High Temperatures and Kidney Disease Morbidity: A Systematic Review and Meta-analysis

Objectives In recent years, serious concerns have been raised regarding the impacts of rising temperatures on health. The present study was conducted to investigate the relationship between elevated temperatures and kidney disease through a systematic review and meta-analysis. Methods In October 2017, 2 researchers independently searched related studies in PubMed and Embase. A meta-analysis was conducted using a random-effects model, including only studies that presented odds ratios, relative risks, or percentage changes, along with 95% confidence intervals (CIs). The characteristics of each study were summarized, and the Egger test and funnel plots were used to evaluate publication bias. Results Eleven studies that met the criteria were included in the final analysis. The pooled results suggest an increase of 30% (95% CI, 20 to 40) in kidney disease morbidity with high temperatures. In a disease-specific subgroup analysis, statistically significant results were observed for both renal colic or kidney stones and other renal diseases. In a study design–specific subgroup analysis, statistically significant results were observed in both time-series analyses and studies with other designs. In a temperature measure–specific subgroup analysis, significant results were likewise found for both studies using mean temperature measurements and studies measuring heat waves or heat stress. Conclusions Our results indicate that morbidity due to kidney disease increases at high temperatures. We also found significant results in subgroup analyses. However, further time-series analyses are needed to obtain more generalizable evidence

Soluble Epoxide Hydrolase Activity Determines the Severity of Ischemia-Reperfusion Injury in Kidney

Soluble epoxide hydrolase (sEH) in endothelial cells determines the plasma concentrations of epoxyeicosatrienoic acids (EETs), which may act as vasoactive agents to control vascular tone. We hypothesized that the regulation of sEH activity may have a therapeutic value in preventing acute kidney injury by controlling the concentration of EETs. In this study, we therefore induced ischemia-reperfusion injury (IRI) in C57BL/6 mice and controlled sEH activity by intraperitoneal administration of the sEH inhibitor 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA). The deterioration of kidney function induced by IRI was partially moderated and prevented by AUDA treatment. In addition, AUDA treatment significantly attenuated tubular necrosis induced by IRI. Ischemic injury induced the down-regulation of sEH, and AUDA administration had no effect on the expression pattern of sEH induced by IRI. In vivo sEH activity was assessed by measuring the substrate epoxyoctadecenoic acid (EpOME) and its metabolite dihydroxyoctadec-12-enoic acid (DHOME). Ischemic injury had no effects on the plasma concentrations of EpOME and DHOME, but inhibition of sEH by AUDA significantly increased plasma EpOME and the EpOME/DHOME ratio. The protective effect of the sEH inhibitor was achieved by suppression of proinflammatory cytokines and up-regulation of regulatory cytokines. AUDA treatment prevented the intrarenal infiltration of inflammatory cells, but promoted endothelial cell migration and neovascularization. The results of this study suggest that treatment with sEH inhibitors can reduce acute kidney injury

Functional and structural characteristics of anticancer peptide Pep27 analogues

BACKGROUND: A secreted peptide Pep27 initiates the cell death program in S. pneumoniae through signal transduction. This study was undertaken to evaluate the relation between the structure and cytotoxic activity of Pep27 and its analogues on cancer cells. RESULTS: Pep27anal2 characterized substituting ((2)R→W), ((4)E→W), ((11)S→W) and ((13)Q→W) in native Pep27, exhibited greater hydrophobicity and anticancer activity than Pep27 and other analogues. The IC(50 )values of Pep27anal2 were approximately 10 – 30 μM in a number of cell lines (AML-2, HL-60, Jurkat, MCF-7 and SNU-601). Confocal microscopy showed that Pep27anal2-FITC was localized in the plasma membrane, and then moving from the membrane to subcellular compartments with the initiation of membrane blebbing. Flow cytometric analysis using propidium iodide and Annexin V also revealed that Pep27anal2 induced apoptosis with minor membrane damage. Electron microscopy revealed that Pep27 induced apoptosis in Jurkat cells. The anticancer activity of Pep27anal2 was neither abrogated by pan-caspase inhibitor (Z-VAD-fmk) nor related to cytochrome c release from mitochondria. The 3D solution structures of these two Pep27 peptides revealed that both form a random coil conformation in water; however, they adopted stable α-helical conformations in solutions. CONCLUSION: The results indicate that Pep27anal2 can penetrate the plasma membrane, and then induce apoptosis in both caspase-and cytochrome c-independent manner. The hydrophobicity of Pep27anal2 appears to play an important role in membrane permeabilization and/or anticancer properties. The structure-functional relationships of these peptides are also discussed. It is proposed that Pep27anal2 is a potential candidate for anticancer therapeutic agents

Respiratory viral infections and the risk of rheumatoid arthritis

Background We aimed to investigate the effects of ambient respiratory viral infections in the general population on rheumatoid arthritis (RA) development. Methods Data of weekly incident RA (2012–2013) were obtained from the Korean National Health Insurance claims database, and those of weekly observations on eight respiratory viral infections were obtained from the Korea Centers for Disease Control and Prevention database. We estimated the percentage change in incident RA associated with ambient mean respiratory viral infections using a generalized linear model, after adjusting for time trend, air pollution, and meteorological data. Results A total of 24,117 cases of incident RA (mean age 54.7 years, 18,688 [77.5%] women) were analyzed. Ambient respiratory viral infections in the population were associated with a higher number of incident RA over time, and its effect peaked 6 or 7 weeks after exposure. Among the 8 viruses, parainfluenza virus (4.8% for 1% respiratory viral infection increase, 95% CI 1.6 to 8.1, P = .003), coronavirus (9.2%, 3.9 to 14.8, P < .001), and metapneumovirus (44%, 2.0 to 103.4, P = .038) were associated with increased number of incident RA. The impact of these respiratory viral infections remained significant in women (3.8%, 12.1%, and 67.4%, respectively, P < .05) and in older patients (10.7%, 14.6%, and 118.2%, respectively, P < .05). Conclusions Ambient respiratory viral infections in the population were associated with an increased number of incident RA, especially in women and older patients, suggesting that respiratory viral infections can be a novel environmental risk factor for the development of RA

Canine adipose tissue-derived MSCs engineered with mRNA to overexpress TSG-6 and enhance the anti-inflammatory effects in canine macrophages

BackgroundMesenchymal stem cells (MSCs) are useful agents in the treatment of various inflammatory diseases. The immunomodulatory effects of MSCs are largely related to their secretory properties. mRNA engineering emerged as a safe alternative to enhance the secretory function of MSCs. Optimization of the untranslated region (UTR) sequence is important for enhancing the translational efficiency of exogenous mRNAs. However, research on the optimization of UTR in canine MSCs has not yet been conducted.ObjectivesWe aimed to identify the UTR sequence related to the expression efficiency of in vitro transcription (IVT) mRNA in canine MSCs and investigate whether mRNA-engineered MSCs that overexpress TSG-6 exhibit enhanced anti-inflammatory effects.MethodsCanine adipose tissue-derived (cAT)-MSCs were transfected with green fluorescence protein (GFP) mRNA with three different UTRs: canine hemoglobin subunit alpha-like 1 (HBA1), HBA2, and hemoglobin subunit beta-like (HBB). The translation efficacy of each mRNA was evaluated using relative fluorescence. TSG-6 mRNA was produced with the UTR optimized according to relative fluorescence results. cAT-MSCs were transfected with TSG-6 mRNA (MSCTSG-6), and TSG-6 expression was analyzed using real-time quantitative PCR, ELISA, and western blotting. To evaluate the anti-inflammatory effects of MSCsTSG-6, DH82 cells were co-cultured with MSCsTSG-6 or treated with dexamethasone, and changes in the expression of inflammatory cytokines were analyzed using qPCR.ResultsThe highest fluorescence level was observed in the HBA1 UTR at 24 h post-transfection. TSG-6 mRNA transfection yielded high levels of TSG-6 in the cAT-MSCs. In DH82 cells co-cultured with MSCsTSG-6, the expression of inflammatory cytokines decreased compared to that in co-culturing with naïve MSCs and dexamethasone treatment.ConclusionsOptimization of the HBA1 UTR improved the translation efficiency of IVT mRNA in canine MSCs. cAT-MSCs engineered with TSG-6 mRNA effectively enhanced the anti-inflammatory effects of the MSCs when co-cultured with LPS-activated DH82 cells