The natural product micheliolide promotes the nuclear translocation of GAPDH via binding to Cys247 and induces glioblastoma cell death in combination with temozolomide.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is significantly upregulated in glioblastoma (GBM) and plays a crucial role in cell apoptosis and drug resistance. Micheliolide (MCL) is a natural product with a variety of antitumour activities, and the fumarate salt form of dimethylamino MCL (DMAMCL; commercial name ACT001) has been tested in clinical trials for recurrent GBM; this compound suppresses the proliferation of GBM cells by rewiring aerobic glycolysis. Herein, we demonstrated that MCL directly targets GAPDH through covalent binding to the cysteine 247 (Cys247) residue.

A-kinase anchor protein 12 promotes oligodendrogenesis and cognitive recovery in carbon monoxide therapy for traumatic brain injury.

Therapeutic drug development for central nervous system injuries, such as traumatic brain injury (TBI), presents significant challenges. TBI results in primary mechanical damage followed by secondary injury, leading to cognitive dysfunction and memory loss. Our recent study demonstrated the potential of carbon monoxide-releasing molecules (CORMs) to improve TBI recovery by enhancing neurogenesis.

Nanosuspension Innovations: Expanding Horizons in Drug Delivery Techniques.

Nanosuspensions (NS), with their submicron particle sizes and unique physicochemical properties, provide a versatile solution for enhancing the administration of medications that are not highly soluble in water or lipids. This review highlights recent advancements, future prospects, and challenges in NS-based drug delivery, particularly for oral, ocular, transdermal, pulmonary, and parenteral routes. The conversion of oral NS into powders, pellets, granules, tablets, and capsules, and their incorporation into film dosage forms to address stability concerns is thoroughly reviewed.

Revisiting the Metabolism of Donepezil in Rats Using Non-Targeted Metabolomics and Molecular Networking.

: Although donepezil, a reversible acetylcholinesterase inhibitor, has been in use since 1996, its metabolic characteristics remain poorly characterized. Therefore, this study aims to investigate the in vivo metabolism of donepezil using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) based on a molecular networking (MN) approach integrated with a non-targeted metabolomics approach. : After the oral administration of donepezil (30 mg/kg) in rats, urine, feces, and liver samples were collected for LC-HRMS analysis.

Enhancing Patient-Centric Drug Development: Coupling Hot Melt Extrusion with Fused Deposition Modeling and Pressure-Assisted Microsyringe Additive Manufacturing Platforms with Quality by Design.

In recent years, with the increasing patient population, the need for complex and patient-centric medications has increased enormously. Traditional manufacturing techniques such as direct blending, high shear granulation, and dry granulation can be used to develop simple solid oral medications. However, it is well known that "one size fits all" is not true for pharmaceutical medicines.

()-Glucosciadopitysin, a New Biflavonoid Glycoside from the Leaves of and Osteogenic Activity of Bioflavonoids.

The leaves of have been used in treating freckles and effectively reducing cough and sputum in folk medicines. Recently, investigations into the correlation between ginkgo leaves and the proliferative activity of osteogenic differentiation have been conducted. However, bioactive compounds that enhance osteogenesis or exhibit osteoporosis prevention from have not been fully identified.

Nrf2 Activation as a Therapeutic Target for Flavonoids in Aging-Related Osteoporosis.

Biological aging is a substantial change that leads to different diseases, including osteoporosis (OP), a condition involved in loss of bone density, deterioration of bone structure, and increased fracture risk. In old people, there is a natural decline in bone mineral density (BMD), exacerbated by hormonal changes, particularly during menopause, and it continues in the early postmenopausal years. During this transition time, hormonal alterations are linked to elevated oxidative stress (OS) and decreased antioxidant defenses, leading to a significant increase in OP.

High-Yield Production of Polyhydroxybutyrate and Poly(3-hydroxybutyrate--3-hydroxyhexanoate) from Crude Glycerol by a Newly Isolated Species Oh_219.

Crude glycerol (CG), a major biodiesel production by-product, is the focus of ongoing research to convert it into polyhydroxyalkanoate (PHA). However, few bacterial strains are capable of efficiently achieving this conversion. Here, 10 PHA-producing strains were isolated from various media.

Neuroprotective Actions of Cannabinoids in the Bovine Isolated Retina: Role of Hydrogen Sulfide.

Both hydrogen sulfide and endocannabinoids can protect the neural retina from toxic insults under in vitro and in vivo conditions. The aim of the present study was two-fold: (a) to examine the neuroprotective action of cannabinoids [methanandamide and 2-arachidonyl glycerol (2-AG)] against hydrogen peroxide (HO)-induced oxidative damage in the isolated bovine retina and (b) to evaluate the role of endogenously biosynthesized hydrogen sulfide (HS) in the inhibitory actions of cannabinoids on the oxidative stress in the bovine retina. Isolated neural retinas from cows were exposed to oxidative damage using HO (100 µM) for 10 min.

Syringaldehyde Alleviates Cardiac Hypertrophy Induced by Hyperglycemia in H9c2 Cells Through GLP-1 Receptor Signals.

Cardiac hypertrophy is a significant complication of diabetes, often triggered by hyperglycemia. Glucagon-like peptide-1 (GLP-1) receptor agonists alleviate cardiac hypertrophy, but their efficacy diminishes under GLP-1 resistance. Syringaldehyde (SA), a natural phenolic compound, may activate GLP-1 receptors and mitigate hypertrophy.

Ceftazidime-Avibactam Versus Colistin for the Treatment of Multidrug-Resistant Infections: A Multicenter Cohort Study.

To evaluate the real-world evidence of ceftazidime-avibactam (CAZ-AVI) compared to intravenous colistin for the treatment of multidrug-resistant (MDR) infections. This is a multicenter, retrospective cohort study conducted in the period between 2017 and 2023 at five institutions for patients who received either CAZ-AVI or colistin-based regimens for treating MDR infections. Outcomes were compared using multivariate logistic regression analysis.

Design, Synthesis, and Antioxidant and Anti-Tyrosinase Activities of ()-5-Benzylidene-2-(naphthalen-1-ylamino)thiazol-4(5)-one Analogs: In Vitro and In Vivo Insights.

Fifteen compounds (-) constructed on a hybrid structure combining a β-phenyl-α,β-unsaturated carbonyl template and a 2-aminothiazol-4(5)-one scaffold were designed and synthesized as potential novel anti-tyrosinase substances. Two compounds ( and ) showed more potent inhibition against mushroom tyrosinase than kojic acid, and the inhibitory activity of (IC value: 1.60 μM) was 11 times stronger than that of kojic acid.

In Vivo and In Vitro Models of Hepatic Fibrosis for Pharmacodynamic Evaluation and Pathology Exploration.

Hepatic fibrosis (HF) is an important pathological state in the progression of chronic liver disease to end-stage liver disease and is usually triggered by alcohol, nonalcoholic fatty liver, chronic hepatitis viruses, autoimmune hepatitis (AIH), or cholestatic liver disease. Research on novel therapies has become a hot topic due to the reversibility of HF. Research into the molecular mechanisms of the pathology of HF and potential drug screening relies on reliable and rational biological models, mainly including animals and cells.

Phlorofucofuroeckol-A: A Natural Compound with Potential to Attenuate Inflammatory Diseases Caused by Airborne Fine Dust.

: Persistent exposure to airborne fine dust (FD) particles contributing to air pollution has been linked to various human health issues, including respiratory inflammation, allergies, and skin diseases. We aimed to identify potential seaweed anti-inflammatory bioactive reagents and determine their effects on systemic inflammatory responses induced by FD particles. : While exploring anti-inflammatory bioactive reagents, we purified compounds with potential anti-inflammatory effects from the seaweed extracts of , , and .

Unveiling as a Novel Prognostic Biomarker for Prostate Cancer Recurrence: From Gene to Prognosis.

Prostate cancer is a major global health burden, with biochemical recurrence (BCR) following radical prostatectomy affecting 20-40% of patients and posing significant challenges to prognosis and treatment. Emerging evidence suggests a critical role for differentially expressed in normal and neoplastic cell () domain-containing genes in oncogenesis; however, their implications in prostate cancer and BCR risk remain underexplored. This study systematically evaluated 151 single-nucleotide polymorphisms in domain-containing genes in 458 patients with prostate cancer and BCR, followed by validation in an independent cohort of 185 patients.

Assessment of Protein Quality and Nutritional Characteristics of Commonly Consumed Pulses in the Caribbean Diet by Different In Vitro Assays.

Pulses, the dried seeds of leguminous plants, form an important part of the diets of many cultures, including Caribbean cuisine, and are a rich source of protein, carbohydrates, and antioxidants while being low in fats. This study examined the effect of a traditional home-cooking method on the nutritional characteristics of pulses commonly consumed in the Caribbean: red kidney beans and cranberry beans ( L.), cowpeas ( L.

[Regulatory roles of and genes in plant oil synthesis].

There is a large gap between production and demand of plant oil in China, which leads to the heavy reliance on imports. Diacylglycerol acyltransferase (DGAT) and phospholipid: diacylglycerol acyltransferase (PDAT) are two key enzymes responsible for the synthesis of triacylglycerol, thereby affecting the yield and quality of plant oil. This paper comprehensively reviews the research progress in and in terms of their biological functions in plant oil synthesis, the molecular mechanisms of regulating plant lipid metabolism, growth, and development under stress, and their roles in driving oil synthesis under the background of synthetic biology.

An ER Stress and Mitochondrial Apoptosis Co-inducer for Enhanced Cancer Immunotherapy.

Though immunogenic cell death (ICD) has garnered significant attention in the realm of anticancer therapies, effectively stimulating strong immune responses with adequate antigen presentation in deep-seated cancers remains challenging. Herein, to promote antigen presentation, an efficient dual-targeted photodynamic ICD inducer is developed. Due to the enhanced spin-orbit coupling and electron structure modulation, the Cy5-I-CF probe showcases exceptional reactive oxygen species (ROS) generation capacity within cancer cells.

Recent advances in small molecule design strategies against hepatic fibrosis.

Hepatic fibrosis, a widespread pathological process observed across various liver diseases, is acknowledged as a potentially reversible condition. In recent years, liver fibrosis has garnered extensive research attention, with a primary emphasis on developing drugs that can directly block or reverse this condition. This paper presents a comprehensive review of the design strategies for various anti-hepatic fibrosis agents that have been many efficacious small-molecule drugs.

Discovery of 1,4-Disubstituted Cyclohexene Analogues as Selective GPR119 Agonists for the Treatment of Type 2 Diabetes.

GPR119 has emerged as a promising target for treating type 2 diabetes and associated obesity, as its stimulation induces the secretion of glucagon-like peptide-1 and glucose-dependent insulinotropic peptide in the intestinal tract as well as the glucose-dependent release of insulin in pancreatic β-cells. We describe the design and synthesis of novel GPR119 agonists containing a 1,4-disubstituted cyclohexene scaffold. Compound displayed nanomolar potency (EC = 3.

Personalized Risk Assessment for Taxane-Induced Hypersensitivity Reactions: A Systematic Review and Meta-Analysis.

Taxanes, including paclitaxel and docetaxel, are widely used in cancer treatment but frequently cause hypersensitivity reactions (HSRs), disrupting treatment continuity. This meta-analysis aimed to identify consistent risk factors for taxane-induced HSRs to support personalized risk assessments and optimize therapeutic outcomes. This systematic review and meta-analysis followed the PRISMA guidelines and was registered with PROSPERO (CRD42023476738).

Permeation Enhancer in Microemulsions and Microemulsion-Based Gels: A Comparison of Diethylene Glycol Monoethyl Ether and Oleyl Alcohol.

Microemulsions have been commonly used with various permeation enhancers to improve permeability through the skin. The purpose of this study was to compare the release and permeation ability of two commonly used permeation enhancers-diethylene glycol monoethyl ether (DGME) and oleyl alcohol-by the changes in oil composition, the addition of a gelling agent, and water content using ibuprofen as a model drug. Four microemulsions were formulated, selection was based on ternary phase diagrams, and physicochemical properties were evaluated.

Impact of Exercise on Tramadol-Conditioned Place Preference.

Background: Tramadol (TRA) is an opioid that is used to manage moderate to severe pain. Long-term use of TRA can lead to the development of opioid use disorder.

Objectives: This study investigates the role of forced exercise in reducing TRA-seeking behavior.

Thymoquinone-loaded Nanosized Ethosomal-based Hydrogels: Their Preparation, Characterization, in Vitro, Ex Vivo, and Antimicrobial Evaluation against Staphylococcus aureus.

Background: Thymoquinone (TQ) is found in the seeds of Nigella sativa. It has immunomodulatory, antibacterial, anti-inflammatory, antioxidant, astringent, antifungal, and antihistaminic properties, making it a highly valuable compound of interest. However, the use of it as a therapeutic drug is highly challenging because of its poor solubility, low bioavailability, and short-term stability.

Polydatin enhances oxaliplatin-induced cell death by activating NOX5-ROS-mediated DNA damage and ER stress in colon cancer cells.

Background: Polydatin (3,4',5-trihydroxy-3-β-d-glucopyranoside, PD) is known for its antioxidant and anti-inflammatory properties. Oxaliplatin (OXA)-based chemotherapy is the first-line treatment for metastatic and recurrent colorectal cancer (CRC). However, the lack of selectivity for normal cells often results in side effects.