Association of BDNF gene polymorphism with endophenotypes in posttraumatic stress disorder.

OBJECTIVE To explore the association of brain-derived neurotrophic factor gene (BDNF) polymorphism with the latent cognitive endophenotype of posttraumatic stress disorder (PTSD) after major natural disasters in Hainan Province, China. METHODS A total of 300 patients with PTSD and 150 healthy controls (HC) were surveyed by psychoanalysis scale to assess their cognitive functions. Polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) were used to detect the BDNF gene polymorphism. RESULTS In terms of the cognitive function, the scores in the PTSD group were worse than those of the HC group (P < 0.05 or P < 0.01). There was a significant difference in the distribution of BDNF genotype and allele frequency between the two groups (P < 0.05). PTSD endophenotypes were significantly different among the BDNF genotypes in the PTSD group (P ≤ 0.01). CONCLUSION There is a statistically significant difference in the polymorphism of BDNF gene between PTSD and HC groups, and the alleles are associated with the incidence of PTSD. Thus, it may be a risk factor for PTSD.

Association of BDNF gene polymorphism with endophenotypes in posttraumatic stress disorder

SUMMARY OBJECTIVE To explore the association of brain-derived neurotrophic factor gene (BDNF) polymorphism with the latent cognitive endophenotype of posttraumatic stress disorder (PTSD) after major natural disasters in Hainan Province, China. METHODS A total of 300 patients with PTSD and 150 healthy controls (HC) were surveyed by psychoanalysis scale to assess their cognitive functions. Polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) were used to detect the BDNF gene polymorphism. RESULTS In terms of the cognitive function, the scores in the PTSD group were worse than those of the HC group (P < 0.05 or P < 0.01). There was a significant difference in the distribution of BDNF genotype and allele frequency between the two groups (P < 0.05). PTSD endophenotypes were significantly different among the BDNF genotypes in the PTSD group (P ≤ 0.01). CONCLUSION There is a statistically significant difference in the polymorphism of BDNF gene between PTSD and HC groups, and the alleles are associated with the incidence of PTSD. Thus, it may be a risk factor for PTSD.

RESUMO OBJETIVO Explorar a associação do polimorfismo do gene fator neurotrófico derivado do cérebro (BDNF) com o endofenótipo cognitivo latente de transtorno de estresse pós-traumático (TEPT) após grandes desastres naturais na província de Hainan, China. MÉTODOS Um total de 300 doentes com TEPT e 150 controles saudáveis (HC) foi investigado pela escala de psicanálise para avaliar as suas funções cognitivas. A reação em cadeia polimerase (PCR) e a eletroforese em gel de poliacrilamida (Page) foram usadas para detectar o polimorfismo do gene BDNF. RESULTADOS Em termos de função cognitiva, as pontuações no grupo TEPT foram piores do que as do grupo HC (P<0,05 ou P<0,01). Houve uma diferença significativa na distribuição do genótipo de BDNF e frequência do alelo entre os dois grupos (P<0,05). Os endofenótipos de TEPT foram significativamente diferentes entre os genótipos de BDNF do grupo TEPT (P≤0,01). CONCLUSÃO Existe uma diferença estatisticamente significativa no polimorfismo do gene BDNF entre o TEPT e os grupos HC, e os alelos estão associados à incidência do TEPT. Assim, pode ser um fator de risco para TEPT.

Silencing of long noncoding RNA HOXA11-AS inhibits the Wnt signaling pathway via the upregulation of HOXA11 and thereby inhibits the proliferation, invasion, and self-renewal of hepatocellular carcinoma stem cells.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths, but its molecular mechanisms are not yet well characterized. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis, including that of HCC. However, the role of homeobox A11 antisense (HOXA11-AS) in determining HCC stem cell characteristics remains to be explained; hence, this study aimed to investigate the effects of HOXA11-AS on HCC stem cell characteristics. Initially, the expression patterns of HOXA11-AS and HOXA11 in HCC tissues, cells, and stem cells were determined. HCC stem cells, successfully sorted from Hep3B and Huh7 cells, were transfected with short hairpin or overexpression plasmids for HOXA11-AS or HOXA11 overexpression and depletion, with an aim to study the influences of these mediators on the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo. Additionally, the potential relationship and the regulatory mechanisms that link HOXA11-AS, HOXA11, and the Wnt signaling pathway were explored through treatment with Dickkopf-1 (a Wnt signaling pathway inhibitor). HCC stem cells showed high expression of HOXA11-AS and low expression of HOXA11. Both HOXA11-AS silencing and HOXA11 overexpression suppressed the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo, as evidenced by the decreased expression of cancer stem cell surface markers (CD133 and CD44) and stemness-related transcription factors (Nanog, Sox2, and Oct4). Moreover, silencing HOXA11-AS inactivated the Wnt signaling pathway by decreasing the methylation level of the HOXA11 promoter, thereby inhibiting HCC stem cell characteristics. Collectively, this study suggested that HOXA11-AS silencing exerts an antitumor effect, suppressing HCC development via Wnt signaling pathway inactivation by decreasing the methylation level of the HOXA11 promoter.

Functional rs6265 polymorphism in the brain-derived neurotrophic factor gene confers protection against neurocognitive dysfunction in posttraumatic stress disorder among Chinese patients with hepatocellular carcinoma.

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that plagues trauma survivors. Evidence shows that brain-derived neurotrophic factor (BDNF) may be involved in the occurrence and development of PTSD. Here we tried to demonstrate whether BDNF gene polymorphisms are correlated with neurocognitive function following PTSD in patients with hepatocellular carcinoma (HCC). This study included 102 patients with HCC complicated with PTSD, 146 HCC patients, and 152 healthy volunteers. Initially, we evaluated the neurocognitive function of the study subjects. Next, we measured BDNF G11757C and rs6265 polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. The correlation of BDNF polymorphisms and BDNF level with HCC complicated with PTSD was evaluated. The results revealed that HCC complicated with PTSD showed decreased serum BDNF level and Mini-mental state examination (MMSE) score. Serum BDNF level of HCC and HCC complicated with PTSD was positively correlated with MMSE score. GA + AA allele and A allele of rs6265 increased the risk of PTSD among patients with HCC. GA and AA genotypes of rs6265 were correlated with the decreased MMSE score of HCC complicated with PTSD. Haplotype GA of rs6265 and G11757C increased the risk of PTSD for HCC, while haplotype CG decreased this risk. Lastly, the logistic regression analysis suggested that low BDNF level was a contributor to HCC complicated with PTSD, while GG genotype of rs6265 served as a protective factor. Collectively, this study defines the GG genotype of BDNF rs6265 polymorphism as a protector to HCC complicated with PTSD. In addition, these results provided a promising target for PTSD prevention in patients with HCC.

Ultrasound-guided intertumoral injection of contrast agents combined with human p53 gene for the treatment of breast cancer.

The objective of this study was to investigate the effects of ultrasound-guided injection of ultrasound contrast agents (UCAs) and the p53 gene on the treatment of rats with breast cancer (BC). Assembly of the p53 expression vector as well as that of a rat model with BC consisted of 200 successfully modeled rats randomly divided into 5 groups: p53 gene introduction, p53 gene introduction + ultrasound irradiation, p53 gene introduction + UCAs, p53 gene introduction + UCA + ultrasound irradiation, and UCA + ultrasound irradiation groups. Expression of p53 was detected via quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemical staining. In the p53 gene introduction + ultrasound irradiation group, we observed increased tumor volume with blood flow signals around and necrotic tumor tissues with an inhibition rate of 36.30%, as well as higher expression of p53 than that in the p53 gene introduction group and p53 gene introduction + UCA group. In the p53 gene introduction + UCA + ultrasound irradiation group, tumor volume increased slightly with reduced blood flow signals and massive degenerative necrosis of tumor cells was identified with inhibition rate of 62.62%, and expression of p53 was higher than that in the rest groups. Taken together, the key findings obtained from the present study elucidate that injection of p53 gene and UCA microbubbles guided by ultrasound could increase the expression of p53, thus inhibiting the tumor growth in rats with BC.

Correlations of Four Genetic Single Nucleotide Polymorphisms in Brain-Derived Neurotrophic Factor with Posttraumatic Stress Disorder.

OBJECTIVE: To investigate the correlations of four genetic single nucleotide polymorphisms (SNPs) of brain-derived neurotrophic factor (BDNF) with posttraumatic stress disorder (PTSD). METHODS: A total of 300 patients with sporadic PTSD and 150 healthy subjects (the control group) were selected according to the diagnostic criteria of PTSD (DSM-IV), and the genotypes of the BDNF SNPs G-712A, C270T, rs6265, and rs7103411 were detected by polymerase chain reaction and direct DNA sequencing to determine intergroup differences in the genotypes and allele frequencies; the p values were corrected with the permutation test. RESULTS: The genotypes and allele frequencies of the SNPs G-712A, rs6265, and rs7103411 of BDNF showed no significant intergroup differences (p>0.05). However, the genotype and allele frequencies of C270T showed significant differences between the PTSD group and the control group (p<0.05). CONCLUSION: The SNP C270T of BDNF may be associated with PTSD. Individuals carrying the polymorphic T allele of C270T may be more likely to suffer from PTSD.

CpG methylation of brain-derived the neurotrophic factor gene promoter as a potent diagnostic and prognostic biomarker for post-traumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a common response to traumatic events. Many PTSD patients recover in the next few months, but in a significant subgroup, the symptoms persist, often for years. The present study shows that brain-derived neurotrophic factor (BDNF) gene is related to the pathological mechanism of a variety of mental diseases. Here we investigate the effect of methylation of BDNF gene and different loci on the occurrence and development of PTSD. Initially, using case-control method, 322 PTSD patients as well as 215 normal controls were selected as the subjects. Following peripheral venous blood being collected from the subjects, genomic DNA was extracted. Methylation of the cytosine-guanine dinucleotide (CpG) island in BDNF gene promoter was then modified by bisulfite and detected through direct sequencing. Methylation of CpG in BDNF gene promoter was closely related to PTSD, and the methylation level of CpG in BDNF gene promoter may serve as a biomarker for PTSD diagnosis. Types of trauma of PTSD patients may have a certain effect on the methylation level of BDNF gene promoter. Methylation level of the BDNF promoter, depressive degree score, poor sleep quality score, early trauma score, mental stress score, and trauma type were closely related to the occurrence and development of PTSD. Taken together, our data support the notion that stressful life events may directly cause CpG methylation in the BDNF promoter of PTSD patients. Stress types may be associated with methylation levels of CpG1, CpG7, and CpG18 in the BDNF promoter of PTSD patients. These findings provide a new way for the diagnosis and treatment of PTSD.

Post-traumatic stress disorder after typhoon disaster and its correlation with platelet 5-HT concentrations.

OBJECTIVE: To investigate residents' psychological stress factors and research the correlation between post-traumatic stress disorder (PTSD) and platelet 5-HT concentrations so as to provide scientific bases for diagnosis and treatment of PTSD and psychological intervention for people in the disaster area. METHODS: A questionnaire survey of 5500 residents who have accepted psychological help was conducted by the emphatic investigation method. While high performance liquid chromatography was used to detect the platelet serotonin concentration of 100 PTSD patients and 100 healthy people. RESULTS: (1) Of the 5114 cases, 3167 (61.93%) showed positive results in screening for psychological stress symptoms, and 399 (7.8%) were tested having apparent PTSD symptoms. Male and female prevalence showed no significant difference (χ(2) = -0.380, P = 0.704). The differences of prevalence between different age groups were statistically significant (χ(2) = 381.89, P = 0.000). (2) The differences in the level of platelet 5-HT between PTSD patients and normal control group were statistically significant. CONCLUSIONS: The typhoon of Hainan Province caused relatively large psychological problems to the disaster victims. Compared with normal control group, the platelet 5-HT levels of PTSD patients in the disaster areas are lower. It may be related to incidents exposure levels, cultural background, religious ideas, social concerns and psychological rescue of the residents who live in the disaster areas of Hainan.

Clinical effects of comprehensive therapy of early psychological intervention and rehabilitation training on neurological rehabilitation of patients with acute stroke.

OBJECTIVE: To evaluate the clinical effects of comprehensive therapy of psychological intervention and rehabilitation training on the mental health of the patients with acute stroke. METHODS: A total of 120 patients with acute stroke were randomly divided into trial group and control group. Both groups were given the corresponding drug therapy, medical basic nursing and convention nursing. Besides, psychological intervention and comprehensive rehabilitation training were added to the trial group. SCL-90, Europ stroke scales (ESS) score were assessed with each patient on day 3 for the first time and on day 21 for the second time; Barthel index was assessed on the day 90. RESULTS: After psychological intervention, SCL-90 declined significantly in the trial group comparing with the control group, there were significant differences in the somatization, obsession, depression, anxiety, fear, ESS score, Barthel index and other psychological factors between the trial group and control group (P < 0.05). CONCLUSIONS: Comprehensive therapy of early psychological intervention and rehabilitation training can significantly improve the mental health, limb movement function, stress ability and activity of daily living on the patients with acute stroke.

Clinical effects of psychological intervention and drug therapy against peptic ulcer.

OBJECTIVE: To evaluate the clinical effects of psychological interventions and drug therapy against peptic ulcer. METHODS: 96 patients with peptic ulcer were divided into control group with Tagamet 800 mg per evening p.o. and trial group with psychological intervention on the basis of drug treatment. RESULTS: There were significant differences between the two groups (P<0.05), the trial group showed that the anxiety and depression cases declined obviously and effective rate of ulcer therapy was much higher than control group. CONCLUSIONS: In sum, psychological intervention combined with drug therapy provides an effective method for ulcer treatment.

Study on serum cytokine levels in posttraumatic stress disorder patients.

OBJECTIVE: To evaluate serum IL-2, IL-4, IL-6, IL-8, IL-10 and TNF-α levels in posttraumatic stress disorder (PTSD) patients. METHODS: We utilized ELISA technology to examine cytokines such as IL-2, IL-4, IL-6, IL-8, IL-10 and TNF-α in serum from 50 well-characterized individuals with a primary DSM-IV PTSD diagnosis, and 50 age- and gender-matched healthy controls. We conservatively employed a Mann-Whitney U testing. RESULTS: Individuals with primary PTSD had significantly elevated peripheral cytokine levels for all 6 different cytokines compared to age- and gender-matched healthy controls (all P<0.01). CONCLUSIONS: These findings suggest that a generalized inflammatory state may be present in individuals with PTSD.

Study of the hippocampus and the anterior cingulate gyrus by proton MR spectroscopy in patients with post-traumatic stress disorder.

OBJECTIVE: To explore the characteristics of metabolic changes in patients with post-traumatic stress disorder through 1H-MRS in neuroanatomical circuit comparing with age-matches controls. METHODS: Fifty patients with post-traumatic stress disorder and 50 gender-and age-matched normal controls were involved. The neurochemical abnormalities including the levels of choline (Cho)/creatine(Cr) and N-acetylaspartate (NAA)/Cr were measured respectively in hippocampus and the anterior cingulate gyrus with three-dimension 1H-proton spectroscopy(3D 1H-MRS). RESULTS: The values of NAA/Cr ratios in hippocampus and the anterior cingulate gyrus were significant lower in patients with post-traumatic stress disorder(1.71±0.32, left 1.58±0.29, right 1.55±0.31) than that in controls(2.24±0.41, left 1.98±0.27, right 2.02±0.36)(P<0.05), but the values of Cho/Cr in hippocampus(left 1.64±0.23, right 1.66±0.34) were no significant with that of controls (left 1.48±0.29, right 1.54±0.38). Values of Cho/Cr in cingulate gyrus were significant higher in post-traumatic stress disorder patients (1.88±0.44) than that in controls (1.37.±0.32) (P<0.05). CONCLUSIONS: The results indicate some special neurochemical and histological structure changes in post-traumatic stress disorder patients, which might occurre earlier in anterior cingulate gyrusthe than in hippocampus.