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1.
Nucleic Acids Res ; 51(D1): D192-D198, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36350671

RESUMO

Long non-coding RNAs (lncRNAs) act as versatile regulators of many biological processes and play vital roles in various diseases. lncRNASNP is dedicated to providing a comprehensive repository of single nucleotide polymorphisms (SNPs) and somatic mutations in lncRNAs and their impacts on lncRNA structure and function. Since the last release in 2018, there has been a huge increase in the number of variants and lncRNAs. Thus, we updated the lncRNASNP to version 3 by expanding the species to eight eukaryotic species (human, chimpanzee, pig, mouse, rat, chicken, zebrafish, and fruitfly), updating the data and adding several new features. SNPs in lncRNASNP have increased from 11 181 387 to 67 513 785. The human mutations have increased from 1 174 768 to 2 387 685, including 1 031 639 TCGA mutations and 1 356 046 CosmicNCVs. Compared with the last release, updated and new features in lncRNASNP v3 include (i) SNPs in lncRNAs and their impacts on lncRNAs for eight species, (ii) SNP effects on miRNA-lncRNA interactions for eight species, (iii) lncRNA expression profiles for six species, (iv) disease & GWAS-associated lncRNAs and variants, (v) experimental & predicted lncRNAs and drug target associations and (vi) SNP effects on lncRNA expression (eQTL) across tumor & normal tissues. The lncRNASNP v3 is freely available at http://gong_lab.hzau.edu.cn/lncRNASNP3/.


Assuntos
Bases de Dados de Ácidos Nucleicos , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante , Animais , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo
2.
Nucleic Acids Res ; 50(D1): D46-D53, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34551433

RESUMO

Enhancer RNAs (eRNAs) are a class of non-coding RNAs transcribed from enhancers. As the markers of active enhancers, eRNAs play important roles in gene regulation and are associated with various complex traits and characteristics. With increasing attention to eRNAs, numerous eRNAs have been identified in different human tissues. However, the expression landscape, regulatory network and potential functions of eRNAs in animals have not been fully elucidated. Here, we systematically characterized 185 177 eRNAs from 5085 samples across 10 species by mapping the RNA sequencing data to the regions of known enhancers. To explore their potential functions based on evolutionary conservation, we investigated the sequence similarity of eRNAs among multiple species. In addition, we identified the possible associations between eRNAs and transcription factors (TFs) or nearby genes to decipher their possible regulators and target genes, as well as characterized trait-related eRNAs to explore their potential functions in biological processes. Based on these findings, we further developed Animal-eRNAdb (http://gong_lab.hzau.edu.cn/Animal-eRNAdb/), a user-friendly database for data searching, browsing and downloading. With the comprehensive characterization of eRNAs in various tissues of different species, Animal-eRNAdb may greatly facilitate the exploration of functions and mechanisms of eRNAs.


Assuntos
Bases de Dados Genéticas , Elementos Facilitadores Genéticos/genética , RNA/genética , Software , Animais , Biologia Computacional , Regulação da Expressão Gênica/genética , Regiões Promotoras Genéticas/genética , Transcrição Gênica
3.
Brief Bioinform ; 22(6)2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34015824

RESUMO

Expression quantitative trait loci (eQTL) analysis has been widely used in interpreting disease-associated loci through correlating genetic variant loci with the expression of specific genes. RNA-sequencing (RNA-Seq), which can quantify gene expression at the genome-wide level, is often used in eQTL identification. Since different normalization methods of gene expression have substantial impacts on RNA-seq downstream analysis, it is of great necessity to systematically compare the effects of these methods on eQTL identification. Here, by using RNA-seq and genotype data of four different cancers in The Cancer Genome Atlas (TCGA) database, we comprehensively evaluated the effect of eight commonly used normalization methods on eQTL identification. Our results showed that the application of different methods could cause 20-30% differences in the final results of eQTL identification. Among these methods, COUNT, Median of Ratio (MED) and Trimmed Mean of M-values (TMM) generated similar results for identifying eQTLs, while Fragments Per Kilobase Million (FPKM) or RANK produced more differential results compared with other methods. Based on the accuracy and receiver operating characteristic (ROC) curve, the TMM method was found to be the optimal method for normalizing gene expression data in eQTLs analysis. In addition, we also evaluated the performance of different pairwise combinations of these methods. As a result, compared with single normalization methods, the combination of methods can not only identify more cis-eQTLs, but also improve the performance of the ROC curve. Overall, this study provides a comprehensive comparison of normalization methods for identifying eQTLs from RNA-seq data, and proposes some practical recommendations for diverse scenarios.


Assuntos
Biologia Computacional , Estudos de Associação Genética/métodos , Predisposição Genética para Doença , Locos de Características Quantitativas , Algoritmos , Biologia Computacional/métodos , Bases de Dados Genéticas , Expressão Gênica , Genótipo , Humanos , Curva ROC , Reprodutibilidade dos Testes , Fluxo de Trabalho
4.
AIDS Behav ; 27(8): 2669-2680, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36738344

RESUMO

Understanding the roots of Covid-19 vaccine hesitancy in at-risk groups, such as persons living with HIV (PLWH), is of utmost importance. We developed a modified Vaccine Hesitancy Scale (VHS) questionnaire using items from the National Advisory Committee on Immunization Acceptability Matrix. To examine factors associated with receiving COVID-19 vaccine and the link between vaccine attitudes and beliefs with vaccine behavior, PLWH were recruited via social media and community-based organizations (February-May 2022). Descriptive statistics were used to summarize results. Total VHS score was generated by adding Likert scale scores and linear regression models used to compare results between participants who received or did not receive COVID-19 vaccines. Logistic regression models were used to identify factors associated with vaccine uptake. A total of 246 PLWH indicated whether they received a COVID-19 vaccine. 89% received ≥ 1 dose. Mean total VHS(SD) for persons having received ≥ 1 COVID-19 vaccine was 17.8(6.2) vs. 35.4(9.4) for participants not having received any COVID-19 vaccine. Persons who received ≥ 1 dose were significantly older than those who had not received any (48.4 ± 13.8 vs. 34.0 ± 7.7 years, p < 0.0001). The majority of participants considered COVID-19 vaccination important for their health(81.3%) and the health of others(84.4%). Multivariate logistic regression revealed the odds of taking ≥ 1dose were increased 2.4-fold [95% CI 1.6, 3.5] with each increase in age of 10 years (p < 0.0001). Sex and ethnicity were not different between groups. In conclusion, PLWH accept COVID-19 vaccines for both altruistic and individual reasons. With evolving recommendations and increasing numbers of booster vaccines, we must re-examine the needs of PLWH regularly.


Assuntos
COVID-19 , Infecções por HIV , Humanos , Criança , Vacinas contra COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Canadá/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Etnicidade , Vacinação
5.
Nucleic Acids Res ; 49(D1): D1480-D1488, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33137192

RESUMO

Genotype imputation is a process that estimates missing genotypes in terms of the haplotypes and genotypes in a reference panel. It can effectively increase the density of single nucleotide polymorphisms (SNPs), boost the power to identify genetic association and promote the combination of genetic studies. However, there has been a lack of high-quality reference panels for most plants, which greatly hinders the application of genotype imputation. Here, we developed Plant-ImputeDB (http://gong_lab.hzau.edu.cn/Plant_imputeDB/), a comprehensive database with reference panels of 12 plant species for online genotype imputation, SNP and block search and free download. By integrating genotype data and whole-genome resequencing data of plants from various studies and databases, the current Plant-ImputeDB provides high-quality reference panels of 12 plant species, including ∼69.9 million SNPs from 34 244 samples. It also provides an easy-to-use online tool with the option of two popular tools specifically designed for genotype imputation. In addition, Plant-ImputeDB accepts submissions of different types of genomic variations, and provides free and open access to all publicly available data in support of related research worldwide. In general, Plant-ImputeDB may serve as an important resource for plant genotype imputation and greatly facilitate the research on plant genetic research.


Assuntos
Bases de Dados Genéticas , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Genótipo , Proteínas de Plantas/genética , Plantas/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Produtos Agrícolas , Estudos de Associação Genética , Internet , Anotação de Sequência Molecular , Melhoramento Vegetal/métodos , Proteínas de Plantas/metabolismo , Plantas/classificação , Plantas/metabolismo , Polimorfismo de Nucleotídeo Único , Padrões de Referência , Software
6.
Nucleic Acids Res ; 49(D1): D47-D54, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-32986825

RESUMO

Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism that recognizes different polyadenylation signals on transcripts, resulting in transcripts with different lengths of 3' untranslated regions and thereby influencing a series of biological processes. Recent studies have highlighted the important roles of APA in human. However, APA profiles in other animals have not been fully recognized, and there is no database that provides comprehensive APA information for other animals except human. Here, by using the RNA sequencing data collected from public databases, we systematically characterized the APA profiles in 9244 samples of 18 species. In total, we identified 342 952 APA events with a median of 17 020 per species using the DaPars2 algorithm, and 315 691 APA events with a median of 17 953 per species using the QAPA algorithm in these 18 species, respectively. In addition, we predicted the polyadenylation sites (PAS) and motifs near PAS of these species. We further developed Animal-APAdb, a user-friendly database (http://gong_lab.hzau.edu.cn/Animal-APAdb/) for data searching, browsing and downloading. With comprehensive information of APA events in different tissues of different species, Animal-APAdb may greatly facilitate the exploration of animal APA patterns and novel mechanisms, gene expression regulation and APA evolution across tissues and species.


Assuntos
Processamento Alternativo , Biologia Computacional/métodos , Bases de Dados Genéticas , Poliadenilação , RNA Mensageiro/genética , Software , Regiões 3' não Traduzidas , Animais , Humanos , Motivos de Nucleotídeos , Navegador
7.
Nucleic Acids Res ; 48(D1): D659-D667, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31584087

RESUMO

Animal-ImputeDB (http://gong_lab.hzau.edu.cn/Animal_ImputeDB/) is a public database with genomic reference panels of 13 animal species for online genotype imputation, genetic variant search, and free download. Genotype imputation is a process of estimating missing genotypes in terms of the haplotypes and genotypes in a reference panel. It can effectively increase the density of single nucleotide polymorphisms (SNPs) and thus can be widely used in large-scale genome-wide association studies (GWASs) using relatively inexpensive and low-density SNP arrays. However, most animals except humans lack high-quality reference panels, which greatly limits the application of genotype imputation in animals. To overcome this limitation, we developed Animal-ImputeDB, which is dedicated to collecting genotype data and whole-genome resequencing data of nonhuman animals from various studies and databases. A computational pipeline was developed to process different types of raw data to construct reference panels. Finally, 13 high-quality reference panels including ∼400 million SNPs from 2265 samples were constructed. In Animal-ImputeDB, an easy-to-use online tool consisting of two popular imputation tools was designed for the purpose of genotype imputation. Collectively, Animal-ImputeDB serves as an important resource for animal genotype imputation and will greatly facilitate research on animal genomic selection and genetic improvement.


Assuntos
Biologia Computacional/métodos , Bases de Dados Genéticas , Variação Genética , Genótipo , Algoritmos , Animais , Frequência do Gene , Estudo de Associação Genômica Ampla , Genômica , Haplótipos , Internet , Polimorfismo de Nucleotídeo Único , Linguagens de Programação , Valores de Referência , Especificidade da Espécie , Interface Usuário-Computador
8.
Nucleic Acids Res ; 48(D1): D956-D963, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31410488

RESUMO

Numerous studies indicate that non-coding RNAs (ncRNAs) have critical functions across biological processes, and single-nucleotide polymorphisms (SNPs) could contribute to diseases or traits through influencing ncRNA expression. However, the associations between SNPs and ncRNA expression are largely unknown. Therefore, genome-wide expression quantitative trait loci (eQTL) analysis to assess the effects of SNPs on ncRNA expression, especially in multiple cancer types, will help to understand how risk alleles contribute toward tumorigenesis and cancer development. Using genotype data and expression profiles of ncRNAs of >8700 samples from The Cancer Genome Atlas (TCGA), we developed a computational pipeline to systematically identify ncRNA-related eQTLs (ncRNA-eQTLs) across 33 cancer types. We identified a total of 6 133 278 and 721 122 eQTL-ncRNA pairs in cis-eQTL and trans-eQTL analyses, respectively. Further survival analyses identified 8312 eQTLs associated with patient survival times. Furthermore, we linked ncRNA-eQTLs to genome-wide association study (GWAS) data and found 262 332 ncRNA-eQTLs overlapping with known disease- and trait-associated loci. Finally, a user-friendly database, ncRNA-eQTL (http://ibi.hzau.edu.cn/ncRNA-eQTL), was developed for free searching, browsing and downloading of all ncRNA-eQTLs. We anticipate that such an integrative and comprehensive resource will improve our understanding of the mechanistic basis of human complex phenotypic variation, especially for ncRNA- and cancer-related studies.


Assuntos
Biologia Computacional/métodos , Bases de Dados Genéticas , Neoplasias/genética , Locos de Características Quantitativas , RNA não Traduzido , Alelos , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Software , Design de Software , Interface Usuário-Computador , Navegador
9.
Nucleic Acids Res ; 48(D1): D226-D232, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31511885

RESUMO

Alternative polyadenylation (APA) is an important post-transcriptional regulation that recognizes different polyadenylation signals (PASs), resulting in transcripts with different 3' untranslated regions, thereby influencing a series of biological processes and functions. Recent studies have revealed that some single nucleotide polymorphisms (SNPs) could contribute to tumorigenesis and development through dysregulating APA. However, the associations between SNPs and APA in human cancers remain largely unknown. Here, using genotype and APA data of 9082 samples from The Cancer Genome Atlas (TCGA) and The Cancer 3'UTR Altas (TC3A), we systematically identified SNPs affecting APA events across 32 cancer types and defined them as APA quantitative trait loci (apaQTLs). As a result, a total of 467 942 cis-apaQTLs and 30 721 trans-apaQTLs were identified. By integrating apaQTLs with survival and genome-wide association studies (GWAS) data, we further identified 2154 apaQTLs associated with patient survival time and 151 342 apaQTLs located in GWAS loci. In addition, we designed an online tool to predict the effects of SNPs on PASs by utilizing PAS motif prediction tool. Finally, we developed SNP2APA, a user-friendly and intuitive database (http://gong_lab.hzau.edu.cn/SNP2APA/) for data browsing, searching, and downloading. SNP2APA will significantly improve our understanding of genetic variants and APA in human cancers.


Assuntos
Bases de Dados de Ácidos Nucleicos , Neoplasias/genética , Poliadenilação , Polimorfismo de Nucleotídeo Único , Estudo de Associação Genômica Ampla , Técnicas de Genotipagem , Humanos , Neoplasias/mortalidade , Locos de Características Quantitativas , Análise de Sobrevida
10.
BMC Surg ; 22(1): 225, 2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35690775

RESUMO

BACKGROUND: The gastric conduit is the best replacement organ for oesophageal reconstruction, but a reversed gastric conduit (RGC) is rare. Oesophageal reconstruction for oesophageal cancer patients with a previous history of complicated gastrointestinal surgery is rather difficult. Here, we report a case in which oesophageal reconstruction was successfully managed using RGC based solely on the left gastroepiploic artery supply. CASE PRESENTATION: A 69-year-old man with oesophageal cancer had a history of endoscopic intestinal polypectomy and pylorus-preserving pancreaticoduodenectomy (PPPD). The right gastroepiploic artery and right gastric artery had been completely severed. The only supply artery that could be used for the gastric conduit was just the left gastroepiploic artery. Because of the complex history of abdominal surgery, we had no choice but to use the RGC to complete the oesophageal reconstruction, in which the gastric conduit was passed reversely through the hiatus to the oesophageal bed and layered end-to-side manual intrathoracic anastomosis with the esophagus. The patient had transient feeding problems with postoperative delayed thoracic stomach emptying but no anastomotic stenosis or thoracic stomach fistula. He was satisfied with his life and had no long-term complications. There was no significant effect on gut physiological function, and RGC could work normally. CONCLUSIONS: Oesophageal reconstruction with RGC is a feasible procedure for complex oesophageal carcinoma that can simplify complicated surgical procedures, has less influence on gut function, is less invasive, and is safe.


Assuntos
Neoplasias Esofágicas , Esvaziamento Gástrico , Idoso , Anastomose Cirúrgica , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/cirurgia , Humanos , Masculino , Pancreaticoduodenectomia/métodos , Complicações Pós-Operatórias/cirurgia , Piloro/cirurgia , Estômago/irrigação sanguínea , Estômago/cirurgia
11.
Drug Dev Res ; 83(5): 1167-1175, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35470469

RESUMO

Arteriovenous fistula (AVF) is frequently believed to be the best vascular access for chronic renal failure (CRF) patients. Vascular endothelial cell dysfunction has been implicated in AVF maturation. Quercetin (Quer) is a natural polyphenolic compound widely used in traditional Chinese medicine. We aimed to uncover the impacts of Quer on vascular endothelial cells in a CRF rat model and human umbilical vein endothelial cells (HUVECs) stimulated by lipopolysaccharide (LPS) and serum from rat with CRF. Blood urea nitrogen and serum creatinine levels were tested in CRF rat model after administration of Quer. H&E staining was used to estimate endothelial damage. Nitric oxide (NO), endothelial NO synthase (eNOS), EPH receptor B4 (EphB4), EphrinB2, and p-caveolin-1 (p-Cav-1) levels in the serum were examined by enzyme-linked immunosorbent assay. Western blot was employed to analyze the expressions of eNOS, phosphorylated (p)-eNOS, EphB4, and Cav-1 in arterial tissues and HUVECs. Cell counting kit-8 was applied for assessing cell proliferation. TUNEL (terminal-deoxynucleotidyl transferase-mediated nick end labeling) assay was employed to estimate cell apoptosis. Results showed that Quer ameliorated renal function impairment and endothelial injury in vivo. Meanwhile, Quer boosted the proliferation and suppressed the apoptosis of HUVECs stimulated by LPS and serum from rat with CRF. Additionally, Quer elevated NO and eNOS levels, upregulated p-eNOS expression but downregulated EphB4, EphrinB2, and p-Cav-1 expressions. Moreover, EphB4 inhibitor had the similar effect as Quer treatment in HUVECs stimulated by LPS and serum from rat with CRF. Collectively, Quer might effectively regulate vascular function to prevent AVF failure in CRF via modulation of Eph/Cav-1 signaling.


Assuntos
Endotélio Vascular , Falência Renal Crônica , Animais , Endotélio Vascular/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/metabolismo , Lipopolissacarídeos/farmacologia , Óxido Nítrico/metabolismo , Quercetina/farmacologia , Ratos
12.
J Stroke Cerebrovasc Dis ; 30(1): 105436, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33171426

RESUMO

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic agent, which has shown an effect on reducing blood loss in many diseases. Many studies focus on the effect of TXA on cerebral hemorrhage, however, whether TXA can inhibit hematoma expansion is still controversial. Our meta-analysis performed a quantitative analysis to evaluate the efficacy of TXA for the hematoma expansion in spontaneous and traumatic intracranial hematoma. METHOD: Pubmed (MEDLINE), Embase, and Cochrane Library were searched from January 2001 to May 2020 for randomized controlled trials (RCTs). RESULT: We pooled 3102 patients from 7 RCTs to evaluate the efficacy of TXA for hematoma expansion. Hematoma expansion (HE) rate and hematoma volume (HV) change from baseline were used to analyze. We found that TXA led to a significant reduction in HE rate (P = 0.002) and HV change (P = 0.03) compared with the placebo. Patients with moderate or serious hypertension benefit more from TXA. (HE rate: P = 0.02, HV change: P = 0.04) TXA tends to have a better efficacy on HV change in intracerebral hemorrhage (ICH). (P = 0.06) CONCLUSIONS: TXA showed good efficacy for hematoma expansion in spontaneous and traumatic intracranial hemorrhage. Patients with moderate/severe hypertension and ICH may be more suitable for TXA administration in inhibiting hematoma expansion .


Assuntos
Antifibrinolíticos/uso terapêutico , Hemorragia Encefálica Traumática/tratamento farmacológico , Hemorragia Cerebral/tratamento farmacológico , Hematoma/tratamento farmacológico , Ácido Tranexâmico/uso terapêutico , Antifibrinolíticos/efeitos adversos , Hemorragia Encefálica Traumática/diagnóstico por imagem , Hemorragia Encefálica Traumática/mortalidade , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/mortalidade , Progressão da Doença , Hematoma/diagnóstico por imagem , Hematoma/mortalidade , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ácido Tranexâmico/efeitos adversos , Resultado do Tratamento
13.
Ann Surg Oncol ; 27(11): 4384-4393, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32642997

RESUMO

PURPOSE: The purpose of this study was to evaluate the short- and long-term outcomes of video-assisted thoracoscopic surgery (VATS) versus open thoracotomy bronchial sleeve lobectomy (BSL) for patients with central lung cancer. METHODS: This is a retrospective cohort study. Perioperative outcomes and long-term survival of patients who underwent VATS versus open thoracotomy BSL for central lung cancer from June 2010 and June 2018 in the Western China Lung Cancer Database were compared using propensity score matching (PSM) between the two surgical approaches. RESULTS: The retrospective study included 187 patients who divided into VATS group (n = 44) and open group (n = 143) according to surgical approach, and PSM resulted in 43 patients in each group, which were well matched by 11 potential prognostic factors. The VATS group was associated with lower overall incidence of postoperative complications (20.3% vs. 30.2%, P = 0.029), less postoperative drainage (875 ml [250-3960] vs. 1280 ml [100-4890], P = 0.039). The 5-year overall survival (OS) and disease-free survival (DFS) were comparable between the VATS and open groups (55.9% vs. 65.2% P = 0.836 and 54.1% vs. 60.2% P = 0.391, respectively) after matching. Multivariable adjusted analysis demonstrated that the surgical approach was not an independent favorable prognostic factor for OS (hazard ratio [HR] = 0.922; 95% confidence interval [CI], 0.427-1.993; P = 0.836) but just the pTNM stage (HR = 2.003; 95% CI 1.187-3.382; P = 0.009). CONCLUSIONS: VATS BSL may achieve equivalent long-term outcomes for central lung cancer patients when comparing with open thoracotomy. Although slightly longer duration of surgery, VATS approach may be a feasible option for lung cancer patients requiring BSL.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Cirurgia Torácica Vídeoassistida , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Estudos de Coortes , Humanos , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Pontuação de Propensão , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/métodos , Resultado do Tratamento
14.
J Headache Pain ; 21(1): 14, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046655

RESUMO

BACKGROUND: Galcanezumab is a novel monoclonal antibody that target to calcitonin gene-related peptide (CGRP). It has been tested for the preventive treatment of migraine and episodic cluster headache by multiple randomized clinical trials (RCTs) and have been found to reduce headache frequency. METHODS: We systematically searched PubMed and Embase on Cochrane Central Register of Controlled Trials (CENTRAL) from the earliest date to August 1, 2019. Relative risk (RR) and weighted mean difference (WMD) were used to evaluate clinical outcomes. RESULTS: Seven studies were pooled with 3889 patients. Subcutaneous injection of Galcanezumab at 120 mg, 240 mg leads to a statistically significant response rate for the treatment of migraine compared with placebo (120 mg: RR = 1.51; 95% CI, 1.33 to 1.70; P < 0.001; 240 mg: RR = 1.58; 95% CI, 1.43 to 1.76; P < 0.001). Among them, 120 mg group has the same treatment efficacy with 240 mg group (50% response: RR = 1.06; 95% CI, 0.92 to 1.22; P = 0.425; 75% response: RR = 1.07; 95% CI, 0.94 to 1.23; P = 0.301; 100% response; RR = 1.06; 95% CI, 0.81 to 1.37; P = 0.682; MHD: RR = - 0.08; 95% CI, - 0.55 to - 0.40; P = 0.748) while related to a lower risk for adverse events for the treatment of migraine (120 mg RR = 1.06; 95% CI, 0.99 to 1.14; P = 0.084; 240 mg: RR = 1.17; 95% CI, 1.09 to 1.25; P < 0.001). 300 mg per month galcanezumab is effective for the prevention of episodic cluster headache measured by at least 50% reduction of cluster headache frequency at week 3 (RR = 1.36; 95% CI, 1.00-1.84; P = 0.048). CONCLUSIONS: Use of galcanezumab is related to a significantly reduced monthly headache frequency compared with placebo for the treatment of migraine and episodic cluster headache, 120 mg has the same treatment efficacy with 240 mg group while related to a lower risk for adverse effects for the treatment of migraine. 300 mg per month galcanezumab is effective for the prevention of episodic cluster headache with no significantly increased adverse events.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Cefaleia Histamínica/tratamento farmacológico , Transtornos de Enxaqueca/tratamento farmacológico , Peptídeo Relacionado com Gene de Calcitonina , Método Duplo-Cego , Humanos , Injeções Subcutâneas , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
15.
J Biol Chem ; 293(17): 6230-6240, 2018 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-29588369

RESUMO

Membrane biology seeks to understand how lipids and proteins within bilayers assemble into large structures such as organelles and the plasma membranes. Historically, lipids were thought to merely provide structural support for bilayer formation and membrane protein function. Research has now revealed that phospholipid metabolism regulates nearly all cellular processes. Sophisticated techniques helped identify >10,000 lipid species suggesting that lipids support many biological processes. Here, we highlight the synthesis of the most abundant glycerophospholipid classes and their distribution in organelles. We review vesicular and nonvesicular transport pathways shuttling lipids between organelles and discuss lipid regulators of membrane trafficking and second messengers in eukaryotic cells.


Assuntos
Membrana Celular/metabolismo , Bicamadas Lipídicas/metabolismo , Organelas/metabolismo , Fosfolipídeos/metabolismo , Animais , Transporte Biológico Ativo/fisiologia , Humanos
16.
J Biol Chem ; 292(34): 14292-14307, 2017 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-28698382

RESUMO

Caveolae are bulb-shaped nanodomains of the plasma membrane that are enriched in cholesterol and sphingolipids. They have many physiological functions, including endocytic transport, mechanosensing, and regulation of membrane and lipid transport. Caveola formation relies on integral membrane proteins termed caveolins (Cavs) and the cavin family of peripheral proteins. Both protein families bind anionic phospholipids, but the precise roles of these lipids are unknown. Here, we studied the effects of phosphatidylserine (PtdSer), phosphatidylinositol 4-phosphate (PtdIns4P), and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) on caveolar formation and dynamics. Using live-cell, single-particle tracking of GFP-labeled Cav1 and ultrastructural analyses, we compared the effect of PtdSer disruption or phosphoinositide depletion with caveola disassembly caused by cavin1 loss. We found that PtdSer plays a crucial role in both caveola formation and stability. Sequestration or depletion of PtdSer decreased the number of detectable Cav1-GFP puncta and the number of caveolae visualized by electron microscopy. Under PtdSer-limiting conditions, the co-localization of Cav1 and cavin1 was diminished, and cavin1 degradation was increased. Using rapamycin-recruitable phosphatases, we also found that the acute depletion of PtdIns4P and PtdIns(4,5)P2 has minimal impact on caveola assembly but results in decreased lateral confinement. Finally, we show in a model of phospholipid scrambling, a feature of apoptotic cells, that caveola stability is acutely affected by the scrambling. We conclude that the predominant plasmalemmal anionic lipid PtdSer is essential for proper Cav clustering, caveola formation, and caveola dynamics and that membrane scrambling can perturb caveolar stability.


Assuntos
Cavéolas/metabolismo , Caveolina 1/metabolismo , Membrana Celular/metabolismo , Modelos Biológicos , Fosfatidilserinas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Cavéolas/química , Cavéolas/ultraestrutura , Caveolina 1/antagonistas & inibidores , Caveolina 1/química , Caveolina 1/genética , Linhagem Celular , Membrana Celular/química , Membrana Celular/ultraestrutura , Rastreamento de Células , Cricetulus , Humanos , Cinética , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Mesocricetus , Microscopia Eletrônica de Transmissão , Microscopia de Vídeo , Fosfatidilinositol 4,5-Difosfato/química , Fosfatidilinositol 4,5-Difosfato/metabolismo , Fosfatos de Fosfatidilinositol/química , Fosfatos de Fosfatidilinositol/metabolismo , Fosfatidilserinas/química , Transporte Proteico , Interferência de RNA , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/genética , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Imagem com Lapso de Tempo
17.
Biochem Biophys Res Commun ; 451(4): 632-6, 2014 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-25130461

RESUMO

Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. We hypothesized that the products of lipoprotein hydrolysis generated by LPL promote atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To test this hypothesis, we treated human THP-1 macrophages with total lipoproteins that were hydrolyzed by LPL and we found significantly reduced transcript levels for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor BI. These decreases were likely due to significant reductions for the nuclear receptors liver-X-receptor-α, peroxisome proliferator activated receptor (PPAR)-α, and PPAR-γ. We prepared a mixture of free fatty acids (FFA) that represented the ratios of FFA species within lipoprotein hydrolysis products, and we found that the FFA mixture also significantly reduced cholesterol transporters and nuclear receptors. Finally, we tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I, and we found that the treatment of THP-1 macrophages with the FFA mixture significantly attenuated cholesterol efflux. Overall, these data show that the FFA component of lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL.


Assuntos
Colesterol/metabolismo , Ácidos Graxos não Esterificados/farmacologia , Lipase Lipoproteica/metabolismo , Lipoproteínas/metabolismo , Macrófagos/metabolismo , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/metabolismo , Aterosclerose/etiologia , Ácidos Graxos não Esterificados/metabolismo , Células HEK293 , Humanos , Receptores Depuradores Classe B/metabolismo
18.
Plants (Basel) ; 13(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38891379

RESUMO

The MYB transcription factors (TFs) have substantial functions in anthocyanin synthesis as well as being widely associated with plant responses to various adversities. In the present investigation, we found an unreported MYB TF from Solanum aculeatissimum (a wild relative of eggplant) and named it SaMYB113 in reference to its homologous gene. Bioinformatics analysis demonstrated that the open reading frame of SaMYB113 was 825 bp in length, encoding 275 amino acids, with a typical R2R3-MYB gene structure, and predicted subcellular localization in the nucleus. Analysis of the tissue-specific expression pattern through qRT-PCR showed that the SaMYB113 was expressed at a high level in young stems as well as leaves of S. aculeatissimum. Transgenic Arabidopsis and tobacco plants overexpressing SaMYB113 pertinent to the control of the 35S promoter exhibited a distinct purple color trait, suggesting a significant change in their anthocyanin content. Furthermore, we obtained three tobacco transgenic lines with significant differences in anthocyanin accumulation and analyzed the differences in anthocyanin content by LC-MS/MS. The findings demonstrated that overexpression of SaMYB113 caused tobacco to have considerably raised levels of several anthocyanin components, with the most significant increases in delphinidin-like anthocyanins and cyanidin-like anthocyanins. The qRT-PCR findings revealed significant differences in the expression levels of structural genes for anthocyanin synthesis among various transgenic lines. In summary, this study demonstrated that the SaMYB113 gene has a substantial impact on anthocyanin synthesis, and overexpression of the SaMYB113 gene leads to significant modifications to the expression levels of a variety of anthocyanin-synthesizing genes, which leads to complex changes in anthocyanin content and affects plant phenotypes. This present research offers the molecular foundation for the research of the mechanism of anthocyanin formation within plants, as well as providing some reference for the improvement of traits in solanum crops.

19.
Plants (Basel) ; 13(4)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38498531

RESUMO

Capsicum baccatum is a close relative of edible chili peppers (Capsicum annuum) with high economic value. The CBF gene family plays an important role in plant stress resistance physiology. We detected a total of five CBF genes in the C. baccatum genome-wide sequencing data. These genes were scattered irregularly across four chromosomes. The genes were categorized into three groupings according to their evolutionary relationships, with genes in the same category showing comparable principles for motif composition. The 2000 bp upstream of CbCBF contains many resistance-responsive elements, hormone-responsive elements, and transcription factor binding sites. These findings emphasize the crucial functions of these genes in responding to challenging conditions and physiological regulation. Analysis of tissue-specific expression revealed that CbCBF3 exhibited the greatest level of expression among all tissues. Under conditions of low-temperature stress, all CbCBF genes exhibited different levels of responsiveness, with CbCBF3 showing a considerable up-regulation after 0.25 h of cold stress, indicating a high sensitivity to low-temperature response. The importance of the CbCBF3 gene in the cold response of C. baccatum was confirmed by the use of virus-induced gene silencing (VIGS) technology, as well as the prediction of its protein interaction network. To summarize, this study conducts a thorough bioinformatics investigation of the CbCBF gene family, showcases the practicality of employing VIGS technology in C. baccatum, and confirms the significance of the CbCBF3 gene in response to low temperatures. These findings provide significant references for future research on the adaptation of C. baccatum to low temperatures.

20.
Bioelectrochemistry ; 159: 108748, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38824746

RESUMO

In this study, we have designed an electrochemical biosensor based on topological material Bi2Se3 for the sensitive detection of SARS-CoV-2 in the COVID-19 pandemic. Flake-shaped Bi2Se3 was obtained directly from high-quality single crystals using mechanical exfoliation, and the single-stranded DNA was immobilized onto it. Under optimal conditions, the peak current of the differential pulse voltammetry method exhibited a linear relationship with the logarithm of the concentration of target-complementary-stranded DNA, ranging from 1.0 × 10-15 to 1.0 × 10-11 M, with a detection limit of 3.46 × 10-16 M. The topological material Bi2Se3, with Dirac surface states, enhanced the signal-to-interference plus noise ratio of the electrochemical measurements, thereby improving the sensitivity of the sensor. Furthermore, the electrochemical sensor demonstrated excellent specificity in recognizing RNA. It can detect complementary RNA by amplifying and transcribing the initial DNA template, with an initial DNA template concentration ranging from 1.0 × 10-18 to 1.0 × 10-15 M. Furthermore, the sensor also effectively distinguished negative and positive results by detecting splitting-synthetic SARS-CoV-2 pseudovirus with a concentration of 1 copy/µL input. Our work underscores the immense potential of the electrochemical sensing platform based on the topological material Bi2Se3 in the detection of pathogens during the rapid spread of acute infectious diseases.


Assuntos
Técnicas Biossensoriais , Bismuto , COVID-19 , Técnicas Eletroquímicas , Limite de Detecção , SARS-CoV-2 , Técnicas Biossensoriais/métodos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , COVID-19/diagnóstico , COVID-19/virologia , Bismuto/química , Técnicas Eletroquímicas/métodos , Humanos , DNA de Cadeia Simples/química , DNA de Cadeia Simples/genética , RNA Viral/genética , RNA Viral/análise , Compostos de Selênio/química
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