An overview of matrix metalloproteinase-12 in multiple disease conditions, potential selective inhibitors, and drug designing strategies.

Matrix metalloproteases (MMPs) are the proteolytic enzymes accountable for extracellular matrix (ECM) modification through their Zn-dependent catalytic activity. Among these, MMP-12 is one of the crucial MMPs that contributes to various disease states including different types of cancers and other major pathophysiological conditions including COPD, asthma, emphysema, skin diseases, arthritis, vascular diseases, and neurological disorders. The majority of the MMP-12 inhibitors should have three constitutional pharmacophoric features (i.

The Effect of Cancer Cell-Derived Exosomal Proteins on Macrophage Polarization: An In-depth Review.

Background: Cancer is characterized by unregulated cell proliferation, enabling it to invade and spread to different organs and tissues in the body. Cancer progression is intricately influenced by the complex dynamics within the tumor microenvironment (TME). The tumor microenvironment (TME) is a composite and dynamic network comprising cancer cells and various immune cells, including tumor-associated macrophages.

GC-MS and HPTLC Fingerprinting Analysis and Evaluation of Antimicrobial Activity of Naga Chilli: An In Vitro and In Silico Approach.

Naga chilli (Capsicum chinense Jacq.) have garnered significant attention due to the plant's possible health benefits and variety of phytochemical components. Utilizing cutting-edge analytical techniques such as gas chromatography-mass spectrometry (GC-MS) and high-performance thin layer chromatography (HPTLC) in conjunction with bioautography, this study conducts a thorough phytochemical profiling and biological activity assessment of the Naga chilli plant.

Gellan gum-based in-situ gel formulations for ocular drug delivery: A practical approach.

Ophthalmic disorders significantly impact global health, affecting millions worldwide. Conventional treatments often face challenges related to poor bioavailability and short residence times on the ocular surface. In recent years, in-situ gels prepared using different natural gums including gellan gum has been investigated as a viable means of improving ocular medication delivery.

Probing the synergistic effect of metal-organic framework derived Co-Nx rich interwoven hierarchical porous carbon tube encapsulated dual redox active nanoalloy for high-performance Zn-air battery and supercapacitor applications.

Rechargeable zinc-air batteries (ZABs) with high-performance and stability is desirable for encouraging the transition of the technology from academia to industries. However, achieving this balance remains a formidable challenge, primarily due to the requirement of robust, earth-abundant reversible oxygen electrocatalyst. The present study introduces a simple strategy to synthesize Co-N rich nanoalloy with N-doped porous carbon tubes (NiCo@NPCTs).

Derivatives of D(-)-glutamine-based MMP-2 inhibitors as an effective remedy for the management of chronic myeloid leukemia-Part-III: Synthesis, biological screening and in silico binding interaction analysis.

Tyrosine kinase inhibitors (TKIs) have markedly improved the overall survival rate of patients with chronic myeloid leukemia (CML), enabling them to achieve a normal life expectancy. However, toxicity, relapse, and drug resistance continue to pose major challenges in the clinical treatment of CML. The progression of leukemia is directly connected to higher expression levels and enzymatic actions of matrix metalloproteinase-2 (MMP-2).

Nano-assisted delivery tools for plant genetic engineering: a review on recent developments.

Conventional approaches like Agrobacterium-mediated transformation, viral transduction, biolistic particle bombardment, and polyethylene glycol (PEG)-facilitated delivery methods have been optimized for transporting specific genes to various plant cells. These conventional approaches in genetically modified crops are dependent on several factors like plant types, cell types, and genotype requirements, as well as numerous disadvantages such as time-consuming, untargeted distribution of genes, and high cost of cultivation. Therefore, it is suggested to develop novel techniques for the transportation of genes in crop plants using tailored nanoparticles (NPs) of manipulative and controlled high-performance features synthesized using green and chemical routes.

Targeted Ganglionated Plexi Ablation With Nanoformulated Calcium Suppresses Postoperative AF Via Vagosympatholytic and Anti-Inflammatory Effects.

Background: The mechanisms underlying postoperative atrial fibrillation (POAF) remain unclear.

Objectives: The aim of this study was to test the hypothesis that targeted chemical ganglionated plexi (GP) modulation of all major left atrial-pulmonary vein GP using novel nanoformulated calcium chloride (nCaCl) can reverse postoperative neuroelectrical remodeling by suppressing vagosympathetic nerve activity and the localized inflammatory process, both critical substrates of POAF.

Methods: In a novel canine model of POAF with serial thoracopericardiotomies, sympathetic nerve activity (SNA), vagal nerve activity (VNA) and GP nerve activity (GPNA) were recorded; spontaneous and in vivo AF vulnerability were assessed; and atrial and circulating inflammatory markers and norepinephrine (NE) were measured to determine the neuroelectrical remodeling that promotes POAF and its subsequent modulation with nCaCl GP treatment (n = 6) vs saline sham controls (n = 6).

Interval variational approach for production control and waste reduction using artificial hummingbird algorithm.

Nowadays, consumers show more interest towards eco-friendly products. To meet this demand, however, manufacturing processes often generate a lot of hazardous waste, which creates challenges for companies. To tackle these issues, this work develops an optimization model to help companies with managing production, reduce waste, and maintain green product standards.

An innovative Community Mobilisation and Community Incentivisation for child health in rural Pakistan (CoMIC): a cluster-randomised, controlled trial.

Background: Infectious diseases remain the leading cause of death among children younger than 5 years due to disparities in access and acceptance of essential interventions. The Community Mobilisation and Community Incentivisation (CoMIC) trial was designed to evaluate a customised community mobilisation and incentivisation strategy for improving coverage of evidence-based interventions for child health in Pakistan.

Methods: CoMIC was a three-arm cluster-randomised, controlled trial in rural areas of Pakistan.

Oxymatrine ameliorates epithelial mesenchymal transition in IgA nephropathy induced rats.

In this study, we investigated the efficacy of oxymatrine, a phytochemical alkaloid, in reducing inflammation and fibrosis in a rat model of IgA nephropathy (IgAN) through modulation of the TGF-β/SMAD signaling pathway. Thirty Sprague Dawley rats were randomized into control, IgAN, and treatment groups, the latter receiving oxymatrine postinduction of IgAN. Induced by bovine serum albumin, carbon tetrachloride, and lipopolysaccharides, the disease model was validated by immunofluorescence and histopathological analyses, confirming significant renal deposition of IgA and increased fibrosis markers (IL-6, TGF-β, SMAD 3, and α-SMA).

Sleep spindle variation in patients with Parkinson's disease on first nights of sub-optimal deep brain stimulation.

Objective: Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) is a common treatment for motor symptoms of Parkinson's disease but its influence on non-motor symptoms is less clear. Sleep spindles are known to be reduced in patients with Parkinson's disease, but the effect of STN DBS is unknown. The objective of our study was to address this knowledge gap.

Insights into AI advances in immunohistochemistry for effective breast cancer treatment: a literature review of ER, PR, and HER2 scoring.

Breast cancer is a significant health challenge, with accurate and timely diagnosis being critical to effective treatment. Immunohistochemistry (IHC) staining is a widely used technique for the evaluation of breast cancer markers, but manual scoring is time-consuming and can be subject to variability. With the rise of Artificial Intelligence (AI), there is an increasing interest in using machine learning and deep learning approaches to automate the scoring of ER, PR and HER2 biomarker in IHC-stained images for effective treatment.

"The COVID-19 pandemic in BRICS: Milestones, interventions, and molecular epidemiology".

Brazil, Russia, India, China, and South Africa (BRICS) are a group of developing countries with shared economic, healthcare, and scientific interests. These countries navigate multiple syndemics, and the COVID-19 pandemic placed severe strain on already burdened BRICS' healthcare systems, hampering effective pandemic interventions. Genomic surveillance and molecular epidemiology remain indispensable tools for facilitating informed pandemic intervention.

Assessing Policy Impacts on Chronic Disease Risk Reduction: The Science and Art of Policy Rating Systems.

Public policies have been instrumental in influencing population health, and the desire to study their impact led to the development of the fields of policy surveillance and legal epidemiology. The standardized practice of creating policy measurement systems allows researchers to track and evaluate policy impacts across jurisdictions and over time. Policy measures may take many forms, including dichotomous measures, ordinal ratings, composite measures, or scale measures.

FDA Approval Summary: Nadofaragene firadenovec-vncg for bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer.

On December 16, 2022, the FDA approved the adenoviral vector-based gene therapy nadofaragene firadenovec-vncg (brand name Adstiladrin) for the treatment of adult patients with high-risk bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). The product represents the first approved adenoviral vector-based gene therapy and the first approved gene therapy for bladder cancer. Determination of efficacy was based on results from Study rAd-IFN-CS-003 (Study CS-003), a single-arm trial in 98 evaluable patients with BCG-unresponsive NMIBC with CIS who received intravesical instillations of the gene therapy product (75 mL of nadofaragene firadenovec at 3 × 1011 viral particles per mL) once every 3 months.

Cerebral spinal fluid analyses and therapeutic implications for leptomeningeal metastatic disease.

Purpose: To review applications of cerebral spinal fluid (CSF) biomarkers for the diagnosis, monitoring and treatment of leptomeningeal metastatic disease (LMD) among patients with metastatic solid tumors.

Methods: A narrative review identified original research related to CSF biomarkers among patients with metastatic solid tumors and LMD. Pre-clinical research (e.

Efficacy of probiotics for treatment of acute or persistent diarrhoea in children from birth till 10 years: Systematic review and meta-analysis.

Background: Numerous studies have investigated the efficacy of probiotics in treating acute and persistent diarrhoea. However, probiotics have not been established as a recommended management option for diarrhoeal illness by the World Health Organization (WHO). Therefore, we conducted a systematic review of randomised controlled trials to assess the efficacy of probiotics for the management of acute and persistent diarrhoea in children.

Integrated bioinformatics and interaction analysis to advance chronotherapies for mental disorders.

Introduction: Robust connections have been identified between the pathophysiology of mental disorders and the functioning of the circadian system. The overarching objective of this study was to investigate the potential for circadian rhythms to be leveraged for therapeutics in mental disorders.

Methods: We considered two approaches to chronotherapy-optimal timing of existing medications ("clocking the drugs") and redressing circadian abnormalities with small molecules ("drugging the clock").

Inhibiting brushite crystal growth: molecular docking exploration of phytoconstituents and their interaction with human serum albumin.

In our preliminary studies, the extract demonstrated inhibition of calcium phosphate (brushite) crystals. Human serum albumin (HSA) is known to act as a promoter of brushite crystal growth. Therefore, the present study aims to explore the molecular mechanisms involved in brushite crystal nephrolithiasis by conducting molecular docking of phytoconstituents from with HSA.

Trypanosomatid DRBD9s are likely to be eIF4B orthologues.

Initiation of protein translation is one of the key steps in protein synthesis carried out by translation initiation factors in conjunction with ribosomes. The roles and mechanisms of these initiation factors in prokaryotic and eukaryotic protein synthesis are well understood. However, they are only beginning to be understood in trypanosomatids.

AMPK Activates Cellulase Secretion in Penicillium funiculosum by Downregulating P-HOG1 MAPK Levels.

Cellulase production for hydrolyzing plant cell walls is energy-intensive in filamentous fungi during nutrient scarcity. AMP-activated protein kinase (AMPK), encoded by snf1, is known to be the nutrient and energy sensor in eukaryotes. Previous studies on AMPK identified its role in alternate carbon utilization in pathogenic fungi.

Complete percutaneous repair of Tetralogy of Fallot in adult: a case report.

Tetralogy of Fallot (TOF) is the most common congenital cyanotic heart disease and is characterized by an antero-superior deviation of the infundibular septum with a consequent large malaligned ventricular septal defect (VSD) and a pulmonary and sub-pulmonary (infundibular) stenosis. Surgical repair has been the cornerstone of treatment that is electively performed early in their lives between 3 and 6 months of age. With advancements in transcatheter interventions, the complete percutaneous repair of TOF, a complex disease with multiple treatable lesions, is becoming a conceivable possibility.

Estimates of life expectancy and premature mortality among multidimensional poor and non-poor in India.

Background: In Low and Middle Income Countries (LMICs), reduction of multidimensional poverty and the increase in longevity are concomitant. Although a number of studies have estimated multidimensional poverty, studies on estimates of life expectancy and pre-mature mortality by multidimensional poverty are limited. We estimated life expectancy and premature mortality among multidimensionally poor and multidimensionally non-poor in India.

The landscape of primary mismatch repair deficient gliomas in children, adolescents, and young adults: a multi-cohort study.

Background: Gliomas are a major cause of cancer-related death among children, adolescents, and young adults (age 0-40 years). Primary mismatch repair deficiency (MMRD) is a pan-cancer mechanism with unique biology and therapeutic opportunities. We aimed to determine the extent and impact of primary MMRD in gliomas among children, adolescents, and young adults.