Autophagy is necessary for neuronal homeostasis and its dysfunction has been implicated in Parkinson's disease (PD) as it can exacerbate endoplasmic reticulum (ER) stress and ER stress-induced apoptosis. Quercetin is a flavonoid known for its neuroprotective and antioxidant effects. The present study investigated the protective, autophagy-modulating effects of quercetin in the rotenone rat model of PD. Rotenone was intraperitoneally injected at dose of 2 ml/kg/day for 4 weeks. Simultaneous intraperitoneal injection of quercetin was given at a dose of 50 mg/kg/day also for 4 weeks. Neurobehavioral changes were studied. Oxidative/antioxidant status, C/EBP homologous protein (CHOP), Beclin-1, and dopamine levels were assessed. DNA fragmentation and histopathological changes were evaluated. This research work revealed that quercetin significantly attenuated rotenone-induced behavioral impairment, augmented autophagy, ameliorated ER stress- induced apoptosis with attenuated oxidative stress. From the current study, quercetin can act as an autophagy enhancer in PD rat model and modulates the microenvironment that leads to neuronal death.

AimThe aim of this study was to investigate the status and effects of vitamin D supplement as adjuvant therapy in the management of respiratory distress syndrome (RDS) in preterm infants.Patient and MethodsVitamin D was prospectively studied in 196 preterm neonates, 96 of them developed RDS, which further subdivided into three subgroups (subgroup received just conventional therapy, subgroup received conventional therapy plus vitamin D 400 IU/day, and subgroup received conventional therapy plus vitamin D 800 IU/day). The patient selection for each treatment subgroup was done by computed randomization, and all the patients had the same treatment protocols assigned for each subgroup.ResultsThe preterm group who developed RDS had lower vitamin D concentrations than the preterm group without RDS (*P < .001). Also, the subgroups supplemented with vitamin D had lower Downes Respiratory Distress score and PaCO2 levels, less duration of hospitalization, and complications rates than the subgroup without vitamin D supplementation. The subgroup supplemented with 800 IU/day vitamin D showed also significantly improvement, less hospitalization duration, and less complications than those supplemented with 400 IU/day.Conclusions25‐hydroxyvitamin D concentration was deficient in most preterm babies especially those who developed RDS. Administration of 800 IU/day vitamin D as an adjuvant therapy in cases of RDS was associated with significant decreased in severity, rate of complications, and duration of hospital stay in preterm neonates with RDS.

Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease. Nod-like receptors nucleotide-binding domain and leucine-rich repeat pyrin-3 domain (NLRP3) inflammasome displays a considerable role in the chronic inflammatory state observed in diabetic patients. Urinary heat shock protein 72 (uHSP72) is a sensitive and specific biomarker for the early detection of acute kidney injury. The aim of this study was to evaluate NLRP3 relative gene expression, its correlation with inflammatory and oxidative stress markers, and to assess the value of uHSP72 in the early detection of DN in type 2 diabetic patients with different degrees of DN. Forty-five type 2 diabetic patients: 15 normoalbuminuric, 15 microalbuminuric, 15 macroalbuminuric, in addition to 15 healthy controls were enrolled in this study. Clinical examination and routine laboratory investigations were performed. NLRP3 mRNA expression was assessed by real time polymerase chain reaction. Serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), interleukin 1β (IL-1β), and uHSP72 levels were estimated by enzyme-linked immunosorbent assay. Serum chitotriosidase (CHIT1) activity was examined. NLRP3 mRNA relative expression, serum levels of 8-OHdG, IL-1β, and uHSP72, in addition to CHIT 1 activity were significantly increased in the macroalbuminuric patient group as compared to control and the other two diabetic groups. Also, a significant positive correlation was documented between the previously mentioned parameters and urinary albumin/creatinine ratio, serum creatinine, and HbA1c. Multiple linear regression analysis using urinary albumin/creatinine ratio as dependent variable confirmed that uHSP72 and NLRP3 mRNA relative expression were the independent predictors of DN (β were 0.432 and 0.448 respectively, P < 0.001). Receiver operating characteristic analyses revealed that both NLRP3 mRNA relative expression and uHSP72 levels were useful biomarkers discriminating DN patients from patients with type 2 diabetes mellitus (AUC were 0.957 and 0.983, respectively). uHSP72 may be considered as a novel potential diagnostic biomarker for the early detection of DN. Moreover, these data support the pivotal role of NLRP3 in the development and progression of DN. © 2017 IUBMB Life, 69(8):623-630, 2017.

Background: Worldwide growing rates of obesity are correlated with the rising prevalence of nonalcoholic fatty liver disease (NAFLD) with limited available therapeutics. Aim: The present study was undertaken to investigate the modulatory effects of dietary supplementation fisetin on hepatocyte nuclear factor 4 α (HNF4α) gene expression, hepatic lipin-1 signaling, thioredoxin-interacting protein (TXNIP) levels, poly-(ADP-ribose)-polymerase-1 (PARP-1) activity, as well as some oxidative stress parameters in a rat model of high-fat/high-sucrose (HFHS) induced NAFLD.Methods: Sixty male albino rats were allocated into four equal groups: normal control group, fisetin-treated control group, NAFLD group, and fisetin-treated NAFLD group. Gene expression levels of HNF4-α were estimated using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR), while Lipin-1, TXNIP levels, and PARP-1 activity were estimated by enzyme-linked immunosorbent assay (ELISA); lipid profile, hepatic lipid contents, hepatic lipoperoxides, fatty acid synthase activity, and total antioxidant capacity were also assessed colorimetrically.Results: Fisetin ameliorated HFHS-induced NAFLD; where it suppressed hepatic lipid accumulation, upregulated HNF4-α /lipin-1 signaling, mitigated oxidative stress, inhibited reactive oxygen species (ROS)-mediated TXNIP induction, and PARP-1 activation. In conclusion, fisetin could confer protection against NAFLD and impede its progression. However,additional experimental scrutiny is needed to verify these findings. K E Y W O R D Sfisetin, hepatocyte nuclear factor 4 α, lipin-1, nonalcoholic fatty liver disease, poly-(ADP-ribose)polymerase-1, thioredoxin-interacting protein

Steroid-resistant nephrotic syndrome represents about 10-20% of pediatrics' nephrotic syndrome. The regeneration of glomerular barrier seems pivotal for cessation of proteinuria. Nephronectin (NPNT) plays a major role in nephrogenesis, signal transduction, and epithelial-mesenchymal interactions. This study aims to preliminary assess NPNT as potential noninvasive biomarker of glomerular regeneration and its ability to identify steroid resistance. In this case control study, 80 retrospectively selected patients with nephrotic syndrome were enrolled in addition to 40 healthy controls. Forty patients were steroid sensitive (SSNS) and the other 40 patients were steroid-resistant (SRNS), NPTN concentration was measured using ELISA and NPNT mRNA expression was assayed using real-time PCR. NPTN concentrations were significantly higher in SSNS than both SRNS and controls (The means were 4.64 ± 3.05, 0.69 ± 0.44, and 1.63 ± 0.59, respectively). Moreover, NPTN concentrations were significantly lower in SRNS than controls. NPTN was significantly overexpressed in SSNS compared to both SRNS and controls (the means were 10.82 ± 7.39, 1.19 ± 0.94, and 1.04 ± 0.10, respectively) with no statistically significant difference between SRNS and controls. ROC curves analysis showed that both NPNT expression and NPNT serum level are of promising diagnostic performance (ROC 0.948 and 0.896, respectively). Regression analysis showed that both NPNT expression and NPNT serum level can be independent predictors of steroid resistance. The present study shows for the first time an enhanced expression of NPNT in steroid-sensitive nephrotic syndrome patients suggesting NPNT as a marker of glomerular regeneration. Also, serum NPNT can be a useful noninvasive biomarker of steroid resistance.

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This study aimed to investigate the protective effects of berberine (BBR) against D-galactose (D-gal)-induced renal aging in rats, pointing to its ability to modulate phosphatase and tensin homolog deleted on chromosome ten (PTEN)/Akt signalling, and to attenuate oxidative stress, inflammation and apoptosis. Renal aging was induced by subcutaneous injection of D-gal for six consecutive weeks along with simultaneous oral administration of BBR and compared to control rats and rats received individual doses of either drug. BBR treatment significantly reduced the serum levels of urea and creatinine, retrieved the alterations in kidney histopathology, and restored redox balance evidenced by alleviations of the level of malondialdehyde, 8-hydroxy-2'-deoxyguanosine and activating heme oxygenase-1 enzyme. Moreover, it markedly reduced the serum levels of pro-inflammatory mediators, along with down-regulation of PTEN expression, enhanced Akt activity, as well as significantly higher immunostaining of the anti-apoptotic marker (Bcl-2). These findings hold a great promise for the use of BBR as a protecting agent against renal aging.

Doxorubicin (DOX) is an anticancer antibiotic which has various effects in human cancers. It is one of the commonly known causes of drug-induced nephrotoxicity, which results in acute renal injury. Adrenomedullin (ADM), a vasodilator peptide, is widely distributed in many tissues and has potent protective effects. Therefore, the current study aimed to examine the protective potential mechanisms of ADM against DOX-induced nephrotoxicity. A total of 28 male Wistar rats were randomized into four groups: control group, doxorubicin group (15 mg/kg single intraperitoneal injection of DOX), adrenomedullin + doxorubicin group (12 μg/kg/day intraperitoneal injection of ADM) 3 days prior to DOX injection and continuing for 14 days after the model was established, and adrenomedullin group. Kidney function biomarkers, oxidative stress markers, and inflammatory mediators (TNF-α, NLRP3, IL-1β, and IL-18) were assessed. The expressions of gasdermin D and ASC were assessed by real-time PCR. Furthermore, the abundances of caspase-1 (p20), Bcl-2, and Bax immunoreactivity were evaluated. ADM administration improved the biochemical parameters of DOX-induced nephrotoxicity, significantly reduced oxidative damage markers and inflammatory mediators, and suppressed both apoptosis and pyroptosis. These results were confirmed by the histopathological findings and revealed that ADM’s antioxidant, anti-inflammatory, anti-apoptotic, and anti-pyroptotic properties may have prospective applications in the amelioration of DOX-induced nephrotoxicity.