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1.
Cancer Sci ; 115(8): 2646-2658, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38889220

RESUMO

RNA-binding proteins can regulate nucleotide metabolism and gene expression. UPF3B regulator of nonsense mediated mRNA decay (UPF3B) exhibits dysfunction in cancers. However, its role in the progression of hepatocellular carcinoma (HCC) is still insufficiently understood. Here, we found that UPF3B was markedly upregulated in HCC samples and associated with adverse prognosis in patients. UPF3B dramatically promoted HCC growth both in vivo and in vitro. Mechanistically, UPF3B was found to bind to PPP2R2C, a regulatory subunit of PP2A, boosting its mRNA degradation and activating the PI3K/AKT/mTOR pathway. E2F transcription factor 6 (E2F6) directly binds to the UPF3B promoter to facilitate its transcription. Together, the E2F6/UPF3B/PPP2R2C axis promotes HCC growth through the PI3K/AKT/mTOR pathway. Hence, it could be a promising therapeutic target for treating HCC.


Assuntos
Carcinoma Hepatocelular , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Proteínas de Ligação a RNA , Serina-Treonina Quinases TOR , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Animais , Linhagem Celular Tumoral , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Serina-Treonina Quinases TOR/metabolismo , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Fosfatase 2/metabolismo , Proteína Fosfatase 2/genética , Transdução de Sinais , Masculino , Proliferação de Células/genética , Prognóstico , Feminino , Camundongos Nus , Regulação para Cima
2.
Funct Integr Genomics ; 24(4): 123, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38992207

RESUMO

Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis. It has been proven that long non-coding RNAs (lncRNAs) play an essential role in regulating HCC progression. However, the involvement of LINC01094 in regulating epithelial-mesenchymal transition (EMT) in HCC remains unclear. LINC01094 expression in HCC patients was retrieved from the Cancer Genome Atlas database. Overexpressing and downregulating LINC01094 were conducted to investigate its biological functions using Hep3B, SNU-387, and HuH-7 cells. Western blotting and morphological observation were performed to study the EMT in HCC cells. Transwell assay was adopted to determine the migration and invasion of HCC cells. The underlying mechanism of competitive endogenous RNAs (ceRNAs) was investigated using bioinformatics analysis, quantitative reverse-transcription polymerase chain reaction, and rescue experiments. Elevated LINC01094 expression was observed in HCC and associated with a poor prognosis. Knockdown of LINC01094 expression in SNU-387 and HuH-7 cells could inhibit migration, invasion, and EMT markers. Overexpression of LINC01094 indicated that LINC01094 promoted EMT via the TGF-ß/SMAD signaling pathway. The bioinformatics analysis revealed that miR-122-5p was a target of LINC01094. The miRWalk database analysis showed that TGFBR2, SMAD2, and SMAD3 were downstream targets of miR-122-5p. Mechanically, LINC01094 acted as a ceRNA that facilitated HCC metastasis by sponging miR-122-5p to regulate the expression of TGFBR2, SMAD2, and SMAD3. Further, TGF-ß1 could enhance the expression of LINC01094, forming a positive feedback loop. TGF-ß1-induced LINC01094 expression promotes HCC cell migration and invasion by targeting the miR-122-5p/TGFBR2-SMAD2-SMAD3 axis. LINC01094 may be a potential prognostic biomarker and therapeutic target for HCC metastasis.


Assuntos
Carcinoma Hepatocelular , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Receptor do Fator de Crescimento Transformador beta Tipo II , Proteína Smad3 , Fator de Crescimento Transformador beta1 , Humanos , Transição Epitelial-Mesenquimal/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Proteína Smad3/metabolismo , Proteína Smad3/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais
3.
Mol Cell Biochem ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512536

RESUMO

In recent years, nonalcoholic fatty liver disease (NAFLD) has become a more serious public health issue worldwide. This study strived to investigate the molecular mechanism of pathogenesis of NAFLD and explore promising diagnostic and therapeutic targets for NAFLD. Raw data from GSE130970 were downloaded from the Gene Expression Omnibus database. We used the dataset to analyze the expression levels of cuproptosis-related genes in NAFLD patients and healthy controls to identify the differentially expressed cuproptosis-related genes (DECRGs). The relationship and potential mechanism between DECRGs and clinicopathological factors were examined by enrichment analysis and two consensus clustering methods. We screened key DECRGs based on Random Forest (RF), and then verified the key DECRGs in NAFLD patients, high-fat diet (HFD)-fed mice, and palmitic acid-induced AML12 cells. ROC analysis showed good diagnostic function of DECRGs in normal and NAFLD liver tissue. Two consensus clusters indicated the important role of cuproptosis in the development of NAFLD. We screened for key DECRGs (DLD, DLAT) based on RF and found a close relationship between the DECRGs and clinicopathological factors. We collected clinical blood samples to verify the differences in gene expression levels by qPCR. In addition, we further verified the expression levels of DLD and DLAT in HFD mice and AML12 cells, which showed the same results. This study provides a novel perspective on the pathogenesis of NAFLD. We identified two cuproptosis-related genes that are closely related to NAFLD. These genes may play a significant role in the molecular pathogenesis of NAFLD, which may be useful to make progress in the diagnosis and treatment of NAFLD.

4.
Pestic Biochem Physiol ; 203: 106002, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39084798

RESUMO

Nitrogen (N) is one of the most intensively used fertilizers in cropping system and could exert a variety of bottom-up effects on the ecological fitness of herbivores. However, the effects of increased N inputs on insect pesticide tolerance have not been comprehensively understood. Bioassays showed that high N (HN) applied to maize plants significantly increased larval tolerance of Spodoptera litura to multiple insecticides. Activities of detoxification enzymes were significantly higher in the larvae fed on maize plants supplied with HN. RNA-seq analysis showed that numerous GST and cuticle-related genes were induced in the larvae fed on HN maize. RT-qPCR analysis further confirmed four GST genes and larval-specific cuticle gene LCP167. Furthermore, when injected with dsRNA specific to GSTe1, GSTs5, and LCP167, the mortality of larvae treated with methomyl was about 3-fold higher than that of dsGFP-injected larvae. Electron microscope observation showed that cuticle of the larvae fed on HN maize was thicker than the medium level of N. These findings suggest that increased application of N fertilizer enhances insecticide tolerance of lepidopteran pests via induction of detoxification enzymes and intensification of cuticle. Thus, overuse of N fertilizer may increase pest insecticide tolerance and usage of chemical insecticides.


Assuntos
Inseticidas , Larva , Nitrogênio , Spodoptera , Zea mays , Animais , Zea mays/genética , Spodoptera/efeitos dos fármacos , Spodoptera/genética , Nitrogênio/metabolismo , Inseticidas/farmacologia , Inseticidas/toxicidade , Larva/efeitos dos fármacos , Resistência a Inseticidas/genética , Fertilizantes , Glutationa Transferase/metabolismo , Glutationa Transferase/genética , Inativação Metabólica , Herbivoria/efeitos dos fármacos
5.
Int J Mol Sci ; 25(5)2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38473905

RESUMO

Chronic kidney disease (CKD) affects > 10% of the global adult population and significantly increases the risk of cardiovascular disease (CVD), which remains the leading cause of death in this population. The development and progression of CVD-compared to the general population-is premature and accelerated, manifesting as coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. CKD and CV disease combine to cause multimorbid cardiorenal syndrome (CRS) due to contributions from shared risk factors, including systolic hypertension, diabetes mellitus, obesity, and dyslipidemia. Additional neurohormonal activation, innate immunity, and inflammation contribute to progressive cardiac and renal deterioration, reflecting the strong bidirectional interaction between these organ systems. A shared molecular pathophysiology-including inflammation, oxidative stress, senescence, and hemodynamic fluctuations characterise all types of CRS. This review highlights the evolving paradigm and recent advances in our understanding of the molecular biology of CRS, outlining the potential for disease-specific therapies and biomarker disease detection.


Assuntos
Síndrome Cardiorrenal , Doenças Cardiovasculares , Insuficiência Cardíaca , Insuficiência Renal Crônica , Humanos , Doença Crônica , Insuficiência Renal Crônica/complicações , Inflamação/complicações
6.
Anal Chem ; 93(41): 13815-13822, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34609844

RESUMO

Brain pH has been proven to be a key factor in maintaining normal brain function. The relationship between local pH fluctuation and brain disease has not been extensively studied due to lack of the accurate in situ analysis technology. Herein, we have for the first time proposed a voltammetric pH sensor by measuring the ratio of current signals instead of the previously reported potential based on the Nernst equation. Single-walled carbon nanotubes (CNT) were first self-assembled on the electrode surface of a carbon-fiber nanotip electrode (CFNE). Then, poly-o-phenylenediamine (PoPD) molecules were deposited as pH-responsive molecules through in situ electrochemical polymerization. The compact CFNE/CNT/PoPD exhibited a good redox process with the on-off-on ratiometric electrochemical response to pH ranging from 4.5 to 8.2, providing self-correction for in situ pH detection. Thus, the proposed sensor enabled the accurate measurement of pH with excellent selectivity even in the presence of proteins or electroactive species. In addition, the sensor showed high repeatability, reproducibility, and reversibility in measuring pH and even demonstrated good stability when it was exposed to air for 5 months. Finally, we successfully detected the fluctuation of pH in rat brains with cerebral ischemia and rat whole blood. Overall, this research not only provides a good tool for the detection of rat brain pH but also provides a new strategy for further designing nanosensors for intracellular or subcellular pH.


Assuntos
Nanotubos de Carbono , Animais , Encéfalo , Técnicas Eletroquímicas , Eletrodos , Concentração de Íons de Hidrogênio , Ratos , Reprodutibilidade dos Testes
7.
Pestic Biochem Physiol ; 154: 60-66, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30765057

RESUMO

Generalist phytophagous insects adapt to adventurous chemical environment in a wide variety of host plants by extraordinary detoxifying metabolic abilities. However, how polyphagous insect cope with the diversity of plant defenses remains largely unknown and only a few counter-defense genes detoxifying a wide range of toxic secondary metabolites have been well characterized. Here, we identify a cytochrome P450 gene (CYP6AB60) from tobacco cutworm (Spodoptera litura) in response to three different plant's defense metabolites. After being exposed to artificial diet supplemented with coumarin (COU), xanthotoxin (XAN) or tomatine (TOM), activities of P450 and CYP6AB60 transcript levels in both midgut and fat body tissues were significantly increased. Developmental expression analysis revealed that CYP6AB60 was expressed highly during the larval stages, and tissue distribution analysis showed that CYP6AB60 was expressed extremely high in the midgut, which correspond to the physiological role of CYP6AB60 from S. litura larvae in response to plant allelochemicals. Furthermore, when larvae are injected with double-stranded RNA (dsRNA) specific to CYP6AB60, levels of this transcript in the midgut and fatbody decrease and the negative effect of plant's defense metabolites on larval growth is magnified. These data demonstrate that the generalist insect S. litura might take advantage of an individual detoxificative gene CYP6AB60 to toxic secondary metabolites from different host plants. The CYP6AB60 can be a potential gene to carry out RNAi-mediated crop protection against the major polyphagous pest S. litura in the future.


Assuntos
Família 6 do Citocromo P450/genética , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Proteínas de Insetos/genética , Larva/efeitos dos fármacos , Feromônios/farmacologia , Spodoptera/efeitos dos fármacos , Animais , Cumarínicos/farmacologia , Tolerância a Medicamentos/genética , Larva/genética , Metoxaleno/farmacologia , Interferência de RNA , Spodoptera/genética , Tomatina/farmacologia
8.
Cell Physiol Biochem ; 48(3): 934-946, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30036879

RESUMO

BACKGROUND/AIMS: Diabetic cardiomyopathy (DCM) is a serious complication of diabetes. It is therefore crucial to elucidate the characteristic metabolic changes that occur during the development of diabetes to gain an understanding the pathogenesis of this disease and identify potential drug targets involved. METHODS: 1H nuclear magnetic resonance-based metabonomics combined with HPLC measurements were used to determine the metabolic changes in isolated cardiac tissues after 5 weeks, 9 weeks, and 15 weeks in rats treated with streptozotocin. RESULTS: Pattern recognition analysis clearly discriminated the diabetic rats from time-matched control rats, suggesting that the metabolic profile of the diabetic group was markedly different from that of the controls. Quantitative analysis showed that the levels of energy metabolites, such as the high-energy phosphate pool (ATP and creatine), significantly decreased in a time-dependent manner. Correlation analysis revealed the inhibition of glycolysis and the tricarboxylic acid (TCA) cycle, enhanced lipid metabolism, and changes in some amino acids, which may have led to the decline in energy production in the DCM rats. CONCLUSIONS: The results indicated that the administration of energy substances or the manipulation of myocardial energy synthesis induced by increased glucose oxidation may contribute to the amelioration of cardiac dysfunction in diabetes.


Assuntos
Cardiomiopatias Diabéticas/patologia , Metabolismo Energético , Metaboloma , Trifosfato de Adenosina/análise , Aminoácidos/análise , Aminoácidos/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Creatina/análise , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Cardiomiopatias Diabéticas/etiologia , Análise Discriminante , Análise dos Mínimos Quadrados , Espectroscopia de Ressonância Magnética , Masculino , Metabolômica , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley
9.
Artigo em Inglês | MEDLINE | ID: mdl-29932974

RESUMO

The major yolk protein precursors (YPP) gene, vitellogenin (Vg), usually considered as a reproductive indicator and molecular marker for evaluating insect fecundity, is controlled by insect hormone (mainly ecdysteroids and juvenile hormone), transcription factors and many other fecundity-related genes. To better understand the underlying molecular regulation mechanisms of the NlVg in the brown planthopper Nilaparvata lugens (N. lugens), the correlation between one early ecdysone response gene E74 and one important fecundity-related gene angiotensin converting enzyme (ACE) on the regulation of Vg gene expression, was investigated. We first showed that the mRNA expression level of NlACE were significantly higher in a high-fecundity population (HFP) than a low-fecundity population (LFP) at different development stages, and knockdown of NlACE expression by RNA interference (RNAi) results in a reduced level of NlVg expression and N. lugens fecundity. Subsequently, we analyzed the promoter of NlACE and found an E74A binding site, which was also differentially expressed in HFP and LFP. Then a gene putatively encoding E74A, namely NlE74A, predominant in the ovary and fat body was cloned and characterized. Furthermore, the developmental profile during female adult and the tissue-specific expression pattern of NlACE and NlE74A were similar to the expression pattern of NlVg gene, implying that both NlACE and NlE74A may be involved in regulating the expression of NlVg. Finally, after injecting the dsRNA of NlE74A, the NlACE expression levels were significantly reduced simultaneously at 24 h and 48 h post-injection, and the NlVg expression level was significant reduced at 24 h post-injection and the downswing was more significant at 48 h post-injection. These results imply that regulation of NlE74A on NlVg transcription might be mediated by NlACE through the E74 binding site at the NlACE promoter region in N. lugens.


Assuntos
Fertilidade/genética , Hemípteros/fisiologia , Proteínas de Insetos/metabolismo , Peptidil Dipeptidase A/metabolismo , Polimorfismo de Nucleotídeo Único , Vitelogeninas/genética , Animais , DNA Complementar/biossíntese , DNA Complementar/genética , Regulação da Expressão Gênica/fisiologia , Hemípteros/enzimologia , Hemípteros/metabolismo , Proteínas de Insetos/genética , Peptidil Dipeptidase A/genética , Regiões Promotoras Genéticas , Ligação Proteica , RNA/isolamento & purificação , Interferência de RNA , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição/metabolismo , Transcrição Gênica/fisiologia
10.
Korean J Physiol Pharmacol ; 18(4): 313-20, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25177163

RESUMO

The study was conducted to investigate the role of vitamin E in the high altitude hypoxia-induced damage to the intestinal barrier in rats. Sprague-Dawley rats were divided into control (Control), high altitude hypoxia (HH), and high altitude hypoxia+vitamin E (250 mg/kg BW*d) (HV) groups. After the third day, the HH and HV groups were placed in a hypobaric chamber at a stimulated elevation of 7000 m for 5 days. The rats in the HV group were given vitamin E by gavage daily for 8 days. The other rats were given equal volume saline. The results showed that high altitude hypoxia caused the enlargement of heart, liver, lung and kidney, and intestinal villi damage. Supplementation with vitamin E significantly alleviated hypoxia-caused damage to the main organs including intestine, increased the serum superoxide dismutase (SOD) (p< 0.05), diamino oxidase (DAO) (p< 0.01) levels, and decreased the serum levels of interleukin-2 (IL-2) (p< 0.01), interleukin-4 (IL-4) (p<0.001), interferon-gamma (IFN-γ) (p<0.01) and malondialdehyde (MDA) (p<0.001), and decreased the serum erythropoietin (EPO) activity (p<0.05). Administration of vitamin E significantly increased the S-IgA (p<0.001) in ileum and significantly improved the expression levels of occludin and IκBα, and decreased the expression levels of hypoxia-inducible factor 1 alpha and 2 alpha (HIF-1α and HIF-2α), Toll-like receptors (TLR4), P-IκBα and nuclear factor-κB p65(NF-κB P65) in ileum compared to the HH group. This study suggested that vitamin E protectis from intestinal injury caused by high altitude hypoxia environment. These effects may be related to the HIF and TLR4/NF-κB signaling pathway.

11.
J Pharm Biomed Anal ; 245: 116184, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38692214

RESUMO

The plant of Paeonia lactiflora Pall. belongs to Ranunculaceae, and its root can be divided into two categories according to different processing methods, which included that one was directly dried without peeling the root of the P. lactiflora (PR), and the other was peeled the root of the P. lactiflora (PPR) after boiled and dried. To evaluate the difference of chemical components, UPLC-ESI-Q-Exactive Focus-MS/MS and UPLC-QQQ-MS were applied. The distribution of chemical components in different tissues was located by laser microdissection (LMD), especially the different ingredients. A total of 86 compounds were identified from PR and PPR. Four kind of tissues were isolated from the fresh root of the P. lactiflora (FPR), and 54 compounds were identified. Especially the content of gallic acid, albiflorin, and paeoniflorin with high biological activities were the highest in the cork, but they were lower in PR than that in PPR, which probably related to the process. To illustrate the difference in pharmacological effects of PR and PPR, the tonifying blood and analgesic effects on mice were investigated, and it was found that the tonifying blood and analgesic effects of PPR was superior to that of PR, even though PR had more constituents. The material basis for tonifying blood and analgesic effect of the root of P. lactiflora is likely to be associated with an increase in constituents such as paeoniflorin and paeoniflorin lactone after boiled and peeled. The study was likely to provide some theoretical support for the standard and clinical application.


Assuntos
Glucosídeos , Monoterpenos , Paeonia , Raízes de Plantas , Animais , Masculino , Camundongos , Analgésicos/farmacologia , Analgésicos/química , Analgésicos/análise , Hidrocarbonetos Aromáticos com Pontes , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Ácido Gálico/análise , Ácido Gálico/química , Glucosídeos/análise , Glucosídeos/química , Lasers , Espectrometria de Massa com Cromatografia Líquida , Microdissecção/métodos , Monoterpenos/farmacologia , Monoterpenos/análise , Monoterpenos/química , Paeonia/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos
12.
Waste Manag ; 186: 35-45, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38852375

RESUMO

The active graphite felt (GF) catalytic layer was effectively synthesized through a wet ultrasonic impregnation-calcination method, modified with CB and PTFE, and implemented in a pioneering side-aeration electrochemical in-situ H2O2 reactor. The optimal mass ratio (CB: PTFE 1:4) for the modified cathode catalytic layer was determined using a single-factor method. Operating under optimum conditions of initial pH 5, 0.5 L/min air flow, and a current density of 9 mA/cm2, the system achieved a remarkable maximum H2O2 accumulation of 560 mg/L, with the H2O2 production capacity consistently exceeding 95 % over 6 usage cycles. The refined mesoporous structure and improved three-phase interface notably amplified oxygen transfer, utilization, and H2O2 yield. Side aeration led to an oxygen concentration near the cathode reaching 20 mg/L, representing a five-fold increase compared to the 3.95 mg/L achieved with conventional bottom aeration. In the final application, the reaction system exhibited efficacy in the degradation of landfill leachate concentrate. After a 60-minute reaction, complete removal of chroma was attained, and the TOC degradation rate surpassed 60 %, marking a sixfold improvement over the conventional system. These results underscore the substantial potential of the system in H2O2 synthesis and environmental remediation.


Assuntos
Eletrodos , Peróxido de Hidrogênio , Poluentes Químicos da Água , Peróxido de Hidrogênio/química , Poluentes Químicos da Água/química , Técnicas Eletroquímicas/métodos , Catálise , Grafite/química , Oxigênio/química
13.
Clin Exp Metastasis ; 41(2): 81-90, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38396262

RESUMO

OBJECTIVE: Aberrant expression of CD276 has been reported in malignant tumors. However, the exact role and mechanisms of CD276 influence the progression of esophageal squamous cell carcinoma (ESCC) still need to be understood. METHODS: Bioinformatics analysis of data from The Cancer Genome Atlas and Gene Expression Omnibus databases, along with immunohistochemistry staining, was used to explore the expression patterns of CD276 in ESCC. Cell counting kit-8 and Transwell assays were employed to evaluate the effects of CD276 expression on tumor cell proliferation and motility. Western blotting and Transwell assays were used to explore the potential pathways through which CD276 mediates the progression of ESCC. Moreover, the in vivo role of CD276 in tumor progression was investigated by establishing a lung metastasis mouse model. RESULTS: A significant upregulation of CD276 was observed in ESCC tissues compared to adjacent tissues. The inhibition of CD276 had no evident impact on ESCC cell proliferation but notably hindered their migratory and invasive properties and the expression of epithelial-mesenchymal transition (EMT) markers. Inversely, overexpressing CD276 led to an upregulation of EMT markers, underscoring the capacity of CD276 to amplify the motility of ESCC cells. Furthermore, CD276 was found to enhance the migratory and invasive abilities of ESCC cells by activating the TGF-ß/SMAD signaling but not the PI3K/AKT pathway. In vivo studies demonstrated that CD276 facilitates pulmonary metastasis. CONCLUSION: CD276 is significant upregulation in ESCC tissues and facilitates the EMT process in ESCC cells via the TGF-ß/SMAD signaling, thus promoting the progression of ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Animais , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , Fosfatidilinositol 3-Quinases , Fatores de Transcrição/genética , Fator de Crescimento Transformador beta
14.
JACC Basic Transl Sci ; 9(5): 607-627, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38984053

RESUMO

Patients with chronic kidney disease (CKD) face a high risk of cardiovascular disease. Previous studies reported that endogenous thrombospondin 1 (TSP1) involves right ventricular remodeling and dysfunction. Here we show that a murine model of CKD increased myocardial TSP1 expression and produced left ventricular hypertrophy, fibrosis, and dysfunction. TSP1 knockout mice were protected from these features. In vitro, indoxyl sulfate is driving deleterious changes in cardiomyocyte through the TSP1. In patients with CKD, TSP1 and aryl hydrocarbon receptor were both differentially expressed in the myocardium. Our findings summon large clinical studies to confirm the translational role of TSP1 in patients with CKD.

15.
J Thorac Dis ; 15(4): 1994-2002, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37197504

RESUMO

Background: The incidence of non-small cell lung cancer ranks second among malignant tumors, while the mortality rate ranks first. We established a prediction model for the long-term prognosis of lung cancer patients to accurately identify patients with a high risk of postoperative death and provide a theoretical basis for improving the prognosis of patients with non-small cell lung cancer. Methods: The data of 277 non-small cell lung cancer patients who underwent radical lung cancer resection at Shanghai Fengxian District Central Hospital between January 2016 and December 2017 were retrospectively collected. The patients, who were followed up for 5 years, were divided into a deceased group (n=127) and survival group (n=150) according to whether the patients had died 5 years after surgery or not. The clinical characteristics of the two groups were observed, and the risk factors of death within 5 years of surgery in lung cancer patients were analyzed. A nomogram predictive model was then established to analyze the value of the model in predicting the death within 5 years of surgery in patients with non-small cell lung cancer. Results: Multivariate logistics regression analysis showed that carcinoembryonic antigen (CEA) >193.5 ng/mL, stage III lung cancer, peritumor invasion, and vascular tumor thrombus were independent risk factors of tumor-specific death after surgery in patients with non-small cell lung cancer (P<0.05). R 4.0.3 statistical software was used to randomly divide the dataset into a training set and validation set. The sample size of the training set was 194, and the sample size of the validation set was 83. The area under the receiver operating characteristic (ROC) curve was 0.850 [95% confidence interval (CI): 0.796-0.905] in the training set, and it was 0.779 (95% CI: 0.678-0.880) in the validation set. In the validation set, the model was assessed using the Hosmer-Lemeshow goodness-of-fit test, with a chi-square value of 9.270 and a P value of 0.320. Conclusions: Our model could accurately identify high risk of death within 5 years of surgery in non-small cell lung cancer patients. Strengthening the management of high-risk patients may help improve the prognosis of these patients.

16.
Sci Rep ; 13(1): 2687, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36792673

RESUMO

China is a major coal producer, with huge differences in coal production and safety situations between the South and the North. Taking province A as an example, its coal enterprises have low output, poor efficiency, backward equipment, and low-quality personnel. The output accounts for 0.08% of the country, and the number of deaths accounts for 2.2% of the country, the safety situation of coal enterprises in province A is severe. In order to study the safety risk situation of coal mines under difficult conditions, this paper screens 98 factor indexes including multiple subjects such as enterprise managers, front-line workers, government supervisors, external environment, work quality, stress factors, economic factors, and other dimensions. For different data, the indicator weights were calculated using triangular fuzzy number, entropy weight method, CRITIC method, and three rough set methods in a total of six methods. The comprehensive weights of the indicators were obtained using the proposed new comprehensive weight method. The current situation of safety work of four coal mining enterprises and three levels of government supervision departments was evaluated, and the evaluation results were compared with other existing data to verify the reliability of the evaluation system. The horizontal comparison of the evaluation results indicates the main problems of each subject; the longitudinal comparison points out the problems that need to be solved with the assistance of higher-level enterprises and the central government, and corresponding suggestions for coal mining enterprises and government departments are put forward to reduce the safety risks of troubled coal mining enterprises.

17.
Environ Sci Pollut Res Int ; 29(59): 88540-88556, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35836044

RESUMO

In this study, experimental studies on atomization process and dust reduction performance of four swirl nozzles with different inlet/outlet diameter ratio (D) were performed. The results of the atomization process study of the nozzle show that with the increase of D, the droplet breakup range of the spray field is gradually increasing, but the droplet breakup intensity of the spray field is gradually decreasing. At D = 3.33 and 3.63, droplet breakup occurs mainly in the range of 0-4 mm in the strong turbulent region. At D = 3.75, droplet breakup occurs mainly in the range of 0-2 mm in the strong turbulent region. At D = 3.96, droplet breakup occurs mainly in the range of 0-1 mm in the strong turbulent region. Droplet breakup in the spray field at D = 3.33 and D = 3.67 was better than that at D = 3.75 and D = 3.96. From the dust reduction experimental results, the dust reduction efficiency increases and then decreases with the increase of D. The dust reduction efficiency is highest among the four nozzles at D = 3.67. Based on the dust reduction curves of four different D of nozzles, it is predicted that the optimal dust reduction condition will be achieved at D of 3.60, which provides a reference for the design and optimization of nozzles.


Assuntos
Poeira , Tamanho da Partícula
18.
Materials (Basel) ; 15(7)2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35407778

RESUMO

The preparation of a high-strength biodegradable plastic has always been the focus of academia. Here, we prepared two biodegradable composites using silane coupling-agent-modified hemp fibers (Si-HF) and unmodified hemp fibers (HF) with butylene adipate-co-terephthalate (PBAT), respectively. We compared the differences of Si-HF/PBAT and HF/PBAT in terms of micromorphology, density, mechanical properties, thermal stability and biodegradability. The Si-HF has better interface interaction between the hemp and the PBAT matrix than the HF, which makes Si-HF/PBAT have better tensile properties. Moreover, Si-HF/PBAT has stronger tensile strength and modulus than HF/PBAT. Our results also show that the two composites have good biodegradability. This study provides an important reference for the subsequent development and utilization of hemp fibers.

19.
Environ Sci Pollut Res Int ; 29(49): 74895-74908, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35641752

RESUMO

Surfactants can reduce the surface tension of water and improve the efficiency of spray dust reduction, but the synergistic mechanism of composite surfactant solutions wetting coal dust remains unclear. In this study, sodium dodecyl sulfonate (SDDS)/sodium dodecylbenzene sulfonate (SDBS) solution and SDDS/primary alcohol ethoxylate (AEO-9) solution were prepared to wet three types of coal with different deterioration degrees. The surface tension, contact angle, and functional group composition were measured. The results show that SDDS/AEO-9 solution had lower surface tension and critical micelle concentration than SDDS/SDBS solution at the same mixing ratio. When the ratio of SDDS: SDBS was 2:1, it had the best wetting effect on coal dust. It is found that for SDDS/SDBS solutions, aliphatic hydrocarbons and surface tension have a positive correlation with the contact angle, and hydroxyl groups have a negative correlation with the contact angle. For SDDS/AEO-9 solution, only the surface tension and contact angle show a significant linear relationship. The main factors that affect the wetting change with the combination of surfactants. AEO-9 has an electrostatic shielding effect on SDDS, while SDBS increases the electrostatic repulsion between SDDS solution and electronegative functional groups of coal. The synergism among these surfactants plays an important role in the process of wetting coal.


Assuntos
Carvão Mineral , Tensoativos , Dapsona/análogos & derivados , Poeira , Micelas , Simulação de Dinâmica Molecular , Sódio , Água
20.
Environ Sci Pollut Res Int ; 29(46): 69771-69784, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35578079

RESUMO

Aiming at the problems of complex environment and serious dust pollution in large open-pit coal yards, a dust suppression gel with a dual network structure was prepared by modifying the soluble starch and sodium alginate with iron ions. The changes of functional groups, thermal stability, and morphology structure before and after the reaction were analyzed by FTIR, TG-DSC, and SEM, and the formation mechanism of the dual network was revealed by XPS. Furthermore, the water absorption and water retention experiments proved that the dual network structure is more conducive to water retention than the single-layer network. According to molecular dynamics simulations and contact angle experiments, gel and adsorbed water molecules can approach coal dust molecules on their own to contact, wet, and combine with coal dust. The adhesion test proved that the dust suppression gel with iron ions had better adhesion to dust. The anti-freezing test shows that the dust suppression gel has good anti-freezing performance. The antifreeze test shows that the dust suppression gel still has excellent freeze-thaw resistance at the test temperature of -20℃. The mechanical property test shows that the dust suppressant gel can prevent the product from being damaged by external force. The acid and alkali resistance experiments showed that the acid and alkali resistance of the gel was improved under the condition of iron ion modification, and the flying of coal powder was effectively prevented. This research provides a new theoretical idea for coal dust control in complex environment.


Assuntos
Alginatos , Poeira , Alginatos/química , Carvão Mineral/análise , Poeira/análise , Íons , Ferro , Minerais , Pós , Amido , Água
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