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1.
Pharmacol Res ; 204: 107212, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38749377

RESUMO

Triggering receptor expressed on myeloid cells 1 (TREM1) is a cell surface receptor expressed on neutrophils, monocytes and some tissue macrophages, where it functions as an immunoregulator that controls myeloid cell responses. The activation of TREM1 is suggested to be an upregulation-based, ligands-induced and structural multimerization-mediated process, in which damage- and pathogen-associated molecular patterns play important roles. Activated TREM1 initiates an array of downstream signaling pathways that ultimately result in the production of pro-inflammatory cytokines and chemokines, whereby it functions as an amplifier of inflammation and is implicated in the pathogenesis of many inflammation-associated diseases. Over the past decade, there has been growing evidence for the involvement of TREM1 overactivation in tumor stroma inflammation and cancer progression. Indeed, it was shown that TREM1 promotes tumor progression, immunosuppression, and resistance to therapy by activating tumor-infiltrating myeloid cells. TREM1-deficiency or blockade provide protection against tumors and reverse the resistance to anti-PD-1/PD-L1 therapy and arginine-deprivation therapy in preclinical models. Here, we first review the structure, activation modes and signaling pathways of TREM1 and emphasize the role of soluble TREM1 as a biomarker of infection and cancer. We then focus on the role of TREM1 in cancer and systematically summarize its expression patterns, upregulation mechanisms and functions in tumor development and progression. Lastly, we discuss the therapeutic prospects of TREM1 inhibition, via effective pharmacological inhibitors, in treating cancer and other diseases.


Assuntos
Neoplasias , Transdução de Sinais , Receptor Gatilho 1 Expresso em Células Mieloides , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Receptor Gatilho 1 Expresso em Células Mieloides/antagonistas & inibidores , Receptor Gatilho 1 Expresso em Células Mieloides/genética , Humanos , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/genética , Neoplasias/patologia , Animais , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia
2.
Cancer Immunol Immunother ; 72(3): 647-664, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36036290

RESUMO

CD8 + T lymphocytes are immune cells that play a crucial anti-tumor role in the human body, and prognostic value of CD8 + T cell-related regulatory genes in PAAD remains elusive. Data on 179 expression profiles across 13 immune cell datasets were downloaded from the GEO database, and the expression profiles of CD8 + T cell-related genes were obtained using WGCNA. Molecular subtypes based on CD8 + T cell-related genes were constructed using the ConsensusClusterPlus algorithm. Lasso regression analysis was performed to build a 10-gene signature. GSVA was performed to explore the pathways related to these ten genes. The IMvigor210 cohort was used to explore the predictive efficacy of the signature in terms of immunotherapy response. Four hundred and forty-six CD8 + T cell-related genes were obtained. One hundred and nine genes in TCGA and GEO datasets were closely related to the prognosis of patients and were included in the next study. PAAD samples were divided into two subtypes (IC1 and IC2) according to consensus cluster analysis. These two immune subtypes were significantly different in terms of immune checkpoint genes, immune function, and drug treatment response. Additionally, the 10-gene signature constructed based on CD8 + T cell-related genes showed a stable prognostic performance in TCGA and GEO cohorts. Moreover, it served as an independent prognostic factor for patients with PAAD. Furthermore, the 10-gene signature could effectively predict the response to immunotherapy. The immunophenotyping-derived prognostic model based on CD8 T cell-related genes provides a basis for the clinical treatment of pancreatic cancer.


Assuntos
Neoplasias Pancreáticas , Humanos , Prognóstico , Linfócitos T CD8-Positivos , Algoritmos , Neoplasias Pancreáticas
3.
Cancer Cell Int ; 21(1): 621, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34819088

RESUMO

BACKGROUND: The aim of this study was to construct a model based on the prognostic features associated with epithelial-mesenchymal transition (EMT) to explore the various mechanisms and therapeutic strategies available for the treatment of metastasis and invasion by hepatocellular carcinoma (HCC) cells. METHODS: EMT-associated genes were identified, and their molecular subtypes were determined by consistent clustering analysis. The differentially expressed genes (DEGs) among the molecular subtypes were ascertained using the limma package and they were subjected to functional enrichment analysis. The immune cell scores of the molecular subtypes were evaluated using ESTIMATE, MCPcounter, and GSCA packages of R. A multi-gene prognostic model was constructed using lasso regression, and the immunotherapeutic effects of the model were analyzed using the Imvigor210 cohort. In addition, immunohistochemical analysis was performed on a cohort of HCC tissue to validate gene expression. RESULTS: Based on the 59 EMT-associated genes identified, the 365-liver hepatocellular carcinoma (LIHC) samples were divided into two subtypes, C1 and C2. The C1 subtype mostly showed poor prognosis, had higher immune scores compared to the C2 subtype, and showed greater correlation with pathways of tumor progression. A four-gene signature construct was fabricated based on the 1130 DEGs among the subtypes. The construct was highly robust and showed stable predictive efficacy when validated using datasets from different platforms (HCCDB18 and GSE14520). Additionally, compared to currently existing models, our model demonstrated better performance. The results of the immunotherapy cohort showed that patients in the low-risk group have a better immune response, leading to a better patient's prognosis. Immunohistochemical analysis revealed that the expression levels of the FTCD, PON1, and TMEM45A were significantly over-expressed in 41 normal samples compared to HCC samples, while that of the G6PD was significantly over-expressed in cancerous tissues. CONCLUSIONS: The four-gene signature construct fabricated based on the EMT-associated genes provides valuable information to further study the pathogenesis and clinical management of HCC.

4.
Pharmacol Res ; 164: 105370, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33316381

RESUMO

The prognoses of patients with pancreatic adenocarcinoma (PAAD) remain poor due to the lack of biomarkers for early diagnosis and effective prognosis prediction. RNA sequencing, single nucleotide polymorphism, and copy number variation data were downloaded from The Cancer Genome Atlas (TCGA). Univariate Cox regression was used to identify prognosis-related genes. GISTIC 2.0 was used to identify significantly amplified or deleted genes, and Mutsig 2.0 was used to analyze the mutation data. The Lasso method was used to construct a risk prediction model. The Rms package was used to evaluate the overall predictive performance of the signature. Finally, Western blot and polymerase chain reaction were performed to evaluate gene expression. A total of 54 candidate genes were obtained after integrating the genomic mutated genes and prognosis-related genes. The Lasso method was used to ascertain 9 characteristic genes, including UNC13B, TSPYL4, MICAL1, KLHDC7B, KLHL32, AIM1, ARHGAP18, DCBLD1, and CACNA2D4. The 9-gene signature model was able to help stratify samples at risk in the training and external validation cohorts. In addition, the overall predictive performance of our model was found to be superior to that of other models. KLHDC7B, AIM1, DCBLD1, TSPYL4, and MICAL1 were significantly highly expressed in tumor tissues compared to normal tissues. ARHGAP18 and CACNA2D4 had no difference in expression between tumor and normal tissues. UNC13B and KLHL32 expression in the normal group was higher than in the tumor group. The 9-gene signature constructed in this study can be used as a novel prognostic marker to predict the survival of patients with pancreatic adenocarcinoma.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Modelos Biológicos , Neoplasias Pancreáticas/genética , Adenocarcinoma/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Variações do Número de Cópias de DNA , Feminino , Genoma , Humanos , Masculino , Mutação , Pâncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Fatores de Risco , Transcriptoma
5.
Pharmacol Res ; 163: 105265, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33129983

RESUMO

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality; it has been reported that immune cell infiltration is a prognosis factor. Here we identified genes that associated with tumor immune cell infiltrate; the underlying mechanism was verified by in vivo and in vitro experiment. In this study, Weighted correlation network analysis (WGCNA) and CIBERSORT tool were used to identify MTIF2 as the hub tumor immune infiltrating gene in HCC. To investigate the underlying role played by MTIF2, MTIF2 was knocked down by transfection of shRNA targeting MTIF2, CCK8, and EdU incorporation assay was used to evaluate the effect of MTIF2 on proliferation, wound heal assay and transwell assay was used to confirm its effect on cell migration. Ecto-calreticulin on the cell surface was evaluated by flow cytometry, ATP, and HMGB1 secretion were tested to the investigated effect of MTIF2 on the immunogenic cell death (ICD) process. We found that down-regulation of MTIF2 impaired proliferation and migration capacity of HCC cells, chemoresistance to 5-Fluorouracil (5-FU) weakened after MTIF2 was knocked down. Reduced release of damage-associated molecular patterns (DAMP) was observed after MTIF2 was overexpressed, which subsequently impaired dendritic cell (DC) maturation and proliferation of CD8 + T cells. Mechanically, the co-IP experiment confirmed that MTIF2 could interact with AIFM1, prevents AIFM1 induced transcription of caspase3, and finally suppress apoptosis. In vivo experiment also used to confirm our previously conclusion, our result indicated that MTIF2 overexpression suppresses tumor apoptosis and immune cell activity in the 5-FU therapy in vivo model, by suppression maturation of tumor-infiltrated DC. Collectively, our study confirmed that MTIF2 impair drug-induced immunogenic cell death in hepatocellular carcinoma cells.


Assuntos
Carcinoma Hepatocelular/genética , Fatores de Iniciação em Eucariotos/genética , Morte Celular Imunogênica/genética , Neoplasias Hepáticas/genética , Proteínas Mitocondriais/genética , Idoso , Animais , Antimetabólitos Antineoplásicos , Apoptose , Fator de Indução de Apoptose/metabolismo , Carcinoma Hepatocelular/metabolismo , Caspase 3/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Citocinas/metabolismo , Regulação para Baixo , Fatores de Iniciação em Eucariotos/metabolismo , Feminino , Fluoruracila , Humanos , Imunossupressores , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/metabolismo , Prognóstico
6.
Eur J Nutr ; 60(8): 4505-4517, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34129072

RESUMO

PURPOSE: We aimed to investigate whether the gut microbiota and fecal short-chain fatty acids (SCFAs) are associated with bone mass in healthy children aged 6-9 years. METHODS: In this study, 236 healthy children including 145 boys and 91 girls were enrolled. 16S rRNA gene sequencing was used to characterize the composition of their gut microbiota. Total and 10 subtypes of SCFAs in the fecal samples were determined by high-performance liquid chromatography. Dual X-ray absorptiometry was used to measure the bone mineral density (BMD) and bone mineral content (BMC) for total body (TB) and total body less head (TBLH). Z score of TBLH BMD was calculated based on the recommended reference. RESULTS: Four gut microbiota principal components (PCs) were identified by the compositional principal component analysis at the genus level. After adjustment of covariates and controlling for the false discovery rate, multiple linear regression analysis showed that PC3 score (positive loadings on genera Lachnoclostridium and Blautia) was significantly negatively associated with TBLH BMD/BMC/Z score, TB BMC and pelvic BMD (ß: - 0.207 to - 0.108, p: 0.002-0.048), whereas fecal total and several subtypes of SCFAs were correlated positively with TBLH BMD/Z score and pelvic BMD (ß: 0.118-0.174, p: 0.038-0.048). However, these associations disappeared after additional adjustment for body weight. Mediation analysis suggested that body weight significantly mediated 60.4% and 78.0% of the estimated association of PC3 score and SCFAs with TBLH BMD Z score, respectively. CONCLUSIONS: The associations of gut microbiota composition and fecal SCFA concentrations with bone mass in children were largely mediated by body weight.


Assuntos
Densidade Óssea , Microbioma Gastrointestinal , Absorciometria de Fóton , Criança , Estudos Transversais , Ácidos Graxos Voláteis , Feminino , Humanos , Masculino , RNA Ribossômico 16S/genética
9.
Arch Virol ; 161(4): 1087-90, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26795159

RESUMO

The complete genome sequence of a novel virus, provisionally named tobacco virus 1 (TV1), was determined, and this virus was identified in leaves of tobacco (Nicotiana tabacum) exhibiting leaf mosaic and yellowing symptoms in Anhui Province, China. The genome sequence of TV1 consists of 15,395 nucleotides with 61.6 % nucleotide sequence identity to mint virus 1 (MV1). Its genome organization is similar to that of MV1, containing nine open reading frames (ORFs) that potentially encode proteins with putative functions in virion assembly, cell-to-cell movement and suppression of RNA silencing. Phylogenetic analysis of the heat shock protein 70 homolog (HSP70h) placed TV1 alongside members of the genus Closterovirus in the family Closteroviridae. To our knowledge, this study is the first report of the complete genome sequence of a closterovirus identified in tobacco.


Assuntos
Closteroviridae/genética , Genoma Viral , Nicotiana/virologia , Filogenia , RNA Viral/genética
10.
Clin Lab ; 62(9): 1795-1802, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28164573

RESUMO

BACKGROUND: Although many epidemiological studies have investigated the CYP1A1 exon7 polymorphism and -GSTM1 interaction with esophageal cancer (EC), definite conclusions cannot be drawn. This study was conducted to explore this association in the Chinese population using meta-analysis. METHODS: Relevant studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine databases published through August 2015. The association of CYP1A1 exon7 polymorphisms and EC risk was estimated by odds ratio (ORs) with 95% confidence intervals (CIs). In addition, the interaction between the CYP1A1 exon7 and GSTM1 genotypes was assessed. RESULTS: A total of 13 case-control studies including 1781 EC cases and 1996 controls were included in this metaanalysis. Overall, significantly increased EC risk was associated with the CYP1A1 exon7 polymorphism (G vs. A OR = 1.36, 95% CI = 1.14 - 1.64; GG vs. AA: OR = 1.85, 95% CI = 1.22 - 2.79; GG vs. AG: OR = 1.41, 95% CI = 1.01 - 1.96; GG + AG vs. AA: OR = 1.47, 95% CI = 1.28 - 1.68; GG vs. AA + AG: OR = 1.60, 95% CI = 1.10 - 2.31). In a subgroup analyses stratified by geographic areas, histopathology type and source of controls, the significant risk was found in hospital-based population, in South and North China. Analysis of CYP1A1- GSTM1 interaction did find synergistic interaction between these two genes. CONCLUSIONS: This meta-analysis provides the evidence that CYP1A1 exon7 polymorphism may contribute to the EC development in the Chinese population, and CYP1A1- GSTM1 interaction might elevate the risk.


Assuntos
Citocromo P-450 CYP1A1/genética , Neoplasias Esofágicas/genética , Éxons/genética , Glutationa Transferase/genética , Polimorfismo Genético , Povo Asiático , Estudos de Casos e Controles , China , Deleção de Genes , Predisposição Genética para Doença , Humanos , Mutação , Razão de Chances , Fatores de Risco
11.
Gynecol Endocrinol ; 31(11): 840-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26370772

RESUMO

In view of the controversies surrounding the glutathione-S-transferases (GST) M1/T1-endometriosis association, a meta-analysis of the GSTM1/GSTT1 genetic association studies of endometriosis was performed in Chinese populations. PubMed, Springer Link, OvidSP, and Chinese databases were searched for related studies. A total of nine studies on GSTM1-endometriosis involved 874 cases and 997 controls, and five studies on GSTT1 involved 404 cases and 513 controls were included in this meta-analysis. Overall, the null genotype of GSTM1/GSTT1 was significantly related to endometriosis risk in Chinese populations (GSTM1, OR = 2.21, 95% CI: 1.22-4.01; GSTT1, OR = 2.31, 95% CI: 1.34-3.99). In subgroup analyses stratified by ethnicity and source of controls, the same results were observed in Chinese Han and population-based studies. The sensitivity analysis confirmed the reliability and stability of the meta-analysis. No publication bias was found among studies by Egger's test. In conclusion, our meta-analysis supports that the GSTM1/GSTT1 null genotype might contribute to individual susceptibility to endometriosis in Chinese populations, especially in Chinese Han.


Assuntos
Povo Asiático/genética , Endometriose/genética , Glutationa Transferase/genética , China , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único
12.
Mycologia ; 107(6): 1130-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26297780

RESUMO

Sclerotinia sclerotiorum is a necrotrophic plant-pathogenic fungus that infects more than 400 species of plants. In this study the nascent polypeptide-associated complex α subunit gene of S. sclerotiorum (SsNACα; accession No. XP_001593856.1) was cloned and characterized. The relative transcript expression of SsNACα at different morphological stages of asexual development of S. sclerotiorum were analyzed by quantitative real time PCR (qRT-PCR). RNAi-mediated gene silencing was successful for SsNACα, and the mutated strains exhibited less than 15% of the relative expression of SsNACα were obtained and used for studying the biological functions of the gene. A delay in sclerotial maturation for S. sclerotiorum was observed in the SsNACα mutants. The significant elevations for both the activities of pectin-degrading enzymes and the expression of polygalacturonase genes also were associated with the mutated strains, indicating that SsNACα could negatively influence polygalacturonases expression and modulate the pathogenicity of S. sclerotiorum.


Assuntos
Ascomicetos/enzimologia , Ascomicetos/patogenicidade , Proteínas Fúngicas/genética , Regulação Enzimológica da Expressão Gênica , Chaperonas Moleculares/metabolismo , Doenças das Plantas/microbiologia , Poligalacturonase/genética , Ascomicetos/genética , Ascomicetos/metabolismo , Brassica rapa/microbiologia , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Chaperonas Moleculares/genética , Poligalacturonase/metabolismo , Nicotiana/microbiologia , Virulência
13.
Soc Sci Med ; 345: 116668, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38382333

RESUMO

In this paper, we documented the association between specific wordings regarding domestic violence within gender equality laws and women's attitudes towards domestic violence in African countries. To do so, we used data on the longitudinal Demographic and Health Survey conducted between 2003 and 2018, and we empirically conducted a difference-in-differences analysis that captures variations in the country and timing of the inclusion of specific wordings addressing domestic violence in the legislative framework that encompasses the general principle of gender equality. The empirical analysis showed that the inclusion of a specific article criminalizing domestic violence within a country's general gender equality law contributed to a statistically significant and substantial decrease in the likelihood of women deeming wife-beating behaviors justifiable. We further conducted an analysis of heterogeneity by socioeconomic status, as defined by urban status, wealth, literacy, and access to information; we found that the association between laws' wordings and attitudes towards domestic violence appeared statistically significant and sizeable in all socioeconomic groups.

14.
Sci Total Environ ; 927: 172318, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38608886

RESUMO

Low temperature stress has adverse effects on fish growth and reproduction, causing huge economic losses to the aquaculture industry. Especially, black porgy (Acanthopagrus schlegelii) farming industry in north of Yangtze River has been severely affected by low temperature for a long time. To explore the tolerance mechanism of black porgy to low temperature stress, the experiment was designed. The liver and gill tissues of black porgy were taken from the water temperature point of 15 °C (control group named as CG), 3.8 °C (cold sensitive group named as CS) and 2.8 °C (cold tolerant group named as CT) with a cooling rate of 3 °C/d from 15 °C for histophysiology, transcriptomics and metabolomics analysis. After cold stress, the histological results showed that the nucleus of the black porgy liver tissue appeared swelling, the cell arrangement was disordered; meanwhile the gill lamellae were twisted and broken, the epidermis was detached and aneurysm appeared. In addition, the expression of antioxidant, glucose metabolism and immune-related enzymes in the liver and gill of black porgy also changed significantly after low temperature stress. By analyzing the transcriptome and metabolome dates of black porgy liver, 3474 differentially expressed genes (DEGs) and 689 differentially expressed metabolites (DEMs) involved in low temperature stress were identified, respectively. The results of the transcriptome and metabolome combined analysis showed that individuals in the CS group mainly supplied energy to the body through lipid metabolism and amino acid metabolism, and meanwhile the apoptosis pathway was activated. While, individuals in the CT group mainly through glucose metabolism and steroid hormone biosynthesis to supply energy for the body. The validation results of qPCR on eight functional genes further demonstrated the reliability of RNA-Seq data. In summary, the results provide molecular information about adaptation to climate change and genetic selection of black porgy.


Assuntos
Metaboloma , Perciformes , Transcriptoma , Animais , Perciformes/fisiologia , Perciformes/genética , Temperatura Baixa , Estresse Fisiológico , Fígado/metabolismo , Resposta ao Choque Frio/fisiologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-38547756

RESUMO

Black porgy (Acanthopagrus schlegelii) is an important marine aquaculture species in China. It is an ideal object for the cultivation of low-salinity aquaculture strains in marine fish and the study of salinity tolerance mechanisms in fish because of its strong low-salinity tolerance ability. Gill is the main osmoregulatory organ in fish, and the liver plays an important role in the adaptation of the organism to stressful environments. In order to understand the coping mechanisms of the gills and livers of black porgy in different salinity environments, this study explored these organs after 30 days of culture in hypoosmotic (0.5 ppt), isosmotic (12 ppt), and normal seawater (28 ppt) at histologic, physiologic, and transcriptomic levels. The findings indicated that gill exhibited a higher number of differentially expressed genes than the liver, emphasizing the gill's heightened sensitivity to salinity changes. Protein interaction networks and enrichment analyses highlighted energy metabolism as a key regulatory focus at both 0.5 ppt and 12 ppt salinity in gills. Additionally, gills showed enrichment in ions, substance transport, and other metabolic pathways, suggesting a more direct regulatory response to salinity stress. The liver's regulatory patterns at different salinities exhibited significant distinctions, with pathways and genes related to metabolism, immunity, and antioxidants predominantly activated at 0.5 ppt, and molecular processes linked to cell proliferation taking precedence at 12 ppt salinity. Furthermore, the study revealed a reduction in the volume of the interlamellar cell mass (ILCM) of the gills, enhancing the contact area of the gill lamellae with water. At 0.5 ppt salinity, hepatic antioxidant enzyme activity increased, accompanied by oxidative stress damage. Conversely, at 12 ppt salinity, gill NKA activity significantly decreased without notable changes in liver structure. These results underscore the profound impact of salinity on gill structure and function, highlighting the crucial role of the liver in adapting to salinity environments.


Assuntos
Brânquias , Fígado , Perciformes , Salinidade , Animais , Brânquias/metabolismo , Fígado/metabolismo , Perciformes/genética , Perciformes/metabolismo , Perciformes/fisiologia , Transcriptoma , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica
16.
J Neurooncol ; 112(1): 17-25, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23322077

RESUMO

The zinc finger transcription factor ZFX functions as an important regulator of self-renewal in multiple stem cell types, as well as a sex determinant of mammals. Moreover, ZFX expression is abnormally elevated in several cancers, and correlates with malignancy grade. To investigate its role in the pathogenesis of gliomas, we used lentivirus-mediated RNA interference (RNAi) to knockdown ZFX expression in human glioma cell lines. Our results demonstrate that ZFX plays a crucial role in glioma proliferation and survival, confirming recent reports. We also show for the first time that ZFX knockdown decreases the in vivo growth potential of U87 glioma xenografts in both subcutaneous and intracranial models in nude mice. We conclude that lentivirus-mediated RNAi targeting of ZFX may serve as a promising strategy for glioma therapy.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Proliferação de Células , Glioma/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Envelhecimento/efeitos dos fármacos , Animais , Antivirais/farmacologia , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Citometria de Fluxo , Glioma/patologia , Humanos , Marcação In Situ das Extremidades Cortadas , Fatores de Transcrição Kruppel-Like/genética , Lentivirus/genética , Lentivirus/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Camundongos Nus , Proteína Oncogênica v-akt/metabolismo , RNA Interferente Pequeno/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Ensaio Tumoral de Célula-Tronco , Tunicamicina/farmacologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Ensaios Antitumorais Modelo de Xenoenxerto , beta-Galactosidase/genética , beta-Galactosidase/metabolismo
17.
Mitochondrial DNA B Resour ; 8(12): 1435-1439, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38173917

RESUMO

In this study, the mitochondrial genome was sequenced in a new commercial species, spotted knifejaw (O. punctatus), using next-generation sequencing and PCR-based methods. The overall length of the female O. punctatus mitochondrial genome was 16,508 bp. It contained 13 PCGs, 2 r-RNA genes, 22 t-RNA genes, and a displacement loop locus (a control region). The total nucleotide composition was 28.75% A, 25.69% T, 29.70% C, and 15.86% G, with a total A + T content of 54.44%. The results demonstrated that the mitochondrial genome of O. punctatus has a high sequence identity with that of another species of Perciformes. This finding provides a deeper understanding of mitogenomic diversity and evolution in marine fish.

18.
Front Plant Sci ; 14: 1162826, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37546249

RESUMO

Terpenes are the main class of secondary metabolites produced in response to pest and germ attacks. In maize (Zea mays L.), they are the essential components of the herbivore-induced plant volatile mixture, which functioned as a direct or indirect defense against pest and germ attacks. In this study, 43 maize terpene synthase gene (ZmTPS) family members were systematically identified and analyzed through the whole genomes of maize. Nine genes, including Zm00001d032230, Zm00001d045054, Zm00001d024486, Zm00001d004279, Zm00001d002351, Zm00001d002350, Zm00001d053916, Zm00001d015053, and Zm00001d015054, were isolated for their differential expression pattern in leaves after corn borer (Ostrinia nubilalis) bite. Additionally, six genes (Zm00001d045054, Zm00001d024486, Zm00001d002351, Zm00001d002350, Zm00001d015053, and Zm00001d015054) were significantly upregulated in response to corn borer bite. Among them, Zm00001d045054 was cloned. Heterologous expression and enzyme activity assays revealed that Zm00001d045054 functioned as d-limonene synthase. It was renamed ZmDLS. Further analysis demonstrated that its expression was upregulated in response to corn borer bites and Fusarium graminearum attacks. The mutant of ZmDLS downregulated the expressions of Zm00001d024486, Zm00001d002351, Zm00001d002350, Zm00001d015053, and Zm00001d015054. It was more attractive to corn borer bites and more susceptible to F. graminearum infection. The yeast one-hybrid assay and dual-luciferase assay showed that ZmMYB76 and ZmMYB101 could upregulate the expression of ZmDLS by binding to the promoter region. This study may provide a theoretical basis for the functional analysis and transcriptional regulation of terpene synthase genes in crops.

19.
In Vitro Cell Dev Biol Anim ; 59(5): 381-393, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37195553

RESUMO

It is known that IL-17A inhibits autophagy of hepatocellular carcinoma (HCC) cells, thus contributing to the carcinogenesis of HCC. Starvation therapy can promote the autophagic death of HCC cells by blocking the nutrition supply. The purpose of this study was to explore whether the pharmacological antagonist of IL-17A, secukinumab, and starvation therapy have a synergistic effect on the autophagic cell death of HCC. Here, it could be observed that compared with serum-free condition, the combination of secukinumab and serum-free status better promoted autophagy (observed by LC3 conversion rate, p62 protein expression and the formation of autophagosomes), and more significantly inhibited the survival and function (observed by Trypan blue staining, CCK-8, Transwell, and scratch assays) in HCC HepG2 cells. Moreover, secukinumab significantly decreased BCL2 protein expression under serum-normal and serum-free conditions. However, both the addition of recombinant IL-17A and overexpression of BCL2 blocked the regulation of secukinumab on the survival and autophagy in HepG2 cells. Nude mice experiments demonstrated that compared to the lenvatinib-alone group, the combination group of lenvatinib and secukinumab better inhibited the in vivo tumorigenesis of HepG2 cells and enhanced autophagy in xenotumor tissues. Furthermore, secukinumab significantly decreased BCL2 protein expression in xenotumor tissues without or with lenvatinib application. In conclusion, the antagonism of IL-17A with secukinumab, due to the upregulation on BCL2-related autophagic cell death, can cooperate with starvation therapy in inhibiting HCC carcinogenesis. Our data suggested that secukinumab can become an effective adjuvant for the treatment of HCC.


Assuntos
Morte Celular Autofágica , Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Autofagia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Interleucina-17/metabolismo , Neoplasias Hepáticas/metabolismo , Camundongos Nus , Proteínas Proto-Oncogênicas c-bcl-2 , Humanos
20.
Life (Basel) ; 13(3)2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36983876

RESUMO

High nutritional value and the development of efficient biotechnological methods of controlled production have made black porgy (Acanthopagrus schlegelii) an economically important fish in Chinese aquaculture in recent years. However, aquaculture production of the species faces multiple issues associated with reduced growth rate, low reproduction ability, and high mortality during production, which are associated with the species' limited tolerance to low temperatures. To date, comprehensive information on the genetic-based mechanisms of cold tolerance and adaptation to low temperature in the species are still unavailable. In this study, the HiSeq™2500 (Illumina) sequencing platform was used to analyze the transcriptomic profile of the liver tissue in the black porgy subjected to different extents of cold shock, including a control temperature group (AS, T = 15 °C), an intermediate temperature group (AL1, T = 10 °C), and an acute low-temperature stress group (AL2, T = 5 °C). For this purpose, three standardized cDNA libraries of AS, AL1, and AL2 were established. We obtained 43,258,908, 48,239,072, and 38,983,833 clean reads from the AS group, AL1 group, and AL2 group, respectively. After pairwise comparison, 70 differentially expressed genes (DEGs) were identified in the examined fish groups. Among them, 60 genes were found to be significantly differentially expressed after trend analysis. GO annotation and enrichment results showed that they were mainly enriched into three categories: biological processes (12 subcategories), molecular functions (7 subcategories), and cellular components (7 subcategories). KEGG analysis results indicated that all significantly differentially expressed genes were annotated to 102 signaling pathways, including biological rhythm, cholesterol metabolism, glycerolipid metabolism, animal autophagy, FoxO signaling pathway, steroid biosynthesis, and regulation of adipocyte lipolysis and apoptosis. Four of them, namely: G6PC, GPX1, GCK, and HSPE1 were randomly selected for further qRT-PCR verification of data reliability obtained by RNA-Seq technology. In this study, we found that environmental acute cold stress mainly affected the black porgy's biological processes related to metabolism, apoptosis, and signal transduction. The data that we have reported provides baseline information for further studies concerning the genetic responses of the black porgy under cold stress conditions, the improvement of its aquaculture production, and other economically important matters regarding their limited tolerance to cold shock.

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