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Apelin is a novel adipocytokine participating in diabetes, but its role in diabetic retinopathy (DR) is unknown. Our study aimed to investigate the effect of apelin on the proliferative potential in DR along with its antagonist inhibitory effects. Strong staining of apelin, co-localized with glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) was observed in the retina of diabetic rats. Apelin, GFAP, and VEGF mRNA and protein levels were significantly increased in the sample's retinas. Moreover, exogenous apelin promoted retinal Müller cell proliferation in vivo. Simultaneously, apelin induced GFAP and VEGF expression. F13A markedly reduced retinal gliosis caused by diabetes. Furthermore, F13A suppressed both GFAP and VEGF expression in vivo. Our results strongly suggest that apelin is associated with the development of DR and contributes to changes in the retinas of diabetic rats. Apelin induced promotion of cell proliferation lends support to the possibility that apelin may play a role in the progression of DR to a proliferative phase. This possible role deserves further investigation, which may offer new perspectives in the early prevention and treatment of DR.

Diabetic retinopathy (DR) is one of the most common causes of blindness globally. Proliferative DR (PDR), an advanced stage of DR, is characterized by the formation of fibrotic membranes at the vitreoretinal interface. The proliferation, migration, and secretion of extracellular matrix molecules in retinal pigment epithelial (RPE) cells contribute to the formation of fibrotic membranes in PDR. Gremlin has been reported to be upregulated in response to elevated glucose levels in the retina of diabetic rat and bovine pericytes. However, the role of gremlin in PDR remains unclear. In the present study, the vitreous concentrations of gremlin were significantly higher in the PDR (67.79±33.96) group than in the control (45.31±12.31) group, and high glucose levels induced the expression of gremlin in RPE cells. The elevated expression of extracellular matrix molecules, such as fibronectin and collagen IV, was significantly reduced by gremlin siRNA in human RPE cells under high-glucose conditions. Thus, gremlin may play a vital role in the development of PDR.

Diabetic macular edema is major cause of vision loss associated with diabetic retinopathy. Breakdown of blood-retinal barrier, especially inner BRB, is an early event in pathogenesis of DR. Apelin, an endogenous ligand of APJ, mediates angiogenesis and is involved in the development of DR. The present study aimed to investigate effects and mechanism of apelin-13 in vascular permeability during DME. We verified apelin-13 was upregulated in DME patients’ vitreous. High glucose incubation led to a progressive increase of apelin-13, APJ, cytoskeleton, and tight junction proteins, including VE-Cadherin, FAK, Src, ZO-1, and occludin. Apelin-13 promoted HRMEC proliferation and migration and phosphorylation of both cytoskeleton and tight junction under both normal and high glucose conditions. Besides, apelin-13 activated PI-3K/Akt and MAPK/Erk signaling pathways, including PLCγ1, p38, Akt, and Erk both in HRMEC and in C57BL/6 mice. Meanwhile, F13A performed opposite effects compared with apelin-13. In in vivo study, apelin-13 was also upregulated in retina of db/db mice. Taken together, apelin-13 increased biologic activity of HRMEC, as well as expression of both cytoskeleton and tight junction in DME via PI-3K/Akt and MAPK/Erk signaling pathways. Apelin-13 as an early promoter of vascular permeability may offer a new perspective strategy in early treatment of DR.

Uncoordinate-45B (UNC-45B) is a myosin chaperone in striated muscles. Heat shock leads to myosin denaturation, and UNC-45B is involved in myosin refolding. Pacific bluefin tuna (PBT) was chosen for this study because of its high value and severe “burnt meat” problem in summer. cDNA cloning and expression analysis were carried out to evaluate the heat stress response of PBT UNC-45B. The cDNA of PBT unc-45b was cloned, and two isoforms were detected successfully. Isoform 1 consisted of 2994 bp encoding 931 amino acids, and isoform 2 consisted of 3071 bp encoding 930 amino acids. To clarify the effects of heat stress on UNC-45B, cultured PBT were sampled in summer (29.2 °C) and winter (20.9 °C), and analyzed by qPCR and immunoblotting. Compared with winter, both transcriptional and translational expression of UNC-45B in summer were dramatically higher. In addition, from the mRNA expression results, we found that PBT UNC-45B isoform 2 mainly responded to heat stress. Our findings indicate that an increase in UNC-45B expression levels can sensitively reflect the heat stress response in PBT. Therefore, UNC-45B may be considered as a candidate biomarker to evaluate heat stress tolerance in PBT. This will improve aquaculture development by enabling the selection of heat stress-tolerant juveniles.

Modori-inducing proteinases (MIPs) in horse mackerel and the effect of sodium citrate on the modori phenomenon were investigated. Cysteine protease caused the modori phenomenon only at 60 ℃, while metalloproteinase caused it at both 60 ℃ and 70 ℃. Moreover, the autolysis of myofibrillar proteins was mainly inhibited by ethylene diamine tetra-acetic acid (EDTA), verifying the existence of insoluble metalloproteinase. From the results comparing thermal gel properties and protease activities, we confirmed that increased activity of insoluble metalloproteinase corresponded to the weakening of the thermal gel. Thus, insoluble metalloproteinase was the major MIP in horse mackerel. Moreover, sodium citrate could markedly inhibit insoluble metalloproteinase activity at 60 ℃. The addition of sodium citrate significantly improved the breaking force of the thermal gel at 60 ℃ and 70 ℃, suggesting that sodium citrate could suppress the modori phenomenon by inhibiting insoluble metalloproteinase. Therefore, it is desirable to use sodium citrate in horse mackerel surimi-based products to prevent the modori phenomenon.

Tangeretin, a natural compound extracted from citrus plants, has been reported to have antiproliferative, antidiabetic, anti-invasive, and antioxidant properties. However, the role of tangeretin in diabetic retinopathy (DR) is unknown. In the present study, we investigated whether tangeretin had any effect on the expression of interleukin 1 beta (IL-1β), interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-β1), and vascular endothelial growth factor (VEGF) in human retinal pigment epithelial (RPE) cells under high-glucose (HG) conditions. Our results illustrated that HG levels induced IL-1β, IL-6, TGF-β1, and VEGF expression and that tangeretin significantly reduced HG-induced IL-1β, IL-6, TGF-β1, and VEGF expression in human RPE cells. Moreover, tangeretin efficiently inhibited the activation of the protein kinase B (Akt) signalling pathway in HG-stimulated RPE cells. Therefore, tangeretin may serve a role in the treatment of DR.

Tangeretin, a natural compound extracted from citrus plants, has been reported to have antiproliferative, antidiabetic, anti-invasive, and antioxidant properties. However, the role of tangeretin in diabetic retinopathy (DR) is unknown. In the present study, we investigated whether tangeretin had any effect on the expression of interleukin 1 beta (IL-1 ), interleukin 6 (IL-6), transforming growth factor beta 1 (TGF- 1), and vascular endothelial growth factor (VEGF) in human retinal pigment epithelial (RPE) cells under high-glucose (HG) conditions. Our results illustrated that HG levels induced IL-1 , IL-6, TGF- 1, and VEGF expression and that tangeretin significantly reduced HG-induced IL-1 , IL-6, TGF- 1, and VEGF expression in human RPE cells. Moreover, tangeretin efficiently inhibited the activation of the protein kinase B (Akt) signalling pathway in HG-stimulated RPE cells. Therefore, tangeretin may serve a role in the treatment of DR.

We prepared solid dispersions (SDs) of tanshinone IIA (TSIIA) with silica nanoparticles, which function as dispersing carriers, using a spray-drying method and evaluated their in vitro dissolution and in vivo performance. The extent of TSIIA dissolution in the silica nanoparticles/TSIIA system (weight ratio, 5:1) was approximately 92% higher than that of the pure drug after 60 minutes. However, increasing the content of silica nanoparticles from 5:1 to 7:1 in this system did not significantly increase the rate or extent of TSIIA dissolution. The physicochemical properties of SDs were investigated using scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, and Fourier transforms infrared spectroscopy. Studying the stability of the SDs of TSIIA revealed that the drug content of the formulation and dissolution behavior was unchanged under the applied storage conditions. In vivo tests showed that SDs of the silica nanoparticles/TSIIA had a significantly larger area under the concentration-time curve, which was 1.27 times more than that of TSIIA (P < 0.01). Additionally, the values of maximum plasma concentration and the time to reach maximum plasma concentration of the SDs were higher than those of TSIIA and the physical mixing system. Based on these results, we conclude that the silica nanoparticle based SDs achieved complete dissolution, increased absorption rate, maintained drug stability, and showed improved oral bioavailability compared to TSIIA alone.

Background In Coats’ disease, the most recent development in the treatment has been the intravitreal injection of anti-VEGF agents. The purpose of this article was to evaluate the effect of intravitreal bevacizumab as the initial treatment for Coats’ disease in children and adults. Methods The study included 14 pediatric patients and five adult patients with Coats’ disease. They were treated with intravitreal bevacizumab (1.25 mg/0.05 ml) as the initial treatment, combined with or without other treatments. The analyses included the evaluation of basic clinical conditions. Results In the pediatric group, after a mean of 9.1 months of follow-up, the differences in visual acuity were significant for the comparisons between the baseline examination and the follow-up examinations carried out at weeks 6, 12, and 24 after the baseline ( P  = 0.006, P  = 0.004, P  = 0.005 respectively). Vitreoretinal fibrosis was observed in three patients ( n  = 3, 21.4 %), among whom two showed fibrosis before treatment. All of the pediatric patients showed a resolution of fluid and exudation, and regression of the telangiectasia. In the adult group, after a mean of 10.6 months of follow-up, the differences in visual acuity were not statistically significant ( P  > 0.05) between the baseline and follow-up examinations. Vitreoretinal fibrosis ( n  = 2, 40 %) was observed in two patients who both showed fibrosis before treatment. All of the adult patients showed a resolution of fluid and exudation, and regression of the telangiectasia. The differences in the change of BCVA between children and adults were not significant ( P  > 0.05) during the follow-up examinations. Conclusion The intravitreal injection of bevacizumab as the initial treatment is associated with a measurable gain in visual acuity in patients with Coats’ disease. Resolution of the subretinal fluid and exudation, and regression of the telangiectasia were observed in both pediatric and adult patients. Vitreoretinal fibrosis may be one of the natural courses of Coats’ disease, and it remains uncertain whether bevacizumab accelerates the fibrosis phenomenon.

Background Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT). Although much effort has been put into dealing with CMV retinitis secondary to acquired immunodeficiency syndrome (AIDS), the few reports which have been published have mainly focused on treatment of CMVR after HSCT. Methods This clinical interventional retrospective study included 14 patients (eight men; mean age 23.89 ± 12.09; 23 eyes) who suffered from CMV retinitis after stem-cell transplantation, in order to evaluate the efficacy and safety of multiple intravitreal injections of ganciclovir (IVG) for patients with CMV retinitis. All patients received 4 injections of IVG of 1 mg at 1 week intervals, and were followed up weekly for at least 2 months with measurement of best-corrected visual acuity (BCVA) and CMV levels in anterior aqueous humor with real-time polymerase chain reaction. Anterior aqueous humor was obtained before each injection. Results The levels of CMV in anterior aqueous humor showed significant decrease from (6.34 ± 15.78) × 10 5 copies/ml at baseline to (5.22 ± 12.15) × 10 3 copies/ml at 1 month ( P  < 0.001, Mann–Whitney U test). CMV couldn’t be detected in 11 eyes (47.8 %) after two injections, and this rose to 18 eyes (78.3 %) at 1 month. The mean logMAR BCVA was 0.659 ± 0.572 at baseline and 0.680 ± 0.527 at 2 months, which suggested no significant improvement ( P  = 0.736, Mann–Whitney U test) during the procedure. All patients experienced improved vitreous opacity and diminished area of the lesion under funduscopy after 4 injections of IVG. No severe complications developed. Conclusions Multiple IVG seemed to be beneficial for patients with CMV retinitis after stem-cell transplantation, in reducing CMV levels in aqueous humor. Further study to optimize the dose of ganciclovir is needed in order to achieve better treatment outcomes.