Concomitant suppression of COX-1 and COX-2 is insufficient to induce enteropathy associated with chronic NSAID use.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medications for the management of chronic pain; however, they are associated with gastrointestinal (GI) adverse events. Although many mechanisms have been suggested, NSAID-induced enteropathy has been thought to be primarily due to inhibition of both cyclooxygenases (COX) -1 and -2, which results in suppression of prostaglandin synthesis. Here we report that concomitant postnatal deletion of and over 10 months failed to cause intestinal injury in mice unless they were treated with naproxen or its structural analog, phenylpropionic acid, which is not a COX inhibitor.

Disruption of the PGE synthesis / response pathway restrains atherogenesis in programmed cell death-1 (Pd-1) deficient hyperlipidemic mice.

Immune checkpoint inhibitors (ICIs) that target programmed cell death 1 (PD-1) have revolutionized cancer treatment by enabling the restoration of suppressed T-cell cytotoxic responses. However, resistance to single-agent ICIs limits their clinical utility. Combinatorial strategies enhance their antitumor effects, but may also enhance the risk of immune related adverse effects of ICIs.

Impact of Social Restrictions During COVID-19 on the Aquatic Levels of Antimicrobials and Other Drugs in Delhi.

The relative contribution of factors responsible for the environmental exposure of active pharmaceutical ingredients (APIs) is of interest for appropriate remedial measures. This study was carried out to evaluate the post-lockdown levels of APIs in water resources, in comparison to our previously published study from 2016. The environmental levels of 28 drugs from different classes were analyzed in surface water (Yamuna River), aquifers, and leachate samples collected from 26 locations in Delhi-NCR using the previously validated liquid chromatography-mass spectrometry (LC-MS/MS) methods.

Differential Impact In Vivo of Pf4-ΔCre-Mediated and Gp1ba-ΔCre-Mediated Depletion of Cyclooxygenase-1 in Platelets in Mice.

Background: Low-dose aspirin is widely used for the secondary prevention of cardiovascular disease. The beneficial effects of low-dose aspirin are attributable to its inhibition of platelet Cox (cyclooxygenase)-1-derived thromboxane A. Until recently, the use of the Pf4 (platelet factor 4) Cre has been the only genetic approach to generating megakaryocyte/platelet ablation of Cox-1 in mice.

PGF2α signaling drives fibrotic remodeling and fibroblast population dynamics in mice.

Idiopathic pulmonary fibrosis (IPF) is a chronic parenchymal lung disease characterized by repetitive alveolar cell injury, myofibroblast proliferation, and excessive extracellular matrix deposition for which unmet need persists for effective therapeutics. The bioactive eicosanoid, prostaglandin F2α, and its cognate receptor FPr (Ptgfr) are implicated as a TGF-β1-independent signaling hub for IPF. To assess this, we leveraged our published murine PF model (IER-SftpcI73T) expressing a disease-associated missense mutation in the surfactant protein C (Sftpc) gene.

Disruption of Prostaglandin F Receptor Signaling Attenuates Fibrotic Remodeling and Alters Fibroblast Population Dynamics in A Preclinical Murine Model of Idiopathic Pulmonary Fibrosis.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic parenchymal lung disease characterized by repetitive alveolar cell injury, myofibroblast proliferation, and excessive extracellular matrix deposition for which unmet need persists for effective therapeutics. The bioactive eicosanoid, prostaglandin F2, and its cognate receptor FPr () are implicated as a TGF1 independent signaling hub for IPF. To assess this, we leveraged our published murine PF model (I - ) expressing a disease-associated missense mutation in the surfactant protein C () gene.

Hydrophilic interaction LC-MS/MS method to avoid endogenous interference in the analysis of 4-hydroxy isoleucine from dietary supplementation of fenugreek.

4-Hydroxy isoleucine is one of the potent hypoglycemic active constituents of fenugreek seeds. A method capable of reducing biological interferences is required for bioavailability studies. An isocratic separation of 4-hydroxy isoleucine from endogenous interferences was achieved in ZIC-cHILIC column using 0.

Ocular surface sphingolipids associate with the refractory nature of vernal keratoconjunctivitis: newer insights in VKC pathogenesis.

Background: The etiopathogenesis of vernal keratoconjunctivitis (VKC) is incompletely understood. Bioactive lipids play a key role in allergic disorders. This study focused on the sphingolipid metabolism on the ocular surface of VKC and to explore if it has a contributory role in the refractoriness of the disease.

Monocarbonyl curcuminoids as antituberculosis agents with their moderate in-vitro metabolic stability on human liver microsomes.

Tuberculosis, an airborne infectious disease, results in a high morbidity and mortality rate. The continuous emergence of TB resistance strains including MDR (multidrug-resistant tuberculosis), XDR (extensive drug-resistant tuberculosis), and especially TDR (totally drug-resistant tuberculosis) is a major public health threat and has intensified the need to develop new antitubercular agents. A natural product, curcumin, possesses diverse biological activities but suffers due to a lack of water solubility and bioavailability.

Effect of rutin on retinal VEGF, TNF-α, aldose reductase, and total antioxidant capacity in diabetic rats: molecular mechanism and ocular pharmacokinetics.

Purpose: The current study was conducted to explore the potential of rutin in preventing sight-threatening diabetic retinopathy.

Methods: Wistar albino rats (either sex) weighing 200-225 g were intraperitoneally injected with 45 mg/kg streptozotocin (pH 4.5).

Hybridization of Fluoro-amodiaquine (FAQ) with Pyrimidines: Synthesis and Antimalarial Efficacy of FAQ-Pyrimidines.

To evade the possible toxicity associated with the formation of quinone-imine metabolite in amodiaquine (AQ), the -hydroxyl group was replaced with a -F atom, and the resulting 4'-fluoro-amodiaquine (FAQ) was hybridized with substituted pyrimidines. The synthesized FAQ-pyrimidines displayed better potency than chloroquine (CQ) against the resistant strain (Dd2), exhibiting up to 47.3-fold better activity (IC: 4.

Molecular and Metabolic Markers of Fructose Induced Hepatic Insulin Resistance in Developing and Adult Rats are Distinct and Aegle marmelos is an Effective Modulator.

The time course of pathogenesis of fructose mediated hepatic insulin resistance (HepIR) is not well-delineated and we chronicle it here from post-weaning to adulthood stages. Weaned rats were provided for either 4 or 8 weeks, i.e.

Un-segregated waste disposal: an alarming threat of antimicrobials in surface and ground water sources in Delhi.

Exposure of active pharmaceutical compounds (APCs) to the environment during human use is of potential importance in the emergence of drug resistance, changing soil microbiota and their residual effect on living organisms. Thus, this study aimed to assess the extent of exposure of APCs in the hydrologic cycle in and around New Delhi. This study analyzed the presence of 28 drugs from different classes in the surface water (river Yamuna) and aquifers collected from 48 places in Delhi (within the radius of 40 km).