Curcumin enhances the oral bioavailability of testosterone by inhibiting its intestinal metabolism.

Hypogonadism, characterized by low testosterone blood levels, affects 3%-5% of males worldwide. Oral testosterone undecanoate (TU) is emerging as a key route of administration due to its better ease of administration; however, it suffers from variable pharmacokinetics and pharmacodynamics. The variability is majorly attributed to intestinal glucuronidation of testosterone to its hydrophilic metabolite, testosterone glucuronide (TG), formed by the polymorphic uridine 5'-diphospho-glucuronosyltransferase 2B17 (UGT2B17).

A Phytobiotic Supersupplement From Improves Growth, Physiological Health, Skin Colour and Pattern in a Wild Ornamental Fish () Under Captivity.

Ornamental fish sector is one of the fastest growing industries in the world with an estimated market value of 18-20 billion USD. Despite its global economic significance, it suffers from several issues notably, high-cost carotenoids, inadequate seed production and antimicrobial resistance (AMR). The existence of multifaceted problems needs an integrated multifunctional solution.

Inter-individual variability, differential tissue abundance, and sub-cellular localization of human aldo-keto reductases (AKRs) and hydroxy-steroid dehydrogenases (HSDs).

Human aldo-keto reductases (AKRs) and hydroxysteroid dehydrogenases (HSDs) are oxidoreductases involved in the metabolism of steroidal hormones and xenobiotics; however, their inter-individual variability, tissue abundance, and subcellular localization remain understudied. This study employed quantitative proteomics to address these knowledge gaps utilizing cryopreserved human hepatocytes and subcellular intestinal and hepatic tissue fractions. Among 12 quantified AKRs, the abundance of AKR1C4 and AKR7A3 increased with age, showing 10- and 9-fold higher abundance in adults than neonates, respectively.

A new naphthalene-based fluorogenic substrate for cytochrome P450 4A11.

We aimed to create a high-throughput fluorimetric assay for the activity of CYP4A11, the major 20-HETE-producing enzyme. To this end, we probed 3-(6-methoxynaphthalen-2-yl)acrylic acid (MONACRA) as a potential CYP4A11 substrate. We studied its metabolism using human liver microsomes (HLM) and recombinant P450 enzymes.

Quantitative Contributions of Hepatic and Renal Organic Cation Transporters to the Clinical Pharmacokinetic Cimetidine-Metformin Interaction.

The widely prescribed oral anti-diabetic drug metformin is eliminated unchanged in the urine primarily through active tubular secretion. This process is mediated by organic cation transporter 2 (OCT2), an uptake transporter expressed on the basolateral membrane of renal proximal tubule cells. Metformin uptake into the liver, the site of action, is mediated by organic cation transporter 1 (OCT1), which is expressed on the sinusoidal membrane of hepatocytes.

Is 1-Methylnicotinamide a Good Organic Cation Transporter 2 (OCT2) Biomarker?

The impact of potential precipitant drugs on plasma or urinary exposure of endogenous biomarkers is emerging as an alternative approach to evaluating drug-drug interaction (DDI) liability. 1-Methylnicotinamide (NMN) has been proposed as a potential biomarker for renal organic cation transporter 2 (OCT2). NMN is synthesized in the liver from nicotinamide by nicotinamide N-methyltransferase (NNMT) and is subsequently metabolized by aldehyde oxidase (AO).

Effects of Chronic Alcohol Intake on the Composition of the Ensemble of Drug-Metabolizing Enzymes and Transporters in the Human Liver.

In this study, to better understand the mechanisms of the profound impact of alcohol consumption on drug pharmacokinetics, efficacy, and toxicity, we characterized the alcohol-induced changes in the ensemble of drug-metabolizing enzymes and transporters (DMETs) in the human liver by performing global proteomic analysis of human liver microsomes from 94 donors. DMET protein levels were analyzed concerning alcohol consumption, smoking history, and sex using non-parametric tests, which were further strengthened by correlational analysis. To this end, we used a provisional index of alcohol exposure formulated based on the relative abundances of four marker proteins best correlating with the level of alcohol consumption.

Replacement of fishmeal with Quinoa Husk (Chenopodium quinoa) for mitigating multiple stresses in Pangasianodon Hypophthalmus.

The fishmeal is boon for aquaculture production in this recent pollution and climate change era. However, the demand of fishmeal is enhancing in many folds which needs to find alternative to fishmeal in cheap price. The present investigation addresses these issues with quinoa husk (QH).

Integrative biomonitoring in Litopenaeus vannamei: Metal analysis and biochemical markers.

Contaminants are a major cause of seafood export rejections in foreign markets and have significantly impacted consumer health. This investigation addresses the issues of metal contamination and biochemical markers in Litopenaeus vannamei from East Midnapore, West Bengal, India. The analyzed metals included vanadium (V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), molybdenum (Mo), silver (Ag), gallium (Ga), germanium (Ge), arsenic (As), selenium (Se), strontium (Sr), tin (Sn), cadmium (Cd), mercury (Hg), and lead (Pb), using Inductively Coupled Plasma Mass Spectrometry (ICP-MS).

Quantitative contributions of hepatic and renal organic cation transporters to the clinical pharmacokinetic cimetidine-metformin interaction.

The widely prescribed oral anti-diabetic drug metformin is eliminated unchanged in the urine primarily through active tubular secretion. This process is mediated by organic cation transporter 2 (OCT2), an uptake transporter expressed on the basolateral membrane of renal proximal tubule cells. Metformin uptake into the liver, the site of action, is mediated by OCT1, which is expressed on the sinusoidal membrane of hepatocytes.

Effect of dietary Anabaena supplementation on nutrient utilization, metabolism and oxidative stress response in Catla catla fingerlings.

A 60-day feeding trial was conducted to evaluate the effects of dietary Anabaena blue-green algae (ABGA) meal on the growth performance, digestibility, and physio-metabolic responses of Catla catla fingerlings (initial average weight 9.45 ± 0.15 g).

Identification of the Biotransformation Pathways of a Potential Oral Male Contraceptive, 11β-Methyl-19-Nortestosterone (11β-MNT) and Its Prodrugs: An In Vitro Study Highlights the Contribution of Polymorphic Intestinal UGT2B17.

11β-Methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC) is a prodrug of 11β-MNT and is being considered as a promising male oral contraceptive candidate in clinical development. However, the oral administration of 11β-MNTDC exhibits an ~200-fold lower serum concentration of 11β-MNT compared to 11β-MNTDC, resulting in the poor bioavailability of 11β-MNT. To elucidate the role of the first-pass metabolism of 11β-MNT in its poor bioavailability, we determined the biotransformation products of 11β-MNT and its prodrugs in human in vitro models.

Comparison of Relative Activity versus Relative Expression Factors (RAF versus REF) in Predicting Glucuronidation Mediated Drug Clearance Using Recombinant UGTs.

Purpose: Predicting the quantitative fraction of glucuronidation (f) by individual UDP-glucuronosyltransferase enzymes (UGTs) is challenging due to the lack of selective inhibitors and inconsistent activity of recombinant UGT systems (rUGTs). Our study compares the relative expression versus activity factors (REF versus RAF) to predict f based on rUGT data to human liver and intestinal microsomes (HLM and HIM).

Methods: REF scalars were derived from a previous in-house proteomics study for eleven UGT enzymes (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT1A10, UGT2B4, UGT2B7, UGT2B10, UGT2B15, and UGT2B17), whereas RAF was calculated by measuring activities in rUGTs to microsomes of selective UGT probe substrates.

Effects of alcohol consumption and tobacco smoking on the composition of the ensemble of drug metabolizing enzymes and transporters in human liver.

We examined the effect of alcohol consumption and smoking on the abundance of drug-metabolizing enzymes and transporters (DMET) in human liver microsomes (HLM) isolated from liver tissues of 94 donors. Global proteomics analysis was performed and DMET protein levels were analyzed in relation to alcohol consumption levels, smoking history, and sex using non-parametric tests (p-value ≤ 0.05; cutoff of 1.

Differential Tissue Abundance of Membrane-Bound Drug Metabolizing Enzymes and Transporter Proteins by Global Proteomics.

Protein abundance data of drug-metabolizing enzymes and transporters (DMETs) are useful for scaling in vitro and animal data to humans for accurate prediction and interpretation of drug clearance and toxicity. Targeted DMET proteomics that relies on synthetic stable isotope-labeled surrogate peptides as calibrators is routinely used for the quantification of selected proteins; however, the technique is limited to the quantification of a small number of proteins. Although the global proteomics-based total protein approach (TPA) is emerging as a better alternative for large-scale protein quantification, the conventional TPA does not consider differential sequence coverage by identifying unique peptides across proteins.

Effect of Cimetidine on Metformin Pharmacokinetics and Endogenous Metabolite Levels in Rats.

Tubular secretion is a primary mechanism along with glomerular filtration for renal elimination of drugs and toxicants into urine. Organic cation transporters (OCTs) and multidrug and toxic extrusion (MATE) transporters facilitate the active secretion of cationic substrates, including drugs such as metformin and endogenous cations. We hypothesized that administration of cimetidine, an Oct/Mate inhibitor, will result in increased plasma levels and decreased renal clearance of metformin and endogenous Oct/Mate substrates in rats.

Characterization of Gla proteoforms and non-Gla peptides of gamma carboxylated proteins: Application to quantification of prothrombin proteoforms in human plasma.

Gamma (γ) carboxylation is an essential post-translational modification in vitamin K-dependent proteins (VKDPs), involved in maintaining critical biological homeostasis. Alterations in the abundance or activity of these proteins have pharmacological and pathological consequences. Importantly, low levels of fully γ-carboxylated clotting factors increase plasma des-γ-carboxy precursors resulting in little or no biological activity.

High-Throughput Assay of Cytochrome P450-Dependent Drug Demethylation Reactions and Its Use to Re-Evaluate the Pathways of Ketamine Metabolism.

In a search for a reliable, inexpensive, and versatile technique for high-throughput kinetic assays of drug metabolism, we elected to rehire an old-school approach based on the determination of formaldehyde (FA) formed in cytochrome P450-dependent demethylation reactions. After evaluating several fluorometric techniques for FA detection, we chose the method based on the Hantzsch reaction with acetoacetanilide as the most sensitive, robust, and adaptable to high-throughput implementation. Here we provide a detailed protocol for using our new technique for automatized assays of cytochrome P450-dependent drug demethylations and discuss its applicability for high-throughput scanning of drug metabolism pathways in the human liver.

The Plasma Membrane Monoamine Transporter is Highly Expressed in Neuroblastoma and Functions as an mIBG Transporter.

Neuroblastoma (NB) is a pediatric cancer with low survival rates in high-risk patients. I-mIBG has emerged as a promising therapy for high-risk NB and kills tumor cells by radiation. Consequently, I-mIBG tumor uptake and retention are major determinants for its therapeutic efficacy.

Nano‑zinc enhances gene regulation of non‑specific immunity and antioxidative status to mitigate multiple stresses in fish.

The toxicity of ammonia surged with arsenic pollution and high temperature (34 °C). As climate change enhances the pollution in water bodies, however, the aquatic animals are drastically affected and extinct from nature. The present investigation aims to mitigate arsenic and ammonia toxicity and high-temperature stress (As + NH + T) using zinc nanoparticles (Zn-NPs) in Pangasianodon hypophthalmus.

Health risk assessment and metal contamination in fish, water and soil sediments in the East Kolkata Wetlands, India, Ramsar site.

East Kolkata Wetlands (EKW) is an important site for fish culture in sewage-fed areas, which are major receivers of pollutants and wastages from Kolkata. EKW is internationally important as the Ramsar site was declared on Aug 2002 with an area of 125 km. EKW is a natural water body where wastewater-fed natural aquaculture has been practiced for more than 70 years.

Morbidity and Mortality of Necrotizing Fasciitis and Their Prognostic Factors in Children.

Background: This is a prospective study of the clinico-etiologic profile and factors affecting outcomes in 40 children managed for necrotizing fasciitis (NF).

Materials And Methods: Demographic details, clinical characteristics, and laboratory parameters were recorded, and the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score was calculated. Primary outcome (survival vs.

Mitigating multiple stresses in Pangasianodon hypophthalmus with a novel dietary mixture of selenium nanoparticles and Omega-3-fatty acid.

Effects of a novel dietary mixture of selenium nanoparticles (Se-NPs) and omega-3-fatty acids i.e., Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on mitigating arsenic pollution, high-temperature stress and bacterial infection were investigated in Pangasianodon hypophthalmus.