Ameliorative effects of endogenous and exogenous indole-3-acetic acid on atrazine stressed paddy field cyanobacterial biofertilizer Cylindrospermum stagnale.

Across the world, paddy fields naturally harbour cyanobacteria that function as biofertilizers and secrete various compounds like Indole-3-acetic acid (IAA) that help organisms in regulating their growth. Also, paddy field farming utilizes large amounts of pesticides (e.g. atrazine); but their continued application in the agricultural field causes toxicity in non-target cyanobacterial species that hinder their performance as a biofertilizer. Hence, the current study is an attempt to ameliorate the atrazine stress in cyanobacterium Cylindrospermum stagnale by addition of IAA (1 mM each) under different atrazine levels (0, 60, 80, 100, 120, 140 µg/l). Atrazine toxicity affected C. stagnale in a dose-dependent manner further experiments revealed that both the exogenous and endogenous IAA mitigated the detrimental effects of atrazine. It reduced MDA content and simultaneously increased chlorophyll content, total protein content, and multiple antioxidant enzyme activities [superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX)] at 140 µg/l. A molecular docking study revealed that the pesticide binds to the D1 protein of the photoelectric chain in photosynthesis. Hence, the application of IAA or cyanobacterial biofertilizer that secretes a sufficient amount of IAA may assist sustainable agriculture in counteracting the atrazine toxicity.

Allosteric cooperation in ß-lactam binding to a non-classical transpeptidase.

L,D-transpeptidase function predominates in atypical 3 → 3 transpeptide networking of peptidoglycan (PG) layer in Mycobacterium tuberculosis. Prior studies of L,D-transpeptidases have identified only the catalytic site that binds to peptide moiety of the PG substrate or ß-lactam antibiotics. This insight was leveraged to develop mechanism of its activity and inhibition by ß-lactams. Here, we report identification of an allosteric site at a distance of 21 Å from the catalytic site that binds the sugar moiety of PG substrates (hereafter referred to as the S-pocket). This site also binds a second ß-lactam molecule and influences binding at the catalytic site. We provide evidence that two ß-lactam molecules bind co-operatively to this enzyme, one non-covalently at the S-pocket and one covalently at the catalytic site. This dual ß-lactam-binding phenomenon is previously unknown and is an observation that may offer novel approaches for the structure-based design of new drugs against M. tuberculosis.

1,3,4-oxadiazole conjugates of capsaicin as potent NorA efflux pump inhibitors of Staphylococcus aureus.

NorA efflux pump pertaining to the major facilitator superfamily (MFS) is known to play a key role in antibiotic and biocide resistance in Staphylococcus aureus (S. aureus). It accounts for the extrusion of antibiotics like fluoroquinolones (e.g. ciprofloxacin). Several compounds including synthetic and natural products have been identified as potential NorA efflux pump inhibitors (EPIs) and found to restore the antibacterial activity of antibiotics. However, none of the reported EPIs have reached to clinical approval probably due to their high toxicity profiles. Considering the NorA efflux pump inhibitory potential of capsaicin, a series of capsaicin-based 1,3,4 oxadiazole conjugates were prepared and evaluated for ciprofloxacin activity potentiating effect. Among the new capsaicinoids tested, 17i displayed a minimum effective concentration (MEC) of 12.5 µg/mL against NorA overexpressing S. aureus strain (SA1199B), whereas capsaicin showed MEC of 50 µg/mL. The kill kinetics curve for the combination showed that ciprofloxacin at a sub-inhibitory concentration (0.25 × MIC) was equipotent in effect, to its MIC. 17i has significantly decreased the ethidium bromide efflux confirming NorA inhibition as the mode of action. Mutation prevention concentration of the ciprofloxacin was reduced in combination with 17i.In silico studies revealed the binding efficiency and binding affinity of 17i with NorA. This compound may serve as a template for the further drug discovery.

Biomedical applications of environmental friendly poly-hydroxyalkanoates.

Biological polyesters of hydroxyacids are known as polyhydroxyalkanoates (PHA). They have proved to be an alternative, environmentally friendly and attractive candidate for the replacement of petroleum-based plastics in many applications. Many bacteria synthesize these compounds as an intracellular carbon and energy compound usually under unbalanced growth conditions. Biodegradability and biocompatibility of different PHA has been studied in cell culture systems or in an animal host during the last few decades. Such investigations have proposed that PHA can be used as biomaterials for applications in conventional medical devices such as sutures, patches, meshes, implants, and tissue engineering scaffolds as well. Moreover, findings related to encapsulation capability and degradation kinetics of some PHA polymers has paved their way for development of controlled drug delivery systems. The present review discusses about bio-plastics, their characteristics, examines the key findings and recent advances highlighting the usage of bio-plastics in different medical devices. The patents concerning to PHA application in biomedical field have been also enlisted that will provide a brief overview of the status of research in bio-plastic. This would help medical researchers and practitioners to replace the synthetic plastics aids that are currently being used. Simultaneously, it could also prove to be a strong step in reducing the plastic pollution that surged abruptly due to the COVID-19 medical waste.

Unravelling the interaction of glipizide with human serum albumin using various spectroscopic techniques and molecular dynamics studies.

Glipizide is known to stimulate insulin secretion by ß-cells of the pancreas. It is a second-generation sulfonylurea drug used in the management of type 2 diabetes. The shorter biological half-life makes it a suitable candidate to be designed as a controlled release formulation. Human serum albumin (HSA), a major plasma protein plays a crucial role in the transportation of drugs, hormones, fatty acids, and many other molecules and determines their physiological fate and biodistribution. In this study, the interaction of glipizide with HSA was investigated under physiological conditions using multi-spectroscopic techniques corroborated with molecular docking and dynamics approach. It was found that glipizide integrates to HSA with a binding constant in the order of 105 M-1. The mode of fluorescence quenching by glipizide is static in nature with one binding site. Glipizide preferentially interacts with sub-domain IIA of HSA and their complexion is thermodynamically favorable. This interaction results in the loss of α-helical content of HSA. The energy transfer efficiency from HSA to glipizide was found to be 26.72%. In silico molecular docking and simulation studies ratified in vitro findings and revealed that hydrogen bonds and hydrophobic interactions are accountable for glipizide-HSA complex formation.Communicated by Ramaswamy H. Sarma.

Study on the interaction of antidiabetic drug Pioglitazone with calf thymus DNA using spectroscopic techniques.

Pioglitazone is an antidiabetic drug used to treat type 2 diabetes mellitus. Interaction of Pioglitazone with calf thymus DNA was investigated using multispectroscopic techniques and molecular docking study. Quenching and binding constant was calculated at 3 different temperatures. The binding constant of Pioglitazone with calf thymus DNA was calculated to be 6.49 × 103 M-1 at 293 K. The quenching mechanism was found to be a static process, and thermodynamic parameters revealed van der Waals interactions and hydrogen bonds to be the major force working in Pioglitazone-DNA interaction. Pioglitazone follows the nonintercalative mode of binding and was involved in complex formation with DNA through minor groove binding and electrostatic interactions. Experiments like KI quenching studies, dye displacement assays, Circular Dichroism (CD) spectroscopy, DNA melting study, and viscosity measurements studies supported the nonintercalative mode of binding. This was further corroborated by molecular docking studies.

Delivering the 48-hour antimicrobial review on inpatient drug charts.

BACKGROUND: Prolonged or inappropriate antibiotic therapy increases the risk of health-care-associated infections and the development of resistance to antibiotics, and lengthens hospital admissions. There are clear guidelines on antimicrobial stewardship which state that antibiotics should be reviewed between 48 and 72 hours from commencement ( National Institute of Health and Care Excellence, 2015 ). Despite these guidelines this review was often not documented as having been carried out on the authors' inpatient wards. METHODS: A quality improvement project was undertaken with the aim of improving the percentage completion of the 48-hour antimicrobial review box section of the inpatient drug charts to over 90% across two 30-bed acute respiratory wards within 7 weeks. The primary outcome measures were percentage completion of 48-hour antibiotic review and number of days on intravenous antibiotics. The quality improvement programme took place over 7 weeks and included seven interventions designed to improve completion of the 48-hour review. RESULTS: During the study, the percentage completion of 48-hour review rose from a baseline median of 68% to 100% and was accompanied by a reduction in the number of days on intravenous antibiotics from a baseline median of 2.25 days to 1.5 days. CONCLUSIONS: This simple quality improvement project led to a greatly improved review of antimicrobial therapy which was associated with significantly reduced time on intravenous antibiotics. The quality improvement methodology could easily be adapted for other inpatient medical wards.

Interaction of procarbazine with calf thymus DNA-a biophysical and molecular docking study.

Interaction of procarbazine (PCZ) with calf thymus DNA was studied using biophysical and molecular docking studies. Procarbazine was to interact with DNA with a binding constant of 6.52 × 103  M-1 as calculated using ultraviolet-visible spectroscopy. To find out the binding mode, molecular docking was performed that predicted PCZ to interact with DNA through groove binding mode with binding affinity of -6.7 kcal/mole. To confirm the groove binding nature, different experiments were performed. Dye displacement assays confirmed the non-intercalative binding mode. Procarbazine displaced Hoechst dye from the minor groove of DNA while it was unable to displace intercalating dyes. There was no increase in the viscosity of DNA solution in presence of PCZ. Also, negligible change in the secondary structure of DNA was observed in presence of PCZ as evident by circular dichroism spectra. Procarbazine caused decrease in the melting temperature of DNA possibly because of decrease in the stability of DNA caused by groove binding interaction of PCZ with DNA.

The global burden of fasciolosis in domestic animals with an outlook on the contribution of new approaches for diagnosis and control.

Fasciolosis is an economically important disease for livestock, as well as being zoonotic. Recent figures on the prevalence of this disease have caused alarm concerning its potential for an increased prevalence in the future. The prevalence of fascioliosis has been documented from different regions of the world, helping us identify areas where future research needs to be focused. This manuscript is a review of the current status of the disease, the pathogenic species involved, diagnostic techniques (with new modifications and comparative specificity, sensitivity, and rapidity of these tests), chemotherapy, and vaccination. This also encompasses inaccurate reports on vaccination and drug development as well as the latest technologies to find promising candidates for drugs and vaccines. Drugs with lower efficacy have been used on some farms which lead to exacerbation of the clinical disease, presumably due to the development of drug resistance. Future studies should be focused on (1) the use of the most reliable diagnostic tests for periodic monitoring of the disease, (2) insights of the ecobiology and transmission dynamics of the snail intermediate host and the best possible methods of their control, (3) in vitro and in vivo testing of chemotherapeutic compounds using sensitive methods, and (4) the identification of novel drug and vaccine candidates using modern molecular markers. This approach may help increase the reliability of chemotherapeutic agents and control nuisance, ultimately reducing the economic losses attributable to the livestock industry around the world.