Bidirectional Electron-Transfer in Polypeptides with Various Secondary Structures.

The protein-mediated bidirectional electron transfer (ET) is the foundation of protein molecular wire, and plays an important role in the rapid detection of oxo-guanine-adenine DNA mismatches by MutY glycosylase. However, the influences of structural transitions on bidirectional ET are still not clear. In this work, the modified through-bond coupling (MTBC) model was further refined to correlate the structural transition and ET rate more quantitatively. With this model, various polyglycine structures (310-helix, α-helix, ß-sheets, linear, polyproline helical I and II) were studied to explore the influences of structural transitions on bidirectional ET. It was found that the HOMO-LUMO gaps (ΔE) in CN (from the carboxyl to amino terminus) direction are much lower than that in opposite direction, except for polypro I. However, with the equal tunneling energy, the differences between bidirectional ET rates are slight for all structures. In structural transitions, we found that the ET rates are not only affected by the Ramachandran angles, but also correlated to the alignment of C = O vectors, the alignment of peptide planes and the rearrangement of other structure factors. The detailed information can be used to rationalize the inhomogeneous ET across different protein structures and design more efficient protein molecular wires.

Dose-dependent effect of Curcuma longa for the treatment of Parkinson's disease.

Curcuma longa is a plant that belongs to the ginger family, Zingiberaceae. It has been used in Siddha medicine for thousands of years in Asia. Parkinson's disease (PD) is a degenerative disorder of the central nervous system that affects the motor system of the brain. Death of dopamine-producing cells in the substantia nigra leads to PD. Exposure to salsolinol, which is an endogenous neurotoxin, has been associated with damage to dopamine-producing cells. The present study assessed the toxicity of salsolinol in SH-SY5Y human neuroblastoma cells and subsequently investigated the neuroprotective potential of C. longa extract in salsolinol-induced toxic conditions in SH-SY5Y cells. Sulphorhodamine-B assay showed the protective effect of the anti-apoptotic effect of treated SH-SY5Y cells. Fluorescence microscopy and confocal laser scanning microscope analysis indicated the anti-apoptotic impact of the C. longa extract. Mitochondria-derived reactive oxygen species were reduced in C. longa extract-treated SH-SY5Y cells. Downregulated mRNA expression levels of p53, Bcl-2-associated X protein and caspase 3 were observed in the C. longa extract-treated SH-SY5Y cells. Caspase 3 activity was reduced in the C. longa extract-treated SH-SY5Y cells. In conclusion, the present findings demonstrated that solsolinol is neurotoxic to SH-SY5Y cells, and C. longa extract may be useful in the treatment of PD.

[Effects of Scalp Acupuncture on Serum NSE and S-100ß Concentrations and Postoperative Cogni- tive Function of Elderly Patients Undergoing Hip Replacement].

OBJECTIVE: To explore the effect of Scalp acupuncture on serum neuron specific enolase (NSE) and S-100ß concentrations, and incidence rates of postoperative delirium (POD) and postoperative cognitive function (POCD) of elderly patients undergoing hip replacement. METHODS: Eighty-four patients undergoing scheduled hip replacement under combined spinal-epidural anesthesia (CSEA) were assigned to the control group (group C) and the scalp acupuncture group (group S) according to random digit table, 42 cases in each group. In group S, scalp acupuncture was additionally performed according to International Standardized Scheme for Scalp Acupuncture. Scalp acupuncture was performed during the operation from the MS1 middle line of forehead [1 cun before Shenting (GV24), including Shenting (GV24)] and MS5 middle line of vertex [from Baihui (DU20) to Qianding (DU21), including Baihui (DU20) and Qianding (DU21)]. The operation time and post-operative length of stay were observed. The midazolam dosage, hemorrhage amount, fluid transfusion amount, urine amount, use rates of ephedrine and atropine during the operation were also observed and compared between the two groups. The occurrence rate of POD and POCD at post-operative day 3 (T1), week 1 (T2), month 3 (T3), and month 6 (T4) were measured. Eighteen patients were randomly selected to collect blood from internal jugular vein before anesthesia t0), immediately after ending the surgery (t1), 6 h after operation (t2), 24 h after operation (t3), and 48 h after operation (t4), respectively. Serum levels of NSE and S-100ß were correspondingly measured. RESULTS: There was no statistical difference in the operation time, midazolam dosage used during the operation, hemorrhage amount, fluid transfusion amount, urine amount, use rates of ephedrine and atropine (P > 0.05). Compared with group C, the post-operative length of stay was shortened in group S (P < 0.05). The incidence rate of POD and that of POCD at each time point were lower in group S (P < 0.05). The expression level of NSE decreased at t2, t3, and t4, and the expression level of S100ß also decreased at t1, t2, t3, and t4(P < 0.05). There was no statistical difference in expression levels of NSE or S100ß between the two groups at other time points (P > 0.05). CONCLUSION: Scalp acupuncture could attenuate central nervous system lesion and improve POCD of elderly patients undergoing hip replacement.

Association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and ischemic stroke in the Chinese population: a meta-analysis.

PURPOSE: The association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and ischemic stroke (IS) has been extensively studied; however, the results from genetic association studies have been inconsistent even in the Chinese population. As far as we know, there was no previous meta-analysis concerning this association in the Chinese population. Therefore, the aim of our meta-analysis was to further evaluate the association in the Chinese population. METHODS: We collected all of the relevant studies from Pubmed, OVID, Embase, Chinese Wan Fang database, CNKI, Chongqing VIP database and CBM up to August 2014. The available data was analyzed by Stata (version 12.0). We used odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to present the strength of the association. Heterogeneity was evaluated by the Q-test and I(2) statistic. Different genetic models, subgroup analysis, publication bias and sensitivity analysis were used to improve the comprehensive understanding. RESULTS: The results showed a significant association between the MTHFR gene C677T polymorphism and IS in six genetic models (additive model: OR = 1.34, 95%CI: 1.17 ∼ 1.54, p < 0.001; dominant model: OR = 1.44, 95% CI:1.26 ∼ 1.64, p < 0.001; recessive model: OR = 1.45, 95% CI: 1.15 ∼ 1.83, p = 0.001; heterozygote model: OR = 1.35, 95% CI: 1.18 ∼ 1.55, p < 0.001; homozygote model: OR = 1.80, 95% CI: 1.34 ∼ 2.41, p < 0.001; and allelic model: OR = 1.34, 95% CI: 1.17 ∼ 1.53, p < 0.001) based on the overall population, as well as subgroup analysis. In addition, the similar results were obtained in the sensitivity analysis based on studies with the high quality. CONCLUSIONS: This meta-analysis presented a significant association between the MTHFR gene C677T polymorphism and IS, the T allele might be a risk factor for IS in the Chinese population.

ATP-binding cassette transporter A1 R219K polymorphism and ischemic stroke risk in the Chinese population: a meta-analysis.

Recently, many studies have been focused on the association between the ATP-binding cassette transporter A1 (ABCA1) gene R219K polymorphism and ischemic stroke (IS). However, the study results have been inconsistent, especially in the Chinese population. Therefore, we performed a meta-analysis to better clarify the association between the ABCA1 gene and IS. All of the relevant studies used in our meta-analysis were identified using PubMed, OVID, Cochrane Library, Chinese Wan Fang database, Chinese VIP database, China National Knowledge Infrastructure (CNKI), and China Biological Medicine Database (CBM) up to May 2013. Statistical analysis was conducted with STATA software version 11.0. Odds ratios with 95% confidence intervals were applied to evaluate the strength of the association between ABCA1 gene R219K polymorphism and IS. Heterogeneity was evaluated using the Q-test and I(2) statistic. The funnel plots, Begg's and Egger's regression tests were used to assess the publication bias. Our meta-analysis showed the dominant genetic model (OR=0.92, 95% CI: 0.88-0.96), the recessive genetic model (OR=0.73, 95% CI: 0.51-1.05), the homozygote genetic model (OR=0.64, 95% CI: 0.44-0.94), the heterozygote genetic model (OR=0.81, 95% CI: 0.69-0.95), and the allelic genetic model (OR=0.83, 95% CI: 0.69-0.99). For R219K in IS, there were significant associations with these genetic models, but not with the recessive genetic model. Our meta-analysis indicated that the ABCA1 gene R219K polymorphism might be associated with IS and the K allele might be a protective factor in the Chinese population.

miR-137, a new target for post-stroke depression?

Expression of miR-137 is downregulated in brain tissue from patients with depression and suicidal behavior, and is also downregulated in peripheral blood from stroke patients. However, it is not yet known if miR-137 acts as a bridge between stroke and depression. To test this, we used middle cerebral artery occlusion and chronic mild stress to establish a post-stroke depression model in rats. Compared with controls, we found significantly lower miR-137 levels in the brain and peripheral blood from post-stroke depression rats. Injection of a miR-137 antagonist into the brain ventricles upregulated miR-137 levels, and improved behavioral changes in post-stroke depression rats. Luciferase assays showed miR-137 bound to the 3'UTR of Grin2A, regulating Grin2A expression in a neuronal cell line. Grin2A gene overexpression in the brain of post-stroke depression rats, noticeably suppressed the inhibitory effect of miR-137 on post-stroke depression. Overall, our results show that miR-137 suppresses Grin2A protein expression through binding to Grin2A mRNA, thereby exerting an inhibitory effect on post-stroke depression. Our results offer a new therapeutic direction for post-stroke depression.

[Expression of sCD40L in peripheral blood and NF-κBp65 in PBMC of patients with acute progressive cerebral infarction].

AIM: To study the expressional changes of soluble CD40 ligand(sCD40L) in peripheral blood serum and nuclear factor-κB (NF-κB) p65 in peripheral blood mononuclear cells (PBMC) of patients with acute progressive cerebral infarction(APCI). METHODS: We selected ninety-nine patients getting APCI less than 7 d of the onset as APCI group by prospective method. Each 100 cases of patients with acute cerebral infarction(ACI) in the same and with cerebral arteriosclerosis(CAS) in the outpatient were respectively selected as ACI and CAS group. The expressional changes of sCD40L in peripheral blood serum and NF-κBp65 in PBMC of patients with CAS on admission, of patients with APCI and ACI when in hospital, on the course of seventh day, of fourteen and of thirtieth were detected respectively. RESULTS: The expression of sCD40L in peripheral blood serum and NF-κBp65 in PBMC of patients of ACI group on admission were obviously higher all than that of CAS group (P<0.05); The expression of sCD40L in peripheral blood serum and NF-κBp65 in PBMC of patients of APCI group when in hospital, on the course of seventh day, of fourteen and of thirtieth were obviously higher all than that of ACI group (P<0.05 ). CONCLUSION: The inflammatory and apoptotic mechanism mediated by expressional excessive increase of CD40-CD40L signal passage and NF-κB in PBMC might be one of the molecular biology mechanisms of onset and progress for APCI.

[Effects of Linggui Bafa on the therapeutic effect and quality of life in patients of post-stroke depression].

OBJECTIVE: To probe into effects of Linggui Bafa (method for picking eight points linked with extraordinary meridians according to time) on the therapeutic effect and quality of life in patients of post stroke depression. METHODS: One hundred and twenty cases were randomly divided into 3 groups, an observation group 1, an observation group 2 and a control group, 40 cases in each group. All patients were given routine clinical treatments and second level medical prevention. Patients in the observation group 1 received Linggui Bafa acupuncture treatment 2 weeks after stroke; at the same time the observation group 2 was treated with oral administration of Sertraline. The control group did not receive any form of either acupuncture or oral medication, but early rehabilitative intervention and psychological treatment were initiated. Curative effects were evaluated with Hamilton Depression Scale (HAMD), Function Independent Measure (FIM), National Institutes of Health Stroke Scale (NIHSS) and SF-36 after the treatment and 6 months later, respectively. RESULTS: The scores of HAMD, FIM (cognition function) and general health, role-physical, role-emotional, social function, vitality, mental health in SF-36 in the observation group 1 were significantly higher than those in the control group after treatment and 6 months later (P<0.01, P<0.05). The scores of physical function in SF-36 after treatment and NIHSS 6 months later in the observation group 1 were significantly improved than those in the control group (P<0.01, P<0.05). The scores of FIM (cognition function) and role-physical, social function, mental health in SF-36 after treatment and HAMD and general health, social function, mental health in SF-36 6 months later in the observation group 2 were significantly better than those in the control group (P<0.01, P<0.05). The scores of HAMD, FIM (cognition function) and general health, role-emotional, social function, vitality, mental health in SF-36 in the observation group 1 were significantly improved than those in the observation group 2 after treatment and 6 months later (P<0.01, P<0.05). The scores of NIHSS and role-physical in SF-36 in the observation group 1 were significantly higher than those in the observation group 2 6 months later (P<0.05). CONCLUSION: Acupuncture can improve depression symptoms and quality of life of patients with post stroke depression and the effects were better than Sertraline.

[Long-term effect of acupuncture on quality of life in patients with early stage of stroke].

OBJECTIVE: To study the long-term effects of acupuncture on quality of life in patients with early stage of stroke. METHODS: Eighty patients were randomly assigned to the acupuncture group and the control group, 40 in each. All received conventional Western medical treatment, but for patients in the acupuncture group, acupuncture was applied additionally immediately from 48 h after patients' life signs were stabilized. Curative effects were evaluated with scores of SF-36, function independent measure (FIM) and NIHSS. RESULTS: Effect evaluated immediately after acupuncture operation showed that all the scores in the acupuncture group, except score of recognition function in FIM, and scores of body pain and physical function in SF-36, were improved more significantly than those in the control group (P < 0.05). The effectiveness improved continuously in the 6-month period after stroke in both groups, but more superiority was shown in the acupuncture group in aspects of emotional function, social function and mental health by SF-36 (P < 0.05). CONCLUSION: Early applying acupuncture could raise the physical, social, and psychological functions of stroke patients. Although the effects might decrease to some extent later, acupuncture still showed markedly effect on patients' psychological and social functions as well as on their life satisfaction.