RESUMO
The cultivated apple (Malus domestica Borkh.) is a cross-pollinated perennial fruit tree of great economic importance. Earlier versions of apple reference genomes were unphased, fragmented, and lacked comprehensive insights into the apple's highly heterozygous genome, which impeded advances in genetic studies and breeding programs. In this study, we assembled a haplotype-resolved telomere-to-telomere (T2T) reference genome for the diploid apple cultivar Golden Delicious. Subsequently, we constructed a pangenome based on 12 assemblies from wild and cultivated species to investigate the dynamic changes of functional genes. Our results revealed the gene gain and loss events during apple domestication. Compared with cultivated species, more gene families in wild species were significantly enriched in oxidative phosphorylation, pentose metabolic process, responses to salt, and abscisic acid biosynthesis process. Our analyses also demonstrated a higher prevalence of different types of resistance gene analogs (RGAs) in cultivars than their wild relatives, partially attributed to segmental and tandem duplication events in certain RGAs classes. Structural variations, mainly deletions and insertions, have affected the presence and absence of TIR-NB-ARC-LRR, NB-ARC-LRR, and CC-NB-ARC-LRR genes. Additionally, hybridization/introgression from wild species has also contributed to the expansion of resistance genes in domesticated apples. Our haplotype-resolved T2T genome and pangenome provide important resources for genetic studies of apples, emphasizing the need to study the evolutionary mechanisms of resistance genes in apple breeding.
Assuntos
Domesticação , Genoma de Planta , Malus , Telômero , Malus/genética , Genoma de Planta/genética , Telômero/genética , Genes de Plantas , Haplótipos/genética , Resistência à Doença/genéticaRESUMO
Colorectal cancer (CRC) is the third most prevalent diagnosed cancer in men and second most prevalent cancer in women. H3K27ac alterations are more commonly than gene mutations in colorectal cancer. Most colorectal cancer genes have significant H3K27ac changes, which leads to an over-expression disorder in gene transcription. Over-expression of STEAP3 is involved in a variety of tumors, participating in the regulation of cancer cell proliferation and migration. The purpose of this work is to investigate the role of STEAP3 in the regulation of histone modification (H3K27ac) expression in colon cancer. Bioinformatic ChIP-seq, ChIP-qPCR and ATAC-seq were used to analyze the histone modification properties and gene accessibility of STEAP3. Western blot and qRT-PCR were used to evaluate relative protein and gene expression, respectively. CRISPR/Cas9 technology was used to knockout STEAP3 on colon cancer cells to analyze the effect of ATF3 on STEAP3. STEAP3 was over-expressed in colon cancer and associated with higher metastases and more invasive and worse stage of colon cancer. ChIP-seq and ChIP-qPCR analyses revealed significant enrichment of H3K27ac in the STEAP3 gene. In addition, knocking down STEAP3 significantly inhibits colon cancer cell proliferation and migration and down-regulates H3K27ac expression. ChIP-seq found that ATF3 is enriched in the STEAP3 gene and CRISPR/Cas9 technology used for the deletion of the ATF3 binding site suppresses the expression of STEAP3. Over-expression of STEAP3 promotes colon cancer cell proliferation and migration. Mechanical studies have indicated that H3K27ac and ATF3 are significantly enriched in the STEAP3 gene and regulate the over-expression of STEAP3.
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Movimento Celular , Proliferação de Células , Neoplasias do Colo , Regulação Neoplásica da Expressão Gênica , Histonas , Humanos , Proliferação de Células/genética , Movimento Celular/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Histonas/metabolismo , Histonas/genética , Acetilação , Feminino , Linhagem Celular Tumoral , Masculino , Fator 3 Ativador da Transcrição/genética , Fator 3 Ativador da Transcrição/metabolismoRESUMO
Esophageal cancer (EC) is a challenging tumor to treat with radiotherapy, often exhibiting resistance to this treatment modality. To explore the factors influencing radioresistance, we focused on the role of hypoxia-induced factor-1α (HIF-1α), and its interaction with the long noncoding RNA long intergenic nonprotein coding RNA 1116 (LINC01116). We analyzed the LINC01116 expression in EC and EC cell lines/human normal esophageal epithelial cell line (Het-1A). LINC01116 was silenced/overexpressed in EC109/KYSE30 cells under hypoxia, followed by radioresistance assessment. We measured HIF-1α levels in hypoxic EC cells and further validated the binding of HIF-1α with LINC01116, analyzing their interaction in EC cells. We then performed experiments in EC109 cells by transfection them with sh-HIF-1α/oe-LINC01116 to verify the effects. Additonally, we analyzed the localization of LINC01116 and its binding with miR-3612, followed by a combined experiment performed to validate the results. Our findings indicated that LINC01116 was highly expressed in EC and further elevated in hypoxic EC cells. LINC01116 was expressed at a high level in EC, which was further elevated in EC cells under hypoxic conditions. Knockdown of LINC01116 triggered EC cell apoptosis, thus suppressing radioresistance. Further investigation revealed that HIF-1α transcriptionally activated LINC01116 expression under hypoxia, and silencing HIF-1α lowered EC cell radioresistance by downregulating LINC01116. Under hypoxic conditions, LINC01116 could function as a sponge for miR-3612 and inhibit its expression. This interaction between LINC01116 and miR-3612 played a crucial role in mediating radioresistance in EC cells. Briefly, under hypoxic conditions, HIF-1α facilitates radioresistance of EC cells by transcriptionally activating LINC01116 expression and downregulating miR-3612.
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Neoplasias Esofágicas , MicroRNAs , Humanos , Hipóxia Celular/genética , Linhagem Celular Tumoral , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/metabolismo , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , MicroRNAs/metabolismo , RNA não Traduzido/genéticaRESUMO
Heparinases, including heparinases I-III (HepI, HepII, and HepIII, respectively), are important tools for producing low-molecular-weight heparin, an improved anticoagulant. The poor thermostability of heparinases significantly hinders their industrial and laboratory applications. To improve the thermostability of heparinases, we applied a rigid linker (EAAAK)5 (R) and a flexible linker (GGGGS)5 (F) to fuse maltose-binding protein (MBP) and HepI, HepII, and HepIII from Pedobacter heparinus, replacing the original linker from the plasmid pMAL-c2X. Compared with their parental fusion protein, MBP-fused HepIs, HepIIs, and HepIIIs with linkers (EAAAK)5 or (GGGGS)5 all displayed enhanced thermostability (half-lives at 30°C: 242%-464%). MBP-fused HepIs and HepIIs exhibited higher specific activity (127%-324%), whereas MBP-fused HepIIIs displayed activity similar to that of their parental fusion protein. Kinetics analysis revealed that MBP-fused HepIIs showed a significantly decreased affinity toward heparin with increased Km values (397%-480%) after the linker replacement, whereas the substrate affinity did not change significantly for MBP-fused HepIs and HepIIIs. Furthermore, it preliminarily appeared that the depolymerization mechanism of these fusion proteins may not change after linker replacement. These findings suggest the superior enzymatic properties of MBP-fused heparinases with suitable linker designs and their potential for the bioproduction of low-molecular-weight heparin.
RESUMO
DNA methylation has a growing potential for use as a biomarker because of its involvement in disease. DNA methylation data have also substantially grown in volume during the past 5 years. To facilitate access to these fragmented data, we proposed DiseaseMeth version 3.0 based on DiseaseMeth version 2.0, in which the number of diseases including increased from 88 to 162 and High-throughput profiles samples increased from 32 701 to 49 949. Experimentally confirmed associations added 448 pairs obtained by manual literature mining from 1472 papers in PubMed. The search, analyze and tools sections were updated to increase performance. In particular, the FunctionSearch now provides for the functional enrichment of genes from localized GO and KEGG annotation. We have also developed a unified analysis pipeline for identifying differentially DNA methylated genes (DMGs) from the original data stored in the database. 22 718 DMGs were found in 99 diseases. These DMGs offer application in disease evaluation using two self-developed online tools, Methylation Disease Correlation and Cancer Prognosis & Co-Methylation. All query results can be downloaded and can also be displayed through a box plot, heatmap or network module according to whichever search section is used. DiseaseMeth version 3.0 is freely available at http://diseasemeth.edbc.org/.
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Metilação de DNA/genética , Bases de Dados Factuais , Perfilação da Expressão Gênica/classificação , Doenças Genéticas Inatas/classificação , Biomarcadores Tumorais/genética , Doenças Genéticas Inatas/genética , Humanos , Neoplasias/classificação , Neoplasias/genética , PubMedRESUMO
BACKGROUND: Prior to December 2022, there were no reports of reinfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Shaanxi province, China. Since then, China has refined its strategy in response to coronaviruses. The purpose of this study was to determine the incidence of SARS-CoV-2 reinfections and its contributing factors, as well as to compare clinical characteristics between first and second episodes of infection in Shaanxi Province, China between December 2022 and February 2023. METHODS: We conducted a cross-sectional study using an epidemiological survey system and electronic questionnaires to investigate the incidence of SARS-CoV-2 reinfection among previously infected individuals during the epidemic wave owing to the Omicron variant that began in December 2022. A logistic regression model was used to determine those factors influencing SARS-CoV-2 reinfections. RESULTS: According to the virus variant that caused the first infection, the rate of reinfection for the Omicron variants was 1.28%, 1.96%, and 5.92% at 2-3 months, 4-5 months, and 7-9 months after the primary infection, respectively. The rate of reinfection for the Delta variants was 25.10% 11-12 months after the primary infection. Females, adults between 18 and 38 years and being a medical worker were associated with an increased risk of reinfection. Fever, cough, sore throat and fatigue were the four most common clinical symptoms during both first and second COVID-19 infections. CONCLUSIONS: In our study, the rate of SARS-CoV-2 reinfection increased over time during epidemic waves predominantly involving the Omicron variant in Shaanxi province, China. Large-scale infections are less likely in subsequent Omicron epidemic waves. Nevertheless, it is essential to continuously monitor cases of infection as well as continue surveillance for emerging SARS-CoV-2 variants.
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COVID-19 , SARS-CoV-2 , Adulto , Feminino , Humanos , SARS-CoV-2/genética , COVID-19/epidemiologia , Estudos Transversais , Reinfecção/epidemiologia , China/epidemiologiaRESUMO
BACKGROUND: Despite many efforts to control leprosy worldwide, it is still a significant public health problem in low- and middle-income regions. It has been endemic in China for thousands of years, and southwest China has the highest leprosy burden in the country. METHODS: This observational study was conducted with all newly detected leprosy cases in southwest China from 2010 to 2020. Data were extracted from the Leprosy Management Information System (LEPMIS) database in China. The Joinpoint model was used to determine the time trends in the study area. Spatial autocorrelation statistics was performed to understand spatial distribution of leprosy cases. Spatial scan statistics was applied to identify significant clusters with high rate. RESULTS: A total of 4801 newly detected leprosy cases were reported in southwest China over 11 years. The temporal trends declined stably. The new case detection rate (NCDR) dropped from 4.38/1,000,000 population in 2010 to 1.25/1,000,000 population in 2020, with an average decrease of 12.24% (95% CI: -14.0 to - 10.5; P < 0.001). Results of global spatial autocorrelation showed that leprosy cases presented clustering distribution in the study area. Most likely clusters were identified during the study period and were frequently located at Yunnan or the border areas between Yunnan and Guizhou Provinces. Secondary clusters were always located in the western counties, the border areas between Yunnan and Sichuan Provinces. CONCLUSIONS: Geographic regions characterized by clusters with high rates were considered as leprosy high-risk areas. The findings of this study could be used to design leprosy control measures and provide indications to strengthen the surveillance of high-risk areas. These areas should be prioritized in the allocation of resources.
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Hanseníase , Humanos , China/epidemiologia , Hanseníase/epidemiologia , Análise Espacial , Análise por Conglomerados , Bases de Dados Factuais , Análise Espaço-TemporalRESUMO
Background: Advanced glycation end products' receptor (AGER) is a multiligand receptor that interacts with a wide range of ligands. Previous studies have shown that abnormal AGER expression is closely related to immune infiltration and tumorigenesis. However, the AGER DNA methylation relationship between prognosis and infiltrating immune cells in LUAD and LUSC is still unclear. Methods: AGER expression in pan-cancer was obtained by using the UALCAN databases. Kaplan-Meier plotter showed the correlation of AGER mRNA expression levels and clinicopathological parameters. The protein expression levels for AGER were derived from Human Protein Atlas Database Analysis. The copy number, somatic mutation, and DNA methylation of AGER were presented with UCSC Xena database. TIMER platform and TISIDB website were used to show the correlation between AGER expression and tumor immune cell infiltration level. Results: The expression level of AGER was significantly reduced in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Low expression of AGER was significantly correlated with histology, stage, lymph node metastasis, and tumor protein 53 (TP53) mutation and could be used as a potential indicator of poor prognosis of LUAD and LUSC. Moreover, AGER expression was positively correlated with the infiltrating immune cells. Further analysis showed that copy number variation (CNV), mutation, and DNA methylation were involved in AGER downregulation. In addition, we also found that hypermethylated AGER was significantly correlated with tumor-infiltrating lymphocytes. Conclusion: AGER may be a candidate for the prognostic biomarker of LUAD and LUSC related to tumor immune microenvironment.
Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Bases de Dados de Proteínas , Variações do Número de Cópias de DNA/genética , Metilação de DNA/genética , Produtos Finais de Glicação Avançada , Pulmão , Neoplasias Pulmonares/genética , Prognóstico , Microambiente Tumoral/genéticaRESUMO
OBJECTIVE: The purpose of this study was to compare the clinical outcomes and toxicities between induction chemotherapy (IC) + chemo-radiotherapy (CRT) and CRT alone in patients with locally advanced esophageal squamous cell carcinoma (ESCC), to explore the appropriate thoracic radiotherapy (TRT) timing after IC and to identify prognostic factors. METHODS: 450 ESCC patients were included from September 2011 to December 2020, 238 of whom received IC/CRT. Propensity score matching was performed to balance potential confounders between the two groups. Multivariate Cox regression analysis was used to identify the independent prognostic factors. RESULTS: Patients who received IC/CRT experienced improved overall survival (OS) (38.5 vs. 28.8 months) and progression-free survival (PFS) (41.0 vs. 22.0 months) before matching, with similar results after matching. In the IC/CRT group, early TRT had more favorable survival than late TRT both matching before and after. In subgroup analysis, early TRT combination concurrent chemotherapy had better OS and PFS than late TRT combination concurrent chemotherapy. In addition, early TRT had better survival benefits regardless of the N stage. Notably, the IC/CRT group and early TRT group had manageable toxicities reaction compared with CRT alone group and the late TRT group. The nomogram was developed to predict the OS and PFS based on multivariate analysis results. The C-index was 0.743 and 0.722, respectively. CONCLUSION: IC/CRT and early TRT could yield satisfactory clinical outcomes and controllable toxicities in locally advanced ESCC. The IC plus early concurrent CRT might be a promising treatment strategy for improving further survival in ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/radioterapia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Quimioterapia de Indução/efeitos adversos , Quimiorradioterapia/efeitos adversos , Estudos RetrospectivosRESUMO
Grapevine fabavirus (GFabV) is a novel member of the Fabavirus genus associated with chlorotic mottling and deformation symptoms in grapevines. To gain insights into the interaction between GFabV and grapevines, V. vinifera cv. 'Summer Black' infected with GFabV was investigated under field conditions through physiological, agronomic, and multi-omics approaches. GFabV induced significant symptoms on 'Summer Black', and caused a moderate decrease in physiological efficiency. In GFabV-infected plants, alterations in carbohydrate- and photosynthesis-related genes might trigger some defense responses. In addition, secondary metabolism involved in plant defense was progressively induced by GFabV. Jasmonic acid and ethylene signaling were down-regulated in GFabV-infected leaves and berries along with the expression of proteins related to LRR and protein kinases, suggesting that GFabV can block the defense in healthy leaves and berries. Furthermore, this study provided biomarkers for early monitoring of GFabV infection in grapevines, and contributed to a better understanding of the complex grapevine-virus interaction.
Assuntos
Fabavirus , Vitis , Transcriptoma , Vitis/genética , Fotossíntese , Metaboloma , Folhas de Planta/metabolismo , Regulação da Expressão Gênica de Plantas , Doenças das PlantasRESUMO
According to our prior findings, ARID1A expression is decreased in colon cancer, which has a poor prognosis. In this study, we investigated the ARID1A-VIM/CDH1 signalling axis's role in colon cancer proliferation and migration. The differentially expressed genes in cells that might be controlled by ARID1A were discovered by a database screening for ARID1A knockout. qPCR was used to analyse ARID1A and EMT markers expression levels in colon cancer. We utilized siRNA RID1A to explore the influence of ARID1A silencing on EMT in CRC cells. The function of ARID1A in the colon was investigated utilizing the wound healing, transwell and CCK-8 WST- assays. The molecular mechanism by which ARID1A regulates VIM and CDH1 was elucidated using chip-qPCR. Numerous genes involved in EMT were dysregulated in the absence of ARID1A. VIM expression increased in cells lacking ARID1A expression and vice versa. Many COAD samples with high ARID1A mRNA expression had low VIM mRNA expression, despite the relevance. CDH1 gene was positively correlated with ARID1A. Moreover, siRNA-ARID1A-transfected cells accelerated cell migration and invasion and increased cell proliferation rate in vitro. Chip-qPCR analysis showed that ARID1A binds to the promoters of both genes and changes their expression in colon cancer. ARID1A inactivation is associated with VIM activation and CDH1 suppression, which might serve as crucial molecules influencing COAD prognosis, accelerate tumour progression, and shorten patients' survival time, and promote metastases of COAD. Thus, depletion of ARID1A can be therapeutically exploited by targeting downstream effects to improve cancer treatment-related outcomes.
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Neoplasias do Colo , Transição Epitelial-Mesenquimal , Humanos , Regulação para Baixo/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Proliferação de Células/genética , Movimento Celular/genética , Neoplasias do Colo/genética , RNA Interferente Pequeno/genética , RNA Mensageiro , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genética , Antígenos CD/genética , Caderinas/genéticaRESUMO
BACKGROUND: Calcium-activated nucleotidase 1 (CANT1), functions as a calcium-dependent nucleotidase with a preference for UDP. However, the potential clinical value of CANT1 in lung adenocarcinoma (LA) has not been fully clarified. Thus, we sought to identify its potential biological function and mechanism through bioinformatics analysis and in vitro experiments in LA. METHODS: In the present study, we comprehensively investigated the prognostic role of CANT1 in LA patients through bioinformatics analysis and in vitro experiments. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were utilized to analyze the expression of CANT1 in LA patients and their clinical-prognostic value. The immunohistochemistry staining was obtained from the Human Protein Atlas (HPA). A Cox regression model was used to evaluate prognostic factors. Gene ontology (GO) and Gene set enrichment analysis (GSEA) was performed to explore the potential regulatory mechanism of CANT1 in the development of LA. Moreover, we also examined the relationship between CANT1 expression and DNA methylation. Finally, we did in vitro experiments to evaluate the biological behavior and role of CANT1 in LA cells (LACs). RESULTS: Our study showed that the CANT1 expression was significantly elevated in the LA tissues compared with the normal lung tissues. Increased CANT1 expression was significantly associated with the TN stage. A univariate Cox analysis indicated that high CANT1 expression levels were correlated with poor overall survival (OS) in LA. Besides, CANT1 expression was independently associated with OS in multivariate analysis. GO and GSEA analysis showed the enrichment of mitotic nuclear division, DNA methylation, and DNA damage. Then we found that the high expression of CANT1 is positively correlated with hypomethylation. The methylation level was associated with prognosis in LA patients. Finally, in vitro experiments indicated that knockdown of CANT1 resulted in decreased cell proliferation, invasion, and G1 phase cell-cycle arrest in LACs. CONCLUSION: The present study suggested that CANT1 may serve as a potential prognosis biomarker in patients with LA. High CANT1 expression and promoter demethylation was associated with worse outcome. Finally, in vitro experiments verified the biological functions and behaviors of CANT1 in LA.
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Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/mortalidade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Nucleotidases/metabolismo , Idoso , Biomarcadores Tumorais/genética , Proliferação de Células/genética , Dano ao DNA/genética , Metilação de DNA/genética , Feminino , Ontologia Genética , Humanos , Masculino , PrognósticoRESUMO
Super-enhancers (SEs) are critical for the transcriptional regulation of gene expression. We developed the super-enhancer archive version 3.0 (SEA v. 3.0, http://sea.edbc.org) to extend SE research. SEA v. 3.0 provides the most comprehensive archive to date, consisting of 164 545 super-enhancers. Of these, 80 549 are newly identified from 266 cell types/tissues/diseases using an optimized computational strategy, and 52 have been experimentally confirmed with manually curated references. We now support super-enhancers in 11 species including 7 new species (zebrafish, chicken, chimp, rhesus, sheep, Xenopus tropicalis and stickleback). To facilitate super-enhancer functional analysis, we added several new regulatory datasets including 3 361 785 typical enhancers, chromatin interactions, SNPs, transcription factor binding sites and SpCas9 target sites. We also updated or developed new criteria query, genome visualization and analysis tools for the archive. This includes a tool based on Shannon Entropy to evaluate SE cell type specificity, a new genome browser that enables the visualization of SE spatial interactions based on Hi-C data, and an enhanced enrichment analysis interface that provides online enrichment analyses of SE related genes. SEA v. 3.0 provides a comprehensive database of all available SE information across multiple species, and will facilitate super-enhancer research, especially as related to development and disease.
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Bases de Dados de Ácidos Nucleicos , Elementos Facilitadores Genéticos , Animais , Sítios de Ligação , Cromatina , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/metabolismoRESUMO
There is in vivo and in vitro evidence that exposure to benzene or its metabolites could affect the mitochondrial function. However, the underlying molecular mechanism of mitochondrial damage remains to be elucidated. In this study, exposure of human promyelocytic leukemia cells (HL-60) to 1,4-benzoquinone (1,4-BQ; an active metabolite of benzene) increased the intracellular reactive oxygen species levels, decreased the mitochondrial membrane potential, adenosine triphosphate production and mitochondrial DNA (mtDNA) copy number, up-regulated the expression of mitochondrial fission proteins Drp1 and Fis1, and down-regulated the expression of mitochondrial fusion proteins Mfn2 and Opa1. Further study showed that 1,4-BQ mediated mitochondrial fission through activation of the AMP-activated protein kinase/mitochondrial fission factor/dynamin-related protein 1 pathway. Additionally, we also examined the role of exosomal secretion in mitochondrial damage under 1,4-BQ treatment. Results showed that 1,4-BQ increased the total protein level and mtDNA content in exosomes. Upon pre-treatment with the mitochondria-targeted antioxidant SS-31, there was attenuation of the mitochondrial damage induced by 1,4-BQ, accompanied by a change in the exosome release characteristics, while inhibition of exosomal secretion using GW4869 aggravated the 1,4-BQ-mediated mitochondrial fission. We concluded that exosomal secretion may serve as a self-protective mechanism of cells against 1,4-BQ-induced mitochondria damage and mitochondrial dynamics interference.
Assuntos
Proteínas Quinases Ativadas por AMP , Dinâmica Mitocondrial , Benzeno , Benzoquinonas/toxicidade , DNA Mitocondrial , Dinaminas/metabolismo , Células HL-60 , Humanos , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismoRESUMO
OBJECTIVE: Sarcopenia is a common complication in patients with end-stage kidney disease. Insulin resistance is present in non-diabetic patients undergoing maintenance hemodialysis (MHD) and is an important factor leading to sarcopenia. The triglyceride-glucose (TyG) index, a reliable indicator for evaluating insulin resistance, is widely used in clinical practice. The present study investigated the association between the TyG index and sarcopenia in non-diabetic patients undergoing MHD. METHODS: Relevant clinical data of non-diabetic patients undergoing MHD at our center were collected. The TyG index was calculated using the following formula: ln(fasting triglycerides(mg/dL)×fasting blood glucose(mg/dL)/2). Multivariate logistic regression analyses were used to evaluate the associations. The receiver-operating characteristic curve was used to analyze the predictive value of the TyG index in sarcopenia. RESULTS: Of the 142 patients undergoing MHD who were included, 75 (52.82%) were men, the mean age was 54.05 ± 13.97 years, and 40 (28.17%) patients satisfied the diagnostic criteria for sarcopenia. The TyG index of participants with sarcopenia was higher compared with those without sarcopenia (8.83 ± 0.45 vs. 8.49 ± 0.50, p < 0.001). The prevalence of sarcopenia increased with increasing TyG index tertile (T1, 8.51%; T2, 31.91%; T3, 43.75%; p = 0.001). Logistic regression analysis indicated that the TyG index was an independent risk factor for sarcopenia (odds ratio, 4.21 [95% confidence interval, 1.85-9.59], p = 0.001). CONCLUSION: A higher TyG index was associated with an increased risk of sarcopenia in non-diabetic patients undergoing MHD; it may be used as a novel marker to reflect the presence of sarcopenia.
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Resistência à Insulina , Sarcopenia , Adulto , Idoso , Biomarcadores , Glicemia , Feminino , Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Fatores de Risco , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Sarcopenia/etiologia , TriglicerídeosRESUMO
Cadmium (Cd) is one of the toxic heavy metals found widely in the environment. Skin is an important target organ of Cd exposure. However, the adverse effects of Cd on human skin are still not well known. In this study, normal human skin keratinocytes (HaCaT cells) were studied for changes in cell viability, morphology, DNA damage, cycle, apoptosis, and the expression of endoplasmic reticulum (ER) stress-related genes (XBP-1, BiP, ATF-4, and CHOP) after exposure to Cd for 24 h. We found that Cd decreased cell viability in a concentration-dependent manner, with a median lethal concentration (LC50) of 11 µM. DNA damage induction was evidenced by upregulation of the level of γ-H2AX. Furthermore, Cd induced G0/G1 phase cell cycle arrest and apoptosis in a dose-dependent manner and upregulated the mRNA levels of ER stress biomarker genes (XBP-1, BiP, ATF4, and CHOP). Taken together, our results showed that Cd induced cytotoxicity and DNA damage in HaCaT cells, eventually resulting in cell cycle arrest in the G0/G1 phase and apoptosis. In addition, ER stress may be involved in Cd-induced HaCaT apoptosis. Our data imply the importance of reducing Cd pollution in the environment to reduce its adverse impacts on human skin.
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Cádmio , Estresse do Retículo Endoplasmático , Apoptose , Cádmio/toxicidade , Humanos , Queratinócitos , RNA MensageiroRESUMO
Luminal breast cancer (BC) accounts for a large proportion of patients in BC, with high heterogeneity. Determining the precise subtype and optimal selection of treatment options for luminal BC is a challenge. In this study, we proposed an MSBR framework that integrate DNA methylation profiles and transcriptomes to identify immune subgroups of luminal BC. MSBR was implemented both on a key module scoring algorithm and "Boruta" feature selection method by DNA methylation. Luminal A was divided into two subgroups and luminal B was divided into three subgroups using the MSBR. Furthermore, these subgroups were defined as different immune subgroups in luminal A and B respectively. The subgroups showed significant differences in DNA methylation levels, immune microenvironment (immune cell infiltration, immune checkpoint PD1/PD-L1 expression, immune cell cracking activity (CYT)) and pathology features (texture, eccentricity, intensity and tumor-infiltrating lymphocytes (TILs)). The results also showed that there is a subgroup in both luminal A and B that has the benefit from immunotherapy. This study proposed a classification of luminal BC from the perspective of epigenetics and immune characteristics, which provided individualized treatment decisions.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/metabolismo , Metilação de DNA , Linfócitos do Interstício Tumoral , Transcriptoma , Imunoterapia , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: Studies have shown that the Sec61 gamma subunit (SEC61G) is overexpressed in several tumors and could serve as a potential prognostic marker. However, the correlation between SEC61G and lung adenocarcinoma (LUAD) remains unclear. In the current study, we aimed to demonstrate the prognostic value and potential biological function of the SEC61G gene in LUAD. METHODS: Public datasets were used for SEC61G expression analyses. The prognostic value of SEC61G in LUAD was investigated using the Kaplan-Meier survival and Cox analyses. The correlation between the methylation level of SEC61G and its mRNA expression was evaluated via cBioPortal. Additionally, MethSurv was used to determine the prognostic value of the SEC61G methylation levels in LUAD. Functional enrichment analysis was conducted to explore the potential mechanism of SEC61G. Also, single sample GSEA (ssGSEA) and TIMER online tool were applied to identify the correlation between SEC61G and immune filtration. Furthermore, cell functional experiments were conducted to verify the biological behavior of SEC61G in lung adenocarcinoma cells (LAC). RESULTS: SEC61G was upregulated in pan-cancers, including LUAD. High SEC61G expression was significantly correlated with worse prognosis in LUAD patients. Multivariate analysis demonstrated that high SEC61G expression was an independent prognostic factor in the TCGA cohort. (HR = 1.760 95% CI: 1.297-2.388, p < 0.001). The methylation level of SEC61G negatively correlated with the SEC61G expression (R = - 0.290, p < 0.001), and patients with low SEC61G methylation had worse overall survival. (p = 0.0014). Proliferation-associated terms such as cell cycle and cell division were significantly enriched in GO and KEGG analysis. Vitro experiments demonstrated that knockdown of SEC61G resulted in decreased cell proliferation, invasion and facilitated apoptosis in LAC. GSEA analysis found that SEC61G expression was associated with the E2F targets. Moreover, SEC61G expression was negatively correlated with the immune cell infiltration including CD4+ T cell, CD8+ T cell, B cell, macrophage, neutrophil, and dendritic cell. CONCLUSION: Our study indicated that overexpression of SEC61G was significantly associated with poor prognosis of LUAD patients and the malignant phenotypes of LUAD cells, suggesting that it could be a novel prognostic biomarker and potential therapeutic target of LUAD.
Assuntos
Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , Canais de Translocação SEC/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Biologia Computacional , Metilação de DNA , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Inativação Gênica , Humanos , Técnicas In Vitro , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Invasividade Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro/metabolismo , Canais de Translocação SEC/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Walnut (Juglans regia) is an important tree cultivated worldwide and is exposed to a series of both abiotic and biotic stress during their life-cycles. The heat stress transcription factors (HSFs) play a crucial role in plant response to various stresses by regulating the expression of stress-responsive genes. HSF genes are classified into 3 classes: HSFA, HSFB, and HSFC. HSFA gene has transcriptional activation function and is the main regulator of high temperature-induced gene expression. HSFB gene negatively regulates plant resistance to drought and NaCl. And HSFC gene may be involved in plant response to various stresses. There are some reports about the HSF family in herbaceous plants, however, there are no reports about the HSFs in walnut. RESULT: In this study, based on the complete genome sequencing of walnut, the bioinformatics method was used and 29 HSF genes were identified. These HSFs covered 18 HSFA, 9 HSFB, and 2 HSFC genes. Phylogenetic analysis of these HSF proteins along with those from Arabidopsis thaliana showed that the HSFs in the two species are closely related to each other and have different evolutionary processes. The distribution of conserved motifs and the sequence analysis of HSF genes family indicated that the members of the walnut HSFs are highly conserved. Quantitative Real-Time PCR (qRT-PCR) analysis revealed that the most of walnut HSFs were expressed in the walnut varieties of 'Qingxiang' and 'Xiangling' under high temperature (HT), high salt and drought stress, and some JrHSFs expression pattern are different between the two varieties. CONCLUSION: The complex HSF genes family from walnut was confirmed by genome-wide identification, evolutionary exploration, sequence characterization and expression analysis. This research provides useful information for future studies on the function of the HSF genes and molecular mechanism in plant stress response.
Assuntos
Fatores de Transcrição de Choque Térmico/genética , Juglans/genética , Estresse Fisiológico/genética , Desidratação/genética , Secas , Regulação da Expressão Gênica de Plantas/genética , Fatores de Transcrição de Choque Térmico/classificação , Resposta ao Choque Térmico/genética , Filogenia , Estresse Salino/genética , Alinhamento de SequênciaRESUMO
OBJECTIVE: To understand the variation of G glycoprotein gene of human respiratory syncytial virus (HRSV) obtained from Sichuan in 2010 and determine the dominant genotypes. METHODS: G glycoprotein gene of seven cases of subtype A and eleven cases of subtype B of HRSV were amplified by RT-PCR and sequenced. The phylogenetic trees were constructed to determine the subtype of samples. And then, the genetic variations of the second hypervariable region of G glycoprotein gene were studied. RESULTS: The nucleotide genetic distances of G glycoprotein gene in subtype A and subtype B HRSV were 0.022 +/- 0.005 and 0.073 +/- 0.010, respectively. Transitions were more prevalent than transversions, GA -AG were the most frequent transitions detected among group A viruses, while UC+CU transitions were the most among group B. Phylogenetic analyses demonstrated that 7 subtype A virus could be clustered into one genotype, genotype GA2, and 11 subtype B virus could be clustered into two genotypes, GB2 and BA. The length of G protein gene in group A was all 298aa, but in group B included 295aa, 312aa and 315aa. Selective pressure was purifying selection in both subtypes. 9 positively selected sites in group A and 1 in group B on the second hypervariable region of G protein were identified. CONCLUSION: GA2, GB2 and BA were the main genotype. The changes may favor virus escape from the host immune response including the variation of the G protein gene length, frequency of nucleotide changes and selective pressure.