A woman in her 80s was diagnosed with colon cancer, and she underwent chemotherapy after surgery. Oxycodone extended-release tablets were initiated for abdominal pain, but oral administration was difficult, leading to a change to fentanyl patches. Owing to severe numbness from the buttocks to the toes, tramadol/acetaminophen (T/A) tablets were initiated at a dose of 2 tablets per day. The fentanyl patch dose was increased to 2 mg/d, and pain was relieved on combination with 2 T/A tablets. The patient subsequently reported behavioral disturbances, including agitation, anxiety, and sudden diarrhea. She had been taking 1 T/A tablet 2 to 3 times per day at her discretion when the pain worsened. Suspecting an additive effect from the combination of the fentanyl patch and T/A tablets, the T/A tablets were immediately discontinued, and the symptoms resolved. Loxoprofen tablets were initiated at 180 mg/d, and the fentanyl patch dose was increased to 4 mg/d, without side effects such as agitation, anxiety, or behavioral disorders. The combined use of tramadol and fentanyl likely induced excessive serotonergic activity; careful observation is required in adult patients and those receiving multiple medications.

Liver disease is a leading cause of global morbidity and mortality, for which virus, toxin and drugs are common risk factors. Paracetamol is a common analgesics and antipyretic drug but at overdose can cause severe hepatotoxicity. Moringa oleifera is a highly nutritious vegetable tree with variety of potential uses which may have hepatoprotective effect. The objective of the study was to observe the effect of Moringa oleifera (Sajna) leaf extract on paracetamol induced liver damage in Wistar albino male rats. This experimental study was carried out in the Department of Physiology, Sir Salimullah Medical College (SSMC), Dhaka, Bangladesh from 1st July 2021 to 30th June 2022. A total number of twenty-four (24) apparently healthy Wistar albino male rats, 90-120 days old, weighing between 200-250gm were taken for this study. After acclimatization for 14 days, they were divided into three groups: Negative control group (Group A), Positive control group (Group B) and Experimental group (Group C). Each of this group was consisted of eight rats. All the rats received basal diet for 28 days. In addition to basal diet Group B and Group C received paracetamol orally (2g/kg/day) for last 3 days (26th to 28th days) of the study period. Again, Group C also received aqueous extract of Moringa oleifera leaf orally (200 mg/kg/day) for 28 days. Then all the rats were sacrificed on 29th day. After sacrifice blood and liver samples were collected. Blood sample was collected from heart. Serum levels of total bilirubin, ALT, AST, ALP, GGT and hepatic contents of malondialdehyde (MDA) were measured by using standard laboratory method. Histopathology of liver was also done by using standard laboratory procedure in the Department of Pathology of SSMC. Statistical analysis was done by using Statistical Package of Social Science (SPSS) for windows version 28.0. Data were presented as mean ±SD. One way ANOVA and post hoc-Bonferroni test, Paired "t" test and Fisher's Exact test were done as applicable. p value ≤0.05 was considered as level of significance. The mean±SD serum total bilirubin level was 0.08±0.03, 2.01±0.34 and 0.16±0.02 mg/dL, mean serum ALT level was 32.88±4.02, 114.50±29.17 and 50.50±6.21 U/L, mean serum AST level was 46.38±8.33, 220.50±17.55 and 106.75±4.36 U/L, mean serum ALP level was 79.25±19.47, 114.50±23.40 and 103.50±5.97 U/L, mean serum GGT level was 6.95±2.08, 14.78±4.02 and 9.61±2.31 U/L, in Group A, Group B and Group C respectively. The mean serum total bilirubin, ALT, AST, ALP and GGT levels were significantly higher in Group B (p<0.001) in comparison to those of Group A whereas, mean±SD serum total bilirubin, ALT, AST and GGT levels were significantly (p<0.001) lower in Group C than that of Group B. The mean±SD MDA level was 3.83±1.21, 12.16±3.14 and 6.89±1.61 nmol/mg protein in Group A, Group B and Group C respectively. The mean±SD MDA level was significantly higher in Group B and Group C (p<0.001 and p<0.05 respectively) in comparison to that of Group A, whereas this level was significantly (p<0.001) lower in Group C than that of Group B. Moreover, abnormal histopathological findings of liver were observed in 100.0% of rats in Group B, 12.5% of rats in Group C. The study reveals that Moringa oleifera leaf extract has hepatoprotective effect on paracetamol induced liver damage in Wistar albino male rats.

Protein S-sulfinylation is a reversible oxidative cysteine modification, but its contribution to acute liver injury such as those induced by acetaminophen (APAP) overdose has not been reported. Sulfiredoxin-1 (SRXN1) is the only oxidoreductase known to reduce the sulfinylated proteins, yet the substrates and mechanisms through which it protects against acute liver injury are unclear. Here, we show that hepatic protein S-sulfinylation was markedly upregulated in APAP-overdose patients and mice. Hepatocyte-specific knockout or pharmacological inhibition of Srxn1 sensitized mice to APAP-induced acute liver injury. In contrast, overexpression of SRXN1, but not its oxidoreductase-dead C99S mutant, protected mice from APAP-induced liver injury. Mechanistically, we identified the deubiquitinase ubiquitin-specific protease 7 (USP7) as an SRXN1 substrate required for hepatoprotection. USP7 inhibition worsened APAP-induced liver injury, whereas its overexpression alleviated injury by stabilizing its deubiquitinase substrate heme oxygenase-1 (HO-1). Loss of SRXN1 enhanced S-sulfinylation of USP7 at Cys315, promoting its ubiquitination and degradation. SRXN1 expression correlated with USP7 levels in human liver samples. Delayed lipid nanoparticle (LNP) delivery of SRXN1 messenger RNA (mRNA) mitigated established APAP-induced liver injury beyond the therapeutic window of N-acetylcysteine. These findings define an SRXN1-USP7-HO-1 axis as a promising therapeutic target for oxidative liver injury and highlight LNP-mediated SRXN1 mRNA delivery as a potential treatment approach.

Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury and acute liver failure, where excessive reactive oxygen species (ROS), particularly superoxide anions (O2˙[-]), play a key early role in oxidative stress. To enable selective imaging of O2˙[-] in biological systems, we developed a red-emissive fluorescent probe (TCFCl-SA) based on a bis(trifluoromethyl)benzenesulfonate-caged fluorophore, exhibiting fluorescence emission centered at 620 nm after activation. The electron-withdrawing protecting group effectively suppresses intramolecular charge transfer, resulting in a weakly fluorescent state, while reaction with O2˙[-] triggers deprotection to release the strongly fluorescent TCFCl. The probe exhibits a linear fluorescence response to O2˙[-] (0-50 µM, R[2] = 0.9991) and high selectivity over various reactive species and biologically relevant ions. In living cells, TCFCl-SA shows low cytotoxicity and enables fluorescence imaging of endogenous and APAP-induced O2˙[-] in RAW 264.7 and HepG2 cells, with signal suppression by ROS scavengers confirming specificity. These results demonstrate that TCFCl-SA is a useful tool for monitoring intracellular O2˙[-] dynamics and investigating APAP-induced oxidative stress at the cellular level.

Abdominal pain is common in inflammatory bowel disease (IBD) and patients may self-medicate with over-the-counter (OTC) analgesics. We examined OTC analgesic use among adults with IBD in a Danish Gastroenterology outpatient clinic. A questionnaire including demographics, disease characteristics, analgesic types and frequencies, and reasons for use was developed and tested. Overall, 216 patients completed the questionnaire (November 2025-February 2026). Analyses were stratified by IBD type and disease activity; associations were assessed using logistic regression. Over 90% used OTC analgesics, predominantly paracetamol, regardless of IBD type and disease activity. Frequent use (≥ 4 days/week) was more common among patients with disease activity than without within 6 months (16% vs. 6%). Adjusted OR for frequent use within 4 weeks and 6 months were 1.69 (95% CI 0.57-4.99) and 2.37 (95% CI 0.79-7.11), respectively. Among patients with disease activity, 54%, 31% and 12% reported 'another reasons than IBD', 'IBD and another reason' and 'IBD', respectively, as reasons for use. Corresponding proportions without disease activity were 81%, 11% and < 6%, respectively. OTC analgesics use was common regardless of disease activity, but frequent use and IBD-related reasons were more prevalent with disease activity; highlighting the need for clinical awareness and appropriate pain management.

Drug-induced liver injury (DILI) is a considerable and potentially severe adverse reaction to medications. As drug abuse continues to rise, managing drug-induced liver toxicity has become a considerable challenge for clinicians. Depression is a chronic neurological disorder with a rising incidence globally in recent years, adding to the overall societal burden. Numerous clinical studies have suggested a link between DILI and mental illnesses, with inflammation potentially playing a mediating role. However, the exact mechanisms remain unclear. Here, we established a mouse model of DILI through acetaminophen (APAP) exposure and assessed the correlation between mental disorder and NLRP3 inflammasome. We found that DILI mice exhibited anxiety- and depressive-like behaviors, along with disrupted blood-brain barrier integrity and a significant increase in hippocampal NLRP3 inflammasome levels. Nlrp3 knockout or hippocampal Nlrp3 knockdown ameliorated DILI-induced anxiety- and depressive-like behaviors. Moreover, N-acetylcysteine, an agent against APAP-induced hepatotoxicity, inhibited NLRP3 inflammasome activation and alleviated anxiety- and depressive-like behaviors in DILI mice. These results indicate that the NLRP3 inflammasome might be a promising target for the treatment of patients with DILI who experience comorbid anxiety and depression.

The increasing emergence of pharmaceutical pollutants in aquatic environments demands the advancement of adsorbents that simultaneously provide high removal performance, rapid uptake, and facile regeneration. Herein, magnetically recoverable Fe3O4-anchored layered bacterial cellulose biochar integrated gelatin-chitosan beads (Fe3O4@LBCB-Gel-CS) were fabricated through a microemulsion-assisted crosslinking strategy for the removal of paracetamol (Para) and sulfamethoxazole (SMX). Optimization studies identified 0.1 g.L[-1] adsorbent dosage, pH 5-6, and a exposure time of 70 min as the ideal conditions, under which the adsorption capacities reached 1033.87 mg.g[-1] for Para and 1272.33 mg.g[-1] for SMX. Model fitting demonstrated that equilibrium was best represented by the KC isotherm (R[2] ≈ 0.990), whereas the Bangham (R[2] ≥ 0.990) and PFO (R[2] ≥ 0.988) models provided the best fits to the adsorption kinetics. The negative ΔG° (-24.31 to -24.05 kJ.mol[-1] for Para; -27.74 to -27.02 kJ.mol[-1] for SMX) together with ΔH° values of -29.76 and - 42.10 kJ.mol[-1], respectively, indicate the spontaneous and exothermic nature of the adsorption process. The adsorption process was likely influenced by the combined contribution of H-bonding, π-π interactions and Fe-assisted interactions. The beads retained 91.8% (Para) and 72.6% (SMX) of their initial performance over eight regeneration cycles and maintained removal efficiencies above 91% and 96%, respectively, in the presence of competing ions (100 mM). Benchmarking the adsorbent using a multi-parameter approach, through the simultaneous achievement of high adsorption capacity, minimal dosage requirements, rapid kinetics, and a near-neutral environment, highlighted the overall performance of Fe3O4@LBCB-Gel-CS and its potential for the development of next-generation adsorbents.