Identification of narciclasine as a novel NRF2 inhibitor.

Cancer genome sequencing studies have identified somatic mutations in the KEAP1/NRF2 pathway. In an effort to identify novel NRF2 small molecule inhibitor(s), we have screened a natural compound library comprising 1,330 chemicals in A549-ARE-GFP-luciferase cells and identified that narciclasine significantly inhibits NRF2-dependent luciferase activity. Narciclasine suppressed the expression of NRF2 and NRF2 target genes, caused significant oxidative stress, and sensitized cisplatin-mediated apoptosis in A549 cells.

New Ionic Liquid Forms of Antituberculosis Drug Combinations for Optimized Stability and Dissolution.

Isoniazid (INH) and rifampicin (RIF) are the two main drugs used for the management of tuberculosis. They are often used as a fixed drug combination, but their delivery is challenged by suboptimal solubility and physical instability. This study explores the potential of active pharmaceutical ingredient-ionic liquids (API-ILs) to improve the physicochemical and pharmaceutical properties of INH and RIF.

Effect of Process Parameters on Nano-Microparticle Formation During Supercritical Antisolvent Process Using Mixed Solvent: Application for Enhanced Dissolution and Oral Bioavailability of Telmisartan Through Particle-Size Control Based on Experimental Design.

This study investigates the impact of supercritical antisolvent (SAS) process parameters on the particle formation of telmisartan, a poorly water-soluble drug. A fractional factorial design was employed to examine the influence of the SAS process parameters, including solvent ratio, drug solution concentration, temperature, pressure, injection rate of drug solution, and CO₂ flow rate, on particle formation. Solid-state characterizations of the SAS process particles using XRD and FT-IR confirmed their amorphous nature.

Small Molecules in Parkinson's Disease Therapy: From Dopamine Pathways to New Emerging Targets.

Parkinson's disease (PD) is a chronic, progressive neurological disorder affecting approximately 10 million people worldwide, with prevalence expected to rise as the global population ages. It is characterized by the degeneration of dopamine-producing neurons in the substantia nigra pars compacta, leading to motor symptoms such as tremor, rigidity, bradykinesia, postural instability, and gait disturbances, as well as non-motor symptoms including olfactory disturbances, sleep disorders, and depression. Currently, no cure exists for PD, and most available therapies focus on symptom alleviation.

Identification of New Polyacetylenes from with PPAR-α Activity Study.

Leveille is a traditional medicine used to treat migraine headache and dysmenorrhea. In this study, three polyacetylenes, methyl (10,9,16)-16-acetoxy-9-hydroxyoctadeca-10,17-dien-12,14-diynoate (), methyl (10,9,16)-9,16-dihydroxyoctadeca-10-en-12,14-diynoate (), and methyl (10,9,16)-9,16-dihydroxyoctadeca-10,17-dien-12,14-diynoate (), were isolated from the aerial parts of . , together with seven known compounds (-).

Machine learning-driven optimization of mRNA-lipid nanoparticle vaccine quality with XGBoost/Bayesian method and ensemble model approaches.

To enhance the efficiency of vaccine manufacturing, this study focuses on optimizing the microfluidic conditions and lipid mix ratios of messenger RNA-lipid nanoparticles (mRNA-LNP). Different mRNA-LNP formulations ( = 24) were developed using an I-optimal design, where machine learning tools (XGBoost/Bayesian optimization and self-validated ensemble (SVEM)) were used to optimize the process and predict lipid mix ratio. The investigation included material attributes, their respective ratios, and process attributes.

Trends and determinants of choline alfoscerate use in newly diagnosed Alzheimer's disease patients in Korea.

Background: Choline alfoscerate, a cholinergic precursor, is widely used in Korea for dementia-related symptoms and is covered by national health insurance (NHI). This study investigates the utilization trends and factors influencing choline alfoscerate prescription in newly diagnosed Alzheimer's disease (AD) patients using real-world data.

Methods: We analyzed data from the Health Insurance Review and Assessment Service (HIRA) for patients aged 60 years and older who were newly diagnosed with AD between 2012 and 2019.

Myeloid-specific deletion of autotaxin inhibits rheumatoid arthritis and osteoclastogenesis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint swelling, pain, and bone remodeling. We previously reported that autotaxin (ATX) deficiency disrupts lipid rafts in macrophages. Lipid raft disruption results in the dysregulation of RANK signaling, which is crucial for osteoclastogenesis and the pathogenesis of RA.

Fabrication of bio-mimic nanozyme based on Mxene@AuNPs and molecular imprinted poly(thionine) films for creatinine detection.

Creatinine (Ctn) is a biomarker for chronic kidney disease (CKD). In this study, a highly sensitive and specific detection method for Ctn based on a molecularly imprinted polymer (MIP) based electrochemical biosensor was developed. Mxene (Mx), which has high absorption properties, was modified using carbon screen-printed electrodes (SPCE).

Nutritional Composition, Phytochemical Profiles, and Pharmacological Effects of Ethiopian Eggplant ( L.).

Natural product therapy has been used to treat illness for thousands of years, and modern-day medicines, such as various anticancer, antihypertensive, and antimigraine drugs, have been developed from natural products. Natural medicines are advantageous as they tend to have fewer side effects and are considered a relatively safe option. L.

Determination of Flavonoid Glycoside Isomers Using Vision Transformer and Tandem Mass Spectrometry.

A vision transformer (ViT)-based deep neural network was applied to classify the flavonoid glycoside isomers by analyzing electrospray ionization tandem mass spectrometry (ESI-MS/MS) spectra. Our model successfully classified the flavonoid isomers with various substitution patterns (3-O, 6-C, 7-O, 8-C, 4'-O) and multiple glycosides, achieving over 80% accuracy during training. In addition, the experimental spectra from flavonoid glycoside standards were acquired with different adducts, and our model showed robust performance regardless of the experimental conditions.

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

Discovery of Cryptic Natural Products Using High-Throughput Elicitor Screening on Agar Media.

It is now well-established that microbial genomes carry sparingly expressed biosynthetic gene clusters (BGCs) that need to be induced in order to characterize their products. To do so, we herein subjected two well-known producers, and , to high-throughput elicitor screening (HiTES), an emerging approach for accessing the products of these "cryptic" BGCs. Both organisms have previously been examined extensively in liquid cultures.

Penfluridol suppresses MYC-driven ANLN expression and liver cancer progression by disrupting the KEAP1-NRF2 interaction.

Hepatocellular carcinoma (HCC) comprises the majority of primary liver cancers and possesses a low 5-year survival rate when in the advanced stages. Anillin (ANLN), a key player in cell growth and cytokinesis, is implicated in HCC development. Currently, no treatment agents are known to suppress ANLN.

New insights into protein-protein interaction modulators in drug discovery and therapeutic advance.

Protein-protein interactions (PPIs) are fundamental to cellular signaling and transduction which marks them as attractive therapeutic drug development targets. What were once considered to be undruggable targets have become increasingly feasible due to the progress that has been made over the last two decades and the rapid technological advances. This work explores the influence of technological innovations on PPI research and development.

Assessment of the neurotoxicity of monosodium glutamate on neural stem cells and hippocampal neurogenesis in a rodent model.

Monosodium glutamate (MSG) is a widely used flavor enhancer in processed foods and valued for its ability to enhance the savory taste known as umami. MSG is classified as non-toxic and recognized as a safe food additive with no specific usage restrictions in many countries. However, neurotoxic studies on MSG have primarily focused on neurons, and the effects of MSG on neural stem cells (NSCs) have not been reported.

Chronic hyperglycemia induces hepatocyte pyroptosis via Gα/Gα-associated endoplasmic reticulum stress: Effect of pharmacological intervention.

Aims: Hyperglycemia induces pathophysiological changes. Endoplasmic reticulum (ER) stress with Gα overexpression may promote hepatocyte death. This study investigated whether sustained hyperglycemia triggers ER stress-associated pyroptosis and fibrosis in the liver alongside an overexpression of Gα, and examined the potential link with VEGF-A levels.

Unraveling the impact of miRNAs on gouty arthritis: diagnostic significance and therapeutic opportunities.

Gouty arthritis is a prevalent inflammatory illness. Gout attacks begin when there is an imbalance in the body's uric acid metabolism, which leads to urate buildup and the development of the ailment. A family of conserved, short non-coding RNAs known as microRNAs (miRNAs) can regulate post-transcriptional protein synthesis by attaching to the 3' untranslated region (UTR) of messenger RNA (mRNA).

Cycloartane-type triterpenoids from Combretum quadrangulare Kurz with PCSK9 secretion inhibitory activities.

Nine previously undescribed (1-9) and seven known (10-16) cycloartane-type triterpenoids were isolated and characterized from Combretum quadrangulare Kurz using physicochemical and spectroscopic methods. The absolute configurations of these compounds were determined through modified Mosher's method and quantum chemical calculation of electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectra. Their inhibitory activities against PCSK9 secretion were assessed, and a plausible structure-activity relationship was delineated.

Integrative transcriptomic analysis identifies emetine as a promising candidate for overcoming acquired resistance to ALK inhibitors in lung cancer.

Anaplastic lymphoma kinase (ALK; also known as ALK tyrosine kinase receptor) inhibitors (ALKi) are effective in treating lung cancer patients with chromosomal rearrangement of ALK. However, continuous treatment with ALKis invariably leads to acquired resistance in cancer cells. In this study, we propose an efficient strategy to suppress ALKi resistance through a meta-analysis of transcriptome data from various cell models of acquired resistance to ALKis.

Piperine solubility enhancement via DES formation: Elucidation of intermolecular interactions and impact of counterpart structure via computational and spectroscopic approaches.

The development of new forms of existing APIs with enhanced physicochemical properties is critical for improving their therapeutic potential. In this context, ionic liquids (ILs) and deep eutectic solvents (DESs) have gained significant attention in recent years due to their unique properties and potential for solubility enhancement. In this study, we explore the role of different counterparts in the formation of IL/DESs with piperine (PI), a poorly water-soluble drug.

Predicting antioxidant activity of compounds based on chemical structure using machine learning methods.

Oxidative stress is a well-established risk factor for numerous chronic diseases, emphasizing the need for efficient identification of potent antioxidants. Conventional methods for assessing antioxidant properties are often time-consuming and resource-intensive, typically relying on laborious biochemical assays. In this study, we investigated the applicability of machine learning (ML) algorithms for predicting the antioxidant activity of compounds based solely on their molecular structure.

Therapeutic Potential of Pomegranate Extract for Women's Reproductive Health and Breast Cancer.

Pomegranate extract has potential benefits for women's reproductive health, including fertility enhancement, menstrual cycle regulation, pregnancy support, and polycystic ovary syndrome (PCOS) treatment. It possesses antioxidant properties, reducing oxidative stress and improving fertility. Pomegranate extract may help regulate hormonal imbalances and promote regular menstrual cycles.