LIN28A attenuates high glucose-induced retinal pigmented epithelium injury through activating SIRT1-dependent autophagy.

AIM: To evaluate the effects of LIN28A (human) on high glucose-induced retinal pigmented epithelium (RPE) cell injury and its possible mechanism. METHODS: Diabetic retinopathy model was generated following 48h of exposure to 30 mmol/L high glucose (HG) in ARPE-19 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot tested the expression of the corresponding genes and proteins. Cell viability as well as apoptosis was determined through cell counting kit-8 (CCK-8) and flow cytometry assays. Immunofluorescence assay was adopted to evaluate autophagy activity. Caspase 3 activity, oxidative stress markers, and cytokines were appraised adopting their commercial kits, respectively. Finally, ARPE-19 cells were preincubated with EX527, a Sirtuin 1 (SIRT1) inhibitor, prior to HG stimulation to validate the regulatory mechanism. RESULTS: LIN28A was downregulated in HG-challenged ARPE-19 cells. LIN28A overexpression greatly inhibited HG-induced ARPE-19 cell viability loss, apoptosis, oxidative damage as well as inflammatory response. Meanwhile, the repressed autophagy and SIRT1 in ARPE-19 cells challenged with HG were elevated after LIN28A overexpression. In addition, treatment of EX527 greatly inhibited the activated autophagy following LIN28A overexpression and partly abolished the protective role of LIN28A against HG-elicited apoptosis, oxidative damage as well as inflammation in ARPE-19 cells. CONCLUSION: LIN28A exerts a protective role against HG-elicited RPE oxidative damage, inflammation, as well as apoptosis via regulating SIRT1/autophagy.

Efficacy and safety of single-dose intravitreal dexamethasone implant in non-infectious uveitic macular edema: A systematic review and meta-analysis.

Purpose: We conducted a systematic review and meta-analysis to investigate the efficacy and safety of single-dose intravitreal dexamethasone (DEX) implant for treating non-infectious uveitic macular edema (UME). Methods: Studies including clinical outcomes of the DEX implant in UME were comprehensively searched in PubMed, Embase, and Cochrane databases for potential studies from inception to July 2022. The primary outcomes were best corrected visual acuity (BCVA) and central macular thickness (CMT) during the follow-up period. Stata 12.0 was used to perform the statistical analyses. Results: Six retrospective studies and one prospective investigation involving 201 eyes were ultimately included. Significantly improved BCVA was observed from baseline to 1 month (WMD = -0.15, 95%CI = -0.24, -0.06), 3 months (WMD = -0.22, 95%CI = -0.29, -0.15), and 6 months (WMD = -0.24, 95%CI = -0.35, -0.13), after single-dose DEX implant. When considering CMT, macular thickness of 1 month (WMD = -179.77, 95%CI = -223.45, -136.09), 3 months (WMD = -179.13, 95%CI = -232.63, -125.63), and 6 months (WMD = -140.25, 95%CI = -227.61, -52.88) decreased in comparison with baseline, with statistical significance. Conclusion: Based on the current results, this meta-analysis confirmed favorable visual prognosis and anatomical improvement in patients with UME, after receiving the single-dose DEX implant. The most common adverse event is increased intraocular pressure, which could be controlled with topical medications.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022325969.

[Effects of environment and canopy structure on stem sap flow in a Larix principis-rupprechtii plantation.] / çŽ¯å¢ƒå’Œå† å±‚ç»“æž„å¯¹åŽåŒ—è½å¶æ¾æž—æ ‘å¹²æ¶²æµçš„å½±å“.

Accurately quantifying the impacts of environmental factors and canopy structure on stem sap flow is of great significance for deeply understanding water use strategies of trees in changing environment. The stem sap flow of Larix principis-rupprechtii plantation was observed using thermal diffusion probes from June to September of 2019 in the Xiangshuihe small watershed of Liupan Mountains, with the meteorological conditions, root-zone soil water content and canopy structure being simultaneously recorded. We first analyzed the relationships of sap flow rate (Jc) to potential evapotranspiration (PET), relative extract water (REW) and canopy leaf area index (LAI), and then quantified their relative contribution to Jc. The results showed that the response of Jc to PET, LAI, and REW conformed to binomial, linearly increase and saturated exponential function, respectively. The Jc model coupling multiple factors was established as a continuous multiplication of the response functions of Jc to PET, REW and LAI, which had good simulation precision. PET was the main factor leading to the difference of Jc in different weather conditions. The average contribution rate of PET had obvious difference in sunny (with a contribution rate of 40.3%), cloudy (4.3%), and rainy days (-26.3%). PET and LAI were the leading factors affecting the Jc variation among months. The ranges of the contribution rates of PET and LAI were from -23.1% to 16.8% and from -12.3% to 11.0%, respectively. The Jc model coupling the multi-factor effect developed in this study could be used to predict Jc, and quantify the impacts of each leading factor, which had the potential to be an effective tool to analyze the water use of trees in the changing environment.

Calcium mediates high glucose-induced HIF-1α and VEGF expression in cultured rat retinal Müller cells through CaMKII-CREB pathway.

AIM: To investigate the effects of high glucose (HG) medium on expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in cultured rat retinal Müller cells and to determine the signaling pathways mediating the effects. METHODS: Primary cultures of retinal Müller cells were prepared from Sprague-Dawley rats, and incubated in a medium containg HG (30 mmol/L) in the presence of the membrane-permeable Ca(2+) chelator BAPTA-AM (10 µmol/L) or the CaMKII inhibitor KN93 (10 µmol/L). The levels of CaMKII, p-CaMKII, CREB, p-CREB, HIF-1α, and VEGF proteins were measured with Western blotting, while HIF-1á and VEGF mRNA levels were determined using real-time RT-PCR. RESULTS: The stimulation of retinal Müller cell with HG for 24 h remarkably increased the expression levels of HIF-1α and VEGF. These responses were significantly inhibited in the presence of BAPTA-AM or KN93. Both BAPTA-AM and KN93 also significantly inhibited HG-induced phosphorylation of CaMKII and CREB in the cultured retinal Müller cells. Transfection of the cultured retinal Müller cells with antisense CREB oligonucleotide (300 nmol/L) was similarly effective in blocking the HG-induced increase of HIF-1α and VEGF. CONCLUSION: HG-induced HIF-1α and VEGF expression in cultured rat retinal Müller cells depends on intracellular free Ca(2+) and activation of CaMKII-CREB pathway. The activation of CaMKII-CREB pathway by HG may be a possible mechanism underlying the pathogenesis of diabetic retinopathy.

[The serum levels of cytokines in patients with rheumatoid arthritis associated interstitial lung disease and their clinical significance].

OBJECTIVE: To study the clinical significance of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases (TIMPs) and transforming growth factor beta 1 (TGF-beta1) in the serum of patients with rheumatoid arthritis (RA) associated interstitial lung disease (ILD). METHODS: Twenty-nine patients with RA only (the RA group) and 28 patients with RA associated ILD (the RA-ILD group) were included in the study. Patients in the RA-ILD group were divided into 2 subgroups, 16 in the early RA-ILD group and 12 in the late RA-ILD group. Twenty-nine healthy volunteers served as the control group. ELISA was used to detect the levels of MMP-9, TIMP-1, TGF-beta1 in the serum of the three groups. RESULTS: The TIMP-1 levels of both the RA and the RA-ILD groups [(645 +/- 220) microg/L, (536 +/- 188) microg/L] were significantly higher than that of the control group [(392 +/- 92) microg/L, F = 15.221, P < 0.01]. The TGF-beta1 level of the RA-ILD group [(13.1 +/- 10.0) microg/L] was significantly higher than those of the control group and the RA group [(3.9 +/- 2.9) microg/L, (2.4 +/- 1.7) microg/L, F = 26.455, P < 0.01]. There was no difference in the TIMP-1 level between RA-ILD and RA groups, the TGF-beta1 level between the control group and the RA group, the MMP-9 level and MMP-9/TIMP-1 ratio among the three groups. The TIMP-1 level in the late RA-ILD group [(690 +/- 110) microg/L] was higher than that of the early RA-ILD group [(420 +/- 147) microg/L, t = -5.347, P < 0.01]. The TGF-beta1 level in the late RA-ILD group [(17.9 +/- 8.2) microg/L] was higher than that of the early RA-ILD group [(9.5 +/- 9.9) microg/L, t = - 2.39, P < 0.05]. The MMP-9/TIMP-1 ratio of the late RA-ILD group (0.9 +/- 0.1) was lower than that of the early RA-ILD group (1.2 +/- 0.4, z = 4.307, P < 0.01). There was no statistic significance in the MMP-9 level between the early and the late RA-ILD groups [(537 +/- 309) microg/L, (595 +/- 110) microg/L, t = - 1.397, P = 0.174]. CONCLUSIONS: TGF-beta1, can be used as a diagnostic marker of ILD in RA patients and it also reflects the pathological change of the lung. The decrease of MMP-9/TIMP-1 ratio in RA patients with ILD can reflect the severity degree of lung pathological changes.