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1.
Sci Rep ; 14(1): 18132, 2024 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103418

RESUMO

The aim of this study is to investigate the influence of psychological capital on college students' entrepreneurial intentions. Through a combination of relevant analysis and linear regression, the primary focus is on exploring the relationship between psychological capital and its four dimensions with entrepreneurial intentions. Firstly, the items in the psychological capital questionnaire were revised to align more closely with entrepreneurial contexts. Subsequently, the average deviations and standard deviations of each dimension of psychological capital were analyzed. Then, the correlation between psychological capital and entrepreneurial intentions was examined to explore the extent of their relationship. Finally, regression analysis was conducted on both psychological capital and entrepreneurial intentions, and utilizing a recurrent neural network model, the covariant relationship between entrepreneurial psychological capital and intentions was explored. The results indicated that the average scores for entrepreneurial self-efficacy, optimism, hope, and resilience were 3.91, 4.27, 4.19, and 4.15, respectively. The average value of psychological capital was 4.13, indicating a moderately high level. The correlation analysis between psychological capital and entrepreneurial intentions yielded a result of 0.562, indicating a moderate degree of correlation. The correlation coefficients of the four dimensions with entrepreneurial intentions were 0.390, 0.494, 0.531, and 0.467, respectively. The standardized coefficients for psychological capital and its four dimensions were 0.564, 0.382, 0.510, 0.536, and 0.468, all of which were statistically significant. Overall, psychological capital exhibited better predictive power for entrepreneurial intentions than its individual dimensions. The results from the deep learning model similarly demonstrated the positive role of psychological capital in entrepreneurial intentions, though the influence of ideological and political education (IPE) factors was relatively weaker. In conclusion, both psychological capital and IPE have a promotive effect on entrepreneurial intentions. This study provides a reference for the accurate evaluation of college students' entrepreneurial intentions.


Assuntos
Aprendizado Profundo , Empreendedorismo , Intenção , Estudantes , Humanos , Feminino , Masculino , Estudantes/psicologia , Inquéritos e Questionários , Adulto Jovem , Autoeficácia , Esperança , Adulto , Política , Otimismo/psicologia
2.
Gen Psychiatr ; 36(6): e101050, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38155841

RESUMO

Background: Pharmacogenomics (PGx) is a promising tool to realise tailored drug therapy for depression. Aims: To investigate the treatment efficacy of PGx for treatment-resistant depression (TRD) compared with treatment as usual. Methods: A systematic search was conducted in PubMed, Embase, the Cochrane Library, Web of Science and PsycINFO to identify relevant studies published from inception to 15 April 2023. Two-arm randomised controlled trials (RCTs) exploring the efficacy of PGx-guided versus unguided treatment for TRD were included. The risk of bias in the included studies was evaluated using the Cochrane risk of bias assessment tool. The overall quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Results: Seven RCTs (n=3003) comparing PGx-guided (n=1492) and unguided (n=1511) groups were identified and analysed. PGx-guided treatment was superior to treatment as usual in response (relative risk (RR)=1.31; 95% confidence interval (95% CI): 1.15 to 1.49; p<0.001) and remission (RR=1.40; 95% CI: 1.09 to 1.80; p=0.009) improvements. Effect sizes for acceptability (RR=0.90; 95% CI: 0.80 to 1.02; p=0.100) and side effect burden (RR=0.58; 95% CI: 0.29 to 1.15; p=0.120) between the two groups were not statistically different. The overall quality of evidence was rated from 'very low' (25%) to 'low' (75%) based on the GRADE criteria. Conclusions: PGx-guided treatment has shown a small overall effect in improving the response and remission rates for patients with TRD. However, these results should be interpreted cautiously because of the few included studies and the low quality of evidence. Further high-quality clinical trials are warranted to confirm the findings. PROSPERO registration number: CRD42022340182.

3.
BMC Pregnancy Childbirth ; 23(1): 129, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36855088

RESUMO

BACKGROUND: Pregnancy-related intracranial hemorrhage (ICH) is a rare but potentially life-threatening event with complex and varied cause, such as HELLP syndrome and hemophagocytic syndrome. CASE PRESENTATION: A 33-year-old patient underwent a cesarean section with a preliminary diagnosis of "severe preeclampsia and class3 HELLP syndrome ". The patient had poor response to language before surgery, and the catheter drainage fluid was hematuria. Later, the surgeon reported severe bleeding in the operation. Following thromboelastography (TEG) result and postoperative laboratory tests confirmed class1 HELLP syndrome and ICH occurred on the second day after the surgery, and hemophagocytic syndrome was diagnosed during subsequent treatments. CONCLUSION: For patients with HELLP syndrome, we should pay attention to their coagulation condition. The coagulation tests and platelet counts should be repeated if their clinical presentation changed. Those with neurological alarm signs should receive CT or MRI scan. If a pregnant woman had prolonged hemocytopenia and thrombocytopenia, not only the HELLP but also the hemophagocytic syndrome should be considered.


Assuntos
Síndrome HELLP , Linfo-Histiocitose Hemofagocítica , Pré-Eclâmpsia , Gravidez , Humanos , Feminino , Adulto , Síndrome HELLP/diagnóstico , Cesárea/efeitos adversos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/etiologia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Hemorragias Intracranianas
4.
IEEE Trans Neural Netw Learn Syst ; 34(10): 7286-7298, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35230953

RESUMO

Cyber-physical-social systems (CPSS), an emerging cross-disciplinary research area, combines cyber-physical systems (CPS) with social networking for the purpose of providing personalized services for humans. CPSS big data, recording various aspects of human lives, should be processed to mine valuable information for CPSS services. To efficiently deal with CPSS big data, artificial intelligence (AI), an increasingly important technology, is used for CPSS data processing and analysis. Meanwhile, the rapid development of edge devices with fast processors and large memories allows local edge computing to be a powerful real-time complement to global cloud computing. Therefore, to facilitate the processing and analysis of CPSS big data from the perspective of multi-attributes, a cloud-edge-aided quantized tensor-train distributed long short-term memory (QTT-DLSTM) method is presented in this article. First, a tensor is used to represent the multi-attributes CPSS big data, which will be decomposed into the QTT form to facilitate distributed training and computing. Second, a distributed cloud-edge computing model is used to systematically process the CPSS data, including global large-scale data processing in the cloud, and local small-scale data processed at the edge. Third, a distributed computing strategy is used to improve the efficiency of training via partitioning the weight matrix and large amounts of input data in the QTT form. Finally, the performance of the proposed QTT-DLSTM method is evaluated using experiments on a public discrete manufacturing process dataset, the Li-ion battery dataset, and a public social dataset.

5.
Psychopharmacology (Berl) ; 240(2): 283-293, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36580134

RESUMO

BACKGROUND: Depression is associated with circadian disturbances in which melanopsin was a key mechanism. Further studies have demonstrated that melanopsin gene variations are associated with some depressive disorders and aberrant light can impair mood through melanopsin-expressing retinal ganglion cells (mRGCs). The goal of this study was to explore the direct relationship between depression and melanopsin. METHODS: Adult C57BL/6 male mice were physically restrained for 16 h in a 50-ml polypropylene centrifuge tube and all behavioral tests were performed after CRS treatment. Western blot analysis and immunofluorescence were used to detect melanopsin expression in the retina of C57BL/6 mice. And we observed the change of the electrophysiological function and release of glutamate of mRGCs. RESULTS: The melanopsin expression upregulate in mRGCs of chronic restraint stress (CRS)-treating mice which exhibit depression-like behavior. The frequency of blue light-induced action potentials and light-induced glutamate release mediated by melanopsin also increase significantly. This change of melanopsin is mediated by the CRS-induced glucocorticoid. CONCLUSIONS: CRS may induce the depression-like behavior in mice via glucocorticoid-melanopsin pathway. Our findings provide a novel mechanistic link between CRS-induced depression and melanopsin in mice.


Assuntos
Depressão , Glucocorticoides , Masculino , Camundongos , Animais , Regulação para Cima , Depressão/etiologia , Glucocorticoides/metabolismo , Camundongos Endogâmicos C57BL , Retina/metabolismo
6.
BMC Anesthesiol ; 22(1): 396, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36539707

RESUMO

BACKGROUND: The tourniquet technique is often used in total knee arthroplasty (TKA). However, its effect on postoperative delirium (POD) in elderly patients undergoing TKA is unknown.  METHODS: This prospective randomized controlled trial assessed the eligibility of 245 elderly patients. A total of 197 patients who met the inclusion criteria were randomly divided into a tourniquet group (n = 98) and a non-tourniquet group (n = 99). The primary outcome was the incidence of POD within 72 h after surgery. The secondary outcome was the quality of rehabilitation, including inflammatory reaction, postoperative pain, hypoproteinemia and anemia. RESULTS: Of 245 patients, 184 patients completed this clinical trial, with 92 cases in each group. There were 14 patients (15.22%) with POD in the tourniquet group and 5 patients (5.43%) in the non-tourniquet group (95% CI 1.076 to 9.067, P = 0.029). The changes in white blood cell count (WBC), the proportion of neutrophils (NEUT%), c-reactive protein (CRP), interleukin-6 (IL-6) and middle patellar circumference in the tourniquet group were higher than those in the non-tourniquet group (P < 0.05). The visual analog scale (VAS) at rest and activity in the tourniquet group were higher than those in the non-tourniquet group (F = 170.102, P < 0.001 F = 75.391, P < 0.001). There were 41 (44.57%) patients with hypoproteinemia in the tourniquet group and 26 (28.26%) in the non-tourniquet group (95% CI 1.106 to 3.765, P = 0.022). CONCLUSION: The application of the tourniquet technique in elderly patients with TKA procedures increased the incidence of POD. This may be attributed to the increased inflammatory reaction, severe postoperative pain and hypoproteinemia caused by the tourniquet technique. TRIAL REGISTRATION: Clinical trial registration number: ChiCTR2100045711. Full date of the first registration: 23/04/2021.


Assuntos
Artroplastia do Joelho , Delírio do Despertar , Hipoproteinemia , Humanos , Idoso , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Delírio do Despertar/complicações , Estudos Prospectivos , Método Simples-Cego , Perda Sanguínea Cirúrgica , Dor Pós-Operatória/etiologia , Inflamação/complicações , Hipoproteinemia/complicações
7.
Pharmacogenomics ; 23(10): 575-583, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35698907

RESUMO

Aim: To investigate whether the TNIK gene affects risperidone treatment outcomes in the Chinese population. Methods: A total of 148 unrelated inpatients who received risperidone for six weeks were enrolled. The selected single nucleotide polymorphisms (SNPs; rs2088885, rs7627954 and rs13065441) were genotyped using the MassARRAY® SNP IPLEX platform. Results: The analysis showed that one novel SNP of TNIK, rs7627954, had a significant association with the response to risperidone (χ2 = 4.472; p = 0.034). This work also identified rs2088885 as significantly associated with risperidone response (χ2 = 5.257; p = 0.022). The result revealed that the rs2088885-rs7627954 C-T haplotype was more prevalent in good responders than in poor responders (p = 0.0278). Conclusion: This study revealed that the rs2088885 and rs7627954 SNPs of TNIK are associated with risperidone treatment response.


Assuntos
Antipsicóticos , Proteínas Serina-Treonina Quinases/genética , Esquizofrenia , Antipsicóticos/uso terapêutico , China , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único/genética , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico
8.
Front Mol Neurosci ; 15: 836534, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493320

RESUMO

Postoperative delirium (POD) is a common postoperative complication in elderly patients and seriously affects postoperative recovery. The exact mechanism of POD is still unclear. Therefore, it is necessary to explore the mechanism of POD in transcriptional regulation. At present, circRNAs have been proven to play an important role in a variety of mental health and cognitive disorders, such as Alzheimer's disease, depression and schizophrenia. To reveal the effect of circRNA on POD, we used microarray to analyze the differential expression profiles of circRNAs in the hippocampus of 12-month-old mice between the tibial fracture and control groups. A total of 1,4236 circRNAs were identified. Compared with the control group, there were 500 circRNAs with increased expression and 187 with decreased expression. The accuracy of the microarray data was further verified by qRT-PCR. Finally, GO enrichment and KEGG pathway analyses indicated that changes in axon orientation, ubiquitin-mediated proteolysis, glutamate synapses, the estrogen signaling pathway, the RAS signaling pathway and other systems may be important potential pathological mechanisms in the progression of POD. In particular, we found that the HOMER1 gene and its transcript mmu_circRNA_26701 are specifically expressed in the glutamate synapse, which may provide new clues and intervention targets for the progression of this refractory disease.

9.
Aging (Albany NY) ; 14(6): 2736-2747, 2022 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-35333773

RESUMO

BACKGROUND: Accumulated studies have pointed out the striking association between variants in or near APOC3, GCKR, PNPLA3, and nonalcoholic fatty liver disease (NAFLD) at various ages from multiple ethnic groups. This association remained unclear in the Chinese Han elderly population, and whether this relationship correlated to any clinical parameters was also unclear. OBJECTIVES: This study aims to decipher the complex relevance between gene polymorphisms, clinical parameters, and NAFLD by association study and mediation analysis. METHODS: Eight SNPs (rs2854116, rs2854117, rs780093, rs780094, rs1260362, rs738409, rs2294918, and rs2281135) within APOC3, GCKR, and PNPLA3 were genotyped using the MassARRAY® platform in a large Chinese Han sample comprising of 733 elderly NAFLD patients and 824 age- and ethnic-matched controls. Association and mediation analysis were employed by R. RESULTS: The genotypic frequencies of rs1260326 and rs780094 were significantly different between NAFLD and control (rs1260326: P=0.004, Pcorr=0.020, OR [95%CI]= 0.69 [0.54-0.89]; rs780094: P=0.005, Pcorr=0.025, OR [95%CI]= 0.70 [0.55-0.90]). Particularly, an increased triglyceride level was observed in carriers of rs1260326 T allele (1.94±1.19 mmol/L) compared with non-carriers (1.73±1.05 mmol/L).no significant results were observed in rs780094. Notably, triglyceride levels had considerably indirect impacts on association between NAFLD and rs1260326 (ß =0.01, 95% CI: 0.01-0.02), indicating that 12.7% of the association of NAFLD with rs1260326 was mediated by triglyceride levels. CONCLUSIONS: Our results identified a prominent relationship between GCKR rs1260326 and NAFLD, and highlighted the mediated effect of triglyceride levels on the that association in the Chinese Han elderly.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Idoso , Estudos de Casos e Controles , China/epidemiologia , Predisposição Genética para Doença , Genótipo , Humanos , Lipase/genética , Proteínas de Membrana/genética , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/genética , Polimorfismo de Nucleotídeo Único , Triglicerídeos
11.
Psychopharmacology (Berl) ; 238(11): 3283-3292, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34350475

RESUMO

RationaleTraf2- and Nck-interacting kinase (TNIK), a member of germinal center kinase (GCK) family, has been implicated as a risk factor in schizophrenia and bipolar disorder as well as the action of antipsychotics. TNIK is an essential activator of Wnt/ß-catenin signaling pathway which has been identified involved in the mechanism underlying the effects of antipsychotics. Thus, the effects of TNIK on antipsychotics may be achieved by influencing Wnt/ß-catenin signaling pathway proteins.Objectives and methodsIn the current study, the effects of up- or downregulated TNIK on ß-catenin, T-cell factor 4 (TCF-4), glycogen synthase kinase-3ß (GSK3ß), and phosphorylated GSK3ß (p-GSK3ß) were examined in the human glioma U251 cells. Then, we observed the effects of antipsychotics (clozapine and risperidone) on the above proteins and evaluated the role of differentially expressed TNIK on antipsychotic-treated cell groups.ResultsThe result showed that clozapine treatment decreased ß-catenin and TCF-4 levels in U251 cells, and risperidone had the similar effects on ß-catenin and p-GSK3ß. The downregulated TNIK using siRNA impeded the regulation of antipsychotics on Wnt pathway proteins via increasing the expression levels of TCF-4, ß-catenin, or p-GSK3ß, whereas the upregulated TNIK made no significant change.ConclusionsThe influence of TNIK on the effects of antipsychotics may be partly through Wnt/ß-catenin signaling pathway.


Assuntos
Antipsicóticos , Via de Sinalização Wnt , Antipsicóticos/farmacologia , Quinases do Centro Germinativo , Glicogênio Sintase Quinase 3 beta , Humanos , Proteínas Serina-Treonina Quinases , Proteínas Wnt , beta Catenina
12.
Hepatology ; 73(1): 303-317, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32259305

RESUMO

BACKGROUND AND AIMS: Up-regulation of the E2F-dependent transcriptional network has been identified in nearly every human malignancy and is an important driver of tumorigenesis. Two members of the E2F family, E2F7 and E2F8, are potent repressors of E2F-dependent transcription. They are atypical in that they do not bind to dimerization partner proteins and are not controlled by retinoblastoma protein. The physiological relevance of E2F7 and E2F8 remains incompletely understood, largely because tools to manipulate their activity in vivo have been lacking. APPROACH AND RESULTS: Here, we generated transgenic mice with doxycycline-controlled transcriptional activation of E2f7 and E2f8 and induced their expression during postnatal development, in adulthood, and in the context of cancer. Systemic induction of E2f7 and, to lesser extent, E2f8 transgenes in juvenile mice impaired cell proliferation, caused replication stress, DNA damage, and apoptosis, and inhibited animal growth. In adult mice, however, E2F7 and E2F8 induction was well tolerated, yet profoundly interfered with DNA replication, DNA integrity, and cell proliferation in diethylnitrosamine-induced liver tumors. CONCLUSION: Collectively, our findings demonstrate that atypical E2Fs can override cell-cycle entry and progression governed by other E2F family members and suggest that this property can be exploited to inhibit proliferation of neoplastic hepatocytes when growth and development have subsided during adulthood.


Assuntos
Proliferação de Células , Fator de Transcrição E2F7/fisiologia , Hepatócitos/metabolismo , Neoplasias Hepáticas/patologia , Proteínas Repressoras/fisiologia , Animais , Apoptose/fisiologia , Ciclo Celular/fisiologia , Dano ao DNA , Fator de Transcrição E2F7/deficiência , Fator de Transcrição E2F7/genética , Células HeLa , Humanos , Neoplasias Hepáticas/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Repressoras/deficiência , Proteínas Repressoras/genética , Ativação Transcricional
13.
Cell Rep ; 33(9): 108449, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33264622

RESUMO

E2F transcription factors control the expression of cell-cycle genes. Cancers often demonstrate enhanced E2F target gene expression, which can be explained by increased percentages of replicating cells. However, we demonstrate in human cancer biopsy specimens that individual neoplastic cells display abnormally high levels of E2F-dependent transcription. To mimic this situation, we delete the atypical E2F repressors (E2F7/8) or overexpress the E2F3 activator in untransformed cells. Cells with elevated E2F activity during S/G2 phase fail to exit the cell cycle after DNA damage and undergo mitosis. In contrast, wild-type cells complete S phase and then exit the cell cycle by activating the APC/CCdh1 via repression of the E2F target Emi1. Many arrested wild-type cells eventually inactivate APC/CCdh1 to execute a second round of DNA replication and mitosis, thereby becoming tetraploid. Cells with elevated E2F transcription fail to exit the cell cycle after DNA damage, which potentially causes genomic instability, promotes malignant progression, and reduces drug sensitivity.


Assuntos
Dano ao DNA/genética , Fatores de Transcrição E2F/metabolismo , Análise de Sequência de RNA/métodos , Ciclo Celular , Humanos
14.
Aging (Albany NY) ; 12(24): 25819-25827, 2020 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-33232281

RESUMO

OBJECTIVE: Metabolic syndrome (MetS) is a cluster of health problems that places individuals at higher risk of developing cardiovascular disease, diabetes and stroke. The prevalence of MetS is increasing worldwide. It is also well accepted that genetic and environmental factors play significant roles in the occurrence/development of MetS, but studies exploring genetic factors are still lacking. Here, we aimed to investigate the association of ADIPOQ gene variants with MetS in an elderly Chinese Han population. RESULTS: We found that the allelic frequencies of rs6773957 and rs3774261 were significantly different between MetS and the control (p = 0.031; p = 0.049). Furthermore, a reduction in luciferase activity was observed when HEK293T cells were transfected with rs6773957 mutant fragments compared with wild type. CONCLUSION: Our results suggest that rs6773957 and rs3774261 of ADIPOQ were associated with MetS in the elderly Chinese Han population. The functional assays performed indicate that the rs6773957 variant might be pathogenic and may provide evidence for mechanistic studies of MetS in the future. METHODS: Four single nucleotide polymorphisms (SNPs) were selected and genotyped (rs6773957, rs182052, rs3774261 and rs17366568) in 1337 subjects, including 569 healthy controls and 768 MetS cases. The clinical characteristics of all the subjects were obtained and analyzed. Additionally, a functional study of rs6773957 in regulating the expression of ADIPOQ was performed in this study.


Assuntos
Adiponectina/genética , Predisposição Genética para Doença/genética , Síndrome Metabólica/genética , Idoso , Povo Asiático/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
15.
Genes Dis ; 7(2): 245-252, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32215294

RESUMO

Propofol is widely used as an intravenous drug for induction and maintenance in general anesthesia. Hypoxemia is a common complication during perianesthesia. We want to know the effect of propofol on spatial memory and LTP (Long-term potentiation) under hypoxic conditions. In this study, 84 seven-day-old Sprague-Dawley rats were randomly assigned into six groups (n = 14)-four control groups: lipid emulsion solvent + 50% oxygen (CO), lipid emulsion solvent + room air (CA), lipid emulsion solvent + 18% oxygen (CH), and propofol + 50% oxygen (propofol-oxygen, PO); and two experiment groups: propofol + room air (propofol-air, PA), and propofol + 18% oxygen (propofol-hypoxia, PH). After receiving propofol (50 mg/kg) or the same volume of intralipid intraperitoneal (5.0 ml/kg), injected once per day for seven consecutive days, the rats were exposed to 18% oxygen, 50% oxygen and air, until recovery of the righting reflex. We found that the apoptotic index and activated caspase-3 increased in the PH group (P < 0.05) compared with the PA group, fEPSP (field excitatory postsynaptic) potential and success induction rate of LTP reduced in all propofol groups (P < 0.05). Compared with the PO group, the fEPSP and success induction rate of LTP reduced significantly in the PA and PH groups (P < 0.05). Moreover, compared with CH group, the average time of escape latency was longer, and the number of platform location crossings was significantly reduced in the PH group (P < 0.05). Thus, we believe that adequate oxygen is very important during propofol anesthesia.

16.
Psychiatr Genet ; 30(1): 30-33, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31842058

RESUMO

OBJECTIVE: Major depressive disorder (MDD) is a global mental health problem. As a serotonin-noradrenaline reuptake inhibitor (SNRI), the antidepressant venlafaxine is used to alleviate MDD clinically. Recent research has shown that Cytochrome P450 (CYP) enzymes affect venlafaxine efficacy by mediating its metabolism. The present study investigates genetic polymorphisms of cytochrome P450 family 2 subfamily C member 19 (CYP2C19) are associated with remission after venlafaxine treatment for MDD. METHODS: A total of 175 Han Chinese patients with depression were recruited to accept a 6-week treatment with venlafaxine. Three single-nucleotide polymorphisms of CYP2C19 were selected from dbSNP and previous literature to compare the allele and genotype frequencies between patients in remission and nonremission. Seventeen items Hamilton Depression Scale (17-HAMD) was used to access the outcomes of patients' depressive symptoms through the study. Our results denied the role of CYP2C19 polymorphisms for remission after venlafaxine treatment in MDD patients. RESULT & CONCLUSION: CYP2C19 genetic polymorphism may not have association with SNRI venlafaxine treatment remission in the Han Chinese population.


Assuntos
Citocromo P-450 CYP2C19/genética , Transtorno Depressivo Maior/genética , Cloridrato de Venlafaxina/uso terapêutico , Adulto , Antidepressivos/uso terapêutico , Povo Asiático/genética , Biomarcadores Farmacológicos/sangue , China , Citocromo P-450 CYP2C19/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Escalas de Graduação Psiquiátrica , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Resultado do Tratamento
17.
Psychiatry Res ; 284: 112690, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31757642

RESUMO

OBJECTIVE: We aimed to study the association among venlafaxine antidepressive outcome, NR3C2 gene polymorphisms and the change of two neuroendocrine hormones during treatment. METHODS: 195 Chinese Han major depressive disorder (MDD) patients were recruited and received a 6-week venlafaxine treatment in this study. Adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH) levels were measured at the beginning and at the end of treatment. Six single-nucleotide polymorphisms (SNPs) (NR3C2: rs1512325, rs1512342, rs2070951; NR3C1: rs6191, rs6196, rs10482614) were selected for high-throughput SNP genotyping. Allele and genotype frequencies of them were compared between remission and non-remission groups. RESULTS: We found that genotype frequency of the rs1512325 located in the NR3C2 gene was significantly different between remission and non-remission groups respectively (p < 0.05). Meanwhile, the frequency of the rs1512325 C-allele was significantly lower (p < 0.05) in remission group. The TSH concentration significantly increased after venlafaxine treatment in remission group (p < 0.05). CONCLUSION: The rs1512325 in NR3C2 gene and TSH concentration may be related to venlafaxine treatment outcome in Chinese Han MDD patients.


Assuntos
Antidepressivos/farmacologia , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Receptores de Mineralocorticoides/efeitos dos fármacos , Cloridrato de Venlafaxina/farmacologia , Adulto , Alelos , Povo Asiático/genética , Transtorno Depressivo Maior/sangue , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Receptores de Mineralocorticoides/genética , Tireotropina/sangue , Resultado do Tratamento
18.
EMBO J ; 38(20): e101430, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31475738

RESUMO

E2F7 and E2F8 act as tumor suppressors via transcriptional repression of genes involved in S-phase entry and progression. Previously, we demonstrated that these atypical E2Fs are degraded by APC/CCdh1 during G1 phase of the cell cycle. However, the mechanism driving the downregulation of atypical E2Fs during G2 phase is unknown. Here, we show that E2F7 is targeted for degradation by the E3 ubiquitin ligase SCFcyclin F during G2. Cyclin F binds via its cyclin domain to a conserved C-terminal CY motif on E2F7. An E2F7 mutant unable to interact with SCFcyclin F remains stable during G2. Furthermore, SCFcyclin F can also interact and induce degradation of E2F8. However, this does not require the cyclin domain of SCFcyclin F nor the CY motifs in the C-terminus of E2F8, implying a different regulatory mechanism than for E2F7. Importantly, depletion of cyclin F causes an atypical-E2F-dependent delay of the G2/M transition, accompanied by reduced expression of E2F target genes involved in DNA repair. Live cell imaging of DNA damage revealed that cyclin F-dependent regulation of atypical E2Fs is critical for efficient DNA repair and cell cycle progression.


Assuntos
Ciclinas/metabolismo , Reparo do DNA , Fator de Transcrição E2F7/metabolismo , Fase G2/fisiologia , Proteólise , Proteínas Repressoras/metabolismo , Pontos de Checagem do Ciclo Celular , Ciclinas/genética , Dano ao DNA , Replicação do DNA , Fator de Transcrição E2F7/genética , Células HeLa , Humanos , Ligação Proteica , Proteínas Repressoras/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
19.
Gen Psychiatr ; 32(5): e100096, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552391

RESUMO

BACKGROUND: Subjective well-being (SWB), also known as happiness, plays an important role in evaluating both mental and physical health. Adolescents deserve specific attention because they are under a great variety of stresses and are at risk for mental disorders during adulthood. AIM: The present paper aims to predict undergraduate students' SWB by machine learning method. METHODS: Gradient Boosting Classifier which was an innovative yet validated machine learning approach was used to analyse data from 10 518 Chinese adolescents. The online survey included 298 factors such as depression and personality. Quality control procedure was used to minimise biases due to online survey reports. We applied feature selection to achieve the balance between optimal prediction and result interpretation. RESULTS: The top 20 happiness risks and protective factors were finally brought into the predicting model. Approximately 90% individuals' SWB can be predicted correctly, and the sensitivity and specificity were about 92% and 90%, respectively. CONCLUSIONS: This result identifies at-risk individuals according to new characteristics and established the foundation for adolescent prevention strategies.

20.
Metab Brain Dis ; 34(6): 1607-1613, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31410775

RESUMO

Schizophrenia is a kind of neurodevelopmental disease. Epidemiological data associates schizophrenia with prenatal exposure to famine. Relevant prenatal protein deprivation (PPD) rodent models support this result by observing decreasing prepulse inhibition, altered hippocampal morphology and impaired memory in offspring. All these abnormalities are highly consistent with the pathophysiology of schizophrenia. We developed a prenatal famine rat model by restricting daily diet of the pregnant rat to 50% of low protein diet. A metabolomics study of prefrontal cortex was performed to integrate GC-TOFMS and UPLC-QTOFMS. Thirteen controls and thirteen famine offspring were used to differentiate in PLS-DA (partial least squares-discriminate analysis) model. Furthermore, metabolic pathways and diseases were enriched via KEGG and HMDB databases, respectively. A total of 67 important metabolites were screened out according to the multivariate analysis. Schizophrenia was the most statistical significant disease (P = 0.0016) in our famine model. These metabolites were enriched in key metabolic pathways related to energy metabolism and glutamate metabolism. Based on these important metabolites, further discussion speculated famine group was characterized by higher level of oxidized damage compared to control group. We proposed that oxidative stress might be the pathogenesis of prenatal undernutrition which is induced schizophrenia.


Assuntos
Desnutrição/metabolismo , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Estresse Oxidativo/fisiologia , Córtex Pré-Frontal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Esquizofrenia/metabolismo , Animais , Dieta com Restrição de Proteínas , Modelos Animais de Doenças , Feminino , Espectrometria de Massas , Metaboloma , Metabolômica , Gravidez , Ratos , Ratos Sprague-Dawley
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