Autoimmune Regulator Gene Polymorphisms and the Risk of Primary Immune Thrombocytopenic Purpura: A Case-Control Study.

This study aimed to assess the possible association between two single nucleotide polymorphisms (SNPs) of the autoimmune regulator (AIRE) gene (rs2075876 G/A and rs760426 A/G) with the risk of primary immune thrombocytopenia (ITP), as well as AIRE serum levels, in the Egyptian population. In this case-control study, 96 cases with primary ITP and 100 healthy subjects were included. Two SNPs of the AIRE gene (rs2075876 G/A and rs760426 A/G) were genotyped via Taqman allele discrimination real-time polymerase chain reaction (PCR). Additionally, serum AIRE levels were measured using the enzyme-linked immunosorbent assay (ELISA) technique. After adjusting for age, gender, and family history of ITP, the AIRE rs2075876 AA genotype and A allele were associated with increased ITP risk (adjusted odds ratio (aOR): 4.299, p = 0.008; aOR: 1.847, p = 0.004, respectively). Furthermore, there was no significant association between AIRE rs760426 A/G different genetic models and ITP risk. A linkage disequilibrium revealed that A-A haplotypes were associated with an increased ITP risk (aOR: 1.821, p = 0.020). Serum AIRE levels were found to be significantly lower in the ITP group, positively correlated with platelet counts, and were even lower in the AIRE rs2075876 AA genotype and A allele, as well as A-G and A-A haplotype carriers (all p < 0.001). The AIRE rs2075876 genetic variants (AA genotype and A allele) and A-A haplotype are associated with an increased ITP risk in the Egyptian population and lower serum AIRE levels, whereas the SNP rs760426 A/G is not.

The Prospective Ameliorative Role of Zinc Oxide Nanoparticles in STZ-Induced Diabetic Nephropathy in Rats: Mechanistic Targeting of Autophagy and Regulating Nrf2/TXNIP/NLRP3 Inflammasome Signaling.

Diabetic nephropathy (DN) as one of the common microvascular complications of diabetes mellitus, is the main cause of end-stage renal disease. Zinc oxide nanoparticles (ZnO NPs) have been employed in several biomedical aspects. This study purposed to explore the mechanistic renoprotective effects of ZnO NPs in STZ-induced DN. Sixty male Wistar rats were allocated into four equal groups: control, ZnO NPs control, STZ, and STZ + ZnO NPs groups. At the end of the experiment, blood and urine biochemical parameters were assayed. Renal tissue level of advanced glycation end products (AGEs) was assayed spectrofluorometrically, moreover, nuclear factor erythroid 2-related factor 2 (Nrf2) DNA-binding activity and IL-1ß levels were detected by ELISA. The gene expression levels of thioredoxin-interacting protein (TXNIP) and NOD-like receptor family pyrin domain containing 3 (NLRP3) were detected by quantitative real-time PCR. Oxidative stress markers were determined spectrophotometrically. Also, renal tissue histopathological and immunohistochemical analyses were determined. After 6 weeks of treatment, ZnO NPs markedly improved the biochemical, renal functions, and histopathological findings. Furthermore, ZnO NPs significantly increased Nrf2-DNA-binding activity and downregulated TXNIP gene expression leading to restoration of the redox status. Additionally, ZnO NPs ameliorated AGEs levels, enhanced autophagy activity, and attenuated inflammasome activation via downregulation of NLRP3 expression and reducing IL-1ß levels. Based on our results, we concluded that ZnO NPs can be considered as a promising agent for slowing the progression of DN via interplay between autophagy and Nrf2/TXNIP/NLRP3 inflammasome signaling.

Netrin-1 and clusterin: Innovative potential diagnostic biomarkers for early renal damage in ß-thalassemia major children.

BACKGROUND: Children with ß-thalassemia major (ß-TM) suffer from tubular dysfunction even before the onset of any renal impairment symptoms and/or clinical signs. Therefore, identifying innovative biomarkers allowing early renal damage detection has focused attention. AIM: This study aims to preliminary assess Netrin-1(NTN-1) and clusterin (CLU) in ß-TM children and explore their possible roles as surrogate noninvasive biomarkers of renal tubular dysfunction. SUBJECTS AND METHODS: In this study, 40 ß-TM children and 30 healthy children were enrolled. Routine serum and urinary biochemical variables were determined. Urinary NTN-1 and CLU levels were measured using ELISA and their mRNA expression in PBMCs were assayed using real-time PCR. Serum TNF-α, MDA levels and GST activity were measured. RESULTS: Urinary NTN-1 and CLU concentrations and mRNA relative expression levels in PBMCs were significantly increased in ß-TM children relative to controls. Oxidative stress and inflammatory markers revealed significant elevation in ß-TM children compared to controls. The change in these parameters correlated significantly with other renal parameters. ROC curves analysis showed that urinary NTN-1 and CLU levels are of promising diagnostic performance. CONCLUSION: Our results suggest that NTN-1 and CLU are qualified as new noninvasive biomarker panels for early detection of renal injury in ß-TM children. Moreover, urinary NTN-1 is recommended as a precise one during the clinical practices.

Interleukin-31 interaction with inflammasome: A promising diagnostic and prognostic panel for early sepsis identification in critically ill patients.

PURPOSE: This case-control study aimed to evaluate the ability to use a panel of IL-31, IL-1ß and NLRP3 to differentiate sepsis from systemic inflammatory response syndrome (SIRS) and to predict septic shock. METHODS: Serum levels of IL-31, IL-1ß and NLRP3 were measured by ELISA in 149 participants; 38 with sepsis, 51 with SIRS, 30 with septic shock and 30 healthy controls. RESULTS: Lower levels of IL-31 were found in sepsis (10.21 ± 4.34 pg/ml) compared to SIRS (16.74 ± 3.18 pg/ml) and to controls with the lowest levels detected in septic shock (6.26 ± 2.72 pg/ml). IL-1ß and NLRP3 levels were higher in sepsis (54.99 ± 14.11 pg/ml and 9.93 ± 2.38 ng/ml) compared to SIRS (27.8 ± 6.94 pg/ml and 4.86 ± 1.33 ng/ml) with the highest levels seen in septic shock (125.1 ± 32.79 pg/ml and 19.43 ± 6.48 ng/ml) respectively. IL-31 discriminated sepsis in patients showing SIRS with 80% sensitivity and 70% specificity and, identified septic shock with 78.6% sensitivity and 60.3% specificity. IL-1ß identified sepsis from SIRS with 93.3% and 83.3% specificity. NLRP3 discriminated sepsis from SIRS with 94.5% sensitivity and 93.3% specificity. And, with sensitivity 99.1% and 90.1% and specificity 98.9% and 80% IL-1ß and NLRP3 could respectively define septic shock. A panel of combined markers provided 100% sensitivity and specificity. The three biomarkers proved to be independent prognostic biomarkers. At 95% CI, IL-31 hazard ratio (HR) was 0.716, p = 0.001; IL-1ß HR was 1.023, p ≤ 0.001; and NLRP3 HR was 1.114, p ≤ 0.001. Additionally, IL-1ß proved to be an independent predictor of septic shock (ß = 0.355; p = 0.035). CONCLUSION: The cross-relation between IL-31, IL-1ß and NLRP3 in sepsis can provide a promising diagnostic and prognostic panel.