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METTL3 has been shown to be involved in regulating a variety of biological processes. However, the relationship between METTL3 expression and glycolysis, cuproptosis-related genes and the ceRNA network in oesophageal carcinoma (ESCA) remains unclear. ESCA expression profiles from databases were obtained, and target genes were identified using differential analysis and visualization. Immunohistochemistry (IHC) staining assessed METTL3 expression differences. Functional enrichment analysis using GO, KEGG and GSEA was conducted on the co-expression profile of METTL3. Cell experiments were performed to assess the effect of METTL3 interference on tumour cells. Correlation and differential analyses were carried out to assess the relationship between METTL3 with glycolysis and cuproptosis. qRT-PCR was used to validate the effects of METTL3 interference on glycolysis-related genes. Online tools were utilized to screen and construct ceRNA networks based on the ceRNA theory. METTL3 expression was significantly higher in ESCA compared to the controls. The IHC results were consistent with the above results. Enrichment analysis revealed that METTL3 is involved in multiple pathways associated with tumour development. Significant correlations were observed between METTL3 and glycolysis-related genes and cuproptosis-related gene. Experiments confirmed that interfered with METTL3 significantly inhibited glucose uptake and lactate production in tumour cells, and affected the expression of glycolytic-related genes. Finally, two potential ceRNA networks were successfully predicted and constructed. Our study establishes the association between METTL3 overexpression and ESCA progression. Additionally, we propose potential links between METTL3 and glycolysis, cuproptosis and ceRNA, presenting a novel targeted therapy strategy for ESCA.
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Carcinoma , Neoplasias Esofágicas , Metiltransferases , Humanos , Biomarcadores , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Glicólise/genética , Ácido Láctico , Metiltransferases/genética , RNA Endógeno CompetitivoRESUMO
BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Ginsenoside may be an ideal agent for UC treatment. However, its efficacy and safety are unknown. We aim to conduct a systematic evaluation to assess the effects and potential mechanisms of ginsenosides in animal models of UC. METHODS: Six electronic databases will be searched (PubMed, Embase, Web of Science, China Knowledge Network (CNKI), China Science and Technology Journal Database (CQVIP), and Wanfang Data Knowledge). SYRCLE list will be used to assess the quality of literature, and STATA 15.1 for data analysis. Time-dose effects analysis will be used to reveal the time-dosage response relations between ginsenosides and UC. RESULTS: Ultimately, fifteen studies involving 300 animals were included. Preliminary evidence was shown that ginsenosides could reduce Disease Activity Index (DAI) scores, weight loss, histological colitis score (HCS), spleen weight, Malondialdehyde (MDA), Myeloperoxidase (MPO) activity, interleukin-1ß (IL-1ß), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and increase colon length (CL), myeloperoxidase (GSH), interleukin 4 (IL-4), interleukin 10 (IL-10), Zonula Occludens-1 (ZO-1) and occludin. Results of time-dose interval analysis indicated that ginsenosides at a dosage of 5-200 mg/kg with an intervention time of 7-28 days were relatively effective. CONCLUSIONS: Preclinical evidence suggests that ginsenoside is a novel treatment for UC. And the mechanisms of ginsenosides in treating UC may involve anti-inflammatory, antioxidant, barrier protection, intestinal flora regulation, and immune regulation. Although, due to the high heterogeneity, further large-scale and high-quality preclinical studies are needed to examine the protection of ginsenosides against UC.
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To explore the underlying mechanism of lncRNA MALAT1 in the pathogenesis of diabetic cardiomyopathy (DCM). DCM models were confirmed in db/db mice. MiRNAs in myocardium were detected by miRNA sequencing. The interactions of miR-185-5p with MALAT1 and RhoA were validated by dual-luciferase reporter assays. Primary neonatal cardiomyocytes were cultured with 5.5 or 30 mmol/L D-glucose (HG) in the presence or absence of MALAT1-shRNA and fasudil, a ROCK inhibitor. MALAT1 and miR-185-5p expression were determined by real-time quantitative PCR. The apoptotic cardiomyocytes were evaluated using flow cytometry and TUNEL staining. SOD activity and MDA contents were measured. The ROCK activity, phosphorylation of Drp1S616 , mitofusin 2 and apoptosis-related proteins were analysed by Western blotting. Mitochondrial membrane potential was examined by JC-1. MALAT1 was significantly up-regulated while miR-185-5p was down-regulated in myocardium of db/db mice and HG-induced cardiomyocytes. MALAT1 regulated RhoA/ROCK pathway via sponging miR-185-5p in cardiomyocytes in HG. Knockdown of MALAT1 and fasudil all inhibited HG-induced oxidative stress, and alleviated imbalance of mitochondrial dynamics and mitochondrial dysfunction, accompanied by reduced cardiomyocyte apoptosis. MALAT1 activated the RhoA/ROCK pathway via sponging miR-185-5p and mediated HG-induced oxidative stress, mitochondrial damage and apoptosis of cardiomyocytes in mice.
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MicroRNAs , RNA Longo não Codificante , Camundongos , Animais , Miócitos Cardíacos/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Apoptose/genética , Estresse Oxidativo , Glucose/toxicidade , Glucose/metabolismo , Mitocôndrias/metabolismoRESUMO
Potassium-ion batteries (PIBs) have broad application prospects in the field of electric energy storage systems because of its abundant K reserves, and similar "rocking chair" operating principle as lithium-ion batteries (LIBs). Aiming to the large volume expansion and sluggish dynamic behavior of anode materials for storing large sized K-ion, bismuth telluride (Bi2 Te3 ) nanoplates hierarchically encapsulated by reduced graphene oxide (rGO), and nitrogen-doped carbon (NC) are constructed as anodes for PIBs. The resultant Bi2 Te3 @rGO@NC architecture features robust chemical bond of BiâOâC, tightly physicochemical confinement effect, typical conductor property, and enhanced K-ion adsorption ability, thereby producing superior electrochemical kinetics and outstanding morphological and structural stability. It is visually elucidated via high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) that conversion-alloying dual-mechanism plays a significant role in K-ion storage, allowing 12 K-ion transport per formular unit employing Bi as redox site. Thus, the high first reversible specific capacity of 322.70 mAh g-1 at 50 mA g-1 , great rate capability and cyclic stability can be achieved for Bi2 Te3 @rGO@NC. This work lays the foundation for an in-depth understanding of conversion-alloying mechanism in potassium-ion storage.
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BACKGROUND: Cytoplasmic activation/proliferation-associated protein-1 (Caprin-1) is implicated in cancer cell proliferation and tumorigenesis; however, its role in the development of esophageal carcinoma (ESCA) has not been examined. METHODS: Biological methods and data analysis were used to investigate the expression of Caprin-1 in ESCA tissue and cell lines. We comprehensively analyzed the mRNA expression and prognostic values, signalling pathways of CAPRIN1 in ESCA using public databases online. Biological functions of CAPRIN1 were performed by clorimetric growth assay, EdU staining, colony formation, flow cytometry, apoptosis analysis, Western blot, lactate detection assay, extracellular acidification rates. The underlying mechanism was determined via flow cytometric analysis, Western blot and rescue experiments. In addition, xenograft tumor model was constructed to verify the phenotypes upon CAPRIN1 silencing. RESULTS: Caprin-1 expression was significantly elevated in both ESCA tumor tissues and cell lines compared with that in normal adjacent tissues and fibroblasts. Increased CAPRIN1 mRNA expression was significantly associated with clinical prognosis and diagnostic accuracy. The GO enrichment and KEGG pathway analysis CAPRIN1 might be related to immune-related terms, protein binding processes, and metabolic pathways. A significant positive correlation was observed between high Caprin-1 protein levels and lymph node metastasis (P = 0.031), ki-67 (P = 0.023), and 18F- FDG PET/CT parameters (SUVmax (P = 0.002) and SUV mean (P = 0.005)) in 55 ESCA patients. At cut-off values of SUVmax 17.71 and SUVmean 10.14, 18F- FDG PET/CT imaging predicted Caprin-1 expression in ESCA samples with 70.8% sensitivity and 77.4% specificity. In vitro and in vivo assays showed that Caprin-1 knockdown affected ESCA tumor growth. Silencing Caprin-1 inhibited ESCA cell proliferation and glycolysis, and decreased the expression of methyltransferase-like 3 (METTL3) and Wilms' tumor 1-associating protein (WTAP). However, this effect could be partially reversed by the restoration of METTL3 and WTAP expression. CONCLUSIONS: Our data suggest that Caprin-1 could serve as a prognostic biomarker and has an oncogenic role in ESCA.
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Carcinoma , Neoplasias Esofágicas , Humanos , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Esofágicas/genética , Proliferação de Células/genética , RNA Mensageiro , Metiltransferases/genética , Fatores de Processamento de RNA , Proteínas de Ciclo CelularRESUMO
BACKGROUND: This study investigated the correlation between the expression of DARS2 and metabolic parameters of 18F-FDG PET/CT, and explored the potential mechanisms of DARS2 affecting the proliferation and glycolysis of lung adenocarcinoma (LUAD) cells. METHODS: This study used genomics and proteomics to analyze the difference in DARS2 expression between LUAD samples and control samples. An analysis of 62 patients with LUAD who underwent 18F-FDG PET/CT examinations before surgery was conducted retrospectively. The correlation between DARS2 expression and PET/CT metabolic parameters, including SUVmax, SUVmean, MTV, and TLG, was examined by Spearman correlation analysis. In addition, the molecular mechanism of interfering with DARS2 expression in inhibiting LUAD cell proliferation and glycolysis was analyzed through in vitro cell experiments. RESULTS: DARS2 expression was significantly higher in LUAD samples than in control samples (p < 0.001). DARS2 has high specificity (98.4%) and sensitivity (95.2%) in the diagnosis of LUAD. DARS2 expression was positively correlated with SUVmax, SUVmean, and TLG (p < 0.001). At the same time, the sensitivity and specificity of SUVmax in predicting DARS2 overexpression in LUAD were 88.9% and 65.9%, respectively. In vitro cell experiments have shown that interfering with DARS2 expression can inhibit the proliferation and migration of LUAD cells, promote cell apoptosis, and inhibit the glycolytic activity of tumor cells by inhibiting the expression of glycolytic related genes SLC2A1, GPI, ALDOA, and PGAM1. CONCLUSIONS: Overexpression of DARS2 is associated with metabolic parameters on 18F-FDG PET/CT, which can improve LUAD diagnosis accuracy. DARS2 may be a useful biomarker to diagnose, prognosis, and target treatment of LUAD patients.
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Adenocarcinoma de Pulmão , Aspartato-tRNA Ligase , Neoplasias Pulmonares , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Estudos Retrospectivos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/genética , Glicólise , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genéticaRESUMO
Bacterial infections can significantly impede wound healing and pose a serious threat to the patient's life. The excessive use of antibiotics to combat bacterial infections has led to the emergence of multi-drug-resistant bacteria. Therefore, there is a pressing need for alternative approaches, such as photothermal therapy (PTT), to address this issue. In this study, for the first time, CuS NPs with photothermal properties were synthesized using sericin as a biological template, named CuS@Ser NPs. This method is simple, green, and does not produce toxic and harmful by-products. These nanoparticles were incorporated into a mixture (XK) of xanthan gum and konjac glucomannan (KGM) to obtain XK/CuS NPs composite hydrogel, which could overcome the limitations of current wound dressings. The composite hydrogel exhibited excellent mechanical flexibility, photothermal response, and biocompatibility. It also demonstrated potent antibacterial properties against both Gram-positive and negative bacteria via antibacterial experiments and accelerated wound healing in animal models. Additionally, it is proved that the hydrogel promoted tissue regeneration by stimulating collagen deposition, angiogenesis, and reducing inflammation. In summary, the XK/CuS NPs composite hydrogel presents a promising alternative for the clinical management of infected wounds, offering a new approach to promote infected wound healing.
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Infecções Bacterianas , Hidrogéis , Animais , Hidrogéis/farmacologia , Cicatrização , Antibacterianos/farmacologia , ColágenoRESUMO
In this study, we examined the effect of the GP130-targeting molecule, LMT-28, on lipopolysaccharide- (LPS-) induced bone resorption around implants in diabetic models using in vitro and rat animal experiments. First, LMT-28 was added to osteoblasts stimulated by LPS and advanced glycation end products (AGEs), and nuclear factor-κB receptor-activating factor ligand (RANKL) and associated pathways were evaluated. Then, LMT-28 was administered by gavage at 0.23 mg/kg once every 5 days for 2 weeks to type 2 diabetic rats with peri-implantitis induced by LPS injection and silk ligature. The expression of IL-6 and RANKL was evaluated by immunohistochemistry, and the bone resorption around implants was evaluated by microcomputed tomography. The results showed that LMT-28 downregulated the expression of RANKL through the JAK2/STAT3 signaling pathway in osteoblasts stimulated by LPS and AGEs, reduced bone resorption around implants with peri-implantitis, decreased the expression of IL-6 and RANKL, and decreased osteoclast activity in type 2 diabetic rats. This study confirmed the ability of LMT-28 to reduce LPS-induced bone resorption around implants in diabetic rats.
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Reabsorção Óssea , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Peri-Implantite , Animais , Ratos , Reabsorção Óssea/metabolismo , Receptor gp130 de Citocina , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Interleucina-6/metabolismo , Janus Quinase 2/metabolismo , Lipopolissacarídeos , Osteoclastos/metabolismo , Peri-Implantite/metabolismo , Ligante RANK/metabolismo , Transdução de Sinais , Microtomografia por Raio-XRESUMO
Monocyclic aromatic hydrocarbons (MAHs) and polycyclic aromatic hydrocarbons (PAHs) are both well known as hazardous air pollutants and also important anthropogenic precursors of tropospheric ozone (O3) and secondary organic aerosols (SOA). In recent years, there have been intensive studies covering MAHs emission from various sources and their behavior under stimulated photochemical conditions. Yet in-situ measurements of PAHs presence and variations in ambient air are sparse. Herein we conducted large geometrical scale mobile measurements for 16 aromatic hydrocarbons (AHs, including 7 MAHs and 9 PAHs) in eastern China between October 27 and November 8, 2019. This unique dataset has allowed for some insights in terms of AHs concentration variations, accompanying chemical composition, source contributions and spatial distributions in eastern China. In general, AHs showed a clear concentration variability between the south and the north of the Yangtze River Delta (YRD). The concentrations of PAHs were approximately 9% of AHs, but contributed 23% of SOA formation potential. Source apportionment via positive matrix factorization (PMF) model revealed that industrial processes as the largest source (44%) of observed AHs, followed by solvent usage (21%), vehicle exhaust (19%), coal combustion (11%) and coking processes (6%). In the perspective of PAHs sources, coal combustion emissions were identified as the dominating factor of a share of 41%-52% in eastern China. Our findings complemented the simultaneously monitoring information of PAHs and MAHs in eastern China, revealed the importance of PAHs to SOA formation and highlighted the necessity of formulating strategies to reduce emissions from anthropogenic sources and reduce risks to human health.
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Poluentes Atmosféricos , Ozônio , Hidrocarbonetos Policíclicos Aromáticos , Humanos , Monitoramento Ambiental , Poluentes Atmosféricos/análise , Emissões de Veículos/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , China , Carvão Mineral/análiseRESUMO
The investigation of carbonaceous-based anode materials will promote the fast application of low-cost potassium-ion batteries (PIBs). Here a nitrogen and oxygen co-doped yolk-shell carbon sphere (NO-YS-CS) is constructed as anode material for K-ion storage. The novel architecture, featuring with developed porous structure and high surface specific area, is beneficial to achieving excellent electrochemical kinetics behavior and great electrode stability from buffering the large volume expansion. Furthermore, the N/O heteroatoms co-doping can not only boost the adsorption and intercalation ability of K-ion but also increase the electron transfer capability. It is also demonstrated by experimental results and DFT calculations that K-ion insertion/extraction proceeds through both intercalation and surface capacitive adsorption mechanisms. As expected, the NO-YS-CS electrodes show high initial charge capacity of 473.7 mAh g-1 at 20 mA g-1 , ultralong cycling life over 2500 cycles with the retention of 85.8% at 500 mA g-1 , and superior rate performance (183.3 mAh g-1 at 1.0 A g-1 ). The K-ion full cell, with a high energy density of 271.4 Wh kg-1 and an excellent cyclic stability over 500 cycles, is successfully fabricated with K2 Fe[Fe(CN)6 ] cathode. This work will provide new insight on the synthesis and mechanism understanding of high-performance hard carbon anode for PIBs.
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BACKGROUND: Although eukaryotic initiation factor 6 (eIF6) is a novel therapeutic target, data on its importance in the development of esophageal carcinoma (ESCA) remains limited. This study evaluated the correlation between eIF6 expression and metabolic analysis using fluorine-18 fluorodeoxyglucose (18F-FDG) -Positron emission tomography (PET) and immune gene signatures in ESCA. METHODS: This study employed The Cancer Genome Atlas (TCGA) to analyze the expression and prognostic value of eIF6, as well as its relationship with the immune gene signatures in ESCA patients. The qRT-PCR and Western blot analyses were used to profile the expression of eIF6 in ESCA tissues and different ESCA cell lines. The expression of tumor eIF6 and glucose transporter 1 (GLUT1) was examined using immunohistochemical tools in fifty-two ESCA patients undergoing routine 18F-FDG PET/CT before surgery. In addition, the cellular responses to eIF6 knockdown in human ESCA cells were assessed via the MTS, EdU, flow cytometry and wound healing assays. RESULTS: Our data demonstrated that compared with the normal esophageal tissues, eIF6 expression was upregulated in ESCA tumor tissues and showed a high diagnostic value with an area under curve of 0.825 for predicting ESCA. High eIF6 expression was significantly correlated with shorter overall survival of patients with esophagus adenocarcinoma (p = 0.038), but not in squamous cell carcinoma of the esophagus (p = 0.078). In addition, tumor eIF6 was significantly associated with 18F-FDG PET/CT parameters: maximal and mean standardized uptake values (SUVmax and SUVmean) and total lesion glycolysis (TLG) (rho = 0.458, 0.460, and 0.300, respectively, p < 0.01) as well as GLUT1 expression (rho = 0.453, p < 0.001). A SUVmax cutoff of 18.2 led to prediction of tumor eIF6 expression with an accuracy of 0.755. Functional analysis studies demonstrated that knockdown of eIF6 inhibited ESCA cell growth and migration, and fueled cell apoptosis. Moreover, the Bulk RNA gene analysis revealed a significant inverse association between eIF6 and the tumor-infiltrating immune cells (macrophages, T cells, or Th1 cells) and immunomodulators in the ESCA microenvironment. CONCLUSION: Our study suggested that eIF6 might serve as a potential prognostic biomarker associated with metabolic variability and immune gene signatures in ESCA tumor microenvironment.
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Carcinoma de Células Escamosas , Fluordesoxiglucose F18 , Biomarcadores , Transportador de Glucose Tipo 1 , Humanos , Fatores de Iniciação de Peptídeos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Prognóstico , Microambiente TumoralRESUMO
We aim to discuss the role of miR-431-5p in colorectal cancer (CRC) progression via regulating peroxiredoxin 1 (PRDX1). miR-431-5p and PRDX1 expression were detected in CRC tissues and cells, and the relationship between miR-431-5p expression and prognosis of CRC patients was analyzed. Exosomes were extracted from human umbilical cord mesenchymal stem cells (hUCMSCs) and co-cultured with LoVo cells. MTT assay, flow cytometry and Transwell assay were implemented to test cell viability, apoptosis and invasion and migration ability, respectively. The tumor growth was determined as well, and the binding relation between miR-431-5p and PRDX1 was confirmed. miR-431-5p was downregulated and PRDX1 was upregulated in CRC, and miR-431-5p downregulation was associated with poor prognosis. hUCMSC-Exos suppressed the malignant behaviors of LoVo cells, and overexpression of miR-431-5p further aggravated the inhibitory effect of hUCMSC-Exos on LoVo cells. hUCMSC-Exos inhibited PRDX1 expression via miR-431-5p. PRDX1 was targeted by miR-431-5p. miR-431-5p serves as a prognostic biomarker in CRC, and hUCMSC-Exos transfer of miR-431-5p decelerates CRC cell growth by inhibiting PRDX1.
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Neoplasias Colorretais , Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Exossomos/genética , Exossomos/metabolismo , Células-Tronco Mesenquimais/patologia , Cordão Umbilical/metabolismo , Cordão Umbilical/patologia , Neoplasias Colorretais/metabolismo , Proliferação de Células/genéticaRESUMO
PURPOSE: This study investigated the correlation of nucleophosmin 1 (NPM1) expression with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computerised tomography scan (PET/CT)-related parameters and compared the diagnostic value of NPM1 with that of the positive biomarker TTF1 in lung adenocarcinoma patients. METHODS: Forty-six lung adenocarcinoma patients who underwent 18F-FDG PET/CT before pulmonary surgery were retrospectively analysed. Metabolic parameters including SUVmax, SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated from 18F-FDG PET imaging data. The expression levels of NPM1 and TTF1 were assessed using The Cancer Genome Atlas (TCGA) database and immunohistochemistry of tumour tissues and adjacent normal lung tissues. We examined the association between the frequency of NPM1 and TTF1 expression and the metabolic parameters. RESULTS: Lung adenocarcinoma samples expressed higher levels of NPM1 than adjacent normal lung epithelial tissues. NPM1 showed higher specificity and sensitivity for lung adenocarcinoma compared with TTF1 (p < 0.001). SUVmax, SUVmean and TLG correlated with NPM1 expression (p < 0.001). MTV was inversely correlated with TTF1 (p < 0.01). SUVmax was the primary predictor of NPM1 expression by lung adenocarcinoma (p < 0.01). A cutoff value for the SUVmax of 3.93 allowed 90.9% sensitivity and 84.6% specificity for predicting NPM1 overexpression in lung adenocarcinoma. CONCLUSION: NPM1 overexpression correlated with 18F-FDG PET/CT metabolic parameters and improved diagnostic accuracy in lung adenocarcinoma. SUVmax on 18F-FDG PET/CT may estimate NPM1 expression for targeted therapy of lung adenocarcinoma.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/genética , Fluordesoxiglucose F18 , Glicólise , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Proteínas Nucleares , Nucleofosmina , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Carga TumoralRESUMO
Autophagy is a basic catabolic response that eukaryotic cells use to degrade unnecessary or dysfunctional cellular components in an orderly and regulated manner. It plays important roles in maintaining cellular homeostasis, energy homeostasis, response to environmental stimuli, and the development of cancer. In solid tumors, hypoxia induces an increased HIF-1a that activates autophagy. However, the exact mechanism by which induced HIF-1a stimulates autophagy in cancer cells remains elusive. In the present study, we confirmed that ANKRD37 is upregulated in colon cancer tissue. Moreover, the higher expression level of ANKRD37 is related to a poorer survival rate. Using RNA interference, immunoblot, and immunofluorescence, we discovered that in cancer cell line RKO, hypoxia-induced HIF-1a regulates autophagy activity by increasing ANKRD37 level. In addition, intranuclear ANKRD37 played an important role in the regulation of hypoxia-induced autophagy. The translocation of ANKRD37 into cell nuclear is required for promoting cell growth and HIF-1a induced autophagy. These findings provide new insights to understand the hypoxia regulation mechanisms and the role of autophagy in cancer development.
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Autofagia/efeitos dos fármacos , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Autofagia/genética , Autofagia/fisiologia , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/farmacologia , Interferência de RNA/efeitos dos fármacos , Interferência de RNA/fisiologia , Ativação Transcricional/fisiologiaRESUMO
BACKGROUND: The prognostic significance of peripheral blood-derived inflammation markers in patients with gastric cancer (GC) has not been elucidated. This study aimed to investigate the relationship between systemic inflammatory markers and GC prognosis. METHODS: A prospective observational cohort study involving 598 patients was conducted to analyze the prognosis of GC based on systemic inflammatory markers. The following peripheral blood-derived inflammation markers were evaluated: the neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), systemic immune-inflammation index (SII), C-reactive protein/albumin (CRP/Alb) ratio, Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), prognostic nutrition index (PNI), and prognostic index (PI). The receiver operating characteristics (ROC) curve and the Youden index were used to determine the optimal cutoff values. Univariate and multivariate analysis of prognostic factors was conducted accordingly. RESULTS: The optimal cutoff values of the PNI, fibrinogen, NLR, PLR, SII, and CRP/Alb were 49.5, 397 ng/dl, 2.5, 154, 556, and 0.05, respectively. Multivariate analysis showed that age, PLR, TNM stage, and chemotherapy were the independent prognostic factors for advanced gastric cancer (AGC). Adjuvant chemotherapy improved the long-term prognosis of patients with PLR ≥154, but chemotherapy had no significant effect on the survival of patients with PLR < 154. CONCLUSIONS: Our findings show that higher PLR (≥154) is an independent risk factor for poor prognosis in GC patients. Besides, PLR can predict adjuvant chemotherapy (oxaliplatin/5-fluorouracil combination) response in patients with GC after surgery.
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Inflamação/sangue , Neoplasias Gástricas/cirurgia , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Linfócitos , Masculino , Neutrófilos , Prognóstico , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Quality Protein Maize (QPM) is a hard kernel variant of the high-lysine mutant opaque2. Using γ-irradiation, we created opaque QPM variants to identify opaque2 modifier genes and to investigate deletion mutagenesis combined with Illumina sequencing as a maize (Zea mays) functional genomics tool. A K0326Y QPM deletion mutant was null for the 27- and 50-kD γ-zeins and abolished vitreous endosperm formation. Illumina exon and RNA sequencing revealed a 1.2-megabase pair deletion encompassing the 27- and 50-kD γ-zein genes on chromosome 7 and a deletion of at least 232 kb on chromosome 9. Protein body number was reduced by over 90%, while protein body size is similar to the wild type. Kernels hemizygous for the γ-zein deletion had intermediate 27- and 50-kD γ-zein levels and were semivitreous, indicating haploinsufficiency of these gene products in opaque2 endosperm modification. The γ-zein deletion further increased lysine in QPM in its homozygous and hemizygous states. This work identifies 27-kD γ-zein as an opaque2 modifier gene within the largest QPM quantitative trait locus and may suggest the 50-kD γ-zein also contributes to this quantitative trait locus. It further demonstrates that genome-wide deletions in nonreference maize lines can be identified through a combination of assembly of Illumina reads against the B73 genome and integration of RNA sequencing data.
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Endosperma/genética , Haploinsuficiência/genética , Zea mays/genética , Zeína/genética , Cromossomos de Plantas , Éxons , Raios gama , Deleção de Genes , Regulação da Expressão Gênica de Plantas , Lisina/metabolismo , Dados de Sequência Molecular , Mutagênese , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Locos de Características Quantitativas , RNA de Plantas , Zea mays/efeitos da radiaçãoRESUMO
Several empirical studies, particularly those conducted in developed countries, have linked social support to quality of life among persons living with HIV/AIDS (PLWA). However, few studies have been conducted in developing countries, such as China; therefore, the question of any association being present between social support and quality of life in PLWA in China remains unanswered. This retrospective cross-sectional study was conducted to examine the relationships between social support and quality of life among PLWA in the Jiangxi and Zhejiang provinces of China. A total of 377 PLWA participated in this study, and questionnaires used included demographics, the Chinese Medical Outcomes Study Short Form-36, and a Social Support Rating Scale, all of which were collected through face-to-face interviews between 1 March and 15 April 2013 in six different County Centers of Disease Control and Prevention in Jiangxi and Zhejiang provinces, and one hospital in the Jiangxi. The health-related quality of life score was 64.7±13.5 (out of a total score of 100), which was significantly lower than the national norm level of 78.2±15.9. The total score of social support was 29.4±7.8 (full score 66). The canonical correlation between social support and quality of participants' lives was shown to be statistically significant (p<0.0001). The relationship between subjective support and quality of life among PLWA was also significant (p=0.004). Subjective support and the use of social support showed a positive correlation with vitality, role-physical, and role-emotional, and a negative correlation with body pain. The current study suggests that PLWA with lower social support have diminished quality of life.
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Infecções por HIV/psicologia , Qualidade de Vida , Apoio Social , Adaptação Psicológica , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto JovemRESUMO
The immobilization of pre-dispersed TiO2 colloids onto the external surface of the clay mineral montmorillonite (Mt) was accomplished and regulated via a self-assembly method employing the cationic surfactant cetyltrimethylammonium bromide (CTAB). The role of CTAB in the synthesis process was investigated by preparing a series of TiO2-CTAB-Mt composites (TCM) with various CTAB doses. The results indicated that a uniform and continuous TiO2 film was deposited on the external surface of montmorillonite in the composite synthesized with 0.1 wt.% of CTAB, and the TCM nano-composites showed much higher values for specific surface area, average pore size and pore volume than the raw montmorillonite clay. Then, the formed TCM materials were applied in photocatalytic degradation of 2,4-dichlorophenol (2,4-DCP) in aqueous solution. The degradation efficiency reached as high as 94.7%. Based on the degradation intermediates benezoquinone, fumaric acid and oxalic acid identified by LC-MS analysis, a mechanism for the photocatalytic oxidation of 2,4-DCP on TiO2/Mt nano-composites is proposed.
Assuntos
Bentonita/química , Nanopartículas/química , Titânio/química , Águas Residuárias/análise , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Catálise , Microscopia Eletrônica de Varredura , Processos Fotoquímicos , Propriedades de Superfície , Águas Residuárias/química , Difração de Raios XRESUMO
Zeins, the maize (Zea mays) prolamin storage proteins, accumulate at very high levels in developing endosperm in endoplasmic reticulum membrane-bound protein bodies. Products of the multigene α-zein families and the single-gene γ-zein family are arranged in the central hydrophobic core and the cross-linked protein body periphery, respectively, but little is known of the specific roles of family members in protein body formation. Here, we used RNA interference suppression of different zein subclasses to abolish vitreous endosperm formation through a variety of effects on protein body density, size, and morphology. We showed that the 27-kilodalton (kD) γ-zein controls protein body initiation but is not involved in protein body filling. Conversely, other γ-zein family members function more in protein body expansion and not in protein body initiation. Reduction in both 19- and 22-kD α-zein subfamilies severely restricted protein body expansion but did not induce morphological abnormalities, which result from reduction of only the 22-kD α-zein class. Concomitant reduction of all zein classes resulted in severe reduction in protein body number but normal protein body size and morphology.
Assuntos
Endosperma/metabolismo , Proteínas de Plantas/metabolismo , Zea mays/metabolismo , Zeína/metabolismo , Endosperma/genética , Endosperma/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Dados de Sequência Molecular , Família Multigênica , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Interferência de RNA , Zea mays/genéticaRESUMO
Ammonia-oxidizing bacteria (AOB) are ubiquitous on the earth and have broad applications in bioremediation. However, the number of their species with standing in nomenclature and deposited in Microbial Culture Collections still remains low. Moreover, only a few novel species have been reported over the last decades. In this study, we sealed agar in serum bottles to develop a kind of solid agar plate with the oxygen concentration in the headspace maintained at low levels. By using these plates, eight AOB isolates including two novel species were obtained. When AOB cells were grown on the sealed solid agar plates, the time to form visible colonies was largely reduced and the maximum diameter of colonies reached 2 mm, which makes the process of AOB isolation rapid and efficient. Based on five AOB isolates, the headspace oxygen concentration had a significant influence on AOB growth either on solid plate or in liquid culture. Especially, when grown under 21 % O2, the number of colonies formed on solid agar plates was very low and sometimes no visible colony formed. Besides the application on AOB isolation, the sealed solid agar plate was also effective for the enumeration and preservation of AOB cells. When preserved under room temperature for more than ten months, the AOB colonies on the plate could still be recovered. This method provides a feasible way to isolate more novel AOB species from the environment and deposit more species in Microbial Culture Collections.