Objective To compare the effectiveness of platelet‐rich plasma (PRP), autologous blood (AB), and corticosteroid injections in patients with lateral epicondylitis. Type of Study Network meta‐analysis. Literature Survey Randomized controlled trials (RCTs) that compared any two forms of injections among PRP, AB, and corticosteroid for the treatment of lateral epicondylitis were searched from inception to 30 November 2018, on PubMed, Embase, and Cochrane library. Methodology Two researchers independently selected and assessed the quality of RCTs with the Cochrane Risk of Bias Tool. All relevant data from the included studies were extracted and heterogeneity was checked by Cochran's Q test and inconsistency statistic (I2). Publication bias was evaluated by constructing contour‐enhanced funnel plots. Stata 15 software was applied for pairwise meta‐analysis and network meta‐analysis. To explore the efficacy between different follow‐up periods, we considered the duration within 2 months to be short term, whereas 2 months or more was considered long term. Synthesis Twenty RCTs (n = 1271) were included in this network meta‐analysis. According to ranking probabilities, corticosteroid ranked first for visual analog score (VAS) (surface under the cumulative ranking [SUCRA] = 90.7), modified Nirschl score (82.9), maximum grip strength (69.5), modified Mayo score (MMS) (77.9), and Patient‐Related Tennis Elbow Evaluation (PRTEE) score (93.3) for the short‐term period. For the long‐term period, PRP ranked first for VAS (94.3), pressure pain threshold (99.8), Disabilities of Arm Shoulder and Hand (DASH) score (75.2), MMS (88.2), and the PRTEE score (81.8). Conclusion PRP was associated with more improvement in pain intensity and function in the long term than were the comparators. However, in the short term, corticosteroids were associated with the most improvement.

Central serous chorioretinopathy (CSC) is a vision‐threatening disease with no validated treatment and unclear pathogenesis. It is characterized by dilation and leakage of choroidal vasculature, resulting in the accumulation of subretinal fluid, and serous detachment of the neurosensory retina. Numerous studies have demonstrated that melatonin had multiple protective effects against endothelial dysfunction, vascular inflammation, and blood–retinal barrier (BRB) breakdown. However, the effect of melatonin on CSC, and its exact pathogenesis, is not well understood thus far. In this study, an experimental model was established by intravitreal injection of aldosterone in rats, which mimicked the features of CSC. Our results found that melatonin administration in advance significantly inhibited aldosterone‐induced choroidal thickening and vasodilation by reducing the expression of calcium‐activated potassium channel KCa2.3, and attenuated tortuosity of choroid vessels. Moreover, melatonin protected the BRB integrity and prevented the decrease in tight junction protein (ZO‐1, occludin, and claudin‐1) levels in the rat model induced by aldosterone. Additionally, the data also showed that intraperitoneal injection of melatonin in advance inhibited aldosterone‐induced macrophage/microglia infiltration, and remarkably diminished the levels of inflammatory cytokines (interleukin‐6 [IL‐6], IL‐1β, and cyclooxygenase‐2), chemokines (chemokine C–C motif ligand 3, and C–X–C motif ligand 1), and matrix metalloproteinases (MMP‐2 and MMP‐9). Luzindole, as the nonselective MT1 and MT2 antagonist, and 4‐phenyl‐2‐propionamidotetraline, as the selective MT2 antagonist, neutralized the melatonin‐induced inhibition of choroidal thickening and choroidal vasodilation, indicating that melatonin might exert the effects via binding to its receptors. Furthermore, the IL‐17A/nuclear factor‐κB signaling pathway was activated by intravitreal administration of aldosterone, while it was suppressed in melatonin‐treated in advance rat eyes. This study indicates that melatonin could serve as a promising safe therapeutic strategy for CSC patients.

Purpose This study aimed to investigate the age-dependent anti-angiogenic capability of melatonin in choroidal neovascularization (CNV) and to explore the underlying molecular mechanisms. Methods In the present study, a laser-induced CNV model was established in both young (three months of age) and old (18 months of age) mice, and the size of CNV lesions and vascular leakage was detected by morphological and imaging examination. Next, Western blot and immunostaining were used to observe the levels of M2 markers, senescence-related markers, and molecules involved in IL-10/STAT3 pathway. Additionally, colivelin was used to study the effect of IL-10/STAT3 pathway activation on the expression of M2 markers and senescence-related markers by Western blot and immunostaining. Finally, the effects of colivelin on melatonin-induced reduction of CNV size and vascular leakage in mice at different ages were assessed using morphological and imaging examination. Results Our results revealed that aging promoted M2 macrophage/microglia polarization, and aggravated CNV and vascular leakage. Melatonin significantly inhibited the M2 polarization of senescent macrophage/microglia and reduced the CNV area and vascular leakage. Moreover, melatonin markedly suppressed IL-10/STAT3 pathway activation in the macrophage/microglia of old mice, and STAT3 activator colivelin reversed the suppressive effect of melatonin on M2 polarization of senescent macrophage/microglia and laser-induced CNV in old mice. Conclusions Our data demonstrated that melatonin significantly prevented the M2 polarization of senescent macrophage/microglia by inhibiting the IL-10/STAT3 pathway, and eventually attenuated senescence-associated CNV. These findings suggested that melatonin could serve as a promising therapeutic agent to treat CNV and other age-related ocular diseases.

Purpose Strategies for neuroprotection are the main targets of glaucoma research. The neuroprotective properties of SRT2104 administration have been proven in central nervous system degeneration diseases through the activation of nicotinamide adenine dinucleotide-dependent deacetylase-silence information regulator 1 (Sirt1). Here, we investigated whether SRT2104 could protect the retina from ischemia/reperfusion (I/R) injury and the underlying mechanisms. Methods SRT2104 was intravitreally injected immediately after I/R induction. RNA and protein expression were detected by quantitative real-time PCR and Western blot. Protein expression and distribution were examined by immunofluorescence staining. Retinal structure and function were analyzed by hematoxylin and eosin staining, optical coherence tomography, and electroretinogram. Optic nerve axons were quantified using toluidine blue staining. Cellular apoptosis and senescence were evaluated by TUNEL assay and SA-β-gal staining. Results The protein expression of Sirt1 decreased dramatically after I/R injury and SRT2104 administration effectively enhanced the stability of Sirt1 protein without significantly influencing Sirt1 mRNA synthesis. SRT2104 administration alone exerted no influence on the structure and function of normal retinas. However, SRT2104 intervention significantly protected the inner retinal structure and neurons; partially restored retinal function after I/R injury. I/R-induced cellular apoptosis and senescence were effectively alleviated by SRT2104 administration. Additionally, SRT2104 intervention markedly reduced neuroinflammation, including reactive gliosis, retinal vascular inflammation, and the overexpression of pro-inflammatory cytokines after I/R injury. Mechanistically, I/R-induced acetylation of p53, NF-κB p65, and STAT3 was significantly reversed by SRT2104 intervention. Conclusions We demonstrated that SRT2104 exerted potent protective effects against I/R injury by enhancing Sirt1-mediated deacetylation and suppressing apoptosis, senescence, and neuroinflammation-related pathways.

Purpose KC7F2 is a novel molecule compound that can inhibit the translation of hypoxia-inducible factor 1α (HIF1α). It has been reported to exhibit potential antiangiogenic effect. We hypothesized that KC7F2 could inhibit oxygen-induced retinal neovascularization (RNV). The purpose of this study was to investigate this assumption. Methods Oxygen-induced retinopathy (OIR) models in C57BL/6J mice and Sprague-Dawley rats were used for in vivo study. After intraperitoneal injections of KC7F2, RNV was detected by immunofluorescence and hematoxylin and eosin staining. Retinal inflammation was explored by immunofluorescence. EdU incorporation assay, cell counting kit-8 assay, scratch test, transwell assay, and Matrigel assay were used to evaluate the effect of KC7F2 on the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVEC) induced by vascular endothelial growth factor (VEGF) in vitro. Protein expression was examined by Western blot. Results KC7F2 treatment (10 mg/kg/d) in OIR mice significantly attenuated pathological neovascularization and decreased the number of preretinal neovascular cell nuclei, without changing the avascular area, which showed the same trends in OIR rats. Consistently, after the KC7F2 intervention (10 µM), cell proliferation was inhibited in VEGF-induced HUVEC, which was in agreement with the trend observed in the retinas of OIR mice. Meanwhile, KC7F2 suppressed VEGF-induced HUVEC migration and tube formation, and decreased the density of leukocytes and microglia colocalizing neovascular areas in the retinas. Moreover, the HIF1α–VEGF pathway activated in retinas of OIR mice and hypoxia-induced HUVEC, was suppressed by KC7F2 treatment. Conclusions The current study revealed that KC7F2 was able to inhibit RNV effectively via HIF1α–VEGF pathway, suggesting that it might be an effective drug for RNV treatment.