A Computational Approach for Defining a Signature of ß-Cell Golgi Stress in Diabetes.

The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic ß-cell has not been tested. We used an informatics-based approach to develop a transcriptional signature of ß-cell GA stress using existing RNA sequencing and microarray data sets generated using human islets from donors with diabetes and islets where type 1 (T1D) and type 2 (T2D) diabetes had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. In parallel, we generated an RNA-sequencing data set from human islets treated with brefeldin A (BFA), a known GA stress inducer. Overlapping the T1D and T2D groups with the BFA data set, we identified 120 and 204 differentially expressed genes, respectively. In both the T1D and T2D models, pathway analyses revealed that the top pathways were associated with GA integrity, organization, and trafficking. Quantitative RT-PCR was used to validate a common signature of GA stress that included ATF3, ARF4, CREB3, and COG6 Taken together, these data indicate that GA-associated genes are dysregulated in diabetes and identify putative markers of ß-cell GA stress.

ApAGP-fabricated silver nanoparticles induce amendment of murine macrophage polarization.

M2 polarization of macrophages is predominant in case of tumors and some other infectious diseases for disease progression. Repolarization of the M2 phenotype to the M1 state may be required to cure diseases. Hence, it is of great interest to find out a material that would repolarize the M2 phenotype to the M1 state. Herein, the arabinogalactan protein from Andrographis paniculata (ApAGP) was used to prepare a silver nanoparticle-ApAGP (SNP-ApAGP) bioconjugate, which was characterized via UV-vis spectroscopy, zeta potential analysis, FT-IR spectroscopy, and HR-TEM. Studies suggest that SNP-ApAGP (2.5 µg mL-1) up-regulates ROS generation, NO generation, and pro-inflammatory cytokine release (IL-12, IFN-γ, TNF-α, and IL-6). SNP-ApAGP also down-regulates the arginase-1 activity and anti-inflammatory cytokine release (IL-4 & IL-10) in M0, M1, and M2-polarized peritoneal macrophages in vitro. Therefore, SNP-ApAGP induces M1 polarization in M0 macrophages, enhances the pro-inflammatory activity of the M1 phenotype, and can also repolarize M2 macrophages into the M1 phenotype. Therefore, SNP-ApAGP could be used for treating various infectious diseases and cancers where repolarization of M2 macrophages may be required to cure the disease.

Comparative evaluation of superoxide dismutase, alpha-tocopherol, and 10% sodium ascorbate on reversal of shear bond strength of bleached enamel: An in vitro study.

OBJECTIVE: The aim of this study was to investigate the neutralizer effect of antioxidant agents on the bond strength of bleached enamel. MATERIALS AND METHODS: Sixty enamel slabs were prepared from 60 freshly extracted maxillary central incisors and were divided into six groups. The negative control group received no bleaching treatment and the other groups were bleached with 35% carbamide peroxide (Opalescence Quick; Ultradent, South Jordan, USA). In Group II, composite was built immediately after bleaching and cured without any antioxidants. In Group III, bleached specimens received composite build ups delayed by 1 week. In Groups IV, V, and VI bleached specimens received applications of superoxide dismutase (SOD), sodium ascorbate (SA), and tocopherol solutions, respectively, for 10 min. Following composite bonding, the micro shear bond strength (µSBS) was measured at a speed of 1 mm/min in universal testing machine. STATISTICAL ANALYSIS USED: The µSBS values of all the groups were analyzed using the analysis of variance followed by Tukey honestly significant difference post-hoc test. RESULTS: Bonding of composites to unbleached group (Group I) exhibited the highest mean SBS values and among the antioxidant-treated groups, the highest SBS values were seen with SOD (Group IV) treated samples (23.0040 ± 4.30565 MPa). CONCLUSIONS: Application of SA, alpha-tocopherol, and SOD can effectively reverse the bond strength with bleached enamel. SOD gave a comparatively more promising reversal of bond strength than SA and alpha-tocopherol, and deserves further studies.