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1.
Proc Natl Acad Sci U S A ; 119(30): e2201967119, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35858435

RESUMO

Major depressive disorder (MDD) is a prevalent and devastating mental illness. To date, the diagnosis of MDD is largely dependent on clinical interviews and questionnaires and still lacks a reliable biomarker. DNA methylation has a stable and reversible nature and is likely associated with the course and therapeutic efficacy of complex diseases, which may play an important role in the etiology of a disease. Here, we identified and validated a DNA methylation biomarker for MDD from four independent cohorts of the Chinese Han population. First, we integrated the analysis of the DNA methylation microarray (n = 80) and RNA expression microarray data (n = 40) and identified BICD2 as the top-ranked gene. In the replication phase, we employed the Sequenom MassARRAY method to confirm the DNA hypermethylation change in a large sample size (n = 1,346) and used the methylation-sensitive restriction enzymes and a quantitative PCR approach (MSE-qPCR) and qPCR method to confirm the correlation between DNA hypermethylation and mRNA down-regulation of BICD2 (n = 60). The results were replicated in the peripheral blood of mice with depressive-like behaviors, while in the hippocampus of mice, Bicd2 showed DNA hypomethylation and mRNA/protein up-regulation. Hippocampal Bicd2 knockdown demonstrates antidepressant action in the chronic unpredictable mild stress (CUMS) mouse model of depression, which may be mediated by increased BDNF expression. Our study identified a potential DNA methylation biomarker and investigated its functional implications, which could be exploited to improve the diagnosis and treatment of MDD.


Assuntos
Metilação de DNA , Transtorno Depressivo Maior , Hipocampo , Proteínas Associadas aos Microtúbulos , Animais , DNA/metabolismo , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/genética , Modelos Animais de Doenças , Regulação para Baixo , Técnicas de Silenciamento de Genes , Marcadores Genéticos , Hipocampo/metabolismo , Humanos , Camundongos , Proteínas Associadas aos Microtúbulos/genética , RNA Mensageiro/metabolismo , Estresse Psicológico/genética
2.
Sensors (Basel) ; 22(6)2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35336448

RESUMO

In recent years, interest in aquaculture acoustic signal has risen since the development of precision agriculture technology. Underwater acoustic signals are known to be noisy, especially as they are inevitably mixed with a large amount of environmental background noise, causing severe interference in the extraction of signal features and the revelation of internal laws. Furthermore, interference adds a considerable burden on the transmission, storage, and processing of data. A signal recognition curve (SRC) algorithm is proposed based on higher-order cumulants (HOC) and a recognition-sigmoid function for feature extraction of target signals. The signal data of interest can be accurately identified using the SRC. The analysis and verification of the algorithm are carried out in this study. The results show that when the SNR is greater than 7 dB, the SRC algorithm is effective, and the performance improvement is maximized when the SNR is 11 dB. Furthermore, the SRC algorithm has shown better flexibility and robustness in application.


Assuntos
Acústica , Algoritmos , Aquicultura , Ruído , Registros
3.
Anticancer Drugs ; 31(4): 403-410, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31917701

RESUMO

Our retrospective study assessed the efficacy and safety of irinotecan plus raltitrexed in esophageal squamous cell cancer (ESCC) patients who were previously treated with multiple systemic therapies. Between January 2016 and December 2018, records of 38 ESCC patients who underwent irinotecan plus raltitrexed chemotherapy after at least one line of chemotherapy were reviewed. Efficacy assessment was performed every two cycles according to the RECIST version 1.1. A total of 95 cycles of chemotherapy were administered, and the median course was 3 (range 2-6). There was no treatment-related death. Nine patients had partial response, 21 had stable disease and eight had progressive disease. The overall objective response rate was 23.68% (9/38) and the disease control rate was78.94% (30/38). After a median follow-up of 18.5 months, the median progression-free survival and overall survival were 105 and 221 days, respectively. There were five patients (13.15%) with grade 3/4 leukopenia, three patients (7.89%) with grade 3/4 neutropenia and one patient (2.63%) with grade 3/4 diarrhea. The combination of irinotecan plus raltitrexed was effective for pretreated ESCC patients. Further studies are needed to determine the optimal dose of the two drugs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Seguimentos , Humanos , Irinotecano/administração & dosagem , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Quinazolinas/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida , Tiofenos/administração & dosagem
4.
BMC Plant Biol ; 17(1): 42, 2017 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-28193161

RESUMO

BACKGROUND: Long non-coding RNA (lncRNA) is a class of non-coding RNA with important regulatory roles in biological process of organisms. The systematic comparison of lncRNAs with protein coding mRNAs in population expression and their response to environmental change are still poorly understood. Here we identified 17,610 lncRNAs and calculated their expression levels based on RNA-seq of 80 individuals of Miscanthus lutarioriparius from two environments, the nearly native habitats and transplanted field, respectively. RESULTS: LncRNAs had significantly higher expression diversity and lower expression frequency in population than protein coding mRNAs in both environments, which suggested that lncRNAs may experience more relaxed selection or divergent evolution in population compared with protein coding RNAs. In addition, the increase of expression diversity for lncRNAs was always significantly higher and the magnitude of fold change of expression in new stress environment was significantly larger than protein-coding mRNAs. These results suggested that lncRNAs may be more sensitive to environmental change than protein-coding mRNAs. Analysis of environment-robust and environment-specific lncRNA-mRNA co-expression network between two environments revealed the characterization of lncRNAs in response to environmental change. Furthermore, candidate lncRNAs contributing to water use efficiency (WUE) identified based on the WUE-lncRNA-mRNA co-expression network suggested the roles of lncRNAs in response to environmental change. CONCLUSION: Our study provided a comprehensive understanding of expression characterization of lncRNAs in population for M. lutarioriparius under field condition, which would be useful to explore the roles of lncRNAs and could accelerate the process of adaptation in new environment for many plants.


Assuntos
Proteínas de Plantas/genética , Poaceae/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , China , Ecossistema , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Proteínas de Plantas/metabolismo , Poaceae/fisiologia , RNA de Plantas , Água/metabolismo
5.
Mol Ecol ; 26(21): 5911-5922, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28833782

RESUMO

The use of transcriptome data in the study of the population genetics of a species can capture faint signals of both genetic variation and expression variation and can provide a broad picture of a species' genomic response to environmental conditions. In this study, we characterized the genetic and expression diversity of Miscanthus lutarioriparius by comparing more than 16,225 transcripts obtained from 78 individuals, belonging to 10 populations distributed across the species' entire geographic range. We only observed a low level of nucleotide diversity (π = 0.000434) among the transcriptome data of these populations, which is consistent with highly conserved sequences of functional elements and protein-coding genes captured with this method. Tests of population divergence using the transcriptome data were consistent with previous microsatellite data but proved to be more sensitive, particularly if gene expression variation was considered as well. For example, the analysis of expression data showed that genes involved in photosynthetic processes and responses to temperature or reactive oxygen species stimuli were significantly enriched in certain populations. This differential gene expression was primarily observed among populations and not within populations. Interestingly, nucleotide diversity was significantly negatively correlated with expression diversity within populations, while this correlation was positive among populations. This suggests that genetic and expression variation play separate roles in adaptation and population persistence. Combining analyses of genetic and gene expression variation represents a promising approach for studying the population genetics of wild species and may uncover both adaptive and nonadaptive processes.


Assuntos
Variação Genética , Genética Populacional , Poaceae/genética , Transcriptoma , Produtos Agrícolas/genética , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único
6.
J Exp Bot ; 66(20): 6415-29, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26175351

RESUMO

Understanding the genetic basis of water use efficiency (WUE) and its roles in plant adaptation to a drought environment is essential for the production of second-generation energy crops in water-deficit marginal land. In this study, RNA-Seq and WUE measurements were performed for 78 individuals of Miscanthus lutarioriparius grown in two common gardens, one located in warm and wet Central China near the native habitats of the species and the other located in the semiarid Loess Plateau, the domestication site of the energy crop. The field measurements showed that WUE of M. lutarioriparius in the semiarid location was significantly higher than that in the wet location. A matrix correlation analysis was conducted between gene expression levels and WUE to identify candidate genes involved in the improvement of WUE from the native to the domestication site. A total of 48 candidate genes were identified and assigned to functional categories, including photosynthesis, stomatal regulation, protein metabolism, and abiotic stress responses. Of these genes, nearly 73% were up-regulated in the semiarid site. It was also found that the relatively high expression variation of the WUE-related genes was affected to a larger extent by environment than by genetic variation. The study demonstrates that transcriptome-wide correlation between physiological phenotypes and expression levels offers an effective means for identifying candidate genes involved in the adaptation to environmental changes.


Assuntos
Produtos Agrícolas/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Poaceae/genética , Água/metabolismo , China , Produtos Agrícolas/metabolismo , Secas , Ecossistema , Variação Genética , Proteínas de Plantas/metabolismo , Poaceae/metabolismo , Análise de Sequência de RNA
7.
J Integr Plant Biol ; 57(3): 284-99, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25251542

RESUMO

While it is widely accepted that genetic diversity determines the potential of adaptation, the role that gene expression variation plays in adaptation remains poorly known. Here we show that gene expression diversity could have played a positive role in the adaptation of Miscanthus lutarioriparius. RNA-seq was conducted for 80 individuals of the species, with half planted in the energy crop domestication site and the other half planted in the control site near native habitats. A leaf reference transcriptome consisting of 18,503 high-quality transcripts was obtained using a pipeline developed for de novo assembling with population RNA-seq data. The population structure and genetic diversity of M. lutarioriparius were estimated based on 30,609 genic single nucleotide polymorphisms. Population expression (Ep ) and expression diversity (Ed ) were defined to measure the average level and the magnitude of variation of a gene expression in the population, respectively. It was found that expression diversity increased while genetic diversity decreased after the species was transplanted from the native habitats to the harsh domestication site, especially for genes involved in abiotic stress resistance, histone methylation, and biomass synthesis under water limitation. The increased expression diversity could have enriched phenotypic variation directly subject to selections in the new environment.


Assuntos
Adaptação Fisiológica/genética , Variação Genética , Poaceae/genética , Transcriptoma/genética , Produtos Agrícolas/genética , Regulação da Expressão Gênica de Plantas , Genética Populacional , Genoma de Planta , Filogenia , Folhas de Planta/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Padrões de Referência
8.
Neuroscience ; 558: 30-36, 2024 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-39067681

RESUMO

Schizophrenia (SCZ) is a highly heterogeneous, severe neuropsychiatric disorder of unknown etiopathology. Increasing data indicate an overlap between schizophrenia and pathological processes related to immunological dysregulation as well as inflammation, such as high levels of pro-inflammatory substances in patients' blood and cerebrospinal fluid and autoantibodies against synaptic and nerve cell membrane proteins. Autoantibodies against SFT2D2 have been reported in patients with SCZ. However, their roles in inflammation have not yet been established. We performed a continuous intracerebroventricular infusion of polyclonal rabbit anti-SFT2D2-IgG in male C57BL/6 mice. Behavioral tests were conducted after 2 weeks of treatment. Our results showed an increased density of microglia and activated astrocytes in the primary somatosensory cortex of the anti-SFT2D2-IgG-infused mice. Quantitative reverse transcription-polymerase chain reactions showed that the expression of pro-inflammatory genes was upregulated in the primary somatosensory cortex and hippocampus of the anti-SFT2D2-IgG-infused mice. Additionally, the mice exhibited defective sensorimotor gating, memory deficits, motor impairment, and anxiety-related behaviors without signs of depression. These findings indicate that anti-SFT2D2 autoantibodies can induce encephalitis, cause a series of behavioral changes associated with schizophrenia, and offer a model for testing novel therapies to improve treatment strategies for a subgroup of patients with SCZ.


Assuntos
Autoanticorpos , Modelos Animais de Doenças , Esquizofrenia , Animais , Masculino , Camundongos , Astrócitos/metabolismo , Astrócitos/imunologia , Autoanticorpos/imunologia , Hipocampo/imunologia , Hipocampo/metabolismo , Camundongos Endogâmicos C57BL , Microglia/imunologia , Microglia/metabolismo , Esquizofrenia/imunologia , Filtro Sensorial/efeitos dos fármacos , Córtex Somatossensorial/imunologia , Córtex Somatossensorial/efeitos dos fármacos
9.
PeerJ ; 12: e17930, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39210920

RESUMO

Introduction: To evaluate the recovery quality between remimazolam and propofol after general anesthesia surgery. Methods: We included eligible randomized controlled trials (RCTs) in EMBASE, PubMed, Cochrane Central, Scopus, and Web of Science up to June 26, 2024 for comparison the recovery quality of remimazolam and propofol after general anaesthesia. The primary outcomes were the total Quality of Recovery-15 (QoR-15) and five dimensions of QoR-15 on postoperative day 1 (POD1). Secondary outcomes were adverse events, the Quality of Recovery-40 (QoR-40) on POD1, and the intraoperative and postoperative time characteristics. Results: Thirteen RCTs with a total of 1,305 patients were included in this meta-analysis. Our statistical analysis showed that remimazolam group had higher QoR-15 score on POD1, with no significant difference (Mean Difference (MD) = 1.24; 95% confidence interval (CI), [-1.67-4.15]; I2 = 75%; P = 0.41). In the five dimensions of QoR-15, remimazolam group was superior to propofol group in terms of physical independence (MD = 0.79; 95% CI [0.31-1.27]; I2 = 0%; P = 0.001). Remimazolam group was lower than propofol group in incidence of hypotension (Risk Ratio (RR) = 0.48; 95% CI [0.40-0.59]; I2 = 14%; P < 0.00001), bradycardia (RR = 0.18; 95% CI [0.08-0.38]; I2 = 0%; P < 0.0001) and injection pain (RR = 0.03; 95% CI [0.01-0.12]; I2 = 48%; P < 0.00001), respectively. The intraoperative and postoperative time characteristics and the QoR-40 were similar in the two groups. Conclusions: Our analysis showed that the recovery quality of the remimazolam group after general anaesthesia was similar to propofol group, while the incidence of adverse events was low in remimazolam group. As a potential anesthetic, remimazolam can be used in place of propofol for surgical general anesthesia.


Assuntos
Período de Recuperação da Anestesia , Anestesia Geral , Benzodiazepinas , Propofol , Humanos , Anestesia Geral/efeitos adversos , Anestésicos Intravenosos/efeitos adversos , Anestésicos Intravenosos/administração & dosagem , Benzodiazepinas/efeitos adversos , Benzodiazepinas/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/uso terapêutico , Propofol/efeitos adversos , Propofol/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
J Psychiatr Res ; 171: 99-107, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38262166

RESUMO

BACKGROUND: Autoimmunity plays an important role in schizophrenia (SCZ). Autoantibodies against SFT2D2 have been reported in patients with SCZ; however, the specific mechanism remains unclear. This study aimed to describe an autoimmune model, namely, mice immunized against SFT2D2-peptides. METHODS: ApoE-/- and WT mice (C57BL/6) were immunized four times (day 0, day 14, day 21, day 35) with SFT2D2 peptide or KLH via subcutaneous injection. Behavioral tests were conducted after the third immunization, and immunochemistry of brain tissue were performed after the sacrifice of the mice. RESULTS: Active immunization with KLH-coupled SFT2D2-derived peptides in both WT and ApoE-/- (compromised blood-brain barrier) mice led to high circulating levels of anti-SFT2D2 IgG. While there was no detectable deficit in WT mice, impaired pre-pulse inhibition, motor impairments, and reduced cognition in ApoE-/- mice, without signs of anxiety and depression were observed. In addition, immunohistochemical assays demonstrated that activated microglia and astrocytes were increased but neuronal dendritic spine densities were decreased, accompanied by increased expression of complement molecule C4 across brain regions in ApoE-/- mice. CONCLUSIONS: In model mice with compromised blood-brain barrier, endogenous anti-SFT2D2 IgG can activate glial cells and modulate synaptic plasticity, and induce a series of psychosis-like changes. These antibodies may reveal valuable therapeutic targets, which may improve the treatment strategies for a subgroup of SCZ patients.


Assuntos
Autoanticorpos , Imunoglobulina G , Humanos , Camundongos , Animais , Camundongos Endogâmicos C57BL , Imunoglobulina G/metabolismo , Apolipoproteínas E , Peptídeos , Dendritos/metabolismo
11.
Schizophr Bull Open ; 5(1): sgac047, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39144109

RESUMO

Background and Hypothesis: Environmental stressors may influence immune surveillance in B lymphocytes and stimulate autoimmune responses via epigenetic DNA methylation modifications in schizophrenia (SCZ). Study Design: A total of 2722, Chinese Han origin subjects were recruited in this study (2005-2011), which included a discovery follow-up cohort with 40 remitters of SCZ (RSCZ), 40 nonremitters of SCZ (NRSCZ), and 40 controls (CTL), and a replication follow-up cohort (64 RSCZ, 16 NRSCZ, and 84 CTL), as well as a case-control validation cohort (1230 SCZ and 1208 CTL). Genomic DNA methylation, target gene mRNA transcripts, and plasma autoantibody levels were measured across cohorts. Study Results: We found extensive differences in global DNA methylation profiles between RSCZ and NRSCZ groups, wherein differential methylation sites (DMS) were enriched with immune cell maturation and activation in the RSCZ group. Out of 2722 participants, the foremost DMS cg14341177 was hyper-methylated in the SCZ group and it inhibited the alternative splicing of its target gene BICD2 and may have increased its autoantigen exposure, leading to an increase in plasma anti-BICD2 IgG antibody levels. The levels of cg14341177 methylation and anti-BICD2 IgG decreased significantly in RSCZ endpoint samples but not in NRSCZ endpoint samples. There are strong positive correlations between cg14341177 methylation, anti-BICD2 IgG, and positive and negative syndrome scale (PANSS) scores in the RSCZ groups, but not in the NRSCZ groups. Conclusions: These data suggest that abnormal DNA methylation could affect autoreactive responses in SCZ, and that cg14341177 methylation and anti-BICD2 IgG levels may potentially serve as useful biomarkers.

12.
Genes (Basel) ; 14(4)2023 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-37107637

RESUMO

Microtia is a congenital malformation characterized by a small, abnormally shaped auricle (pinna) ranging in severity. Congenital heart defect (CHD) is one of the comorbid anomalies with microtia. However, the genetic basis of the co-existence of microtia and CHD remains unclear. Copy number variations (CNVs) of 22q11.2 contribute significantly to microtia and CHD, respectively, thus suggesting a possible shared genetic cause embedded in this genomic region. In this study, 19 sporadic patients with microtia and CHD, as well as a nuclear family, were enrolled for genetic screening of single nucleotide variations (SNVs) and CNVs in 22q11.2 by target capture sequencing. We detected a total of 105 potential deleterious variations, which were enriched in ear- or heart-development-related genes, including TBX1 and DGCR8. The gene burden analysis also suggested that these genes carry more deleterious mutations in the patients, as well as several other genes associated with cardiac development, such as CLTCL1. Additionally, a microduplication harboring SUSD2 was validated in an independent cohort. This study provides new insights into the underlying mechanisms for the comorbidity of microtia and CHD focusing on chromosome 22q11.2, and suggests that a combination of genetic variations, including SNVs and CNVs, may play a crucial role instead of single gene mutation.


Assuntos
Microtia Congênita , Cardiopatias Congênitas , MicroRNAs , Humanos , Microtia Congênita/genética , Variações do Número de Cópias de DNA/genética , Proteínas de Ligação a RNA/genética , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/diagnóstico , Testes Genéticos , Cromossomos Humanos Par 2
13.
Fundam Res ; 2(6): 851-858, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38933390

RESUMO

Rare and undiagnosed diseases tend to be diverse, misdiagnosed, and difficult to diagnose. In some cases, the disease is progressive and life-threatening. Yet, to date, an estimated 95% of rare diseases have no approved therapy. Therefore, rare and undiagnosed diseases are considered the ultimate challenges for understanding human diseases. Here, we review the research progress, research frontiers, and important scientific issues related to rare and undiagnosed diseases. We mainly focus on five topics: (1) the identification and functional analysis of disease-causing genes; (2) the construction of cells, organoids, and animal models for mechanism validation; (3) subtyping and diagnosis; (4) treatment and drug screening based on causative genes and mutations; and (5) new technologies and methods for studying rare and undiagnosed diseases. In this review, we briefly update and discuss the pathogenic mechanisms and precision medicine for rare and undiagnosed diseases.

14.
Front Neurol ; 13: 1037777, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36619926

RESUMO

Background: The relative risk of GWAS-confirmed loci strongly associated with schizophrenia may be underestimated due to the decay of linkage disequilibrium between index SNPs and causal variants. This study is aimed to investigate schizophrenia-associated signals detected in the 1q24-25 region in order to identify a causal variant in LD with GWAS index SNPs, and the potential biological functions of the risk gene. Methods: Re-genotyping analysis was performed in the 1q24-25 region that harbors three GWAS index SNPs associated with schizophrenia (rs10489202, rs11586522, and rs6670165) in total of 9801 case-control subjects of Chinese Han origin. Circulating autoantibody levels were assessed using an in-house ELISA against a protein derived fragment encoded by SFT2D2 in total of 682 plasma samples. Results: A rare variant (rs532193193) in the SFT2D2 locus was identified to be strongly associated with schizophrenia. Compared with control subjects, patients with schizophrenia showed increased anti-SFT2D2 IgG levels. Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve (AUC) of 0.803 with sensitivity of 28.57% against specificity of 95% for the anti-SFT2D2 IgG assay. Discussion: Our findings indicate that SFT2D2 is a novel gene for risk of schizophrenia, while endogenous anti-SFT2D2 IgG may underlie the pathophysiology of the immunological aspects of schizophrenia.

15.
Nat Commun ; 12(1): 6937, 2021 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-34836959

RESUMO

Post-transcriptional modifications of RNA, such as RNA methylation, can epigenetically regulate behavior, for instance learning and memory. However, it is unclear whether RNA methylation plays a critical role in the pathophysiology of major depression disorder (MDD). Here, we report that expression of the fat mass and obesity associated gene (FTO), an RNA demethylase, is downregulated in the hippocampus of patients with MDD and mouse models of depression. Suppressing Fto expression in the mouse hippocampus results in depression-like behaviors in adult mice, whereas overexpression of FTO expression leads to rescue of the depression-like phenotype. Epitranscriptomic profiling of N6-methyladenosine (m6A) RNA methylation in the hippocampus of Fto knockdown (KD), Fto knockout (cKO), and FTO-overexpressing (OE) mice allows us to identify adrenoceptor beta 2 (Adrb2) mRNA as a target of FTO. ADRB2 stimulation rescues the depression-like behaviors in mice and spine loss induced by hippocampal Fto deficiency, possibly via the modulation of hippocampal SIRT1 expression by c-MYC. Our findings suggest that FTO is a regulator of a mechanism underlying depression-like behavior in mice.


Assuntos
Adenosina/análogos & derivados , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Transtorno Depressivo Maior/genética , Receptores Adrenérgicos beta 2/genética , Adenosina/metabolismo , Adulto , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Animais , Estudos de Casos e Controles , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/patologia , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Técnicas de Silenciamento de Genes , Voluntários Saudáveis , Hipocampo/patologia , Humanos , Masculino , Metilação , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Adulto Jovem
17.
J Vasc Surg Venous Lymphat Disord ; 8(6): 919-929, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32205131

RESUMO

OBJECTIVE: Peripherally inserted central venous catheter (PICC)-related thrombosis (PRT) is a serious complication that can lead to interruptions in chemotherapy and other supportive care, as well as increased hospital stay and costs. We conducted a retrospective study to evaluate the patterns of symptomatic PRT in patients with cancer undergoing chemotherapy and their risk factors. METHODS: A retrospective study of 938 PICC patients from our institution between November 2014 and July 2017 was performed. Symptomatic PRT events were confirmed by color Doppler ultrasonography or computed tomography pulmonary angiography in the presence of clinical symptoms. The variables of interest were extracted from the electronic medical record system. Logistic regression analysis was used to determine the risk factors for PRT. RESULTS: Of the 938 patients who were followed up for more than 120,000 patient-days, 63 patients (6.7%; 0.51 per 1000 catheter-days) had symptomatic PRT. Sixty-one patients were diagnosed with upper extremity venous thrombosis (UEVT), of which 18 were isolated superficial vein thrombosis (SVT), 19 were isolated deep vein thrombosis (DVT), and 24 were extensive venous thrombosis (EVT). Two patients were diagnosed with pulmonary embolism, and two patients were diagnosed with UEVT with pulmonary embolism. The symptomatic SVT occurred in 42 of 938 patients with cancer (4.5%), which accounted for 68.9% of all UEVT events. The median time to PRT was 21 days, and the median time to catheter removal in the PRT group was 66 days as compared with 117 days in the no PRT group. Predictors associated with increased risk of PRT were age >60 years (odds ratio [OR], 2.142; 95% confidence interval [CI], 1.118-4.103) and a chemotherapy regimen containing fluorouracil (OR, 2.429; 95% CI, 1.013-5.825). Hypertension with medication was a protective factor for PRT (OR, 0.306; 95% CI, 0.113-0.828). Among the 28 patients who did not remove their PICCs immediately after PRT was diagnosed, patients with SVT, DVT, and EVT had similar success rates of retaining catheters in situ after anticoagulant therapy (SVT, 83.3%; DVT, 62.5%; EVT, 75.0%; P = .667). CONCLUSIONS: Age >60 years and chemotherapy regimens containing fluorouracil were independent risk factors for PRT and hypertension with medication was associated with a lower risk of PRT in patients with cancer with PICCs receiving chemotherapy. PICCs-related SVT was a frequent type of PRT, which might need a better understanding and anticoagulant therapy in patients with cancer with PICCs.


Assuntos
Antineoplásicos/administração & dosagem , Obstrução do Cateter/etiologia , Cateterismo Venoso Central/efeitos adversos , Cateterismo Periférico/efeitos adversos , Neoplasias/tratamento farmacológico , Trombose Venosa/etiologia , Administração Intravenosa , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
18.
Drug Des Devel Ther ; 13: 539-553, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30787595

RESUMO

PURPOSE: Fluoropyrimidine plus platinum (FP) is currently the standard treatment for esophageal cancer (EC). In recent years, taxane-based chemotherapy has also been used and has shown good efficacy in EC. This study aims to investigate the advantages of taxane-based over FP chemotherapy, as well as discuss its drawbacks, in the treatment of EC. PATIENTS AND METHODS: A literature search was done for studies comparing clinical outcomes between taxane-based and FP chemotherapy in EC. Pooled analyses were performed to compare the efficacy and grade 3/4 adverse events in patients who received neoadjuvant chemotherapy (NACT), neoadjuvant chemoradiotherapy (NACRT), or definitive chemoradiotherapy (dCRT). Subgroup analyses were also conducted in esophageal squamous cell carcinoma (ESCC). RESULTS: Thirty-one studies with a total of 3,912 patients were included in the analysis. Better long-term survival was found in patients who received taxane-based NACT (progression-free survival (PFS): pooled HR=0.58, P=0.0008; and overall survival (OS): pooled HR=0.50, P<0.00001) and dCRT (PFS: pooled HR=0.75, P<0.0001). In NACRT, taxane-based treatment and FP showed similar efficacy. In ESCC patients, taxane-based treatment showed better OS (NACT: pooled HR=0.57, P=0.02; NACRT: pooled HR=0.51, P=0.03; and dCRT: pooled HR=0.73, P<0.0001) than FP chemotherapy. Furthermore, taxane-based therapy also showed a better short-term response (complete response (CR), objective response rate (ORR), disease control rate (DCR), or pathologic complete response (pCR). However, taxane-based therapy was significantly correlated with a higher incidence of grade 3/4 leukopenia, neutropenia, and diarrhea. CONCLUSION: Compared to FP, taxane-based therapy produced better clinical response and outcomes in EC patients receiving NACT or dCRT, and in all types of therapy in patients with ESCC. Taxane-based treatment is associated with more frequent toxicity.


Assuntos
Antineoplásicos/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Compostos Organoplatínicos/uso terapêutico , Pirimidinas/uso terapêutico , Taxoides/uso terapêutico , Antineoplásicos/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Humanos , Taxoides/efeitos adversos
20.
Plant Genome ; 10(2)2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28724071

RESUMO

Adaptation is a characteristic that enhances the survival or reproduction of organisms; selection is the critical process leading to adaptive evolution. Therefore, detecting selection is important in studying evolutionary biology. Changes in allele frequency are fundamental to adaptive evolution. The allele frequency of entire genes at the genomic scale is more intensive and precise for analyzing selection effects, compared with simple sequence repeat and single nucleotide polymorphism (SNP) alleles from nuclear gene fragments. Here, we analyzed 29,094 SNPs derived from 80 individuals of 14 L. Liou ex S.L. Chen & Renvoize populations planted near their native habitat (Jiangxia, Hubei Province, JH) and a stressful environment (Qingyang, Gansu Province, QG) to detect selection during initial adaptation. The nucleotide diversity of over 60% of genes was decreased in QG compared with JH, suggesting that most genes were undergoing selection in the stressful environment. We explored a new approach based on haplotype data inferred from RNA-seq data to analyze the change in frequency between two sites and to detect selection signals. In total, 402 and 51 genes were found to be targets of positive and negative selection, respectively. Among these candidate genes, the enrichment of abiotic stress-response genes and photosynthesis-related genes might have been responsible for establishment in the stressful environment. This is the first study assessing the change in allele frequency at the genomic level during adaptation. The method in which allele frequency detects selection during initial adaptation using population RNA-seq data would be useful for developing evolutionary biology.


Assuntos
Haplótipos , Poaceae/genética , Seleção Genética , Transcriptoma , Frequência do Gene , Genes de Plantas , Variação Genética , Polimorfismo de Nucleotídeo Único
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