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1.
Dev Comp Immunol ; 110: 103728, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32387557

RESUMO

In mammals, interleukin 21 (IL-21) is a type I four-helical bundle cytokine produced by activated T cells that has pleiotropic functions on immune cells. Although IL-21 has been discovered in fish, the splicing variants of this cytokine and their functions on B cells are unclear. In this study, based on the original transcript of grass carp IL-21 (named gcIL-21sv1 in this study), two alternative splicing variants, named gcIL-21sv2 and gcIL-21sv3, were cloned and characterized. The protein sequences of gcIL-21sv1 and gcIL-21sv2 consist of four α-helixes, and only the six amino acid residues at the C-terminal are different. Unlike gcIL-21sv1 and gcIL-21sv2, gcIL-21sv3 lacks the C-terminal region. The expression analysis showed that gcIL-21sv1, gcIL-21sv2, and gcIL-21sv3 were constitutively expressed in all the tested tissues, and their expression could be significantly up-regulated by LPS and Poly (I:C) in head kidney leukocytes (HKLs), with the fold change of gcIL-21sv1 being higher than that of gcIL-21sv2 and gcIL-21sv3. Recombinant gcIL-21sv1 and gcIL-21sv2, but not gcIL-21sv3, could induce the proliferation of IgM+ B cells and the secretion of IgM, with the activity of gcIL-21sv1 being stronger than that of gcIL-21sv2, indicating that the C-terminal region plays important roles in the function of gcIL-21. Taken together, this study found that, like IL-21 in human and mouse, IL-21 splicing variants also exist in fish, and the regulatory activities of these variants in humoral immunity are differ, suggesting that grass carp may balance the immune response mediated by IL-21 through alternative splicing.

2.
Braz J Psychiatry ; 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32401875

RESUMO

OBJECTIVE: The purpose of this study was to investigate the lifetime suicide attempt rate, clinical characteristics and cognitive function of Chinese patients with chronic schizophrenia who had attempted suicide. METHODS: We collected data from 908 schizophrenia inpatients about suicide attempts through interviews with the patients and their families, as well as through medical records. All patients were assessed with the Positive and Negative Syndrome Scale, the Rating Scale for Extrapyramidal Side Effects, the Abnormal Involuntary Movement Scale, and the Repeated Battery for the Assessment of Neuropsychological Status. RESULTS: Of this sample, 97 (10.68%) had attempted suicide. Patients who had attempted suicide were younger, had longer illness duration, and more severe general psychopathology and depressive symptoms than those who had not. Logistic regression analysis confirmed that suicide attempts were correlated with age, smoking, and depression. No cognitive performance differences were observed between patients who had and had not attempted suicide. CONCLUSIONS: In China, patients with chronic schizophrenia may have a higher prevalence of lifetime suicide attempts than the general population. Some demographic and clinical variables were related to suicide attempts in patients with chronic schizophrenia.

3.
J Affect Disord ; 273: 18-23, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32421600

RESUMO

BACKGROUND: Suicide has become one of the most prominent concerns for public health and wellness; however, detecting suicide risk factors among individuals remains a big challenge. The aim of this study was to develop a machine learning algorithm that could effectively and accurately identify the probability of suicide attempts in medical college students. METHODS: A total of 4,882 medical students were enrolled in this cross-sectional study. Self-report data on socio-demographic and clinical characteristics were collected online via website or through the widely used social media app, WeChat. 5-fold cross validation was used to build a random forest model with 37 suicide attempt predictors. Model performance was measured for sensitivity, specificity, area under the curve (AUC), and accuracy. All analyses were conducted in MATLAB. RESULTS: The random forest model achieved good performance [area under the curve (AUC) = 0.9255] in predicting suicide attempts with an accuracy of 90.1% (SD = 0.67%), sensitivity of 73.51% (SD = 2.33%) and specificity of 91.68% (SD = 0.82%). LIMITATION: The participants are primarily females and medical students. CONCLUSIONS: This study demonstrates that the random forest model has the potential to predict suicide attempts among medical college students with high accuracy. Our findings suggest that application of the machine learning model may assist in improving the efficiency of suicide prevention.

4.
Ann Palliat Med ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32434348

RESUMO

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is recognized as an independent risk factor of cardiovascular disease. The release of Ca2+ mediated by transient receptor potential canonical (TRPC) channels participates in the hypoxia-induced pathophysiological changes in the cardiovascular systems in case of OSAHS. This study aimed to investigate which subtypes of TRPCs were involved in OSAHS in a rat model of intermittent hypoxia. METHODS: OSAHS was induced by exposure of rats to intermittent hypoxia. The expression of TRPCrelated genes and proteins in the cardiomyocytes by qRT-PCR and Western Blotting, respectively. RESULTS: The mRNA expression of TRPC3/TRPC4/TRPC5 increased significantly in OSAHS group compared with the control group (P<0.05). The TRPC5 protein expression was significantly higher in the OSAHS control than the control group (P<0.05). CONCLUSIONS: The TRPC5 channel is likely to be involved in the OSAHS induced pathophysiological changes in the myocardium and may become a target to prevent OSAHS related cardiac damage.

6.
Lipids Health Dis ; 19(1): 97, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32430016

RESUMO

OBJECTIVES: Numerous studies have reported that lipid metabolic abnormalities may play an important role in the development of Parkinson's disease (PD), with mixed results. This meta-analysis aims to systematically assess the relationship between serum cholesterol or triglyceride and the PD risk and to further determine the role of dyslipidemia in potential predictive value. METHODS: This research systematically consulted and screened observational studies to evaluate the association of serum lipids with the risk of PD as of April 01, 2020 based on the inclusion and exclusion criteria. Two researchers screened and extracted the data independently. Then this article summarized the characteristics of all clinical studies and collected the corresponding data to perform pooled and sensitivity analyses. The meta-analysis was performed by using the RevMan 5.3 software after data extraction, quality assessment and analysis of publication bias. RESULTS: Twenty-one related studies (13 case-control and 8 cohort studies) were selected with a total of 980,180 subjects, including 11,188 PD patients. Meta-analysis showed that higher levels of serum triglyceride (S-TG) [standard mean different (SMD) = - 0.26 (95% confidence interval (CI): - 0.39 to - 0.13, p<0.00001), relative risk (RR) = 0.67 (95% CI: 0.60 to 0.75, p<0.00001)] could be considered as protective factors for the pathogenesis of PD. However, there was no significant association between serum high density lipoprotein cholesterol (S-HDL) and the risk of PD. Meanwhile, serum low density lipoprotein cholesterol (S-LDL) [SMD = -0.26 (95% CI: - 0.43 to - 0.07, p = 0.006), RR = 0.76 (95% CI: 0.59 to 0.97, p = 0.03)] and serum total cholesterol (S-TC) levels [SMD = -0.21 (95% CI: - 0.33 to - 0.10, p = 0.0002), RR = 0.86 (95% CI: 0.77 to 0.97, p = 0.01)] were negatively associated with PD risk. CONCLUSIONS: This systematic review suggests that elevated serum levels of TG, LDL and TC may be protective factors for the pathogenesis of PD. Further longitudinal and well-designed prospective studies with a large sample size are needed to confirm the findings in this meta-analysis.

7.
BMC Musculoskelet Disord ; 21(1): 187, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32209088

RESUMO

BACKGROUND: Approximately 80% of adolescent scoliosis cases are idiopathic, and some non-idiopathic scoliosis cases caused by spinal cord abnormalities are misdiagnosed as idiopathic scoliosis. This study examined the risk factors for non-idiopathic scoliosis with intramedullary abnormalities, explored the feasibility of whole-spine MRI, and provided a theoretical basis for the routine diagnosis and treatment of adolescent idiopathic scoliosis. METHOD: The clinical data of adolescent scoliosis patients who were admitted to Shanghai Tongren Hospital and Shanghai Changhai Hospital between July 1, 2013, and December 31, 2018, were reviewed. According to the whole-spine MRI results, the patients were divided into either the idiopathic group or the intramedullary abnormality group. Sex, age, main curvature angle, main curvature direction, kyphosis angle, scoliosis type, coronal plane balance, sagittal plane balance, abdominal wall reflex, sensory abnormality, ankle clonus and tendon reflexes were compared between the two groups. Student's t test was used to evaluate the differences in the continuous variables, and the chi-square test was used to evaluate the differences in the categorical variables. Fisher's exact test was applied to detect the difference in the rate of intraspinal anomalies between the groups. Logistic regression was used to evaluate the correlation between the multivariate risk factors and intramedullary abnormalities. RESULT: A total of 714 adolescent scoliosis patients with a mean age of 13.5 (10-18 years) were included in the study, and intramedullary abnormalities were found in 68 (9.5%) patients. There were statistically significant differences in the incidence rates of intramedullary abnormalities between males and females, left and right thoracic curvatures, angular scoliosis and smooth scoliosis, and abnormal abdominal wall reflex and ankle clonus (P < 0.01). Logistic regression showed that the ratios for sex, scoliosis direction, scoliosis type, abdominal wall reflex and ankle clonus were 2.987, 3.493, 4.823, 3.94 and 8.083, respectively. The ROC curve showed a sensitivity of 66.18% and a specificity of 89.01%, and the Youden index corresponding to the optimal critical point was 0.5519. CONCLUSION: Risk factors associated with adolescent scoliosis caused by abnormal intramedullary abnormalities included male sex, thoracic scoliosis on the left side, sharp curvature of the spine, abnormal abdominal wall reflex and ankle clonus. In adolescent scoliosis patients, the incidence of scoliosis caused by intramedullary abnormalities was approximately 9.5%. These clinical indicators suggest that there is a high-risk adolescent scoliosis population who should undergo whole-spinal MRI preoperatively to rule out intramedullary abnormalities.

8.
J Affect Disord ; 268: 82-87, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32158010

RESUMO

BACKGROUND: The ß2 subunit of the voltage-gated l-type calcium channel gene(CACNB2) rs11013860 polymorphism is a putative genetic susceptibility marker for bipolar disorder (BD). However, the neural effects of CACNB2 rs11013860 in BD are largely unknown. METHODS: Forty-six bipolar patients with first-episode mania and eighty-three healthy controls (HC) were genotyped for CACNB2 rs11013860 and were scanned with a 3.0 Tesla structural magnetic resonance imaging system to measure cortical thickness of prefrontal cortex (PFC) components (superior frontal cortex, orbitofrontal cortex, middle and inferior frontal gyri). RESULTS: Cortical thickness was thinner in patients on all PFC measurements compared to HC (p < 0.050). Moreover, we found a significant interaction between CACNB2 genotype and diagnosis for the right superior frontal cortical thickness (F = 8.190, p = 0.040). Bonferroni corrected post-hoc tests revealed that, in CACNB2 A-allele carriers, patients displayed thinner superior frontal thickness compared to HC (p < 0.001). In patients, CACNB2 A-allele carriers also exhibited reduced superior frontal thickness compared to CACNB2 CC-allele carriers (p = 0.016). LIMITATIONS: Lithium treatment may influence our results, and the sample size in our study is relatively small. CONCLUSIONS: Our results suggest that the CACNB2 rs11013860 might impact PFC thickness in patients with first-episode mania. These findings provide evidence to support CACNB2 rs11013860 involvement in the emotion-processing neural circuitry abnormality in the early stage of BD, which will ultimately contribute to revealing the link between the variation in calcium channel genes and the neuropathological mechanism of BD.

9.
Aging (Albany NY) ; 12(2): 1159-1170, 2020 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-31955154

RESUMO

Hydrogen peroxide (H2O2) induces oxidative injury to human osteoblasts. The expression and potential function of circular RNA HIPK3 (circHIPK3) in H2O2-treated human osteoblasts were tested. We show that H2O2 significantly downregulated circHIPK3 in OB-6 cells and primary human osteoblasts. Furthermore, circHIPK3 levels were decreased in the necrotic femoral head tissues of dexamethasone-treated patients. In OB-6 osteoblastic cells and primary human osteoblasts, forced overexpression of circHIPK3 by a lentiviral construct alleviated H2O2-induced viability reduction, cell death and apoptosis. Contrarily, circHIPK3 silencing by targeted shRNA potentiated H2O2-induced cytotoxicity in OB-6 cells and primary human osteoblasts. Moreover, circHIPK3 downregulation by H2O2 induced miR-124 accumulation in OB-6 cells and primary human osteoblasts. On the contrary, miR-124 inhibition by transfection of the miR-124 inhibitor protected human osteoblasts from H2O2. Importantly, forced overexpression of miR-124 by transfection of the miR-124 mimic induced significant cytotoxicity in OB-6 cells and primary human osteoblasts. H2O2 downregulated miR-124's targets, cyclin dependent kinase 6 and Rho-Associated Protein Kinase 1, in human osteoblasts. In conclusion circHIPK3 downregulation mediates H2O2-induced cytotoxicity in human osteoblasts.

10.
Vet Immunol Immunopathol ; 221: 110009, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31945652

RESUMO

A 14-day experiment was conducted to explore the pathological process and immune response of soybean meal (SBM) induced enteritis (SBMIE) in grass carp (Ctenopharyngodon idellus). The complete replacement of dietary fish meal (FM) with SBM resulted in a remarkable reduction in final body weight, weight gain ratio, and feed conversion efficiency (p < 0.05). The typical histopathological changes of SBMIE appeared starting at day 4, and progressively increased in severity until day 8, then gradually subsided after day 11. The course of SBMIE could be divided into incubation period (days 1-2), prodromal period (days 3-6), symptomatic period (days 7-10), and convalescent period (days 11-14). Transcription levels of pro-inflammatory cytokines, including IL-1ß, TNF-α, IL-6, IL-8, IL-17A/F1 and IFN-γ2, were up-regulated during the prodromal period, and then down-regulated during the convalescent period. Transcript levels of anti-inflammatory cytokines (IL-10 and TGFß1) and their receptors (IL-10R1 and TßRII), were up-regulated during the prodromal and convalescent periods. Transcript levels of MHCIIß, Igµ, Igτ, TCRδ, TCRß, CD4, and CD8α were altered in SBMIE. Furthermore, expression levels of T-bet, IFN-γ2, RORγ2 and IL-17A/F1 were significantly increased in the initiation of enteritis, whereas the transcript levels of Foxp3 and IL-2/15Ra were significantly up-regulated in the repair of enteritis. In conclusion, grass carp SBMIE is regulated by the adjustment of SBM-based diet intake, and the changes of the above-mentioned genes expression suggest that these genes may be involved in SBMIE.

11.
J Proteome Res ; 19(3): 1298-1309, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-31994402

RESUMO

The proto-oncogene serine/threonine-protein kinase PIM3 plays critical roles in cancer, and it has been extensively exploited as a drug target. Here, we investigated the quantitative changes in the cellular proteome and phosphoproteome in liver cancer cells overexpressing PIM3 to obtain a better understanding of the regulatory functions of PIM3 and the underlying molecular mechanisms. This work depicted the landscape of gene expression and protein phosphorylation potentially regulated by PIM3. A signaling network analysis showed that PIM3 may coordinate various cellular processes, for example, signal transduction, cell cycle, apoptosis, and so forth. Intriguingly, quantitative phosphoproteomics revealed that the PIM3 overexpression elevated the phosphorylation of multiple Rho GTPase modulators that target RhoA, a central modulator of cell movement. Further investigations confirmed that PIM3 activated RhoA to subsequently regulate cytoskeletal rearrangements and cell migration. Taken together, this study comprehensively mapped the proteome and phosphoproteome regulated by PIM3 and revealed its role in promoting liver cancer cell migration and invasion by modulating Rho GTPase signaling.

12.
Dev Comp Immunol ; 106: 103613, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31935401

RESUMO

Teleost fish are the most primitive bony vertebrates that contain B cells; thus, comparative analysis of teleost naïve/mature B cells and plasma cells can provide helpful evidence for understanding the evolution paradigms of these two B-cell subpopulations in vertebrates. In this study, we developed monoclonal antibody against grass carp IgM and identified two different IgM+ cell subsets: IgM+ lymphocytes (Lym), resembling naïve/mature B cells, and IgM+ myeloid cells (Mye), resembling plasma cells. Like plasma cells in mammals, the size of IgM+ Mye is significantly larger than that of IgM+ Lym, as revealed by flow cytometric analysis and transmission electron microscopy. The IgM+ Mye were further verified as plasma cells because they showed gene expression patterns similar with those of human plasma cells and a great capacity to secrete IgM. Like mammalian IgM+ and IgA+ plasma cells, not IgG+ plasma cells, grass carp IgM+ Mye also expressed membrane immunoglobulins, a feature conserved in IgM+ plasma cells in vertebrates. Furthermore, recombinant CD40L or IL-21 alone could induce the plasma cell generation and IgM secretion, while the combination of CD40L and IL-21 had greater effect on IgM secretion, but not on plasma cell generation. This study fills an important gap in the knowledge of plasma cells in teleost fish and provides critical insights into the conserved evolution of IgM+ plasma cells in vertebrates.

13.
Spectrochim Acta A Mol Biomol Spectrosc ; 230: 118061, 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-31958606

RESUMO

Thiophenol has a broad application in agriculture and industry. However, thiophenol can harm to the environment and health for its high toxicity. Developing an effective method for detection of thiophenol in the field of environmental and biology is valuable. In this work, we construct a reaction-based ratiometric fluorescent probe (E)-4-(2-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)vinyl)-1-(4-(2,4-dinitrophenoxy)benzyl)pyridin-1-ium bromide (DCVP-DNP) for probing thiophenol in environment and cells by employing (E)-7-(diethylamino)-3-(2-(pyridin-4-yl)vinyl)-2H-chromen-2-one (DCVP) as the fluorophore and 2,4-dinitrophenyl (DNP) ether as the recognition group for the first time. The probe has high selectivity for thiophenol though thiophenol-triggered nucleophilic substitution reaction. In addition, the ratio of emission intensities of the probe has linearly with thiophenol concentration in the range of 0-65 µM and the detection limit of thiophenol is as low as 4.8 × 10-8 M. Moreover, the probe can not only be applied for detection of thiophenol in water samples, but also image thiophenol in living cells, suggesting its potential application in environment and biological system.

14.
J Affect Disord ; 263: 500-506, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31759662

RESUMO

BACKGROUND: Few systemic studies of psychotic depression (PD) have been conducted in first-episode and drug-naïve (FEDN) patients. This study was to examine the prevalence of PD and its clinical correlates in a large sample of FEDN outpatients with major depressive disorder (MDD) in a Chinese Han population, which to our best knowledge has not been studied. METHODS: In this cross-sectional study, a total of 1718 FEDN MDD outpatients were recruited. All patients were rated on the positive symptom subscale of the Positive and Negative Syndrome Scale (PANSS) for psychotic symptoms, the 17-item Hamilton Depression Rating Scale (HAMD-17) for depression and Hamilton Anxiety Rating Scale (HAMA) for anxiety. RESULTS: The prevalence of PD was 10.0% (171/1718) in MDD patients. Compared to the non-PD patients, PD patients had significantly older age, lower educational levels, higher anxiety symptom score and were more likely to attempt suicide. Further logistic regression analysis indicated that PD was associated with older age, suicide attempt and comorbid anxiety (all p < 0.05). Multiple regression analyses showed that both HAMD and HAMA total scores were significantly associated with PANSS positive symptom subscale score. LIMITATIONS: Our cross-sectional study design does not show a direct causal relationship between psychiatric symptoms and related factors in patients with MDD. CONCLUSIONS: Our results suggest a high prevalence of PD in MDD patients in the acute early stage in a Chinese Han population, which is associated with demographic variables and clinical symptoms.

15.
Schizophr Res ; 215: 270-276, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31653580

RESUMO

The prevalence of obesity in schizophrenia patients is high, especially in chronic and medicated patients. Few studies have explored the relationships between obesity, cognition and clinical correlates in patients with schizophrenia. This study was designed to assess the prevalence and clinical correlates of obesity and its relationship to cognitive impairment in Chinese patients with schizophrenia. We recruited 633 inpatients and collected clinical, demographic data and lipid parameters. The Positive and Negative Syndrome Scale (PANSS) and its five-factor model were adopted for psychopathological symptoms. The prevalence of comorbid obesity in schizophrenia patients was 16.4%. The plasma levels of glucose, triglyceride, low density lipoprotein (LDL), apolipoprotein B, and cholesterol were higher, but high density lipoprotein (HDL) levels were lower in obese patients than those in non-obese patients (all p < 0.05). Furthermore, obese patients had lower PANSS negative symptom, cognitive factor and total scores than non-obese patients (all p < 0.05). Correlation analysis showed a significant correlation between BMI and the following variables: age, marriage, gender, negative symptoms, general psychopathological symptoms, cognitive factor, PANSS total score, glucose, triglycerides, HDL, LDL, cholesterol and apolipoprotein B (all p < 0.05). Further multiple regression showed that PANSS cognitive factor, PANSS total score, and triglyceride were important independent predictors of obesity. Our results indicate a high prevalence of obesity in Chinese patients with chronic schizophrenia. Multiple demographics, clinical variables, and lipid parameters are associated with obesity in schizophrenia. Moreover, obesity appears to be a protective factor for psychological symptoms. However, not having objective assessments for cognition in this study is a limitation.

16.
Horm Behav ; 117: 104604, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31655035

RESUMO

BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis is the main neuroendocrine system that controls stress responses, including fear learning. To further understand the correlation between the HPA axis and stress- and fear-related symptoms in humans, the current study investigated the relationship between HPA axis gene polymorphisms and a stress- and fear-related disorder, posttraumatic stress disorder (PTSD). This is the first study that systematically investigates the correlations between HPA axis genes and distinct PTSD symptom clusters. METHODS: Participants included 1132 Chinese earthquake survivors (772 women and 360 men). PTSD symptoms were measured by the PTSD Checklist for DSM-5 (PCL-5), and the severity (total symptoms) and symptom clusters were calculated according to the hybrid seven-factor model of DSM-5 PTSD. We genotyped eight single nucleotide polymorphisms (SNPs) of three HPA axis genes, including FKBP5, CRHR1 and CRHR2. RESULTS: The main effects of the CRHR2 SNP rs2267715 were associated with PTSD severity (P = 0.0035) and all PTSD symptom clusters except dysphoric arousal (P ranging from 0.0011 to 0.048). In women, a gene-environment interaction (G × E) effect of FKBP5 (rs3800373 × trauma exposure) was correlated with PTSD severity (P = 0.038), externalizing behaviors, anxious arousal and dysphoric arousal symptoms (P ranging from 0.014 to 0.028); the G × E effect of CRHR1 (rs4458044 × trauma exposure) was associated with anxious arousal symptoms (P = 0.016). In men, a gene-gene interaction (G × G) effect of FKBP5-CRHR1 (rs9470080 × rs4458044) was associated with PTSD severity (P = 0.0091), intrusion, negative affect, externalizing behaviors and anxious arousal (P ranging 0.012-0.049). CONCLUSION: Our results systematically revealed that the main effects and G × E and G × G effects of some genetic polymorphisms of HPA axis genes are involved in the severity and distinct symptom clusters of PTSD.

17.
Schizophr Res ; 215: 134-139, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31753594

RESUMO

BACKGROUND: Cognitive deficit is a fundamental trait of schizophrenia, but its mecwhanisms remain unknown. The neuregulin 3 (NRG3) gene, involving in neuronal function, has been considered to be associated with schizophrenia and cognition. However, no study has investigated the effects of NRG3 polymorphism on cognitive deficits in a large sample of the patients with schizophrenia. METHODS: A total of 1112 schizophrenia patients and 423 controls were recruited and genotyped with NRG3 rs10748842. Among them, 864 patients and 403 controls were assessed for cognition through the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). SHEsis was applied and followed by logistic regression analysis. The models of analyses of covariance (ANCOVA) were constructed to examine the effects of NRG3 rs10748842 on cognitive deficits. RESULTS: No differences in NRG3 rs10748842 allele and genotype were found between patients and controls (both p > 0.05). With the exception of Visuospatial/construction, the other RBANS scores were significantly lower in patients compared to controls after adjusting for gender and education (all p < 0.001). Interestingly, we found that NRG3 rs10748842 was associated with cognitive deficit in schizophrenia, showing that patients carrying C allele had lower attention and total scores than those with TT genotype (both p < 0.05). CONCLUSION: NRG3 rs10748842 may not confer susceptibility to schizophrenia, but may be more closely associated with cognitive deficit, especially attention performance in chronic schizophrenia.

18.
Dev Comp Immunol ; 105: 103576, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31846686

RESUMO

Tumor necrosis factor-α (TNF-α) plays crucial roles in cell development, proliferation, apoptosis, inflammation, and immunity. TNF-α genes have been identified in various fish species, however, their biological functions remain to be further clarified. In this study, we identified a novel TNF-α homologue (LcTNF-α2) from large yellow croaker (Larimichthys crocea), which shares a low amino acid sequence identity to the previously reported large yellow croaker TNF-α (LcTNF-α1). The open reading frame of LcTNF-α2 is 714 nucleotides long, encoding a peptide of 237 amino acids (aa). The deduced LcTNF-α2 protein contains a 23-aa transmembrane region, a TACE restriction site at residues T71/L72, a TNF family signature (I108- F135), and two conserved cysteine residues (C39 and C179), as found in other known TNF-α sequences. Both LcTNF-α1 and LcTNF-α2 genes were constitutively expressed in all examined tissues and significantly up-regulated in the spleen and head kidney by Vibrio alginolyticus. Their transcripts were also detected in primary head kidney monocytes/macrophages (MO/Mϕs), lymphocytes (PKLs), granulocytes (PKGs), and large yellow croaker head kidney (LYCK) cell line and significantly increased in these cell types by inactivated Vibrio alginolyticus. Recombinant LcTNF-α1 and LcTNF-α2 proteins (rLcTNF-α1 and rLcTNF-α2) produced in Pichia pastoris not only significantly increased the production of reactive oxygen species (ROS), but also promoted the expression of proinflammatory cytokines (IL-1ß, IL-6,IL-8, and TNF-α1) in MO/Mϕs from large yellow croaker. Even more, after stimulation with rLcTNF-α1 and rLcTNF-α2, the production of nitrogen oxide (NO) and the expression of inducible NO synthase (iNOS) gene were significantly up-regulated. However, only rLcTNF-α1 remarkedly enhanced the phagocytosis of MO/Mϕs and increased the expression of TNF-α2 in MO/Mϕs. These results therefore indicated that LcTNF-α1 and LcTNF-α2 both play roles in promoting activation of head kidney MO/Mϕs.

19.
J Affect Disord ; 260: 91-96, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31493645

RESUMO

BACKGROUND: Major depressive disorder (MDD) patients with comorbid anxiety symptoms showed obvious cognitive deficits. However, it remains unclear whether comorbid anxiety symptoms will make a specific contribution to cognitive deficits in MDD. METHODS: Executive function, processing speed, attention and memory were assessed in 162 MDD patients, and 142 healthy controls (HCs) by a comprehensive neuropsychological battery. 14-item Hamilton Anxiety Rating Scale (HAM-A) was used for anxiety symptoms and MDD patients with HAM-A total score >14 were classified into MDD with comorbid anxiety (MDDA) group. A multivariate analysis of covariance and regression models was conducted to evaluate the effects of anxiety symptoms on cognitive deficits. RESULTS: There were no significantly differences in all 4 cognitive domains between MDD alone and MDDA patients (all p < 0.05). In MDDA subgroup, HAM-A total score contributed to executive function and memory (both p < 0.05), while HAM-A psychic symptoms contributed to all 4 domains (all p < 0.05). Moreover, after controlling for the severity of depression, either anxiety symptoms shown as HAMA total score or psychic anxiety symptoms only contributed significantly to the executive function performance. LIMITATIONS: The cross-sectional design made it hard to acquire a cognitive performance trajectory accompanied by the fluctuations in anxiety symptoms. CONCLUSION: Our findings suggest that there is no significant difference in cognitive performance between MDD alone and MDDA patients. However, comorbid anxiety, especially psychic anxiety may contribute to extensive cognitive deficits in MDDA patients. Notably, anxiety symptoms only independently triggered executive dysfunction when eliminating effect of the severity of depression.

20.
Psychoneuroendocrinology ; 111: 104473, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31655452

RESUMO

Executive dysfunction is increasingly recognized as one of the widely observed dimensions of cognitive impairments in the course of schizophrenia (SCZ). However, the potential molecular pathological mechanisms remain elusive. Previous studies have demonstrated that decreased brain-derived neurotrophic factor (BDNF) and oxidative damage may be associated with the psychopathology and cognitive impairment of SCZ. The present study aims to assess whether the interaction between BDNF and oxidative damage is involved in the disruption of executive function (EF) in patients with chronic SCZ. Serum BDNF and plasma oxidative stress markers were measured in 189 patients and 60 control subjects. EFs were evaluated by Wisconsin card sorting tests (WCST), Stroop word/color test (Stroop), and verbal fluency tests (VFT). The results showed that patients performed worse in the VFT, WCST and Stroop tests than healthy subjects. Moreover, patients had lower activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and lower BDNF levels, but higher malondialdehyde (MDA) levels than healthy controls. In patients, BDNF was negatively correlated with SOD (p < 0.01). For patients, catalase (CAT) activity was negatively associated with WCST error score (p = 0.02) and BDNF was positively correlated to VFT score (p = 0.02). However, all these correlations between biomarkers and EF domains did not pass Bonferroni corrections. Finally, multiple regression analyses identified BDNF × SOD activity and BDNF × MDA as influencing factors for VFT score in patients (both p < 0.05). Our results highlight the complex interplay between OS parameters and BDNF in the pathophysiology of EF impairment in SCZ, consistent with its neurodevelopmental hypothesis.

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