Unraveling Interleukin-1β inhibition: Computational insights into anti-inflammatory compound selection for inflammatory disorders.

The multifaceted impact of IL-1β has been proposed to have a central role in a spectrum of immunological responses spanning physiological reactions to aggressive inflammatory reactions and autoimmune disorders. Once IL-1β binds to its cognate receptor it initiates IL-1R1/TLR4 signaling cascade, leading to transcriptional modifications that sustain the inflammatory response. Extensive structural and functional investigations on IL-1β have yielded various inhibitors aimed at disrupting the formation of ligand receptor complex.

Shifting paradigms: The promise of allosteric inhibitors against dengue virus protease.

Dengue, a mosquito-borne viral infection caused by the dengue virus (DENV), is a global health challenge. Annually, approximately 400 million cases are reported worldwide, signaling a persistent upward trend from previous years and projected a manifold increase in the future. There is a growing need for innovative and integrated approaches aimed at effective disease management.

Maple compounds prevent biofilm formation in via sortase inhibition.

The Pss exopolysaccharide (EPS) enhances the ability of the foodborne pathogen to colonize and persist on surfaces of fresh fruits and vegetables. Eradicating listeria within EPS-rich biofilms is challenging due to their increased tolerance to disinfectants, desiccation, and other stressors. Recently, we discovered that extracts of maple wood, including maple sap, are a potent source of antibiofilm agents.

Temporal and spatial patterns of eggs: a potential threat to human health in Pakistan.

This study investigates the presence of eggs in soil samples collected from urban areas in Lahore, Pakistan. A total of 3600 soil samples were collected over two years from Lahore's urban regions. The detection of helminth eggs in these samples was performed using sodium hypochlorite (NaOCl) as a diagnostic technique.

Uncovering PPAR-γ agonists: An integrated computational approach driven by machine learning.

Peroxisome proliferator-activated receptor gamma (PPAR-γ) serves as a nuclear receptor with a pivotal function in governing diverse facets of metabolic processes. In diabetes, the prime physiological role of PPAR-γ is to enhance insulin sensitivity and regulate glucose metabolism. Although PPAR-γ agonists such as Thiazolidinediones are effective in addressing diabetes complications, it is vital to be mindful that they are associated with substantial side effects that could potentially give rise to health challenges.

Starvation induces changes in abundance and small RNA cargo of extracellular vesicles released from Plasmodium falciparum infected red blood cells.

The lethal malaria parasite Plasmodium falciparum needs to constantly respond and adapt to changes within the human host in order to survive and transmit. One such change is composed of nutritional limitation, which is augmented with increased parasite loads and intimately linked to severe disease development. Extracellular vesicles released from infected red blood cells have been proposed as important mediators of disease pathogenesis and intercellular communication but whether important for the parasite response to nutritional availability is unknown.

Glutamate Dehydrogenase (GdhA) of Streptococcus pneumoniae Is Required for High Temperature Adaptation.

During its progression from the nasopharynx to other sterile and nonsterile niches of its human host, Streptococcus pneumoniae must cope with changes in temperature. We hypothesized that the temperature adaptation is an important facet of pneumococcal survival in the host. Here, we evaluated the effect of temperature on pneumococcus and studied the role of glutamate dehydrogenase (GdhA) in thermal adaptation associated with virulence and survival.

Outcomes of Spousal versus Parental Donor Kidney Transplants: A Comparative Study.

Introduction: Parents and spouse constitute 70% of organ donors in India. Some centres use induction immunosuppression (IS) for all spousal transplants considering it as an immunologically high risk. This study was designed to compare the outcomes of transplant recipients who received parental donors (PDs) and spousal donors (SDs) without any induction IS.

The Rgg1518 transcriptional regulator is a necessary facet of sugar metabolism and virulence in Streptococcus pneumoniae.

Rggs are a group of transcriptional regulators with diverse roles in metabolism and virulence. Here, we present work on the Rgg1518/SHP1518 quorum sensing system of Streptococcus pneumoniae. The activity of Rgg1518 is induced by its cognate peptide, SHP1518.

2,4-Dichlorophenoxyacetic acid induced hepatic and renal toxicological perturbations in rat model: Attenuation by selenium supplementation.

2,4-Dichlorophenoxyacetic acid (2,4-D) is a commercially used herbicide to manage broadleaf weeds that have various toxicological and ecological effects. In view of ever-escalating use of 2,4-D, risk assessment becomes mandatory to ensure the safety of both human health and the ecosystem. Oxidative injury has been expected as a possible mechanism implicated in 2,4-D toxicity.

Clarithromycin Exerts an Antibiofilm Effect against Serovar Typhimurium rdar Biofilm Formation and Transforms the Physiology towards an Apparent Oxygen-Depleted Energy and Carbon Metabolism.

Upon biofilm formation, production of extracellular matrix components and alteration in physiology and metabolism allows bacteria to build up multicellular communities which can facilitate nutrient acquisition during unfavorable conditions and provide protection toward various forms of environmental stresses to individual cells. Thus, bacterial cells within biofilms become tolerant against antimicrobials and the immune system. In the present study, we evaluated the antibiofilm activity of the macrolides clarithromycin and azithromycin.

Draft Genome Sequence of the Urinary Catheter Isolate CEB04 with High Biofilm Forming Capacity.

is a fermentative Gram-negative environmental species and accidental human pathogen that belongs to the complex with the general characteristics of the genus Enterobacter. The clinical isolate CEB04 was derived from a urinary tract catheter of an individual not suffering from catheter-associated urinary tract infection. The draft genome sequence of the high biofilm forming CEB04 was determined by PacBio sequencing.

TprA/PhrA Quorum Sensing System Has a Major Effect on Pneumococcal Survival in Respiratory Tract and Blood, and Its Activity Is Controlled by CcpA and GlnR.

is able to cause deadly diseases by infecting different tissues, each with distinct environmental and nutritional compositions. We hypothesize that the adaptive capabilities of the microbe is an important facet of pneumococcal survival in fluctuating host environments. Quorum-sensing (QS) mechanisms are pivotal for microbial host adaptation.

Magnesium supplementation ameliorates toxic effects of 2,4-dichlorophenoxyacetic acid in rat model.

2,4-Dichlorophenoxyacetic acid (2,4-D) is an extensively used herbicide in the field of agriculture, its ever-escalating use induces toxicity, health effects, and environmental impact. Oxidative stress plays a key role in pathogenesis of 2,4-D-induced liver and kidney damage. Magnesium (Mg) is a highly effective antioxidant agent in restoring oxidative damage by directly influencing the metabolic and physiological processes.

Impact of manganese on biofilm formation and cell morphology of Candida parapsilosis clinical isolates with different biofilm forming abilities.

The commensal species Candida parapsilosis is an emerging human pathogen that has the ability to form biofilms. In this study, we explored the impact of the divalent cations cobalt (Co2+), copper (Cu2+), iron (Fe3+), manganese (Mn2+), nickel (Ni2+) and zinc (Zn2+) on biofilm formation of clinical isolates of C. parapsilosis with no, low and high biofilm forming abilities at 30 and 37°C.

JAGN1 is required for fungal killing in neutrophil extracellular traps: Implications for severe congenital neutropenia.

Mutations in the gene JAGN1 were recently discovered in patients with severe congenital neutropenia (SCN). Neutrophils release neutrophil extracellular traps (NETs) consisting of decondensed chromatin decorated with various granular proteins such as neutrophil elastase and myeloperoxidase (MPO) to combat microbial infections. However, whether JAGN1 is required for the formation or function of NETs is not known.

NADH-Mediated Gene Expression in and Role of Rex as a Transcriptional Repressor of the Rex-Regulon.

Nicotinamide adenine dinucleotides (NAD(H)) play a vital role in various biological processes, including keeping the cellular redox balance. In this study, we investigate the regulatory responses of D39 to NADH and characterize the role of the Rex protein as a transcriptional repressor of the , and genes. Transcriptomic analysis was used to observe the response of D39 to NADH.

Rgg-Shp regulators are important for pneumococcal colonization and invasion through their effect on mannose utilization and capsule synthesis.

Microbes communicate with each other by using quorum sensing (QS) systems and modulate their collective 'behavior' for in-host colonization and virulence, biofilm formation, and environmental adaptation. The recent increase in genome data availability reveals the presence of several putative QS sensing circuits in microbial pathogens, but many of these have not been functionally characterized yet, despite their possible utility as drug targets. To increase the repertoire of functionally characterized QS systems in bacteria, we studied Rgg144/Shp144 and Rgg939/Shp939, two putative QS systems in the important human pathogen Streptococcus pneumoniae.

Modulation of Quorum Sensing in a Gram-Positive Pathogen by Linear Molecularly Imprinted Polymers with Anti-infective Properties.

We describe the development, characterization, and biological testing of a new type of linear molecularly imprinted polymer (LMIP) designed to act as an anti-infective by blocking the quorum sensing (QS) mechanism and so abrogating the virulence of the pathogen Streptococcus pneumoniae. The LMIP is prepared (polymerized) in presence of a template molecule, but unlike in traditional molecular imprinting approaches, no cross-linker is used. This results in soluble low-molecular-weight oligomers that can act as a therapeutic agent in vitro and in vivo.

CodY Regulates Thiol Peroxidase Expression as Part of the Pneumococcal Defense Mechanism against HO Stress.

is a facultative anaerobic pathogen. Although it maintains fermentative metabolism, during aerobic growth pneumococci produce high levels of HO, which can have adverse effects on cell viability and DNA, and influence pneumococcal interaction with its host. The pneumococcus is unusual in its dealing with toxic reactive oxygen species (ROS) in that it neither has catalase nor the global regulators of peroxide stress resistance.

Methionine-mediated gene expression and characterization of the CmhR regulon in .

This study investigated the transcriptomic response of D39 to methionine. Transcriptome comparison of the D39 wild-type grown in chemically defined medium with 0-10 mM methionine revealed the elevated expression of various genes/operons involved in methionine synthesis and transport (, , , , , , , , , and ). Furthermore, -galactosidase assays and quantitative RT-PCR studies demonstrated that the transcriptional regulator, CmhR (SPD-0588), acts as a transcriptional activator of the , , , , and genes.

Niacin-mediated Gene Expression and Role of NiaR as a Transcriptional Repressor of , and in .

NAD (Nicotinamide Adenine Dinucleotide) biosynthesis is vital for bacterial physiology and plays an important role in cellular metabolism. A naturally occurring vitamin B complex, niacin (nicotinic acid), is a precursor of coenzymes NAD and NADP. Here, we study the impact of niacin on global gene expression of D39 and elucidate the role of NiaR as a transcriptional regulator of , and .

Impact of aspirin on the transcriptome of D39.

Aspirin or acetylsalicylic acid (ASA) is a medicine used to treat pain, fever, and inflammation. Here, we for the very first time reported the genome-wide transcriptional profiling of aspirin-regulated genes in in the presence of 5 mM aspirin in chemically-defined medium (CDM) using microarray analysis. Our results showed that expression of several genes was differentially expressed in the presence of aspirin.

Pneumococcal galactose catabolism is controlled by multiple regulators acting on pyruvate formate lyase.

Catabolism of galactose by Streptococcus pneumoniae alters the microbe's metabolism from homolactic to mixed acid fermentation, and this shift is linked to the microbe's virulence. However, the genetic basis of this switch is unknown. Pyruvate formate lyase (PFL) is a crucial enzyme for mixed acid fermentation.

Cysteine-Mediated Gene Expression and Characterization of the CmbR Regulon in .

In this study, we investigated the transcriptomic response of D39 to cysteine. Transcriptome comparison of the D39 wild-type grown at a restricted concentration of cysteine (0.03 mM) to one grown at a high concentration of cysteine (50 mM) in chemically-defined medium (CDM) revealed elevated expression of various genes/operons, i.