An innovative prognostic model based on autophagy-related long noncoding RNA signature for low-grade glioma

Autophagy is a highly conserved lysosomal degradation process essential in tumorigenesis. However, the involvement of autophagy-related long noncoding RNAs (lncRNAs) in low-grade glioma (LGG) remains unclear. In this study, we established an autophagy-related lncRNA prognostic signature for patients with LGG and assess its underlying functions. We used univariate Cox, least absolute shrinkage and selection operator and multivariate Cox regression models to establish an autophagy-related lncRNA prognostic signature. Kaplan–Meier survival analysis, receiver operating characteristic curve, nomogram, C-index, calibration curve and clinical decision-making curve were used to assess the predictive capability of the identified signature. A signature comprising nine autophagy-related lncRNAs (AL136964.1, ARHGEF26-AS1, PCED1B-AS1, AS104072.1, PRKCQ-AS1, LINC00957, AS125616.1, PSMB8-AS1 and AC087741.1) was identified as a prognostic model. Patients with LGG were divided into the high- and low-risk cohorts based on the median model-based risk score. The survival analysis revealed a 10-year survival rate of 9.3% (95% CI 1.91–45.3%) and 13.48% (95% CI 4.52–40.2%) in high-risk patients in the training and validation sets, respectively, and 48.4% (95% CI 24.7–95.0%) and 48.4% (95% CI 28.04–83.4%) in low-risk patients in the training and validation sets, respectively. This finding suggested a relatively low survival in high-risk patients. In addition, the lncRNA signature was independently prognostic and potentially associated with the progression of LGG. Therefore, the 9-autophagy-related-lncRNA signature may play a crucial role in the diagnosis and treatment of LGG, which may offer new avenues for tumour-targeted therapy.

     

Chiral Pool‐Based Synthesis of Naphtho‐Fused Isocoumarins

A variety of chiral derivatives of benzo[d]naphtho[1,2‐b]pyran‐6‐one were prepared in a single step by Et₃N‐mediated condensation of homophthalic anhydride with different derivatives of (S)‐amino acid chlorides at –5 °C by employing a chiral pool methodology. Chirality 27:951–957, 2015. © 2015 Wiley Periodicals, Inc.     

Chemical Composition,Antibacterial, Antioxidant and in Vitro Antidiabetic Activities of Essential Oils from Eruca vesicaria

This work describes the study of the chemical composition and bioactivity of the essential oils (EOs) of the different organs (leaves, flowers, stems and roots) from Eruca vesicaria. According to the GC and GC/MS analysis, all the EOs were dominated by erucin (4‐methylthiobutyl isothiocyanate) with a percentage ranging from 17.9 % (leaves) to 98.5 % (roots). The isolated EOs were evaluated for their antioxidant (DPPH, ABTS and β‐carotene/linoleic acid), antibacterial and inhibitory property against α‐amylase and α‐glucosidase. Most EOs exhibited an interesting α‐glucosidase and α‐amylase inhibitory potential. The roots essential oil was found to be the most active with IC₅₀ values of 0.80±0.06 and 0.11±0.01 μg mL^?1, respectively. The essential oil of roots exhibited the highest antioxidant activity (DPPH, PI=92.76±0.01 %; ABTS, PI=78.87±0.19; and β‐carotene, PI=56.1±0.01 %). The isolated oils were also tested for their antibacterial activity against two Gram‐positive and three Gram‐negative bacteria. Moderate results have been noted by comparison with Gentamicin used as positive control.     

The Role of Iex-1 in the Pathogenesis of Venous Neointimal Hyperplasia Associated with Hemodialysis Arteriovenous Fistula

Arteriovenous fistulas (AVFs) used for hemodialysis fail because of venous neointimal hyperplasia (VNH). There are 1,500,000 patients that have end stage renal disease worldwide and the majority requires hemodialysis. In the present study, the role of the intermediate early response gene X-1 (IEX-1), also known as IER-3 in the pathogenesis of VNH was evaluated. In human samples removed from failed AVF, there was a significant increase in IEX-1 expression localized to the adventitia. In Iex-1 ^−/− mice and wild type (WT) controls, chronic kidney disease was induced and an AVF placed 28 days later by connecting the carotid artery to jugular vein. The outflow vein was removed three days following the creation of the AVF and gene expression analysis demonstrated a significant decrease in vascular endothelial growth factor-A (Vegf-A) and monocyte chemoattractant protein-1 (Mcp-1) gene expression in Iex-1 ^−/− mice when compared to WT mice (P<0.05). At 28 days after AVF placement, histomorphometric and immune-histochemical analyses of the outflow vein demonstrated a significant decrease in neointimal hyperplasia with an increase in average lumen vessel area associated with a decrease in fibroblast, myofibroblast, and Ly6C staining. There was a decrease in proliferation (Ki-67) and an increase in the TUNEL staining in Iex-1 KO mice compared to WT. In addition, there was a decrease in Vegf-A, Mcp-1, and matrix metalloproteiniase-9 (Mmp-9) staining. Iex-1 expression was reduced in vivo and in vitro using nanoparticles coated with calcitriol, an inhibitor of Iex-1 that demonstrated that Iex-1 reduction results in decrease in Vegf-A. In aggregate, these results indicate that the absence of IEX-1 gene results in reduced VNH accompanied with a decrease in proliferation, reduced fibroblast, myofibroblast, and Ly6C staining accompanied with increased apoptosis mediated through a reduction in Vegf-A/Mcp-1 axis and Mmp-9. Adventitial delivery of nanoparticles coated with calcitriol reduced Iex-1 and VNH.     

Simultaneous determination of different endogenetic plant growth regulators in common green seaweeds using dispersive liquid–liquid microextraction method

A simple and rapid HPLC-based method was developed for simultaneous determination of major classes of plant growth regulators (PGRs) in Monostroma and different species of Ulva. The plant growth regulators determined included gibberellic acid (GA₃), indole-3-acetic acid (IAA), abscisic acid (ABA), indole-3-butyric acid (IBA), salicylic acid and kinetin riboside (KR) and their respective elution time was 2.75, 3.3, 3.91, 4.95, 5.39 and 6.59 min. The parameters optimized for distinct separation of PGRs were mobile phase (60:40 methanol and 0.6% acetic acid in water), column temperature (35 °C) and flow rate (1 ml/min). This method presented an excellent linearity (0.2–100 μg/ml) with limit of detection (LOD) as 0.2 μg/ml for ABA, 0.5 μg/ml for KR and salicylic acid, and 1 μg/ml for IAA, IBA and GA₃. The precision and accuracy of the method was evaluated after inter and intra day analysis in triplicates. The effect of plant matrix was compensated after spiking and the resultant recoveries estimated were in the range of 80–120%. Each PGR thereby detected were further characterized by ESI-MS analysis. The method optimized in this study determined IBA along with IAA for the first time in the seaweed species investigated except Ulva linza where the former was not detected. In all the species studied, ABA level was detected to be the highest while kinetin riboside was the lowest. In comparison to earlier methods of PGR analysis, sample preparation and analysis time were substantially reduced while allowing determination of more classes of PGRs simultaneously.     

Minicells: versatile vectors for targeted drug or si/shRNA cancer therapy

Effective cancer therapy continues to be a daunting challenge due mainly to considerable tumor cell heterogeneity, drug-resistance, and dose-limiting toxicity of therapeutics. Here we review a versatile nano-cellular (minicell) delivery vehicle that can be packaged with therapeutically effective concentrations of chemotherapeutic drugs, siRNAs or shRNAs and can be targeted to tumors via minicell-surface attached bispecific antibodies. A range of minicell-based therapeutics have shown highly effective tumor stabilization/regression in the murine xenograft model and in case studies in canines with late-stage endogenous tumors. Repeat intravenous dosing shows absence of toxicity or immunogenicity in both species. The minicell-based therapeutic has potential applications in personalized cancer medicine.     

Ameliorative effect of carnosine and N-acetylcysteine against sodium nitrite induced nephrotoxicity in rats

The widespread use of sodium nitrite (NaNO₂) for various industrial purposes has increased human exposure to alarmingly high levels of nitrate/nitrite. Because NaNO ₂ is a strong oxidizing agent, induction of oxidative stress is one of the mechanisms by which it can exert toxicity in humans and animals. We have investigated the possible protection offered by carnosine (CAR) and N-acetylcysteine (NAC) against NaNO ₂-induced nephrotoxicity in rats. Animals orally received CAR at 100 mg/kg body weight/d for seven days or NAC at 100 mg/kg body weight/d for five days followed by a single oral dose of NaNO ₂ at 60 mg/kg body weight. The rats were killed after 24 hours, and the kidneys were removed and processed for various analyses. NaNO ₂ induced oxidative stress in kidneys, as shown by the decreased activities of antioxidant defense, brush border membrane, and metabolic enzymes. DNA-protein crosslinking and DNA fragmentation were also observed. CAR/NAC pretreatment significantly protected the kidney against these biochemical alterations. Histological studies supported these findings, showing kidney damage in NaNO ₂-treated animals and reduced tissue impairment in the combination groups. The protection offered by CAR and NAC against NaNO ₂-induced damage, and their nontoxic nature, makes them potential therapeutic agents against nitrite-induced nephrotoxicity.     

Synthetic β-hydroxy ketone derivative inhibits cholinesterases,rescues oxidative stress and ameliorates cognitive deficits in 5XFAD mice model of AD

Molecular Biology Reports - Alzheimer's disease (AD) is a progressive, chronic and age-related neurodegenerative disorder that affects millions of people across the world. In pursuit of new...