Ligand interaction landscape of transcription factors and essential enzymes in E. coli.

Knowledge of protein-metabolite interactions can enhance mechanistic understanding and chemical probing of biochemical processes, but the discovery of endogenous ligands remains challenging. Here, we combined rapid affinity purification with precision mass spectrometry and high-resolution molecular docking to precisely map the physical associations of 296 chemically diverse small-molecule metabolite ligands with 69 distinct essential enzymes and 45 transcription factors in the gram-negative bacterium Escherichia coli. We then conducted systematic metabolic pathway integration, pan-microbial evolutionary projections, and independent in-depth biophysical characterization experiments to define the functional significance of ligand interfaces.

Pharmacological, computational, and mechanistic insights into triptolide's role in targeting drug-resistant cancers.

As a promising candidate for tackling drug-resistant cancers, triptolide, a diterpenoid derived from the Chinese medicinal plant Tripterygium wilfordii, has been developed. This review summarizes potential antitumor activities, including the suppression of RNA polymerase II, the suppression of heat shock proteins (HSP70 and HSP90), and the blockade of NF-kB signalling. Triptolide is the first known compound to target cancer cells specifically but spare normal cells, and it has success in treating cancers that are difficult to treat, including pancreatic, breast, and lung cancers.

Biosynthesis, characterization, and multifaceted applications of Elytraria acaulis synthesized silver and gold nanoparticles: Anticancer, antibacterial, larvicidal, and photocatalytic activities.

Green synthesis of metal nanoparticles using plant extracts has emerged as an eco-friendly alternative to conventional methods, offering potential applications in biomedicine and environmental remediation. This study demonstrates the successful biosynthesis of silver nanoparticles (SNPs) and gold nanoparticles (GNPs) using Euphorbia acaulis leaf extract as a reducing and capping agent. The nanoparticles were thoroughly characterized using UV-Vis spectroscopy, HR-SEM, EDX, TEM, AFM, XRD, and FTIR analyses, confirming their successful synthesis and revealing their predominantly spherical morphology with sizes ranging from 1 to 100 nm.

Pooling the complex survey data across the 64 lower and middle-income countries: A study on antibiotic usage in under-five children.

Background: Antibiotic exposure for fever/cough has been rising alarmingly, especially among children under five in low- and middle-income countries (LMICs). This excessive use could result in higher healthcare costs, and antibiotic resistance is an alarming trend in developing countries. As a result, it's crucial to look at the variables that affect antibiotic exposure and highlight the subgroups among whom antibiotic abuse is the most prevalent.

The interplay of senescence and MMPs in myocardial infarction: implications for cardiac aging and therapeutics.

Aging is associated with a marked increase in cardiovascular diseases, such as myocardial infarction (MI). Cellular senescence is also a crucial factor in the development of age-related MI. Matrix metalloproteinases (MMPs) interaction with cellular senescence is a critical determinant of MI development and outcomes, most notably in the aged heart.

Targeting senescence and GATA4 in age-related cardiovascular disease: a comprehensive approach.

The growing prevalence of age-related cardiovascular diseases (CVDs) poses significant health challenges, necessitating the formulation of novel treatment approaches. GATA4, a vital transcription factor identified for modulating cardiovascular biology and cellular senescence, is recognized for its critical involvement in CVD pathogenesis. This review collected relevant studies from PubMed, Google Scholar, and Science Direct using search terms like 'GATA4,' 'cellular senescence,' 'coronary artery diseases,' 'hypertension,' 'heart failure,' 'arrhythmias,' 'congenital heart diseases,' 'cardiomyopathy,' and 'cardiovascular disease.

The role of GATA4 in mesenchymal stem cell senescence: A new frontier in regenerative medicine.

The Mesenchymal Stem Cell (MSC) is a multipotent progenitor cell with known differentiation potential towards various cell lineage, making it an appealing candidate for regenerative medicine. One major contributing factor to age-related MSC dysfunction is cellular senescence, which is the hallmark of relatively irreversible growth arrest and changes in functional properties. GATA4, a zinc-finger transcription factor, emerges as a critical regulator in MSC biology.

Novel, standardized sample collection from the brain-nose interface.

Background: Diagnostics for neurodegenerative diseases lack non-invasive approaches suitable for early-stage biochemical screening and routine examination of neuropathology. Biomarkers of neurodegenerative diseases pass through the brain-nose interface (BNI) and accumulate in nasal secretion. Sample collection from the brain-nose interface presents a compelling prospect as basis for a non-invasive molecular diagnosis of neuropathologies.

Chronic kidney disease and aging: dissecting the p53/p21 pathway as a therapeutic target.

Chronic kidney diseases (CKD) are a group of multi-factorial disorders that markedly impair kidney functions with progressive renal deterioration. Aging contributes to age-specific phenotypes in kidneys, which undergo several structural and functional alterations, such as a decline in regenerative capacity and increased fibrosis, inflammation, and tubular atrophy, all predisposing them to disease and increasing their susceptibility to injury while impeding their recovery. A central feature of these age-related processes is the activation of the p53/p21 pathway signaling.

Fish in focus: Navigating organ damage assessment through analytical avenues - A comprehensive review.

Aquatic ecosystems, critical for biodiversity and food production, confront escalating threats from anthropogenic activities like pollution and climate change, impacting fish health. This review outlines various assays used to study organ damage in fish, ranging from traditional histopathology to advanced molecular and biochemical methods. The aim is to guide researchers in selecting suitable assays for their specific questions, considering the advantages and limitations of each technique.

Exosome-mediated delivery of CRISPR-Cas9: A revolutionary approach to cancer gene editing.

Several molecular strategies based on targeted gene delivery systems have been developed in recent years; however, the CRISPR-Cas9 technology introduced a new era of targeted gene editing, precisely modifying oncogenes, tumor suppressor genes, and other regulatory genes involved in carcinogenesis. However, efficiently and safely delivering CRISPR-Cas9 to cancer cells across the cell membrane and the nucleus is still challenging. Using viral vectors and nanoparticles presents issues of immunogenicity, off-target effects, and low targeting affinity.

Liquid biopsies and exosomal ncRNA: Transforming pancreatic cancer diagnostics and therapeutics.

Pancreatic cancer is a highly fatal malignancy due to poor early detection rate and resistance to conventional therapies. This review examines the potential for liquid biopsy as a transformative technology to identify diagnostic and therapeutic targets in pancreatic cancer. Specifically, we explore emerging biomarkers such as exosomal non-coding RNAs (ncRNAs), circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs).

Prediction of mortality in sepsis patients using stacked ensemble machine learning algorithm.

Introduction: Machine learning (ML) has been tried in predicting outcomes following sepsis. This study aims to identify the utility of stacked ensemble algorithm in predicting mortality.

Methods: The study was a cohort of adults admitted to a medical unit of a tertiary care hospital with sepsis.

Rhinitis Caseosa: A Forgotten Entity.

Rhinitis caseosa, also known as nasal cholesteatoma, is an uncommon disorder marked by the growth of caseous masses of material in the nose and, rarely, the maxillary antrum. This disease can be caused by tuberculosis, syphilis, erysipelas, Strepthrix alba infection, polyp degeneration, or suppuration due to protracted blockage. Patients mostly present with complaints of nasal obstruction with foul-smelling nasal discharge and can mimic features of sinonasal malignancy or fungal rhinosinusitis.

Cavernous Lymphangioma of the Neck: An Extraordinary Case.

Cervical lymphangioma is a congenital malformation of the lymphatic system that shows a predilection for the head and neck regions. They are most common in children between the ages of three and five and are rarely present in adults. While over 90% of lymphatic malformations are congenital, they can also manifest later due to factors such as trauma, infection, tumors, or medical procedures.

Targeting protein homeostasis with small molecules as a strategy for the development of pan-coronavirus antiviral therapies.

The COVID-19 pandemic has created a global health crisis, with challenges arising from the ongoing evolution of the SARS-CoV-2 virus, the emergence of new strains, and the long-term effects of COVID-19. Aiming to overcome the development of viral resistance, our study here focused on developing broad-spectrum pan-coronavirus antiviral therapies by targeting host protein quality control mechanisms essential for viral replication. Screening an in-house compound library led to the discovery of three candidate compounds targeting cellular proteostasis.

Unmasking Infection Risks in Multiple Myeloma: Insights from a Retrospective Analysis.

Multiple myeloma (MM) has witnessed significant therapeutic advancements through the introduction of proteasome inhibitors and immunomodulators, leading to improved treatment outcomes. However, infections remain a formidable challenge for MM patients. The objective of our research is to investigate the factors that can forecast infection risk in MM patients.