Metformin encapsulated gold nanoparticles (MTF-GNPs): A promising antiglycation agent.

The generation of advanced glycation end products (AGEs) through nonenzymatic protein glycation contributes to the pathogenesis of long-lived diabetic problems. Metformin (MTF) is the very first drug having antihyperglycemic effects on type II diabetes mellitus which also possess interaction with dicarbonyl compounds and blocks the formation of AGEs. In the current study, MTF is bioconjugated with glycation-derived synthesized gold nanoparticles (GNPs) of significant size. Additionally, using various biophysical and biochemical approaches, we investigated the antiglycating capacity MTF-GNPs in contrast to MTF against d-ribose-derived glycation of bovine serum albumin. Our key findings via utilizing various assays demonstrated that MTF-GNPs were able to inhibit AGEs development by reducing hyperchromicity, early glycation products, carbonyl content, hydxoxymethylfurfural content, production of fluorescent AGEs, normalizing the loss of secondary structure (i.e., α-helix and ß-sheets) of proteins, elevating the levels of free lysine and free arginine more efficiently compared to pure MTF. Based on these results, we concluded that MTF-GNPs possess a considerable antiglycation property and may be developed as an outstanding anti-AGEs treatment drug. Further in vivo and clinical research are necessary to determine the therapeutic effects of MTF-GNPs against AGE-related and metabolic disorders.

Molecular and Source-Specific Profiling of Hospital Staphylococcus aureus Reveal Dominance of Skin Infection and Age-Specific Selections in Pediatrics and Geriatrics.

Staphylococcus aureus is a major human-associated pathogen that causes a wide range of clinical infections. However, the increased human dynamics and the changing epidemiology of the species have made it imperative to understand the population structure of local ecotypes, their transmission dynamics, and the emergence of new strains. Since the previous methicillin-resistant S. aureus (MRSA) pandemic, there has been a steady increase in global healthcare-associated infections involving cutaneous and soft tissue and resulting in high morbidities and mortalities. Limited data and paucity of high-quality evidence exist for many key clinical questions about the pattern of S. aureus infections. Using clinical, molecular, and epidemiological characterizations of isolates, hospital data on age and infection sites, as well as antibiograms, we have investigated profiles of circulating S. aureus types and infection patterns. We showed that age-specific profiling in both intensive care unit (ICU) and non-ICU revealed highest infection rates (94.7%) in senior-patients > 50 years; most of which were MRSA (81.99%). However, specific distributions of geriatric MRSA and MSSA rates were 46.5% and 4.6% in ICU and 35.48% and 8.065% in non-ICU, respectively. Intriguingly, the age groups 0−20 years showed uniquely similar MRSA patterns in ICU and non-ICU patients (13.9% and 9.7%, respectively) and MSSA in ICU (11.6%). The similar frequencies of both lineages in youth at both settings is consistent with their increased socializations and gathering strongly implying carriage and potential evolutionary replacement of MSSA by MRSA. However, in age groups 20−50 years, MRSA was two-fold higher in non-ICU (35%) than ICU (18.6%). Interestingly, a highly significant association was found between infection-site and age-groups (p-value 0.000). Skin infections remained higher in all ages; pediatrics 32.14%, adults 56%, and seniors 25% while respiratory infections were lower in pediatrics (14.3%) and adults (17%) while it was highest in seniors (38%). Blood and "other" sites in pediatrics were recorded (28.6%; 25%, respectively), and were slightly lower in adults (18.6%; 8.6%) and seniors (14%; 22.8%), respectively. Furthermore, a significant association existed between infection-site and MRSA (Chi-Square Test, p-value 0.002). Thus, the common cutaneous infections across all age-groups imply that skin is a significant reservoir for endogenous infections; particularly, for geriatrics MRSA. These findings have important clinical implications and in understanding S. aureus profiles and transmission dynamics across different age groups that is necessary for strategic planning in patient management and infection control.

Emphasizing the role of Wnt5a protein expression to predict favorable outcome after radical prostatectomy in patients with low-grade prostate cancer.

Wnt5a, a member of non-canonical wingless-related MMTV integration site family is a secreted glycoprotein that plays important roles in development and disease. Recent studies have shown that Wnt5a protein levels are up-regulated in prostate cancer, but contrasting reports exist on the role of Wnt5a to predict outcome after radical prostatectomy in patients with localized prostate cancer. Our group has recently shown that preserved high protein expression of Wnt5a in prostate cancer is associated with longer relapse-free time after radical prostatectomy. The present tissue microarray study emphasizes the role of Wnt5a protein expression in a different, well-defined, and independent cohort consisting of 312 prostate cancer patients. Kaplan-Meier curves plotted between Wnt5a expression and time to biochemical recurrence revealed that in low-grade prostate cancer, patients with preserved high-Wnt5a protein levels in their tumor cells have a lower risk of recurrence after radical prostatectomy compared to patients with low-Wnt5a protein expression. When Wnt5a protein expression was added to a Cox regression multivariate analysis, both Wnt5a protein expression and surgical margin status independently predict biochemical free survival. Herein we confirm Wnt5a positivity as a prognostic factor and show that preserved overexpression of Wnt5a protein is associated with increased time to biochemical recurrence in localized low-grade prostate cancer patients after radical prostatectomy. Our results emphasize that Wnt5a can be used as a predictive biomarker, and favoring the view of Wnt5a as a future therapeutic target in prostate cancer patients with tumor cells displaying low expression of Wnt5a.

ß2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity.

Although Rac and its activator Tiam1 are known to stimulate cell-cell adhesion, the mechanisms regulating their activity in cell-cell junction formation are poorly understood. Here, we identify ß2-syntrophin as a Tiam1 interactor required for optimal cell-cell adhesion. We show that during tight-junction (TJ) assembly ß2-syntrophin promotes Tiam1-Rac activity, in contrast to the function of the apical determinant Par-3 whose inhibition of Tiam1-Rac activity is necessary for TJ assembly. We further demonstrate that ß2-syntrophin localizes more basally than Par-3 at cell-cell junctions, thus generating an apicobasal Rac activity gradient at developing cell-cell junctions. Targeting active Rac to TJs shows that this gradient is required for optimal TJ assembly and apical lumen formation. Consistently, ß2-syntrophin depletion perturbs Tiam1 and Rac localization at cell-cell junctions and causes defects in apical lumen formation. We conclude that ß2-syntrophin and Par-3 fine-tune Rac activity along cell-cell junctions controlling TJ assembly and the establishment of apicobasal polarity.