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Physiol Behav ; 217: 112805, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31954148


Extracellular signal-regulated kinase (ERK) signal transduction is known to be associated with neurogenesis and neuronal differentiation and as such may be related to the synaptic plasticity associated with cognitive function. Although antipsychotic drug studies have suggested a potential role for the ERK cascade in schizophrenia, the mechanistic basis is unknown. The maternal immune activation (MIA) rat model is a well-known to simulate many of the clinical symptoms of schizophrenia, including cognitive deficits, but a role in this model for dynamic changes in ERK has not been established. In this study, polyinosinic:polycytidylic acid was administered to rats intravenously at a dose of 10 mg/kg on embryonic day 9.5 to produce MIA. The effect of MIA on behavior and ERK phosphorylation within the prefrontal cortex and the hippocampus of adolescent and adult offspring were explored. We also examined neurofilaments, a marker of neurogenesis, which have been reported to be modulated by ERK signaling. The results demonstrate an age- and region-specific profile of ERK expression and phosphorylation and suggest possible relationships among ERK, neurofilament expression, and cognitive performance in schizophrenia.

Behav Brain Funct ; 15(1): 3, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30836963


BACKGROUND: Maternal immune activation (MIA) during gestation can increase the later risk of schizophrenia in adult offspring. Neuroinflammation is believed to underlie this process. Postmortem brain studies have found changes in the neuroimmune systems of patients with schizophrenia. However, little is known about the dynamic changes in cerebral inflammation and behavior during the course of the disease. METHODS: Here, the prepulse inhibition (PPI) test was conducted in adolescent and adult Sprague-Dawley rats prenatally challenged with polyriboinosinic-polyribocytidylic acid (Poly I:C) on gestational day 9 to determine the behavioral trajectory triggered by early exposure to Poly I:C. Brain immune changes were determined in the prefrontal cortex (PFC) and hippocampus (HC) at both ages. The status of the microglia and astrocytes was determined with immunohistochemical staining. The levels of IL-6, IL-1ß, and TNF-α in both brain regions were evaluated with enzyme-linked immunosorbent assays. RESULTS: Disrupted PPI, the core phenotype of schizophrenia, only emerged in adulthood. Behavioral changes during puberty and adulthood were both accompanied by the activation of microglia (PFC and HC). Astrocytes were only activated at PN60. The levels of proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) in the offspring of the Poly I:C-exposed mothers differed with brain region and time, with more cytokines elevated during periadolescence than during adulthood. CONCLUSIONS: Our findings indicate that immune activation emerged before symptom manifestation in the offspring of MIA rats. We conclude that early prenatal Poly I:C challenge can lead to age-related behavioral and neuroinflammatory changes. These data provide new insight into the neuroinflammatory and neuropathological mechanisms underlying the development of schizophrenia. They also suggest that periadolescence could be more important than adulthood in the prevention and treatment of schizophrenia.

Poli I-C/efeitos adversos , Fatores Etários , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Modelos Animais de Doenças , Feminino , Hipocampo/efeitos dos fármacos , Masculino , Microglia/efeitos dos fármacos , Neuroimunomodulação/fisiologia , Poli I-C/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Inibição Pré-Pulso/fisiologia , Ratos , Ratos Sprague-Dawley
Psychiatry Res ; 269: 271-277, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30170285


Schizophrenia presents with a broad range of negative, positive, and cognitive symptoms, and comprehensive treatment is still a challenge. Sodium nitroprusside (SNP) has been reported to rapidly reduce psychotic symptoms and improve cognitive functions in patients with schizophrenia, providing a new possible direction for treatment. In this study, we tested whether SNP can improve psychotic symptoms and cognitive function in schizophrenia patients with longer disease history. This was a randomized, double-blind, placebo-controlled trial conducted between May 2016 and April 2017. Forty-two schizophrenia patients aged 18-45 years were recruited from Henan Province Mental Hospital. Baseline psychiatric symptoms were measured using the Positive and Negative Syndrome Scale (PANSS), and baseline cognitive functions were measured using the Wechsler Adult Intelligence Scale. Patients received two SNP or placebo infusions (0.5 µg/kg per min for 4 h) at a one-week interval. We reassessed psychiatric symptoms and cognitive functions using the same tests shortly after the first and second infusions and 4 weeks after the second infusion. We did not find any significant effect of SNP over placebo on psychotic symptoms or cognitive functions, although SNP was relatively well tolerated with a good safety profile.

Antipsicóticos/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Nitroprussiato/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Disfunção Cognitiva/psicologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/psicologia , Psicologia do Esquizofrênico , Resultado do Tratamento , Adulto Jovem
J Hum Genet ; 63(1): 47-54, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29167551


Single-nucleotide polymorphisms (SNPs) in the promoter region of long intergenic non-coding RNAs (lincRNAs) could play a regulatory role in its expression level and then get involved in colorectal cancer (CRC). Thus, we conducted a two-stage case-control study to investigate the associations of Tag SNPs within the promoter region of selected lincRNAs from microarray data with risk of CRC. A total of 320 cases and 319 controls were recruited in the test set to explore the associations between 16 SNPs with no deviations from Hardy-Weinberg equilibrium (HWE) and risk of CRC. Furthermore, 501 cases and 538 controls were included as the validation set to confirm the significant associations. RP11-3N2.1 rs13230517 polymorphism was found to be negatively associated with CRC in both test set (AA vs. GG, OR = 0.68, 95% CI = 0.48-0.96) and validation set (AA vs. GG, OR = 0.76, 95% CI = 0.59-0.98). Pooled analysis showed that individuals with GA/AA genotypes had a significantly decreased risk of CRC when compared with those carrying GG genotype (OR = 0.74, 95% CI = 0.60-0.90) in the combined set. The crossover analysis revealed that rs13230517 GA/AA carriers had a decreased risk of CRC than GG carriers among non-drinkers in both test and combined set. However, no gene-environment multiplicative interactions were found on risk of CRC. Our findings suggest that rs13230517 polymorphism might participate in the pathogenesis of CRC and have the potential to be a biomarker for predicting the risk of CRC.

Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Genótipo , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Idoso , Biomarcadores Tumorais/biossíntese , Estudos de Casos e Controles , Neoplasias Colorretais/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante/biossíntese , RNA Neoplásico/biossíntese , Fatores de Risco
Cancer Epidemiol ; 50(Pt A): 46-52, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28803070


PURPOSE: To describe the sex-specific incidence rates and the male-to-female incidence-rate ratios (IRRs) of different cancer types, and to explore the corresponding sex disparities in an area of Eastern China. METHODS: We used data from the Cancer Registry in Jiashan County, and calculated the sex-specific age-standardized (2010 China standard population) incidence rates and the male-to-female IRRs for different cancer types during the period 1995-2014. RESULTS: The age-standardized incidence rates of all cancers for the whole period 1995-2014 were 151.48 per 100,000 person-years for males and 83.75 per 100,000 person-years for females, and the corresponding male-to-female IRR was 1.81 (95% confidence interval: 1.77-1.85). Specifically, males presented higher incidences in most types of cancer with the exceptions of cancers of connective and other soft tissues, gallbladder (including extrahepatic bile ducts), and thyroid gland. In addition, the age-specific incidences of the ten most common cancers in males were higher than those in females in most age groups. CONCLUSIONS: Our results reveal a male predominance in incidence for a majority of cancers in Jiashan County, Eastern China. Possible explanations for these sex disparities in cancer incidence may include lifestyle factors, particularly smoking.

Neoplasias/epidemiologia , Sistema de Registros/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Fatores Sexuais , Fatores de Tempo , Adulto Jovem
J Nephrol ; 27(4): 411-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24737246


OBJECTIVE: To investigate urinary nephrin and podocalyxin standardized by aquaporin (AQP)-2 using the enzyme-linked immunosorbent assay (ELISA) method in adult nephrotic syndrome (NS) patients. METHODS: In 107 adult NS patients (27 proliferative nephritis, 77 non-proliferative, and 3 amyloidosis) undergoing renal biopsy, urinary nephrin, podocalyxin and AQP2 were measured by ELISA. Urinary nephrin and podocalyxin were standardized by AQP2 (neph/AQP and PCX/AQP) and values were compared with 11 healthy controls. RESULTS: Urinary neph/AQP correlated positively to PCX/AQP (r = 0.51, p < 0.001). Urinary neph/AQP and PCX/AQP were lower in controls than NS patients. Both proliferative and non-proliferative NS patients excreted high urinary neph/AQP and PCX/AQP without a significant difference between them (p > 0.05). Patients with focal segmental glomerular sclerosis (FSGS) excreted higher urinary neph/AQP (p = 0.09) and PCX/AQP (p < 0.05) compared to the other patients. Urinary neph/AQP and PCX/AQP were increased in the immunoglobulin M nephropathy patients. Amyloidosis patients excreted lower neph/AQP and PCX/AQP. The sensitivity was 0.87 and specificity 0.37 when the neph/AQP borderline value of 0.16 was adopted [area under the curve (AUC) = 0.61]. The sensitivity was 0.74 and specificity 0.61 when the PCX/AQP borderline value was 3.06 (AUC = 0.69). CONCLUSIONS: Urinary neph/AQP and PCX/AQP are increased in NS patients, with FSGS patients showing the highest levels. To distinguish FSGS from other NS forms, the measurement of urinary PCX/AQP may be a practical method, and superior to neph/AQP.

Amiloidose/urina , Aquaporina 2/urina , Glomerulonefrite/urina , Proteínas de Membrana/urina , Síndrome Nefrótica/urina , Podócitos , Sialoglicoproteínas/urina , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrose Lipoide/urina , Síndrome Nefrótica/patologia , Sensibilidade e Especificidade , Urina/citologia , Adulto Jovem