Restoration of psychosocial functioning in remitted major depressive disorder patients: A 1-year longitudinal study.

BACKGROUND: The recovery of psychosocial functioning is an important treatment goal for patients with depression. The aim of the present study is to investigate psychosocial functioning restoration 1 year after major depressive disorder (MDD) remission. METHODS: Depression symptoms and psychosocial functioning were assessed in 167 remitted MDD patients at baseline, as well as 1, 2, 6, 9, and 12 months following remission, according to the Hamilton Depression Scale (HAMD-17) and Generic Quality of Life Inventory (GQOLI-74). RESULTS: Of the 167 MDD patients, 85 completed the final evaluation at 1 year, 32 relapsed, and 50 dropped out. The total relapse rate over 1 year was 27%. A rapid increase in psychosocial functioning was found in the first 2 months after remission in the non-relapse group. In the non-relapse group, psychosocial functioning was higher at 2 months than at baseline. At baseline and 2 months, psychosocial functioning was lower in the relapse group patients compared to those in the non-relapse group. CONCLUSIONS: Patients with MDD showed continuous improvement in psychosocial functioning during the first year after remission, though psychosocial functioning in the relapse group remained the same during the first two months, suggesting possible further relapse.

Triptolide dysregulates glucose uptake via inhibition of IKKß-NF-κB pathway by p53 activation in cardiomyocytes.

Triptolide (TP), a principal bioactive component extracted from traditional Chinese medicine Tripterygium wilfordii Hook. F. (TWHF), has attracted wide attention of its therapeutic effects on inflammation and autoimmune diseases. However, the therapeutic application of TP is hindered by severe cardiomyocyte toxicity and narrow therapeutic window. We previously identified that the p53 was an indispensable contributor in TP-induced myocardial injury. p53 has an inhibitory effect on IKKß-NF-κB pathway that regulates glucose transporters (GLUT) expression. Based on these evidences, we speculate that p53 mediates TP-disturbed glucose uptake by blocking IKKß-NF-κB signaling. This study focused on the effect of TP on cardiac glucose uptake and the role of p53 in glucose metabolism in cardiomyocytes, and p53 -/- mice. TP treatment depressed glucose consumption and ATP production resulting in myocardial damage. Incubation with ATP (5 mM) remarkably decreased the cellular damage. Immunoblotting and immunofluorescence identified that TP suppressed glucose uptake by restricting IKKß-NF-κB signaling activation, GLUT1 and GLUT4 expression. p53 inhibition alleviated the cell damage and the compromise of glucose uptake. Mechanistically, p53 antagonist PFTα abolished TP-induced the inhibition of IKKß, IκBα phosphorylation, p65 nuclear translocation, and GLUT1, GLUT4 expression. Consistently, in acute heart injury models, p53 deficiency upregulated IKKß-NF-κB activation and GLUT1, GLUT4 protein levels which was also indicated as amelioration of heart histological injury after 1.2 mg kg-1 TP administration. The present findings indicate that TP-induced p53 overactivation suppresses glucose uptake by inhibiting IKKß-NF-κB pathway and downregulating NF-κB-dependent GLUT1 and GLUT4 expression.

An Alternative Hot Start PCR Method Using a Nuclease-Deficient ExoIII from Escherichia coli.

The Hot Start polymerase chain reaction (Hot Start PCR) is designed to reduce off-target amplification by blocking DNA polymerase extension at room temperature until the desired temperature is reached. In this study, we investigated a new method of Hot Start PCR that uses a modified Escherichia coli Exonuclease III (EcoExoIIIM) by substituting residues in the DNA-binding pocket and catalytic center. The results showed that PCR amplification yield and specificity were significantly promoted by the addition of EcoExoIIIM. We hypothesize that non-specific binding of primers at room temperature is prevented by binding of the primed template by EcoExoIIIM, which is then released from the DNA by heat denaturation before the first PCR cycle. Through this mechanism, PCR would be enhanced by reducing off-target extension at room temperature.

The small subunit of DNA polymerase D (DP1) associates with GINS-GAN complex of the thermophilic archaea in Thermococcus sp. 4557.

The eukaryotic GINS, Cdc45, and minichromosome maintenance proteins form an essential complex that moves with the DNA replication fork. The GINS protein complex has also been reported to associate with DNA polymerase. In archaea, the third domain of life, DNA polymerase D (PolD) is essential for DNA replication, and the genes encoding PolDs exist only in the genomes of archaea. The archaeal GAN (GINS-associated nuclease) is believed to be a homolog of the eukaryotic Cdc45. In this study, we found that the Thermococcus sp. 4557 DP1 (small subunit of PolD) interacted with GINS15 in vitro, and the 3'-5' exonuclease activity of DP1 was inhibited by GINS15. We also demonstrated that the GAN, GINS15, and DP1 proteins interact to form a complex adapting a GAN-GINS15-DP1 order. The results of this study imply that the complex constitutes a core of the DNA replisome in archaea.

Ulinastatin attenuates LPS-induced inflammation in mouse macrophage RAW264.7 cells by inhibiting the JNK/NF-κB signaling pathway and activating the PI3K/Akt/Nrf2 pathway.

Ulinastatin (UTI) is a broad-spectrum serine protease inhibitor isolated and purified from human urine with strong anti-inflammatory and cytoprotective actions, which is widely used for the treatment of various diseases, such as pancreatitis and sepsis. Although the therapeutic effects of UTI are reported to be associated with a variety of mechanisms, the signaling pathways mediating the anti-inflammatory action of UTI remain to be elucidated. In the present study we carried out a systematic study on the anti-inflammatory and anti-oxidative mechanisms of UTI and their relationships in LPS-treated RAW264.7 cells. Pretreatment with UTI (1000 and 5000 U/mL) dose-dependently decreased the mRNA levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, iNOS) and upregulated anti-inflammatory cytokines (IL-10 and TGF-ß1) in LPS-treated RAW264.7 cells. UTI pretreatment significantly inhibited the nuclear translocation of NF-κB by preventing the degradation of IκB-α. UTI pretreatment only markedly inhibited the phosphorylation of JNK at Thr183, but it did not affect the phosphorylation of JNK at Tyr185, ERK-1/2 and p38 MAPK; JNK was found to function upstream of the IκB-α/NF-κB signaling pathway. Furthermore, UTI pretreatment significantly suppressed LPS-induced ROS production by activating PI3K/Akt pathways and the nuclear translocation of Nrf2 via promotion of p62-associated Keap1 degradation. However, JNK was not involved in mediating the anti-oxidative stress effects of UTI. In summary, this study shows that UTI exerts both anti-inflammatory and anti-oxidative effects by targeting the JNK/NF-κB and PI3K/Akt/Nrf2 pathways.

[Perceived stress in general public during prevalence of severe acute respiratory syndrome and its impact on health behavior].

OBJECTIVE: To find out the perceived stress in general public during prevalence of severe acute respiratory syndrome (SARS) and its impact on health behavior. METHODS: A retrospective survey was conducted in Guangzhou, Hangzhou, and Taiyuan according to the epidemic situations of SARS, and 2532 subjects were randomly selected from constructive industry, school, and commercial business and residents in urban and rural areas. The perceive stress was measured by Chinese perceived stress scale (CPSS), and health related behavior during SARS was tested by uniform and self-made questionnaire. EpiData 2.0 was used for data management and CPSS value was calculated according to answer to 14 questions contained in the scale. Health risk stress among different population group and health related behavior among low, medium and high stress state were analyzed by SPSS 11.5. RESULTS: 2424 subjects were involved in the survey. The CPSS value was measured from 0 - 49 (22.7 +/- 6.8), M = 24.0. 39.3% (953/2379) subjects were under the health risk stress. The health related behaviors such as washing hands, opening the window for air, keeping away from others when cough and sneeze, doing exercises etc were reduced with the stress increased. Logistic regression indicated that compared with the persons with the thoughts of nothing serious of SARS, without any dread of SARS, and knowing nothing about prevention of SARS, the perceived stress was significantly related with perceiving of the thread to certain extent (beta = 0.41, Wald chi(2) = 4.84, P = 0.03), worrying little about the epidemic (beta = 0.50, Wald chi(2) = 6.69, P = 0.01), worrying about it to certain extent (beta = 1.39, Wald chi(2) = 48.59, P = 0.00) and scared so much (beta = 1.77, Wald chi(2) = 53.59, P = 0.00), and knowing little about the prevention (beta = 0.74, Wald chi(2) = 4.48, P = 0.03), knowing something about prevention (beta = -0.98, Wald chi(2) = 8.29, P = 0.00) and knowing the prevention very well (beta = -1.18, Wald chi(2) = 10.66, P = 0.00). CONCLUSION: The adoption of health related behaviors declined with increase of perceived stress. Opening connection to authority and government, enhancing the awareness of outburst affairs among general public and providing positive social support may be effective ways to reduce the population perceived stress.

Spatial subunit distribution and in vitro functions of the novel trimeric PCNA complex from Sulfolobus tokodaii.

The relationships among three PCNA (proliferating cell nuclear antigen) subunits in the hyperthermophilic archaeon Sulfolobus tokodaii (StoPCNAs) were analyzed and the effects of two PCNA complexes on the activities of the DNA helicase Hjm, DNA Ligase I, and Holliday junction specific endonuclease Hjc were tested. There was no strong self-interaction of each StoPCNA. StoPCNA1 and StoPCNA3 interacted with each other, so did StoPCNA2 and StoPCNA3, but no interaction between StoPCNA1 and StoPCNA2 was observed. Two trimeric complexes (designed StoPCNA123 and StoPCNA323) were formed in vitro and it was determined that StoPCNA323 was composed of one StoPCNA2 and two StoPCNA3 subunits, with StoPCNA2 bridging the two StoPCNA3 subunits. Both complexes inhibited the unwinding activity of Hjm and the ligation activity of DNA Ligase I. In contrast, both stimulated the Holliday junction cleavage activity of Hjc. Our results provide further evidence that in crenarchaea, the PCNAs exhibit diversity in subunit interaction and complex formation.

Hjm/Hel308A DNA helicase from Sulfolobus tokodaii promotes replication fork regression and interacts with Hjc endonuclease in vitro.

Hjm and Hel308a are novel, RecQ-like DNA helicases recently identified in the euryarchaeotes Pyrococcus furiosus and Methanothermobacter thermautotrophicus, respectively. In this study, an Hjm/Hel308 homologue (designated StoHjm) from Sulfolobus tokodaii, a hyperthermophilic archaeon belonging to the Crenarchaeota subdomain of archaea, was cloned, purified, and characterized. Unlike Hjm and Hel308a, which unwind DNA in a 3'-to-5' direction, StoHjm unwound DNA in both 3'-to-5' and 5'-to-3' directions. Remarkably, StoHjm exhibited structure-specific single-stranded-DNA-annealing and fork regression activities in vitro. In addition, gel filtration, affinity pulldown, and yeast two-hybrid analyses revealed that StoHjm physically interacted with StoHjc, the Holliday junction-specific endonuclease from S. tokodaii. This interaction may have functional significance, because the unwinding activity of StoHjm was inhibited by StoHjc in vitro. These results may suggest that the Hjm/Hel308 family helicases, in association with Hjc endonucleases, are involved in processing of stalled replication forks.

[The change of health related behavior during and after severe acute respiratory syndrome prevalence].

OBJECTIVE: To describe the changes of health related behavior and influencing factor during and after the prevalence of severe acute respiratory syndrome (SARS), as to providing evidence for inducing public health related behavior to cope with the emergent infectious public health hazards. METHODS: According to the epidemic strength of SARS, Guangzhou, Taiyuan, Hangzhou were selected to be the research areas, and convenience sampling was used to identify 200 city residents, 200 country residents and 400 occupational populations from each area. The uniform and self-made questionnaire was carried out by about 2400 residents. RESULTS: All 2424 subjects completed the questionnaire. The correlation coefficient of scores of health related behavior during and after SARS was 0.782 (P < 0.01). And 39.3% subjects were considered as under the health risked stress by CPSS. Multiple linear regression indicated that the scores of health related behavior were significantly related to the perceived stress, demographic characteristics and recognition of SARS. CONCLUSIONS: The public health related behavior should be developing in the SARS, and part of health related behavior had been kept after SARS and part been decreased. Behavior change should depends on the prevalence of the disease, cultural heritage and behavior variability. More attention should be paid to induce the public psychology and behavior and enhance the degree of recognition on related knowledge through health education as to relieving the stress in populations when we conduct to cope with the emergent public health hazards.

Pancreatoduodenectomy with vascular reconstruction in treating carcinoma of the pancreatic head.

BACKGROUND: The incidence of carcinoma of the pancreas is increasing in the world. Pancreatic carcinoma is characterized by early local extension to contiguous structures and metastases to regional lymph nodes and the liver. This study was conducted to increase the rate of pancreatoduodenectomy combined with vascular reconstruction. METHODS: Pancreatoduodenectomy with vascular reconstruction was performed for 79 patients at a number of hospitals in Fujian Province, Zhejiang Province, Shanghai and Xinjiang Uyghur Autonomous Region from April 1994 to December 2003. One of these patients also underwent right hemicolectomy; but all received through superior mesenteric vein (SMV)-portal vein (PV) reconstruction. The reconstructions of the superior mesenteric artery (SMA) and hepatic artery (HA) were performed in 4 patients, and reconstructions of the SMA or HA were carried out in 7 and 4 patients respectively. Partial reconstruction of the inferior vena cava (ICV) was done in 2 patients when the tumor was adhering to the wall of the inferior caval vein. RESULTS: Four patients died during the peri-operative period, with a mortality rate of 5%. No complications such as biliary or pancreatic fistulae or artificial blood vessel infection were noted. Histological examination showed one patient with neuroendocrine cancer and the other 78 patients with adenocarcinoma of the pancreatic head. Resected endothelia and vascular margins proved to be microscopically tumor-free. Follow-up for 3 months to 10 years for all except two patients showed 7 of the 9 patients who had undergone resection and reconstruction of the SMA and HA died 7 months or 4 years after operation and 37 survived for over 3 years and 12 for more than 5 years. The rest are still under follow-up. CONCLUSION: Pancreatoduodenectomy with vascular reconstruction for carefully selected patients with carcinoma of the pancreatic head has proved to be a safe and reliable treatment, capable of raising the rates of tumor resection and survival.