Evaluation of microleakage of mineral trioxide aggregate and biodentine as apical barriers in simulated young permanent teeth.

Background: Apexification is a procedure that promotes apical closure by forming mineralized tissue in the apex region of a nonvital young permanent tooth. Calcium silicate-based cement like Mineral trioxide aggregate (MTA) and Biodentine are commonly employed as apical barriers to facilitate this process. Microleakage, defined as the leakage along the junction between the canal wall and filling material, is a crucial aspect to assess in MTA and Biodentine applications as apical barriers, as it directly impacts the prevention of bacterial seepage and maintenance of structural integrity.

Mechanistic and structural insights into vitamin B metabolizing enzyme riboflavin kinase from Leishmania donovani.

Leishmania donovani relies on specific vitamins and cofactors crucial for its survival and pathogenesis. Tailoring therapies to disrupt these pathways offers a promising strategy for the treatment of Visceral Leishmaniasis. Current treatment regimens are limited due to drug resistance and high costs.

A comprehensive review on the current status of CRISPR based clinical trials for rare diseases.

A considerable fraction of population in the world suffers from rare diseases. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and its related Cas proteins offer a modern form of curative gene therapy for treating the rare diseases. Hereditary transthyretin amyloidosis, hereditary angioedema, duchenne muscular dystrophy and Rett syndrome are a few examples of such rare diseases.

Unraveling Amentoflavone's Therapeutic Potential in Alzheimer's Disease: A Preclinical Assessment.

Alzheimer's disease is one of the neurodegenerative diseases which causes cognition deficit. There are currently few medications available to treat Alzheimer's disease, even though researchers have devoted a great deal of time studying the condition and offering many benefits. Thus, only a few drugs are available for the treatment of Alzheimer's disease.

Pyridoxal kinase gene deletion leads to impaired growth, deranged redox metabolism and cell cycle arrest in Leishmania donovani.

Pyridoxal kinase (PdxK) is a vitamin B salvage pathway enzyme which produces pyridoxal phosphate. We have investigated the impact of PdxK deletion in Leishmania donovani on parasite survivability, infectivity and cellular metabolism. LdPdxK mutants were generated by gene replacement strategy.

Clotrimazole causes membrane depolarization and induces sub G cell cycle arrest in Leishmania donovani.

Clotrimazole is an FDA approved drug and is widely used as an antifungal agent. An extensive body of research is available about its mechanism of action on various cell types but its mode of killing of Leishmania donovani parasites is unknown. L.

Use of Eravacycline for Infections: A Case Series.

This case series describes the clinical course of 10 patients who received eravacycline antimicrobial therapy for a variety of different infection types at a community care hospital.

Analytical method development, validation, and out-of-specification investigations for polyethylene glycol.

This work was motivated by the United States Pharmacopeia monograph modernization initiative and European directorate for the quality of medicines and healthcare. An out-of-specification (OOS) occurrence prompted OOS investigations for the cGMP (cGMP refers to the Current Good Manufacturing Practice regulations enforced by the FDA) release testing of residual ethylene oxide in polyethylene glycol (PEG) according to the standards detailed within the United States Pharmacopeia/National Formulary (USP-NF) for polyethylene glycol, and the European Pharmacopoeia (Ph. Eur.

Insights into potassium channel family and their biological functions.

Unlabelled: is the causative organism for visceral leishmaniasis. Although this parasite was discovered over a century ago, nothing is known about role of potassium channels in Potassium channels are known for their crucial roles in cellular functions in other organisms. Recently the presence of a calcium-activated potassium channel in was reported which prompted us to look for other proteins which could be potassium channels and to investigate their possible physiological roles.

Role of Alpha-7-Nicotinic Acetylcholine Receptor in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder affecting millions worldwide. One of the leading hypotheses for the underlying cause of AD is a reduction in nicotinic receptor levels in the brain. Among the nicotinic receptors, the alpha-7-nicotinic acetylcholine receptor (α7nAChR) has received particular attention due to its involvement in cognitive function.

Molecular Docking and Dynamic Simulation to Identify α7nAChR Binding Affinity of Flavonoids for the Treatment of Alzheimer's Disease.

Background: Alpha-7-nicotinic acetylcholine receptor (α7nAChR), a ligand-gated ion channel is one of the important parts of the cholinergic pathway in the brain and has a remarkable role in Alzheimer's disease (AD). It has been documented that the modulation of α7nAChR with the help of phytoconstituent can be helpful in the treatment of AD.

Method: The binding efficacy of fifty flavonoids was evaluated for human α7nAChR using molecular docking.

Highly variable hearing loss due to POU4F3 (c.37del) is revealed by longitudinal, frequency specific analyses.

Genotype-phenotype correlations add value to the management of families with hereditary hearing loss (HL), where age-related typical audiograms (ARTAs) are generated from cross-sectional regression equations and used to predict the audiogram phenotype across the lifespan. A seven-generation kindred with autosomal dominant sensorineural HL (ADSNHL) was recruited and a novel pathogenic variant in POU4F3 (c.37del) was identified by combining linkage analysis with whole exome sequencing (WES).

Leishmania donovani 6-phosphogluconolactonase: Crucial for growth and host infection?

The hexose monophosphate shunt is a crucial pathway in a variety of microorganisms owing to its vital metabolic products and intermediates such as NADPH, ribose 5-phosphate etc. The enzyme 6-phosphogluconolactonase catalyses the second step of this pathway, converting 6-phosphogluconolactone to 6-phosphogluconic acid. This enzyme has been known to have a significant involvement in growth, pathogenesis and sensitivity to oxidative stress in bacterial and protozoal pathogens.

Bilateral chancre of the tongue: An unusual presentation of primary syphilis.

Syphilis is a sexually transmitted infectious disease caused by the spirochete bacterium . A characteristic lesion of primary syphilis is chancre. It can develop over genital or extra genital sites, depending on the site of contact with the infectious agent.

Outbreak of colistin resistant, carbapenemase ( , ) producing causing blood stream infection among neonates at a tertiary care hospital in India.

Infections caused by multi-drug resistant are a leading cause of mortality and morbidity among hospitalized patients. In neonatal intensive care units (NICU), blood stream infections by are one of the most common nosocomial infections leading to poor clinical outcomes and prolonged hospital stays. Here, we describe an outbreak of multi-drug resistant among neonates admitted at the NICU of a large tertiary care hospital in India.

Targeting Parallel Topology of G-Quadruplex Structures by Indole- Fused Quindoline Scaffolds.

Preferential stabilization of G-quadruplex (G4) structures using small-molecule ligands has emerged as an effective approach to develop anticancer drugs. Herein, we report the synthesis of three indole-fused quindoline derivatives with varying lengths of side chains (, , ) as selective ligands for promoter G4 structures. The ligands stabilize the parallel topology of and promoter G4 DNAs over telomeric and duplex DNAs, as evident from the circular dichroism melting and polymerase stop-assay experiments.

Visceral leishmaniasis in the COVID-19 pandemic era.

Visceral l eishmaniasis (VL), also known as kala-azar, had once been targeted for elimination in 2020, which now has been shifted to 2030. The year 2020 was also the year in which the world was gripped by the coronavirus disease 2019 (COVID-19) pandemic. This review sheds light on the impact of COVID-19 on VL elimination programmes and the increasing incidences of COVID-19/VL cases.

Molecular explorations of the Leishmania donovani 6-phosphogluconolactonase enzyme, a key player in the pentose phosphate pathway.

The enzymes of the pentose phosphate pathway are vital to survival in kinetoplastids. The second step of the pentose phosphate pathway involves hydrolytic cleavage of 6-phosphogluconolactone to 6-phosphogluconic acid by 6- phosphogluconolactonase (6PGL). In the present study, Leishmania donovani 6PGL (Ld6PGL) was cloned and overexpressed in bacterial expression system.

An insight into the morphology of DNA compaction induced by homobinuclear Ru(II) polypyridyl complexes.

Binuclear Ru(II) polypyridyl complexes [Ru(NN)(BIPMB)] (1-4), where N-N = 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), dipyrido [3,2-d:2',3'-f] quinoxaline (dpq), and dipyrido[3,2-a:2',3'-c]phenazine (dppz), have been synthesized using suitable precursors and bridging ligand (BIPMB), where BIPMB = 3,3'-bis-{(imidazol-1-yl)-[4,5-f]-1,10-phenanthroline) methyl}-1,1'-biphenyl. The binding mode and affinity of complexes 1-4 with Calf Thymus DNA (CT-DNA) were determined by absorption and steady-state fluorescence spectroscopy. The decrease in viscosity of CT-DNA on sequential addition of these complexes indicated DNA condensation and the result was corroborated by circular dichroism (CD).

A Core-Linker-Polyamine (CLP) Strategy Enables Rapid Discovery of Antileishmanial Aminoalkylquinolinecarboxamides That Target Oxidative Stress Mechanism.

A Core-Linker-Polyamine (CLP) strategy has been exploited to develop new antileishmanial agents. It involves the linker-based assembly of alkyl-polyamine side chain as a potential pharmacophore motif with a privileged heterocyclic motif, 4-arylquinoline. A series of aminoalkyl 4-arylquinoline-2-carboxamides and their analogs were synthesized and tested against L.

Identification of 2-arylquinazolines with alkyl-polyamine motifs as potent antileishmanial agents: synthesis and biological evaluation studies.

2-Arylquinazolines with a range of alkyl polyamines as side chain/ring functional motifs at the 4th-position were considered for antileishmanial study with the rationale that related heterocyclic scaffolds and polyamine functionalities are present in drugs, clinical trial agents, natural products and anti-parasitic/leishmanial agents. Synthesis involves construction of the 2-arylquinazolin-4-one ring and deoxyamination deoxychlorination followed by SAr-based amination or a methodology of SAr-deoxyamination driven by BOP-mediated hydroxyl-activation. Various alkyl-polyamines important for activities were incorporated.

Autosomal dominant non-syndromic hearing loss maps to DFNA33 (13q34) and co-segregates with splice and frameshift variants in ATP11A, a phospholipid flippase gene.

Sequencing exomes/genomes have been successful for identifying recessive genes; however, discovery of dominant genes including deafness genes (DFNA) remains challenging. We report a new DFNA gene, ATP11A, in a Newfoundland family with a variable form of bilateral sensorineural hearing loss (SNHL). Genome-wide SNP genotyping linked SNHL to DFNA33 (LOD = 4.

Stabilization and fluorescence light-up of G-quadruplex nucleic acids using indolyl-quinolinium based probes.

G-Quadruplexes (G4s) are four-stranded motifs formed by G-rich nucleic acid sequences. These structures harbor significant biological importance as they are involved in telomere maintenance, transcription, and translation. Owing to their dynamic and polymorphic nature, G4 structures relevant for therapeutic applications need to be stabilized by small-molecule ligands.

Identification of a novel calcium activated potassium channel from Leishmania donovani and in silico predictions of its antigenic features.

Visceral Leishmaniasis is a major neglected tropical disease with increasing incidences of drug resistance. This has led to the search for a suitable drug target for chemotherapeutic intervention. Potassium channels are a family of membrane proteins which play a vital role in homeostasis and any perturbation in them alters cell survival which makes them an attractive target.

Deletion of Glutamine Synthetase Gene Disrupts the Survivability and Infectivity of .

Glutamine synthetase (GS) is one of the most important metabolic enzymes which catalyzes ligation of glutamate and ammonia to form glutamine. Previous studies from our lab had revealed significant differences in parasite and host GS enzyme which warranted us to further work on its relevance in parasite. To analyze glutamine synthetase function in , we generated GS overexpressors and knockout mutants and evaluated their ability to grow in monocyte differentiated macrophage and by infections in BALB/c mice.