A multimodal approach to smart and sustained drug delivery for corneal wound management: the GelPol nanoformulation.

Background: This study aims to develop a thermo-photo dual-stimuli-responsive hydrogel matrix and ROS-responsive engineered nanocarriers-based composite GelPol nanoformulation for corneal wound management. GelPol is composed of modified gelatin and poloxamer 407SH holding nanoparticles (NPs) loaded with dexamethasone, rapamycin, and ciprofloxacin.

Research Design And Methods: Dual-stimuli-responsive hydrogel and ROS-responsive NPs were synthesized and characterized.

Non-Invasive Prenatal Screening for Down Syndrome: A Review of Mass-Spectrometry-Based Approaches.

Down Syndrome or Trisomy 21 (T21) is a complex genetic disease characterized by the presence of an extra chromosome 21, which leads to multiple clinical features and manifestations that severely affect the patient's quality of life. Various methods of prenatal screening have been developed over time, allowing informed decision-making. However, a common drawback of the current methods for detecting T21 is their invasive nature.

Cinnabarinic acid protects against metabolic dysfunction-associated steatohepatitis by activating aryl hydrocarbon receptor-dependent AMPK signaling.

Metabolic dysfunction-associated steatohepatitis (MASH) is an advanced form of metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by the accumulation of fats in the liver, chronic inflammation, hepatocytic ballooning, and fibrosis. This study investigates the significance of hepatic aryl hydrocarbon receptor (AhR) signaling in cinnabarinic acid (CA)-mediated protection against MASH. Here, we report that livers of high-fat, high-fructose, high-cholesterol diet-fed hepatocyte-specific aryl hydrocarbon receptor knockout mice (AhR-hKO) exhibited aggravated steatosis, inflammation, and fibrosis compared with control AhR-floxed livers.

Dual stimuli-responsive and sustained drug delivery NanoSensoGel formulation for prevention of cisplatin-induced ototoxicity.

Cisplatin (CisPt)-induced ototoxicity (CIO) is delineated as a consequence of CisPt-induced intracellular generation of reactive oxygen species (ROS) which can be circumvented by Bucillamine (BUC; an antioxidant drug with sulfhydryl groups) and Diltiazem (DLT, L-type calcium channel blocker). However, its effective accumulation in the Organ of Corti and cell cytoplasm is desired. Therefore, a biocompatible BUC- and DLT-nanoparticles (NPs)-impregnated dual stimuli-responsive formulation (NanoSensoGel) presented here with ROS- and thermo-responsive properties for the sustained and receptive delivery of drugs.

Role of ERK1/2 Signaling in Cinnabarinic Acid-Driven Stanniocalcin 2-Mediated Protection against Alcohol-Induced Apoptosis.

We have previously shown that a bona fide aryl hydrocarbon receptor (AhR) agonist, cinnabarinic acid (CA), protects against alcohol-induced hepatocyte apoptosis via activation of a novel AhR target gene, stanniocalcin 2 (Stc2). Stc2 translates to a secreted disulfide-linked hormone, STC2, known to function in cell development, calcium and phosphate regulation, angiogenesis, and antiapoptosis-albeit the comprehensive mechanism by which the CA-AhR-STC2 axis confers antiapoptosis is yet to be characterized. In this study, using RNA interference library screening, downstream antiapoptotic molecular signaling components involved in CA-induced STC2-mediated protection against ethanol-induced apoptosis were investigated.

The Use of the QbD Approach to Optimize the Co-Loading of Simvastatin and Doxorubicin in Liposomes for a Synergistic Anticancer Effect.

The present study aimed to optimize a liposomal formulation co-encapsulating simvastatin (SIM) and doxorubicin (DOX) that has future perspectives in anticancer therapy. The optimization process was performed by implementing the Quality by Design concept and by considering the results of a previous screening study. Failure Mode and Effects Analysis was used for the identification of the potential critical factors, i.

Cinnabarinic Acid Provides Hepatoprotection Against Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a chronic condition in which excess lipids accumulate in the liver and can lead to a range of progressive liver disorders including non-alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. While lifestyle and diet modifications have proven to be effective as NAFLD treatments, they are not sustainable in the long-term, and currently no pharmacological therapies are approved to treat NAFLD. Our previous studies demonstrated that cinnabarinic acid (CA), a novel endogenous Aryl hydrocarbon Receptor (AhR) agonist, activates the AhR target gene, Stanniocalcin 2, and confers cytoprotection against a plethora of ER/oxidative stressors.

Decoding Cinnabarinic Acid-Specific Stanniocalcin 2 Induction by Aryl Hydrocarbon Receptor.

Aryl hydrocarbon receptor (AhR) is a ligand-mediated transcription factor known for regulating response to xenobiotics, including prototypical 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) through the activation of CYP1A1 expression. Upon ligand-binding, AhR translocates to the nucleus, interacts with the AhR nuclear translocator, and binds to xenobiotic response elements (XREs; GCGTG) present in the promoter region of AhR-regulated genes. Recently, we identified a novel tryptophan catabolite, cinnabarinic acid (CA), as an endogenous AhR agonist capable of activating expression of AhR target gene stanniocalcin 2 (stc2).

Gemcitabine Direct Electrochemical Detection from Pharmaceutical Formulations Using a Boron-Doped Diamond Electrode.

The development of fast and easy-to-use methods for gemcitabine detection is of great interest for pharmaceutical formulation control in both research laboratories and hospitals. In this study, we report a simple, fast and direct electrochemical method for gemcitabine detection using a boron-doped diamond electrode. The electrochemical oxidation of gemcitabine on a boron-doped diamond electrode was found to be irreversible in differential pulse voltammetry, and scan rate influence studies demonstrated that the process is diffusion-controlled.

An Electrochemical Strategy for the Simultaneous Detection of Doxorubicin and Simvastatin for Their Potential Use in the Treatment of Cancer.

The aim of this study was to develop a disposable, simple, fast, and sensitive sensor for the simultaneous electrochemical detection of doxorubicin (DOX) and simvastatin (SMV), which could be used in preclinical studies for the development of new pharmaceutical formulations for drug delivery. Firstly, the electrochemical behavior of each molecule was analyzed regarding the influence of electrode material, electrolyte solution, and scan rate. After this, the proper electrode material, electrolyte solution, and scan rate for both active substances were chosen, and a linear sweep voltammetry procedure was optimized for simultaneous detection.