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Deterioration of the ecological environment in the upper and middle reaches of the Yellow River in China substantially impacts the growth and development of aquatic organisms in the drainage basin. This paper builds a conceptual model by applying flow components and fish ecological requirements relation with a relevant object of main fish in the upper and middle reaches of the Yellow River. The paper utilized the flow restoration method by employing the River2D model (two-dimensional model of river hydrodynamics and fish habitat), and a one-dimensional hydrodynamics HEC-RAS (hydrologic engineering center’s-river analysis system). The calculation result showed that the runoff condition required for Silurus lanzhouensis survival is that the monthly lowest flow in a year is 150 m3·s−1, and the lowest flow for suitable flow from April to October is 150 m3·s−1, and 300 m3·s−1 from November to March. The research result is closer to the actual condition and has more outstanding operability. Meanwhile, the results proposed the coupling method of ecological water requirement for the mainstream of the Yellow River. Moreover, the results portrayed the ecological flow process according to the upper envelope of minimum and maximum ecological water requirements of each fracture surface. It is regarded that the ecological flow process is deemed as the initial value of the reservoir regulation model.

BackgroundRecent studies have reported the effects of metabolic syndrome (MetS) and its components on atrial fibrillation (AF), but the results remain controversial. Therefore, we performed a meta-analysis to evaluate the relationship between MetS and AF risk.MethodsStudies were searched from the Cochrane library, PubMed, and Embase databases through May 2020. Adjusted hazard ratios (HRs) and its corresponding 95% confidence intervals (CIs) were extracted and then pooled by using a random effects model.ResultsA total of 6 observational cohort studies were finally included. In the pooled analysis, MetS was associated with an increased risk of AF (HR 1.57; 95% CI 1.40–1.77;P P P P P P = 0.82) was not.ConclusionsOur present meta-analysis suggested that MetS, as well as its components including abdominal obesity, elevated blood pressure, elevated fasting glucose and low HDL cholesterol were associated with an increase in the risk of AF.

Age-related macular degeneration (AMD) is a multifactor disease, which is primarily characterized by retinal pigment epithelium (RPE) cell loss. Since the retina is the most metabolically active tissue, RPE cells are exposed to consistent oxidative environment. So, oxidation-induced RPE cell death has long been considered a contributor to the onset of AMD. Here, we applied a retinal degeneration (RD) rat model induced by blue light-emitting diode (LED) and a cell model constructed by H2O2 stimulus to mimic the prooxidant environment of the retina. We detected that the expression of miR-27a was upregulated and the expression of FOXO1 was downregulated in both models. So, we furtherly investigated the role of miR-27a-FOXO1 axis in RPE in protesting against oxidants. Lentivirus-mediated RNA was injected intravitreally into rats to modulate the miR-27a-FOXO1 axis. Retinal function and histopathological changes were evaluated by electroretinography (ERG) analysis and hematoxylin and eosin (H&E) staining, respectively. Massive photoreceptor and RPE cell death were examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The damage to the retina was aggravated in the FOXO1 gene-knockdown and miR-27a-overexpression groups after exposure to LED but was alleviated in the FOXO1 gene-overexpression or miR-27a-knockdown groups. Dual luciferase assay was used to detect the binding site of miR-27a and FOXO1. Upregulated miR-27a inhibited the expression of FOXO1 by directly binding to the FOXO1 mRNA 3 ′ UTR and decreased the autophagy activity of ARPE-19 cells, resulting in the accumulation of reactive oxygen species (ROS) and decrease of cell viability. The results suggest that miR-27a is a negative regulator of FOXO1. Also, our data emphasize the prominent role of miR-27a/FOXO1 axis in modulating ROS accumulation and cell death in RPE cell model under oxidative stress and influencing the retinal function in the LED-induced RD rat model.

Purpose. To determine the effectiveness and safety of trabeculectomy along with amniotic membrane transplantation (AMT) for glaucoma. Methods. This systematic review was performed using RevMan 5.3. We searched PubMed, EMBASE, and the Cochrane Library and included studies published until September 2019. The treatment group included patients with AMT and trabeculectomy (group A), and the control group had only trabeculectomy (group B). We only included randomized controlled trials. The outcomes were intraocular pressure (IOP), complete success rate, number of antiglaucoma medications, and complications. Results. Five studies, including 174 eyes (87 eyes in the AMT group and 87 eyes in the control group), were eligible in this review. The parameters had no significant difference in heterogeneity between the AMT and control groups preoperatively. In the AMT group, the mean IOP was significantly lower at 3 and 12 months after operation (P P = 0.02, respectively), while the number of complete successes in the AMT group was significantly higher at 6 and 12 months (P = 0.02 and P = 0.003, respectively) compared with the control group. Complications, including a flat anterior chamber and hyphema, appeared to be decreased in the AMT group compared to the control group (P = 0.02 and P = 0.02, respectively). No differences were observed in the number of antiglaucoma medications, hypotony, encapsulated bleb, or choroidal detachment. Conclusion. Compared with only trabeculectomy, it is more efficient and safer to add AMT to trabeculectomy during glaucoma filtering surgery.

Age-related macular degeneration (AMD) is a leading cause of irreversible visual loss among elderly persons, of which wet AMD is characterized by choroidal neovascularization (CNV). We herein developed nanoparticles with good biosafety for effective treatment of choroidal neovascularization (CNV). S-PEG-ICG-RGD-RBZ NPs were synthesized and characterized by ZP, DLS, UV-Vis, TEM and Coomassie Brilliant Blue staining analyses. In our study, the S-PEG-ICG-RGD-RBZ NPs exhibited good biocompatibility in vitro and in vivo. There was no cellular toxicity, dead cells, apoptosis or genotoxicity in the studied concentration range in vitro; meanwhile, intravenous injection of the designed NPs did not cause histological damage or apoptosis in the organs in vivo, including the heart, liver, spleen, lung, kidneys and brain. The designed NPs inhibited VEGF-induced proliferation, cell migration, tube formation and expression of CD31 and VEGF in vitro. Meanwhile, in vivo studies also indicated the inhibition of CNV development by NPs. What's more, the CNV area was imaged after intravenous injection of NPs modified with indocyanine green. The NPs were mainly targeted to CNV areas and did not remain in the other organs. In summary, S-PEG modified with RGD was designed as a powerful carrier to deliver anti-VEGF agents to CNV areas. The smart NPs, which have good cellular compatibility, hold great potential for drug delivery in CNV treatment.

Single cell transcriptome sequencing has become extremely useful for cell typing. However, such differential expression data has shed little light on regulatory relationships among genes. Here, by examining pairwise correlations between mRNA levels of any two genes under steady-state conditions, we uncovered correlated gene modules (CGMs), clusters of intercorrelated genes that carry out certain biological functions together. We report a novel single-cell RNA-seq method called MALBAC-DT with higher detectability and accuracy, allowing determination of the covariance matrix of the expressed mRNAs for a homogenous cell population. We observed a prevalence of positive correlations between pairs of genes, with higher correlations corresponding to higher likelihoods of protein-protein interactions. Some CGMs, such as the p53 module in a cancer cell line, are cell type specific, while others, such as the protein synthesis CGM, are shared by different cell types. CGMs distinguished direct targets of p53 and exposed different modes of regulation of these genes in different cell types. Our covariance analyses of steady-state fluctuations provides a powerful way to advance our functional understanding of gene-to-gene interactions.

Background. Uveal melanoma (UM) is the most common primary intraocular tumor in adults and arises from the uvea. Marital status was a vital factor among physical conditions and social networks of cancer patients. Our study aimed to evaluate the impact of marital status on the outcomes among patients with UM. Methods. Patients with UM newly diagnosed from 2004 to 2015 were extracted, and the data were extracted from Surveillance, Epidemiology, and End Results (SEER) program. Overall survival (OS) was measured via the log-rank test, as well as cancer-specific survival (CSS) was also calculated via the same method. Cox proportional hazards models were applied to assess whether marital status was related to both OS and CSS. Furthermore, we performed subgroup analysis depending on different sexes and SEER stages. Results. In total, 4217 eligible patients were involved. Of these patients, 66.2% (n = 2793) were married, 14.6% (n = 615) were single, and 9.0% (n = 379) were divorced or separated, as well as widowed were 10.2% (n = 430). The 5-year OS of married, single, divorced or separated, and widowed patients was 74.0%, 72.8%, 68.6%, and 55.8%, respectively. The results indicating better OS and CSS occurred among married patients. Other factors such as sex, age at diagnosis, and SEER stage were also correlated with survival in UM patients. Furthermore, subgroup analyses were consistent with the results above. Conclusion. Marital status was proved to be an independent prognostic value for survival in UM patients. In addition, contrast to married patients, widowed individuals showed poor OS and CSS at different subgroup analyses.

Qingquan Wei,1,* Xiuwei Liang,2,* Ye Peng,3,* Donghui Yu,1 Ruiling Zhang,1 Huizi Jin,1 Jiaqi Fan,1 Wenting Cai,1 Chengda Ren,1 Jing Yu1,4 1Department of Ophthalmology, Shanghai Tenth People’s Hospital Affiliated with Tongji University, Shanghai, People’s Republic of China; 2Department of Ophthalmology, Nanchang University, Nanchang, People’s Republic of China; 3Department of Clinical Laboratory, Shanghai Tenth People’s Hospital Affiliated with Tongji University, Shanghai, People’s Republic of China; 4Department of Ophthalmology, Ninghai First Hospital, Zhejiang, People’s Republic of China *These authors contributed equally to this work Purpose: This study aimed to assess the effects of 17β-estradiol (βE2) on blue light-emitting diode (LED)-induced retinal degeneration (RD) in rats and hydrogen peroxide (H2O2)-induced retinal pigment epithelium cell injury in humans and elucidate the protective mechanism of βE2 underlying these processes.Methods: Female ovariectomized (OVX) rats were intravitreally injected with βE2 before blue LED exposure (3,000lux, 2hours). Retinal function and morphology were assayed via electroretinogram (ERG) and H&E, respectively. Cell viability was assayed using the Cell Counting Kit-8. Cell ROS were measured using dichlorofluorescein fluorescence. Apoptosis was evaluated by TUNEL and Annexin V/propidium iodide staining. Gene expression and protein expression were quantified using quantitative real-time RT-PCR, Western blotting, and immunohistochemistry. Autophagosomes were examined by electron microscopy.Results: Female OVX rats were exposed to blue LED, inducing RD. βE2 significantly prevented the reduction in the a- and b-wave ERG amplitudes and the disruption of retinal structure, the loss of photoreceptor cells, and the decrease in the thickness of the outer nuclear layer caused by blue LED exposure. βE2 also decreased cell apoptosis in the retina in blue LED-induced RD. Additionally, βE2 reduced ROS levels and apoptosis in H2O2-treated human retinal pigment epithelial (ARPE-19) cells. Furthermore, βE2 increased the protein expression of p-Akt and Bcl-2 and decreased the protein expression of cleaved caspase-3 and Bax during blue LED-induced retinal damage and in H2O2-treated ARPE-19 cells. βE2 also increased the number of autophagosomes and upregulated the expression of LC3-II/LC3-I and Beclin 1 in these processes.Conclusion: βE2 protects against blue LED-induced RD and H2O2-induced oxidative stress by acting as an antioxidant, and its protective mechanism might occur by reducing apoptosis and enhancing autophagy; βE2 may be a novel and effective therapy for age-related macular degeneration. Keywords: 17β-estradiol, hydrogen peroxide, retinal blue light-emitting diode degeneration, oxidative stress, apoptosis, autophagy

Bacterial keratitis (BK) is one of the most commonly leading causes of visual impairment and blindness worldwide, and suffers the risk of drug-resistant infections due to the abuse of antibiotics. Herein, we report a cationic diphenyl luminogen with aggregation-induced emission called IQ-Cm containing isoquinolinium and coumarin units for theranostic study of BK. IQ-Cm has no obvious cytotoxicity to mammalian cells below a certain concentration, and could preferentially bind to bacteria over mammalian cells. IQ-Cm can be used as a sensitive self-reporting probe to rapidly discriminate live and dead bacteria by the visual emission colors. The intrinsic dark toxicity to bacteria and generation of reactive oxygen species under light irradiation endow IQ-Cm with excellent antibacterial activity in vitro and in BK rabbit models infected with S. aureus . The present study provides a sensitive and efficient theranostic strategy for rapid discrimination of various bacterial states and the combined treatment of BK based on the intrinsic dark antibacterial activity and photodynamic therapy effect.

Background Individuals with diabetes have a high risk of cardiovascular disease (CVD). However, the association between type 1 diabetes mellitus (T1DM) and the risk of CVD has not been well addressed. This meta-analysis aimed to investigate the association between T1DM and CVD. Methods We searched the PubMed and EMBASE for studies that examined the association between T1DM and CVD until October 2020. We calculated the pooled risk ratios (RRs) with confidence intervals (CIs) from individual studies based on a random-effects model. Results We included 10 observational studies involving 166,027 patients with T1DM, and individuals were matched controls from the general population. Among T1DM patients, the RR of CVD was 5.09 (95% CI, 3.72–6.96), of coronary heart disease (CHD) was 9.38 (95% CI, 5.56–15.82), and of myocardial infarction was 6.37 (95% CI, 3.81–10.66). The RR of heart failure was 4.29 (95% CI, 3.54–5.19), of atrial fibrillation was 1.36 (95% CI, 1.17–1.59), and of stroke was 4.08 (95% CI, 3.42–4.86). Moreover, there was an increased RR among females for CHD, CVD, myocardial infarction, and stroke associated with T1DM. Conclusions This study suggests that T1DM is associated with an increased risk of several types of CVD. However, the possible mechanisms for the increased risk of CVD remain unclear.

Aim: To improve the retention of fluorescein sodium (FS) as a kind of clinical contrast agent for fundus fluorescein angiography (FFA). Materials & methods: Polyethyleneimine (PEI) was designed to synthesize PEI–NHAc–FS nanoparticles (NPs), and the formed NPs were characterized by both physicochemical properties and their effects on FFA. Results: Compared with free FS, PEI–NHAc–FS NPs showed similar optical performance, and could obviously reduce cellular adsorption and uptake both in vitro and in vivo, which could promote the metabolism of NPs in ocular blood vessels. Conclusion: PEI–NHAc–FS NPs represent a smart nanosize fluorescence contrast agent, which hold promising potential for clinical FFA diagnosis, therapy and research work.

Wenting Cai,1,* Donghui Yu,1,* Jiaqi Fan,2 Xiuwei Liang,3 Huizi Jin,1 Chang Liu,2 Meijiang Zhu,1 Tianyi Shen,1 Ruiling Zhang,1 Weinan Hu,4 Qingquan Wei,1 Jing Yu1,5 1Department of Ophthalmology, Shanghai Tenth People’s Hospital Affiliated with Tongji University, Shanghai, People’s Republic of China; 2Department of Ophthalmology, Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Ophthalmology, Nanchang University, Nanchang, People’s Republic of China; 4Department of Ophthalmology, Anhui University of Science and Technology, Huainan, People’s Republic of China; 5Department of Ophthalmology, Ninghai First Hospital, Zhejiang, People’s Republic of China *These authors contributed equally to this work Purpose: The purpose of this study was to evaluate the effect and mechanism of quercetin on TGF-β1-induced retinal pigment epithelial (RPE) cell proliferation, migration, and extracellular matrix secretion. Materials and methods: Cell counting kit-8, transwell, wound-healing assays, and ELISA were used to assess viability, migration, and collagen I secretion, respectively. Western blot analysis and qPCR were employed to detect mRNA and protein expression levels, respectively. Results: Quercetin suppressed TGF-β1-induced cell proliferation, migration, and collagen I secretion. The results also showed that mRNA and protein expression of epithelial–mesenchymal transition (EMT)-related markers such as alpha-smooth muscle actin and N-cadherin was downregulated by quercetin in TGF-β1-treated RPE cells; conversely, quercetin upregulated the expression of E-cadherin and tight junction protein 1 (ZO-1). In addition, quercetin could inhibit mRNA and protein expression of matrix metalloproteinases. Quercetin may reverse the progression of EMT via the Smad2/3 pathway. Conclusion: Our results demonstrate the protective effects of quercetin on RPE cell EMT, revealing a potential therapeutic agent for proliferative vitreoretinopathy treatment. Keywords: proliferative vitreoretinopathy, quercetin, epithelial–mesenchymal transition, transforming growth factor-β1

The aim of the present study was to investigate the effects of bradykinin (BK) on an epithelial-mesenchymal transition (EMT) model in retinal pigment epithelium (RPE) cells through exposure to transforming growth factor-β1 (TGF-β1). The aim was to improve the effect of BK on proliferative vitreoretinopathy (PVR) progression, and to find a novel method of clinical prevention and treatment for PVR. The morphology of ARPE-19 cells was observed using an inverted phase-contrast microscope. A Cell Counting Kit-8 was used to assess the effects of TGF-β1 on the proliferation of ARPE-19 cells. Western blotting and immunofluorescence were used to detect the expression levels of the epithelial marker E-cadherin, mesenchymal markers α-smooth muscle actin (SMA) and vimentin, and phosphorylated (p) mothers against decapentaplegic homolog (Smad)3 and Smad7 of the TGF/Smad signaling pathway. Wound healing tests and Transwell assays were performed to detect cell migration ability. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was performed to detect the expression levels of pSmad3 and Smad7 in the TGF/Smad signaling pathway. The results revealed that the addition of 10 ng/ml TGF-β1 resulted in the expression of factors associated with EMT in ARPE-19 cells. BK decreased the expression levels of the mesenchymal markers α-SMA and vimentin, and increased the expression of the epithelial marker E-cadherin. BK decreased cell migration in TGF-β1-induced EMT. These effects were reversed by HOE-140, a specific BK 2 receptor antagonist. BK significantly downregulated the expression of pSmad3 and upregulated the expression of Smad7 in TGF-β1-treated ARPE-19 cells, and the protective alterations produced by BK were inhibited by HOE-140. In conclusion, 10 ng/ml TGF-β1 resulted in EMT in ARPE-19 cells and BK served a negative role in TGF-β1-induced EMT. BK had effects in TGF-β1-induced EMT by upregulating the expression of Smad7 and downregulating the expression of pSmad3 in TGF-β/Smad signaling pathway, indicating that BK may be a novel and effective therapy for PVR.

The purpose of this meta-analysis was to compare the efficacy and safety of the combination of bevacizumab and photodynamic therapy (PDT) with bevacizumab monotherapy for the treatment of age-related macular degeneration (AMD). Patients with active choroidal neovascularization (CNV) secondary to AMD were included in the present study. The treatment group included patients treated with a combination of bevacizumab and PDT and patients treated with bevacizumab monotherapy. Only randomized controlled trials (RCTs) were included in the analysis. The PubMed, EMBASE and Cochrane Central Register of Controlled Trials databases were searched. Meta-analysis was performed using RevMan v.5.3 software, and best-corrected visual acuity (BCVA), central retinal thickness (CRT) and the average number of bevacizumab retreatments were assessed. A total of 5 RCTs were included in the analysis. There were no significant differences observed in the mean BCVA change between the combination treatment group and the bevacizumab monotherapy group [standard mean difference 0.20; 95% confidence interval (CI) −0.53, 0.93, P=0.59]. There were also no significant differences in the CRT increases between the two groups [weighted mean difference (WMD) −22.16, 95% CI −52.01 to 7.69, P=0.15]. No significant differences were observed in the proportions of patients gaining >15 letters between the two groups [risk ratio (RR) 0.86, 95% CI 0.64, 1.15, P=0.30]. However, the average number of the ranibizumab retreatments was significantly lower in the combination treatment group compared with the bevacizumab monotherapy group (WMD, −2.70, 95% CI −3.93 to −1.46; P15 letters, or the incidences of ocular adverse events and systemic adverse events. However, combination treatment may significantly reduce the average number of bevacizumab retreatments compared with monotherapy.

Aim To assess the corneal sensitivity and the incidences of dry eye after small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK). Methods The Meta-analysis was performed using RevMan 5.3. We searched on PubMed from inception to March 2016. Summary weighted mean difference (WMD) and 95% confidence intervals (CIs) were used to analyze the datum. Random-effects or fixed-effects models were chosen up to between-study heterogeneity. The main outcomes were composed of the Ocular Surface Disease Index (OSDI) scores, tear film break-up time (TBUT), Schirmer Test and corneal sensitivity. Results Eight eligible studies including 772 eyes (386 in SMILE group and 386 in FS-LASIK group) were identified. The parameters have no significiant difference heterogeneity between SMILE and FS-LASIK group preoperatively. There were significant differences between the two groups in OSDI scores at one and three months postoperatively, in TBUT at one and three months postoperatively, in corneal sensitivity at one week, about one month and three months postoperatively. However, there was no significant difference observed in Schirmer Test at the follow-up periods. Conclusion Compare to FS-LASIK, dry eye and the corneal sensitivity recover better in the SMILE group, in first three months after the surgery.

Qingyu Liu,1,* Junling Liu,1,* Chengda Ren,1 Wenting Cai,1 Qingquan Wei,2 Yi Song,3 Jing Yu1 1Department of Ophthalmology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 2Department of Ophthalmology, Nanchang University, Nanchang, 3Department ofOphthalmology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’sRepublic of China *These authors contributed equally to this work Background: The purpose of this study was to investigate whether acupuncture is effective at treatingdry eye disease among postmenopausal women and to identify the possible mechanisms. Methods: Twenty-eight postmenopausal women with dry eye disease were randomly divided into two groups: an acupuncture plus artificial tears (AC + AT) group and an artificial tears (AT) only group. After baseline examination of clinical parameters and tear sample collection, each patient received the designated modality of topical therapy for 2 months. Posttreatment documentation of clinical parameters was recorded, and tear samples were collected. Tear samples from the AC + AT group were subjected to two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry (2D nano-LC-MS/MS). Western blot analysis was also performed on tear samples from both groups. Results: After treatment, the Ocular Surface Disease Index scores, symptom assessment scores, scores of sign assessment, and tear break-up time were significantly improved in both groups (P=0.000). Symptom assessment scores were significantly improved in the AC + AT group (P=0.000) compared with the AT group. 2D nano-LC-MS/MS identified 2,411 proteins, among which 142 were downregulated and 169 were upregulated. After combined AC + AT treatment, the abundance of secreted proteins was increased, whereas that of cytoplasmic proteins decreased (Pearson’s χ2 test, P=0.000, P=0.000, respectively). Proteins involved in immunity and regulation were also more abundant (Pearson’s χ2 test, P=0.040, P=0.016, respectively), while components and proliferation-related proteins were downregulated (Pearson’s χ2 test, P=0.003, P=0.011, respectively). Conclusion: AC + AT treatment increased protein synthesis and secretion, and improved clinical symptoms. These results indicate that acupuncture may be a complimentary therapy for treating postmenopausal dry eye disease. Keywords: acupuncture, menopausal dry eye, proteomics

The aims of this study were to evaluate the effects of CM082 on the development of choroidal neovascularization (CNV) in a laser-induced CNV rat model and to determine the drug concentration in the ocular tissues. After the laser-induced CNV model was established in rats, CM082 was orally administered. The effects of CM082 on the CNV lesions were assessed using fundus fluorescein angiography (FFA), CNV histology, and retinal pigment epithelium- (RPE-) choroid-sclera eyecup analysis. The concentrations of CM082 in the plasma and eye tissues were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results of FFA, histology, and RPE-choroid-sclera eyecup analysis demonstrated that the CM082-treated (10 mg/kg/d or 30 mg/kg/d) rats exhibited significantly less neovascularization than did the control group. The total concentration of CM082 in the eyes (172.86 ± 57.11 ng/g) was similar to that in the plasma (196.87 ± 73.13 ng/ml). Within the eye, the concentrations of CM082 and its metabolites were highest in the retina-sclera. The orally administered CM082 thus effectively passed through the blood-retina barrier (BRB) to reach the retina in the Brown Norway rats. Therefore, at both 10 mg/kg/d and 30 mg/kg/d, CM082 was able to reduce CNV lesions in the laser-induced CNV rat model.

Backgroud: Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness of the elder people. This research was intended to demonstrate the different expression of microRNAs (miRNA) in AMD patients and whether they can be used as biomarkers for AMD. Methods: MiRNAs expression was measured by microarray of 6 AMD cases and 6 gender matched controls. In a larger-sample case-control study with 126 AMD cases and 140 controls, whole blood samples were detected for the differences of miRNA expression. Results: A total of 216 differentially expressed miRNAs (111 increased and 105 decreased miRNAs) were detected from circulating miRNA microarray. Expanded case-control study results showed that the expression of miR-27a-3p, miR-29b-3p and miR-195-5p was increased significantly. Moreover, the level of miR-27a is higher in patients with wet AMD compared to patients with dry AMD. All 3 miRNAs showed a potential diagnostic value for AMD. Conclusion: Circulating miRNA levels were significantly varied in AMD patients. Three miRNAs, miR-27a-3p, miR-29b-3p and the miR-195-5p, might be potential diagnostic biomarkers for AMD.

Monocrotophos (MCP) is listed as a Prior Informed Consent chemical, and it is still used extensively in developing countries. It has been seen that MCP shows high toxicity in fish and aquatic ecosystems. To confirm whether MCP shows estrogenic effects on fish, the induction of vitellogenin (VTG) in male goldfish (Carassius auratus) following a 21 day exposure to 0.01, 0.10 and 1.00 mg x L(-1) 40% MCP pesticide in a semi-static exposure system was evaluated by hepatic mRNA and plasma protein. Real-time reverse transcriptase polymerase chain reaction assay showed that MCP significantly increased hepatic mRNA expression of VTG in male goldfish in a dose-dependent manner. Western blot analysis revealed the presence of two VTG subunits with molecular masses of 134 kDa and 110 kDa in the plasma of the exposure groups, which were not observed in that of the control males, indicating the induction of VTG protein synthesis and secretion by MCP in male goldfish. Furthermore, the levels of plasma VTG protein in the control group and the 0.01, 0.10 and 1.00 mg x L(-1) 40% MCP pesticide exposure groups were quantified by enzyme-linked immunoassay, and revealed concentrations of 53.8+/-5.6 ng x mL(-1), 285.5+/-5.0 ng x mL(-1), 972.9+/-7.4 ng x mL(-1) and 678.4+/-38.0 ng x mL(-1), respectively. The overlapping results of VTG mRNA and protein indicated that MCP had significant estrogenic properties and was thus a potential endocrine disruptor.

Myelinated Schwann cells in the peripheral nervous system express the p75 nerve growth factor receptor (p75NGFR) as a consequence of Schwann cell dedifferentiation during Wallerian degeneration. p75NGFR has been implicated in the remyelination of regenerating nerves. Although many studies have shown various mechanisms underlying Schwann cell dedifferentiation, the molecular mechanism contributing to the re-expression of p75NGFR in differentiated Schwann cells is largely unknown. In the present study, we found that lysosomes were transiently activated in Schwann cells after nerve injury and that the inhibition of lysosomal activation by chloroquine or lysosomal acidification inhibitors prevented p75NGFR expression at the mRNA transcriptional level in an ex vivo Wallerian degeneration model. Lysosomal acidification inhibitors suppressed demyelination, but not axonal degeneration, thereby suggesting that demyelination mediated by lysosomes may be an important signal for inducing p75NGFR expression. Tumor necrosis factor-α (TNF-α) has been suggested to be involved in regulating p75NGFR expression in Schwann cells. In this study, we found that removing TNF-α in vivo did not significantly suppress the induction of both lysosomes and p75NGFR. Thus, these findings suggest that lysosomal activation is tightly correlated with the induction of p75NGFR in demyelinating Schwann cells during Wallerian degeneration.

Background To evaluate the effect of bradykinin (BK) on TGF-β1-induced retinal pigment epithelial (RPE) cell proliferation and extracellular matrix secretion and to elucidate the relationship between BK and the Erk/Akt signaling pathway. Methods The effects of BK on TGF-β1-induced RPE cell proliferation were examined via CCK-8 assay. Cell culture supernatant collagen I concentrations were measured via ELISA. Fibronectin (Fn), matrix metalloproteinase-2 (MMP-2) and MMP-9 mRNA and protein expression levels were measured via q-PCR and Western blotting, respectively. Changes in Akt/Erk phosphorylation induced by BK and HOE-140 were evaluated via Western blotting. Results TGF-β1 stimulated ARPE-19 cell proliferation, which was inhibited by BK, whose effects were inhibited by HOE-140. BK inhibited TGF-β1-induced collagen I, Fn and MMP-2 secretion in RPE cells, and these effects were inhibited by HOE-140. BK also inhibited TGF-β1-induced Akt phosphorylation in RPE cells, and these effects were blocked by HOE-140. BK had no significant effect on Erk-mediated signaling. Conclusions The findings from this study indicate that BK could be novel therapeutic targets for the treatment of PVR.