Systematic Evaluation of Tyrosine Kinase Inhibitors as OATP1B1 Substrates Using a Competitive Counterflow Screen.

Unlabelled: Although the primary elimination pathway for most tyrosine kinase inhibitors (TKI) involves CYP3A4-mediated metabolism, the mechanism by which these agents are brought into hepatocytes remains unclear. In this study, we optimized and validated a competitive counterflow (CCF) assay to examine TKIs as substrates of the hepatic uptake transporter OATP1B1. The CCF method was based on the stimulated efflux of radiolabeled estradiol-17β-glucuronide under steady-state conditions in HEK293 cells engineered to overexpress OATP1B1.

An improved method for measuring catalase activity in biological samples.

Catalase (CAT) is an important enzyme that protects biomolecules against oxidative damage by breaking down hydrogen peroxide (HO) into water and oxygen. CAT is present in all aerobic microbes, animals, and plants. It is, however, absent from normal human urine but can be detected in pathological urine.

Darolutamide does not interfere with OATP-mediated uptake of docetaxel.

The addition of darolutamide, an androgen receptor signalling inhibitor, to therapy with docetaxel has recently been approved as a strategy to treat metastatic prostate cancer. OATP1B3 is an SLC transporter that is highly expressed in prostate cancer and is responsible for the accumulation of substrates, including docetaxel, into tumours. Given that darolutamide inhibits OATP1B3 in vitro, we sought to characterise the impact of darolutamide on docetaxel pharmacokinetics.

Facile encapsulation of cyanoacrylate-based bioadhesive by electrospray method and investigation of the process parameters.

Polymer microcapsules containing cyanoacrylates have represented a promising option to develop self-healing biomaterials. This study aims to develop an electrospray method for the preparation of capsules using poly(methyl methacrylate) (PMMA) as the encapsulant and ethyl 2-cyanoacrylate (EC) as the encapsulate. It also aims to study the effect of the electrospray process parameters on the size and morphology of the capsules.

High-performance photocatalytic degradation and antifungal activity of chromium-doped nickel oxide nanoparticles.

The elimination of pollutants such as dyes and fungi has become a tedious process hence there is a need for multifunctional materials that can be used for the removal or degradation of various pollutants from wastewater. Here, a nickel oxide nanoparticle (NiONPs) was synthesized by the co-precipitation method. In the current study, a composite of nickel oxide nanoparticles (NiONPs) was synthesized using nitrogen and chromium as dopants to create (N/NiONPs) and (Cr/N/NiONPs), respectively and used for the removal of dyes and fungi.

Transforming Growth Factor Beta 2 (TGFB2) and Interferon Gamma Receptor 2 (IFNGR2) mRNA Levels in the Brainstem Tumor Microenvironment (TME) Significantly Impact Overall Survival in Pediatric DMG Patients.

This hypothesis-generating study characterized the mRNA expression profiles and prognostic impacts of antigen-presenting cell (APC) markers (CD14, CD163, CD86, and ITGAX/CD11c) in pediatric brainstem diffuse midline glioma (pbDMG) tumors. We also assessed the mRNA levels of two therapeutic targets, transforming growth factor beta 2 (TGFB2) and interferon gamma receptor 2 (IFNGR2), for their biomarker potentials in these highly aggressive pbDMG tumors. The expressions of CD14, CD163, and ITGAX/CD11c mRNAs exhibited significant decreases of 1.

Exploring pharmacokinetics of talazoparib in ABCB1/ABCG2-deficient mice using a novel UHPLC-MS/MS method.

A rapid, sensitive, and simple UHPLC-MS/MS method for the determination of the PARP inhibitor talazoparib in mouse plasma was developed and validated using [C,H]-talazoparib as an internal standard (IS). The assay procedure involved extraction of talazoparib and the IS from plasma using a single-step deproteination and separation of the analytes was achieved on an ACQUITY UPLC RP18 HSS T3 column with a mobile phase gradient at a flow rate of 0.4 mL/min in a run time of 5 min.

Novel fluorometric protocol for assessing myeloperoxidase activity.

Neutrophil myeloperoxidase (MPO) is an essential enzyme for the innate immune system. Measuring MPO activity is vital for understanding neutrophil characteristics and functions in various diseases. MPO activity can be measured using several methods, including spectrophotometric and fluorometric protocols.

The Effects of 3-Month Rosuvastatin Adjuvant Therapy on Post Thrombotic Syndrome following Deep Vein Thrombosis; a Randomized Clinical Trial.

Introduction: Statins are known to have anticoagulation and anti-inflammatory effects. This study aimed to investigate the effect of Rosuvastatin in reduction of post thrombotic syndrome (PTS) following deep vein thrombosis (DVT).

Methods: In this randomized clinical trial, patients who were diagnosed with DVT of lower extremity were randomly assigned to 4 treatment groups: group 1: Warfarin, group 2: Warfarin + Rosuvastatin, group 3: Rivaroxaban, and group 4: Rivaroxaban + Rosuvastatin.

Chemical Analysis, Antioxidant, and Antibacterial Potential of Aqueous Extract of Broccoli () Using GC-ms.

Antioxidant and antibacterial chemicals are key sources in medicinal plants. Alkaloids, phenolics, steroids, terpenes, flavonoids, terpenes, and volatile oils are a few of these plants' secondary metabolites. Phytochemicals, particularly the secondary metabolites produced by plants, are important for human nutrition, well-being, illness prevention, and antibacterial properties.

Determination and disposition of meta-iodobenzylguanidine in plasma and heart of transporter-deficient mice by UPLC-MS/MS.

A simple LC-MS/MS method for the quantitative determination of the norepinephrine analogue meta-iodobenzyl-guanidine (mIBG) was developed and validated for mouse plasma and tissues, including salivary gland and heart. The assay procedure involved a one-step solvent extraction of mIBG and the internal standard N-(4-fluorobenzyl)-guandine from plasma or tissue homogenates with acetonitrile. An Accucore aQ column was used to separate analytes using a gradient elution with a total run time of 3.

Prevalence of anemia and its associated factors among patients with type 2 diabetes mellitus in a referral diabetic clinic in the north of Iran.

Background: PURPOSE: This study intended to investigate the prevalence of anemia and its associated factors among patients with type 2 diabetes mellitus (T2DM) in Gorgan, Iran.

Methods: This cross-sectional study was conducted on 415 (109 men) patients with T2DM referred to the referral diabetes clinic of Sayad Shirazi Hospital in Gorgan in 2021. Demographic information, anthropometric indices, past medical history,  and some laboratory data on cell counts, serum blood glucose, HbA1c, creatinine, lipid/iron profiles, and urinary albumin were collected.

Targeting OCT2 with Duloxetine to Prevent Oxaliplatin-Induced Peripheral Neurotoxicity.

Unlabelled: Oxaliplatin-induced peripheral neurotoxicity (OIPN) is a debilitating side effect that afflicts ~90% of patients that is initiated by OCT2-dependent uptake of oxaliplatin in DRG neurons. The antidepressant drug duloxetine has been used to treat OIPN, although its usefulness in preventing this side effect remains unclear. We hypothesized that duloxetine has OCT2-inhibitory properties and can be used as an adjunct to oxaliplatin-based regimens to prevent OIPN.

Itraconazole-Induced Increases in Gilteritinib Exposure Are Mediated by CYP3A and OATP1B.

Gilteritinib, an FDA-approved tyrosine kinase inhibitor approved for the treatment of relapsed/refractory FLT3-mutated acute myeloid leukemia, is primarily eliminated via CYP3A4-mediated metabolism, a pathway that is sensitive to the co-administration of known CYP3A4 inhibitors, such as itraconazole. However, the precise mechanism by which itraconazole and other CYP3A-modulating drugs affect the absorption and disposition of gilteritinib remains unclear. In the present investigation, we demonstrate that pretreatment with itraconazole is associated with a significant increase in the systemic exposure to gilteritinib in mice, recapitulating the observed clinical drug-drug interaction.

Pharmacogenomics in Cytotoxic Chemotherapy of Cancer.

Pharmacogenetic testing in patients with cancer requiring cytotoxic chemotherapy offers the potential to predict, prevent, and mitigate chemotherapy-related toxicities. While multiple drug-gene pairs have been identified and studied, few drug-gene pairs are currently used routinely in the clinical status. Here we review what is known, theorized, and unknown regarding the use of pharmacogenetic testing in cancer.

Pharmacogenomics in Targeted Therapy and Supportive Care Therapies for Cancer.

Targeted therapies have significantly altered the landscape of available cancer therapies across all diagnoses and patient populations, and supportive care therapies have steadily improved throughout the years to make therapy more tolerable for patients. Even so, these therapies have varied efficacy and toxicity among patients with cancer, and pharmacogenomics presents an opportunity to identify which patients are most at risk of toxicities and most likely to benefit from them. While the field of pharmacogenomics in targeted cancer therapy is still growing, we review current knowledge, hypotheses, and clinical practices in this chapter, along with a brief review of pharmacogenomics in supportive therapies in cancer treatment.

An optimized protocol for estimating cellulase activity in biological samples.

Cellulase is a microbial enzyme responsible for degrading the β-1,4 glycoside bond in polysaccharide cellulose, which is abundant in various animal foodstuffs. Cellulase is an important industrial enzyme used for various purposes, including biopolishing textile fibers, softening garments, biostoning denim fabric, and removing excess color from textiles. In the food industry, cellulase is combined with pectinase and hemicellulase.

The role of OATP1B1 and OATP1B3 transporter polymorphisms in drug disposition and response to anticancer drugs: a review of the recent literature.

Introduction: Members of the solute carrier family of organic anion transporting polypeptides are responsible for the cellular uptake of a broad range of endogenous compounds and xenobiotics in multiple tissues. In particular, the polymorphic transporters OATP1B1 and OATP1B3 are highly expressed in the liver and have been identified as critical regulators of hepatic elimination. As these transporters are also expressed in cancer cells, the function alteration of these proteins have important consequences for an individual's susceptibility to certain drug-induced side effects, drug-drug interactions, and treatment efficacy.

MATE1 Deficiency Exacerbates Dofetilide-Induced Proarrhythmia.

Dofetilide is a rapid delayed rectifier potassium current inhibitor widely used to prevent the recurrence of atrial fibrillation and flutter. The clinical use of this drug is associated with increases in QTc interval, which predispose patients to ventricular cardiac arrhythmias. The mechanisms involved in the disposition of dofetilide, including its movement in and out of cardiomyocytes, remain unknown.

Interaction of Antifungal Drugs with CYP3A- and OATP1B-Mediated Venetoclax Elimination.

Venetoclax, a BCL-2 inhibitor used to treat certain hematological cancers, exhibits low oral bioavailability and high interpatient pharmacokinetic variability. Venetoclax is commonly administered with prophylactic antifungal drugs that may result in drug interactions, of which the underlying mechanisms remain poorly understood. We hypothesized that antifungal drugs may increase venetoclax exposure through inhibition of both CYP3A-mediated metabolism and OATP1B-mediated transport.

and Inhibition of MATE1 by Tyrosine Kinase Inhibitors.

The membrane transport of many cationic prescription drugs depends on facilitated transport by organic cation transporters of which several members, including OCT2 (), are sensitive to inhibition by select tyrosine kinase inhibitors (TKIs). We hypothesized that TKIs may differentially interact with the renal transporter MATE1 () and influence the elimination and toxicity of the MATE1 substrate oxaliplatin. Interactions with FDA-approved TKIs were evaluated in transfected HEK293 cells, and pharmacokinetic studies were performed in wild-type, MATE1-deficient, and OCT2/MATE1-deficient mice.

Mesoporous silica aerogel reinforced dental composite: Effects of microstructure and surface modification.

A mesoporous silica aerogel (SiA) with a high specific surface area was synthesized through the sol-gel process and subsequently modified with two different silane-based modifiers to reveals the effect of microstructure and surface modification on the fracture mechanics of a dental composite. The synthesized and modified aerogel were characterized using field-emission scanning electron microscopy (FESEM), nitrogen adsorption-desorption, and Fourier-transform infrared spectroscopy (FTIR). The prepared aerogels were then incorporated within methacrylate-based dental composites with the filler content of 0-35 wt%.

Assessment of the Risk of Breast Cancer Development Applying NCI Tool among Iraqi Women.

Objective: As part of the bioinformatics studies, we utilized National Cancer Institute (NCI)'s Breast Cancer Risk Assessment Tool to estimate the five-year period and lifetime risk of breast cancer development among Iraqi risky women.

Methods: Totally, 110 risky women aged 21-67 (mean=36±7.4) years were interviewed by a series of questions regarding the risk of breast cancer development.