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AIMS: Endoplasmic reticulum protein 29 (ERP29) is crucial for endoplasmic reticulum stress (ERS). M6A plays an important role in the progression of endometrial cancer (EC). The study investigated the role of ERS-related gene (ERP29) and m6A in EC. MATERIALS AND METHODS: We screened ERS-related genes based on the GEO dataset, GSEA dataset and TCGA-UCEC database using WGCNA and two machine learning algorithms. The m6A-related GEO dataset was employed to identify the ERS-related hub genes with m6A. Expression of hub genes in different cell types were visualize through scRNA-seq data analyzing. Using qPCR, Western blot, and Immunohistochemical assays to detect the expression of ERP29, the effect of ERP29 on cancer cell proliferation was investigated through CCK8, EdU and clone formation experiments. M6A modifications were studied using m6A Dot blot and MeRIP-qPCR. Finally, we conducted rescue experiments. KEY FINDINGS: Ten ERS-related hub genes with m6A were identified. ERP29 is highly expressed in EC. ERP29 knockdown inhibits EC cell proliferation. METTL3 overexpression increases the ERP29 mRNA m6A and decreases the expression of ERP29. Cycloleucine (Cyc), a nucleic acid methylation inhibitor, treatment reduces ERP29 mRNA m6A and increases the expression of ERP29. Cyc rescue the low expression of ERP29 caused by overexpression of METTL3 through m6A. ERP29 knockdown rescued the increased proliferation of EC cells caused by low m6A. SIGNIFICANCE: ERP29 is highly expressed in EC. m6A regulates ERP29 expression and affects the proliferation of endometrial cancer cells. This represents the premise for applying ERP29 and m6A modifications in diagnosing and treating EC.
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Kiwifruit bacterial canker, caused by Pseudomonas syringae pv. actinidiae (PSA), poses a grave threat to the global kiwifruit industry. In this study, we examined the role of microRNAs (miRNAs) in kiwifruit's response to PSA. Kiwifruit seedlings subjected to PSA treatment showed significant changes in both miRNA and gene expression compared to the control group. We identified 364 differentially expressed miRNAs (DEMs) and 7170 differentially expressed genes (DEGs). Further analysis revealed 180 miRNAs negatively regulating 641 mRNAs. Notably, two miRNAs from the miRNA482 family, miRNA-215-3p and miRNA-29-3p, were found to increase kiwifruit's sensitivity to PSA when overexpressed. These miRNAs were linked to the regulation of NBS-LRR target genes, shedding light on their role in kiwifruit's defence against PSA. This study offers insights into the miRNA482-NBS-LRR network as a crucial component in enhancing kiwifruit bioresistance to PSA infestation and provides promising candidate genes for further research.
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Hypoxia and Ferroptosis are associated with the malignant behaviour of cervical cancer. Endothelial PAS domain-containing protein 1 (EPAS1) contributes to the progression of cervical cancer. EPAS1 plays important roles in hypoxia and ferroptosis. Using the GEO dataset, machine-learning algorithms were used to screen for hypoxia- and ferroptosis-related genes (HFRGs) in cervical cancer. EPAS1 was identified as the hub gene. qPCR and WB were used to investigate the expression of EPAS1 in normal and cervical cancer tissues. The proliferation, invasion and migration of EPAS1 cells in HeLa and SiHa cell lines were detected using CCK8, transwell and wound healing assays, respectively. Apoptosis was detected by flow cytometry. A dual-luciferase assay was used to analyse the MALAT1-miR-182-5P-EPAS1 mRNA axis and core promoter elements of the super-enhancer. EPAS1 was significantly overexpressed in cervical cancer tissues. EPAS1 could increase the proliferation, invasion, migration of HeLa and SiHa cells and reduce the apoptosis of HeLa and SiHa cell. According to the double-luciferase assay, EPAS1 expression was regulated by the MALAT1-Mir-182-5p-EPAS1 mRNA axis. EPAS1 is associated with super-enhancers. Double-luciferase assay showed that the core elements of the super-enhancer were E1 and E3. EPAS1, an HFRG, is significantly overexpressed in cervical cancer. EPAS1 promotes malignant behaviour of cervical cancer cells. EPAS1 expression is regulated by super-enhancers and the MALAT1-miR-182-5P- EPAS1 mRNA axis. EPAS1 may be a target for the diagnosis and treatment of cervical cancer.
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Apoptose , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Movimento Celular , Proliferação de Células , Ferroptose , Regulação Neoplásica da Expressão Gênica , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Feminino , Ferroptose/genética , Proliferação de Células/genética , Movimento Celular/genética , Apoptose/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Células HeLa , RNA Longo não Codificante/genética , RNA Endógeno CompetitivoRESUMO
INTRODUCTION: In patients with stroke, poststroke dysphagia (PSD) is a common complication that plays an important role in morbidity and mortality. The aim of this paper was to assess the prevalence and risk factors of PSD using a systemic review and meta-analysis. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were systematically searched for potentially eligible studies published until September 2023. Further, the pooled incidence and risk factors for PSD were determined using a random-effects model. Overall, 58 studies involving 37,404 patients with acute stroke were selected for the meta-analysis. RESULTS: The pooled incidence of PSD in patients with acute stroke was 42% (95% confidence interval [CI]: 36-48%), which is the highest in South America (47%) and lowest in Asia (37%). Notably, older age (odds ratio [OR]: 2.13; 95% CI: 1.53-2.97; p < 0.001), hypertension (OR: 1.23; 95% CI: 1.06-1.44; p = 0.007), diabetes mellitus (OR: 1.22; 95% CI: 1.04-1.44; p = 0.014), stroke history (OR: 1.26; 95% CI: 1.04-1.53; p = 0.019), and atrial fibrillation (OR: 1.58; 95% CI: 1.02-2.44; p = 0.039) were found to be associated with an increased risk of PSD. Conversely, sex differences, smoking, alcoholism, obesity, hyperlipidemia, ischemic heart disease, stroke type, and the hemisphere affected were not associated with the risk of PSD. CONCLUSION: The abstract reports the prevalence of PSD in patients with acute stroke and identified potential risk factors for PSD, including older age, hypertension, diabetes mellitus, stroke history, and atrial fibrillation.
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BACKGROUND: Increasing global overweight and obesity rates not only increase the prevalence of myocardial infarction (MI), but also exacerbate ischemic injury and result in worsened prognosis. Currently, there are no drugs that can reverse myocardial damage once MI has occurred, therefore discovering drugs that can potentially limit the extent of ischemic damage to the myocardium is critical. Resveratrol is a polyphenol known for its antioxidant properties, however whether prolonged daily intake of resveratrol during obesity can protect against MI-induced damage remains unexplored. METHODS: We established murine models of obesity via high-fat/high-fructose diet, along with daily administrations of resveratrol or vehicle, then performed surgical MI to examine the effects and mechanisms of resveratrol in protecting against myocardial ischemic injury. RESULTS: Daily administration of resveratrol in obese mice robustly protected against myocardial ischemic injury and improved post-MI cardiac function. Resveratrol strongly inhibited oxidative and DNA damage via activating SIRT3/FOXO3a-dependent antioxidant enzymes following MI, which were completely prevented upon administration of 3-TYP, a selective SIRT3 inhibitor. Hence, the cardioprotective effects of prolonged resveratrol intake in protecting obese mice against myocardial ischemic injury was due to reestablishment of intracellular redox homeostasis through activation of SIRT3/FOXO3a signaling pathway. CONCLUSION: Our findings provide important new evidence that supports the daily intake of resveratrol, especially in those overweight or obese, which can robustly decrease the extent of ischemic damage following MI. Our study therefore provides new mechanistic insight and suggests the therapeutic potential of resveratrol as an invaluable drug in the treatment of ischemic heart diseases.
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Proteína Forkhead Box O3 , Homeostase , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade , Oxirredução , Resveratrol , Transdução de Sinais , Sirtuína 3 , Animais , Resveratrol/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sirtuína 3/metabolismo , Masculino , Oxirredução/efeitos dos fármacos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Obesidade/complicações , Proteína Forkhead Box O3/metabolismo , Homeostase/efeitos dos fármacos , Camundongos , Antioxidantes/farmacologia , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/tratamento farmacológico , Cardiotônicos/farmacologia , Estilbenos/farmacologia , Estilbenos/uso terapêuticoRESUMO
Type 2 diabetes (T2D) is a metabolic disorder that causes numerous complications including impaired wound healing and poses a significant challenge for the management of diabetic patients. Epigallocatechin-3-gallate (EGCG) is a natural polyphenol that exhibits anti-inflammatory and anti-oxidative benefits in skin wounds, however, the direct effect of EGCG on epidermal keratinocytes, the primary cells required for re-epithelialization in wound healing remains unknown. Our study aims to examine the underlying mechanisms of EGCG's ability to promote re-epithelialization and wound healing in T2D-induced wounds. Murine models of wound healing in T2D were established via feeding high-fat high-fructose diet (HFFD) and the creation of full-thickness wounds. Mice were administered daily with EGCG or vehicle to examine the wound healing response and underlying molecular mechanisms of EGCG's protective effects. Systemic administration of EGCG in T2D mice robustly accelerated the wound healing response following injury. EGCG induced nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and promoted cytokeratin 16 (K16) expression to activate epidermal keratinocytes and robustly promoted re-epithelialization of wounds in diabetic mice. Further, EGCG demonstrated high binding affinity with Kelch-like ECH-associated protein 1 (KEAP1), thereby inhibiting KEAP1-mediated degradation of NRF2. Our findings provide important evidence that EGCG accelerates the wound healing response in diabetic mice by activating epidermal keratinocytes, thereby promoting re-epithelialization of wounds via K16/NRF2/KEAP1 signaling axis. These mechanistic insights into the protective effects of EGCG further suggest its therapeutic potential as a promising drug for treating chronic wounds in T2D.
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Catequina/análogos & derivados , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Humanos , Camundongos , Animais , Reepitelização , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Queratinócitos , CicatrizaçãoRESUMO
BACKGROUD: Previous in vitro studies have indicated that pyrimidinergic receptor P2Y6 (P2RY6, P2Y6 receptor) may function as a cancer-promoting factor in lung adenocarcinoma (LUAD). However, the prognostic significance of P2RY6 expression in LUAD has not been investigated. OBJECTIVE: This study aimed to assess the impact of P2RY6 expression on the survival of patients with LUAD. METHODS: First, we assessed P2RY6 mRNA and protein expression in LUAD and non-cancerous lung tissues using the online bioinformatics analysis tool GEPIA, fresh LUAD tissues, and LUAD tissue microarrays (TMAs). Second, we investigated the correlation between P2RY6 expression and clinicopathological parameters of LUAD patients based on data from The Cancer Genome Atlas (TCGA) database and TMAs. Finally, we analyzed the prognostic significance of P2RY6 expression in LUAD using the online survival analysis tool Kaplan-Meier Plotter and data from TMAs. RESULTS: We demonstrated that P2RY6 mRNA and protein expression levels in LUAD tissues were significantly higher than those in non-cancerous lung tissues. The expression of P2RY6 in LUAD was positively correlated with poor differentiation, more lymph node metastasis, and more advanced clinical stage. Higher P2RY6 expression level was correlated with shorter survival of the LUAD patients. Univariate and multivariate Cox regression analyses indicated that higher P2RY6 tumor expression was an independent unfavorable prognostic factor for LUAD patients. CONCLUSIONS: P2RY6 expression was elevated in LUAD and correlated with poor prognosis.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/patologia , Pulmão/patologia , Neoplasias Pulmonares/patologia , Prognóstico , RNA Mensageiro/genéticaRESUMO
BACKGROUND: Pathological cardiac hypertrophy is a hallmark of various cardiovascular diseases (CVD) including chronic heart failure (HF) and an important target for the treatment of these diseases. Aberrant activation of Angiotensin II (Ang II)/AT1R signaling pathway is one of the main triggers of cardiac hypertrophy, which further gives rise to excessive inflammation that is mediated by the key transcription factor NF-κB. Resveratrol (REV) is a natural polyphenol with multiple anti-inflammatory and anti-oxidative effects, however the ability of REV in preventing Ang II-induced cardiac hypertrophy in combination with NF-κB signaling activation remains unclear. METHODS: Murine models of cardiac hypertrophy was conducted via implantation of Ang II osmotic pumps. Primary neonatal rat cardiomyocyte and heart tissues were examined to determine the effect and underlying mechanism of REV in preventing Ang II-induced cardiac hypertrophy. RESULTS: Administrations of REV significantly prevented Ang II-induced cardiac hypertrophy, as well as robustly attenuated Ang II-induced cardiac fibrosis, and cardiac dysfunction. Furthermore, REV not only directly prevented Ang II/AT1R signal transductions, but also prevented Ang II-induced expressions of pro-inflammatory cytokines and activation of NF-κB signaling pathway. CONCLUSIONS: Our study provides important new mechanistic insight into the cardioprotective effects of REV in preventing Ang II-induced cardiac hypertrophy via inhibiting adverse NF-κB signaling activation. Our findings further suggest the therapeutic potential of REV as a promising drug for the treatment of cardiac hypertrophy and heart failure.
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Insuficiência Cardíaca , NF-kappa B , Ratos , Camundongos , Animais , NF-kappa B/metabolismo , Resveratrol/efeitos adversos , Angiotensina II/farmacologia , Transdução de Sinais , Cardiomegalia/induzido quimicamente , Cardiomegalia/tratamento farmacológico , Cardiomegalia/metabolismo , Miócitos Cardíacos , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismoRESUMO
BACKGROUND: Piebaldism is a rare, autosomal dominant, and congenital pigmentary disorder characterized by stable depigmentation of the skin and white forelock. Mutations in KIT or SLUG genes result in piebaldism. Most individuals with piebaldism have a family history of the disorder. METHODS: In this paper, we report a case of piebaldism with café-au-lait macules resulting from a novel mutation of KIT gene c.1982C > T (p.Thr661Ile) in a three-generation Chinese family. The whole-exome sequencing, mitochondrial gene 3000X, and bioinformatics tools were used to identify the mutation in this new-found pedigree. In addition, we searched the databases of "Punmed, Chinese National Knowledge Infrastructure, CMJD, WANFANG MED ONLINE", reviewed 88 cases of piebaldism caused by KIT gene mutation, and summarized the relationship between clinical phenotype and genotype of piebaldism through logistic regression and other statistical methods. RESULTS: The proband and her affected mother carried a heterozygous c.1982C > T missense mutation (p.Thr661Ile) on KIT gene. Bioinformatics analysis hinted that it had potential pathogenicity. The data showed that piebaldism patients with cafè-au-lait macules had KIT mutations almost located in the intracellular tyrosine kinase domain and were mostly related to the severe clinical phenotype of piebaldism. CONCLUSION: The new heterozygous c.1982C > T missense mutation on KIT caused piebaldism with café-au-lait macules in this Chinese family. This study provides a new reference index for clinicians to judge the severity of clinical phenotypes of piebaldism, broadens the understanding of the correlation between clinical phenotypes and genotypes of piebaldism, and provides reference of genetic counseling and prenatal diagnosis for affected families.
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Piebaldismo , Transtornos da Pigmentação , Humanos , Feminino , Piebaldismo/genética , Proteínas Proto-Oncogênicas c-kit/genética , Manchas Café com Leite/diagnóstico , Manchas Café com Leite/genética , Mutação/genéticaRESUMO
BACKGROUND: Cancer cachexia is a common but severe condition that causes muscle wasting, body weight loss, and progressive functional impairment, affecting over 50% of cancer patients. Currently, there are no effective treatments that can alleviate cachexia, and hence the discovery of new therapeutics that can effectively prevent or even reverse cancer cachexia is crucial. Babao Dan (BBD) is a Traditional Chinese Medicine (TCM) formula that has been used clinically in combating various cancers, however, its therapeutic potential in alleviating cancer cachexia remains unexplored. Our current study aims to determine the anti-cachectic effects of BBD treatment in alleviating cancer cachexia, as well as determining the underlying mechanisms involved. METHODS: Mouse models of cancer cachexia were induced via implantation of CT26 colon adenocarcinoma cells, and the anti-cachectic effects and mechanisms of BBD were determined via examinations of body weight and muscle mass, as well as serum and muscle markers of cachexia and muscle atrophy. RESULTS: CT26 tumor implantation reduced in the rapid occurrence of cancer cachexia characterized by marked reductions in body weight and muscle mass, functional decrease in muscle function and accelerated deaths. BBD administration not only demonstrated robust anti-cachectic ability via preventing decreases in body weight, muscle mass, and muscle atrophy, but also markedly prolonged survival. The effects of BBD in alleviating cancer cachexia and its associated adverse effects were due to its ability in preventing the activation of IL-6/STAT3 signaling post-CT26 tumor implantation. CONCLUSION: Our findings demonstrated the robust ability of BBD in preventing cancer cachexia and alleviating the main cachexia-induced symptoms as well as prolonging survival via inhibiting activation of IL-6/STAT3 signaling pathway. Therefore, our study demonstrating the strong anti-cachectic effects of BBD in mice may provide a theoretical basis for the use of BBD as a safe and effective drug in the treatment of cancer cachexia.
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Adenocarcinoma , Neoplasias do Colo , Camundongos , Animais , Caquexia/tratamento farmacológico , Caquexia/etiologia , Caquexia/metabolismo , Interleucina-6 , Adenocarcinoma/tratamento farmacológico , Neoplasias do Colo/complicações , Neoplasias do Colo/tratamento farmacológico , Atrofia Muscular , Transdução de Sinais , Peso CorporalRESUMO
Goose gout disease is a high morbidity and mortality disease caused by novel serotype 1 goose astrovirus (GAstV-1), which has resulted in huge economic loss to the goose industry of China. However, few diagnostic methods have been developed for serological surveillance of GAstV-1. In our previous study, several novel B cell epitopes were identified in the ORF2 protein of GAstV-1. In this study, one novel peptide of 627-646 aa in the ORF2 recognized by monoclonal antibody (mAb) 6C6 was used as an antigen to develop an efficient peptide-based ELISA (pELISA) for detection of antibodies against GAstV-1. Specificity analysis showed that the pELISA only reacted with sera against GAstV-1, but not with sera against other pathogens tested. The sensitivity of the pELISA in detecting positive sera was higher than that of the IFA (Indirect immunofluorescence assay). The coefficients of variation (CV) of the intra-assay and inter-assay were both < 10%, indicating that the reproducibility of pELISA was good. For detection of clinical samples, the pELISA had 87.5% concordance with the IFA. Our data demonstrate that the pELISA generated here provides an accurate, rapid, and economical method for the detection antibodies against GAstV-1 for serological surveillance.
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Gansos , Peptídeos , Animais , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ensaio de Imunoadsorção Enzimática/métodosRESUMO
Organic dyes are widely used in the textile, biological, medical and other fields. However, a serious environmental problem has appeared because of the presence of organic dyes in industrial aqueous effluents. Thus, the efficient treatment of organic dyes in industrial wastewaters is currently in real demand. The current study investigated the oxidative degradation of the organic dye gentian violet by meso-tetra(carboxyphenyl) porphyriniron(III), [FeIII(TCPP)] as a cytochrome P450 model and iodosylbenzene (PhIO) as an oxidant at room temperature. The degradation reaction was monitored by UV-vis absorption spectroscopy via the observation of UV-vis spectral changes of the gentian violet. The results showed that the efficiency of catalyzed degradation reached more than 90% in 1 h, indicating the remarkable oxidative degradation capacity of the [FeIII(TCPP)]/PhIO system, which provided an efficient approach for the treatment of dyeing wastewater.
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Porfirinas , Poluentes Químicos da Água , Corantes/química , Ferro/química , Violeta Genciana , Poluentes Químicos da Água/química , Águas Residuárias/química , Sistema Enzimático do Citocromo P-450RESUMO
Recently, the outbreak of the infection of Duck adenovirus 3 (DAdV-3) characterized by swelling and hemorrhagic liver and kidney has caused huge economic losses to duck industry since 2014 in China. To date, the B cell epitopes in the Fiber-1 protein and the underlying infection mechanism of DAdV-3 have not been investigated. In this study, the recombinant Fiber-1 protein was first expressed in E. coli and six novel monoclonal antibodies (mAbs) against Fiber-1 were generated, designated as 1D8, 1E6, 3G6, 4G1, 4G2, and 6F10, respectively. Moreover, mAbs 3G6 and 6F10 could efficiently immunoprecipitate the Fiber-1 in LMH cells infected with DAdV-3 or transfected with pcDNA3.1-Fiber-1. Notably, mAbs 3G6 and 4G2 also showed certain neutralizing activity against DAdV-3 infection in vitro. Epitopes mapping revealed that the B cell epitope recognized by 6F10, 3G6, 4G1, 1D8, 4G2, and 1E6 was located in 34-66aa, 67-99aa, 64-296aa, 297-329aa, 330-362aa, and 363-395aa, respectively. Sequence alignments further found that the six epitopes recognized by these mAbs were highly conserved among different DAdV-3 isolates. The generated mAbs specific to Fiber-1 and their defined epitopes provide powerful tools for establishing rapid and efficient diagnostics for the detection of DAdV-3 and pave the way for further studying on the critical role of Fiber-1 in mediating the infection of DAdV-3.
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Nasopharyngeal carcinoma (NPC), which is marked by a distinct distribution, is a common subtype of epithelial carcinoma arising from the nasopharyngeal mucosal lining. SRGN acts as an important and poor prognostic factor of NPC through multiple different mechanisms. However, the biological role and mechanism of SRGN in NPC remain unknown. Expression levels of miR-148a-5p, CREB1, FoxO1, and SRGN in NPC tissues and cell lines were tested by qRT-PCR or/and Western blot. The impacts of miR-148a-5p, CREB1, FoxO1, and SRGN on NPC cell viability, proliferation, migration, and invasion were estimated in vitro by CCK-8, colony formation, wound healing and Transwell experiments, and in vivo by a xenograft tumor model. JASPAR analysis was used to predict the binding activity of Foxo1 (CREB1) with the miR-148a-5p (SRGN) promoter, and the interaction was validated by EMSA and ChIP assays. The miR-148a-5p-CREB1 interaction was validated by a dual-luciferase reporter and RIP assays. CREB1 and SRGN were increased while miR-148a-5p was decreased in NPC. Silencing of SRGN and CREB1, as well as miR-148a-5p overexpression, repressed NPC tumor progression in vitro and in vivo. CREB1 promoted SRGN expression in NPC by targeting the promoter area of SRGN. Silencing of FoxO1 facilitated NPC tumor progression, while silencing of STAT3 repressed NPC tumor progression. FoxO1 bound to and regulated miR-148a-5p in NPC, and miR-148a-5p targeted CREB1. Additionally, FoxO1 knockdown abolished the downregulation of CREB1 and SRGN induced by STAT3 silencing. Our results suggest that STAT3 regulates SRGN and promotes the growth and metastasis of NPC through the FoxO1-miR-148a-5p-CREB1 axis.
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MicroRNAs , Neoplasias Nasofaríngeas , Proteoglicanas/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Proteína Forkhead Box O1 , Regulação Neoplásica da Expressão Gênica , Humanos , Carcinoma Nasofaríngeo , Processos Neoplásicos , Fator de Transcrição STAT3RESUMO
Since 2015, the outbreaks of hydropericardium-hepatitis syndrome (HHS) and inclusion body hepatitis (IBH) caused by the highly pathogenic serotype 4 fowl adenovirus (FAdV-4) and serotype 8 fowl adenovirus (FAdV-8), respectively, have caused huge economic losses to the poultry industry. Although several vaccines have been developed to control HHS or IBH, a recombinant genetic engineering vaccine against both FAdV-4 and FAdV-8 has not been reported. In this study, recombinant FAdV-4 expressing the fiber of FAdV-8b, designated as FA4-F8b, expressing fiber of FAdV-8b was generated by the CRISPR-Cas9 and homologous recombinant techniques. Infection studies in vitro and in vivo revealed that the FA4-F8b replicated efficiently in LMH cells and was also highly pathogenic to 2-week-old SPF chickens. Moreover, the inoculation of inactivated the FA4-F8b in chickens could not only induce highly neutralizing antibodies, but also provide efficient protection against both FAdV-4 and FAdV-8b. All these demonstrate that the inactivated recombinant FA4-F8b generated here can act as a vaccine candidate to control HHS and IBH, and FAdV-4 can be an efficient vaccine vector to deliver foreign antigens.
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Infecções por Adenoviridae/prevenção & controle , Aviadenovirus/genética , Galinhas , Doenças das Aves Domésticas/prevenção & controle , Vacinas Virais/administração & dosagem , Infecções por Adenoviridae/veterinária , Infecções por Adenoviridae/virologia , Animais , Anticorpos Neutralizantes/sangue , Sistemas CRISPR-Cas , Edição de Genes , Doenças das Aves Domésticas/virologia , Sorogrupo , Vacinas Sintéticas/administração & dosagemRESUMO
OBJECTIVE: The aim of this study was to develop a nomogram-based model to predict the three-year and five-year overall survival (OS) of patients with stage II/III colon cancer following radical resection. METHODS: A total of 1156 patients with stage II/III colon cancer who underwent radical resection at the Affiliated Hospital of Guizhou Medical University between December 2012 and December 2018 were enrolled. Lasso regression was used to screen out 12 variables: age, prealbumin, albumin, degree of differentiation, total tumor-node-metastasis (TNM) stage, T stage, N stage, prognostic nutritional index (PNI), platelet/lymphocyte count, carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9), and postoperative adjuvant chemotherapy. The data set was then randomly split into a modeling set and a validation set, and the bootstrap method was used to verify the internal validity of the final model. A nomogram was then used to present the model, and the risk groups were categorized according to the total score in the nomogram. RESULTS: This study established and developed a simple, easy-to-use predictive model that included age, degree of differentiation, N stage, CA19-9, PNI, and postoperative chemotherapy as variables. In the multivariate Cox regression analysis, only postoperative chemotherapy was identified as an independent risk factor for death in patients with colon cancer. The receiver operating characteristic curve showed that the model demonstrated good resolution, with an area under the curve of 0.803. Decision curve analysis indicated that the model had a good positive net gain, and the bootstrap method was used to verify its stability. In the OS rate, the C-index was 0.78. According to the total score of the nomogram, the risk group was layered by drawing the Kaplan-Meier (K-M) curve. In the three-year OS K-M curve, the survival rates of the low-risk group, the medium-risk group, and the high-risk group were 96%, 93%, and 82%, respectively. In the five-year OS K-M curve, the survival rates of the low-risk group, the medium-risk group, and the high-risk group were 94%, 90%, and 73%, respectively. CONCLUSION: The nomogram-based prediction model developed in this study is stable and has good resolution, reliability, and net gain. It will therefore be useful for clinicians performing risk stratification and postoperative monitoring and in the development of personalized treatment options for patients with stage II/III colon cancer.
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Critical in revealing cell heterogeneity and identifying new cell subtypes, cell clustering based on single-cell RNA sequencing (scRNA-seq) is challenging. Due to the high noise, sparsity, and poor annotation of scRNA-seq data, existing state-of-the-art cell clustering methods usually ignore gene functions and gene interactions. In this study, we propose a feature extraction method, named FEGFS, to analyze scRNA-seq data, taking advantage of known gene functions. Specifically, we first derive the functional gene sets based on Gene Ontology (GO) terms and reduce their redundancy by semantic similarity analysis and gene repetitive rate reduction. Then, we apply the kernel principal component analysis to select features on each non-redundant functional gene set, and we combine the selected features (for each functional gene set) together for subsequent clustering analysis. To test the performance of FEGFS, we apply agglomerative hierarchical clustering based on FEGFS and compared it with seven state-of-the-art clustering methods on six real scRNA-seq datasets. For small datasets like Pollen and Goolam, FEGFS outperforms all methods on all four evaluation metrics including adjusted Rand index (ARI), normalized mutual information (NMI), homogeneity score (HOM), and completeness score (COM). For example, the ARIs of FEGFS are 0.955 and 0.910, respectively, on Pollen and Goolam; and those of the second-best method are only 0.938 and 0.910, respectively. For large datasets, FEGFS also outperforms most methods. For example, the ARIs of FEGFS are 0.781 on both Klein and Zeisel, which are higher than those of all other methods but slight lower than those of SC3 (0.798 and 0.807, respectively). Moreover, we demonstrate that CMF-Impute is powerful in reconstructing cell-to-cell and gene-to-gene correlation and in inferring cell lineage trajectories. As for application, take glioma as an example; we demonstrated that our clustering methods could identify important cell clusters related to glioma and also inferred key marker genes related to these cell clusters.
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Nasopharyngeal carcinoma (NPC) is a common tumor in the head and neck and is prevalent in China, especially in the southern regions. Molecular mechanisms have attracted much attention in NPC research. FOXD1 has been reported to be a tumor promoter in various cancers. The present study was designed to explore the function of FOXD1 in NPC cells. Functional analyses, including the trypan blue staining assay, EdU and JC-1 assay, and flow cytometry analysis, revealed that FOXD1 facilitated NPC cell proliferation and inhibited NPC cell apoptosis. Next, by means of "starBase" database and mechanism analyses, such as RIP assay, RNA pull-down assay and luciferase reporter assay, miR-378a-3p was found to target FOXD1 and negatively regulate FOXD1 expression in NPC cells. Moreover, miR-378a-3p plays a suppressive role in NPC cells. LINC00641 was identified as a sponge of miR-378a-3p and positively modulated FOXD1 expression in NPC cells. Finally, a series of rescue assays indicated that LINC00641 accelerated NPC cell proliferation and hindered NPC cell apoptosis through FOXD1 upregulation. In conclusion, the present study demonstrated an innovative ceRNA mechanism of LINC00641/miR-378a-3p/FOXD1 in NPC cells, which might provide new insights into NPC treatment.
Assuntos
Fatores de Transcrição Forkhead , MicroRNAs , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Proliferação de Células , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Regulação para CimaRESUMO
This study aimed to investigate the diagnostic value of heparin-binding protein (HBP) in the cerebrospinal fluid of children with purulent meningitis (PM). This study included 118 children with PM diagnosed at our hospital from January 2018 to January 2020, 110 children with viral meningitis (VM) and 80 children with suspected meningitis who were ruled out by cerebrospinal fluid (CSF) analysis during the same period. HBP and white blood cell (WBC) count in the CSF, and inflammatory factors, including C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and procalcitonin (PCT), were measured. Receiver-operator characteristic curves were used to analyze the predictive value of HBP, CRP, PCT, and TNF-α levels in the diagnosis of PM by CSF analysis. HBP levels in the CSF of children with PM were higher, while the CRP and serum PCT and TNF-α levels were elevated in all groups (P<0.05). In addition, HBP levels in the CSF were more accurate for the diagnosis of PM than traditional diagnostic indexes. HBP levels in the CSF can be used as an important reference for early diagnosis of PM.
Assuntos
Meningites Bacterianas , Meningite Viral , Peptídeos Catiônicos Antimicrobianos , Proteínas Sanguíneas , Proteína C-Reativa , Criança , Humanos , Meningites Bacterianas/diagnóstico , Pró-CalcitoninaRESUMO
The implementation of an electrochemical flow cell has enabled improved efficiency for CO2 reduction. However, in situ spectroscopic insights into the interface are still lacking. Here, we investigate a series of copper layers with different thicknesses on gas diffusion electrodes as a benchmark, with the best-performing one showing a Faradaic efficiency of 59.5% and a partial current density of -170 mA cm-2 for ethylene formation in 1 M KOH at -0.70 V against a reversible hydrogen electrode. By comparing the geometric as well as specific current density for ethylene on four Cu catalysts with different thicknesses, we illustrate the effects of bulk pH, local pH, and diffusion of CO2 on C-C coupling. We also reveal that the flexible rotation of the Cu-C bond of the *CO intermediate adsorbed on Cu, as shown by in situ Raman spectroscopy, is likely to be the key factor for efficient C-C coupling in a flow cell.