Key epigenetic enzymes modulated by natural compounds contributes to tumorigenicity.

Dysregulation of epigenetic regulation is observed in numerous tumor cells. The therapeutic effects of natural products on tumors were investigated through a comprehensive analysis of active ingredients derived from various structured natural products. The analysis focuses on regulating key enzymes involved in epigenetic control.

A benzoxazolyl urea inhibits VraS and enhances antimicrobials against vancomycin intermediate-resistant Staphylococcus aureus.

Vancomycin intermediate-resistant Staphylococcus aureus (VISA) is a pathogen of concern. VraS, a histidine kinase, facilitates the VISA phenotype. Here, we reveal a benzoxazolyl urea (chemical 1) that directly inhibits VraS and enhances vancomycin to below the clinical breakpoint against an archetypal VISA strain, Mu50.

Assessing the Impacts of Drug Loading and Polymer Type on Dissolution Behavior and Diffusive Flux of GDC-6893 Amorphous Solid Dispersions.

It is desirable but remains challenging to develop high drug load amorphous solid dispersions (ASDs) without compromising their quality attributes and bio-performance. In this work, we investigated the impacts of formulation variables, such as drug loading (DL) and polymer type, on dissolution behavior, diffusive flux, and in vitro drug absorption of ASDs of a high T compound, GDC-6893. ASDs with two polymers (HPMCAS and PVPVA) and various DLs (20 - 80%) were produced by spray drying and their drug-polymer miscibility was evaluated using solid-state nuclear magnetic resonance (ssNMR).

The impact of glidant addition on the loss-in-weight feeding of active pharmaceutical ingredients.

In recent years, continuous manufacturing (CM) has become increasingly popular in the pharmaceutical industry for the production of oral solid dosage (OSD) forms. Most of the newly developed active pharmaceutical ingredients (APIs) nowadays are extremely cohesive and sticky with a mean particle size particle of <100μm, a wide particle size distribution (PSD) and a high tendency to agglomerate, making them difficult to accurately dose using loss-in-weight equipment during CM. In this research paper, the effect of various glidants on the volumetric and gravimetric feeding of several APIs was assessed.

Development of Chimeric Nanobody-Granzyme B Functionalized Ferritin Nanoparticles for Precise Tumor Therapy.

T-cell lymphomas (TCLs) are heterogeneous malignancies with limited treatment options and poor outcomes. The efficacy of traditional T-cell therapies, including chimeric antigen receptor (CAR) T cells, is often constrained by immunosuppressive factors and the tumor microenvironment. On the other hand, although direct Granzyme B (GrB) administration can effectively induce tumor cell apoptosis, it lacks universal tumor targeting and efficient cellular entry mechanisms.

The Mechanism of Bovis Culus Sativus Protecting BBB Damage in Stroke: Insights from Network Pharmacology, Bioinformatics, and Experiments.

Ethnopharmacological Relevance: Bovis calculus (BC) has a medicinal history of over 2,000 years in treating stroke in China. Bovis Culus Sativus (BCS) has similar pharmacological effects to BC. Due to the scarcity of BC, BCS is often used as a substitute for BC in clinical practice for treating stroke in traditional Chinese medicine.

The role of carbon and nitrogen ratio on sewage sludge microbiota for producing polyhydroxyalkanoates.

The products of an advanced sewage sludge fermentation process can be used to generate polyhydroxyalkanoates (PHAs), precursors of bioplastics considered excellent candidates for replacing petroleum-derived plastics. The aerobic feast-anoxic famine cycling strategy has proven to be an efficient method for enriching sewage sludge microbiota with PHA-producing microorganisms. This work evaluated the effect of different carbon to nitrogen ratios (C/N) of 3.

Assessing the impact of non-pharmaceutical interventions against COVID-19 on 64 notifiable infectious diseases in Australia: A Bayesian Structural Time Series model.

Background: Several studies have examined the effect of non-pharmaceutical interventions (NPIs) on COVID-19 and other infectious diseases in Australia and globally. However, to our knowledge none have sufficiently explored their impact on other infectious diseases with robust time series model. In this study, we aimed to use Bayesian Structural Time Series model (BSTS) to systematically assess the impact of NPIs on 64 National Notifiable Infectious Diseases (NNIDs) by conducting a comprehensive and comparative analysis across eight disease categories within each Australian state and territory, as well as nationally.

On the formation and stability mechanisms of diverse lipid-based nanostructures for drug delivery.

In the evolving landscape of nanotechnology and pharmaceuticals, lipid nanostructures have emerged as pivotal areas of research due to their unique ability to mimic biological membranes and encapsulate active molecules. These nanostructures offer promising avenues for drug delivery, vaccine development, and diagnostic applications. This comprehensive review explores the complex mechanisms underlying the formation and stability of various lipid nanostructures, including lipid liquid crystalline nanoparticles and solid lipid nanoparticles.

Synthesis and biological evaluation of new dual APN/NEP inhibitors as potent analgesics.

An alternative approach for the management of acute and chronic pains involves prolonging the half-life of endogenous opiates, such as enkephalins that are released in response to nociceptive stimuli. This can be achieved through the inhibition of enzymatic pathways responsible for the hydrolysis of these peptides, particularly targeting Aminopeptidase N (APN) and Neutral Endopeptidase (NEP). In this study, we designed and synthesized a series of dual enkephalinase inhibitors (DENKIs) targeting both APN and NEP as novel analgesic treatments.

Fragment-Based Drug Discovery: Small Fragments, Big Impact - Success Stories of Approved Oncology Therapeutics.

Fragment-Based Drug Discovery (FBDD) has revolutionized drug discovery by overcoming the challenges of traditional methods like combinatorial chemistry and high-throughput screening (HTS). Leveraging small, low-molecular-weight fragments, FBDD achieves higher hit rates, reduced screening costs, and faster development timelines for clinically relevant drug candidates. This review explores FBDD's core principles, innovative methodologies, and its success in targeting diverse protein classes, including previously "undruggable" targets.

Design, Synthesis, Biocompatibility, molecular docking and molecular dynamics studies of novel Benzo[b]thiophene-2-carbaldehyde derivatives targeting human IgM Fc Domains.

In this study, three novel derivatives of benzo[b]thiophene-2-carbaldehyde (BTAP1, BTAP2, and BTAP3) were successfully synthesized and comprehensively characterized using spectroscopic techniques including FTIR, UV-VIS, HNMR, and CNMR. Thermal analysis through TGA and DTA demonstrated remarkable thermal stability with a maximum threshold at 270 °C. Spectroscopic investigations revealed π → π* transitions in all compounds, attributed to the conjugated system comprising benzothiophene rings connected to bromophenyl/ aminophenyl/phenol rings via α, β-unsaturated ketone bridges.

Safety and efficacy of tamoxifen in non-ambulant patients with Duchenne muscular dystrophy: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (TAMDMD Group B).

Most patients with Duchenne muscular dystrophy (DMD) are non-ambulant. Preserving proximal motor function is crucial, rarely studied. Tamoxifen, a selective oestrogen receptor modulator, reduced signs of muscular pathology in a DMD mouse model.

What happens after menopause? (WHAM): A prospective controlled study of cognition 24 months after premenopausal risk-reducing salpingo-oophorectomy.

Objective: Women with BRCA1/2 pathogenic variants considering risk-reducing bilateral oophorectomy (RRSO) may be concerned about potential effects of surgical menopause on cognition. Whether RRSO affects cognition and whether hormone therapy (HT) modifies this effect remains uncertain. This study aimed to prospectively measure the effect of premenopausal RRSO on cognition and the modifying effects of HT up to 24 months.

Ficus carica leaves extract loaded PLGA nanoparticles: preparation, characterization, and in vitro anticancer activity on TFK-1 cell line.

Ficus Carica extract (FC) is a natural herb that has received a lot of interest in cancer treatment due to its potential anticancer activities against various malignancies. However, due to FC's low bioavailability and low solubility, its clinical use as an anti-cancer medicine is constrained. The current study aimed to prepare FC-loaded PLGA nanoparticles (NPs) for cancer treatment.

Evaluation of the Recent Dynamics for Funding Medicinal Chemistry Projects in Academia. Results of a Survey Conducted by IUPAC Division VII (Chemistry and Human Health).

Data collected from scholars across twenty-three countries over the past decade (2010-2019) reveals a 40% decrease in financial support for medicinal chemistry projects. The decline is especially notable among projects focused on small organic molecules. This drop in grants indicates a troubling trend that could jeopardize future drug development by undermining research in this crucial field.

Fatuamide A, a Hybrid PKS/NRPS Metallophore from a sp. Marine Cyanobacterium Collected in American Samoa.

A structurally novel metabolite, fatuamide A (), was discovered from a laboratory cultured strain of the marine cyanobacterium sp., collected from Faga'itua Bay, American Samoa. A bioassay-guided approach using NCI-H460 human lung cancer cells directed the isolation of fatuamide A, which was obtained from the most cytotoxic fraction.

Role of the Mobile Active Site Flap in IMP Dehydrogenase Inhibitor Binding.

Inosine 5'-monophosphate dehydrogenase (IMPDH) is a promising antibiotic target. This enzyme catalyzes the NAD-dependent oxidation of inosine 5'-monophosphate (IMP) to xanthosine 5'-monophosphate (XMP), which is the rate-limiting step in guanine nucleotide biosynthesis. Bacterial IMPDH-specific inhibitors have been developed that bind to the NAD site.

Small Molecule Modulators of AMP-Activated Protein Kinase (AMPK) Activity and Their Potential in Cancer Therapy.

AMP-activated protein kinase (AMPK) is a central mediator of cellular metabolism and is activated in direct response to low ATP levels. Activated AMPK inhibits anabolic pathways and promotes catabolic activities that generate ATP through the phosphorylation of multiple target substrates. AMPK is a therapeutic target for activation in several chronic metabolic diseases, and there is increasing interest in targeting AMPK activity in cancer where it can act as a tumor suppressor or conversely it can support cancer cell survival.

Prebiotics Beyond the Gut: Omics Insights, Artificial Intelligence, and Clinical Trials in Organ-Specific Applications.

Prebiotics, traditionally linked to gut health, are increasingly recognized for their systemic benefits, influencing multiple organ systems through interactions with the gut microbiota. Compounds like inulin, fructooligosaccharides (FOS), and galactooligosaccharides (GOS) enhance short-chain fatty acid (SCFA) production, benefiting neurocognitive health, cardiovascular function, immune modulation, and skin integrity. Advances in biotechnology, including deep eutectic solvents (DES) for extraction and machine learning (ML) for personalized formulations, have expanded prebiotic applications.

Eco-friendly zinc oxide nanoparticle biosynthesis powered by probiotic bacteria.

The rapid advancement of nanotechnology, particularly in the realm of pharmaceutical sciences, has significantly transformed the potential for treating life-threatening diseases. A pivotal aspect of this evolution is the emergence of "green nanotechnology," which emphasizes the environmentally sustainable synthesis of raw materials through biological processes. This review focuses on the biological synthesis and application of zinc oxide (ZnO) nanoparticles (NPs) from probiotic bacteria, particularly those sourced from wastewater.

2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione protects against MPP-induced neurotoxicity by ameliorating oxidative stress, apoptosis and autophagy in SH-SY5Y cells.

2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) is a cyclohexanedione compound extracted from the roots of Averrhoa carambola L. Several studies have documented its beneficial effects on diabetes, Alzheimer's disease, and cancer. However, its potential neuroprotective effects on Parkinson's disease (PD) have not yet been explored.

Nano-delivery of a novel inhibitor of ERCC1-XPF for targeted sensitization of colorectal cancer to platinum-based chemotherapeutics.

In this study, a novel inhibitor of ERCC1/XPF heterodimerization, A4, was used as an inhibitor of repair for DNA damage by platinum-based chemotherapeutics. Nano-formulations of A4 were developed, using self-assembly of the following block copolymers: methoxy-poly(ethylene oxide)-block-poly(α-benzyl carboxylate-ε-caprolactone) (PEO-b-PBCL), methoxy-poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL), or methoxy-poly(ethylene oxide)-block-poly (D, L, lactide) (PEO-b-PDLA 50-50). The nano-formulations were characterized for their average diameter, polydispersity, morphology, A4 encapsulation and in vitro release.

Bioactivities of secondary metabolites of two actinomycetes Streptomyces parvulus GloL3, and Streptomyces lienomycini SK5, endophytes of two Indian medicinal herbs- Globba marantina L. and Selaginella kraussiana (Kunze) A. Braun.

Endophytic actinomycetes are potential sources of novel pharmaceutically active metabolites, significantly advancing natural product research. In the present investigation, secondary metabolites from two endophytic actinomycetes, Streptomyces parvulus GloL3, and Streptomyces lienomycini SK5, isolated from medicinal plant taxa, Globba marantina, and Selaginella kraussiana, exhibited broad-spectrum bioactivity. Ethyl Acetate (EA) extract of SK5 showed antimicrobial activity against nine human pathogens, including Methicillin-resistant Staphylococcus aureus (MRSA), Candida tropicalis, and C.