Drug-induced liver injury (DILI) is a serious adverse reaction with limited therapeutic options. Taraxasterol (TAS), a natural triterpenoid with hepatoprotective potential, suffers from poor aqueous solubility and low oral bioavailability, hindering its clinical application. Here, we develop an integrated oral delivery platform comprising TAS nanocrystals (TAS NCs) stabilized by D-α-tocopherol polyethylene glycol succinate (TPGS), embedded within chitosan-carbopol polyelectrolyte complex (EPC) micropatches, and encapsulated in enteric-coated capsules (TAS NCs@EPC/CAP). This design sequentially overcomes multiple absorption barriers through a multi-stage process: nanocrystallization enhances dissolution and permits TPGS-mediated P-glycoprotein inhibition and hepatocyte uptake; the mucoadhesive EPC micropatches prolong intestinal residence and transiently open tight junctions; and enteric coating ensures site-specific release in the small intestine. In mice, TAS NCs@EPC/CAP dramatically improved oral bioavailability (AUC increased 3.1-fold vs. free TAS) and achieved sustained liver enrichment. In both acetaminophen-induced intrinsic and isoniazid/rifampicin-induced idiosyncratic DILI models, TAS NCs@EPC/CAP exerted superior hepatoprotection, as evidenced by normalized liver function markers (ALT, AST, LDH), attenuated oxidative stress (ROS, MDA, GSH, SOD), suppressed inflammation (IL-1β, IL-6, TNF-α), and reduced hepatocyte apoptosis. Integrated network pharmacology and experimental validation revealed that TAS NCs@EPC/CAP potentiates the effects of TAS, leading to enhanced activation of the Nrf2/HO-1 antioxidant signaling, more pronounced inhibition of JNK-mediated stress pathways, and greater modulation of the Bax/Bcl-2/caspase-3 apoptotic cascade. This study establishes a clinically translatable oral delivery strategy for TAS and provides a versatile platform for enhancing the bioavailability of poorly soluble natural products, with potent efficacy against diverse forms of DILI.

The increasing contamination of water sources due to industrialization and population growth poses significant environmental and health risks, even at trace pollutant concentrations. Enzymatic bioremediation, particularly using horseradish peroxidase (HRP), has shown great potential in pollutant degradation due to its high selectivity and catalytic efficiency. However, limitations such as poor operational stability and reusability hinder its large-scale application. The degradation of structurally diverse emerging pollutants by UiO-66-NH2-immobilized HRP, including the influence of redox mediation, remains insufficiently investigated. This study addresses this gap by immobilizing HRP onto UiO-66-NH2, a metal-organic framework (MOF) with high stability and surface area. HRP@UiO-66-NH2 was characterized using SEM-EDX, PXRD, FTIR, TGA, and BET analyses, while pollutant degradation was quantified by LC-MS/MS. HRP loading concentrations ranging from 0.5 to 4 mg/mL were evaluated, and 1 mg/mL was selected for subsequent experiments. The immobilized HRP exhibited an optimum H2O2 concentration of 1.08 mM within the tested range of 0-2.43 mM. Both free and immobilized HRP showed maximum activity at pH 4, while the optimum temperature shifted from 30°C for free HRP to 40°C following immobilization. The immobilized enzyme also retained approximately 95% of its initial activity after four reuse cycles. HRP@UiO-66-NH2 was evaluated for the degradation of nine emerging pollutants, including 2-mercaptobenzothiazole, paracetamol, sulfamethoxazole, methylparaben, salicylic acid, lincomycin hydrochloride, atenolol, thiabendazole, and DEET. It degraded 99.7% of 2-mercaptobenzothiazole and 97.4% of paracetamol within 30 min. The addition of 1-hydroxybenzotriazole (HOBT) increased the degradation of sulfamethoxazole, methylparaben, and salicylic acid from 23.3%, 14.5%, and 12.4% to 53.1%, 57.6%, and 54.3%, respectively. The greater thermal and H2O2 tolerance of immobilized HRP suggests a protective effect of the UiO-66-NH2 framework, while the variable response to HOBT indicates pollutant-dependent redox mediation. These findings highlight HRP@UiO-66-NH2 as a promising biocatalyst for sustainable water remediation, warranting further studies to elucidate the underlying degradation mechanisms and optimize real-world applications.

Supraparticles (SPs) are secondary particles formed through nanoparticle self-assembly with porous architectures and bioinspired structural features suitable for drug delivery applications. Although binder-mediated structural control influences SP assembly, how different loaded drugs systematically alter amyloid nanofibril (ANF) and SP structures remains unclear. In this study, neutral, basic, and acidic model drugs-acetaminophen (ACP), fluconazole (FCZ), and proglumide (PGM), respectively-were incorporated into spray-dried SPs composed of silica nanoparticles (SiNPs) and ANFs to investigate the effects of drug properties on SP structure and release behavior. All drugs exhibited nearly 100% loading efficiency, and powder X-ray diffraction analysis revealed that they were in an amorphous state within the SPs. ACP- and FCZ-loaded SPs maintained their characteristic ANF-induced wrinkled morphology, whereas PGM-loaded SPs exhibited a pronounced loss of wrinkling at pH 2, indicating that acidic drugs can disrupt ANF-mediated assembly during SP formulation. Drug release studies further showed that ANFs suppressed the initial burst release and slowed the overall release by restricting diffusion pathways within the SP structures. This suppression was the most pronounced in PGM-loaded SPs, likely owing to drug retention within the assembled ANF domains. These findings demonstrate that drug acid-base properties critically modulate SP morphology and release behavior, highlighting the importance of drug-biomaterial interactions in designing SP-based delivery platforms.

Poisoning by acetaminophen is a serious public health concern because of its accessibility and the ease with which overdoses can occur accidentally or on purpose. The liver metabolizes acetaminophen, and when taken in excess, it is transformed into a poisonous metabolite that seriously damages the liver and may result in hepatic failure and death. The cornerstone of treatment is the early administration of N-acetylcysteine, which is most effective within 8 hours of ingestion. Co-ingestants, therapy timing, and pre-existing liver diseases are some of the factors that affect toxicity. Both unintentional overdoses and deliberate poisonings have legal and forensic ramifications, especially where minors or self-harm are involved. In fatal cases, a toxicological investigation is essential to identify the cause of death and differentiate acetaminophen poisoning from other possible causes. Regulations such as age restrictions, pack-size constraints, and improved labeling have demonstrated the potential to reduce the prevalence of acetaminophen toxicity. Intentional and accidental overdoses can be avoided in part by raising public awareness and educating healthcare professionals. To lessen the impact of acetaminophen poisoning on public health systems, more research is required to enhance early identification, improve treatment techniques, and guide policy decisions. This review aims to familiarize clinicians and forensic professionals with the pharmacology, clinical presentation, management, and medicolegal aspects of acetaminophen toxicity..

The improper disposal of pharmaceuticals such as paracetamol and propranolol represent a significant environmental concern due to their high persistence in the environment and low removal efficiency by conventional wastewater treatment processes. In this context, this work aimed to develop and evaluate five adsorbents derived from peanut shells precursor for removal of paracetamol and propranolol in a binary mixture (228 and 279 nm), an application that has not yet been explored for this bioresidue. Among the produced adsorbents, phosphoric-acid-modified activated carbon (CAH3PO4) presented the best performance, achieving removal efficiencies of 99.40% and 99.47% at wavelengths of 228 and 279 nm, respectively. This result can be attributed to its high specific surface area (547 m[2] g [-1]) and the presence of oxygenated and phosphorylated functional groups on the CAH3PO4 surface, formed through thermochemical treatment. The kinetic data were best fitted to pseudo-second order model, indicating the predominance of chemical interactions between adsorbate and adsorbent. In the equilibrium study, the data best fitted the Sips model, suggesting a surface with both homogeneous and heterogeneous adsorption sites. Thermodynamic analysis revealed that the adsorption process is exothermic, indicating spontaneous and energetically favorable interactions. These results highlight the high adsorption potential of CAH3PO4 as an effective and viable alternative for the treatment of pharmaceutical-contaminated effluents.

Objective: To describe the timing, frequency, and accessibility of Instagram posts from pediatric health institutions during the 2025 acetaminophen-autism controversy.Methods: Cross-sectional audit of public Instagram accounts of 62 pediatric health institutions from September 22 to November 15, 2025. The a priori sampling frame comprised the top 50 US children's hospitals for pediatric behavioral health, the top 10 Honor Roll children's hospitals (US News and World Report), 5 national medical societies, and health departments of the 10 states with the largest pediatric populations. Posts were extracted with a web-scraping tool and manually verified. Two reviewers independently coded relevant posts for prespecified content and accessibility features. Readability was assessed with two validated measures.Results: Twelve of 62 institutions (19%) posted relevant content. The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists posted on day 0, while hospital time to first post ranged from 3 to 51 days. No state health department posted. Nonresponding institutions remained active: 1 hospital published 108 unrelated posts. The 26 relevant posts had a mean Flesch-Kincaid Grade Level of 11.4 and SMOG Index of 10.2. Among coded features, 88% included resource links, 73% directed audiences to a health care provider, 46% featured a named clinician, 42% discussed risks and benefits, and none were multilingual.Conclusions: Most sampled institutions published no relevant content during an active health controversy despite remaining active. Readability of relevant posts exceeded recommended targets, and none were multilingual. These gaps in institutional communication infrastructure could be addressed.

Recent studies indicate that injury-induced dedifferentiation generates transient regenerative progenitors (TRPs), which support tissue repair across multiple organs, including the liver. In vivo partial reprogramming using Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc; OSKM) produces intestinal TRPs closely resembling those arising from injury-induced dedifferentiation, but transgenic or viral approaches raise safety concerns because of prolonged expression. Here, we show that transient OSKM induction generates two distinct liver progenitor-like cell (LPLC) populations without injury and with limited activation of injury-associated immune responses. Single-nucleus RNA sequencing shows that one population resembles injury-induced LPLCs observed in acetaminophen-injured mouse and human livers. To develop a temporally controlled regenerative strategy, we establish a liver-targeted lipid nanoparticle system for OSKM mRNA delivery. OSKM mRNA-LNP treatment induces hepatocyte dedifferentiation and Sox9[+] LPLC-like cell formation and is associated with enhanced regeneration after acetaminophen-induced injury. Together, these findings identify transient hepatic reprogramming as a strategy for inducing regenerative plasticity and support liver-targeted OSKM mRNA delivery as a potential approach for acute liver injury.

Real-world evidence on systemic diclofenac patch use in cancer pain is limited. We described prescribing patterns in oncology practice. In this single-center retrospective descriptive study, we reviewed consecutive patients with cancer who received a systemic diclofenac patch (75 mg per patch) for cancer-related pain at a Japanese university hospital (n = 48). The usual regimen was two 75-mg patches once daily (150 mg/day); one patient started one 75-mg patch/day. Among 48 patients, 35 (73%) retained oral medication intake and 32 (67%) were receiving ongoing anticancer therapy at patch initiation. Gastroprotective agents were co-prescribed in 31 patients (65%), any acetaminophen in 29 (60%; scheduled acetaminophen in 28 [58%]), and opioids in 28 (58%). Transdermal fentanyl-containing regimens were observed in 9 patients (19%), whereas strict all-transdermal scheduled baseline analgesia was identified in 3 (6%). No recipient had documented clinically apparent gastrointestinal bleeding or symptomatic peptic ulcer during available follow-up. The systemic diclofenac patch was prescribed to selected patients with cancer-related pain in routine Japanese practice and was commonly incorporated into multimodal analgesic regimens. These findings describe prescribing patterns and chart-documented observations only; prospective studies with standardized outcomes are needed to clarify effectiveness, safety, and patient-centered impact.

N-acetylcysteine (NAC) is used in small-animal medicine as an antidote, mucolytic, thiol donor, and cytoprotective adjunct, yet its evidentiary basis varies markedly among indications and between dogs and cats. We systematically evaluated species-specific pharmacokinetic, clinical, experimental, and in vitro evidence to distinguish established uses from extrapolated practice.