Genomic analysis and preclinical evaluation of two hydrogel-formulated novel virulent phages isolated against a carbapenem-resistant Acinetobacter baumannii.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) has recently become a serious cause for global concern because of non-susceptibility to multiple antimicrobial classes, its prevalence in nosocomial infections, and the lack of effective treatments against such a pathogen.

Methods: This study isolated two lytic phages from hospital sewage, purified, propagated, characterized morphologically by transmission electron microscopy, and genomically by Oxford Nanopore Sequencing. The phage lysates were then formulated individually as carboxymethylcellulose (CMC) 5 % w/v hydrogels.

Succinic acid enhances sedative activity of diazepam through GABAergic receptor modulation: Evidence from behavioral approach and computational insights.

Insomnia, a widespread neurological condition, is often managed with diazepam (DZP), a gamma-aminobutyric acid A (GABA) receptor agonist, though prolonged use raises concerns about dependence and cognitive impairment. This study investigated the sedative and locomotor-suppressive effects of succinic acid (SUC), alone and in combination with DZP, supported by behavioral and computational analyses. Swiss albino mice were treated intraperitoneally (i.

Deregulated cell cycle control: The interplay between non-coding RNAs and cyclin-dependent kinases in tumorigenesis.

Cyclin-dependent kinases (CDKs) are a group of serine/threonine kinases that are at the center of cell cycle progression. Dysregulated CDK activity, found in a range of human cancers, leads to uncontrolled cell growth and development. Non-coding RNAs (ncRNAs), which include microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are emerging as critical regulators of gene expression and cellular processes, playing an important and often complex role in cancer development and progression.

Evaluation of different sedation scales in the ICU management of COVID-19 patients.

This study evaluated the inter-rater reliability and diagnostic validity of different sedation scales for COVID-19 patients in the ICU, focusing on optimizing patient management and outcomes amidst unique pathophysiological challenges. Seventy-three mechanically ventilated COVID-19 patients sedated with intravenous ketamine (10-20 µg/kg/min) were evaluated at Ali Ibn Abi Talib Hospital, Zahedan, Iran, in 2022 and 2023. The sample size was calculated to detect significant differences with a 95% confidence level.

Recent advances in nanozymes based on mesoporous materials for enhancing the performance of colorimetric biosensors: Applications and challenges.

Despite significant advancements in colorimetric assays, challenges in their sensitivity and selectivity remain, hindering their widespread applications. The nanotechnology revolution has played a pivotal role in developing sensitive and selective colorimetric biosensing assays, especially through the use of mesoporous materials to improve the performance of nanozymes and mesoporous nanozymes in colorimetric sensing. The role of mesoporous materials in these systems can be classified into three main types: supporting matrix, coating agent, and nanozymes themselves.

Efficient synthesis of N-(ethylcarbamothioyl)-1-naphthamide: X-ray structure, Hirshfeld surface analysis, DFTs, and molecular modelling investigations as selective inhibitor of alkaline phosphatase.

Naphthyl Thiourea based derivative N-(ethylcaramothbioyl)-1-naphthamide (NA-MT) was synthesized by freshly prepared 1-naphthoyl isothiocyanate with ethyl amine to afford the products (NA-MT) high purity and characterized via spectroscopic techniques including FTIR, H-NMR, C-NMR, elemental and HRMS analysis and single crystal X-ray diffraction. In-vitro analysis showed that the compound (NA-MT) possesses potent inhibitory effect with IC = 9.875 ± 0.

Optimization of Pyrocatechol and p-Cresol adsorption onto a composite of Chitosan and polyacrylamide incorporated with zeolitic imidazolate Framework-8.

The objective of the current research was to adsorb pyrocatechol and p-cresol from a water-based solution using CS-PAA-ZIF-8. Response surface methodology (RSM) using central composite design (CCD) was utilized to examine and optimize the process variables. These variables included pH, concentrations of pyrocatechol and p-cresol, mass of the adsorbent, and contact time.

Synthesis and evaluation of thiazolyl coumarin drug conjugates as carbonic anhydrase isozyme inhibitors by using integrated invitro and insilico approaches.

A new series of thiazolyl-coumarin-drug conjugates were synthesized through the reaction of 3-bromoacetylcoumarin and N-substituted and N, N-di-substituted thioureas. The synthesized compounds were characterized byH-NMR,C-NMR and FTIR spectroscopy and thoroughly analyzed through in-vitro and in-silico studies. Among these, derivatives 8b and 8d demonstrated significant inhibitory effects during in vitro analysis.

Coumarin derivatives as anticancer agents targeting PI3K-AKT-mTOR pathway: a comprehensive literature review.

Coumarin is a natural benzopyrone compound known for its diverse pharmacological activities, including anticancer, anti-inflammatory, and antioxidant properties. But its derivatives' exploration in cancer, specially PI3K-AKT-mTOR pathways-based cancer activity not explored yet. This review aims to evaluate the anticancer potential of coumarin derivatives' by exploring their modulatory effects on the PI3K-AKT-mTOR signaling pathway across diverse cancer types.

Taurine and Neuroprotection: A Potential Shield Against Methylglyoxal-Induced Toxicity in SH-SY5Y Cells.

Methylglyoxal (MG) is thought to have harmful effects on Alzheimer's disease (AD). On the other hand, taurine demonstrates promising potential for treating AD. Therefore, we examined the neuroprotective properties of taurine against MG in the SH-SY5Y cells.

Solid-state fermentation of pristinamycin by Streptomyces pristinaespiralis NRRL ISP-5338 using D-optimal design.

Pristinamycin (PST), produced by Streptomyces pristinaespiralis NRRL ISP-5338, is a streptogramin antibiotic with remarkably broad-spectrum bactericidal activity. The production of PST from its natural producer remains challenging. In the literature, a few reports examined PST production using submerged liquid fermentation (SLF).

Anticancer, antimicrobial and molecular docking analysis of newly synthesized iodoquinazoline derivatives.

The 4-anilinoquinazoline sulfonamide derivatives in medicinal chemistry are well-known antitumor backbones via different mechanisms. Herein, we reported the synthesis of five new 2,4-disubstituted-6-iodoquinazoline derivatives coded compounds 3a-e. The respective compounds were examined for their antiproliferative, antimicrobial, and carbonic anhydrase XII (CAXII) inhibitory activity against four cancerous cell lines.

Molecular assessment of carbapenem-resistant and ESBL Klebsiella pneumoniae clinical isolates to decipher the correlation of antimicrobial resistance with virulence traits.

Klebsiella pneumoniae is a nosocomial pathogen that poses a serious concern due to the high prevalence of extended-spectrum beta-lactamases (ESBL) and carbapenem-resistant K. pneumoniae (CRKP) strains. However, the data on the prevalence of contributing virulence determinants are limited in the Pakistani population.

Unveiling the anticancer potential of Pinostrobin: mechanisms of action, pharmacokinetic insights, and therapeutic prospects.

Pinostrobin (PIN), a natural flavonoid found in Boesenbergia rotunda, Alpinia zerumbet, and other botanicals, has shown promising anticancer potential due to its multitargeted mechanisms and favorable safety profile. This review consolidates current evidence on PIN's anticancer properties, focusing on its molecular mechanisms, pharmacokinetics (PKs), and therapeutic potential. A systematic literature search was conducted using PubMed, Scopus, ScienceDirect, and Google Scholar to identify preclinical studies on PIN's bioactivity, PK, and toxicity.

EZH2 in digestive system cancers: Epigenetic regulation, oncogenic interactions, and therapeutic potential.

EZH2 (enhancer of zeste homolog 2) is an important component of the Polycomb Repressive Complex 2 (PRC2) and is essential for the epigenetic regulation of gene expression. EZH2 primarily methylates histone H3 at lysine 27 (H3K27me3) to repress target gene transcription, particularly concerning tumor suppressor genes. The silencing of these genes ultimately promotes cancer by facilitating several important processes, a notable one being epithelial-mesenchymal transition (EMT), which promotes the invasiveness and metastatic potential of cancer cells, particularly in digestive system cancers.

Unraveling the global landscape of Elizabethkingia antibiotic resistance: A systematic review and meta-analysis.

Background: The emergence of antibiotic-resistant Elizabethkingia strains poses a significant challenge in clinical settings. This systematic review and meta-analysis provide a comprehensive assessment of the prevalence of antibiotic resistance among Elizabethkingia isolates across different regions worldwide.

Methods: A systematic literature search was conducted across PubMed, Embase, Web of Science, and Scopus from 1998 to January 9, 2024, using predefined search strategies.

The exploring AI-generated pyrazalone derivatives as antifungal agents: Bringing together molecular docking and quantum chemical approaches.

Candida albicans, an opportunistic fungal pathogen, is the most prevalent species among the twenty types of Candida responsible for candidiasis in humans. The condition is characterized by symptoms such as itching, redness, skin rashes, fever, septic shock, and infections of mucous membranes. This study explores the potential of pyrazolones and their AI-generated derivatives as effective treatments for these fungal infections.

D-optimal design model and biosynthetic pathway for gentamicin production by Micromonospora purpureochromogenes NRRL B-16094.

Background: Micromonospora purpureochromogenes NRRL B-16094, a natural producer of gentamicin (GEN), a 5,6-diglycosylated 2-dexoystreptamine-aminoglycoside antibiotic (2DOS-AGA) broad-spectrum bactericidal activity. In literature, limited studies are concerned with the biosynthetic route and various cultural conditions influencing GEN production.

Methods: Therefore, this study aimed to explore the GEN biosynthesis pathway and compare it to that of fortimicin and kanamycin.

In vitro, genomic characterization and pre-clinical evaluation of a new thermostable lytic Obolenskvirus phage formulated as a hydrogel against carbapenem-resistant Acinetobacter baumannii.

The urgent threat of carbapenem-resistant Acinetobacter baumannii (CRAB) necessitates the development of new antimicrobial strategies. Bacteriophage (phage) therapy is one of the most promising alternative strategies that can be implemented to combat multidrug-resistant (MDR) bacterial infections. Herein, an A.

Medicinal plants: bioactive compounds, biological activities, combating multidrug-resistant microorganisms, and human health benefits - a comprehensive review.

In recent years, medicinal plants have gained significant attention in modern medicine due to their accessibility, affordability, widespread acceptance, and safety, making herbal remedies highly valued globally. Consequently, ensuring medicinal plants' quality, efficacy, and safety has become a critical concern for developed and developing nations. The emergence of multidrug-resistant microorganisms poses a serious global health threat, particularly in low-income regions, despite significant advancements in antimicrobial drugs and medical research over the past century.

Identifying potent Janus kinase 3 inhibitors using structure-guided virtual screening for inflammatory and neoplastic disease therapy.

Janus kinases (JAKs) are potential therapeutic targets for anti-inflammatory and anti-cancer agents due to their involvement in cytokine signaling and cell proliferation. One of the major issues in the development of JAK inhibitors is the problem of selectivity for certain isoforms; since the isoforms are highly homologous, selective targeting is difficult. Of the JAKs, Janus kinase 3 (JAK3) which is mainly found in immune cells, is the most suitable isoform to target selectively to enhance the efficacy of treatment.

A novel thermostable lytic phage vB_EF_Enf3_CCASU-2024-3 against clinical Enterococcus faecium and Enterococcus faecalis.

Enterococci, Gram-positive bacteria, have become a major concern in healthcare settings due to their significant virulence and antibiotic resistance. This research focuses on isolating, phenotypic, and genotypic analysis of enterococci-specific lytic phages to be used as potential candidates in combating multidrug-resistant (MDR) Enterococcus clinical isolates. The virulence of Enterococcus isolates was analyzed by testing for gelatinase and biofilm formation.

A mathematical framework of HIV and TB co-infection dynamics.

The biological processes involved in diseases like human immunodeficiency virus (HIV) and tuberculosis (TB) require extensive research, particularly when both diseases occur together. This piece of research delves to explore a new fractional-order mathematical model that examines the co-dynamics of HIV and TB, taking into account the treatment effects. Although no definitive vaccine or cure for HIV exists, antiretroviral therapy (ART) can slow disease spread and prevent subsequent complications.

Evaluation of the taxonomic classification tools and visualizers for metagenomic analysis using the Oxford nanopore sequence database.

Microbial metagenomic identification is generally attributed to the specificity and type of the bioinformatic tools, including classifiers and visualizers. In this study, the performance of two major classifiers, Centrifuge and Kraken2, and two visualizers (Recentrifuge and Krona) has been thoroughly investigated for their efficiency in the identification of the microorganisms using the Whole-Genome Sequence (WGS) database and four targeted databases including NCBI, Silva, Greengenes, and Ribosomal Database Project (RDP). Two standard DNA metagenomic library replicates, Zymo and Zymo-1, were used as quality control.

The multifaceted role of CS1 (SLAMF7) in immunoregulation: Implications for cancer therapy and autoimmune disorders.

CS1 (SLAMF7), a pivotal immune receptor, plays a dual role in modulating immune responses in autoimmune diseases and cancer. In autoimmunity, aberrant CS1 signaling contributes to the activation of autoreactive lymphocytes, driving pathologies such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Conversely, in oncology, CS1 serves as a promising immunotherapeutic target, exemplified by the efficacy of the monoclonal antibody Elotuzumab in multiple myeloma.