The anti-inflammatory potential of Oroxylum indicum (OI), a traditional medicinal plant, was evaluated through in vitro, ex vivo, and molecular docking studies. The stem bark extract exhibited a significant, dose-dependent inhibition of protein denaturation in both egg albumin and bovine serum albumin assays at concentrations of 10, 30, and 100µg/mL. Molecular docking revealed strong binding affinities of key bioactive compounds, especially Oroxylin B (docking score -8.79), to the cyclooxygenase-2 (COX-2) enzyme, suggesting a mechanistic basis for anti-inflammatory effects. The extract exhibited no cytotoxicity on human lymphocytes across tested concentrations (20-200µg/mL) in the MTT assay, indicating safety. Ex vivo, OI extract significantly reduced COX-2 enzyme levels from 124.66 ± 0.16ng/mL in radiation controls to 107.33 ± 0.10ng/mL, comparable to diclofenac (106.36 ± 0.08ng/mL). Furthermore, IL-6 and TNF-alpha pro-inflammatory cytokine levels were substantially elevated by radiation but significantly decreased upon treatment with OI extract; IL-6 levels were reduced to 21.74 ± 0.95pg/mL compared to 27.45 ± 0.82pg/mL in radiation controls and TNF-alpha levels were similarly lowered, comparable to the diclofenac-treated group. These findings support the notion that the extract derived from the stem bark of Oroxylum indicum holds considerable strong possibility as a natural anti-inflammatory agent with modulatory effects on key inflammatory enzymes and cytokines, meriting further pharmacological and clinical evaluation.

The immunosuppressive tumor microenvironment (ITME)-marked by acidosis and hypoxia-persists as a critical barrier to cancer immunotherapy, especially for osteosarcoma. Herein, an injectable pH-responsive nanocomposite hydrogel (OP@NPs) is presented to overcome this challenge via coordinated metabolic modulation, vascular normalization, and immune reprogramming. This platform co-delivers a novel lactate metabolism inhibitor (D780, a derivative conjugated by IR780 and diclofenac), Zn[2+], and the anti-angiogenic agent nintedanib (NIB). D780 inhibits key glycolytic enzymes to reduce lactate production, while exerting photothermal/photodynamic effects that directly ablate tumors and mitigate hypoxia. Through metal coordination, Zn[2+] assembles NIB and D780 into NPs. It also blocks GLUT1, boosting D780's inhibition of glycolysis. NIB can restore abnormal vascular structure, thereby alleviating oxidative hypoxia and blocking epithelial-mesenchymal transition. In murine osteosarcoma models, the combined therapy centered on OP@NPs remodelled the tumor immune microenvironment (TME). This transformation led to an accumulation of cytotoxic T cells, dendritic cells and M1 macrophages. The treatment achieved favorable outcomes in inhibiting primary tumor growth and pulmonary metastases. Overall, this work presents a localized targeting strategy to regulate key signaling pathways in osteosarcoma.

Diclofenac (DCF) is a prevalent aquatic contaminant poorly removed by conventional wastewater treatment plants. This study investigates the photocatalytic degradation of DCF under simulated sunlight using nanoparticulate kesterite semiconductors Cu2ZnSnS4 (CZTS) and Cu2ZnSnSe4 (CZTSe), focusing on efficiency, stability, degradation pathways, and environmental implications. CZTSe exhibited superior photocatalytic performance, achieving 83% DCF removal within 60 min with a pseudo-first-order rate constant of 3.0 × 10[- 2] min[- 1], whereas CZTS reached 68% removal with 1.7 × 10[- 2] min[- 1]. Both photocatalysts maintained stable activity after four reuse cycles. Total organic carbon analysis confirmed progressive DCF mineralization, i.e., the conversion of organic carbon into CO2 and inorganic species. HPLC-MS analysis identified six transformation products generated by DCF degradation, corresponding to the conversion of the parent molecule into intermediate compounds. In silico ecotoxicity assessment using predictive computational models indicated reduced bioaccumulation potential of DCF after treatment; however, some transformation products exhibited higher environmental persistence and retained or increased predicted toxicity. Reactive species experiments demonstrated that superoxide radicals (•O2[-]) were the main reactive species, followed by hydroxyl radicals (•OH). These findings demonstrate that CZTS and, particularly, CZTSe are efficient and reusable visible-light photocatalysts for DCF removal while providing new insights into degradation pathways, mineralization, reactive oxygen species, and transformation-product ecotoxicity, underscoring the importance of assessing degradation by-products in advanced oxidation processes.

Interfacial regulation of molecular oxygen activation is critical for controlling reactive oxygen species generation in photocatalytic systems. Here, a copper 4-cyanophenylacetylide/copper phenylacetylide heterointerface (CN-PhC2Cu/PhC2Cu) was constructed through a one-step in situ strategy to regulate interfacial charge transfer and excited-state processes. Cyano functionalization created an electronic difference between the two copper acetylide components, while their related CCCu coordination frameworks favored intimate interfacial coupling. The optimized 75CNPC removed 95.2 ± 3.9% of diclofenac within 60 min under 455 nm visible-light irradiation and retained appreciable activity in the presence of common water constituents and in different aqueous matrices. Optical, electrochemical, and theoretical analyses indicate that interfacial coupling modulates the local electronic structure, facilitates charge separation, and strengthens O2 adsorption. Reactive oxygen species (ROS) measurements further reveal a redistribution of O2 activation channels: electron transfer contributes to ·O2[-] formation, whereas interface-regulated excited-state processes favor triplet-mediated energy transfer and enhanced [1]O2 generation. Liquid chromatography-mass spectrometry (LC-MS) analysis and toxicity evaluation suggest that DCF undergoes initial activation, structural fragmentation, and progressive oxidation, with several identified transformation products exhibiting reduced predicted toxicity relative to the parent compound. These results demonstrate how the CN-PhC2Cu/PhC2Cu coordinates charge transfer, excited-state evolution, and molecular oxygen activation in organometallic photocatalysts.

Pharmaceutical residues are increasingly detected in freshwater systems at concentrations ranging from g/L to /L, raising concerns due to their persistence, bioactivity, and potential ecological and human health impacts. Conventional wastewater treatment plants typically achieve limited removal efficiencies (often 30-60% for many compounds such as carbamazepine and diclofenac), necessitating alternative treatment strategies. This review critically evaluates microalgae-based pond and consortia systems, emphasizing the key removal pathways of bioadsorption (10-40%), bioaccumulation (up to 20-30%), and biodegradation (40-90%, compound and condition dependent). It further examines microalgal physiological responses, including oxidative stress regulation, enzymatic transformation, and adaptive metabolic shifts under pharmaceutical exposure, which influence treatment performance. Major operational constraints, including seasonal variability, affect productivity and toxicity thresholds that inhibit algal growth at elevated contaminant concentrations. Recent advances in strain engineering, co-culture consortia, and process optimization have demonstrated removal efficiencies exceeding 80% under optimized conditions. Moreover, this review provides a systematic synthesis of mechanistic pathways, integrates recent process innovations, and identifies critical knowledge gaps related to by-product toxicity, scale-up stability, and long-term system performance, offering a more quantitative and application-oriented perspective on microalgae-based pharmaceutical removal.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) overlap is a rare, life-threatening mucocutaneous reaction typically induced by medications. Reports from Central America remain scarce. We present two contrasting cases of SJS/TEN overlap from Nicaragua. Case 1 involved a previously healthy 18-year-old male who developed SJS/TEN overlap with 20% total body surface area (TBSA) involvement following exposure to amoxicillin, diclofenac, and levofloxacin. His SCORTEN score was 1 (estimated mortality < 10%). He received systemic corticosteroids and achieved complete recovery with no sequelae. Case 2 involved a 32-year-old female with stage G5 chronic kidney disease (CKD) not on dialysis who developed SJS/TEN overlap with 30% TBSA involvement after metamizole and acetaminophen exposure. Her SCORTEN score was 2 (estimated mortality ~12%). Despite initial cutaneous improvement with corticosteroids, she developed progressive uremia, refused renal replacement therapy, and ultimately died from multiorgan failure on day 28. These cases illustrate that SCORTEN may have limited ability to capture late mortality driven by pre-existing renal dysfunction and systemic complications. Furthermore, they suggest that cutaneous improvement with corticosteroids does not necessarily translate into survival when underlying organ vulnerability exists. Individualized clinical assessment beyond prognostic scores remains essential, particularly in resource-limited settings.

Quinazoline scaffolds are widely recognized in drug discovery for their diverse pharmacological profiles, and several quinazoline derivatives have been reported as phosphodiesterase 7A (PDE7A) inhibitors with potential anti-inflammatory effects. This study aimed to synthesize novel quinazoline derivatives, evaluate their anti-inflammatory activity and investigate their computationally predicted binding to PDE7A. A series of quinazoline hydrazone (6a-j) and benzylthioquinazolinone (7a-c, 8a,b) derivatives were synthesized and structurally characterized using IR, [1]H/[13]C NMR, mass spectrometry, and elemental analysis. Anti-inflammatory activity was evaluated in vivo using the carrageenan-induced rat paw edema model. An acute oral toxicity assessment identified the highest tested doses without observed mortality or overt clinical toxicity of 1000-1200 mg/kg, from which anti-inflammatory test doses of 100-120 mg/kg were selected. Compound 6f produced the highest numerical inhibition among the synthesized derivatives, with 79.39% inhibition at 100 mg/kg. Compounds 6a, 6b, and 8a produced 61.85%, 61.65%, and 60.12% inhibition, respectively, at 120 mg/kg, whereas diclofenac produced 68.21% inhibition at 7.5 mg/kg. Molecular docking, Prime MM-GBSA calculations, and 100-ns molecular dynamics simulations were used to evaluate predicted PDE7A interactions and comparative dynamic behavior. Compound 6f showed the most favorable Glide GScore and IFDScore, persistent Tyr211 and Gln413 hydrogen bonds, and the clearest apparent late-stage stationary root-mean-square deviation regime. In silico ADMET analysis indicated acceptable predicted drug-likeness and absorption-related properties, although moderate-to-low aqueous solubility and predicted hERG liability require experimental evaluation. Overall, compound 6f was prioritized as the leading anti-inflammatory candidate within the evaluated series; however, PDE7A involvement remains computationally inferred and requires direct biochemical and selectivity validation.

A ZnO/CuO@amoxicillin nanocomposite was synthesized via a sol-gel route and characterized as a biphasic wurtzite ZnO-monoclinic CuO system with crystallite sizes of about 10-12 nm and an optical band gap of 3.30-3.36 eV, indicating defect-rich interfaces favorable for redox activity. In antidiabetic assays, the nanocomposite showed strong inhibitory effects on alpha-amylase (IC50 = 21.57 ± 1.68 mg/mL) and alpha-glucosidase (IC50 = 13.95 ± 0.76 mg/mL), with activities comparable to acarbose, while anti-inflammatory tests yielded low IC50 values of 0.22 ± 0.03 mg/mL for egg albumin denaturation and 0.34 ± 0.07 mg/mL for human serum albumin, approaching the performance of diclofenac. Antioxidant performance was outstanding, with total antioxidant capacity of 298.27 ± 4.70 mg ascorbic acid equivalents per gram and ferric reducing antioxidant power of 311.67 ± 2.53 mM Fe[2] [+]/g, both higher than ascorbic acid, alongside efficient hydrogen peroxide scavenging (IC50 = 0.16 ± 0.04 mg/mL) and protection against H2O2/FeCl3-induced hemolysis at an IC50 of 0.007 ± 0.00 mg/mL; together with moderate but significant acetylcholinesterase inhibition (IC50 = 33.16 ± 3.02 mg/mL vs. 21.80 ± 2.74 mg/mL for donepezil), these results support ZnO/CuO@amoxicillin as a multifunctional nano-platform for managing oxidative stress, inflammation, and metabolic disorders.

Actinic keratosis (AK) is a common premalignant skin condition associated with chronic ultraviolet exposure and an increased risk of progression to cutaneous squamous cell carcinoma (cSCC). Its prevalence rises with age and is influenced by multiple factors, including fair skin phototype and immunosuppression. People living with human immunodeficiency virus (HIV) are at increased risk of cSCC due to impaired immune surveillance, highlighting the importance of early diagnosis and effective management of AK in this population. However, data on optimal treatment strategies in individuals with HIV remain limited. Among available therapies, topical 5-fluorouracil (5-FU) is considered one of the most effective field-directed treatments. We describe the case of a 70-year-old man with well-controlled HIV infection who presented with multiple facial actinic keratoses in a field of cancerization. The patient had previously undergone several treatments, including cryotherapy, diclofenac gel, and tirbanibulin, with only temporary improvement. Given the extent of the lesions and prior therapeutic failure, topical 5-FU 4% cream was initiated once daily for 28 days. During treatment, the patient developed a moderate inflammatory reaction characterized by erythema and pruritus, which was expected and did not require discontinuation. At the 3-month follow-up, complete clinical clearance of the lesions was achieved. This case supports the efficacy and acceptable tolerability of topical 5-FU 4% in the treatment of AK in a patient living with HIV, even after previous treatment failure. The results are consistent with existing evidence supporting the use of 5-FU as a first-line field therapy. Given the increased oncologic risk in immunocompromised patients, timely and effective treatment of AK is essential. Nevertheless, the limited evidence available in this specific population underscores the need for further prospective studies to better define management strategies and long-term outcomes.

Acute musculoskeletal injuries are common among sports participants and are frequently treated with topical analgesics; however, the comparative efficacy and safety of topical formulations remain under investigation. The objective of this study was to evaluate the efficacy and safety of topical nonsteroidal anti-inflammatory drugs (NSAIDs) and alternative topical therapies in the management of acute sports-associated soft tissue injuries, including sprains, strains, contusions, and soreness. A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, including randomized controlled trials that evaluated topical NSAIDs or other topical analgesics in patients with acute sports-related musculoskeletal injuries. Bias was assessed with the RoB-2 tool. The primary efficacy outcome was reduction in pain, measured by the visual analog scale (VAS) or similar validated tools, while the primary safety outcome was the incidence of treatment-emergent adverse effects. Eight randomized controlled trials comprising 1027 patient encounters met inclusion criteria. Across studies, topical diclofenac, ibuprofen, ketoprofen, and etofenamate demonstrated statistically significant reductions in VAS pain scores compared with placebo. Meta-analysis of all included trials revealed no significant reduction in pain intensity in active topical interventions versus placebo (95% CI -0.3768-5.2806; p = 0.09). A direct comparative analysis of diclofenac versus other NSAIDs did not demonstrate a statistically significant difference (effect size -2.07; 95% CI -5.60-1.46; p = 0.25), though heterogeneity of studies may limit these findings. Adverse effects were primarily mild and localized and were no different between groups (RR = 0.79; 95% CI 0.45-1.39; p = 0.41). Topical NSAIDs and alternative topical formulations may provide improved pain outcomes but did not show superiority between NSAID agents.

We report a 47-year-old human immunodeficiency virus-positive male with disseminated tuberculosis who developed recurrent maculopapular eruptions with mucosal involvement following exposure to multiple drugs, including diclofenac, rifampicin, and fluoroquinolones. Sequential drug rechallenge strongly implicated fluoroquinolones and rifampicin. He was successfully managed with systemic corticosteroids, intravenous immunoglobulin, and careful sequential reintroduction of nonculprit anti-tubercular therapy drugs. This case highlights the importance of drug reintroduction and cautious use of fluoroquinolones and rifampicin in immunocompromised patients.

In the field of medicinal chemistry, the design of small molecules is acknowledged as an effective strategy. This study may contribute to the global fight against inflammatory diseases by focusing on the synthesis of novel α-aminophosphonate derivatives incorporating para-aminobenzoic acid (PABA) and benzocaine moieties and evaluating their anti-inflammatory and antioxidant activities. Compounds 1a-1i, 2a-2g and 3a-3f were efficiently prepared via a one-pot Kabachnik-Fields reaction in moderate to high yields. Structural characterization was achieved using spectroscopic techniques and single-crystal X-ray diffraction. Antioxidant activity, assessed by ABTS (<0.1 mM) and phenanthroline (<0.5 mM) assays, revealed that several derivatives exhibited significant radical scavenging and reducing power, particularly those bearing electron-donating groups. In vitro anti-inflammatory evaluation using the bovine serum albumin denaturation assay identified compounds 1f, 3f, 2g and 1i as the most active derivatives, with compound 1f (97.63% ± 0.99%) showing activity comparable to that of diclofenac (98.70% ± 0.15%). Toxicity tests on Tenebrio molitor larvae indicated low toxicity at effective concentrations. Compound 1f was only moderately toxic (50% of mortality rate) at the highest concentration tested (4 mM), and no mortality was observed at lower doses. DFT calculations provided insights into the electronic and physicochemical properties of the synthesized compounds. Molecular docking and molecular dynamics simulations generated hypotheses regarding their possible interactions with the COX-2 binding site, while ADMET analyses predicted the potentially acceptable pharmacokinetic profiles of several derivatives. However, these computational findings do not demonstrate direct COX-2 inhibition, target engagement, or selectivity. When considered alongside the preliminary experimental results, they support prioritizing compound 1f for further experimental evaluation.