lncRNA HOTAIR promotes ROS generation and NLRP3 inflammasome activation by inhibiting Nrf2 in diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is a microvascular complication associated with damage to the retina due to inflammation induced by high glucose. Activation of the NLRP3 inflammasome plays a critical role in DR and its prevention is beneficial to patients. However, the regulation of long non-coding RNA (lncRNA) in NLRP3 inflammasome activation of DR is incompletely understood. So, this study aimed to uncover the functional and regulatory mechanism of the lncRNA HOTAIR in NLRP3 inflammasome activation in Dr. METHODS: The vitreous humor was collected from the patients and detected the inflammatory and oxidative stress makers. Human retinal endothelial cells (HRECs) were cultured and stimulated in low D-glucose (5 mmol/L) or high D-glucose (20 mmol/L). Additionally, HRECs were knocked down HOTAIR with a si-RNA. Then, the NLRP3 inflammasome activation was analyzed by western blotting and pyroptosis cell imaging. The ROS was measured by specific probe. The activation of Nrf2 measured by Immunofluorescent staining. The interaction between HOTAIR and Nrf2 was evaluated by co-immunoprecipitation and RNA immunoprecipitation. RESULTS: The expression of HOTAIR was significantly increased in the vitreous of patients with DR and in HRECs stimulated with high glucose. Furthermore, HOTAIR knockdown relieved NLRP3 inflammasome activation. More specifically, HOTAIR knockdown suppressed the expression of NLRP3, pro-caspase-1, and pro-IL-1ß, as well as IL-1ß maturation and pyroptosis. HOTAIR knockdown also interfered with the ROS generation induced by high glucose. Moreover, HOTAIR promoted the interaction between Nrf2 and Keap1 by binding and inactivating Nrf2. CONCLUSION: The lncRNA HOTAIR promotes NLRP3 inflammasome activation and ROS generation by inhibiting Nrf2 in Dr.

Effect of aromatherapy on quality of life in maintenance hemodialysis patients: a systematic review and meta-analysis.

Objective: Aromatherapy has been used for patients on maintenance hemodialysis (MHD), but the outcomes are still controversial. Thus, we conducted this study to systematically evaluate the effect of aromatherapy on the quality of life of patients on MHD.Methods: We searched the PubMed, Embays, Scopus, Web of Science, and CNKI databases for randomized controlled trials that evaluated the use of aromatherapy in dialysis patients and reported at least one outcome of interest.Results: Twenty-two relevant studies were included in the meta-analysis. The meta-analysis revealed that aromatherapy significantly increased subjective sleep quality (a lower score indicates better sleep quality) [standardized mean difference (SMD) = -1.52, 95% CI (-2.38, -0.67), p < 0.01] and reduced fatigue [SMD = -1.14, 95% CI (-1.95, -0.33), p = 0.01], anxiety [SMD = -1.38, 95% CI (-2.09, -0.67), p < 0.01], symptoms of restless legs syndrome [RLS; SMD = -1.71, 95% CI (-2.09, -1.33), p < 0.01], and arteriovenous fistula puncture pain [SMD= -1.56, 95% CI (-2.60, -0.52), p < 0.01].Conclusions: Aromatherapy may be used as a novel complementary and alternative therapy to improve sleep quality and reduce fatigue, anxiety, symptoms of RLS, and arteriovenous fistula puncture pain in patients on MHD.

Effect of Internal Limiting Membrane Peeling or Not on Blood Flow Signal in Macular Area of Diabetic Patients with Preretinal Membrane.

PURPOSE: To study the effect of intraoperative internal limiting membrane (ILM) peeling on the macular vascular structure in patients with diabetic epiretinal membrane (ERM). METHODS: Patients with diabetic ERM were divided into an ERM + ILM peeling group (18 eyes) and an ERM peeling group (19 eyes), all of whom underwent standard vitrectomy and were followed up until 6 months postoperatively. Best-corrected visual acuity (BCVA), Central macular thickness (CMT), Vessel density (VD) and vessel length density (VLD) of the superficial as well as deep retinal capillary plexus were compared between the two groups. RESULTS: There was no significant difference in BCVA (p = .188, .410, .901, .916) and CMT (p = .164, .128, .110, .105) between the two groups at the week 1, month 1, month 3 and month 6 after operation. In the superficial capillary plexus (SCP), the change in VD (p = .106) and VLD (p = .438) was not affected by ILM peeling, and there was no significant difference in VD (p = .154, .063, .100, .162) and VLD (p = .386, .263, .431, .391) between the two groups during the four follow-up after operation. For the deep capillary plexus (DCP), there was an effect of ILM peeling on the changes in VD (p = .024) and VLD (p = .012), ILM peeling delayed the recovery time of the VD and VLD; The VD (p = .026, .000, .003) and VLD (p = .005, .000, .000) of ERM + ILM peeling group were lower than those of ERM peeling group from the month 1 to the month 6 after operation. CONCLUSION: Intraoperative peeling of the ILM in patients with diabetic ERM delayed the improvement of blood flow signal in the DCP but did not affect the recovery of postoperative BCVA and CMT.

5-Nitro-2-(3-phenylpropylamino) Benzoic Acid Inhibits the Proliferation and Migration of Lens Epithelial Cells by Blocking CaMKII Signaling.

Posterior capsule opacification (PCO) is a post-surgery complication of cataract surgery, and lens epithelial cells (LECs) are involved in its development. A suppressive effect on LECs is exerted by the non specific chloride channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) exerts. Herein, the growth and migration inhibitory effects of NPPB on LECs were assessed, and the mechanism underlying the effects were investigated by focusing on Ca2+/CaMKII signaling. LECs were treated with different concentrations of NPPB, and the changes in cell viability, cell-cycle distribution, anchorage-dependent growth, migration, Ca2+ level, and CaMKII expression were evaluated. NPPB inhibited LECs' proliferation and induced G1 cell-cycle arrest in the cells. Regarding LECs' mobility, NPPB suppressed the cells' anchorage-dependent growth ability and inhibited their migration. Changes in cell phenotypes were associated with an increased intracellular Ca2+ level and down-regulation of CaMKII. Together these results confirmed the inhibitory effect of NPPB on the proliferation and migration of LECs, and the effect was shown to be associated with the induced level of Ca2+ and the inhibition of CaMKII signaling transduction.

Comparison of mortality and its causes in patients with complicated systemic lupus erythematosus on hemodialysis versus peritoneal dialysis: A meta-analysis.

BACKGROUND: Lupus nephritis is one of the most serious complications of systemic lupus erythematosus (SLE). Ten percent to 20% of patients with SLE progress to end-stage renal disease and would require renal replacement therapy or renal transplantation. In this analysis, we aimed to systematically compare mortality and the causes of mortality in patients with complicated SLE who were treated on hemodialysis (HD) versus peritoneal dialysis (PD). METHODS: Cochrane Central, Medical Literature Analysis and Retrieval System Online, Google Scholar, Web of Science, Excerpta Medica dataBASE, and http://www.ClinicalTrials.gov were searched for studies that compared HD versus PD in patients with SLE. The RevMan software version 5.4 (RevMan software, Cochrane Collaborations, United Kingdom) was used to analyze data. Heterogeneity was assessed using the Q and the I2 statistical tests. In this analysis, a random effects model was used during data assessment. Risk ratios (RRs) with 95% confidence intervals (CIs) were used to represent the results following analysis. RESULTS: A total number of 3405 SLE participants were included in this analysis, whereby 2841 were assigned to HD and 564 participants were assigned to PD. In patients with SLE who were on dialysis, our analysis showed that the risk of mortality was similar with HD and PD (RR, 0.69; 95% CI, 0.45-1.07; P = .10). When the cause of mortality was analyzed, cardiovascular death (RR, 0.63; 95% CI, 0.31-1.31; P = .22), death due to infection (RR, 0.74; 95% CI, 0.47-1.17; P = .20), death due to a respiratory cause (RR, 1.06; 95% CI, 0.18-6.21; P = .95), cause of death due to SLE flare up (RR, 2.54; 95% CI, 0.39-16.37; P = .33), and other causes of death (RR, 0.79; 95% CI, 0.35-1.77; P = .57) were not significantly different with HD and PD. CONCLUSION: This current analysis showed that in SLE patients who required dialysis, the risk of mortality between HD and PD was similar, and the causes of death including cardiovascular, infective, respiratory, SLE flare up, and other causes were not significantly different. Therefore, both dialysis methods were tolerable in these patients with SLE. Further studies with larger data would be required to confirm this hypothesis.

Association of Mineralocorticoid Receptor Antagonists With the Mortality and Cardiovascular Effects in Dialysis Patients: A Meta-analysis.

Whether Mineralocorticoid receptor antagonists (MRA) reduce mortality and cardiovascular effects of dialysis patients remains unclear. A meta-analysis was designed to investigate whether MRA reduce mortality and cardiovascular effects of dialysis patients, with a registration in INPLASY (INPLASY2020120143). The meta-analysis revealed that MRA significantly reduced all-cause mortality (ACM) and cardiovascular mortality (CVM). Patients receiving MRA presented improved left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF), decreased systolic blood pressure (SBP) and diastolic blood pressure (DBP). There was no significant difference in the serum potassium level between the MRA group and the placebo group. MRA vs. control exerts definite survival and cardiovascular benefits in dialysis patients, including reducing all-cause mortality and cardiovascular mortality, LVMI, and arterial blood pressure, and improving LVEF. In terms of safety, MRA did not increase serum potassium levels for dialysis patients with safety. Systematic Review Registration: (https://inplasy.com/inplasy-protocol-1239-2/), identifier (INPLASY2020120143).

lncNALT knockdown ameliorates hypertensive retinopathy via PTEN/PI3K/AKT pathway.

This study aimed to explore the role of the long non-coding RNA NOTCH1-associated lncRNA in T cell acute lymphoblastic leukemia (lncNALT) in the pathogenesis of hypertensive retinopathy (HR). LncNALT expression levels were determined using reverse transcription-quantitative polymerase chain reaction. The effects of lncNALT knockdown on the viability, proliferation, migration, and invasion of human retinal microvascular endothelial cells (RMECs) were determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, 5-ethynyl-2'-deoxyuridine staining, and Transwell assays. Protein expression levels were determined using western blotting. We found that lncNALT expression levels were increased in RMECs treated with hydrogen peroxide (H2O2), while the knockdown of lncNALT rescued the viability, proliferation, migration, and invasion of RMECs treated with H2O2. Moreover, lncNALT interacted with ELAV like RNA binding protein 1 to affect the phosphatase and tensin homolog (PTEN) expression. Knockdown of lncNALT enhanced the viability, proliferation, migration, and invasion of RMECs via the PTEN/phosphoinositide 3-kinase (PI3K)/serine-threonine kinase (AKT) pathway. Taken together, knockdown of lncNALT enhanced the viability, proliferation, migration, and invasion of RMECs via the PTEN/PI3K/AKT pathway, suggesting that lncNALT could be a potential therapeutic target for patients with HR.

lncNALT interacts with HuR to increase the stability and expression levels of the PTENlncNALT regulates HR via the PTEN/PI3K/AKT pathwaylncNALT may be a potential diagnostic biomarker for HR.

Diagnostic value of phospholipase A2 receptor in idiopathic membranous nephropathy: a systematic review and meta-analysis.

BACKGROUND: Detection of M-type phospholipase A2 receptor (PLA2R) can be used in serologic diagnosis of idiopathic membranous nephropathy (IMN), but there are limited data about the sensitivity and specificity of its diagnostic values. METHODS AND RESULTS: Meta-analysis of diagnostic test studies assessing the values of PLA2R in diagnosis of IMN. MEDLINE, EMBASE, and CENTRAL databases and congress abstracts were searched for studies reporting the value of PLA2R to predict IMN. The quality of the studies was evaluated using the guidelines of the updated Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The results are summarized as sensitivity, specificity, and diagnostic odds ratio (OR). Data from 10 studies involving 1,550 participants were analyzed. Across all settings, the diagnostic OR for serum anti-PLA2R level to predict IMN at different stages was 247.41, with sensitivity of 0.69 and specificity of 0.99. The estimated sensitivity and specificity of serum anti-PLA2R level for diagnosis of IMN in the active stage were 74.0 and 95.0%, respectively, with diagnostic OR of 54.22. The estimated sensitivity and specificity of biopsy anti-PLA2R for diagnosis of IMN at different stages was 73.0 and 83.0%, respectively, with diagnostic OR of 13.75. CONCLUSIONS: This meta-analysis shows that serum anti-PLA2R level is of diagnostic value for IMN in the active stage. Future large-cohort prospective studies are required to reveal the diagnostic value of circulating anti-PLA2R antibodies versus PLA2R antigens in kidney biopsy for IMN at different stages.

[Study on the differentially expressed microRNA of human retinal microvascular endothelial cells in high glucose environment by microRNA gene chip].

OBJECTIVES: To explore the differentially expressed microRNA (miRNA) of human retinal microvascular endothelial cell (HRCEC) in hyperglycemic environment by miRNA gene chip, then adopt bioinformatics methods to forecast target genes of part differentially expressed miRNA. METHODS: Experimental study. HRCEC were cultured. Took the 3-4 generation growth good cells and divided the cells into three groups: (1) normal control group: DMEM medium with 25 mmol/L glucose; (2) high glucose group: conditioned medium with 90 mmol/L glucose; (3) mannitol high permeability control group: conditioned medium with 65 mmol/L mannitol and 25 mmol/L glucose. Each group cells were cultured in the above conditions for five days, then used in situ cell death detection kit for apoptosis detection; the total RNA was isolated and examined; the differentially expressed miRNA were detected by miRNA gene chip, part results of miRNA array were verified by real-time quantitate polymerase chain reaction (PCR), potential miRNA targets were analyzed by bioinformatics methods. RESULTS: Observed apoptotic HRCEC by fluorescence microscope: the nucleus of normal control group and mannitol control group were dyed by DAPI and appeared blue fluorescence, but hadn't apoptosis fluorescent signals; the nucleus of high glucose group also appeared blue fluorescence, and had green apoptosis fluorescent signals. Quality testing of total RNA: with spectrophotometer measurement, the ratio of absorbance of total RNA in normal control group at A(260)/A(280) nm was 1.99, at A(260)/A(230) was 2.05;total RNA of high glucose group at A(260)/A(280) was 1.98, at A(260)/A(230) was 2.26. The results of formaldehyde degeneration agarose gel electrophoresis showed that the electrophoresis strips were clear and complete, indicated that the total RNA had better quality and high purity. Compared with normal control group, 49 miRNAs were found to be differentially expressed in high glucose group (fold change > 2 and fold change < 0.5), including 31 up-regulated miRNAs and 18 down-regulated miRNAs. The results of real-time quantity PCR revealed that hsa-miR-320c and hsa-miR-29a(*) were up-regulated in high glucose group, which were consistence with the miRNA gene chip. Furthermore, the target genes prediction of two above miRNAs were involved many growth factors and proteins. CONCLUSION: miRNA are differently expressed in HRCEC under hyperglycemic conditions.