Acetaminophen (APAP) overdose is a leading cause of severe liver injury and acute liver failure (ALF). Increased hepatic macrophages promote inflammation and clear necrotic cell debris, thereby promoting a regenerative state for liver repair during APAP-induced liver injury. Vacuole membrane protein 1 (VMP1) is an ER transmembrane protein essential for autophagy. Deletion of VMP1 in the liver impairs autophagy. The role of VMP1 in APAP-induced liver injury is unknown. In this study, human APAP ALF RNA sequencing database was analyzed. Liver-specific Vmp1 knockout (Vmp1LKO) and matched wild-type (Vmp1LWT) mice were administered with 500 mg/kg APAP. Liver injury, necrosis and other biochemistry analyses were assessed. Increased mRNA levels of VMP1 and autophagy-related genes were found in human APAP ALF livers. Serum ALT and hepatic necrosis were increased in WT mice following APAP treatment. LC3B-II and p62 were increased, but VMP1 protein decreased in WT mouse livers following APAP treatment. Liver injury was markedly decreased in Vmp1LKO mice compared with their WT littermates. Basal hepatic CYP2E1 and glutathione (GSH) levels were similar between genotypes, but Increased lipid-laden macrophages (foam cells) were present in Vmp1LKO livers. Interestingly, APAP protein adduct formation decreased in Vmp1LKO mouse livers but mitochondrial damage was similar in both phenotypes. Peroxynitrite formation was observed in APAP-treated Vmp1LWT hepatocytes but was limited in foam cells of Vmp1LKO mouse livers. Furthermore, GSH replenishment and liver regeneration were enhanced in Vmp1LKO mouse livers. In conclusion, loss of hepatic VMP1 protects APAP-induced liver injury by replenishing GSH, modulating inflammation and enhancing liver regeneration.

This overview of systematic reviews aimed to identify effective pain management strategies for neonatal blood sampling. Searches were conducted in four databases from 2014 to April 2026. Eligible studies were systematic reviews including randomized or quasi-randomized controlled trials assessing pain management in neonates during blood sampling. Reviews were required to have searched at least two databases within the past 10 years, reported their search strategy, and conducted a risk-of-bias assessment. The search identified 2463 records; 22 reviews (13 Cochrane and two non-Cochrane pairwise reviews, and seven network meta-analyses) met inclusion criteria. Interventions evaluated included opioids, paracetamol, topical anesthetics, breastfeeding or breastmilk, sucrose, music medicine, acupuncture, and other non-pharmacological methods. Sucrose with or without non-nutritive sucking was effective in reducing pain scores during heel pricks in preterm and term neonates (mean difference -1.74, 95% confidence interval [-2.11, -1.37], moderate-certainty). Skin-to-skin contact also reduced pain scores compared with control (mean difference -3.47 [-5.55, -1.38], moderate-certainty). Recent network meta-analyses generally supported parent-led interventions and oral sweet solutions as the most effective strategies. Breastfeeding, supplemental breastmilk, acupuncture, and light reduction were promising but require further evidence. For other interventions, evidence was insufficient to draw conclusions. Evidence from systematic reviews and network meta-analyses indicates that sucrose and skin-to-skin contact effectively reduce procedural pain in neonates. Parent-led and other non-pharmacological interventions, including breastfeeding, also appear beneficial and should increasingly be considered part of family-centred neonatal pain care where feasible.

The issue of drug-alcohol interactions is a major concern in drug therapy and can endanger patient safety. Paracetamol is one of the most widely used analgetic drugs, while ethanol is commonly consumed addictive substance. This study investigated the toxic effects of paracetamol, ethanol, and their mixture at different concentrations on the embryonic development of zebrafish (Danio rerio, D. rerio).

Caffeine supplementation is one of the most commonly used ergogenic aids among soccer players. However, research shows conflicting results regarding the effects of different caffeine forms on muscle strength and power. This study investigated the impact of a high-dose caffeine mouth rinse on isokinetic knee extensor and flexor strength of the dominant leg at high (180°/s-1) and low (60°/s-1) angular velocities. Eight young male soccer players were randomly assigned to three conditions. Ten seconds before the isokinetic strength tests, participants either rinsed with an aspartame solution containing 750 mg of caffeine (Experimental), a calorie-free aspartame solution (Placebo) or did not use any solution (Control). Participants continued the mouth rinse for 10 s. Isokinetic strength measurements were performed at angular velocities of 60°/s-1 (5 repetitions) and 180°/s-1 (15 repetitions) in all interventions. Peak torque (Nm), the H/Q ratio, time to peak torque (ms), and average peak torque (Nm) in extension and flexion were analyzed. Data were tested for normality using the Shapiro-Wilk test, followed by one-way ANOVA and LSD post hoc tests (significance set at p < 0.05). According to the results, a significant difference was found in the H/Q ratio and time to peak torque at the angular velocity of 60°/s-1 (p < 0.05, η2 = 0.290; 0.306). At the angular velocity of 180°/s-1, no significant differences were found among the interventions (p > 0.05). These findings suggest that a high dose of the caffeine mouth rinse was effective at the lower angular velocity (60°/s-1), but had no effect on peak torque at the higher angular velocity (180°/s-1).

Currently, the manufacture of injectable drug products relies on a quality-by-test approach, where product quality is evaluated at fixed manufacturing steps. The introduction of the quality-by-design approach, supported on process analytical technologies (PAT) is changing this paradigm. The US Food and Drug Administration established the foundations for the application of PAT in real-time control of the drug manufacturing process. One of the most versatile PAT tools is the Raman spectroscopy. Nevertheless, the application of this technique to injectables is still underexplored. This work intends to expand the use of Raman spectroscopy as a PAT tool for injectable drug products. A Raman spectroscopy method was developed for the assay of paracetamol in paracetamol infusion solutions, using a PLS (partial least squares) algorithm. The method is specific, with a root mean square error of calibration (RMSEC), cross-validation (RMSECV) and prediction (RMSEP) of 1.067%, 2.591%, and 2.601%, respectively, with R2 of 0.999 and Q2 of 0.992. The method was developed with a hand-held Raman spectrometer and was tested as an at-line PAT tool, rendering similar error levels to the ones found for the validation, with results readily available in ca. 1 min. This work presents a further extension of PAT applied to injectable drug products, specifically with the development of an at-line paracetamol assay method. This approach enables flexible sampling in several manufacturing steps with a single instrument and without adaptation of the manufacturing line. This work marks a significant step towards a comprehensive monitorization and control of the injectable manufacturing process.

Caffeine is an emerging environmental contaminant in freshwater ecosystems that is primarily introduced through wastewater. Even at low concentrations, caffeine can affect the physiology and behaviour of aquatic organisms. Still, its ecological significance remains little understood. We examined the impact of environmentally relevant caffeine concentrations on the anti-predator behaviour of the freshwater amphipod Gammarus pulex. Gammarids play a central role in aquatic decomposition processes and are a primary food source for various aquatic predators. We examined the effects of caffeine in relation to a well-documented effect caused by the manipulative parasite Polymorphus minutus. This acanthocephalan parasite manipulates the anti-predator behaviour of its intermediate host, the gammarid, by altering its photophobia, thereby increasing its transmission to the final host, water birds. Using a two-choice experimental design, we assessed the phototactic behaviour of P. minutus-infected and uninfected G. pulex after 20 h of high- and low-concentration caffeine exposure. High concentrations of caffeine increased the activity of exposed individuals and reduced photophobia to a degree comparable with that of a P. minutus infection. These results suggest that human-derived chemicals can shift antipredator behaviour in a direction similar to an evolved parasite-mediated manipulation, which could increase predation risk and ultimately alter ecosystem dynamics.

Solasodine (SOL) is a steroidal glycoalkaloid that shows a wide range of biological effects, most notably anticancer activities. Eryptosis is the programmed cell death of erythrocytes that leads to anemia. Specifically, chemotherapy-induced anemia can be precipitated in part by eryptosis triggered by anticancer agents. We hypothesize that the cytotoxic effects of SOL observed in cancer cells are nonspecific and extend to human erythrocytes. Eryptosis following SOL exposure was detected by fluorescence-assorted cell sorting analysis in erythrocytes from healthy volunteers. Phosphatidylserine (PS) translocation and cellular volume were measured using annexin-V-FITC and forward scatter (FSC), respectively. Fluo-4/AM was used to detect cytoplasmic Ca2+ and H2DCFDA was employed to probe oxidative stress. Hemolysis was also assessed by hemoglobin leakage. In addition, different incubation media and inhibitors were tested for their potential influence on SOL activity. Exposure to SOL led to modest but significant hemolysis and was paralleled by significant PS translocation, elevated FSC, and echinocyte morphology. Energy restitution through ATP, guanosine, and adenine significantly reversed PS translocation as did the removal of extracellular Ca2+ and the dissipation of the cell membrane K+ gradient. Co-treatment of erythrocytes with SOL and SB203580, NSC 23766, necrosulfonamide, caffeine, and melatonin significantly inhibited SOL-induced PS translocation. In conclusion, SOL is a novel pro-eryptotic compound whose activity is mediated through energy exhaustion, Ca2+ influx, and cytosolic KCl depletion, and requires p38 MAPK/Rac1 GTPase/MLKL signaling. Metabolic substrates, cation channel modulators, and targeted inhibition provide protective adjuncts to improve the therapeutic index of SOL as it advances toward translational applications.