Table_1_Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Protects Against Neuronal Apoptosis via Activation of Akt/MDM2/p53 Signaling Pathway in a Rat Model of Intracerebral Hemorrhage.DOCX

<p>Neuronal apoptosis plays key roles in secondary brain injury caused by intracerebral hemorrhage (ICH). This study first reported the role of mesencephalic astrocyte-derived neurotrophic factor (MANF) in alleviating secondary brain injury through anti-apoptosis in rat model of ICH. The recombinant human-MANF (rh-MANF) and selective Akt inhibitor MK2206 was administrated intracerebroventricularly 1 h after ICH. Brain water content, behavioral assessment, BBB (blood brain barrier) leakage was evaluated 24 h after the induction of ICH. Western blot analysis was used to evaluate the expression level of target proteins (MANF, mouse 3T3 cell double-minute 2 (MDM2), P53, Akt, Bcl-2, Bax, and caspase-3). Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) was applied to evaluate the neuronal cell death. Besides, whether MANF was expressed in neurons was verified with double immunofluorescence staining. The results suggested that the level of MANF, and its downstream proteins, Akt, MDM2 was upregulated and reached peak at 24 h after ICH. MANF was mainly expressed in neurons. The administration of rh-MANF could significantly increase the level of p-Akt, p-MDM2, Bcl/Bax ratio, but reduce the expression of p53, caspase-3 and neuronal death, thus ameliorate the neurological functions at 24 h after ICH. However, these effects of rh-MANF could be obviously reversed by MK2206. MANF could exert its neuronal anti-apoptotic effects via Akt/MDM2/P53 pathways. Therefore, MANF could be a valuable drug target in the treatment of ICH.</p

Longitudinal Impact on Quality of Life for School-aged Children with Amblyopia Treatment: Perspective from Children

<p><i>Background</i>: To evaluate the longitudinal impact on health-related quality of life (HRQOL) during amblyopia treatment for school-aged children from children’s perspective.</p> <p><i>Methods</i>: School-aged children prescribed amblyopia treatment for the first time were recruited into the current study. Using a questionnaire, subjects’ HRQOL was assessed before patching treatment, and at 8 weeks and 16 weeks after the commencement of patching treatment. Evaluation of visual function and psychosocial aspect was included in the questionnaire. Visual acuity and demographic data of the subjects were recorded.</p> <p><i>Results</i>: Forty-four children, aged 7–12 years, with anisometropic amblyopia were included in the study. Visual acuity in the amblyopic eye improved 1.90 (0.41–3.74) and 3.98 (2.22–5.11) lines at follow-up weeks 8 and 16, respectively. Both the total score and subscales of the questionnaire were reduced at the first follow-up and recovered at the second follow-up. Scores at week 16 were higher than those before treatment in the psychosocial aspect (<i>p</i> = 0.003), and lower in the visual function aspect (<i>p</i> < 0.001), without significant difference in total score (<i>p</i> = 0.207). Visual acuity in the amblyopic eye and psychosocial expectations for treatment were the most important factors that influenced HRQOL during treatment.</p> <p><i>Conclusions</i>: From the children’s perspective, the impacts on visual function and psychosocial aspect were significant in the first two months of treatment, and could be adapted during therapy for school-aged children. More attention should be paid to negative effects of treatment on daily life and study at the stage of amblyopia treatment for school-aged children. Meanwhile, necessary precautions should be taken to help reduce the impacts.</p

MOESM1 of Apelin-13/APJ system attenuates early brain injury via suppression of endoplasmic reticulum stress-associated TXNIP/NLRP3 inflammasome activation and oxidative stress in a AMPK-dependent manner after subarachnoid hemorrhage in rats

Additional file 1: Table S1 Study design and animal usage. Table S2. Rats physical data after surgeries. Figure S1. The ventral side was divided into six parts. SAH severity score: a grade from 0-3 is dependent on the amount of blood clot in each segment as follows: grade 0:no blood clot; 1: minimal blood clot; 2: moderate blood clot with recognizable arteries; 3: blood clot obliterating all arteries. The SAH grade was the total scores of the six parts, with minimal score of 0 and maximal score of 18. Figure S2. Effects of apelin-13 on brain edema: the quantification of brain water content of cerebellum and brain stem at 24 h after SAH. Figure S3. Depletion Efficiency of APJ siRNA with Naïve Rats. (A) Representative Western blot images. (B) Quantitative analyses of APJ. n=6 for each group. The bars represent the mean ± SD. *p<0.05 versus naïve

The literature search process.

<p>Flow diagram depicts the screening process of retrieved articles, including the reason for and number of exclusions. CFH = complement factor H; PCV = polypoidal choroidal vasculopathy.</p

Systematic Review and Meta-Analysis of the Association between Complement Factor H I62V Polymorphism and Risk of Polypoidal Choroidal Vasculopathy in Asian Populations

<div><p>Purpose</p><p>To investigate whether the polymorphism rs800292 (184G>A, I62V) in the complement factor H gene is associated with polypoidal choroidal vasculopathy (PCV) and the genetic difference between PCV and neovascular age-related macular degeneration (nAMD), in Asian populations.</p><p>Methods</p><p>A comprehensive literature search was performed in PubMed, Medline, Web of Science, and reference lists. A system review and meta-analysis of the association between I62V and PCV and/or nAMD were performed from 8 studies involving 5,062 subjects. The following data from individual studies were extracted and analyzed: 1) comparison of I62V polymorphisms between PCV and controls; 2) comparison of I62V polymorphisms between PCV and nAMD. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed-effects models. The Q-statistic test was used to assess heterogeneity, and Egger’s test was used to evaluate publication bias. Sensitivity analysis and cumulative meta-analysis were also performed.</p><p>Results</p><p>The I62V polymorphism showed a significant summary OR₁ for genotype GA+GG versus homozygous genotype AA was 3.18 (95% CI, 2.51–4.04, <i>P</i><<i>0.00001</i>), the OR₂ of heterozygous genotype GA versus AA was 2.29 (95% CI: 1.79–2.94, <i>P</i><<i>0.00001</i>), the OR₃ of homozygous genotype GG versus AA was 4.42 (95% CI: 3.45–5.67, <i>P</i><<i>0.00001</i>), and the OR₄ of allele G versus A was 2.04 (95% CI: 1.85–2.26, <i>P</i><<i>0.00001</i>). Sensitivity analysis indicated the robustness of our findings, and evidence of publication bias was not observed in our meta-analysis. Cumulative meta-analysis revealed that the summary ORs were stable. There was no significant difference in every genetic model between PCV and nAMD (n = 5, OR₁ = 0.92, OR₂ = 0.96, OR₃ = 0.90, OR₄ = 0.94).</p><p>Conclusions</p><p>Our analysis provides evidence that the I62V polymorphism is associated with an increased risk of PCV. The variant of I62V could be a promising genetic biomarker of PCV in Asian populations.</p></div

Cumulative meta-analysis of the association between I62V polymorphism and PCV.

<p>Every circle represents the pooled OR when studies accumulated over time, and the horizontal line represents the 95% confidence interval of pooled OR. A: OR₁(GG+GA vs AA); B: OR₂ (GA vs AA); C: OR₃ (GG vs AA); D: OR₄ (G vs A).</p

Results of Leave-One-Out Sensitivity Analysis.

<p>The horizontal axis shows the omitted study. The horizontal axis represents the odds ratio. Every circle indicates the pooled OR when the left study is omitted in this meta-analysis. The two ends of every broken line represent the respective 95% confidence interval. A: OR₁(GG+GA vs AA); B: OR₂ (GA vs AA); C: OR₃ (GG vs AA); D: OR₄ (G vs A).</p

Forest plots of meta-analysis of the association between I62V polymorphism and PCV.

<p>Odds ratios (black <i>squares)</i> and 95% confidence intervals (bars) are given for each study. Also shown are the <i>diamonds</i> of the summary ORs based on the Mantel–Haenszel fixed-effects model (M-H Overall). CI = confidence interval; OR = odds ratio. A: OR₁(GG+GA vs AA); B: OR₂ (GA vs AA); C: OR₃ (GG vs AA); D: OR₄ (G vs A).</p

Allele and Genotype Distribution of the I62V Polymorphism.

<p>HWE = HardyeWeinberg equilibrium; NA = not available; nAMD = neovascular age-related macular degeneration; PCV = polypoidal choroidal vasculopathy.</p

Main Characteristics of the Studies Included in the Meta-Analysis.

<p>NA = not available; nAMD = neovascular age-related macular degeneration; PCV = polypoidal choroidal vasculopathy.</p><p>*The number of cases or controls was changed in the next meta-analysis, but the reason was not given.</p