Protacs in cancer therapy: mechanisms, design, clinical trials, and future directions.

Cancer develops as a result of changes in both genetic and epigenetic mechanisms, which lead to the activation of oncogenes and the suppression of tumor suppressor genes. Despite advancements in cancer treatments, the primary approach still involves a combination of chemotherapy, radiotherapy, and surgery, typically providing a median survival of approximately five years for patients. Unfortunately, these therapeutic interventions often bring about substantial side effects and toxicities, significantly impacting the overall quality of life for individuals undergoing treatment.

"Sunlight-driven catalytic degradation of MB dye and multi-cycle Re-usability analysis of CuSe nanoparticles".

One of the best ways to remove organic dyes based contaminant from water resources and industrial waste water is the sunlight driven photo-catalytic degradation method. The theme of the present investigation is the photocatalytic degradation of methylene blue (MB) dye using economically produced CuSe nanoparticles (NPs) catalyst under solar radiations. The CuSe NPs crystallized in the cubic structural phase with an average crystallite size around 19 nm.

Two-dimensional BiSbTeX (X = S, Se, Te) and their Janus monolayers as efficient thermoelectric materials.

Today, there is a huge need for highly efficient and sustainable energy resources to tackle environmental degradation and energy crisis. We have analyzed the electronic, mechanical and thermoelectric (TE) characteristics of two-dimensional (2D) BiSbTeX (X = S, Se and Te) and Janus BiSbTeXY (X/Y = S, Se and Te) monolayers by implementing first principles simulations. These monolayers' dynamic stability and thermal stability have been demonstrated through phonon dispersion spectra and molecular dynamics (AIMD) simulations, respectively.

Amyloidogenic Propensity of Metabolites in the Uric Acid Pathway and Urea Cycle Critically Impacts the Etiology of Metabolic Disorders.

Novel insights into the etiology of metabolic disorders have recently been uncovered through the study of metabolite amyloids. In particular, inborn errors of metabolism (IEMs), including gout, Lesch-Nyhan syndrome (LNS), xanthinuria, citrullinemia, and hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, are attributed to the dysfunction of the urea cycle and uric acid pathway. In this study, we endeavored to understand and mechanistically characterize the aggregative property exhibited by the principal metabolites of the urea cycle and uric acid pathway, specifically hypoxanthine, xanthine, citrulline, and ornithine.

Locating perpetrators of violence against women in India: An analysis of married men's characteristics associated with intimate partner violence.

Intimate Partner Violence (IPV) against married women is widely prevalent in India. Using recent data from NFHS-5, we analyzed the association between husbands' characteristics and IPV. Separate logistic regression models were developed for three distinct "husband characteristic groups" namely demographic, social and economic groups, and one final model including only statistically significant variables.

The determinants of COVID-19 vaccination intention: a meta-review.

Background: A large number of systematic reviews have been published that synthesized various determinants of COVID-19 vaccination intention (CVI). However, they reported inconsistent evidence. Therefore, we conducted a meta-review (systematic review of systematic reviews) to provide a comprehensive synthesis of factors influencing CVI.

Enhanced Antibacterial and Photoluminescence Activities of ZnSe Nanostructures.

Microorganisms create various health issues; semiconductor nanostructures have raised interest because of antimicrobial properties for suppressing microbial growth. Herein, we report the synthesis of ZnSe nanostructures (NSs) using a green coprecipitation method, and the as-synthesized samples were annealed at 100, 150, and 200 °C temperatures. The synthesized samples were analyzed for structural, morphological, optical, and antibacterial properties.

An Isothiazolanthrone-Based Self-Assembling Anticancer Color-Changing Dye for Concurrent Imaging and Monitoring of Cell Viability.

We report the photophysical properties, self-assembly and biological evaluation of an isothiazolanthrone-based dye, 7-amino-6H-anthra[9,1-cd]isothiazol-6-one (AAT), which reveals anticancer properties and can be potentially used as dye for monitoring cell viability. The solvent-dependent photophysical studies suggest that the emission of AAT is sensitive to environment polarity due to which interesting changes in the colored emission may be observed owing to the charge transfer (CT) processes. AAT also self-assembles to tree-like branched morphologies and produce, a greenish emission inside the cells when imaged after short interval (15 mins) of incubation while a red fluorescence could be noted after 24 h.

Bioconjugate-loaded solid lipid nanoparticles for enhanced anticancer drug delivery to brain cancer cells: An evaluation.

Background & Objectives: The treatment of brain cancer is still challenging for an oncologist due to the presence of the blood-brain barrier (BBB) which inhibits the entry of more than 98 per cent of drugs used during the treatment of brain disease. The cytotoxic drugs used in chemotherapy for brain cancer treatment also affect the normal cells due to lack of targeting. Therefore, the objective of the study was to develop tween 80-coated solid lipid nanoparticles (SLNs) loaded with folic acid-doxorubicin (FAD) conjugate for site-specific drug delivery to brain cancer cells.

Occupational and environmental mercury exposure and human reproductive health - a review.

Mercury is a toxic heavy metal. Humans are exposed to mercury through several sources including environmental, occupational, contaminated food and water and from mercury-containing dental amalgam. Mercury exposure is known to harm the nervous system profoundly, and have a negative impact on digestive and immune systems, and other organs.

An Investigation of Ascorbic Acid Tethered Polymeric Nanoparticles for Effectual Brain Transport of Rivastigmine.

Introduction: The goal of this study was to see if ascorbic acid grafted polylactic glycolic acid-b-polyethylene glycol nanoparticles (PLGA-b-PEG NPs) might boost the carrying or transport capacity of rivastigmine(RSM) to the brain via choroid plexus Sodium-dependent vitamin C transporter 2 (SVCT2 transporters). The IR and 1H NMR, were used to characterise the PLGA-b-PEG copolymer.

Methods: Nanoprecipitation method was used to make PLGA-b-PEG NPs.

Lanthanide-Doped Luminescent Nanophosphors Ionic Liquids.

Lanthanide (Ln) ion(s)-doped or rare-earth ion(s)-doped nanomaterials have been considered a very important class of nanophosphors for various photonic and biophotonic applications. Unlike semiconductors and organic-based luminescent particles, the optical properties of Ln-doped nanophosphors are independent of the size of the nanoparticles. However, by varying the crystal phase, morphology, and lattice strain of the host materials along with making core-shell structure, the relaxation dynamics of dopant Ln ions can be effectively tuned.

Host phospholipase C-γ1 impairs phagocytosis and killing of mycobacteria by J774A.1 murine macrophages.

Macrophages represent the first line of defense against invading Mycobacterium tuberculosis (Mtb). In order to enhance intracellular survival, Mtb targets various components of the host signaling pathways to limit macrophage functions. The outcome of Mtb infection depends on various factors derived from both host and pathogen.

Formulation and investigation of pilocarpine hydrochloride niosomal gels for the treatment of glaucoma: intraocular pressure measurement in white albino rabbits.

The present study was focused on investigating niosomal gels loaded with cholinergic drug; pilocarpine HCl, for prolonged precorneal residence time and improved bioavailability for glaucoma treatment. Pilocarpine HCl niosomes were prepared using various nonionic surfactants (span 20, span 60 and span 80), in the presence of cholesterol in different molar ratios by ether injection method. The selected formulations were incorporated into carbopol 934 and locust bean gum-based gels.

Systematic optimization of cationic surface engineered mucoadhesive vesicles employing Design of Experiment (DoE): A preclinical investigation.

Fungal keratitis (FK) is treated by topical natamycin (Nat) which is an effective antifungal agent. However, it has numerous therapeutic limitations i.e.

Development of liposomes using formulation by design: Basics to recent advances.

In couple of decennia, optimization tactics for drug delivery systems have been explored widely employing Design of Experiments (DoE) for desired outcomes to overcome drawbacks of "One Factor at a Time (OFAT)"conventional technique.. To pace with advances in computational approaches engaged in research domain, QbD-based tactic i.

Phospholipase C-γ2 promotes intracellular survival of mycobacteria.

Mycobacterium tuberculosis (Mtb) infects millions of people each year. These bacilli can survive inside macrophages. To favor their survival, pathogen alters various signal transduction pathways in host cells.

Tuberculosis: Smart manipulation of a lethal host.

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a global threat to human health. Development of drug resistance and co-infection with HIV has increased the morbidity and mortality caused by TB. Macrophages serve as primary defense against microbial infections, including TB.

Immunoporosis: Immunology of Osteoporosis-Role of T Cells.

The role of immune system in various bone pathologies, such as osteoporosis, osteoarthritis, and rheumatoid arthritis is now well established. This had led to the emergence of a modern field of systems biology called as osteoimmunology, an integrated research between fields of immunology and bone biology under one umbrella. Osteoporosis is one of the most common inflammatory bone loss condition with more than 200 million individuals affected worldwide.

Structural exploration of hydroxyethylamines as HIV-1 protease inhibitors: new features identified.

The current study deals with chemometric modelling strategies (Naïve Bayes classification, hologram-based quantitative structure-activity relationship (HQSAR), comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA)) to explore the important features of hydroxylamine derivatives for exerting potent human immunodeficiency virus-1 (HIV-1) protease inhibition. Depending on the statistically validated reliable and robust quantitative structure-activity relationship (QSAR) models, important and crucial structural features have been identified that may be responsible for enhancing the activity profile of these hydroxylamine compounds. Arylsulfonamide function along with methoxy or fluoro substitution is important for enhancing activity.

PknG supports mycobacterial adaptation in acidic environment.

Mycobacterium tuberculosis (Mtb), causative agent of human tuberculosis (TB), has the remarkable ability to adapt to the hostile environment inside host cells. Eleven eukaryotic like serine-threonine protein kinases (STPKs) are present in Mtb. Protein kinase G (PknG) has been shown to promote mycobacterial survival inside host cells.

Design, synthesis, and characterization of 2,2-bis(2,4-dinitrophenyl)-2-(phosphonatomethylamino)acetate as a herbicidal and biological active agent.

The present study was designed to synthesize the bioactive molecule 2,2-bis(2,4-dinitrophenyl)-2-(phosphonatomethylamino)acetate (), having excellent applications in the field of plant protection as a herbicide. Structure of newly synthesized molecule was confirmed by using the elemental analysis, mass spectrometric, NMR, UV-visible, and FTIR spectroscopic techniques. To obtain better structural insights of molecule , 3D molecular modeling was performed using the GAMESS programme.

Ascorbic acid tethered polymeric nanoparticles enable efficient brain delivery of galantamine: An in vitro-in vivo study.

The aim of this work was to enhance the transportation of the galantamine to the brain via ascorbic acid grafted PLGA-b-PEG nanoparticles (NPs) using SVCT2 transporters of choroid plexus. PLGA-b-PEG copolymer was synthesized and characterized by H NMR, gel permeation chromatography, and differential scanning calorimetry. PLGA-b-PEG-NH and PLGA-b-mPEG NPs were prepared by nanoprecipitation method.

Efficient biodegradation of acephate by PS-5 in the presence and absence of heavy metal ions [Cu(II) and Fe(III)], and humic acid.

The present study was intended to investigate the biodegradation of acephate in aqueous media in the presence and in the absence of metal ions [Fe(III) and Cu(II)], and humic acid (HA). Biodegradations were performed using PS-5 (PS-5) isolated from the heavy metal polluted site. Biodegradations were monitored by UV-Visible, FTIR, and electron spray ionization-mass spectrometry (ESI-MS) analyses.