Effect of nonsteroidal anti-inflammatory drugs (aspirin and naproxen) on inflammation-associated proteomic profiles in mouse plasma and prostate during TMPRSS2-ERG (fusion)-driven prostate carcinogenesis.

Recent preclinical studies have shown that the intake of nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin and naproxen could be an effective intervention strategy against TMPRSS2-ERG fusion-driven prostate tumorigenesis. Herein, as a follow-up mechanistic study, employing TMPRSS2-ERG (fusion) positive tumors and plasma from TMPRSS2-ERG. Ptenflox/flox mice, we profiled the stage specific proteomic changes (focused on inflammatory circulating and prostate tissue/tumor-specific cytokines, chemokines, and growth factors/growth signaling-associated molecules) that contribute to prostate cancer (PCa) growth and progression in the TMPRSS2-ERG fusion-driven mouse model of tumorigenesis. In addition, the association of the protective effects of NSAIDs (aspirin 1400 ppm and naproxen 400 ppm) with the modulation of these specific molecular pathways was determined. A sandwich Elisa based membrane array-proteome profiler identifying 111 distinct signaling molecules was employed. Overall, the plasma and prostate tissue sample analyses identified 54 significant and differentially expressed cytokines, chemokines, and growth factors/growth signaling-associated molecules between PCa afflicted mice (TMPRSS2-ERG. Ptenflox/flox, age-matched noncancerous controls, NSAIDs-supplemented and no-drug controls). Bioinformatic analysis of the array outcomes indicated that the protective effect of NSAIDs was associated with reduced expression of (a) tumor promoting inflammatory molecules (M-CSF, IL-33, CCL22, CCL12, CX3CL1, CHI3L1, and CD93), (b) growth factors- growth signaling-associated molecules (Chemerin, FGF acidic, Flt-3 ligand, IGFBP-5, and PEDF), and (c) tumor microenvironment/stromal remodeling proteins MMP2 and MMP9. Overall, our findings corroborate the pathological findings that protective effects of NSAIDs in TMPSS2-ERG fusion-driven prostate tumorigenesis are associated with antiproliferative and anti-inflammatory effects and possible modulation of the immune cell enriched microenvironment.

Adsorptive removal of naproxen onto nano magnesium oxide-modified castor wood biochar: Treatment of pharmaceutical wastewater via sequential Fenton's-adsorption process.

This current investigation explored the thermal conversion process of castor wood into biochar, which was subsequently harnessed for removing naproxen from pharmaceutical industrial effluent via adsorption. Surface composition analyses conducted through scanning electron microscopy-energy dispersive X-ray, laser-induced breakdown spectroscopy, and Fourier-transform infrared studies unveiled the presence of nano MgO particles within the adsorbent material. Employing optimization techniques such as response surface methodology facilitated a refined approach to batch study. The optimized conditions for batch naproxen sodium (NPX) adsorption on nano-MgO-modified biochar were identified as pH 4, 1.5 g/L adsorbent dosage, and a 120-min contact time maintaining a constant NPX concentration of 10 mg/L. The adsorption capacity was calculated to be 123.34 mg/g for a nano-magnesium oxide-modified castor wood biochar (modified biochar) and 99.874 mg/g for pristine castor wood biochar (pristine biochar). Fenton's reagents comprising 15 mM of FeSO4 (7H2O) and 25 mM of H2O2 have been scrutinized under conditions of pH 3.0, a reaction time of 30 min, a temperature of 30°C, and stirring at 120 rpm, followed by batch adsorption treatment. The COD, NH3-N, NO3 -, PO4 3-, and NPX removal percentages was found to be 90%, 87%, 79%, 80%, and 90%, respectively. Thus nano MgO-modified biochar holds promise of treatment of pharmaceutical effluent.

Fast and efficient extraction and determination of nonsteroidal anti-inflammatory drugs using poly(8-hydroxyquinoline)-coated magnetic graphene oxide nanocomposite prior to capillary electrophoresis analysis in wastewater, breast milk, and urine samples.

In this study, magnetic graphene oxide coated with poly(8-hydroxyquinoline) was successfully synthesized, characterized, and utilized as a novel sorbent for the ultrasonic-assisted dispersive magnetic solid-phase extraction of naproxen and ibuprofen. These analytes served as representative analytes for two nonsteroidal anti-inflammatory drugs in various real samples. Characterization techniques, such as IR, X-ray powder diffraction, field emission scanning electron microscopy, energy-dispersive X-ray-mapping, and Brunauer-Emmett-Teller (BET), were used to confirm the correctness synthesis and preparation of the nanocomposites. Effective parameters on the extraction efficiency were investigated to maximize the analytical performance of the developed method. The dynamic range (1-1000 µg L-1), coefficients of determination (R2 ≥ 0.997), the limits of detection (0.3-1.0 µg L-1), and limit of quantification (1.0-3.0 µg L-1), intra-day and inter-day precisions (3.5%-7.2%) were achieved. The method validation results showed extraction recovery ranging from 80.4% to 96.0% and preconcentration factors ranging from 137 to 140.

Designing Powerful Biindole-Based Inherently Chiral Selectors: Enhancing Enantiodiscrimination by Core Functionalization with Additional Coordination Elements.

Among inherently chiral selectors of axial stereogenicity, usually resulting in very good enantiodiscrimination performances, the biindole-based family has the additional advantage of very easy functionalization of the two nitrogen atoms with a variety of substituents with desirable properties. Aiming to evaluate the possibility of exploiting such feature to enhance the enantiodiscrimination ability of the archetype structure, a series of three inherently chiral monomers were designed and synthesized, characterised by a 2,2'-biindole atropisomeric core conjugated to bithiophene wings enabling fast and regular electrooligomerization, and functionalised at the nitrogen atoms with an ethyl, a methoxyethyl, or a hydroxyethyl substituent. Nitrogen alkylation was also exploited to obtain for the first time the chemical resolution of the biindole selectors without employing chiral HPLC. The enantiodiscrimination ability of the selector series was comparatively evaluated in proof-of-concept chiral voltammetry experiments with a "benchmark" chiral ferrocenyl probe as well as with chiral non-steroidal anti-inflammatory drugs naproxen and ketoprofen. The large enantiomer potential differences for all probes increased in the ethyl < methoxyethyl ≪ hydroxyethyl sequence of selector substituents, supporting our assumption on the beneficial role of an additional coordination element. The powerful hydroxyethyl selector was also applied to ketoprofen in a commercial drug matrix.

Exploring the potential of SrTi0.7Fe0.3O3 perovskite/Chitosan nanosheets for the development of a label-free electrochemical sensing assay for determination of naproxen in human plasma samples.

Naproxen is a nonsteroidal anti-inflammatory drug used to treat nonrheumatic inflammation, migraine, and gout. Therefore, the determination of naproxen in pharmaceutical and biological samples is of particular importance. In the present work, SrTi0.7Fe0.3O3 perovskite/Chitosan nanosheets were used to modify the surface of a glassy carbon electrode (GCE) for highly sensitive determination of naproxen. To ensure the successful synthesis of the perovskite nanosheets, morphological studies including scanning electron microscopy (SEM), Energy-dispersive X-ray (EDX), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and X-ray photoelectron spectroscopy (XPS) were carried out. The electrochemical investigations of naproxen on the modified surface of GCE were investigated and the limit of detection (LOD) and limit of quantification (LOQ) were acquired 0.50 and 1.67 µM, respectively. Additionally, the linear range (LR) of 1.99-130.84 µM was obtained for the oxidation of naproxen. The obtained results have been proved that the mentioned method is simple, sensitive, and specific with a short analysis time. The dominant analytical features of the designed sensor are possessing a low detection limit, excellent stability, repeatability, and high selectivity in the presence of naproxen. For investigation of the applicability of the designed assay in real sample analysis, human plasma samples have been examined and a recovery index was acquired 95%.

Strategic Assessment of Boron-Enriched Carbon Dots/Naproxen: Diagnostic, Toxicity, and In Vivo Therapeutic Evaluation.

Cancer is a significant global public health concern, ranking as the leading cause of mortality worldwide. This study thoroughly explores boron-doped carbon dots (B-CDs) through a simple/rapid microwave-assisted approach and their versatile applications in cancer therapy. The result was highly uniform particles with an average diameter of approximately 4 nm. B-CDs exhibited notable properties, including strong fluorescence with a quantum yield of 33%. Colloid stability tests revealed their robustness within a pH range of 6-12, NaCl concentrations up to 0.5 M, and temperatures ranging from 30 to 60 °C. The study also delved into the kinetics of naproxen release from B-CDs as a drug delivery system. The loading efficacy of naproxen exceeded 55.56%. Under varying pH conditions, the release of naproxen from B-CDs conformed to the Peppas-Sahlin model, demonstrating the potential of Naproxen-loaded CDs for cancer drug delivery. In vitro cytotoxicity assessments, conducted using the CCK-8 Assay and flow cytometry, consistently indicated low toxicity with average cell viability exceeding 80%. An in vivo toxicity test on female mice administered 20 mg/kg of B-CDs for 31 days revealed reversible histological changes in the liver and kidneys, while the pancreas remained unaffected. Importantly, B-CDs did not impact the mice's physical behavior, body weight, or survival. In vivo experiments targeting benzo(a)pyrene-induced fibrosarcoma demonstrated the efficacy of B-CDs as naproxen carriers in the treatment of cancer. This in vivo study provides a thorough comprehension of B-CDs synthesis and toxicity and their potential applications in cancer therapy and drug delivery systems.

Biotransformation activities of fungal strain apiotrichum sp. IB-1 to ibuprofen and naproxen.

Ibuprofen (IBU) and naproxen (NPX), as widely prescribed non-steroidal anti-inflammatory drugs (NSAIDs), are largely produced and consumed globally, leading to frequent and ubiquitous detection in various aqueous environments. Previously, the microbial transformation of them has been given a little attention, especially with the isolated fungus. A yeast-like Apiotrichum sp. IB-1 has been isolated and identified, which could simultaneously transform IBU (5 mg/L) and NPX (2.5 mg/L) with maximum efficiencies of 95.77% and 88.31%, respectively. For mono-substrate, the transformation efficiency of IB-1 was comparable to that of co-removal conditions, higher than most of isolates so far. IBU was oxidized mainly through hydroxylation (m/z of 221, 253) and NPX was detoxified mainly via demethylation (m/z of 215) as shown by UPLC-MS/MS results. Based on transcriptome analysis, the addition of IBU stimulated the basic metabolism like TCA cycle. The transporters and respiration related genes were also up-regulated accompanied with higher expression of several dehydrogenase, carboxylesterase, dioxygenase and oxidoreductase encoding genes, which may be involved in the transformation of IBU. The main functional genes responsible for IBU and NPX transformation for IB-1 should be similar in view of previous studies, which needs further confirmation. This fungus would be useful for potential bioremediation of NSAIDs pollution and accelerate the discovery of functional oxidative genes and enzymes different from those of bacteria.

Ultrasound and magnetic resonance imaging-based investigation of the role of perfusion and oxygen availability in menstrual pain.

BACKGROUND: The mechanisms responsible for menstrual pain are poorly understood. However, dynamic, noninvasive pelvic imaging of menstrual pain sufferers could aid in identifying therapeutic targets and testing novel treatments. OBJECTIVE: To study the mechanisms responsible for menstrual pain, we analyzed ultrasonographic and complementary functional magnetic resonance imaging parameters in dysmenorrhea sufferers and pain-free controls under multiple conditions. STUDY DESIGN: We performed functional magnetic resonance imaging on participants with and those without dysmenorrhea during menses and outside menses. To clarify whether regional changes in oxygen availability and perfusion occur, functional magnetic resonance imaging R2∗ measurements of the endometrium and myometrium were obtained. R2∗ measurements are calculated nuclear magnetic resonance relaxation rates sensitive to the paramagnetic properties of oxygenated and deoxygenated hemoglobin. We also compared parameters before and after an analgesic dose of naproxen sodium. In addition, we performed similar measurements with Doppler ultrasonography to identify if changes in uterine arterial velocity occurred during menstrual cramping in real time. Mixed model statistics were performed to account for within-subject effects across conditions. Corrections for multiple comparisons were made with a false discovery rate adjustment. RESULTS: During menstruation, a notable increase in R2∗ values, indicative of tissue ischemia, was observed in both the myometrium (beta ± standard error of the mean, 15.74±2.29 s-1; P=.001; q=.002) and the endometrium (26.37±9.33 s-1; P=.005; q=.008) of participants who experienced dysmenorrhea. A similar increase was noted in the myometrium (28.89±2.85 s-1; P=.001; q=.002) and endometrium (75.50±2.57 s-1; P=.001; q=.003) of pain-free controls. Post hoc analyses revealed that the R2∗ values during menstruation were significantly higher among the pain-free controls (myometrium, P=.008; endometrium, P=.043). Although naproxen sodium increased the endometrial R2∗ values among participants with dysmenorrhea (48.29±15.78 s-1; P=.005; q=.008), it decreased myometrial R2∗ values among pain-free controls. The Doppler findings were consistent with the functional magnetic resonance imaging (-8.62±3.25 s-1; P=.008; q=.011). The pulsatility index (-0.42±0.14; P=.004; q=.004) and resistance index (-0.042±0.012; P=.001; q=.001) decreased during menses when compared with the measurements outside of menses, and the effects were significantly reversed by naproxen sodium. Naproxen sodium had the opposite effect in pain-free controls. There were no significant real-time changes in the pulsatility index, resistance index, peak systolic velocity, or minimum diastolic velocity during episodes of symptomatic menstrual cramping. CONCLUSION: Functional magnetic resonance imaging and Doppler metrics suggest that participants with dysmenorrhea have better perfusion and oxygen availability than pain-free controls. Naproxen sodium's therapeutic mechanism is associated with relative reductions in uterine perfusion and oxygen availability. An opposite pharmacologic effect was observed in pain-free controls. During menstrual cramping, there is insufficient evidence of episodic impaired uterine perfusion. Thus, prostaglandins may have protective vasoconstrictive effects in pain-free controls and opposite effects in participants with dysmenorrhea.

Sumatriptan-naproxen sodium in migraine: A review.

BACKGROUND: Varied responses to acute migraine medications have been observed, with over one-third (34.5%) of patients reporting insufficient headache relief. Sumatriptan-naproxen sodium, a single, fixed-dose combination tablet comprising sumatriptan 85 mg and naproxen sodium 500 mg, was developed with the rationale of targeting multiple putative mechanisms involved in the pathogenesis of migraine to optimise acute migraine care. METHODS: A narrative review of clinical trials investigating sumatriptan-naproxen sodium for both adults and adolescents was performed in March 2024. RESULTS: Across a total of 14 clinical trials in nine publications, sumatriptan-naproxen sodium offered greater efficacy for 2-h pain freedom (14/14) and sustained pain-free response up to 24 h (13/14) compared with monotherapy and/or placebo for both adult and adolescent study participants with an acceptable and well-tolerated adverse effect profile. Clinical trial data also demonstrates the effectiveness of sumatriptan-naproxen sodium in participants with allodynia, probable migraine, menstrual-related migraine and those with poor responses to acute, non-specific, migraine medication. CONCLUSIONS: Multi-mechanistic therapeutic agents offer an opportunity to optimise acute medications by targeting multiple mediators involved in the pathogenesis of migraine. Sumatriptan-naproxen sodium resulted in greater initial and sustained pain freedom, compared with either sumatriptan, naproxen-sodium and/or placebo, for the treatment of single or multiple attacks of migraine across both adult and adolescent study populations.

What a pain in the back: a review of current treatment options with a focus on naproxen sodium.

Non-specific low back pain (LBP) represents a challenging and prevalent condition that is one of the most common symptoms leading to primary care physician visits. While established guidelines recommend prioritizing non-pharmacological approaches as the primary course of action, pharmacological treatments are advised when non-pharmacological approaches are ineffective or based on patient preference. These guidelines recommend non-steroidal anti-inflammatory drugs (NSAIDs) or skeletal muscle relaxers (SMRs) as the first-line pharmacological options for acute or subacute LBP, while NSAIDs are the exclusive first-line pharmacological option for chronic LBP. Although SMRs are generally effective for acute LBP, the available evidence does not support the view that they improve functional recovery, and their comparative efficacy to NSAIDs and other analgesics remains unknown, while studies have shown them to introduce adverse events without significantly reducing LBP. Moreover, opioids continue to be widely prescribed for LBP, despite limited evidence for effectiveness and known risks of addiction and overdose. Broader use of non-opioid pharmacotherapy, including the appropriate use of OTC options, is critical to addressing the opioid crisis. The balance of evidence indicates that NSAIDs have a favorable benefit-risk profile when compared to other available pharmacological treatment options for non-specific LBP, a condition that is primarily acute in nature and well-suited for self-treatment with OTC analgesics. While clinical guidelines do not differentiate between NSAIDs, evidence indicates that OTC naproxen sodium effectively relieves pain across multiple types of pain models, and furthermore, the 14-h half-life of naproxen sodium allows sustained, all day pain relief with reduced patient pill burden as compared to shorter acting options. Choosing the most appropriate approach for managing LBP, including non-pharmacological options, should be based on the patient's condition, severity of pain, potential risks, and individual patient preference and needs.

Testing of acute and sub-acute toxicity profile of novel naproxen sodium nanoformulation in male and female mice.

Nanodrugs offer promising alternatives to conventionally used over the counter drugs. Compared to its free form, therapeutic benefits, and gastric tissue safety of naproxen sodium nanoformulation (NpNF) were recently demonstrated. Essential regulatory safety data for this formulation are, however, not available. To address this, male and female BALB/c mice were subjected to acute and 14-day repeated-oral dose assessments. Our data indicate that NpNF was well tolerated up to 2000 mg/kg b.w. A 14-day subacute toxicity testing revealed that the oral administration of low dose (30 mg/kg) NpNF did not produce any adverse effects on blood profile and serum biochemical parameters. Levels of oxidative stress markers and antioxidant enzymes neared normal. Histology of selected tissues also showed no evidence of toxicity. In contrast, a ten-fold increase in NpNF dosage (300 mg/kg), demonstrated, irrespective of gender, mild to moderate toxicity (p < 0.05) in the brain, stomach, and heart tissues, while ROS, LPO, CAT, SOD, POD, and GSH levels remained unaffected in the liver, kidney, spleen, testis, and seminal vesicles. No effect on serum biochemical parameters, overall indicated a no-observed-adverse-effect level (NOAEL) is 300 mg/kg. Further increase in dosage (1000 mg/kg) significantly altered all parameters demonstrating that high dose is toxic.

Removal of ibuprofen, naproxen and 17-ß-estradiol in water using L. octovalvis constructed wetlands.

This study was developed to evaluate the removal potential of ibuprofen, naproxen and 17-ß-estradiol in artificial wetlands constructed on a laboratory scale, using eight experimental devices planted with L. octovalvis species, tested with gravel substrate and without gravel substrate, which were fortified with synthetic mixtures at concentrations of 1, 2 and 5 mg/L of the three compounds, during a batch exposure time of nine days. The removal efficiency for 17-ß-estradiol was 94.5 ± 2.47%, followed by ibuprofen 94.03 ± 1.96% and naproxen 81.57 ± 8.74%, respectively. The treatment with the highest removal was the one performed without the presence of gravel substrate. The highest removal efficiency occurred from the third day of exposure for the three compounds, so it was established as the optimum residence time. The model that best explained the adsorption process of the three compounds studied, was the Langmuir isotherm. The observed results demonstrate that L. octovalvis can be used as a native species in artificial wetlands for the efficient removal of pharmaceutical compounds.

Through the use of a macrophyte plant native to the state of Morelos, an artificial wetland was built, which was capable of removing several drugs with tolerance to changes in concentration, which constitutes an economic and sustainable alternative that can be coupled to the treatment of wastewater contaminated with this type of compounds.

Amelioration of tableting properties and dissolution rate of naproxen co-grinded with nicotinamide: preparation and characterization of co-grinded mixture.

OBJECTIVE AND SIGNIFICANCE: Reducing the dimensions, when other additives are present, shows potential as a method to improve the dissolution and solubility of biopharmaceutical classification system class II drugs that have poor solubility. In this investigation, the process involved grinding naproxen with nicotinamide with the aim of improving solubility and the rate of dissolution. METHODS: Naproxen was subjected to co-milling with urea, dimethylurea, and nicotinamide using a planetary ball mill for a duration of 90 min, maintaining a 1:1 molar ratio for the excipients (screening studies). The co-milled combinations, naproxen in its pure milled form, and a physical mixture were subjected to analysis using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), and solubility assessment. The mixture displaying the highest solubility (naproxen-nicotinamide) was chosen for further investigation, involving testing for intrinsic dissolution rate (IDR) and Fourier-transform infrared spectroscopy (FTIR) after co-milling for both 90 and 480 min. RESULTS AND CONCLUSION: The co-milled combination, denoted as S-3b and consisting of the most substantial ratio of nicotinamide to naproxen at 1:3, subjected to 480 min of milling, exhibited a remarkable 45-fold increase in solubility and a 9-fold increase in IDR. XRPD analysis of the co-milled samples demonstrated no amorphization, while SEM images portrayed the aggregates of naproxen with nicotinamide. FTIR outcomes negate the presence of any chemical interactions between the components. The co-milled sample exhibiting the highest solubility and IDR was used to create a tablet, which was then subjected to comprehensive evaluation for standard attributes. The results revealed improved compressibility and dissolution properties.

Novel 1,3,4-oxadiazole derivatives of naproxen targeting EGFR: Synthesis, molecular docking studies, and cytotoxic evaluation.

The close association between inflammation and cancer inspired the synthesis of a series of 1,3,4-oxadiazole derivatives (compounds H4-A-F) of 6-methoxynaphtalene. The chemical structures of the new compounds were validated utilizing Fourier-transform infrared, proton nuclear magnetic resonance, and carbon-13 nuclear magnetic resonance spectroscopic techniques and CHN analysis. Computer-aided drug design methods were used to predict the compounds biological target, ADMET properties, toxicity, and to evaluate the molecular similarities between the design compounds and erlotinib, a standard epidermal growth factor receptor (EGFR) inhibitor. The antiproliferative effects of the new compounds were evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, cell cycle analysis, apoptosis detection by microscopy, quantitative reverse transcription-polymerase chain reaction, and immunoblotting, and EGFR enzyme inhibition assay. In silico analysis of the new oxadiazole derivatives indicated that these compounds target EGFR, and that compounds H4-A, H4-B, H4-C, and H4-E show similar molecular properties to erlotinib. Additionally, the results indicated that none of the synthesized compounds are carcinogenic, and that compounds H4-A, H4-C, and H4-F are nontoxic. Compound H4-A showed the best-fit score against EGFR pharmacophore model, however, the in vitro studies indicated that compound H4-C was the most cytotoxic. Compound H4-C caused cytotoxicity in HCT-116 colorectal cancer cells by inducing both apoptosis and necrosis. Furthermore, compounds H4-D, H4-C, and H4-B had potent inhibitory effect on EGFR tyrosine kinase that was comparable to erlotinib. The findings of this inquiry offer a basis for further investigation into the differences between the synthesized compounds and erlotinib. However, additional testing will be needed to assess all of these differences and to identify the most promising compound for further research.

Novel Fe3O4 Nanoparticles with Bioactive Glass-Naproxen Coating: Synthesis, Characterization, and In Vitro Evaluation of Bioactivity.

Immune response to biomaterials, which is intimately related to their surface properties, can produce chronic inflammation and fibrosis, leading to implant failure. This study investigated the development of magnetic nanoparticles coated with silica and incorporating the anti-inflammatory drug naproxen, aimed at multifunctional biomedical applications. The synthesized nanoparticles were characterized using various techniques that confirmed the presence of magnetite and the formation of a silica-rich bioactive glass (BG) layer. In vitro studies demonstrated that the nanoparticles exhibited bioactive properties, forming an apatite surface layer when immersed in simulated body fluid, and biocompatibility with bone cells, with good viability and alkaline phosphatase activity. Naproxen, either free or encapsulated, reduced nitric oxide production, an inflammatory marker, while the BG coating alone did not show anti-inflammatory effects in this study. Overall, the magnetic nanoparticles coated with BG and naproxen showed promise for biomedical applications, especially anti-inflammatory activity in macrophages and in the bone field, due to their biocompatibility, bioactivity, and osteogenic potential.

Photocatalytic Degradation of Naproxen: Intermediates and Total Reaction Mechanism.

Photochemical and photocatalytic oxidation of naproxen (NPX) with UV-A light and commercial TiO2 under constant flow of oxygen have been investigated. Adsorption experiments indicated that 90% of the solute remained in the solution. Combined chemical analysis of samples on the photochemical degradation indicated that NPX in an aqueous solution (20 ppm) is efficiently transformed into other species but only 18% of the reactant is mineralized into CO2 and water after three hours of reaction. Performing the photocatalytic oxidation in the presence of TiO2, more than 80% of the organic compounds are mineralized by reactive oxidation species (ROS) within four hours of reaction. Analysis of reaction mixtures by a combination of analytical techniques indicated that naproxen is transformed into several aromatic naphthalene derivatives. These latter compounds are eventually transformed into polyhydroxylated aromatic compounds that are strongly adsorbed onto the TiO2 surface and are quickly oxidized into low-molecular-weight acids by an electron transfer mechanism. Based on this and previous studies on NPX photocatalytic oxidation, a unified and complete degradation mechanism is presented.

Combination of naproxen and a chemically-stable eicosapentaenoic acid analog provide additive tumor protection in Pirc rats.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. Patients with the genetic disorder Familial Adenomatous Polyposis (FAP) develop hundreds to thousands of polyps that unless removed by prophylactic colectomy will progress to CRC at an early age. Nonsteroidal anti-inflammatory drugs (NSAIDs) and the ω-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA), have been evaluated for their chemopreventive potential in delaying CRC onset in high-risk patients. In our study, we determined whether the NSAID, naproxen, alone or in combination with a chemically-stable EPA analog (TP-252), affects tumor formation in the ApcPirc rat model. When compared to control diet, animals fed naproxen or HD TP-252 had 66% and 82% fewer tumors, respectively. However, animals fed a combination of naproxen and HD TP-252, exhibited a 95% reduction in tumor formation and a 98% reduction in tumor volume, respectively. To elucidate potential mechanisms of tumor protection, a comprehensive, targeted lipidomic analysis was performed on colonic mucosa to determine changes in eicosanoid metabolism. Animals receiving TP-252 alone or in combination with naproxen had significantly reduced mucosal levels of proinflammatory ω-6 eicosanoids (PGE2 , 5-HETE and 14,15-DiHETrE), along with a simultaneous increase in anti-inflammatory EPA-derived ω-3 eicosanoids. A comprehensive lipidomic analysis also uncovered several potential pharmacodynamic (PD) lipid biomarkers, including resolvin E2, 9-HEPE, 12-HEPE and 18-HEPE, that were significantly correlated with tumor protection. Further studies with this drug combination should be focused on dose optimization and the role of EPA-derived lipid mediators in CRC initiation and progression.

Interactions of Nonsteroidal Antiinflammatory Drugs and Aspirin and Risk of Cardiovascular Disease in Patients With Osteoarthritis.

Nonsteroidal antiinf lammatory drugs (NSAIDs) remain the mainstay of the pharmacologic management for relieving osteoarthritis pain, and low-dose aspirin is often prescribed to osteoarthritis patients who are at high risk of cardiovascular disease (CVD). We conducted cohort studies using data from The Health Improvement Network (THIN) database (2000-2019) to assess whether the relationship of initiation of naproxen or ibuprofen vs. initiation of other NSAIDs (excluding both naproxen and ibuprofen), respectively, to the risk of CVD was modified by coprescription of low-dose aspirin among the participants with osteoarthritis. Among participants without coprescription of aspirin, the risk of CVD was lower in naproxen initiators (10.3/1000 person-years) than in other NSAIDs initiators (13.2/1000 person-years; hazard ratio = 0.71, 95% confidence interval: 0.60, 0.85). Among participants with coprescription of aspirin, however, the risk of CVD was higher among naproxen initiators (36.9/1000 person-years) than that among other NSAIDs initiators (34.8/1000 person-years; hazard ratio = 1.48, 95% confidence interval: 1.12, 1.84). The association was significantly modified by coprescription of aspirin (P < 0.001). Similar findings were observed in the association of initiation of ibuprofen vs. other NSAIDs with the risk of CVD, which was significantly modified by coprescription of aspirin (P < 0.001). These findings suggest that osteoarthritis patients and clinicians should be aware of the potential CVD risk of concurrently taking naproxen or ibuprofen and low-dose aspirin.

Naproxen as a Turn-On Chemiluminescent Probe for Real-Time Quantification of Sulfate Radicals.

Current techniques for identifying and quantifying sulfate radicals (SO4·-) in SO4·--based advanced oxidation processes (SR-AOPs) are unsatisfactory due to their low selectivity, poor reliability, and limited feasibility for real-time quantification. In this study, naproxen (NAP) was employed as a turn-on luminescent probe for real-time quantification of SO4·- in SR-AOPs. The chemiluminescence(CL) yield (ΦCL) of the reaction of NAP with SO4·- was first determined to be 1.49 × 10-5 E mol-1 with the bisulfite activation by cerium(IV) [Ce(IV)/BS] process. Then, the maximum peak concentrations of SO4·- in the Ce(IV)/BS-NAP process was quantified to be ∼10-11 M based on the derived equation. Since ΦCL of the reaction of NAP with SO4·- was much greater than that with other reactive oxidizing species (ROS), the developed CL method worked well in selective quantification of SO4·- in various SR-AOPs (e.g., the activation of peroxymonosulfate and persulfate by iron processes). Finally, the electron transfer from NAP to SO4·- was proposed to be the critical step for CL production. This work provides a novel CL method for real-time quantification of SO4·-, which facilitates the development of SR-AOPs and their application in water and wastewater treatment.

HPLC-Fluorescence Detection Method for Concurrent Estimation of Domperidone and Naproxen. Validation and Eco-Friendliness Appraisal Studies.

This work demonstrates a simple and reliable HPLC method with fluorimetric detection for simultaneous estimation of domperidone (DOM) and naproxen (NAP). Successful chromatographic separation was accomplished using Inertsil ODS C18 column (5 µm, 4.6 × 150 mm) with gradient elution of the mobile phase consisting of 0.01 M phosphate buffer (pH 5.5) solution and acetonitrile. The gradient elution started with 25% acetonitrile increased linearly to 65% in 5 min, then kept at this percentage till the end of the run. The mobile phase was pumped at a flow rate of 1.0 mL/min. The excitation wavelength at 284 nm was found suitable for both DOM and NAP since it corresponds to a maximum for the minor component DOM and measurable excitation for NAP, while using 316 and 355 nm as emission wavelengths for DOM and NAP, respectively. Peaks eluted with excellent resolution at retention times 4.4 and 6.3 min for DOM and NAP, respectively. Performance of the proposed method was tested according to ICH guidelines in regard to linearity, ranges, precision, accuracy, robustness, detection and quantitation limits. Calibration curves were linear in the ranges of 0.8-3.6 and 1.0-2.5 µg/mL for DOM and NAP respectively with correlation coefficients not less than 0.9996. The validated method was successfully applied to the analysis of DOM and NAP in their laboratory prepared tablets resembling the commercial dosage form, and assay results were favorably compared with a published reference HPLC method. The method's greenness was assessed using the Analytical Eco-Scale and the novel Analytical Greenness metric (AGREE).