Unveiling the Detrimental Effect of Glipizide on Structure and Function of Catalase: Spectroscopic, Thermodynamics and Simulation Studies.

Free radicals, products of oxidative processes, induce cellular damage linked to diseases like Parkinson's and diabetes due to increased reactive oxygen species (ROS) levels. Catalase, crucial for scavenging ROS, emerges as a therapeutic agent against ailments including atherosclerosis and tumor progression. Its primary function involves breaking down hydrogen peroxide into water and oxygen. Research on catalase-drug interactions reveals structural changes under specific conditions, affecting its activity and cellular antioxidant balance, highlighting its pivotal role in defending against oxidative stress-related diseases. Hence, targeting catalase is considered an effective strategy for controlling ROS-induced cellular damage. This study investigates the interaction between bovine liver catalase and glipizide using spectroscopic and computational methods. It also explores glipizide's effect on catalase activity. More than 20% inhibition of catalase enzymatic activity was recorded in the presence of 50 µM glipizide. To investigate the inhibition of catalase activity by glipizide, we performed a series of binding studies. Glipizide was found to form a complex with catalase with moderate affinity and binding constant in the range of 3.822 to 5.063 × 104 M-1. The binding was spontaneous and entropically favourable. The α-helical content of catalase increased from 24.04 to 29.53% upon glipizide complexation. Glipizide binding does not alter the local environment surrounding the tyrosine residues while a notable decrease in polarity around the tryptophan residues of catalase was recorded. Glipizide interacted with numerous active site residues of catalase including His361, Tyr357, Ala332, Asn147, Arg71, and Thr360. Molecular simulations revealed that the catalase-glipizide complex remained relatively stable in an aqueous environment. The binding of glipizide had a negligible effect on the secondary structure of catalase, and hydrogen bonds persisted consistently throughout the trajectory. These results could aid in the development of glipizide as a potent catalase inhibitor, potentially reducing the impact of reactive oxygen species (ROS) in the human body.

Antiglycation potential of metal ions and polyphenolic extract of chickpea on thiol-protease inhibitor: A management for diabetic complications.

Glycation is the non-enzymatic adduct formation between reducing sugars or dicarbonyls with proteins and is a crucial molecular event under hyperglycaemic conditions of diabetes. The accumulation of advanced glycation end products (AGEs) due to glycation of proteins has been implicated in several diseases associated with ageing and diabetes. Thus, investigating the antiglycation potential of some trace metal ions (Manganese; Mn2+, and Zinc; Zn2+) and polyphenolic extract of chickpea seeds (PEC) on the methylglyoxal (MGO) induced glycation of a phytocystatin isolated from chickpea was taken up to find an inexpensive and non-toxic therapeutic means of medicating protein glycation and associated diabetic complications. The current study focused on the comparative analyses of these micronutrients and herbal extracts in inhibiting protein glycation and AGEs formation in a quest to develop nutraceuticals for managing diabetes. The effect of metals (Mn2+, Zn2+) and PEC on protein glycation was assessed by different techniques, i.e., glycation-specific AGE fluorescence and absorbance, thiol protease inhibitory activity assay, and conformational alterations by spectroscopic assays. This study revealed the significant anti-glycation potencies of Mn2+, Zn2+, and PEC against the MGO-induced glycation of CPC, which might pave the way for resolving pathological complications of diabetes by combining higher levels of efficacy, selectivity, and safety in humans. Moreover, characterization and identification of different AGEs formed during the glycation process in diabetics was done to apply the same for determining the onset of glycation at the early stage so that appropriate steps be taken to address the menace of diabetic complications.

Modulation of quorum sensing and biofilm of Gram-negative bacterial pathogens by Cinnamomum zeylanicum L.

The development of antibiotic resistant microbial pathogens has become a global health threat and a major concern in modern medicine. The problem of antimicrobial resistance (AMR) has majorly arisen due to sub-judicious use of antibiotics in health care and livestock industry. A slow progress has been made in last two decades in discovery of new antibiotics. A new strategy in combatting AMR is to modulate or disarm the microbes for their virulence and pathogenicity. Plants are considered as promising source for new drugs against AMR pathogens. In this study, fraction-based screening of the Cinnamomum zeylanicum extract was performed followed by detailed investigation of antiquorum sensing and antibiofilm activities of the most active fraction that is, C. zeylanicum hexane fraction (CZHF). More than 75% reduction in violacein pigment of C. violaceum 12472 was overserved. CZHF successfully modulated the virulence of Pseudomonas aeruginosa PAO1 by 60.46%-78.35%. A similar effect was recorded against Serratia marcescens MTCC 97. A broad-spectrum inhibition of biofilm development was found in presence of sub-MICs of CZHF. The colonization of bacteria onto the glass coverslips was remarkably reduced apart from the reduction in exopolymeric substances. Alkaloids and terpenoids were found in CZHF. GC/MS analysis revealed the presence of cinnamaldehyde dimethyl acetal, 2-propenal, coumarin, and α-copaene as major phytocompounds. This study provides enough evidence to support potency of C. zeylanicum extract in targeting the virulence of Gram -ve pathogenic bacteria. The plant extract or active compounds can be developed as successful drugs after careful in vivo examination to target microbial infections. RESEARCH HIGHLIGHTS: Hexane fraction of Cinnamomum zeylanicum is active against QS and biofilms. The broad-spectrum antibiofilm activity was further confirmed by microscopic analysis. Dimethyl acetal, 2-propenal, coumarin, α-copaene, and so forth are major phytocompounds.

An environmentally sustainable approach for the utilization of Erigeron bonariensis as a green inhibitor against weathering steel corrosion in acidic media.

In the realm of corrosion mitigation, the search for sustainable and ecologically accountable inhibitors attracts significant interest from the environmental point of view. This study investigates the intriguing possibilities presented by Erigeron bonariensis (EB) as a green and innovative corrosion inhibitor for weathering steel in 1 M H2SO4. EB, a naturally abundant plant species, holds promise as a green and sustainable inhibitor due to its inherent chemical composition in the environment. The intricate interplay between the phytochemical constituents of the extract and the corrosive environment is meticulously deciphered. Furthermore, the environmentally benign nature of the inhibitor adds an extra layer of significance to its application, aligning with contemporary green chemistry principles. The inhibition effect of Erigeron bonariensis (EB) extract on the corrosion of mild steel in acidic media (H2SO4) was studied using weight loss, absorption studies, phytochemical analysis, electrochemical methods, and scanning electron microscopy. The experimental findings revealed that an increase in inhibitor concentration is correlated with higher inhibition efficiency. The adsorption of inhibitor molecules on the mild steel surface was found to agree with the UV-Vis adsorption spectrum. Additionally, a surface study conducted using scanning electron microscopy indicated notable differences in the presence and absence of inhibitors for weathering steel. At 2000 mg L-1, EB extract has the best inhibitory efficiency for weathering steel in 1 M H2SO4 of 99.50% by the leaf part, followed by 94.35% by the flower part, and 85.22% by the stem part. Overall, this study suggests that EB extract serves as a promising alternative for corrosion prevention, demonstrating significant inhibition efficiency.

Diabetes Health Literacy, Drug Adherence and Factors Associated with Them among Urban Patients in Kerala, India.

Aims: The study aimed to assess diabetes health literacy, adherence to diabetes medication, and its associated factors in Kerala, India, the most advanced Indian state in epidemiological transition with the highest literacy level in India. Materials and methods: We conducted a community-based cross-sectional study among 280 diabetes patients (mean age 62 years, male 42%) selected by multistage cluster sampling. Information on sociodemographic variables was collected using a pretested structured interview schedule. Diabetes health literacy was assessed using the revised Michigan Diabetes Knowledge test. Adherence to diabetes medication was assessed using the Hill-Bone subscale. Binary logistic regression analysis was done to find out the factors associated with diabetes health literacy and medication adherence. Results: Good diabetes health literacy was reported by 35.7% [95% confidence interval (CI): 30.1-41.6] of the patients. Perfect adherence to diabetes medication was reported by 33.2% of patients (CI: 27.7-39.1). Patients who reported regular newspaper reading [adjusted odds ratio (AOR) 3.16; CI: 1.57-6.30], using the internet (AOR 2.23; CI: 1.11-4.50) and insulin use (AOR 2.60; CI: 1.35-5.00) were more likely to report good diabetes health literacy compared to their counterparts. Patients who reported reading health magazines (AOR 2.75; CI: 1.01-7.60) were more likely to report perfect medication adherence compared to those who did not. Conclusion: Why diabetes health literacy and medication adherence were low among diabetes patients in the most literate state needs further investigation. Interventions to enhance diabetes health literacy and medication adherence may be undertaken among diabetes patients encouraging them to read newspapers and health magazines regularly and use the internet.

In vitro inhibition of biofilm and virulence factor production in azole-resistant strains of Candida albicans isolated from diabetic foot by Artemisia vulgaris stabilized tin (IV) oxide nanoparticles.

The advent of nanotechnology has been instrumental in the development of new drugs with novel targets. Recently, metallic nanoparticles have emerged as potential candidates to combat the threat of drug-resistant infections. Diabetic foot ulcers (DFUs) are one of the dreadful complications of diabetes mellitus due to the colonization of numerous drug-resistant pathogenic microbes leading to biofilm formation. Biofilms are difficult to treat due to limited penetration and non-specificity of drugs. Therefore, in the current investigation, SnO2 nanoparticles were biosynthesized using Artemisia vulgaris (AvTO-NPs) as a stabilizing agent and were characterized using ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). Furthermore, the efficacy of AvTO-NPs against biofilms and virulence factors of drug-resistant Candida albicans strains isolated from DFUs was assessed. AvTO-NPs displayed minimum inhibitory concentrations (MICs) ranging from 1 mg/mL to 2 mg/mL against four strains of C. albicans. AvTO-NPs significantly inhibited biofilm formation by 54.8%-87%, germ tube formation by 72%-90%, cell surface hydrophobicity by 68.2%-82.8%, and exopolysaccharide (EPS) production by 69%-86.3% in the test strains at respective 1/2xMIC. Biosynthesized NPs were effective in disrupting established mature biofilms of test strains significantly. Elevated levels of reactive oxygen species (ROS) generation in the AvTO-NPs-treated C. albicans could be the possible cause of cell death leading to biofilm inhibition. The useful insights of the present study could be exploited in the current line of treatment to mitigate the threat of biofilm-related persistent DFUs and expedite wound healing.

Resistance against two lytic phage variants attenuates virulence and antibiotic resistance in Pseudomonas aeruginosa.

Background: Bacteriophage therapy is becoming part of mainstream Western medicine since antibiotics of clinical use tend to fail. It involves applying lytic bacteriophages that self-replicate and induce cell lysis, thus killing their hosts. Nevertheless, bacterial killing promotes the selection of resistant clones which sometimes may exhibit a decrease in bacterial virulence or antibiotic resistance. Methods: In this work, we studied the Pseudomonas aeruginosa lytic phage φDCL-PA6 and its variant φDCL-PA6α. Additionally, we characterized and evaluated the production of virulence factors and the virulence in a Galleria mellonella model of resistant mutants against each phage for PA14 and two clinical strains. Results: Phage φDCL-PA6α differs from the original by only two amino acids: one in the baseplate wedge subunit and another in the tail fiber protein. According to genomic data and cross-resistance experiments, these changes may promote the change of the phage receptor from the O-antigen to the core lipopolysaccharide. Interestingly, the host range of the two phages differs as determined against the Pseudomonas aeruginosa reference strains PA14 and PAO1 and against nine multidrug-resistant isolates from ventilator associated pneumonia. Conclusions: We show as well that phage resistance impacts virulence factor production. Specifically, phage resistance led to decreased biofilm formation, swarming, and type III secretion; therefore, the virulence towards Galleria mellonella was dramatically attenuated. Furthermore, antibiotic resistance decreased for one clinical strain. Our study highlights important potential advantages of phage therapy's evolutionary impact that may be exploited to generate robust therapy schemes.

Extraction and Characterization of Polyhydroxybutyrates (PHB) from Bacillus thuringiensisKSADL127 Isolated from Mangrove Environments of Saudi Arabia

ABSTRACTPolyhydroxybutyrate (PHB) is a renowned biodegradable plastic that do not release any toxins or residues in the environment like petroleum based plastics. In the present study, 50 bacteria isolated from mangrove niche, Saudi Arabia, were screened for maximum PHB production. All the 50 strains showed positive for PHB production, of which one strain showed maximum of 137 mgL-1. The most PHB accumulated bacterium was selected and identified asBacillus thuringiensis KSADL127, based on phenotypic characterization and 16S rRNA sequence analysis. Characterization of extracted PHB was carried out by FT-IR, NMR, UV spectroscopy, DSC, TGA, and LC-MS, which later confirmed the presence of intracellular accumulated polymer and substantiated as PHB.