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.

Glycation of Immunoglobulin-G from Pentose Sugar: A Cause for Structural Perturbations.

BACKGROUND: Glycation of immunoglobulin-G (IgG) molecules with monosaccharides may cause significant structural disability, thus resulting in their loss of function. The accumulation of AGEs formed from glycation plays an important role in the aliments associated with metabolic diseases. Therefore, excess sugar in plasma interferes with the functioning of IgG and may contribute to a wide range of diabetes-associated complications. The long-term formation of these heterogeneous AGEs may accumulate and affect plasma proteins, especially long-lived proteins. In this study, we analyze immunoglobulin-G (IgG) glycation with 2'-deoxyribose (deoxyribose) instigated modification in IgG structure and AGEs formation. METHODS: This study aims to glycate IgG from varying concentrations of pentose sugar, 2'-deoxyribose (deoxyribose). Various physicochemical methods and techniques characterized post glycation of IgG, both the native and its glycated analogue. The glycated protein will be assessed for its stability and perturbations by UV-VIS., fluorescence and FT-IR spectroscopic techniques. Moreover, the early glycation product will be done by NBT assay, and other biochemical parameters like HMF, carbonyl content and thioflavin-T assays were also performed to see the biochemical changes induced in the glycated IgG macromolecule. RESULTS: Glycation of protein macromolecules generates stable early glycation products (Amadori products). Later, these Amadori products involved a series of chemical reactions to form more stable advanced glycation end products (AGEs). Our experimental study results could validate the modification in IgG structure and AGEs formation. CONCLUSION: The formation of IgG-AGEs from glycation of IgG with deoxyribose could exert cellular toxicity, and might initiates secondary complications of diabetes. Therefore, this study emphasized the glycation reaction of IgG from deoxyribose, which has not been reported yet.

Delafloxacin-Capped Gold Nanoparticles (DFX-AuNPs): An Effective Antibacterial Nano-Formulation of Fluoroquinolone Antibiotic.

New antibiotics are seen as 'drugs of last resort' against virulent bacteria. However, development of resistance towards new antibiotics with time is a universal fact. Delafloxacin (DFX) is a new fluoroquinolone antibiotic that differs from existing fluoroquinolones by the lack of a protonatable substituent, which gives the molecule a weakly acidic nature, affording it higher antibacterial activity under an acidic environment. Furthermore, antibiotic-functionalized metallic nanoparticles have been recently emerged as a feasible platform for conquering bacterial resistance. In the present study, therefore, we aimed at preparing DFX-gold nano-formulations to increase the antibacterial potential of DFX. To synthesize DFX-capped gold nanoparticles (DFX-AuNPs), DFX was used as a reducing and stabilizing/encapsulating agent. Various analytical techniques such as UV-visible spectroscopy, TEM, DLS, FTIR and zeta potential analysis were applied to determine the properties of the synthesized DFX-AuNPs. The synthesized DFX-AuNPs revealed a distinct surface plasmon resonance (SPR) band at 530 nm and an average size of 16 nm as manifested by TEM analysis. In addition, Zeta potential results (-19 mV) confirmed the stability of the synthesized DFX-AuNPs. Furthermore, FTIR analysis demonstrated that DFX was adsorbed onto the surface of AuNPs via strong interaction between AuNPs and DFX. Most importantly, comparative antibacterial analysis of DFX alone and DFX-AuNPs against Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) verified the superior antibacterial activity of DFX-AuNPs against the tested microorganisms. To sum up, DFX gold nano-formulations can offer a promising possible solution, even at a lower antibiotic dose, to combat pathogenic bacteria.

SARS-CoV-2 vaccines: Clinical endpoints and psychological perspectives: A literature review.

BACKGROUND: About 270 million cases have been confirmed, and 5.3 million fatalities Worldwide due to SARS-CoV-2. Several vaccine candidates have entered phase 3 of the clinical trial and are being investigated to provide immunity to the maximum percentage of people. A safe and effective vaccine is required to tackle the current COVID-19 waves. There have been reports that clinical endpoints and psychological parameters are necessary to consider vaccine efficacy. This review examines the clinical endpoints required for a successful SARS-CoV-2 vaccine and the influences of psychological parameters on its efficacy. METHODS: The main research question was to find out the clinical endpoints that determine the vaccine efficacy? And what kind of psychological parameters affect the vaccine efficacy? The information was taken from several journals, databases, and scientific search engines like Googe scholar, Pubmed, Scopus, Web of Science, Science direct, WHO website, and other various sites. The research studies were searched using keywords; SAR-CoV-2 vaccine efficacy, psychological effect on SARS-CoV-2 vaccine, SARS-CoV-2 vaccine endpoints. RESULTS: This review has highlighted various clinical endpoints that are the main determinants of clinical vaccine efficacy. Currently, vaccinations are being carried out throughout the world; it is important to investigate the main determinants affecting vaccine efficacy. We have focused on the clinical endpoints and the influence of psychological parameters that affect the vaccine efficacy in clinical settings. The primary endpoints include the risk of infection, symptoms, and severity of COVID-19, while hospitalization length, supplemental oxygen requirement, and mechanical ventilation are secondary endpoints in the clinical endpoints. Some tangential endpoints were also considered, including organ dysfunction, stroke, and MI. Many psychological associated things have influenced the vaccine efficacy, like the lower antibody titers in the vaccinated people. In addition to that, Short- and long-term stress and sleep deprivation were also found to affect the vaccine efficacy. CONCLUSION: The review summarizes the important clinical endpoints required for a successful vaccine candidate. In addition to primary and secondary endpoints, auxiliary endpoints and the disease burden also play an important role in modulating vaccine efficacy. Moreover, the psychological perspective also influences vaccine efficacy. Effective follow-up of participants should follow to examine the clinical endpoints to reach any conclusion about vaccine efficacy.

Enhancement of Vancomycin Potential against Pathogenic Bacterial Strains via Gold Nano-Formulations: A Nano-Antibiotic Approach.

The remarkable rise of antibiotic resistance among pathogenic bacteria poses a significant threat to human health. Nanoparticles (NPs) have recently emerged as novel strategies for conquering fatal bacterial diseases. Furthermore, antibiotic-functionalized metallic NPs represent a viable nano-platform for combating bacterial resistance. In this study, we present the use of vancomycin-functionalized gold nanoparticles (V-GNPs) to battle pathogenic bacterial strains. A facile one-pot method was adopted to synthesize vancomycin-loaded GNPs in which the reducing properties of vancomycin were exploited to produce V-GNPs from gold ions. UV-Visible spectroscopy verified the production of V-GNPs via the existence of a surface plasmon resonance peak at 524 nm, whereas transmission electron microscopy depicted a size of ~24 nm. Further, dynamic light scattering (DLS) estimated the hydrodynamic diameter as 77 nm. The stability of V-GNPs was investigated using zeta-potential measurements, and the zeta potential of V-GNPs was found to be -18 mV. Fourier transform infrared spectroscopy confirmed the efficient loading of vancomycin onto GNP surfaces; however, the loading efficiency of vancomycin onto V-GNPs was 86.2%. Finally, in vitro antibacterial studies revealed that V-GNPs were much more effective, even at lower concentrations, than pure vancomycin. The observed antibacterial activities of V-GNPs were 1.4-, 1.6-, 1.8-, and 1.6-fold higher against Gram-negative Escherichia coli, Klebsiella oxytoca, and Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus, respectively, compared to pure vancomycin. Collectively, V-GNPs represented a more viable alternative to pure vancomycin, even at a lower antibiotic dose, in conquering pathogenic bacteria.

Curcumin complexation with cyclodextrins by the autoclave process: Method development and characterization of complex formation.

One approach to enhance curcumin (CUR) aqueous solubility is to use cyclodextrins (CDs) to form inclusion complexes where CUR is encapsulated as a guest molecule within the internal cavity of the water-soluble CD. Several methods have been reported for the complexation of CUR with CDs. Limited information, however, is available on the use of the autoclave process (AU) in complex formation. The aims of this work were therefore to (1) investigate and evaluate the AU cycle as a complex formation method to enhance CUR solubility; (2) compare the efficacy of the AU process with the freeze-drying (FD) and evaporation (EV) processes in complex formation; and (3) confirm CUR stability by characterizing CUR:CD complexes by NMR, Raman spectroscopy, DSC, and XRD. Significant differences were found in the saturation solubility of CUR from its complexes with CD when prepared by the three complexation methods. The AU yielded a complex with expected chemical and physical fingerprints for a CUR:CD inclusion complex that maintained the chemical integrity and stability of CUR and provided the highest solubility of CUR in water. Physical and chemical characterizations of the AU complexes confirmed the encapsulated of CUR inside the CD cavity and the transformation of the crystalline CUR:CD inclusion complex to an amorphous form. It was concluded that the autoclave process with its short processing time could be used as an alternate and efficient methods for drug:CD complexation.