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OBJECTIVE: To explore the factors affecting delayed medical decision-making in older patients with acute ischemic stroke (AIS) using logistic regression analysis and the Light Gradient Boosting Machine (LightGBM) algorithm, and compare the two predictive models. METHODS: A cross-sectional study was conducted among 309 older patients aged ≥ 60 who underwent AIS. Demographic characteristics, stroke onset characteristics, previous stroke knowledge level, health literacy, and social network were recorded. These data were separately inputted into logistic regression analysis and the LightGBM algorithm to build the predictive models for delay in medical decision-making among older patients with AIS. Five parameters of Accuracy, Recall, F1 Score, AUC and Precision were compared between the two models. RESULTS: The medical decision-making delay rate in older patients with AIS was 74.76%. The factors affecting medical decision-making delay, identified through logistic regression and LightGBM algorithm, were as follows: stroke severity, stroke recognition, previous stroke knowledge, health literacy, social network (common factors), mode of onset (logistic regression model only), and reaction from others (LightGBM algorithm only). The LightGBM model demonstrated the more superior performance, achieving the higher AUC of 0.909. CONCLUSIONS: This study used advanced LightGBM algorithm to enable early identification of delay in medical decision-making groups in the older patients with AIS. The identified influencing factors can provide critical insights for the development of early prevention and intervention strategies to reduce delay in medical decisions-making among older patients with AIS and promote patients' health. The LightGBM algorithm is the optimal model for predicting the delay in medical decision-making among older patients with AIS.
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Algoritmos , Tomada de Decisão Clínica , AVC Isquêmico , Humanos , Idoso , Feminino , Masculino , Estudos Transversais , Modelos Logísticos , AVC Isquêmico/terapia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Letramento em Saúde/estatística & dados numéricosRESUMO
Development of cancer has been linked to chronic inflammation, particularly via interleukin-23 (IL-23) and IL-17 signaling pathways. However, the cellular source of IL-17 and underlying mechanisms by which IL-17-producing cells promote human colorectal cancer (CRC) remain poorly defined. Here, we demonstrate that innate γδT (γδT17) cells are the major cellular source of IL-17 in human CRC. Microbial products elicited by tumorous epithelial barrier disruption correlated with inflammatory dendritic cell (inf-DC) accumulation and γδT17 polarization in human tumors. Activated inf-DCs induced γδT17 cells to secrete IL-8, tumor necrosis factor alpha, and GM-CSF with a concomitant accumulation of immunosuppressive PMN-MDSCs in the tumor. Importantly, γδT17 cell infiltration positively correlated with tumor stages and other clinicopathological features. Our study uncovers an inf-DC-γδT17-PMN-MDSC regulatory axis in human CRC that correlates MDSC-meditated immunosuppression with tumor-elicited inflammation. These findings suggest that γδT17 cells might be key players in human CRC progression and have the potential for treatment or prognosis prediction.
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Neoplasias Colorretais/imunologia , Interleucina-17/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Células Th17/imunologia , Proliferação de Células , Células Dendríticas/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Inflamação/imunologia , Interleucina-8/metabolismo , Ativação Linfocitária/imunologia , Células Mieloides/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Although vonoprazan has been proven to be a highly potent drug for Helicobacter pylori eradication, there have been no randomized trials comparing the effectiveness of regimens containing vonoprazan 20 mg daily with alternative standard strategies. We aimed to assess the efficacy, tolerance, and cost-effectiveness of quadruple therapy with vonoprazan 20 mg daily as a first-line therapy for H. pylori eradication. MATERIALS AND METHODS: We conducted a single-center, open-label, noninferiority, randomized controlled study in Zhejiang, China. Treatment-naive H. pylori-positive participants (n = 234) were randomly assigned to three groups in a 1:1:1 ratio: vonoprazan 20 mg daily with amoxicillin 1000 mg, furazolidone 100 mg and colloidal bismuth 200 mg each given twice a day for 10 days (V10) or 14 days (V14), or esomeprazole 20 mg with amoxicillin 1000 mg, furazolidone 100 mg and colloidal bismuth 200 mg each given twice a day for 14 days (E14). The primary endpoint was the eradication rates in each group. The secondary endpoints were the incidence of adverse events (AEs) and compliance. RESULTS: The eradication rates in the V10, V14 and E14 groups were 96.2% (89.2-99.2%), 94.9% (87.4-98.6%), and 93.6% (85.7-97.9%) in the intention-to-treat analysis, and 98.6% (92.7-100.0%), 97.4% (90.8-99.7%), and 94.8% (87.2-98.6%) in the per-protocol analysis, respectively. Quadruple therapy with vonoprazan 20 mg daily was noninferior to the esomeprazole-based regimen (Farrington and Manning test: margin 10%, significance level 2.5%). The adverse event rates were 12.8% versus 3.8% versus 6.4% in the V10, V14, and E14 groups, respectively. All regimens were well tolerated without significant differences (p = 0.096). The cost-effectiveness ratio was 1.32, 1.88, and 3.06 for the V10, V14, and E14 groups in the intention-to-treat analysis, respectively. (NCT04907747). CONCLUSIONS: Vonoprazan (20 mg daily) was as effective as esomeprazole (20 mg twice a day) in quadruple therapies for the eradication of H. pylori, was more economical, and was well tolerated. In addition, the 10-day regimen of vonoprazan (20 mg daily) was comparable to the 14-day regimen.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Esomeprazol , Antibacterianos/efeitos adversos , Bismuto/uso terapêutico , Furazolidona , Quimioterapia Combinada , Amoxicilina/uso terapêutico , Resultado do Tratamento , Inibidores da Bomba de Prótons/uso terapêuticoRESUMO
Plenty of studies have assessed the association between intestinal metaplasia (IM) and gastric cancer risk, while the results were inconsistent. We aimed to assess the risk of gastric cancer among patients with IM. Systematic literature searches were conducted in PubMed, Embase and Cochrane databases. Baseline characteristics and outcomes from the included studies were extracted independently by two investigators. Either a fixed-effects or a random-effects model was used to composite the pooled OR for gastric cancer risk. Finally, a total of 21 studies, which comprised 402,636 participants and 4,535 gastric cancer patients, were finally included in the current meta-analysis. Compared with those participants without IM, IM patients were at a higher risk of gastric cancer (pooled OR = 3.58, 95% CI 2.71-4.73). We observed that incomplete IM (pooled OR = 9.48, 95% CI 4.33-20.78) but not complete IM (pooled OR = 1.55, 95% CI 0.91-2.65) was significantly associated with a higher gastric cancer risk. Besides, it appeared that gastric cancer risk was higher among patients with IM in the corpus (pooled OR = 7.39, 95% CI 4.94-11.06) than those with IM in the antrum only (pooled OR = 4.06, 95% CI 2.79-5.91). And the pooled ORs for gastric noncardia cancer and gastric cardia cancer were 4.98 (95% CI 3.12-7.95) and 1.93 (95% CI 1.15-3.24), respectively. In conclusion, patients with IM were at a higher risk of gastric cancer, especially for incomplete IM and IM in the corpus. The current evidence supports the use of IM subtypes in the surveillance of gastric cancer.
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Mucosa Gástrica/patologia , Intestinos/patologia , Metaplasia/patologia , Neoplasias Gástricas/etiologia , Adulto , Idoso , China/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologiaRESUMO
MiR-592 has been identified as a neural-enriched microRNA, plays an important role in mNPCs differentiation, could induce astrogliogenesis differentiation arrest or/and enhance neurogenesis in vitro Previous studies showed that long noncoding RNAs (lncRNAs) were involved in the neuronal development and activity. To investigate the role of miR-592 in neurogenesis, we described the expression profile of lncRNAs in miR-592 knockout mouse embryonic stem cells (mESCs) and the corresponding normal mESCs by microarray. By the microarray analysis and luciferase reporter assays, we demonstrated that lncRNA - AK048794, regulated by transcription factor GATA1, functioned as a competing endogenous RNA (ceRNA) for miR-592 and led to the de-repression of its endogenous target FAM91A1, which is involved in mESC pluripotency maintenance. Taken together, these observations imply that AK048794 modulated the expression of multiple genes involved in mESC pluripotency maintenance by acting as a ceRNA for miR-592, which may build up the link between the regulatory miRNA network and mESC pluripotency.
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MicroRNAs/genética , Células-Tronco Embrionárias Murinas/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Animais , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Linhagem Celular , Humanos , Camundongos , Camundongos Knockout , MicroRNAs/metabolismo , Análise de Sequência com Séries de OligonucleotídeosRESUMO
BACKGROUND: Long non-coding RNAs have been shown to have critical regulatory roles in cancer biology. However, the contributions of lncRNAs to gastric cancer remain largely unknown. METHODS: The differential expression of lncRNAs in gastric cancer and paired non-cancerous tissues were identified by microarray and validated using quantitative real-time PCR. Gastric samples from patients with gastric cancer were further analyzed for levels of a specifically downregulated lncRNA (termed as LEIGC). RESULTS: We found that there were significantly lower levels of LEIGC expression in cancer tissue than in adjacent non-cancerous tissues in human gastric cancers (P < 0.01). Overexpression of LEIGC suppressed tumor growth and cell proliferation, and enhanced the sensitivity of gastric cancer cells to 5-fluorouracil (5-FU), whereas knockdown of LEIGC showed the opposite effect. We further demonstrated LEIGC functions by inhibiting the epithelial-to-mesenchymal transition (EMT) in gastric cancer. CONCLUSIONS: Our data suggested that LEIGC is a tumor-suppressing lncRNA in gastric cancer, and led us to propose that lncRNAs may play important regulatory roles in cancer development and progression.
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Transição Epitelial-Mesenquimal/genética , Genes Supressores de Tumor , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Análise por Conglomerados , Modelos Animais de Doenças , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/farmacologia , Expressão Gênica , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genéticaRESUMO
Aumolertinib is an irreversible third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), although it has been administered for the treatment of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). However, it is unclear whether aumolertinib combined with ionizing radiation (IR) has potential therapeutic effects in treating brain metastases (BM) tumors from NSCLC. This study explored the anti-tumor effects of aumolertinib combined with IR in epidermal growth factor receptor mutated (EGFRm) NSCLC BM tumors. First, we established a xenograft model of NSCLC BM tumors in BALB/c nude mice and assessed the anti-tumor effects of this combination. Furthermore, we examined the concentrations of aumolertinib in brain tissue and blood using liquid chromatography-mass spectrometry (LC-MS); after that, we used CCK-8, colony formation, flow cytometry assay, and immunofluorescence staining to detect the effects of aumolertinib combined with IR upon PC-9 and NCI-H1975 cells, such as cell proliferation, survival, apoptosis, cycle distribution, the situation of DNA damage, and the expression levels of relevant proteins which were detected via western blotting; finally, we chose a clinical case with which to explore the clinical benefits to the EGFRm NSCLC BM patient after the treatment of the aforementioned combination. The experiments of NSCLC BM tumor animal models demonstrated that the combination enhanced the therapeutic effects and increased the intracranial accumulation of aumolertinib; the combination can inhibit cell proliferation and survival, delay the repair of DNA damage, and increase the rates of cell apoptosis and aumolertinib abrogated G2/M phase arrest, which the IR induced; the clinical study verified that the combination demonstrated better patient benefits. In conclusion, our study demonstrated that combining aumolertinib and IR has promising anti-tumor effects in EGFR-mutant NSCLC and that this combined treatment modality may be employed as a potential therapeutic strategy for EGFR-mutant NSCLC BM patients clinically.
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Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Camundongos , Animais , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Camundongos Nus , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Encéfalo/metabolismo , Radiação Ionizante , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , MutaçãoRESUMO
BACKGROUND: To compare the efficacy and tolerability of minocycline vs. tetracycline in bismuth-containing quadruple therapy for Helicobacter pylori (H. pylori) rescue treatment. METHODS: This study was a multi-center, randomized-controlled, non-inferiority trial. Refractory H. pylori-infected subjects with multiple treatment-failure were randomly (1:1) allocated to receive 14-day therapy with esomeprazole 20 mg b.i.d, bismuth 220 mg b.i.d, plus metronidazole 400 mg q.i.d and minocycline 100 mg b.i.d (minocycline group) or tetracycline 500 mg q.i.d (tetracycline group). Primary outcome was H. pylori eradication rate evaluated by 13C-urea breath test at least 6 weeks after the end of treatment. Antibiotic resistance was determined using E test method. RESULTS: Three hundred and sixty-eight subjects were randomized. The eradication rates in minocycline group and tetracycline group were 88.0% (162/184, 95% CI 83.3-92.8%) and 88.6% (163/184, 95% CI 83.9-93.2%) in intention-to-treat analysis, 98.0% (149/152, 95% CI 95.8-100%) and 97.4% (150/154, 95% CI 94.9-99.9%) in per-protocol analysis, 93.1% (162/174, 95% CI 89.3-96.9%) and 93.1% (163/175, 95% CI 89.4-96.9%) in modified intention-to-treat analysis. Minocycline, tetracycline and metronidazole resistance rates were 0.7%, 1.4% and 89.6%, respectively. Non-inferiority of minocycline was confirmed (P < 0.025). Metronidazole resistance did not affect the efficacy of either therapy. The two therapies exhibited comparable frequencies of adverse events (55.4% vs. 53.3%); almost half of them were mild. Dizziness was the most common adverse events in the minocycline group. CONCLUSIONS: Minocycline can be an alternative for tetracycline in bismuth-containing quadruple therapy for H. pylori empirical rescue treatment, irrespective of metronidazole resistance. However, relatively high incidence of adverse events in both regimens should be emphasized.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Bismuto/efeitos adversos , Minociclina/efeitos adversos , Metronidazol/efeitos adversos , Infecções por Helicobacter/tratamento farmacológico , Antibacterianos/efeitos adversos , Tetraciclina/efeitos adversos , Quimioterapia Combinada , Resultado do Tratamento , Amoxicilina/efeitos adversos , Inibidores da Bomba de PrótonsRESUMO
14C-urea breath tests (UBTs) can be used to diagnose helicobacter pylori (H. pylori) infection. This study aimed to evaluate the accuracy of a solid scintillation 14C-UBT in diagnosing H pylori infection. This open-label, prospective multicenter study enrolled patients who underwent H pylori screening from January 7, 2020, to October 28, 2020, in 3 centers in China. All participants underwent solid scintillation UBT first and then gastroscopy. The rapid urease test and histological examination results were the gold standards (H pylori-positive was defined as the 2 tests being positive; H pylori-negative was defined as both tests being negative). The solid scintillation 14C-UBT involves a scintillation sampling bottle and a 14C-urea capsule. The sampling bottle contains a stack of carbon dioxide-absorbing and scintillation sheets. The test is read using a photomultiplier. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for H pylori infection were evaluated. This study enrolled 239 participants. There were 98 males and 141 females, aged 45.8â ±â 11.9 (range: 21-66) years. Thirty-four participants were excluded due to a discrepancy between the rapid urease test and immunohistochemistry examination. Finally, 205 participants were included in the analysis. According to the gold standard, 87 out of 205 (42.4%) participants were H pylori-positive. Compared with the gold standard, the sensitivity, specificity, accuracy, and positive and negative predictive values of the solid scintillation 14C-UBT were 95.4%, 97.5%, 96.6%, 96.5%, and 96.6% for the solid scintillation UBT, respectively. One participant experienced 1 adverse event (AE) (exacerbation of chronic cholecystitis), and the AE eventually improved by itself. The investigators determined that the AE was unrelated to the study device. The noninvasive solid scintillation 14C-UBT has a high diagnostic value for H pylori infection, comparable to the diagnostic value of the gold standard.
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Infecções por Helicobacter , Helicobacter pylori , Feminino , Masculino , Humanos , Radioisótopos de Carbono , Infecções por Helicobacter/diagnóstico , Estudos Prospectivos , Urease , Testes Respiratórios , UreiaRESUMO
Existing deep learning based face anti-spoofing (FAS) or deepfake detection approaches usually rely on large-scale datasets and powerful networks with significant amount of parameters to achieve satisfactory performance. However, these make them resource-heavy and unsuitable for handheld devices. Moreover, they are limited by the types of spoof in the dataset they train on and require considerable training time. To produce a robust FAS model, they need large datasets covering the widest variety of predefined presentation attacks possible. Testing on new or unseen attacks or environments generally results in poor performance. Ideally, the FAS model should learn discriminative features that can generalize well even on unseen spoof types. In this paper, we propose a fast learning approach called Domain Effective Fast Adaptive nEt-worK (DEFAEK), a face anti-spoofing approach based on the optimization-based meta-learning paradigm that effectively and quickly adapts to new tasks. DEFAEK treats differences in an environment as domains and simulates multiple domain shifts during training. To further improve the effectiveness and efficiency of meta-learning, we adopt the metric learning in the inner loop update with careful sample selection. With extensive experiments on the challenging CelebA-Spoof and FaceForensics++ datasets, the evaluation results show that DEFAEK can learn cues independent of the environment with good generalization capability. In addition, the resulting model is lightweight following the design principle of modern lightweight network architecture and still generalizes well on unseen classes. In addition, we also demonstrate our model's capabilities by comparing the numbers of parameters, FLOPS, and model performance with other state-of-the-art methods.
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Sinais (Psicologia) , Generalização PsicológicaRESUMO
Background: The increasing antimicrobial resistance of Helicobacter pylori (H. pylori) has resulted in a fall in cure rates. We aimed to assess the effectiveness of first-line susceptibility-guided therapy and furazolidone-based quadruple therapy for H. pylori-infected patients. Methods: Subjects with H. pylori-infection were randomly assigned to either 10-day susceptibility-guided treatment or empiric treatment in a 2:1 ratio. Susceptibility-guided therapy was based on susceptibility to clarithromycin, and patients with susceptible strains received clarithromycin 500 mg twice daily and otherwise minocycline 100 mg twice a day was administered. Patients in the empiric therapy group was treated with furazolidone 100 mg twice a day. During treatment, all patients were given esomeprazole 20 mg twice daily, colloidal bismuth pectin 200 mg twice daily, and amoxicillin 1 g twice daily. Results: A total of 248 patients were screened and 201 were finally included. Empiric and susceptibility-guided regimens were both successful with per-protocol eradication rates of 90.5% (57/63) vs. 88.5% (108/122) (p = 0.685) and intent-to-treat eradication rates of 85.1% (57/67) vs. 80.6% (108/134) (p = 0.435). No significant difference in eradication rates were observed among the furazolidone group, clarithromycin group and minocycline group. Conclusion: Both susceptibility-guided therapy and quadruple therapy containing furazolidone can achieve good eradication rates. For population with a high rate of resistance, quadruple therapy containing furazolidone and bismuth may be a more practical choice for first-line treatment.
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In this study, we used neural stem cells (NSCs) as a toxicology tool to assess the potential developmental neurotoxicity of drinking water from Taihu Lake. We found that the condensed drinking water could inhibit the proliferation and differentiation of NSCs, especially the tap water. Inductively coupled plasma mass spectrometry and high-performance liquid chromatography analysis showed that nickel was detected in the tap water with a high concentration. Our study revealed that nickel could inhibit NSCs proliferation and differentiation, which is induced not only by the intracellular reactive oxygen species generation, but also by the protein levels upregulation of p-c-Raf, p-MEK1/2 and p-Erk1/2 through the axon guidance signal pathways. These findings will provide a new way of research insight for investigation of nickel-induced neurotoxicity. Meanwhile, our test method confirmed the feasibility and reliability of stem cell assays for developmental neurotoxicity testing.
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Água Potável/efeitos adversos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citometria de Fluxo , Imuno-Histoquímica , Lagos , Camundongos , Sistema Nervoso/citologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Cancer stem-like cells (CSCs) have been proposed as a key driving force of tumor growth and relapse in colorectal cancer (CRC), and therefore, they are promising targets for cancer therapy. Epidemiological evidence has suggested that the daily use of aspirin reduces overall mortality of CRC and the risk of distant metastasis. We investigated the effect and mechanism of aspirin on CSCs in CRC. Methods: The ratio of CSCs was analyzed after aspirin treatment both in a cell model and patient samples. Chemically modified aspirin and immunoprecipitation were adopted to detect the target proteins of aspirin. A locus-specific light-inducible epigenetic modification system based on CRISPR technology was constructed to verify the causal relationship in these molecular events. In vivo characterization was performed in a xenograft model. Results: We found that aspirin induces apoptosis in enriched colorectal CSCs, inhibits tumor progression, and enhances the anti-neoplastic effects of chemotherapeutic agents. Furthermore, aspirin directly interacts with p300 in the nucleus, promotes H3K9 acetylation, activates FasL expression, and induces apoptosis in colorectal CSCs. Notably, these effects of aspirin are absent in non-CSCs since H3K9 is hypermethylated in non-CSCs and the effects are not induced by other NSAIDs. In addition, aspirin can suppress oxaliplatin-enriched CSCs and serve as an adjuvant therapy. Conclusions: Taken together, we revealed a unique epigenetic and cox-independent pathway (p300-AcH3K9-FasL axis) by which aspirin eliminates colorectal CSCs. These findings establish an innovative framework of the therapeutic significance of aspirin.
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Antineoplásicos/metabolismo , Apoptose , Aspirina/metabolismo , Proteína p300 Associada a E1A/metabolismo , Proteína Ligante Fas/metabolismo , Histonas/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Acetilação , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Humanos , Modelos Teóricos , Processamento de Proteína Pós-TraducionalRESUMO
In order to search for specific genotypes related to this unique phenotype, we used whole genomic DNA microarray to characterize the genomic diversity of Helicobacter pylori (H. pylori) strains isolated from clinical patients in China. The open reading frame (ORF) fragments on our microarray were generated by PCR using gene-specific primers. Genomic DNA of H. pylori 26695 and J99 were used as templates. Thirty-four H. pylori isolates were obtained from patients in Shanghai. Results were judged based on ln(x) transformed and normalized Cy3/Cy5 ratios. Our microarray included 1882 DNA fragments corresponding to 1636 ORFs of both sequenced H. pylori strains. Cluster analysis, revealed two diverse regions in the H. pylori genome that were not present in other isolates. Among the 1636 genes, 1091 (66.7%) were common to all H. pylori strains, representing the functional core of the genome. Most of the genes found in the H. pylori functional core were responsible for metabolism, cellular processes, transcription and biosynthesis of amino acids, functions that are essential to H. pylori's growth and colonization in its host. In contrast, 522 (31.9%) genes were strain-specific genes that were missing from at least one strain of H. pylori. Strain-specific genes primarily included restriction modification system components, transposase genes, hypothetical proteins and outer membrane proteins. These strain-specific genes may aid the bacteria under specific circumstances during their long-term infection in genetically diverse hosts. Our results suggest 34 H. pylori clinical strains have extensive genomic diversity. Core genes and strain-specific genes both play essential roles in H. pylori propagation and pathogenesis. Our microarray experiment may help select relatively significant genes for further research on the pathogenicity of H. pylori and development of a vaccine for H. pylori.
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Variação Genética , Genoma Bacteriano , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Análise de Sequência com Séries de Oligonucleotídeos , Povo Asiático , China , Análise por Conglomerados , Genes Bacterianos , Genômica , Humanos , Fases de Leitura Aberta , Fenótipo , Especificidade da EspécieRESUMO
Coeliac disease (CD) is reported to be associated with risk of malignancy; however, this association remains unclear. We aimed to systematically evaluate the association between CD and risk of all malignancies as well as gastrointestinal (GI) malignancy specifically. The PUBMED and EMBASE databases were searched to identify eligible studies from 1960 to March 2015, without restriction. Two reviewers independently performed the study inclusion and data extraction methods. Odds ratios (ORs), risk ratios, or standardized incidence ratios were pooled using either a fixed- or a random-effects model. Sensitivity and subgroup analyses were used to explore sources of heterogeneity. A total of 17 studies were included in this meta-analysis. The pooled OR for risk of all malignancies was 1.25 (95% confidence interval [CI] 1.09-1.44), whereas the pooled OR for risk of GI malignancy was 1.60 (95% CI 1.39-1.84) and suggested an inverse association with CD. Moreover, patients with CD were at a higher risk of esophageal cancer (pooled ORâ=â3.72, 95% CI 1.90-7.28) and small intestinal carcinoma (pooled ORâ=â14.41, 95% CI 5.53-37.60), whereas no significant associations were observed for other GI cancers, including gastric, colorectal, liver, and pancreatic cancers. Subgroup analyses also indicated that the results were influenced by the CD diagnostic method, as well as the follow-up time after CD diagnosis. CD was associated with increased risk of all malignancies as well as GI malignancies, including esophageal cancer and small intestinal carcinoma.
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Carcinoma/etiologia , Doença Celíaca/complicações , Neoplasias Esofágicas/etiologia , Neoplasias Intestinais/etiologia , Humanos , Medição de RiscoRESUMO
Annexin A2 is a calcium-dependent phospholipid-binding protein, involved in invasion, angiogenesis and migration in cancer cells. The aims of the present study were to evaluate the expression levels of annexin A2 and E-cadherin in gastric adenocarcinoma (GAC), and to investigate the association between the expression of annexin A2 and that of E-cadherin and Ki67, in addition to various clinicopathological factors. This study included 126 patients that were histopathologically diagnosed with GAC. Tissue samples were acquired by surgical resection, and annexin A2 mRNA expression levels were determined using reverse transcription-quantitative polymerase chain reaction. Annexin A2, E-cadherin and Ki67 protein expression levels were detected using western blot analysis and/or immunohistochemical staining. The expression of annexin A2 mRNA and protein was significantly upregulated in the GAC tissues. Annexin A2 expression was detected in 52/126 cases (41.3%) of gastric cancer (GC), and correlations were identified between annexin A2 expression and Tumor, Node, Metastasis (TNM) stage (P=0.002), lymph node metastasis (P=0.016) and distal metastasis (P=0.005). The positive expression rates of E-cadherin and Ki67 in the tumor tissue of patients with GAC were 27.8% (35/126) and 56.2% (71/126), respectively. A negative correlation was observed between the expression of annexin A2 and E-cadherin (P<0.001). No significant association was detected between the expression levels of annexin A2 and Ki67 (P=0.801). In conclusion, upregulated annexin A2 expression was associated with lymph node metastasis, distal metastasis, advanced TNM stage and E-cadherin expression in patients with GAC. The association between the expression of annexin A2 and that of E-cadherin may indicate an underlying mechanism by which annexin A2 contributes to the metastasis in GC, and thus annexin A2 may represent a potential target for the treatment of GAC.
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In the present study, the effects of evodiamine on the apoptosis of human gastric cancer cells was studied in order to assess its antitumor effects and identify the molecular mechanisms involved. SGC7901 gastric cancer cells were treated with evodiamine at various concentrations (0, 3, 6, 12, 24 and 48 µmol/l) for 24 h. Inhibition of the proliferation of SGC7901 cells was assessed using an MTT assay. The morphology of treated SGC7901 cells was observed using optical microscopy; in addition, the effect of evodiamine on the nuclear morphology of cells was analyzed using Hoechst 33258 staining with fluorescence microscopy. Annexin V-fluorescein isothiocyanate/propidium iodide staining and flow cytometric analysis were used for investigating the effect of evodiamine on the induction of apoptosis in SGC7901 cells. Expression levels of survivin and caspase-3 were examined using reverse transcription polymerase chain reaction. The results demonstrated that evodiamine significantly inhibited SGC7901 cell proliferation (P<0.05) and induced apoptosis in a dose-dependent manner (P<0.05). Morphological characteristics of apoptosis were confirmed using optical microscopy and Hoechst 33258 staining analysis indicated that evodiamine treatment resulted in the typical characteristics of apoptotic programmed cell death, including cell shrinkage and apoptotic body formation. Flow cytometric analysis demonstrated that evodiamine induced the dose-dependent apoptosis of SGC7901 cells. Messenger (m)RNA levels of survivin decreased and those of caspase-3 increase in a dose-dependent manner in SGC7901 cells treated with various concentrations of evodiamine for 24 h. In conclusion, the results of the present study demonstrated that evodiamine inhibited proliferation and induced apoptosis in gastric cancer cells via the downregulation of survivin and upregulation of caspase-3 mRNA.
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Gamma delta T (γδT) cells are innate-like lymphocytes with strong, MHC-unrestricted cytotoxicity against cancer cells and show a promising prospect in adoptive cellular immunotherapy for various malignancies. However, the clinical outcome of commonly used Vγ9Vδ2 γδT (Vδ2 T) cells in adoptive immunotherapy for most solid tumors is limited. Here, we demonstrate that freshly isolated Vδ1 γδT (Vδ1 T) cells from human peripheral blood (PB) exhibit more potent cytotoxicity against adherent and sphere-forming human colon cancer cells than Vδ2 T cells in vitro. We also develop an optimized protocol to preferentially expand Vδ1 T cells isolated from PB of both healthy donors and colon cancer patients by in vitro short-term culture with phytohemagglutinin (PHA) and interleukin-7 (IL-7). Expanded Vδ1 T cells highly expressed cytotoxicity-related molecules, chemokine receptors and cytokines with enhanced cytolytic effect against adherent and sphere-forming colon cancer cells in a cell-to-cell contact dependent manner. In addition, PHA and IL-7 expanded Vδ1 T cells showed proliferation and survival advantage partly through an IL-2 signaling pathway. Furthermore, ex vivo expanded Vδ1 T cells also restrained the tumor growth and prolonged the tumor-burdened survival of human colon carcinoma xenografted mice. Our findings suggest that human PB Vδ1 T cells expanded by PHA and IL-7 are a promising candidate for anticancer adoptive immunotherapy for human solid tumors such as colon cancer.
RESUMO
Varicella-zoster virus (VZV) is a type of herpes virus known to cause varicella, mainly in young children, and herpes zoster in adults. Although generally non-lethal, VZV infection can be associated with serious complications, particularly in adults. Acute pancreatitis caused by VZV infection is a rare event, with reports primarily concerning immunocompromised individuals. Here we report a 44-year-old immunocompetent female who developed acute pancreatitis associated with VZV infection. The patient presented with vomiting and persistent pain in the upper quadrant less than one week after diagnosis and treatment for a herpes zoster-related rash with stabbing pain on the abdomen and dorsal right trunk side. A diagnosis of acute pancreatitis was confirmed based on abdominal pain, elevated levels of urine and serum amylase, and findings of peri-pancreatic exudation and effusions by computed tomography and magnetic resonance cholangiopancreatography. This case highlights that, though rare, acute pancreatitis should be considered in VZV patients who complain of abdominal pain, especially in the epigastric area. Early detection and proper treatment are needed to prevent the condition from deteriorating further and to minimize mortality.
Assuntos
Herpes Zoster/virologia , Herpesvirus Humano 3/isolamento & purificação , Pancreatite/virologia , Dor Abdominal/virologia , Doença Aguda , Adulto , Colangiopancreatografia por Ressonância Magnética , Diagnóstico Precoce , Feminino , Herpes Zoster/complicações , Herpes Zoster/diagnóstico , Herpes Zoster/imunologia , Herpes Zoster/terapia , Humanos , Imunocompetência , Pancreatite/diagnóstico , Pancreatite/imunologia , Pancreatite/terapia , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
A Helicobacter pylori whole-genome DNA microarray was constructed to study expression profiles of H. pylori in response to a sudden temperature transfer from 37 degrees C to 20 degrees C. The expression level of the genome at each of four time points (15, 30, 60, and 120 min) after temperature downshift was compared with that just before cold treatment. Globally, 10.2 % (n=167) of the total predicted H. pylori genes (n=1636) represented on the microarray were significantly differentially expressed (p<0.05) over a 120 min period after shift to low temperature. The expression profiles of the differentially expressed genes were grouped, and their expression patterns were validated by quantitative real-time PCR. Up-regulated genes mainly included genes involved in energy metabolism and substance metabolism, cellular processes, protein fate, ribosomal protein genes, and hypothetical protein genes, which indicate the compensational responses of H. pylori to temperature downshift. Those genes play important roles in adaption to temperature downshift of H. pylori. Down-regulation of DNA metabolism genes and cell envelope genes and cellular processes genes may reflect damaged functions under low temperature, which is unfavorable to bacterial infection and propagation. Overall, this time-course study provides new insights into the primary response of H. pylori to a sudden temperature downshift, which allow the bacteria to survive and adapt to the new host environment.