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Introduction: Observational studies have found a correlation between the consumption of tobacco and alcohol and the likelihood of developing renal cell carcinoma. However, whether these associations indicate causal relationships is unclear. Methods: To establish if these connections indicate causal relationships, we performed a Mendelian Randomization (MR) analysis using a two-sample approach. For the number of daily cigarettes, lifetime smoking index, smoking initiation, and weekly drinking, we employed 44, 108, 174, and 76 single nucleotide polymorphisms (SNPs) as instrumental variables. Outcome data were obtained from the FinnGen Alliance, which included a combined total of 429,290 individuals. The MR analysis was conducted using the inverse-variance weighted (IVW) method to estimate causal effects. To address potential violations of MR assumptions due to directional pleiotropy, we performed MR-Egger regression and MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) analysis. Results: Genetically influenced smoking initiation was directly associated with the risk of developing renal cell carcinoma (OR = 1.55, 95% CI: 1.04-2.33; p = 0.03). No causal relationship was found between daily cigarette consumption and lifetime smoking index with the risk of renal cell cancer. Genetic predisposition for weekly alcohol consumption showed a reduced risk of renal cell cancer (OR = 0.45, 95% CI: 0.26-0.81; p = 0.007). Discussion: Our study suggests a potential causal relationship between alcohol consumption and reduced risk of renal cell cancer, while no such association was observed with smoking. Further research is needed to confirm these findings.
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This study aimed to investigate the potential of autophagy-related genes (ATGs) as a prognostic signature for HCC and explore their relationships with immune cells and immune checkpoint molecules. A total of 483 samples were collected from the GEO database (n = 115) and The Cancer Genome Atlas (TCGA) database (n = 368). The GEO dataset was used as the training set, while the TCGA dataset was used for validation. The list of ATGs was obtained from the human autophagy database (HADB). Using Cox regression and LASSO regression methods, a prognostic signature based on ATGs was established. The independent use of this prognostic signature was tested through subgroup analysis. Additionally, the predictive value of this signature for immune-related profiles was explored. Following selection through univariate Cox regression analysis and iterative LASSO Cox analysis, a total of 11 ATGs were used in the GEO dataset to establish a prognostic signature that stratified patients into high- and low-risk groups based on survival. The robustness of this prognostic signature was validated using an external dataset. This signature remained a prognostic factor even in subgroups with different clinical features. Analysis of immune profiles revealed that patients in the high-risk group exhibited immunosuppressive states characterized by lower immune scores and ESTIMATE scores, greater tumour purity, and increased expression of immune checkpoint molecules. Furthermore, this signature was found to be correlated with the infiltration of different immune cell subpopulations. The results suggest that the ATG-based signature can be utilized to evaluate the prognosis of HCC patients and predict the immune status within the tumour microenvironment (TME). However, it is important to note that this study represents a preliminary attempt to use ATGs as prognostic indicators for HCC, and further validation is necessary to determine the predictive power of this signature.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Proteínas de Checkpoint Imunológico , Prognóstico , Autofagia , Microambiente TumoralRESUMO
The incidence of pancreatic duct stones (PDS) is less than 1%. After the formation of stones, the lumen of the pancreatic duct is blocked, and the pancreatic juice cannot be discharged smoothly, resulting in the impairment of the internal and external secretions of the pancreas. Several national guidelines now recommend endoscopic retrograde cholangiopancreatography (ERCP) as the treatment for PDS. The emergence of SpyGlass makes it possible to visualize the ERCP blind area of the pancreatic system directly. Electrohydraulic lithotripsy (EHL) under SpyGlass can crush large and pressure-resistant stones into smaller fragments, significantly improving the success of the endoscopic treatment of large stones. Here, we report a patient presented with acute alcohol-associated pancreatitis, found to have PDS on imaging, who underwent ERCP combined with SpyGlass (EHL), avoiding surgery, reducing trauma, and being discharged from the hospital with a rapid recovery. Therefore, endoscopic therapy is effective and safe for PDS patients. The combination therapy of this patient is the first use of SpyGlass for PDS in our centre, which marks a new stage in the application of endoscopic therapy for pancreatic diseases.
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OBJECTIVE: To explore the effect of phytic acid on the human osteosarcoma U20S cells and its mechanisms in vitro. METHODS: MTT assay was used to examine the cell proliferation. Scanning electron microscope (SEM) was used to observe the surface ultrastructure of U20S cells. Hoechst 33342 fluorescence staining assay were applied to study the pro-apoptosis effects. The immune histochemisty method was used to detect c-myc expression. RESULTS: Phytic acid could significantly inhibit the growth of U20S. The surface ultrastructure of U20S cells showed distinct morphological changes corresponding to a typical cellular surface morphology of apoptosis. From fluorescence staining, we observed chromoplasm pyknosis and apoptotic body. Expression of c-myc protein decreased. CONCLUSION: The anti-osteosarcoma mechanism of phytic acid may be related to its influence on inducing apoptosis and adjusting c-myc expression.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/patologia , Osteossarcoma/patologia , Ácido Fítico/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Proteínas Proto-Oncogênicas c-myc/efeitos dos fármacosRESUMO
Selective inhibition of GluN2B-containing NMDA receptor (GluN2BR) in spinal dorsal horn effectively alleviates inflammatory pain, suggesting the up-regulation of GluN2BR function involved in central sensitization. Previous studies have demonstrated that the increase in GluN2BR synaptic expression serves as a key step to enhance GluN2BR function after intradermal injection of Complete Freund's Adjuvant (CFA). Here, we showed that cAMP-dependent protein kinase (PKA) played an important role in redistributing GluN2BR at synapses, because inhibition of PKA activity impaired GluN2BR accumulation at post-synaptic density (PSD)-enriched fraction in CFA-injected mice, and direct stimulation of PKA in naïve mice mimicked the effect of CFA by recruiting GluN2BR at PSD fraction to evoke pain sensitization. Analysis of PKA-initiated signalings unraveled that PKA was able to activate Src-family protein tyrosine kinases member Fyn, possibly by disrupting Fyn association with its inhibitory partner striatal-enriched protein tyrosine phosphatase 61. The active Fyn then promoted GluN2B phosphorylation at Tyr1472, a molecular event known to prevent GluN2BR endocytosis. As a result, pharmacological or genetic manipulation of Fyn activity greatly depressed GluN2BR accumulation at PSD-enriched fraction and ameliorated mechanical allodynia induced by PKA. Our data thus elucidated a critical role of PKA/Fyn/GluN2B signaling in triggering GluN2BR hyperfunction and pain hypersensitivity.
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Proteínas Quinases Dependentes de AMP Cíclico/fisiologia , Dor/metabolismo , Células do Corno Posterior/metabolismo , Proteínas Proto-Oncogênicas c-fyn/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Animais , Ativação Enzimática/fisiologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dor/enzimologia , Ratos , Ratos Sprague-Dawley , Medula Espinal/enzimologia , Medula Espinal/metabolismoRESUMO
OBJECTIVE: To explore the growth inhibition and apoptosis-inducing effects of phytic acid in human gastric cancer SGC-7901 cells. METHODS: The growth inhibition action of phytic acid on SGC-7901 cells was examined by MTT assay. AO/EB fluorescence staining and DNA ladder assay were applied to study the proapoptosis effects of phytic acid. The expression of apoptosis relative proteins, P53, were analyzed by using immune histochemisty method. RESULTS: Phytic acid treatment significantly inhibited the growth of human gastric cancer cell SGC-7901 and markedly caused their apoptosis following downregulation of P53 protein expression. CONCLUSION: The downregulation of apoptosis relative protein P53 expression was the possible mechanism of phytic acid induced growth inhibition and apoptosis in SGC-7901 cells.
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Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ácido Fítico/farmacologia , Neoplasias Gástricas/patologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Humanos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND/AIMS: The primary objective of this study was to further determine the mechanisms by which isoflavone prevents obesity induced by ovariectomy. METHODS: Female 8-week-old Wistar rats were randomly assigned to 6 groups: a sham-operated group; an ovariectomized (OVX) control group; 3 OVX groups orally administered 400 ppm (L-SI), 1,200 ppm (M-SI) and 3,600 ppm (H-SI) of an isoflavone preparation, respectively, and an OVX group receiving 0.45 ppm of diethylstilbestrol. All animals were allowed free access to a high-fat diet and water for 4 weeks. Some neuropeptides, including ghrelin, neuropeptide Y (NPY), alpha-melanocyte-stimulating hormone (alpha-MSH), cholecystokinin (CCK), peptide YY (PYY), insulin and estradiol (E2), were measured by radioimmunoassay. RESULTS: Compared with the OVX control group, body weight, total abdominal fat, food intake and food availability of the M-SI and H-SI groups were significantly reduced. The results also showed that isoflavone and diethylstilbestrol could decrease ghrelin and NPY levels and increase CCK, PYY and E2 levels. The level of alpha-MSH was not changed. CONCLUSIONS: These findings showed that isoflavone could reduce obesity by decreasing food intake, possibly by (1) reducing ghrelin and NPY levels, thereby decreasing food intake, and (2) increasing CCK and PYY levels, which can induce satiety by irritating the vagal center.
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Peso Corporal , Dieta , Ingestão de Alimentos , Glycine max/química , Isoflavonas/administração & dosagem , Ovariectomia , Tecido Adiposo , Análise de Variância , Animais , Gorduras na Dieta/administração & dosagem , Dietilestilbestrol/administração & dosagem , Dietilestilbestrol/metabolismo , Metabolismo Energético/fisiologia , Estradiol/sangue , Feminino , Isoflavonas/metabolismo , Neuropeptídeos/sangue , Obesidade/prevenção & controle , Tamanho do Órgão , Hormônios Peptídicos/sangue , Distribuição Aleatória , Ratos , Ratos Wistar , Magreza , ÚteroRESUMO
Beta-sitosterol is an important phytosterol found in plant food. It has been shown to have antiproliferative effects on cancers of the colon, breast, and prostate, but its effect on stomach cancer cells in vitro is unknown. Proliferation, cytotoxicity, and apoptosis in SGC-7901 human stomach cancer cells were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, clone formation, lactate dehydrogenase (LDH) leakage assay, acridine orange (AO)/ethidium bromide (EB) double staining, 4',6-diamidine-2'-phenylindole dihydrochloride (DAPI) staining, comet assay, and Western blotting. The results showed that beta-sitosterol suppresses the proliferation and induces the cell cytotoxicity of SGC-7901 stomach cancer cells in a time- and dose-dependent manner. Cells treated with different concentrations of beta-sitosterol also showed changes typical of apoptosis: morphological changes, DNA damage, increased expression of pro-caspase-3 and bax (p < 0.05), and activation of pro-caspase-3 and suppression of bcl-2 expression (p < 0.05). This study therefore revealed that beta-sitosterol significantly inhibits the growth and induces the apoptosis of SGC-7901 human stomach cancer cells in vitro. The decrease of the bcl-2/bax ratio and DNA damage may be the critical mechanisms of apoptosis induced by beta-sitosterol in SGC-7901 human stomach cancer cells.
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Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Sitosteroides/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Gástricas/fisiopatologiaRESUMO
OBJECTIVE: To explore the bcl-2 and the bax protein expression, the effect and possible mechanism of phytic acid (IP6) on cell proliferation in human gastric carcinoma. METHODS: The inhibiting action of IP6 on human gastric carcinoma was examed by MTT assay. The morphological changes of SGC-7901 cells exposed to IP6 was examined by reverse discrepancy microscope. The apoptosis of SGC-7901 cells treated with IP6 was observed by single cell gel electrophoresis. The bax and bcl-2 protein expressions were detected by Western blotting method. RESULTS: MTT assay indicated that the growth of SGC-7901 cells were inhibited by IP6 in dose and time dependent manners. The morphological observation by reverse discrepancy microscope indicated that the growth of cells exposed to IP6 were not well. The DNA damage rates of SGC-7901 cells treated with IP6 were more higher than those of control groups in dose and time dependent manners. The bcl-2 protein expressions treated with IP6 were reduced, and the bax protein expressions treated with IP6 were more than those of control groups in dose and time dependent manners. CONCLUSION: The proliferation of gastric carcinoma SGC-7901 cells inhibitited by IP6 could be associated with apoptosis of gene bax and bcl-2.
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Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ácido Fítico/farmacologia , Neoplasias Gástricas/patologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
OBJECTIVE: To investigate the effects of genistein on human breast cancer cell MCF-7 apoptosis and its probable mechanisms. METHODS: In this study, the methods of MTT, cell apoptosis detecting in fluorescent and electronic microscope and flow cytometry, and expression of Bax and erbB-2 protein were employed. RESULTS: The results showed that genistein could significantly inhibit the growth and induce the apoptosis of MCF-7 cells. Apoptotic cells of morphology from MCF-7 cells treated by different concentrations of genistein were observed by fluorescent and electronic microscope and the frequency of apoptosis in MCF-7 cells by flow cytometry showed increasingly with concentrations of genistein increased. The expression of Bax protein in MCF-7 cells was increased and the expression of erbB-2 protein was decreased with the doses of genistein. CONCLUSION: Genistein can induce MCF-7 cells apoptosis and it may be one of the mechanisms for the inhibitory effect of genistein in human cancer cells.
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Anticarcinógenos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Genisteína/farmacologia , Linhagem Celular Tumoral , Feminino , Humanos , Receptor ErbB-2/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
AIM: To study the blocking effects of genistein on cell proliferation cycle in human gastric carcinoma cells (SGC-7901) and the possible mechanism. METHODS: MTT assay was applied in the detection of the inhibitory effects of genistein on cell proliferation. Flow cytometry was used to analyze the cell cycle distribution. Immunocytochemical technique and Western blotting were performed to detect the protein expression of cyclin D1, cyclin B1 and p21(waf1/cip1). RESULTS: Genistein significantly inhibited the growth and proliferation of human gastric carcinoma cells (SGC-7901). Seven days after treatment with different concentrations of genistein (2.5, 5.0, 10.0, 20.0 microg/mL), the growth inhibitory rates were 11.2%, 28.8%, 55.3%, 84.7% respectively and cell cycles were arrested at the G(2)/ M phase. Genistein decreased cyclin D1 protein expression and enhanced cyclin B1 and p21(waf/cip1) protein expression in a concentration-dependent manner. CONCLUSION: The growth and proliferation of SGC-7901 cells can be inhibited by genistein via blocking the cell cycle, with reduced expression of cyclin D1 and enhanced expression of cyclin B1 and p21(waf/cip1) protein in the concentration range of 0-20 microg/mL.
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Antineoplásicos/farmacologia , Genisteína/farmacologia , Neoplasias Gástricas , Western Blotting , Proteínas de Ciclo Celular/metabolismo , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral/citologia , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/metabolismo , Ciclina B/metabolismo , Ciclina B1 , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21 , Citometria de Fluxo , HumanosRESUMO
The effects of isoflavone on human breast cancer cell line MCF-7 growth and apoptosis and its probable mechanisms were studied in vitro. The results showed that isoflavone could significantly inhibit the growth and induce the apoptosis of MCF-7 cells. Western Blotting showed that isoflavone increased iNOS protein expression. These results suggested that isoflavone significantly inhibited the MCF-7 growth and induced cell apoptosis by regulating iNOS gene expression.