Search Results (1,543)

Background/Objectives: Inflammation plays a role at multiple levels, contributing to tumorigenesis, cellular proliferation, cell survival, and metastasis. The established link between chronic inflammation and tumor development has shifted the therapeutic focus toward nonsteroidal anti-inflammatory drugs, which exert their effects primarily through cyclooxygenase inhibition. Methods: In the present study, the antitumor potential of novel synthesized oxaprozin derivatives was evaluated using the MTT assay. The immunomodulatory effects of the selected derivative were determined in vitro by measuring cytokine concentrations and performing flow cytometry. To investigate the inhibitory capacity of these derivatives against cyclooxygenase enzymes, an in vitro inhibition assay was conducted using fluorometric screening kits, followed by in silico validation. Results: All tested tumor cell lines exhibited sensitivity to compound 1, which demonstrated the lowest cytotoxic effect against non-cancerous mMSCs and MRC-5 cells. This compound can effectively target tumor cells, inducing potent apoptosis in 4T1 breast cancer cells through a strategic shift in the Bax/Bcl-2 balance and the downregulation of the oncogenic driver Bcl-6. Although the synthesized oxaprozin derivatives showed moderate affinity for COX-1, none of the newly synthesized compounds achieved more than 50% inhibition against COX-2 at a concentration of 100 μM. Consistently, in silico procedures validated the results of the in vitro COX inhibition assay. Conclusions: The findings of this study indicate that compound 1 has the ability to modulate immune responses under stimulated conditions, and its potent antitumor activity may not be directly related to cyclooxygenase inhibition, suggesting the involvement of COX-independent pathways. Full article

Background: Many widely used drugs—including non-steroidal anti-inflammatory drugs, tetracyclines and thiazide diuretics—are labelled as photosensitising, yet their phototoxicity has been defined almost entirely by ultraviolet A (UVA) exposure. Whether this risk extends to the near-infrared (NIR) wavelengths of lasers commonly used in aesthetic medicine is unclear, and a history of such medication is often treated as a relative contraindication to laser procedures. Methods: A bibliometric analysis of 391 Scopus-indexed publications using VOSviewer was performed to quantitatively map the thematic structure of the retrieved literature. The bibliometric mapping was complemented by sequential refinement of the Scopus corpus and a focused assessment of the final records to determine whether studies directly addressing the predefined experimental question could be identified. We assessed whether 980 nm diode-laser irradiation of normal human dermal fibroblasts (HDFs) induces phototoxicity in the presence of seven photosensitisers (ketoprofen, meloxicam, hydrochlorothiazide, doxycycline and diclofenac, with chlorpromazine and 8-methoxypsoralen as reference photosensitizers). Cells were irradiated through the closed culture-plate lid at two fluences (62.3 and 34.4 mJ/cm and viability was measured 0.5, 1 and 24 h later. Data were analysed by two-way ANOVA (compound × laser), pairwise Welch tests with Benjamini–Hochberg correction, and equivalence testing against an ISO 10993-5-based margin. Results: Viability remained between 82.7% and 109.6% of control under all conditions and never fell below the 70% cytotoxicity threshold. The compound × laser interaction was non-significant at every time point (p = 0.25–0.69), indicating no drug-specific phototoxicity, and no pairwise comparison remained significant after correction. A small, drug- and fluence-independent reduction of about six percentage points was observed but stayed well within the non-cytotoxic range and was equally present in drug-free controls. Conclusions: Under the specific 980 nm irradiation conditions tested, the photosensitising drugs did not increase phototoxicity in normal human dermal fibroblasts. These findings support a wavelength-specific view of drug photosafety: rigorous UVA-directed photoprotection remains essential, whereas the tested drugs did not increase phototoxicity under the specific in vitro 980 nm irradiation conditions evaluated in this study. Full article

The objective of this experiment was to compare the clinical efficacy of various dosages of phenylbutazone (PBZ) with a negative control. The hypothesis was that higher PBZ doses would result in improved efficacy in a dose-dependent manner. Eight horses were shod with adjustable heart bar shoes on one front foot. Grade 4.0/5.0 lameness was induced every 2 to 4 weeks by tightening a set screw against the heart bar. Heart rate (HR) and lameness score (LS) were monitored at rest; every 20 min after lameness induction for 5 h; and hourly for another 8 h. One hour after lameness induction, treatment was administered IV in a randomized blinded manner and included negative control (isotonic saline: SAL) or PBZ at 2.2 (LOW), 4.4 (MOD), or 8.8 (HIGH) mg/kg body weight. Jugular blood samples were obtained at experiment hours 0, 1:05, 3, 5, 9, and 13, and were evaluated for plasma PBZ concentration. Results were compared using repeated measures analysis of variance and Student–Newman–Keul’s test with the level of significance set at p < 0.05. MOD and HIGH dose PBZ reduced HR from 3.0 h through 12.0 h and LS from 1.67 h through 12.0 h post-administration (p < 0.05); there was no difference in response between MOD and HIGH dose PBZ. Compared to SAL, LOW dose PBZ reduced HR from 3.67 h through 5.0 h and LS from 3.67 h through 4.0 h after administration (p < 0.05). The conclusions were that LOW dose PBZ was clinically effective for only a brief period compared to SAL, and HIGH dose was not more effective than MOD dose PBZ. Full article

Background/Objectives: Topical ketoprofen gels are limited by the need for frequent reapplication, short skin residence time, and the risk of sunlight-induced photoallergic dermatitis. Film-forming solutions (FFSs) allow for extended retention; however, the solvents used may affect the polymer film’s characteristics. The present study aimed to elucidate the effect of macrogol 400 and isopropanol and develop a hypromellose-based ketoprofen FFS using a design of experiments (DoE) approach. Methods: A 3² full factorial design was applied to investigate the effects of macrogol 400 (0–5%, w/w) (X₁) and isopropanol (25–50%, w/w) concentrations (X₂) on film mechanical properties (tensile strength (Y₁), elongation at break (Y₂), and Young’s modulus (Y₃)). The DoE-based placebo and ketoprofen-loaded FFSs were characterized for their physicochemical, rheological, and textural properties, while the corresponding films were evaluated for appearance, weight, stickiness, and mechanical properties. In vitro ketoprofen release from the drug-loaded FFS was also evaluated. Results: Macrogol 400 concentration was identified as a significant factor influencing film mechanical properties. As a film plasticizer, macrogol 400 improved film mechanical properties up to the optimal concentration (2.75%), whereas the water/isopropanol ratio mainly affected the applicative (rheological and textural) properties of the FFSs. Ketoprofen incorporation significantly reduced the film tensile strength and elongation at break. In vitro release testing demonstrated 58.52% ketoprofen release after 6 h, with the Weibull model showing the best fit to the release profile. Conclusions: Macrogol 400 and isopropanol have a complex, mutually conditioned influence on the application characteristics of hypromellose-based FFS and the mechanical characteristics of the films. Incorporation of ketoprofen into the selected placebo formulation significantly reduced film deformability but yielded a thin, transparent film with favorable in vitro drug-release characteristics. The developed FFS represents a promising topical dosage form for non-steroidal anti-inflammatory drugs and warrants further investigation, particularly in terms of skin retention and in vivo performance. Full article

Osteoarthritis (OA) is a common, disabling joint disease characterized by complex inflammatory, oxidative, and catabolic cascades that culminate in progressive cartilage degradation, subchondral bone remodeling, and synovitis. Standard pharmacological treatments such as nonsteroidal anti-inflammatory drugs (NSAIDs) provide symptomatic relief of pain but do not prevent the progression of the disease and are often associated with serious gastrointestinal, renal and cardiovascular side effects following long-term use. Epigallocatechin-3-gallate (EGCG), resveratrol, curcumin, quercetin, luteolin and genistein are naturally occurring polyphenols which have been identified as promising disease-modifying osteoarthritis drugs (DMOADs). Mechanistically, these phytochemicals suppress key pro-inflammatory signaling pathways (NF-κB, MAPK), downregulate matrix-degrading enzymes (MMP-13, ADAMTS-5), mitigate reactive oxygen species (ROS), and attenuate chondrocyte apoptosis and senescence. Polyphenols have been shown in pre-clinical and clinical trials to reduce joint pain and preserve cartilage integrity. They also have a synergistic effect with conventional drugs, resulting in lower doses and reduced toxicity. However, their clinical translation has been hampered by poor oral bioavailability, rapid Phase II metabolism, and short intra-articular retention. Advanced drug-delivery systems, such as nanoparticles, liposomes, and sustained-release hydrogels, are essential to overcome these pharmacokinetic bottlenecks and realize their full therapeutic potential in OA management. Full article

This study presents solid dispersions of naproxen and sodium ibuprofen in porous SiO₂ pellets (manufactured via the hard template method) before and after additional phase manufacture from amine-functionalised silica gel. Nanoscopic pore evolution of the investigated materials was examined at all stages of synthesis using positron annihilation lifetime spectroscopy (PALS). The TG–DSC–FTIR/MS in He and synthetic air provided information on the systems’ thermal transformations. PALS showed that both drugs preferentially occupied smaller mesopores in SiO₂ pellets. Thermal analysis revealed distinct atmosphere- and drug-dependent behaviour. Silica confinement delayed naproxen’s thermal degradation but decreased sodium ibuprofen stability. Interestingly, thermal decomposition of sodium ibuprofen most likely also occurred through the evolution of volatile ibuprofen, as signals assigned to it were detected in both atmospheres, although less extensively in air. Encapsulation of naproxen in the investigated systems made it more resistant to high temperature, whereas for sodium ibuprofen the opposite tendency was observed. The amine-functionalized silica phase increased the overall thermal stability of both dispersions in helium, whereas oxidation in synthetic air seemed to be governed mainly by the NH₂-SiO₂ phase degradation. Full article

Background/Objectives: Fibromyalgia (FM) is common but frequently underdiagnosed, and family medicine physicians are usually the first clinicians consulted by affected patients. This study assessed the knowledge, beliefs, and clinical practices regarding FM among family medicine physicians and residents in Saudi Arabia. Methods: An analytical cross-sectional online survey was conducted between July and December 2025 using convenience sampling and a questionnaire adapted from a previously published instrument. Knowledge (0–18) and belief (0–6) scores were reported descriptively, compared across groups with t-tests and analysis of variance, and explored with multivariable linear regression. Results: Of 113 participants (29.4% of the calculated target of 384), 60.2% were junior residents. The mean knowledge score was 9.7 ± 3.32 (53.6% of the maximum) and the mean belief score 4.1 ± 1.23 (67.5%). Only 39.8% knew the American College of Rheumatology criteria, 47.8% regarded FM as primarily psychological, and 39.8% felt confident differentiating FM from similar conditions; non-steroidal anti-inflammatory drugs were the most frequently selected drug class (62.8%). Belief scores were higher in academic centres (4.7 ± 1.19 vs. 3.9 ± 1.18; p = 0.002). The regression model was not significant overall (F (13, 99) = 1.476; p = 0.140), and its two nominally significant coefficients did not persist after accounting for collinearity. Conclusions: In this exploratory convenience sample, recognition of FM coexisted with limited command of diagnostic criteria, low diagnostic confidence, and guideline-discordant prescribing. The findings are not nationally representative but identify plausible targets for criteria-based training and continuing medical education. Full article

Background/Objectives: Proton pump inhibitors (PPIs) are widely used, but real-world utilisation data from internal medicine settings remain limited. We estimated the screening-period prevalence of self-reported current PPI use among attendees of two internal medicine outpatient clinics and described treatment patterns among current users. Methods: In this single-centre cross-sectional survey in Adana, Türkiye (August 2025–January 2026), 977 consecutively screened adult outpatients were asked about current PPI use; 178 reported current use, and 149 of them (83.7%) completed an investigator-administered questionnaire. Wilson 95% confidence intervals (CIs) were calculated for the prevalence and three prespecified proportions; exploratory ≤6-versus >6-month comparisons used exact tests with Holm adjustment. Results: Current use was reported by 178/977 outpatients (18.2%; 95% CI 15.9–20.8%). Among users (mean age 57.5 ± 13.6 years; 61.1% women), median reported duration was 54 months (interquartile range 18–84); 86.6% reported use for >6 months and 34.2% for >5 years. Pantoprazole was most common (31.5%). Gastroprotection during non-steroidal anti-inflammatory drug (NSAID) or antithrombotic therapy (45.0%) and dyspepsia (35.6%) were the leading reasons; 80.6% of those citing gastroprotection reported current NSAID or antithrombotic use. Ongoing upper-gastrointestinal symptoms were reported by 77.9% (59.7% of those citing gastroprotection; 100.0% of those citing reflux). Conclusions: Nearly one in five screened outpatients reported current PPI use, and reported exposure was predominantly prolonged. Ongoing symptoms and prolonged use without a documented indication are signals that should prompt structured, individualised medication review. Full article

Bacteria of the genus Rhodococcus are degraders of various ecotoxicants, including pharmaceuticals, yet their activity against ketoprofen—a non-steroidal anti-inflammatory drug (NSAID) frequently detected in aquatic environments—remains poorly explored. To address this gap, we assessed the tolerance and removal of ketoprofen across Rhodococcus strains from the Regional Specialised Collection of Alkanotrophic Microorganisms (official acronym IEGM, WFCC number 285). All 175 strains tolerated ketoprofen at minimum inhibitory concentrations far above reported environmental levels. Two particularly resilient strains, R. erythropolis IEGM 712 and R. qingshengii IEGM 746, sustained growth in ketoprofen-supplemented medium. Transmission electron microscopy (TEM) examinations showed that most cells preserved structural integrity and morphology, while energy dispersive X-ray spectroscopy and elemental mapping showed maintenance of K+ homeostasis. Over 14 days of cultivation in the mineral medium with n-hexadecane, these two strains removed 40–58% of ketoprofen. Exposure to ketoprofen altered cellular morphometry and surface charge (ζ-potential) and led to the formation of by-products with a predicted lower ecotoxicity than the parent compound. These findings underscore the potential of Rhodococcus strains for the bioremediation of ketoprofen. Full article

Metal–Organic Frameworks (MOFs) have emerged as promising materials for the removal of pharmaceutical contaminants, including antibiotics and endocrine-disrupting compounds (EDCs), from contaminated water due to their high surface areas, tunable porosity, and versatile chemical functionalities. This review provides a comprehensive and critical assessment of MOF-based approaches for the adsorptive removal of pharmaceutical contaminants, including tetracyclines, sulfonamides, fluoroquinolones, non-steroidal anti-inflammatory drugs (NSAIDs), antidepressants, and EDCs. Particular emphasis is placed on the relationship between MOF characteristics and adsorption performance, including adsorption capacity and specific surface area, as well as on the adsorption isotherm, kinetic, and thermodynamic models used to elucidate adsorption behavior and mechanisms. A distinctive aspect of this review is the integrated evaluation of regeneration and reusability, including regeneration strategies, agents, adsorption–desorption cycles, and their effects on adsorption performance and material stability. Furthermore, FTIR-based evidence is critically examined to identify possible MOF–pharmaceutical interactions by comparing pristine and contaminant-loaded materials. The role of MOF composites and selected catalytic processes as complementary approaches to pharmaceutical removal is also discussed. Finally, challenges related to MOF production cost, metal toxicity, structural stability, scalability, regeneration efficiency, and application under realistic wastewater conditions are evaluated. By integrating adsorption performance, modeling, thermodynamics, regeneration, reusability, and spectroscopic evidence, this review provides a comprehensive and practically oriented perspective on the development of MOF-based technologies for pharmaceutical-contaminated water treatment. Full article

Non-steroidal anti-inflammatory drugs (NSAIDs) have been among the most frequently prescribed medications worldwide for several decades. Ongoing vigilance regarding their potential adverse effects on the gastrointestinal tract and kidneys remains critical. Over the past twenty years, accumulating evidence has indicated an increased cardiovascular (CV) risk associated with NSAID use, posing a significant challenge for both patients and healthcare providers. This issue has prompted the US Food and Drug Administration (FDA) to issue explicit warnings concerning NSAID use. Recent data and comparative analyses of existing publications provide a basis for critically re-evaluating the association between NSAID use and potential CV risk, particularly when NSAIDs are administered for approved indications such as the treatment of pain and inflammation in patients with arthritis. The debate regarding the CV safety of NSAIDs centers on establishing causality. It is necessary to determine whether NSAIDs directly induce CV risks by initiating new pathological processes or act as modulators that influence the severity of pre-existing susceptibilities. The evidence presented in this review supports the view that NSAIDs do not create new CV risks but reduce CV incidents in patients with inflammatory pathologies such as arthritis. Conversely, NSAIDs have been observed to slightly increase CV risk when used at inappropriate high doses or in patients without inflammatory pain, such as those with Alzheimer’s disease or other vulnerable populations. This perspective shifts the focus from causality to context-based risk management. The distinction between risk generation and risk modulation is proposed as a framework for the rational use of NSAIDs. The potential for NSAIDs to exacerbate pre-existing CV risk is dependent on the context of morbidity, and is low when used for anti-inflammatory indications in populations with the highest benefit, i.e., those with inflammatory morbidities. A general condemnation of NSAIDs keeps relevant patient populations from the only anti-inflammatory analgetic pharmacotherapy so far available. Full article

Ibuprofen is a widely used non-steroidal anti-inflammatory drug (NSAID) with antipyretic, analgesic, and anti-inflammatory activity; however, its low aqueous solubility limits its dissolution rate and, consequently, its oral bioavailability. This study aimed to develop and physicochemically characterize an ibuprofen-loaded self-nanoemulsifying drug delivery system (SNEDDS) using a Box–Behnken experimental design. Fifteen formulations were prepared and evaluated based on CQAs: cloud point, robustness to dilution, self-emulsification time, droplet size, zeta potential, and polydispersity index (PDI). The experimental responses were subjected to statistical analysis; robustness to dilution as the only response yielding a statistically valid and predictive model within the studied design space, which was used as the sole optimization criterion. The optimal formulation was evaluated and characterized according to previously established CQAs and subjected to thermodynamic stability testing and stress testing over one month. The optimized formulation exhibited rapid self-emulsification, with a self-emulsification time of 37.02 s, a cloud point of 64.87 °C, and high robustness to dilution across different pH conditions and dilution volumes. Moreover, it exhibited a mean droplet size below 157 nm, a zeta potential of −15.43 ± 0.58 mV, and a PDI of 0.251, suggesting adequate colloidal stability and uniformity of the dispersed system. These physicochemical attributes support the potential of the developed system as a platform for further biopharmaceutical evaluation of ibuprofen oral delivery. Full article

Background: Greater trochanteric pain syndrome (GTPS) may coexist with lumbar degenerative spine disease (LDSD) and complicate pain attribution. Methods: This retrospective cohort study evaluated the observed frequency and short-term clinical course of GTPS in a selected tertiary-care LDSD population and explored factors associated with a previous surgical recommendation. Among 153 consecutive eligible patients with clinically compatible and MRI-documented LDSD, 63 had clinical suspicion of GTPS; all 63 underwent hip MRI, demonstrated findings consistent with trochanteric bursitis, received ultrasound-guided trochanteric bursa injection plus a two-week non-steroidal anti-inflammatory drug course, and completed one- and three-month follow-up. Results: GTPS-related lateral hip pain decreased from 7.65 ± 0.86 at baseline to 2.62 ± 0.68 at one month and 1.97 ± 1.43 at three months (Friedman p < 0.001; Kendall’s W = 0.896). Twenty-five patients (39.7%) had received an outside-center lumbar surgical recommendation before GTPS recognition. In exploratory multivariable analysis, each additional pre-diagnosis outpatient visit (OR 5.82; 95% CI 2.41–14.07) and prior lumbar surgery (OR 8.75; 95% CI 1.23–62.15) were associated with previous surgical recommendation. Conclusions: These findings support careful assessment of extra-spinal pain generators in LDSD, while the retrospective uncontrolled design precludes causal inference. Full article

Background/Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used but can cause clinically significant gastrointestinal adverse events (GI-AEs). However, genetic susceptibility to NSAID-related GI toxicity remains insufficiently characterized in East Asian populations. This exploratory study aimed to identify genetic loci associated with grade ≥ 2 NSAID-related GI-AEs in Korean patients treated with commonly used NSAIDs. Methods: We conducted an exploratory genome-wide association study in a multicenter Korean cohort of NSAID-treated patients recruited from four Korean hospitals. A total of 339 patients were included, comprising 28 cases with grade ≥ 2 GI-AEs and 311 controls without documented GI-AEs. Genotyping was performed using the Korea Biobank Array, followed by imputation and quality control. Genome-wide association analysis was conducted under an additive logistic regression model adjusted for age, sex, and the first two principal components, with additional sensitivity analyses accounting for the specific NSAID type, cumulative DDD, and concomitant medications. Polygenic risk score analysis was performed using summary statistics from an arthritis-treated subset of the KoGES Ansan/Ansung cohort, and the selected variant were further evaluated using multivariable Firth penalized logistic regression. The discriminatory performance of clinical, laboratory, and genetic models was assessed using bootstrap internal validation. Results: The exploratory GWAS identified 20 suggestive variants associated with NSAID-related GI-AEs at p < 1 × 10⁻⁵, although no variant reached genome-wide significance. The KoGES-derived polygenic risk score was significantly associated with GI-AE status in the NSAID cohort, and 10 suggestive variants overlapped with SNPs included in the best-fit PRS model. rs1925245 maintained a consistent association in multivariable Firth penalized logistic regression. Conclusions: These findings suggest that NSAID-related GI-AEs in Korean patients may reflect a multifactorial susceptibility pattern involving both clinical context and polygenic risk. Although exploratory, this study provides candidate genetic signals for future replication and supports the need for larger ancestry-matched pharmacogenomic studies of NSAID-related GI toxicity. Full article

This study explored the potential of gold nanorods (AuNRs) functionalized with polyethylene glycol (PEG) and loaded with non-steroidal anti-inflammatory drugs (NSAIDs) fenamic acid (fenH) or its bromo-derivative (4′BrfenH) for targeted drug delivery and preclinical cancer research, given their pH-dependent drug-release profiles and in vitro cytotoxicity in breast cancer cell models. Both formulations demonstrated strong π–π stacking interactions with calf-thymus DNA, suggesting intercalation, and exhibited significant binding affinity to bovine and human serum albumins. Drug release was markedly higher at alkaline pH. As the fenamates are weak acids that are practically insoluble in their neutral form, this pH dependence is attributed principally to the ionization and solubility of the released drug rather than to a responsive carrier. Cytotoxicity assays revealed that AuNRs@PEG@4′BrfenH significantly reduced cell viability in both aggressive (MDA-MB-231) and less metastatic (MCF-7) breast cancer cell lines, particularly at higher concentrations, and caused structural disorganization in 3D spheroid cultures. These findings highlight the promise of AuNRs@PEG@4′BrfenH as a nanoplatform showing pH-dependent release and significant in vitro anticancer activity in breast cancer cell lines and spheroids, supporting its further investigation in relevant tumor models. Full article