanism study indicated that 6b mediated the degradation of PD-L1 through a proteasome pathway, rather than a lysosome route. These results provided the powerful information for cancer immunotherapy of aloperine derivatives with unique endocyclic skeleton by targeting PD-L1 to activate immune cells to kill cancer cells.


Assuntos
Antineoplásicos/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Regulação para Baixo/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/farmacologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Quinolizidinas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Inibidores de Checkpoint Imunológico/síntese química , Inibidores de Checkpoint Imunológico/química , Camundongos , Camundongos Endogâmicos , Estrutura Molecular , Quinolizidinas/síntese química , Quinolizidinas/química , Relação Estrutura-Atividade
5.
J Org Chem ; 84(2): 536-543, 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30562029

RESUMO

Copper-catalyzed intermolecular annulation of 2-amine-[1,3,5]triazines and aryl nitriles for the synthesis of [1,2,4]triazolo[1,5- a][1,3,5]triazines via N-C bond formation and oxidative N-N coupling [oxidative 3 + 2 cyclization] is presented. A wide range of aryl nitriles, including electron-rich benzonitriles, electron-poor benzonitriles, 2-cyanothiophene, and 4-cyanopyridine, were all functionalized with 2-amine-[1,3,5]triazines. Furthermore, amidation of 2-amine-[1,3,5]triazines via Cu-catalyzed C-CN bond cleavage of phenylacetonitriles is also demonstrated. The reaction occurred in moderate to satisfactory yields and tolerated alkyl- or aryl-substituted 2-amine-[1,3,5]triazines. Aniline, aminopyridine, and aminopyrimidine also afforded the desired products.

6.
BMC Cancer ; 14: 28, 2014 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-24433541

RESUMO

BACKGROUND: Distal esophageal adenocarcinoma is a highly aggressive neoplasm. Despite advances in diagnosis and therapy, the prognosis is still poor. Stathmin (STMN-1) is a ubiquitously expressed microtubule destabilizing phosphoprotein. It promotes the disassembly of microtubules and prevents assembly. STMN-1 can cause uncontrolled cell proliferation when mutated and not functioning properly. Recently, found to be overexpressed in many types of human cancers. However, its clinical significance remains elusive in distal esophageal adenocarcinoma. Here, we reported for the first time that STMN-1 is highly overexpressed in adenocarcinomas of the distal esophagus and strongly associated with lymph node metastasis. METHODS: STMN-1 expression in 63 cases of distal esophageal adenocarcinoma was analyzed by immunoblotting, while expression in esophageal adenocarcinoma cells was determined by immunocytochemistry, immunofluorescence, qRT-PCR and western blotting. Lentivirus-mediated RNAi was employed to knock-down STMN-1 expression in Human esophageal adenocarcinoma cells. The relationship between STMN-1 expression and lymph node metastasis in distal esophageal adenocarcinoma was determined by univariate and multivariate analyses. RESULTS: STMN-1 was detected in 31 (49.21%) of the 63 cases. STMN-1 was highly overexpressed in specimens with lymph node metastasis pN (+), but its expression was almost undetected in pN (-) status. Multivarian regression analysis demonstrated that STMN-1 overexpression is an independent factor for lymph node metastasis in distal esophageal adenocarcinoma. STMN-1 shRNA effectively reduced STMN-1 expression in esophageal adenocarcinoma cells (P < 0.05), which significantly suppressed proliferation (P < 0.05), increased migration (P < 0.05) and invasion ability (P < 0.05) and G1 phase arrest (P < 0.05) which lead to induction of apoptosis in esophageal adenocarcinoma cells in vitro. To verify the in vitro data, we conducted in vivo tumor xenograft studies. Esophageal adenocarcinoma cells stably transfected with STMN-1 shRNA significantly reduced tumor xenografts volume in vivo. CONCLUSIONS: STMN-1 overexpression is associated with lymph node metastasis and increase malignancy in distal esophageal adenocarcinoma. In vivo and in vitro laboratory findings, suggests that STMN-1 may be a suitable target for future therapeutic strategies in distal esophageal adenocarcinoma.


Assuntos
Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/metabolismo , Interferência de RNA , Estatmina/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/secundário , Adenocarcinoma/terapia , Adulto , Apoptose , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular , Humanos , Modelos Logísticos , Metástase Linfática , Masculino , Análise Multivariada , Invasividade Neoplásica , Fenótipo , Estatmina/genética , Fatores de Tempo , Transfecção , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Biomarkers ; 19(1): 81-5, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24410190

RESUMO

The purpose of the study was to explore the significance of FGFR4 protein expression in colorectal cancer. Immunohistochemistry showed 46.8% (148/316) tumors positive for FGFR4 and 7.3% (23/316) for adjacent normal specimens. FGFR4 positivity was correlated with shortened disease free survival (DFS) and overall survival (OS). Multivariate analysis revealed that FGFR4 was an independent prognostic factor. FGFR4 silencing markedly reduced the migration and invasion capacity of colorectal cancer cell lines. These results suggest FGFR4 is a potential prognostic and therapeutic marker for colorectal cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Idoso , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/mortalidade , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética
8.
J Huazhong Univ Sci Technolog Med Sci ; 33(1): 90-95, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23392714

RESUMO

The expression and implication of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in residual hepatic tumor cells after lipiodol embolization were investigated. Two weeks after transplantation of VX2 tumor cells into the livers of rabbits, a xenograft model of the human hepatic neoplasm was successfully established. Forty rabbits were randomly divided into control group (n=20) and lipiodol group (n=20). For the control group, 1 mL normal saline was injected through the gastroduodenal artery, whereas 0.3 mL/kg lipiodol was applied for the lipiodol group. One week after embolization, the expression level of VEGF in the plasma was measured by using enzyme-linked immunosorbent assay (ELISA). A three-step immunohistochemical technique (ABC) was employed to detect the protein levels of VEGF and MMP-9 and the quantitative PCR for their mRNA levels was performed in the residual tumor cells. The VEGF in the plasma was significantly higher in the lipiodol group (1.42±0.29 ng/mL) than in the control group (1.12±0.21 ng/mL) (P<0.01). Moreover, the positive rate of VEGF protein in the residual tumor cells was significantly higher in the lipiodol group (62.13%±7.69%) than in the control group (53.16%±9.17%) (P<0.05). Similarly, the MMP-9 expression in the residual tumor cells was higher in the lipiodol group. The mRNA levels of VEGF (2.9313±2.4231) and MMP-9 (3.5721±1.6107) in the lipiodol group were significantly higher than those in the control group (1.5728±0.9453 and 1.7573±1.0641, respectively, P<0.05). Therefore, it was reasonable to speculate that the increased expression of VEGF and MMP-9 in residual hepatic tumor cells and tumor angiogenesis post-embolization would be responsible for the increased metastatic potentiality and invasiveness of these cells.


Assuntos
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/terapia , Óleo Etiodado/uso terapêutico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Metaloproteinase 9 da Matriz/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Linhagem Celular Tumoral , Embolização Terapêutica/métodos , Hemostáticos/uso terapêutico , Neoplasia Residual/metabolismo , Coelhos , Resultado do Tratamento , Regulação para Cima/efeitos dos fármacos
9.
Water Res ; 211: 118037, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35026550

RESUMO

The increasing requirement for reclaimed water has made it necessary to utilize multiple disinfection processes for efficient removal of organoleptic indicators, while guaranteeing microbial safety. However, there is not a proper way to appropriately distribute the operation load between different disinfection units. This study provides a new method to optimize doses of sequential ozonation, ultraviolet (UV) irradiation and chlorine disinfection units, and investigates the synergistic effects of combined disinfection on the basis of pilot tests. In this method, the minimal ozone dose is determined first for the removal of colority. The chlorine dose is then adjusted according to the required residual chlorine. At last, since it has few side effects and relatively low operating costs, UV dose is determined by the remaining requirement of microbial indicator reduction. By this method, the effluent of disinfection could meet the discharge standards of colority, residual chlorine, and microbial indicators. The operating cost was reduced by 48.7%, mainly by lowering the ozone dosage. The production of disinfection by-products (DBPs) was effectively controlled by decreasing the chlorine dosage compared with the original working conditions in the plant. Moreover, ozone pretreatment effectively improved the coliform inactivation efficiency of chlorine, and the combined disinfection method alleviated the tailing phenomenon and achieved a higher maximum log reduction of coliforms. The proposed method can help water reclamation plants reasonably determine operational loads between disinfection units with low cost and guaranteed performance.


Assuntos
Desinfetantes , Ozônio , Purificação da Água , Cloro , Desinfecção , Raios Ultravioleta
10.
Environ Pollut ; 285: 117257, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33957510

RESUMO

Reusing treated wastewater can effectively alleviate water shortages and water contamination problems but depends on ensuring the safety of the reclaimed water that is produced. The operating and management conditions for water reclamation plants in China have been changed since the outbreak of the COVID-19 epidemic in China at the end of 2019 to prevent emerging viruses being spread through wastewater treatment processes and the reclaimed water that is produced. Removal of pathogens and trace organic compounds (e.g., pharmaceuticals and personal care products and endocrine disrupting chemicals) in a real water reclamation plant after the start of COVID-19 epidemic was studied. Disinfection byproduct formation caused by chlorine being added to meet disinfection requirements was also assessed. The pathogenic microorganism concentrations in effluent were <2 (most probable number)/L, and the removal rates for most trace organic compounds were >80% when advanced treatments were performed using ozone, ultraviolet light, and chlorine doses of 2 mg/L, 20.5 mJ/cm2, and 2-3 mg/L, respectively. The main disinfection byproduct produced at a chlorine dose of 2 mg/L and a residence time of 1 h was chloroform (at concentrations <15 µg/L). The results indicated that the water reclamation processes with modified conditions gave high pathogen and trace organic compound removal rates and reasonably well-controlled disinfection byproduct concentrations.


Assuntos
COVID-19 , Poluentes Químicos da Água , Purificação da Água , Cloro , Desinfecção , Humanos , SARS-CoV-2 , Águas Residuárias , Água , Poluentes Químicos da Água/análise
11.
Spine (Phila Pa 1976) ; 44(7): 494-502, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30234809

RESUMO

STUDY DESIGN: An Internet-based assessment of websites using recognized score systems. OBJECTIVE: To assess the quality, content, and readability of online information for failed back spinal surgery (FBSS). SUMMARY OF BACKGROUND DATA: A significant amount of patients still suffer from chronic or recurrent back pain with or without radicular symptoms after spinal surgery. More and more patients use the Internet to find health-related information. Low-quality or inaccurate information may not only misleading patients but also have a negative impact on the trust between patients and physicians. METHODS: The terms "chronic pain after spinal surgery," "chronic pain after back surgery," "failed back surgery syndrome," "post spinal surgery syndrome," and "post laminectomy syndrome" were entered into three search engines (Google, Yahoo!, and Bing). The first 25 websites from each search were reviewed. The quality, content, and readability of each website were evaluated using DISCERN score, FBSS-specific content score, and the Journal of the American Medical Association (JAMA) benchmark criteria, the first two score systems were assessed by three reviewers independently. The Flesch-Kincaid grade level (FKGL) was used to assess the readability. Each website with or without the Health on the Net Code (HONcode) was also recorded. RESULTS: Seventy-two websites were analyzed in our study. The average DISCERN score for all websites was 35.26 ±â€Š11.45, indicating the quality of the websites was poor. The DISCERN score of physician websites was 31.25 ±â€Š9.08, lower than that of media (36.50 ±â€Š0.71, P = 0.017) and commercial websites (42.55 ±â€Š10.93, P = 0.045). The mean FBSS-specific content score was 9.58 ±â€Š3.90 out of maximum 25. We failed to find any difference of FBSS-specific content score among different type of website. Websites with HONcode certification were associated with higher DISCERN score, FBSS-specific content score, and JAMA benchmark criteria score than non-certified websites. The mean FKGL was 12.19 ±â€Š2.20, and none of the websites' FKGL was lower than the six grade level. CONCLUSION: The quality and content of available online information for FBSS were poor. The readability of online information in our results showed a significantly higher reading level than the sixth-grade level recommended by the AMA and NIH. LEVEL OF EVIDENCE: 4.


Assuntos
Dor nas Costas/etiologia , Dor Crônica/etiologia , Compreensão , Informação de Saúde ao Consumidor/normas , Internet , Coluna Vertebral/cirurgia , Humanos , Dor Pós-Operatória/etiologia , Leitura , Falha de Tratamento
12.
Huan Jing Ke Xue ; 38(12): 5333-5343, 2017 Dec 08.
Artigo em Zh | MEDLINE | ID: mdl-29964598

RESUMO

Based on the winter wheat-summer maize rotation field experiment, the effects of biochar and organic fertilizer on saline-alkali soil N2O emissions in the summer maize season were studied in Binzhou in the Shandong Province to provide a theoretical basis for reducing N2O emissions from saline-alkali soil. The experiment includes six treatments with three replications:CK[N:0.2 t·(hm2·a)-1, P2O5:0.12 t·(hm2·a)-1, K2O:0.2 t·(hm2·a)-1], C1[5 t·(hm2·a)-1biochar], C2[10 t·(hm2·a)-1 biochar], C3[20 t·(hm2·a)-1 biochar], M1[7.5 t·(hm2·a)-1 organic fertilizer], and M2[10 t·(hm2·a)-1 organic fertilizer]. The same nitrogen, phosphorus, and potassium fertilizer was applied for each treatment. The results showed that the dynamic trend of the soil N2O fluxes among different treatments were similar. The peak N2O emissions occurred after fertilization (base fertilizer and topdressing). The N2O cumulative emission fluxes accounted for nearly half of the emissions during the whole growth period, and the N2O emissions of the C1, C2, and C3 treatments were lower than that of CK after fertilization. Compared with CK, the N2O cumulative emissions from C1 and C2 were reduced by 45.3% and 31.6%, respectively, but C3, M1, and M2 increased by 17.3%, 37.4%, and 27.6%, respectively. Biochar and organic fertilizer both affected N2O emission fluxes. Applying biochar can reduce N2O emissions, while organic fertilizer can increase N2O emissions. In summary, biochar has a great advantage in reducing N2O emissions in the farmland.


Assuntos
Carvão Vegetal , Fertilizantes , Óxido Nitroso/análise , Solo/química , Agricultura , Álcalis , China , Salinidade , Triticum , Zea mays
13.
Oncol Lett ; 14(6): 7759-7766, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29344221

RESUMO

Livin is a novel member of the inhibitor of apoptosis protein family, which has been identified to be expressed in various malignancies and is suggested to be associated with poor prognostic significance. However, no data are available concerning the significance of livin in mid-distal rectal cancer. In the present study, livin expression, and its association with clinicopathological characteristics and prognosis was examined in patients with mid-distal rectal cancer. Apoptotic susceptibility, invasion capacity and chemosensitivity of LoVo cells were investigated using small interfering RNA (siRNA)-mediated knockdown of livin. It was revealed that livin was highly expressed in mid-distal rectal cancer tissues compared with the normal rectal mucosal tissues. Livin expression was associated with pathological grade, extent of invasion (T stage) and extent of lymph node metastasis (N stage) of tumor, contributing to poor prognosis of mid-distal rectal cancer following surgery. The data suggest that aggressive surgery should be applied in patients with mid-distal rectal cancer with high expression of livin. It was also revealed that knockdown of livin by siRNA increased the apoptotic rate, suppressed invasion of LoVo cells, and decreased the half-maximal inhibitory concentration of oxaliplatin and 5-fluorouracil by ~50% in LoVo cells significantly compared with control groups. The data suggested that a combination of downregulation of livin and anticancer drugs may significantly decrease the toxicity of anticancer drugs. Taken together, the present study indicated that livin may be a promising target in clinical therapy of mid-distal rectal cancer.

14.
World J Gastroenterol ; 21(17): 5220-30, 2015 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-25954095

RESUMO

Gastric cancer is the second leading cause of cancer-related deaths. Metastasis, which is an important element of gastric cancer, leads to a high mortality rate and to a poor prognosis. Gastric cancer metastasis has a complex progression that involves multiple biological processes. The comprehensive mechanisms of metastasis remain unclear, though traditional regulation modulates the molecular functions associated with metastasis. Long non-coding RNAs (lncRNAs) have a role in different gene regulatory pathways by epigenetic modification and by transcriptional and post-transcription regulation. lncRNAs participate in various diseases, including Alzheimer's disease, cardiovascular disease, and cancer. The altered expressions of certain lncRNAs are linked to gastric cancer metastasis and invasion, as with tumor suppressor genes or oncogenes. Studies have partly elucidated the roles of lncRNAs as biomarkers and in therapies, as well as their gene regulatory mechanisms. However, comprehensive knowledge regarding the functional mechanisms of gene regulation in metastatic gastric cancer remains scarce. To provide a theoretical basis for therapeutic intervention in metastatic gastric cancer, we reviewed the functions of lncRNAs and their regulatory roles in gastric cancer metastasis.


Assuntos
Biomarcadores Tumorais/genética , Movimento Celular , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Animais , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
15.
Neurosci Lett ; 579: 24-9, 2014 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-25017825

RESUMO

Astrocytes become activated in response to central nervous system (CNS) injury, and excessive astrogliosis is considered an impediment to axonal regeneration by forming glial scar. Mitofusin 2 (Mfn2), a key protein in mitochondrial network, has been reported to negatively regulate cell proliferation. The present study aimed to explore whether reactive astrogliosis could be suppressed by Mfn2 overexpression. Scratch injury and starvation-serum stimulation models in cultured astrocytes were combined to address this issue. In scratch model, reactive proliferation status of damaged astrocytes was implicated by migration of high ratio of EdU(+) cells into lesion region and significantly increased expression of GFAP and PCNA. At meantime, Mfn2 expression was found to exert a down-regulated trend both in gen and protein levels. Pretreatment of cells with adenoviral vector encoding Mfn2 gene increased Mfn2 expression and subsequently attenuated injury-induced astrocytes hyperplasia, activation-relevant protein synthesis, cellular proliferation, eventually delayed wound healing process. Furthermore, Mfn2 overexpression markedly inhibited astrocytes proliferation induced by serum stimulation, by arresting the transition of cell cycle from G1 to S phase. Together, these in vitro results demonstrated that reactive astrogliosis can be effectively suppressed by up-regulation of Mfn2, which might contribute to a promising therapeutic intervention in CNS disease characterized by glia-related damage.


Assuntos
Astrócitos/metabolismo , Gliose/metabolismo , Proteínas de Membrana/biossíntese , Proteínas Mitocondriais/biossíntese , Animais , Animais Recém-Nascidos , Astrócitos/patologia , Ciclo Celular/fisiologia , Proliferação de Células , Células Cultivadas , GTP Fosfo-Hidrolases , Gliose/patologia , Ratos , Ratos Sprague-Dawley , Soro , Cicatrização
16.
Chin Med J (Engl) ; 126(16): 3057-63, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23981612

RESUMO

BACKGROUND: Heme oxygenase-1 (HO-1) can be induced by inflammatory cytokines, oxidation, ischemia, hypoxia, and endotoxins. As a "graft survival protective gene," HO-1 is a hot spot in organ transplantation research. However, the role of HO-1 gene expression in the function of human colon adenocarcinoma cell line (Caco-2) cells has not been reported previously. METHODS: The role of HO-1 in the proliferation and migration of Caco-2 cells was analyzed using a stable HO-1 expression plasmid. We constructed a recombinant adeno-associated virus plasmid containing the HO-1 gene, heme oxygenase 1 (HMOX1), which was transfected into Caco-2 intestinal cells. We identified a number of target genes by global microarray analysis combined with real-time polymerase chain reaction (PCR) and chromatin immunoprecipitation assay. RESULTS: Our results showed that significant HO-1 upregulation was demonstrated in the Caco-2 cells after HO-1 transfection. Restoration of HO-1 expression promoted proliferation and invasion in vitro. The CTNND1 gene, a member of the armadillo protein family, was identified as a direct HO-1 target gene. CONCLUSION: Overexpression of HO-1 promotes Caco-2 cell proliferation and migration by targeting the CTNND1 gene.


Assuntos
Cateninas/genética , Movimento Celular , Proliferação de Células , Heme Oxigenase-1/fisiologia , Células CACO-2 , Regulação Neoplásica da Expressão Gênica , Heme Oxigenase-1/genética , Humanos , Reação em Cadeia da Polimerase em Tempo Real , delta Catenina
17.
Chin Med J (Engl) ; 126(4): 640-5, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23422181

RESUMO

BACKGROUND: T-lymphoma and metastasis gene 1 (Tiam1) produces a guanine nucleotide exchange factor (GNEF) that regulates guanosine triphosphatase, which transforms guanosine diphosphate to guanosine triphosphate. Recently published data indicate that Tiam1 was associated with gastric cancer. The aim of this study was to investigate biological effects and potential mechanisms of Tiam1 in gastric carcinoma. METHODS: We analyzed the expression of Tiam1 in 114 pair-matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time PCR. We investigated Tiam1 expression and its prognostic value for gastric cancer. Furthermore, the functions of Tiam1 over-expression were analyzed with stable-expression Tiam1 plasmid in human gastric cancer cell lines. RESULTS: Tiam1 expression was significantly associated with cell differentiation and lymphatic metastasis; expression of Tiam1 mRNA was up-regulated in gastric cancer compared to pair-matched adjacent non-tumor tissues. Analyses of surgical tissue samples and 5-year survival of gastric cancer patients showed that those with strong Tiam1 expression had significantly shorter overall survival time than those with negative Tiam1 expression. Ectopic expression of Tiam1 promoted cell growth, migration and invasion of gastric cancer cells in vitro. CONCLUSIONS: In gastric cancer cells, Tiam1 affects multiple properties associated with acquisition of the metastatic phenotype, and may be a marker of gastric cancer progression and metastasis in a subset of cancer.


Assuntos
Fatores de Troca do Nucleotídeo Guanina/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular/fisiologia , Proliferação de Células , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Metástase Neoplásica/genética , Neoplasias Gástricas/genética , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T
18.
World J Gastroenterol ; 17(14): 1895-902, 2011 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-21528065

RESUMO

AIM: To evaluate the biological and clinical characteristics of miR-622 in gastric cancer. METHODS: We analyzed the expression of miR-622 in 57 pair matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time polymerase chain reaction. Functional analysis of miR-622 expression was assessed in vitro in gastric cancer cell lines with miR-622 precursor and inhibitor. The roles of miR-622 in tumorigenesis and tumor metastasis were analyzed using a stable miR-622 expression plasmid in nude mice. A luciferase reporter assay was used to assess the effect of miR-622 on inhibitor of growth family, member 1 (ING1) expression. RESULTS: Expression of miR-622 was down-regulated in gastric cancer. MiR-622 was found involved in differentiation and lymphatic metastasis in human gastric cancer. Ectopic expression of miR-622 promoted invasion, tumorigenesis and metastasis of gastric cancer cells both in vitro and in vivo. ING1 is a direct target of miR-622. CONCLUSION: These findings help clarify the molecular mechanisms involved in gastric cancer metastasis and indicate that miR-622 modulation may be a bona fide treatment of gastric cancer.


Assuntos
Regulação para Baixo , Peptídeos e Proteínas de Sinalização Intracelular/genética , MicroRNAs/metabolismo , Invasividade Neoplásica , Proteínas Nucleares/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Proteínas Supressoras de Tumor/genética , Idoso , Animais , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteína 1 Inibidora do Crescimento , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Metástase Neoplásica , Transplante de Neoplasias
19.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 42(8): 501-4, 2007 Aug.
Artigo em Zh | MEDLINE | ID: mdl-18001597

RESUMO

OBJECTIVE: To investigate the variation of the corrosion resistance of micro-arc oxidation film on titanium by electrochemical methods in simulated body fluid. METHODS: Micro-arc oxidation film was formed on the titanium surface using micro-arc oxidation. The morphology was observed with scanning electron microscopy (SEM) and the phase composition was analyzed using X-ray diffraction (XRD). Polarization curves and electrochemical impedance spectroscopy (EIS) in simulated body fluid were examined with electrochemical methods. RESULTS: On the titanium surface with micro-arc oxidation, the film consisted of many volcanic micropores. The film formed was a titanium dioxide (TiO(2)) with peaks for both anatase and rutile phases. In addition, hydroxylapatite was also observed. The self-corrosion potential and self-corrosion current density of titanium with micro-arc oxidation film were -0.255 V and 0.80 microA/cm(2) respectively, while those of untreated titanium were -0.358 V and 0.55 microA/cm(2). Electrochemical impedance spectroscopy confirmed the model of equivalent circuits reasonable. CONCLUSIONS: The results of electrochemical examinations indicate that micro-arc oxidation film increases the corrosion resistance of titanium.


Assuntos
Titânio/química , Corrosão , Durapatita/síntese química , Eletroquímica , Oxirredução
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