Resveratrol Promotes Autophagy to Improve neuronal Injury in Parkinson's Disease by Regulating SNHG1/miR-128-3p/SNCA Axis.

BACKGROUND: Parkinson's disease (PD) is seriously threatening the health and life quality of the elderly, who have a high incidence and high disability rate. Resveratrol (RES) was reported to play a protective role in PD. However, the functions and potential mechanism of RES in PD remain unclear, which need to be further explored. METHODS: Human neuroblastoma cells (SH-SY5Y and SK-N-SH) were subjected to 1-Methyl-4-phenylpyridium (MPP+) induction to construct a cell model of PD. Cell viability was evaluated using CCK-8. The gene expression was evaluated using qRT-PCR and western blot. Luciferase activity assay and RIP were performed to validate interactions among SNHG1, miR-128-3p and SNCA. RESULTS: Our results exhibited that RES reduced SNHG1 and SNCA expression but elevated miR-128-3p expression in human neuroblastoma cells upon MPP+ induction. Functionally, RES resulted in the promotion of cell autophagy in MPP+-induced human neuroblastoma cells, while these influences were abolished by SNHG1 overexpression. Mechanistically, SNHG1 could indirectly elevate SNCA expression via sponging miR-128-3p. Moreover, SNCA overexpression reversed SNHG1 silencing-induced cell autophagy in MPP+-induced human neuroblastoma cells upon RES pre-incubation. CONCLUSIONS: RES prevented MPP+-induced repression of cell autophagy through inhibiting the SNHG1/miR-128-3p/SNCA axis, suggesting that RES might play a preventive effect on PD progression.

Phosphodiesterase 4 Inhibitor Roflupram Suppresses Inflammatory Responses Using Reducing Inflammasome in Microglia After Spinal Cord Injury.

Context: Neuroinflammation after spinal cord injury (SCI) can lead to long-term damage in neural tissue, which can cause the destruction and dysfunction of the neurological system. Roflupram (ROF), a selective phosphodiesterase 4 inhibitor, may play a protective role against neuropathological diseases, but the specific role of ROF in SCI treatment is unknown. Objective: The study intended to investigate the anti-inflammatory mechanism and therapeutic effects of ROF to determine if it can attenuate lipopolysaccharide (LPS)-induced microglia that induces neuroinflammation and decrease neural-tissue damage following an SCI. Design: The research team performed an animal study. Setting: The study took place at the Fourth Affiliated Hospital of Harbin Medical University in Harbin, China. Animals: The animals were female C57BL/6 mice, aged 8 weeks and weighing approximately 20 g. Intervention: For the in-vitro study, the research team divided BV2 microglial cells into three groups: (1) the control group, which received no LPS stimuli and no ROF treatment, (2) the LPS group, which received LPS stimuli but no ROF treatment, and (3) LPS+ROF group, which received both LPS stimuli and ROF treatment. For the in-vivo study, the research team randomly divided the mice into three groups: (1) the sham group, for which the team didn't induce SCI and which received no ROF treatment (2) the SCI group, for which the team induced SCI but which received no ROF treatment, and (3) the SCI+ROF group, for which the team induced SCI and which received the ROF treatment. Outcome Measures: The research team evaluated: (1) the cell viability of the BV2 microglia cells after five doses of ROF and the RNA levels of inflammatory-activation-related factors, the inflammatory pathway; (2) in-vitro inhibition of inflammation in LPS-activated microglia; (3) the anti-neuroinflammatory role of ROF after SCI induction in vitro; and (4) the role of ROF in neural-structure protection and locomotor-function recovery in vitro. Results: In the in-vitro study, the ROF attenuated microglial inflammation through the inhibition of the NLRP3 inflammasome in vitro, reduced neuroinflammation, and protected against neuronal loss. In the in-vivo study with mice, the ROF: (1) improved the functional recovery of locomotor skills after induction of SCI; (2) acted in an anti-inflammatory role in SCI, restraining microglial inflammation by inhibition of the "nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3" (NLRP3) inflammasome and reduction of caspase-1-dependent, interleukin-1 beta (IL)-1ß; and (3) reduced neuronal death and protected against tissue loss, improving functional recovery after an SCI. Conclusions: The current study demonstrated that ROF can reduce the levels of inflammation in the tissue after spinal cord injury by modulating the AMPK/NLRP3 signaling pathway, thereby promoting the recovery of motor function in mice. ROF is a promising drug for prevention of neural-tissue damage following neural injury.

Zileuton Ameliorates Neuronal Ferroptosis and Functional Recovery After Spinal Cord Injury.

Context: Ferroptosis is a novel type of cell-death pattern characterized by iron-dependent, oxidative stress, and lipid peroxidation. Neurological pathology, especially in spinal cord injury (SCI), may involve a trace amount of ferroptosis. However, it's uncertain whether zileuton (ZIL), a selective 5-lipoxygenase (5-LO) inhibitor, can inhibit ferroptosis in SCI. Objective: The study intended to investigate the etiology of neuronal ferroptosis and the ameliorative effects of ZIL against it for SCI mice. Design: The research team performed an animal study. Setting: The study took place at the Fourth Affiliated Hospital of Harbin Medical University in Harbin, China. Animals: The animals were adult, male, C57BL/6 mice, about 20 to 25 g in weight. Intervention: The research team: (1) stimulated HT22 cells, an immortalized mouse hippocampal neuronal cell line treated with erastin, and mice induced spinal cord trauma using a moderate hit, and (2) treated the cells and mice with ZIL. Outcome measures: The research team measured: (1) motor function, (2) neurological damage, (3) iron content, (4) lipid oxidation, and (5) neuroinflammation and glial response. Results: ZIL administration attenuated ferroptosis and lipid peroxidation in the HT22 cells. Moreover, ZIL mitigated the ferroptosis and inflammation in the injured spinal cords. Hence, ZIL can decrease neurological damage and improve recovery of motor function, indicating an ameliorative role for ZIL in SCI. Conclusions: ZIL has anti-ferroptosis and anti-oxidative effects in neurons, which can contribute to recovery of motor function after induction of SCI. ZIL is a promising drug for inhibiting ferroptosis and protecting neurological functions after induction of SCI.

Long non-coding RNA TTTY15 sponges miR-520a-3p to exacerbate neural apoptosis induced by cerebral ischemia/reperfusion via targeting IRF9 both in vivo and in vitro.

BACKGROUND: Studies have proven that as competing endogenous RNAs (ceRNAs), long non-coding RNAs (lncRNAs) play vital roles in regulating RNA transcripts in ischemic stroke. It has been reported that TTTY15, a lncRNA, is dysregulated in cardiomyocytes after ischemic injury. We intended to explore the potential regulating mechanism of TTTY15 in ischemic stroke. METHODS: TTTY15 and miR-520a-3p levels in vivo were measured in the cerebral ischemia/reperfusion (I/R) model. Cell apoptosis was measured by flow cytometry. To manifest TTTY15 functions in I/R injury, Neuro 2a (N2a) cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) and treated with si-NC, pcDNA3.1-NC, si-TTTY15 or pcDNA3.1-TTTY15. RESULTS: TTTY15 expression was elevated and miR-520a-3p expression was declined in mouse brains exposed to I/R and in N2a cells exposed to OGD/R. Bioinformatics analyses predicted the binding sites of miR-520a-3p in the 3'-UTRs of interferon regulatory factor 9 (IRF9) and TTTY15. Luciferase reporter assay exhibited that TTTY15 bound to miR-520a-3p directly and IRF9 was targeted by miR-520a-3p. MiR-520a-3p overexpression diminished N2a cell apoptosis caused by OGD/R. TTTY15 overexpression antagonized the inhibitory impacts of miR-520a-3p on IRF9 expression and apoptosis after OGD/R, while TTTY15 knockdown enhanced the inhibitory impacts of miR-520a-3p. Additionally, TTTY15 knockdown alleviated brain damages and neurological deficits induced by I/R in vivo. Our results revealed that TTTY15 modulated IRF9 via acting as a ceRNA for miR-520a-3p. CONCLUSION: The study revealed the roles of TTTY15/miR-520a-3p/IRF9 signaling pathway in regulating cerebral ischemia/reperfusion injury.

Protective Effects of Ursodeoxycholic Acid Against Oxidative Stress and Neuroinflammation Through Mitogen-Activated Protein Kinases Pathway in MPTP-Induced Parkinson Disease.

OBJECTIVES: Parkinson disease (PD) is the second most common neurodegenerative disorder, and no disease-modifying medications are available. Ursodeoxycholic acid (UDCA) has been shown to prevent neuronal damage; however, the effect of UDCA on PD is unclear. This study aimed to the role of UDCA on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. METHODS: Mice were divided into 3 experimental groups: the control group, MPTP group, and UDCA-treat group. Mice were tested for behavioral impairments, and slices at the level of the ventral midbrain were collected to perform hematoxylin and eosin and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and immunohistochemistry. To evaluate the levels of dopamine (DA), serotonin (5-HT), antioxidant markers, and inflammatory cytokines, enzyme-linked immunoassays were carried out. The protein (α-synuclein, p38, phospho-p38, c-Jun N-terminal kinase [JNK], and phospho-JNK) expression was examined adopting Western blot. RESULTS: We found that UDCA reduced the MPTP-induced degeneration of DA neurons, improved behavioral impairments, and decreased the protein level of α-synuclein, accompanied with increases of DA and 5-HT. In the present study, UDCA prevented DA neurons from MPTP toxicity with increased superoxide dismutase, catalase, glutathione, and decreased malondialdehyde levels. Ursodeoxycholic acid prevented DA neurons from MPTP toxicity with decreased levels of tumor necrosis factor α, interferon γ, and interleukin (IL)-1ß, IL-6, and IL-10. Our results demonstrated that UDCA inhibited the phosphorylation of JNK and p38MAPK. CONCLUSIONS: This study revealed protective effects of UDCA against oxidative stress and neuroinflammation through mitogen-activated protein kinases pathways in MPTP-induced PD, suggesting that UDCA may be a novel therapeutic candidate for PD.

Astaxanthin suppresses endoplasmic reticulum stress and protects against neuron damage in Parkinson's disease by regulating miR-7/SNCA axis.

Parkinson's disease (PD) is a common neurodegenerative disorder that featured by the loss of dopaminergic neurons. Astaxanthin (AST), an important antioxidant, is demonstrated to be a neuroprotective agent for PD. However, the underlying mechanisms of AST in PD remain largely unclear. In this study, we found that AST treatment significantly not only abolished the cell viability inhibition and apoptosis promotion induced by 1-methyl-4-phenylpyridinium (MPP+) in SH-SY5Y cells via inhibiting endoplasmic reticulum (ER) stress, but also reversed the MPP+ caused dysregulation of miR-7 and SNCA expression. MiR-7 knockdown and SNCA overexpression were achieved by treating SH-SY5Y cells with miR-7 inhibitor and pcDNA3.1-SNCA plasmids, respectively. MiR-7 could bind to and negatively regulate SNCA in SH-SY5Y cells. Treated SH-SY5Y cells with miR-7 inhibitor or pcDNA3.1-SNCA abrogated the protective effects of AST on MPP+ induced cytotoxicity. Knockdown of miR-7 aggravated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced neuron injury in vivo suggested by athletic performance, histopathological morphology, expression of tyrosine hydroxylase (TH) and TUNEL positvie cells, however, AST treatment could reverse these effects of miR-7 knockdown. Collectively, AST suppressed ER stress and protected against PD-caused neuron damage by targeting miR-7/SNCA axis, implying that AST might be a potential effective therapeutic agent for PD.

Ursodeoxycholic acid protects dopaminergic neurons from oxidative stress via regulating mitochondrial function, autophagy, and apoptosis in MPTP/MPP+-induced Parkinson's disease.

Neuroprotection targeting mitochondrial dysfunction has been proposed as a potential therapeutic strategy for Parkinson's disease (PD). Ursodeoxycholic acid (UDCA) has been shown to prevent neuronal damage; however, the role of UDCA in PD is poorly understood. This study aimed to investigate the neuroprotective effects of UDCA on PD and its underlying mechanisms. We used MPTP/MPP+-induced PD models, including MPTP-induced mice, primary cultures of mice mesencephalic neurons and MPP+-treated neuro-2a cells to examine the effects of UDCA on PD pathogenesis. The results showed that UDCA improved behavioral performance and protected dopaminergic neurons in MPTP mice. UDCA improved cell viability and decreased cell death in MPP+-treated cells. UDCA inhibited reactive oxygen species accumulation, mitochondrial membrane potential collapse, and ATP depletion in neuro-2a cells. UDCA improved movement dysfunction, ameliorated autophagic flux and alleviated apoptosis. Furthermore, UDCA could activate the AMPK/mTOR and PINK1/Parkin pathways. In conclusion, UDCA may improve PD by regulating mitochondrial function, autophagy, and apoptosis, involving AMPK/mTOR and PINK1/Parkin pathways. These results open new perspectives for pharmacological use of UDCA in PD.

Facile synthesis of rGO-supported AgI-TiO2 mesocrystals with enhanced visible light photocatalytic activity.

Facile synthesis of novel rGO-supported AgI decorated TiO2 mesocrystals (AgI-TMCs-rGO) and their photocatalytic activity under visible light irradiation are reported. The catalysts were prepared by combining the hydrothermal reaction process and in situ deposition-precipitation method. The structural features and chemical compositions of the prepared catalysts were investigated by HRTEM (high resolution transmission electron microscopy), XRD (x-ray powder diffraction), Raman spectra, XPS (x-ray photoelectron spectroscopy), UV-vis DRS (UV-vis diffuse reflectance spectra), PLS (photoluminescence spectra), and N2 physisorption measurements. The AgI-TMCs-rGO catalysts featured a large surface area, high adsorption capacity, enhanced photo-induced charge separation and strong absorbance of visible light. The intimate contact of various components and the fast transfer of charge carriers effectively suppresses photolysis of AgI and favors the structural stability of AgI-TMCs-rGO. The photocatalytic activity of the catalysts was evaluated by degrading Rhodamine B (RhB) in an aqueous solution under visible light irradiation. The highest photocatalytic activity was observed in the sample 20%Ag-TMCs-rGO, attributed to the synergistic effects of a lower band gap and a lowerrecombination rate of the charge carriers, along with the larger surface area of the fabricated sample.

Vitamin D receptor gene polymorphisms and the risk of Parkinson's disease.

The effect of vitamin D receptor (VDR) gene polymorphisms on Parkinson's disease (PD) has recently gained interest. However, evidence on this relationship is controversial. We searched PubMed, EMBASE and the Cochrane Library database targeted all studies that evaluated VDR gene polymorphisms and PD up to April 2,014. A meta-analysis was conducted on the association between VDR ApaI, BsmI, TaqI and FokI polymorphisms and PD using (1) allelic contrast, (2) dominant, (3) recessive, and (4) additive models. A total of five relevant studies involving PD patients (n = 1,266) and controls (n = 1,649) were included in the analysis. There was a significant association between FokI polymorphism and PD. In the pooled allelic analysis, the F allele was associated with increased risk of PD (OR 1.41, 95% CI 1.14-1.75). In the genotype analysis, FF + Ff versus ff showed a significant association with PD in the dominant model (OR 2.32, 95% CI 1.49-3.61, P = 0.0002). FF versus ff showed a significant association with PD in the additive model (OR 2.45, 95% CI 1.52-3.93, P = 0.0002). There was also a statistically significant association between VDR BsmI polymorphisms in the recessive model, BB versus Bb + bb showed a significant increased risk of PD (OR 1.37, 95% CI 1.01-1.87, P = 0.04). No significant associations were observed between VDR ApaI and TaqI polymorphisms and PD. To sum up, VDR BsmI and FokI polymorphisms were associated with increased risk of PD.

Vitamin D status and Parkinson's disease: a systematic review and meta-analysis.

To estimate the associations between vitamin D status and Parkinson's disease (PD). We searched electronic databases of the human literature in PubMed, EMBASE and the Cochrane Library up to February, 2014 using the following keywords: 'vitamin D' or '25(OH)D' and 'status' or 'deficiency' or 'insufficiency' and 'Parkinson's disease'. A systematic review and meta-analysis were conducted on observational studies that reported the association between blood vitamin D levels and PD. Seven studies met the inclusion criteria. 1,008 patients and 4,536 controls were included. Results of our meta-analysis show that PD patients had lower mean levels of 25-hydroxyvitamin D [25(OH)D] than healthy controls [weighted mean difference (MD), -16.9, 95 % confidence interval (CI)], -33.5 to -0.2). Patients with vitamin D insufficiency [25(OH)D level <75 nmol/l] had an increased risk of PD (OR 1.5, 95 % CI 1.1-2.0). Patients with vitamin D deficiency [25(OH)D level <50 nmol/l] experienced a twofold increased risk of PD (OR 2.2, 95 % CI 1.5-3.4). Low vitamin D levels are associated with an increased risk of PD.

Effects of oleic acid on the corneal permeability of compounds and evaluation of its ocular irritation of rabbit eyes.

OBJECTIVE: To explore the use of oleic acid (OA) in ocular drug delivery. METHODS: Six compounds, namely rhodamine B, sodium-fluorescein, fluorescein isothiocyanate (FITC) dextrans of 4, 10, 20 and 40 kDa were selected as model drugs. The effect of OA on the corneal permeability of drugs was evaluated in vitro, using isolated rabbit corneas by a Franz diffusion cell. The safety of OA was assessed on the basis of corneal hydration level. The ocular irritation of OA was also tested in rabbits in vivo using the Draize eye test. RESULTS: In the presence of OA, at a concentration of 0.02-0.1%, the maximum increase in the apparent permeability coefficient (Papp) was 3.21-, 1.76- and 1.57-fold for rhodamine B, sodium-fluorescein and FITC-dextran of 4 kDa, respectively. However, no significant permeability enhancement of FITC-dextrans of 4, 10, 20 and 40 kDa was found in the presence of OA. It enhanced the corneal penetration of model compounds in a concentration-dependent manner. The Papp values of rhodamine B decreased with increasing concentration of OA, while the Papp values of sodium-fluorescein and FITC-dextrans of 4 kDa increased. The Papp enhanced by 0.1% OA was logarithmically correlated to the molecular weight of model drugs (R(2) = 0.9991). With the 0.02%, 0.05% and 0.1% oleic application, the corneal hydration values were <83%, and Draize scores were <4. CONCLUSION: OA may have potential clinical benefits in improving the ocular drug delivery of both hydrophilic and lipophilic compounds.

[Drug dynamics research of salvia miltiorrhiza in rabbit plasma and aqueous humor after intravenous injection].

OBJECTIVES: To assess the permeability of Danshensu at blood-ocular barrier and its characteristics of pharmacokinetics by respectively measuring the concentrations of Danshensu in blood plasma and aqueous humor of the rabbit with the high performance liquid chromatography(HPLC). METHODS: It was an experimental study. Seventy-two white rabbits were split into three groups: control group (6 rabbits), plasma group (6 rabbits) and aqueous humor group (60 rabbits). After 0.85% salt water (control group)or salvia miltiorrhiza (1.0 g/kg) (plasma and aqueous group) was injected into the vein of auris-edge. Samples of blood and aqueous humor were obtained for analysis . The analytical column was a BDS C18 stainless steed column(5 µm, 4.6 mm× 250 mm); Precolumn:YWGC18; the mobile phase consists of acetonitrile and 0.01 mol/L KH2PO4 (8:92, adjusted to pH = 2.8 with phosphoric acid). The UV detector was set at 279 nm; the flow rate was 1.0 ml/min;and the column temperature was ordinary temperature. RESULTS: The plasma concentration-time curves of Salvia miltiorrhiza fitted three-compartment model. t1/2 ß (elimination half time): 5.661 min; Cmax (peak concentration): 727.29 mg/L; Tmax(peak time ): 0 min. The aqueous humor concentration-time curves fitted two-compartment model. t1/2 ß: 147.663 min; Cmax: 38.62 mg/L; Tmax: 25 min. CONCLUSIONS: HPLC is a sensitive, specific and accurate method that can be used in pharmacokinetics research on ocular tissue of rabbit for Danshensu, Salvia miltiorrhiza that is dissolvable in water can pass through the blood-ocular barrier after intravenous injection with a relatively stable concentration of danshensu in aqueous humor resulting from a slow rate of removal.

Early amniotomy and early oxytocin for prevention of, or therapy for, delay in first stage spontaneous labour compared with routine care.

BACKGROUND: Caesarean section rates are over 20% in many developed countries. The main diagnosis contributing to the high rate in nulliparae is dystocia or prolonged labour. The present review assesses the effects of a policy of early amniotomy with early oxytocin administration for the prevention of, or the therapy for, delay in labour progress. OBJECTIVES: To estimate the effects of early augmentation with amniotomy and oxytocin for prevention of, or therapy for, delay in labour progress on the caesarean birth rate and on indicators of maternal and neonatal morbidity. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013), MEDLINE (1966 to 4 July 2013), Embase (1980 to 4 July 2013), CINAHL (1982 to 4 July 2013), MIDIRS (1985 to 4 July 2013) and contacted authors for data from unpublished trials. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials that compared oxytocin and amniotomy with expectant management. DATA COLLECTION AND ANALYSIS: Three review authors extracted data independently. We stratified the analyses into 'Prevention Trials' and 'Therapy Trials' according to the status of the woman at the time of randomization. Participants in the 'Prevention Trials' were unselected women, without slow progress in labour, who were randomized to a policy of early augmentation or to routine care. In 'Treatment Trials' women were eligible if they had an established delay in labour progress. MAIN RESULTS: For the 2013 update, we identified and excluded one new clinical trial. This updated review includes 14 trials, randomizing a total of 8033 women. The unstratified analysis found early intervention with amniotomy and oxytocin to be associated with a modest reduction in the risk of caesarean section; however, the confidence interval (CI) included the null effect (risk ratio (RR) 0.89; 95% CI 0.79 to 1.01; 14 trials; 8033 women). In prevention trials, early augmentation was associated with a modest reduction in the number of caesarean births (RR 0.87; 95% CI 0.77 to 0.99; 11 trials; 7753). A policy of early amniotomy and early oxytocin was associated with a shortened duration of labour (average mean difference (MD) - 1.28 hours; 95% CI -1.97 to -0.59; eight trials; 4816 women). Sensitivity analyses excluding four trials with a full package of active management did not substantially affect the point estimate for risk of caesarean section (RR 0.87; 95% CI 0.73 to 1.05; 10 trials; 5165 women). We found no other significant effects for the other indicators of maternal or neonatal morbidity. AUTHORS' CONCLUSIONS: In prevention trials, early intervention with amniotomy and oxytocin appears to be associated with a modest reduction in the rate of caesarean section over standard care.

In vitro evaluation of enhancing effect of borneol on transcorneal permeation of compounds with different hydrophilicities and molecular sizes.

To investigate the enhancing effect of borneol on transcorneal permeation of compounds with different hydrophilicities and molecular sizes. Six compounds, namely rhodamine B, sodium-fluorescein, fluorescein isothiocyanate (FITC) dextrans of 4, 10, 20 and 40 kDa were selected as model drugs. Permeation studies were performed using excised cornea of rabbits by a Franz-type diffusion apparatus. The safety of borneol was assessed on the basis of corneal hydration level and Draize eye test. The application of 0.2% borneol to the cornea increased the apparent permeability coefficient by 1.82-(P<0.05), 2.49-(P<0.05), 4.18-(P<0.05) and 1.11-fold (not significant) for rhodamine B, sodium-fluorescein, FITC-dextrans of 4 and 10 kDa, respectively. No significant permeability enhancement of FITC dextrans of 10, 20 and 40 kDa with borneol was found compared to control. The permeability coefficient enhanced by 0.2% borneol was linear correlated to the molecular weight of model drugs (R(2)=0.9976). With the 0.05%, 0.1% and 0.2% borneol application, the corneal hydration values were <83% and Draize scores were <4. Borneol may improve the transcorneal penetration of both hydrophilic and lipophilic compounds without causing toxic reactions, especially hydrophilic ones. Furthermore, 0.2% borneol can enhance the permeation of hydrophilic compounds with molecular weight ≤4 kDa. Hence, borneol can be considered as a safe and effective penetration enhancer for ocular drug administration.

Maternal vitamin D status and adverse pregnancy outcomes: a systematic review and meta-analysis.

OBJECTIVE: To estimate the associations between maternal vitamin D status and adverse pregnancy outcomes. STUDY DESIGN: We searched electronic databases of the human literature in PubMed, EMBASE and the Cochrane Library up to October, 2012 using the following keywords: "vitamin D" and "status" or "deficiency" or "insufficiency" and "pregnancy". A systematic review and meta-analysis were conducted on observational studies that reported the association between maternal blood vitamin D levels and adverse pregnancy outcomes including preeclampsia, gestational diabetes mellitus (GDM), preterm birth or small-for-gestational age (SGA). RESULTS: Twenty-four studies met the inclusion criteria. Women with circulating 25-hydroxyvitamin D [25(OH)D] level less than 50 nmol/l in pregnancy experienced an increased risk of preeclampsia [odds ratio (OR) 2.09 (95% confidence intervals 1.50-2.90)], GDM [OR 1.38 (1.12-1.70)], preterm birth [OR 1.58 (1.08-2.31)] and SGA [OR 1.52 (1.08-2.15)]. CONCLUSION: Low maternal vitamin D levels in pregnancy may be associated with an increased risk of preeclampsia, GDM, preterm birth and SGA.

Endothelial nitric oxide synthase gene polymorphisms and risk of preeclampsia.

Polymorphisms in endothelial nitric oxide synthase (eNOS) gene may affect the risk of preeclampsia. This systematic review aimed to provide an updated review of the literature to better understand the association between the eNOS gene polymorphisms and the risk of preeclampsia. We searched electronic databases of the human literature in PubMed, EMBASE, and the Cochrane Library up to July 2012. A meta-analysis was conducted on the association of eNOS G894T, T786C, and intron 4b/a polymorphisms with preeclampsia using (1) allele contrast, (2) recessive, (3) dominant, and (4) additive models. Thirty-three studies comprising 10,671 participants met the inclusion criteria. There was statistically significant association between the G894T variant and increased risk of preeclampsia (TT versus TG + GG: odds ratio 1.43, 95% confidence interval: 1.13 to 1.82). However, no significant risk of preeclampsia was observed either in the T786C or the intron 4b/a polymorphism. Homozygosity TT in eNOS G894T variant is significantly associated with an increased risk of preeclampsia.

Preventive effect of danshensu on selenite-induced cataractogenesis in cultured rat lens.

BACKGROUND: To investigate the preventive effect of danshensu on the selenite-induced opacification of cultured rat lenses. METHODS: Isolated lens were divided into three groups with eight lenses in each group. Group I: lenses were incubated with M199 medium alone; Group II: incubated in M199 containing 200 µmol/L sodium selenite; Group III: incubated in M199 containing 200 µmol/L sodium selenite and 500 µmol/L danshensu. Selenite was administered on the third day, and danshensu treatment was from the second to the fifth day. Cataracts development was observed using an inverted microscope, and the lenses were analysed for total anti-oxidative capabilities, mean activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase; levels of reduced glutathione; malondialdehyde; and total sulfhydryl content. RESULTS: All lenses in Group I were clear, whereas all lenses in Group II developed dense vacuolization and opacification. In Group III, 25% lenses revealed minimal vacuolization, and 75% showed no opacification or vacuolization. Total anti-oxidative capabilities and the mean activities of anti-oxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase; levels of glutathione; and total sulfhydryl content were elevated, and the level of malondialdehyde was decreased following treatment with danshensu compared with Group II. CONCLUSION: The anti-oxidative properties of danshensu may play a major role in its contribution to the anticataract effect.

Early amniotomy and early oxytocin for prevention of, or therapy for, delay in first stage spontaneous labour compared with routine care.

BACKGROUND: Caesarean section rates are over 20% in many developed countries. The main diagnosis contributing to the high rate in nulliparae is dystocia or prolonged labour. The present review assesses the effects of a policy of early amniotomy with early oxytocin administration for the prevention of, or the therapy for, delay in labour progress. OBJECTIVES: To estimate the effects of early augmentation with amniotomy and oxytocin for prevention of, or therapy for, delay in labour progress on the caesarean birth rate and on indicators of maternal and neonatal morbidity. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 February 2012), MEDLINE (1966 to 15 February 2012), EMBASE (1980 to 15 February 2012), CINAHL (1982 to 15 February 2012), MIDIRS (1985 to February 2012) and contacted authors for data from unpublished trials. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials that compared oxytocin and amniotomy with expectant management. DATA COLLECTION AND ANALYSIS: Three review authors extracted data independently. We stratified the analyses into 'Prevention Trials' and 'Therapy Trials' according to the status of the woman at the time of randomization. Participants in the 'Prevention Trials' were unselected women, without slow progress in labour, who were randomized to a policy of early augmentation or to routine care. In 'Treatment Trials' women were eligible if they had an established delay in labour progress. MAIN RESULTS: For this update, we have included a further two new clinical trials. This updated review includes 14 trials, randomizing a total of 8033 women. The unstratified analysis found early intervention with amniotomy and oxytocin to be associated with a modest reduction in the risk of caesarean section; however, the confidence interval (CI) included the null effect (risk ratio (RR) 0.89; 95% CI 0.79 to 1.01; 14 trials; 8033 women). In prevention trials, early augmentation was associated with a modest reduction in the number of caesarean births (RR 0.87; 95% CI 0.77 to 0.99; 11 trials; 7753). A policy of early amniotomy and early oxytocin was associated with a shortened duration of labour (average mean difference (MD) - 1.28 hours; 95% CI -1.97 to -0.59; eight trials; 4816 women). Sensitivity analyses excluding four trials with a full package of active management did not substantially affect the point estimate for risk of caesarean section (RR 0.87; 95% CI 0.73 to 1.05; 10 trials; 5165 women). We found no other significant effects for the other indicators of maternal or neonatal morbidity. AUTHORS' CONCLUSIONS: In prevention trials, early intervention with amniotomy and oxytocin appears to be associated with a modest reduction in the rate of caesarean section over standard care.

Intravitreal versus subtenon triamcinolone acetonide injection for diabetic macular edema: a systematic review and meta-analysis.

OBJECTIVE: To compare the efficacy of intravitreal (IV) triamcinolone acetonide (IVTA) versus subtenon (ST) triamcinolone acetonide (STTA) injection for the treatment of diabetic macular edema (DME). METHODS: Searches for randomized clinical trials published between 1 January 1950 and 15 March 2011 were conducted using PubMed, MEDLINE, EMBASE, and the Cochrane Library included in the present meta-analysis are five randomized controlled trials, each with a minimum follow-up of 3 mo. All included studies evaluated the efficacy of TA for the treatment of refractory DME, and compared IVTA with STTA by measuring visual acuity (VA), central macular thickness (CMT), and intraocular pressure (IOP). RESULTS: One mo post-injection, treatment with IVTA had significantly improved VA (MD, -0.14 logMAR; 95% CI = -0.16 to -0.13) and reduced CMT (MD = -174.02 µm; 95% CI = -249.97 to -98.08) compared with STTA. At 3 mo post-injection, treatment with IVTA had significantly improved VA (MD = -0.07 logMAR; 95% CI = -0.09 to -0.05) and reduced CMT (MD = -119.46 µm; 95% CI = -176.55 to -62.36) compared with STTA. The benefits of either treatment were no longer significant at 6 mo, and patients had to be retreated. Compared with STTA, IVTA injections produced no difference in IOPs at 1 mo, higher IOPs at 3 mo, and lower IOP values at 6 months CONCLUSIONS: Within 3 mo, IVTA is more effective than is STTA in improving VA and reducing CMT in patients with refractory DME. However, the benefits of either regimen were no longer evident at 6 mo.

IL-6-174 G/C and -572 C/G polymorphisms and risk of Alzheimer's disease.

Associations between interleukin 6 (IL-6) polymorphisms and Alzheimer's disease (AD) remain controversial and ambiguous. The aim of this meta-analysis is to explore more precise estimations for the relationship between IL-6-174 G/C and -572 C/G polymorphisms and risk for AD. Electronic searches for all publications in databases PubMed and EMBASE were conducted on the associations between IL-6 polymorphisms and risk for AD until January 2012. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated using fixed and random effects models. Twenty-seven studies were included with a total of 19,135 individuals, involving 6,632 AD patients and 12,503 controls. For IL-6-174 G/C polymorphism, the combined results showed significant differences in recessive model (CC vs. CG+GG: OR = 0.65, 95%CI = 0.52-0.82). As regards IL-6-572 C/G polymorphism, significant associations were shown in dominant model (CG+GG vs. CC: OR= 0.73, 95% CI = 0.62-0.86) and in additive model (GG vs. CC, OR= 0.66, 95% CI = 0.46-0.96). In conclusion, genotype CC of IL-6-174 G/C and genotype GG plus GC of IL-6-572 C/G could decrease the risk of AD.