Impacts of inflammatory cytokines on depression: a cohort study.

BACKGROUND: Inflammatory factors are associated with depression. We seek to investigate the correlation between inflammatory cytokines and prognosis of depression or suicidal ideation and behavior at 3 months in depression patients. METHODS: Eighty-two depressed outpatients were recruited and treated as usual. Plasma cytokines were measured at baseline. Patients were followed up with Patient Health Questionnaire-9 and suicidal ideation and behavior according to the item 3 of Hamilton depression scale for 3 months. RESULTS: Compared to the depression patients with low level of interleukin-1ß, the high one had severe depressive symptoms at month 2 and 3 (B 0.92, P < 0.01; B 0.86, P = 0.02; respectively). The incidence of suicidal ideation or behavior was 18.3% at 3 months. Depression patients with high levels of tumor necrosis factor-α showed high risk of suicidal ideation and behavior than the low one (OR 2.16, 95% CI 1.00-4.65, P = 0.04). CONCLUSIONS: High levels of interleukin-1ß and tumor necrosis factor-α were predictive of middle-term severe depressive symptoms and suicidal ideation and behavior respectively.

The application of system epidemiology theory and methodology in occupational epidemiology / 中国职业医学

@#Abstract: Occupational epidemiology aims to explore the effect of occupational hazards on the health of workers and understand ， their mechanisms. It plays an important role in occupational health and occupational medicine.Currently occupational ， ， exposures in the workplace are complex and diverse and multiple factors affect workers´ health at the same time. Therefore it is important to elucidate the pathogenesis of occupational disease caused by occupational hazards and implement early - - intervention. System epidemiology collects data on multi level exposure and multi omics information to conduct network analysis - on the relationship amongrisk factors. and to study the mechanisms of exposures and health outcomes based on multi level data. ， ， ， ， Using the study design of system epidemiology occupational environmental lifestyle and social factors are combined as a ， system to evaluate the health of workers which can better evaluate the adverse health effects caused by occupational hazards. - ， ， The studies base on multi omics design will explore the pathogenesis of occupational diseases at the molecular cellular and tissue levels to evaluate the impact of occupational hazards on workers´ health and to explore interventions from multiple - perspectives to reduce the occurrence of occupational or work related diseases.

Effect of SNPs on creatine kinase structure and function: identifying potential molecular mechanisms for possible creatine kinase deficiency diseases.

Single-nucleotide polymorphisms (SNPs) are common genetic material changes that often occur naturally. SNPs can cause amino acid replacements that may lead to severe diseases, such as the well-known sickle-cell anemia. We constructed eight SNP mutants of human brain-type creatine kinase (CKB) based on bioinformatics predictions. The biochemical and biophysical characteristics of these SNP mutants were determined and compared to those of the wild-type creatine kinase to explore the potential molecular mechanisms of possible creatine kinase SNP-induced diseases. While the reactivation of six SNP mutants after heat shock dropped more than 45%, only three of them showed notable increases in ANS fluorescence intensity and decreases in catalytic efficiency. Among them, H26Y and P36T bind substrates as well as the wild-type form does, but the melting temperatures (T(m)) dropped below body temperature, while the T59I mutant exhibited decreased catalytic activity that was most likely due to the much reduced binding affinity of this mutant for substrates. These findings indicate that SNPs such as H26Y, P36T and T59I have the potential to induce genetic diseases by different mechanisms.

Deceleration of arginine kinase refolding by induced helical structures.

Arginine kinase (AK) is a key metabolic enzyme for keeping energy balance in invertebrates. Therefore, regulation of the enzymatic activity and the folding studies of AK from the various invertebrates have been the focus of investigation. We studied the effects of helical structures by using hexafluoroisopropanol (HFIP) on AK folding. Folding kinetic studies showed that the folding rates of the urea-denatured AKs were significantly decelerated after being induced in various concentrations of HFIP. AK lost its activity completely at concentrations greater than 60%. The results indicated that the HFIP-induced helical structures in the denatured state play a negative role in protein folding, and the helical structures induced in 5% (v/v) HFIP act as the most effective barrier against AK taking its native structure. The computational docking simulations (binding energies for -2.19 kcal/mol for AutoDock4.2 and -20.47 kcal/mol for Dock6.3) suggested that HFIP interacts with the several important residues that are predicted by both programs. The excessively pre-organized helical structures not only hampered the folding process, but also ultimately brought about changes in the three-dimensional conformation and biological function of AK.

Kinetic, structural and molecular docking studies on the inhibition of tyrosinase induced by arabinose.

Tyrosinase plays a central role in biological pigment formation, and hence knowledge of tyrosinase catalytic mechanisms and regulation may have medical, cosmetic, and agricultural applications. We found in this study that arabinose significantly inhibited tyrosinase, and this was accompanied by conformational changes in enzyme structure. Kinetic analysis showed that arabinose-mediated inactivation followed first-order kinetics, and single and multiple classes of rate constants were measured. Arabinose displayed a mixed-type inhibitory mechanism with K(i)=0.22±0.07 mM. Measurements of intrinsic and ANS-binding fluorescence showed that arabinose induced tyrosinase to unfold and expose inner hydrophobic regions. We simulated the docking between tyrosinase and arabinose (binding energies were -26.28 kcal/mol for Dock6.3 and -2.02 kcal/mol for AutoDock4.2) and results suggested that arabinose interacts mostly with His61, Asn260, and Met280. The present strategy of predicting tyrosinase inhibition by simulation of docking by hydroxyl groups may prove useful in screening for potential tyrosinase inhibitors, as shown here for arabinose.

Computational simulations to predict creatine kinase-associated factors: protein-protein interaction studies of brain and muscle types of creatine kinases.

Creatine kinase (CK; EC 2.7.3.2) is related to several skin diseases such as psoriasis and dermatomyositis. CK is important in skin energy homeostasis because it catalyzes the reversible transfer of a phosphoryl group from MgATP to creatine. In this study, we predicted CK binding proteins via the use of bioinformatic tools such as protein-protein interaction (PPI) mappings and suggest the putative hub proteins for CK interactions. We obtained 123 proteins for brain type CK and 85 proteins for muscle type CK in the interaction networks. Among them, several hub proteins such as NFKB1, FHL2, MYOC, and ASB9 were predicted. Determination of the binding factors of CK can further promote our understanding of the roles of CK in physiological conditions.

Trehalose has a protective effect on human brain-type creatine kinase during thermal denaturation.

We investigated the effects of trehalose on thermal inactivation and aggregation of human brain-type creatine kinase (hBBCK) in this study. In the presence of 1.0 M trehalose, the midpoint temperature of thermal inactivation (T (m)) of hBBCK increased by 4.6 °C, and the activation energy (E (a)) for thermal inactivation increased from 29.7 to 41.1 kJ mol(-1). Intrinsic fluorescence spectra also showed an increase in the apparent transition temperature (T (1/2)) of hBBCK from 43.0 °C to 46.5 °C, 47.7 °C, and 49.9 °C in 0, 0.6, 0.8, and 1.2 M trehalose, respectively. In addition, trehalose significantly blocked the aggregation of hBBCK during thermal denaturation. Our results indicate that trehalose has potential applications as a thermal stabilizer and may aid in the folding of other enzymes in addition to hBBCK.

[Public health situation and needs assessment after Wenchuan earthquake in Anxian, Sichuan province].

OBJECTIVE: To explore the public health situation and needs in Anxian after Wenchuan earthquake so as to make an effective strategy for disease control and prevention. METHODS: 69 concentrated settlements with 100 residents were investigated. Probability proportion to size was adopted for sampling of 2200 residents from 687 scattered households (about 440 000 scattered residents). The content of this survey included drinking water, food hygiene, environment sanitation, planning immunity and medical health service, disease surveillance and so on. SPSS 16.0 was used for data analysis, and statistical interpretation was used to describe the results. RESULTS: 90.9% (31/66) resettled residents in Anxian lived in tents, 7.6% (5/66) lived in the movable-plate house, 93.3% (621/666) scattered households lived in tents and 71.9% (446/621) of them lived in tents which were built by residents themselves; the rate of drinking water disinfection in resettlement sites and scattered households were 97.1% (66/68) and 94.6% (650/687); 12.8% scattered residents had mouldy or food; 50% of resettlement sites raised animals; 43.6% (17/39) medical station didn't have bacterin inoculation service; 66.7% (10/15) lacked sufficient disinfection equipment; register rate was 50.0% (33/66) and report rate of symptoms and infectious diseases was 56.1% (37/66). CONCLUSION: There was still some risk of enteric and vector-borne diseases in Anxian, therefore, some tailored measures should be very important.

[Mental health assessment among scattered residents after Wenchuan earthquake in Anxian, Sichuan province].

OBJECTIVE: To explore the mental health status of residents scattered living in Anxian after Wenchuan earthquake so as to provide scientific basis for further mental health intervention. METHODS: A face to face interview was conducted among the scattered residents with designed questionnaire, which had three parts of the physical and emotional reaction, the relax methods and the social care and supports expected. Two-stage probability proportional to size (PPS) sample method was performed to sample 2184 from 0.44 million scattered residents in Anxian. On the basis of statistical description, mental health of different characteristics groups was compared. RESULTS: Three main symptoms of posttraumatic stress disorders in 2184 residents (11.23+/-3.44) were higher than the 103 fire victims in Hunan in 2003 (10.06+/-3.26), three factor scores of SCL-90 (5.76+/-1.74) were higher than normal in 1998 repair mode (n=23 891) (4.72+/-1.44), and the statistical difference was observed (t=10.77, P<0.05; t=706.04, P<0.05). Comparing the mental health of different groups, some significant differences were found by age, gender and education background. CONCLUSION: The earthquake disaster brought prevalent physical and emotional reaction. Elderly people, female, junior students need mental intervention immediately. Therefore, strengthen the mental education and assistance (especially in high risk groups) would be of more significance.

Antigen-expressed recombinant Salmonella typhimurium driven by an in vivo-activated promoter is capable of inducing cellular immune response in transgenic mice.

To explore the approaches and mechanisms for reversing the immune tolerance in transgenic mouse, and the pathogenicity of hepatitis G virus (HGV), the promoter of phoP-activated gene (P(pagC)) of Salmonella typhimurium was used as a transcriptionally regulating element to construct an attenuated S. typhimurium expressing HGV NS3. The recombinant S. typhimurium was orally administered to HGV transgenic mice. As the results, HGV antigen in serum and liver as well as HGV mRNA in liver were decreased significantly, although the serum anti-HGV NS3 remained undetectable as the control transgenic mice. The spleen cell proliferation, in vitro HGV NS3 specific CTL, and IFN-gamma assays with the primed cultured splenocytes indicated the induction of Th1 immune responses in those administered transgenic mice. Adoptive transfer of fractionated primed spleen cells to the transgenic mice showed that T lymphocytes were responsible for, maybe through IFN-gamma, the down-regulation of HGV mRNA transcription. Histological examination found no significant inflammatory changes in liver of the transgenic mice. These findings suggested that the oral inoculation of the HGV NS3-expressed attenuated S. typhimurium driven by an in vivo-activated promoter should be a simple and effective approach for potential treatment of chronic viral infection.