Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 160
Filtrar
1.
Schizophr Bull ; 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33822213

RESUMO

The results generated from large psychiatric genomic consortia show us some new vantage points to understand the pathophysiology of psychiatric disorders. We explored the potential of integrating the transcription output of the core gene underlying the commonality of psychiatric disorders with a clustering algorithm to redefine psychiatric disorders. Our results showed that an extended MHC region was associated with the common factor of schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) at the level of genomic significance, with rs7746199 (P = 4.905e-08), a cis-eQTL to the gene ZNF391, pinpointed as a potential causal variant driving the signals in the region. Gene expression pattern of ZNF391 in the brain led to the emergence of 3 biotypes, independent of disorder. The 3 biotypes performed significantly differently in working memory and demonstrated different gray matter volumes in the right inferior frontal orbital gyrus (RIFOG), with a partial causal pathway arising from ZNF391 to RIFOG to working memory. Our study illustrates the potential of a trans-diagnostic, top-down approach in understanding the commonality of psychiatric disorders.

2.
Theranostics ; 11(8): 3694-3709, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33664856

RESUMO

Immune-mediated inflammatory diseases (IMIDs) are characterized by immune dysregulation and severe inflammation caused by the aberrant and overactive host immunological response. Mycophenolic acid (MPA)-based immunosuppressive drugs are potential treatments for IMIDs because of their mild side-effect profile; however, their therapeutic effects are limited by the high albumin binding rate, unsatisfactory pharmacokinetics, and undefined cellular uptake selectivity. Methods: Polysaccharide mycophenolate was synthesized by conjugating MPA molecules to dextran (a typical polysaccharide widely used in drug delivery) and encapsulated extra free MPA molecules to fabricate MPA@Dex-MPA nanoparticles (NPs). The efficacy of these NPs for mediating immunosuppression and treatment of IMIDs was evaluated in imiquimod-induced psoriasis-like skin inflammation in Balb/c mice, a representative IMID model. Results: The MPA@Dex-MPA NPs exhibited high MPA loading efficiency, low albumin binding rates, and sustained MPA release, resulting in improved pharmacokinetics in vivo. Compared to free MPA, MPA@Dex-MPA NPs induced more robust therapeutic effects on IMIDs. Mechanistic studies indicated that MPA@Dex-MPA NPs were primarily distributed in dendritic cells (DCs) and significantly suppressed the overactivated DCs in vivo and in vitro. Furthermore, the recovered DCs rehabilitated the IL-23/Th17 axis function and significantly ameliorated imiquimod-induced psoriasis-like skin inflammation. Importantly, MPA@Dex-MPA NPs showed favorable safety and biocompatibility in vivo. Conclusion: Our results indicated the polysaccharide mycophenolate-based NPs to be highly promising for IMID treatment.

3.
Int J Mol Sci ; 22(4)2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33670552

RESUMO

Cytoplasmic male sterility (CMS) plays an important role in the application of heterosis in wheat (Triticum aestivum L.). However, the molecular mechanism underlying CMS remains unknown. This study provides a comprehensive morphological and proteomic analysis of the anthers of a P-type CMS wheat line (P) and its maintainer line, Yanshi 9 hao (Y). Cytological observations indicated that the P-type CMS line shows binucleate microspore abortion. In this line, the tapetum degraded early, leading to anther cuticle defects, which could not provide the nutrition needed for microspore development in a timely manner, thus preventing the development of the microspore to the normal binucleate stage. Proteomic analysis revealed novel proteins involved in P-type CMS. Up to 2576 differentially expressed proteins (DEPs) were quantified in all anthers, and these proteins were significantly enriched in oxidative phosphorylation, glycolysis/gluconeogenesis, citrate cycle (TCA cycle), starch and sucrose metabolism, phenylpropanoid biosynthesis, and pyruvate metabolism pathways. These proteins may comprise a network that regulates male sterility in wheat. Based on the function analysis of DEPs involved in the complex network, we concluded that the P-type CMS line may be due to cellular dysfunction caused by disturbed carbohydrate metabolism, inadequate energy supply, and disturbed protein synthesis. These results provide insights into the molecular mechanism underlying male sterility and serve as a valuable resource for researchers in plant biology, in general, and plant sexual reproduction, in particular.

4.
BMC Gastroenterol ; 21(1): 79, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33618667

RESUMO

BACKGROUND: Despite the high number of researches on pancreatic adenocarcinoma (PAAD) over past decades, little progress had been made due to lack of effective treatment regimens. We aimed to investigate the expression level, mutation, and clinical significance of the Frizzled (FZD) family in PAAD so as to establish a sufficient scientific evidence for clinical decisions and risk management. METHODS: PAAD samples were extracted from The Cancer Genome Atlas (TCGA). Oncomine, Gene expression profiling interactive analysis (GEPIA), human protein atlas (HPA), Kaplan-Meier Plotter, cBioPortal, LinkedOmics, DAVID database, and R software (× 64 3.6.2) were used to comprehensively analyze the roles of FZDs. p value below to 0.05 was considered as significant difference. RESULTS: In total, 179 PAAD tissues and 171 paracancerous tissues were included. The expression levels of FZD1, 2, 6, 7, and 8 were higher in PAAD tissues than those in normal pancreatic tissue. The higher the expression levels of FZD2 and FZD7, the higher the clinical stage. The overall survival (OS) time was significantly different between low FZD3, 4, 5, 6, and 9 expression group and high expression group. Multivariable analysis showed that FZD3 and FZD6 were independent prognostic factors. The recurrence free survival (RFS) time was significantly different between low FZD4 and FZD8 expression group and high expression group. The RFS difference between low FZD6 expression group and high expression group had not reached statistical significance (p = 0.067), which might be due to the small sample size. However, multivariable analysis showed that FZD6 was the only independent factor for RFS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that FZDs played a critical role in the Wnt signaling pathway, which was further confirmation that FZDs were transmembrane receptors of Wnt signaling pathway. CONCLUSIONS: Our results strongly indicated a crucial role of the FZD family in PAAD. FZD3 and FZD6 could be potential prognostic and predictive markers, and FZD6 might also function as a potential therapeutic target in PAAD by blocking Wnt/ß-catenin pathway.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33502562

RESUMO

PURPOSE: Knife carrying has caused considerable public concern in the UK. But little is known of the epidemiology and characteristics of men who carry knives. We investigated associations with socioeconomic deprivation, area-level factors, and psychiatric morbidity. METHODS: Cross-sectional surveys of 5005 British men, 18-34 years, oversampling Black and Minority Ethnic (BME) men, lower social grades, and in London Borough of Hackney and Glasgow East. Participants completed questionnaires covering violent behaviour and psychiatric morbidity using standardised self-report instruments. Socioeconomic deprivation measured at small area level. RESULTS: Prevalence of knife carrying was 5.5% (4.8-6.9) and similar among white and BME subgroups. However, prevalence was twice the national rate in Glasgow East, and four times higher among Black men in Hackney, both areas with high levels of background violence and gang activity. Knife carrying was associated with multiple social problems, attitudes encouraging violence, and psychiatric morbidity, including antisocial personality disorder (AOR 9.94 95% CI 7.28-13.56), drug dependence (AOR 2.96 95% CI 1.90-4.66), and paranoid ideation (AOR 6.05 95% CI 4.47-8.19). There was no evidence of a linear relationship with socioeconomic deprivation. CONCLUSION: Men who carry knives represent an important public health problem with high levels of health service use. It is not solely a criminal justice issue. Rates are increased in areas where street gangs are active. Contact with the criminal justice system provides opportunity for targeted violence prevention interventions involving engagement with integrated psychiatric, substance misuse, and criminal justice agencies.

6.
BMC Psychiatry ; 21(1): 45, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33451325

RESUMO

BACKGROUND: Residential mobility during childhood increases risk of psychopathology in adulthood and is a common experience among Chinese children. This study investigated associations between number and age of first move, etiological risk factors for psychopathology, and common mental disorders in adolescence and early adulthood. METHODS: The sample included 39,531 undergraduates (84.5% completion rate) age 15-34 years in their first year at a Chinese comprehensive university in annual cross-sectional surveys during 2014-2018. Common mental disorders measured using standardised self-report instruments. Data analysed using logistic regression models and interaction analysis. RESULTS: Half of all students experienced one or more moves of residence before age 15 years. Outcomes of Depression, Somatisation, Obsessive-compulsive disorder, Hallucinations and Delusions, and Suicide attempts showed dose-response relationships with increasing number of moves. Other etiological risk factors, including childhood disadvantage and maltreatment, showed similar dose response relationships but did not confound associations with mobility. We found interactions between reporting any move and being a left-behind child on depression and somatisation; number of moves and younger age at first move on depression, somatisation, suicide attempts and hallucinations and delusions. CONCLUSIONS: Residential mobility in childhood is associated with psychopathology in adulthood and this association increases with increasing number of moves. Mobility is also associated with childhood disadvantage and maltreatment but associations with psychopathology are independent of these factors. Multiplicative effects were shown for multiple moves starting at a younger age and if the participant had been a left-behind child.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33408329

RESUMO

Schizophrenia is a complex disorder associated with aberrant brain functional connectivity. This study aims to demonstrate the relation of heterogeneous symptomatology in this disorder to distinct brain connectivity patterns within the triple-network model. The study sample comprised 300 first-episode antipsychotic-naive patients with schizophrenia (FES) and 301 healthy controls (HCs). At baseline, resting-state functional magnetic resonance imaging data were captured for each participant, and concomitant neurocognitive functions were evaluated outside the scanner. Clinical information of 49 FES in the discovery dataset were reevaluated at a 6-week follow-up. Differential features between FES and HCs were selected from triple-network connectivity profiles. Cutting-edge unsupervised machine learning algorithms were used to define patient subtypes. Clinical and cognitive variables were compared between patient subgroups. Two FES subgroups with differing triple-network connectivity profiles were identified in the discovery dataset and confirmed in an independent hold-out cohort. One patient subgroup appearing to have more severe clinical symptoms was distinguished by salience network (SN)-centered hypoconnectivity, which was associated with greater impairments in sustained attention. The other subgroup exhibited hyperconnectivity and manifested greater deficits in cognitive flexibility. The SN-centered hypoconnectivity subgroup had more persistent negative symptoms at the 6-week follow-up than the hyperconnectivity subgroup. The present study illustrates that clinically relevant cognitive subtypes of schizophrenia may be associated with distinct differences in connectivity in the triple-network model. This categorization may foster further analysis of the effects of therapy on these network connectivity patterns, which may help to guide therapeutic choices to effectively reach personalized treatment goals.

8.
J Colloid Interface Sci ; 589: 34-44, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33444821

RESUMO

Efficient delivery of active proteins to specific cells and organs is one of the most important issues in medical applications. However, in most cases, proteins without appropriate carriers face numerous barriers when delivered to the target, due to their unsatisfied properties, such as poor stability, short half-life, and low membrane permeability. Herein, we have presented a large-pore mesoporous silica nanoparticle (LPMSN)-based protein delivery system. LPMSNs were obtained with ethyl acetate as a pore expander. A 2,3-dimethylmaleamic acid-containing silane coupling agent was modified on LPMSNs to provide pH-triggered charge reversal. After Cytochrome c (CC) was encapsulated in the large pores of LPMSNs, amino-terminated polyethylene glycol-modified gold nanoparticles (AuNPs) served as gateguards to cap the tunnels of LPMSNs and to avoid the leakage of CC. Above nanocomposites exhibited the capability to deliver active CC into cancer cells, charge reversal-induced protein release, as well as to initiate the apoptosis machinery of cancer cells in vitro. Importantly, the nanocomposites significantly inhibited tumor growth and extended survival rate without obvious side effects. This study provides a smart and efficient protein delivery platform with good safety profiles for efficacious tumor protein therapy in vivo.

9.
J Affect Disord ; 282: 662-668, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33445089

RESUMO

Identifying cognitive dysfunction in the early stages of Bipolar Disorder (BD) can allow for early intervention. Previous studies have shown a strong correlation between cognitive dysfunction and number of manic episodes. The objective of this study was to apply machine learning (ML) techniques on a battery of cognitive tests to identify first-episode BD patients (FE-BD). Two cohorts of participants were used for this study. Cohort #1 included 74 chronic BD patients (CHR-BD) and 53 healthy controls (HC), while the Cohort #2 included 37 FE-BD and 18 age- and sex-matched HC. Cognitive functioning was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). The tests examined domains of visual processing, spatial memory, attention and executive function. We trained an ML model to distinguish between chronic BD patients (CHR-BD) and HC at the individual level. We used linear Support Vector Machines (SVM) and were able to identify individual CHR-BD patients at 77% accuracy. We then applied the model to Cohort #2 (FE-BD patients) and achieved an accuracy of 76% (AUC = 0.77). These results reveal that cognitive impairments may appear in early stages of BD and persist into later stages. This suggests that the same deficits may exist for both CHR-BD and FE-BD. These cognitive deficits may serve as markers for early BD. Our study provides a tool that these early markers can be used for detection of BD.

11.
Scand J Immunol ; : e13007, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33264420

RESUMO

MicroRNAs play an important role in the modulation of the immune system. T helper 17 (Th17) cells are involved in the modulation of the tumor microenvironment. However, the function of miRNA in Th17 cells in the tumor microenvironment is unclear. In this study, we analyzed miR-132 expression in Th17 cells and assessed the function of miR-132 on Th17 cell differentiation. In addition, the effect of miR-132 on Th17 cells in the tumor microenvironment, especially hepatic stellate cells (HSCs), was confirmed. CD4+ IL-17-/+ cells were isolated from hepatocellular carcinoma (HCC) tumor tissues. The expression of miR-132 was higher in CD4+ IL-17+ cells than in CD4+ IL-17- cells. Human primary CD4+ T cells were used for Th17 cell differentiation. Compared with primary CD4+ T cells, Th17 cells expressed high levels of miR-132. During Th17 cell differentiation, a miR-132 mimic and inhibition were applied. After treatment with the miR-132 mimic, the differentiation of Th17 cells accelerated, showing as a higher percentage of Th17 cells and the expression and secretion of IL-17 and IL-22. Smad nuclear interacting protein 1 (SNIP1), as one of the targets of miR-132, decreased during Th17 cell differentiation-related Th17 differentiation and IL-17 expression. The conditioned medium of miR-132-overexpressing Th17 cells could increase the activation of the HSCs, which strongly promoted HCC cell migration and epithelial-mesenchymal transition (EMT). In summary, miR-132 positively regulates Th17 cell differentiation and improves the function of Th17 on HSCs for their tumor-promoting effects.

12.
Artigo em Chinês | MEDLINE | ID: mdl-33254321

RESUMO

Objective:To explore whether the hardness of thyroid nodule could affect the satisfaction of ultrasound-guided coarse and fine needle puncture, so as to choose the best puncture scheme. Method:Clinical data of 164 patients(164 nodes) undergoing ultrasound-guided thyroid nodule biopsy were collected. The conditions for selecting research objects were the nodules size ranging from 0.8 to 2.0 cm. The subjects were divided into group A (0-10%), group B (>10% - 20%) and group C (> 20%) according to the deformation rate of ultrasound elastography (UE). The sample satisfaction of Fine needle aspiration was based on the Bethesda classification, the sample satisfaction of core needle was based on visual observation. Result:Ultrasound-guided core and fine needle biopsy were performed on 164 nodules. the satisfaction of specimens of overall is 84.76% by the coarse needle and 63.41% by the fine needle. The satisfaction of specimens of groups in A1 group: 84.62%, A2 group: 64.10%, B1 group: 80.43%, B2 group: 52.17%, C1 group: 90.00%, C2 group: 75.00%, respectively. The differences of specimen satisfaction are statistically significant between A1 and A2 groups, and between B1 and B2 groups(P<0.05,respectively). but not statistically significant between C1 and C2 groups(P>0.05). Conclusion:The hardness of thyroid nodule can affect the satisfaction of puncture specimens under certain conditions. Combining with the results of ultrasound elastography, the clear assessment of the hardness of thyroid nodule can help to guide the selection of the best puncture scheme, so as to improve the satisfaction of puncture specimens.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33141330

RESUMO

BACKGROUND: The recurrence rate of hepatocellular carcinoma (HCC) after partial hepatectomy is still high. How to choose the most appropriate anti-tumor drug in the early postoperative period is crucial to improve the prognosis of patients. Recently, MiniPDX has been widely used as a new and reliable preclinical research model capable of predicting the sensitivities of anti-tumor drugs. METHODS: Twenty-eight patients with HCC were selected to use the MiniPDX model to screen the most sensitive anti-tumor drugs from five groups of drug regimens for preventive treatment after partial hepatectomy, and another 42 patients with HCC were selected to be treated with Sorafenib during the same period as the control group. The tumor-free survival rate and overall survival rate were analyzed and compared between these two groups. The relationship between drug sensitivity and biomarkers related to HCC was also analyzed. RESULTS: Kaplan-Meier survival curve analysis showed that the tumor-free survival (DFS) of patients in the MiniPDX group was significantly longer than that in the control group (median DFS: 25.8 months vs. 18.2 months, P = 0.022, HR 2.19, 95% CI 1.17-4.12). The overall survival (OS) of the patients in the MiniPDX group was also longer than that in the control group (median OS: 29.4 months vs. 23.8 months, P = 0.039, HR 2.37, 95% CI 1.12-5.00). The longest follow-up period was 36 months. The relationship analyzed between the efficacy of the five drugs (Regorafenib, Regorafenib, Lenvatinib, Gemcitabine, 5-FU + Oxaliplatin) and AFP, Ki-67, VEGFR, FGFR, P53, and Nrf2 showed different correlations. CONCLUSION: The use of the MiniPDX model to select drugs to guide anti-tumor treatment after partial hepatectomy could effectively prolong the survival of patients with HCC.

14.
PLoS One ; 15(10): e0240616, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33035272

RESUMO

Alisma orientale (Sam.) Juzep (A. orientale) is a traditional herb that is often used to treat disease including edema and hyperlipidemia. However, the molecular mechanism by which Alisma orientale (Sam.) Juzep exerts its hypolipidemic effects remains unclear. In this study, a diabetic rat model was established by feeding a high-fat and high-sugar diet combined with a low-dose streptozotocin injection (HFS). Then the rats were treated with an A. orientale water extract (AOW), an A. orientale ethanolic extract (AOE) or metform (MET). The gut microflora and liver transcriptome were analyzed by high-throughput next-generation sequencing. Ultra-performance liquid chromatography-triple quadrupole-mass spectrometry was employed to analyze the major compounds in the AOE. The results showed that the serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels in rats of the AOE group (2.10 g/kg/day, 14 days) were significantly lower than those in the HFS group (p<0.01). Moreover, AOE treatment altered the gut microecology, particularly modulating the relative abundance of gut microflora involved in lipid metabolism compared with the HFS group. Furthermore, compared with the HFS group, the mRNA expression levels of Fam13a, Mapk7, Mpp7, Chac1, Insig1, Mcpt10, Noct, Greb1l, Fabp12 and Hba-a3 were upregulated after the administration of AOE. In contrast, the mRNA expression levels of Lox, Mybl1, Arrdc3, Cyp4a2, Krt20, Vxn, Ggt1, Nr1d1 and S100a9 were downregulated. Moreover, AOE treatment for two weeks markedly promoted the relative abundance of Lachnospiraceae (p = 0.0013). The triterpenoids contents in AOE were alisol A, alisol A 24-acetate, alisol B, alisol B 23-acetate, alisol C 23-acetate, alisol F, alisol F 24-acetate, and alisol G. Our findings above illustrated that the hypolipidemic effect of the triterpenoids of A. orientale is mediated mainly through alteration of the gut microecology and the regulation of genes involved in cholesterol metabolism, especially Insig1.

15.
Theranostics ; 10(24): 11197-11214, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042278

RESUMO

Rationale: The development of a highly effective and tumor-specific therapeutic strategy, which can act against the primary tumor and also condition the host immune system to eliminate distant tumors, remains a clinical challenge. Methods: Herein, we demonstrate a facile yet versatile ZnO-capping and Doxorubicin (DOX)-loaded multifunctional nanocomposite (AuNP@mSiO2@DOX-ZnO) that integrates photothermal properties of gold nanoparticles (NPs), pH-responsive properties and preferential selectivity to tumor cells of ZnO QDs and chemotherapeutic agent into a single NP. The photothermal performance, pH-triggered release and preferential phagocytic ability were assessed. The induced anti-tumor immunity was determined by analyzing immune cell profile in tumor in vivo and molecular mechanism were identified by detecting expression of immunogenic cell death (ICD) markers in vitro. Moreover, mice models of unilateral and bilateral subcutaneous melanoma and lung metastasis were established to evaluate the antitumor effects. Results: As an efficient drug carrier, ZnO-capped NPs guarantee a high DOX payload and an in vitro, efficient release of at pH 5.0. In murine melanoma models, the nanocomposite can significantly inhibit tumor growth for a short period upon low-power laser irradiation. Importantly, ZnO NPs not only demonstrate preferential selectivity for melanoma cells but can also induce ICD. Meanwhile, AuNP@mSiO2-based photothermal therapy (PTT) and DOX are directly cytotoxic towards cancer cells and demonstrate an elevated ICD effect. The induced ICD promotes maturation of dendritic cells, further stimulating the infiltration of effector T cells into tumor sites, preventing tumor growth and distant lung metastases. Conclusions: This study highlights the novel mechanism of ZnO-triggered anti-tumor immunity via inducing ICD. Additionally, we shed light on the multifunctionality of nanocomposites in delivering localized skin tumor therapy as well as inhibiting metastatic growth, which holds great promise in clinical applications.

16.
Onco Targets Ther ; 13: 9797-9806, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061458

RESUMO

Background/Aims: To analyze the clinical significance of miR-196b expression in ovarian cancer and predict the function and possible mechanism of miR-196b. Methods: Both Kaplan-Meier (K-M) and Cox proportional hazards regression model were used to analyze the prognostic factors of patients with ovarian cancer. MiR196-b was modulated in ovarian cancer cells, and the cell viability, cell cycle, and cell cycle-related gene expression were analyzed. The target genes of miR-196b were then predicted and checked the relationship between the target genes. Results: MiR-196b was an independent risk factor, while high expression of miR-196b was associated with poor prognosis of ovarian cancer. MiR-196b overexpression increased cancer cell proliferation. Cdkn1b, as one of the targets of miR-196b, was related to cell viability and mitosis. Conclusion: High expression of miR-196b was significantly associated with poor prognosis of the patients with ovarian cancer. MiR-196b could increase the cell proliferation of ovarian cancer by modulating Cdkn1b expression.

17.
BMC Cancer ; 20(1): 966, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023539

RESUMO

BACKGROUND: Nuclear factor of activated T cells 2 (NFAT2) has been reported to regulate the development and malignancy of few tumors. In this study, we aimed to explore the effect of NFAT2 expression on cell fate of HepG2 cell and its potential mechanisms. METHODS: Firstly, the pcDNA3.1-NFAT2 plasmid was transfected into HepG2 cells to construct NFAT2 overexpressed HepG2 cells. Then, the chemical count kit-8 cell viability assay, Annexin V-FITC apoptosis detection, EdU labeling proliferation detection, transwell and wound healing experiments were performed. The expression of Egr2 and FasL, and the phosphorylation of AKT and ERK, after ionomycin and PMA co-stimulation, was detected, while the Ca2+ mobilization stimulated by K+ solution was determined. At last, the mRNA and protein expression of NFAT2, Egr2, FasL, COX-2 and c-myc in carcinoma and adjacent tissues was investigated. RESULTS: The NFAT2 overexpression suppressed the cell viability, invasion and migration capabilities, and promoted apoptosis of HepG2 cells. NFAT2 overexpression induced the expression of Egr2 and FasL and suppressed the phosphorylation of AKT and ERK. The sensitivity and Ca2+ mobilization of HepG2 cells was also inhibited by NFAT2 overexpression. Compared with adjacent tissues, the carcinoma tissues expressed less NFAT2, Egr2, FasL and more COX-2 and c-myc. CONCLUSION: The current study firstly suggested that NFAT2 suppressed the aggression and malignancy of HepG2 cells through inducing the expression of Egr2. The absence of NFAT2 and Egr2 in carcinoma tissues reminded us that NFAT2 may be a promising therapeutic target for hepatocellular carcinoma treatment.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33113025

RESUMO

Rapid industrialization and urbanization in China have resulted in labor migrants leaving children behind. For left-behind children (LBC), disrupted parental attachment may increase the risk of psychiatric morbidity in adulthood. To investigate psychopathological consequences for university students who were LBC and to estimate the effects of one or both parents being migrants, the duration of left-behind experience, and parental absence during critical periods of growth on psychiatric morbidity. We conducted an annual survey of all freshmen at a Chinese university from 2014 to 2018. The questionnaire collected information on left-behind experiences and psychiatric morbidity using standardized self-report instruments. Regression coefficients derived from logistic regression were used to measure the associations among total time left behind, absence of one parent or both parents, age when left behind and psychopathological consequences. A total of 42,505 students were included. Students who were LBC had more psychopathology, including depression, anxiety, somatoform disorder, obsessive-compulsive disorder, self-reported suicide attempts and deliberate self-harm, than those who were not. Students for whom one or both parents were migrants showed a greater risk of psychiatric morbidity. The risk of psychiatric morbidity increased with the length of parental absence. Left-behind experience during childhood represents sustained impacts for university students into early adulthood. The higher prevalence of psychiatric morbidity in young adults who experienced the absence of one or both of their parents, especially in their early childhood, suggests that other factors besides attachment, such as protection from other risks, are important and that further research is necessary.

19.
BJPsych Open ; 6(6): e126, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33090091

RESUMO

BACKGROUND: Understanding the patterns of treatment response is critical for the treatment of patients with schizophrenia; one way to achieve this is through using a longitudinal dynamic process study design. AIMS: This study aims to explore the response trajectory of antipsychotics and compare the treatment responses of seven different antipsychotics over 6 weeks in patients with schizoprenia (trial registration: Chinese Clinical Trials Registry Identifier: ChiCTR-TRC-10000934). METHOD: Data were collected from a multicentre, randomised open-label clinical trial. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up at weeks 2, 4 and 6. Trajectory groups were classified by the method of k-means cluster modelling for longitudinal data. Trajectory analyses were also employed for the seven antipsychotic groups. RESULTS: The early treatment response trajectories were classified into a high-trajectory group of better responders and a low-trajectory group of worse responders. The results of trajectory analysis showed differences compared with the classification method characterised by a 50% reduction in PANSS scores at week 6. A total of 349 patients were inconsistently grouped by the two methods, with a significant difference in the composition ratio of treatment response groups using these two methods (χ2 = 43.37, P < 0.001). There was no differential contribution of high- and low trajectories to different drugs (χ2 = 12.52, P = 0.051); olanzapine and risperidone, which had a larger proportion in the >50% reduction at week 6, performed better than aripiprazole, quetiapine, ziprasidone and perphenazine. CONCLUSIONS: The trajectory analysis of treatment response to schizophrenia revealed two distinct trajectories. Comparing the treatment responses to different antipsychotics through longitudinal analysis may offer a new perspective for evaluating antipsychotics.

20.
Sci Rep ; 10(1): 17250, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33057145

RESUMO

SQUAMOSA promoter-binding protein (SBP)-box genes encode a family of plant-specific transcription factors that play roles in plant growth and development. The characteristics of SBP-box genes in rice (Oryza sativa) and Arabidopsis have been reported, but their potential roles in wheat (Triticum aestivum) are not fully understood. In this study, 48 SBP-box genes (TaSBPs) were identified; they were located in all wheat chromosomes except for 4B and 4D. Six TaSBPs were identified as tandem duplication genes that formed three tandem duplication pairs, while 22 were segmentally duplicated genes that formed 16 segmental duplication pairs. Subcellular localization prediction showed TaSBPs were located in nucleus. Among the 48 TaSBPs, 24 were predicted to be putative targets of TamiR156. Phylogenetic analysis showed that TaSBPs, AtSBPs, and OsSBPs that shared similar functions were clustered into the same subgroups. The phylogenetic relationships between the TaSBPs were supported by the identification of highly conserved motifs and gene structures. Four types of cis-elements--transcription-related, development-related, hormone-related, and abiotic stress-related elements--were found in the TaSBP promoters. Expression profiles indicated most TaSBPs participate in flower development and abiotic stress responses. This study establishes a foundation for further investigation of TaSBP genes and provides novel insights into their biological functions.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...