Alcohol-associated liver disease (ALD) encompasses a range of hepatic abnormalities, including isolated alcoholic steatosis, steatohepatitis, and cirrhosis. The flavanone-7-O-glycoside narirutin (NRT), the primary flavonoid in citrus peel, has antioxidant, anti-inflammatory, and lipid-lowering activity. We investigated the effects of NRT on liver injury induced by alcohol and explored the underlying mechanisms. Zebrafish larvae were used to investigate the effects of NRT on acute exposure to ethanol (EtOH). Liver phenotypic, morphological, and biochemical assessments were performed to evaluate the hepatoprotective effects of NRT. Network pharmacology and molecular docking analyses were conducted to identify candidate targets of NRT in EtOH-induced liver injury. A drug affinity responsive target stability (DARTS) assay was conducted to evaluate the binding of NRT to mitogen-activated protein kinase 14 (MAPK14). The mechanism of action of NRT was validated by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot analysis. The liver phenotypic, morphological, and biochemical assessments revealed that NRT has potential therapeutic effects against acute EtOH-induced liver injury. RT-qPCR confirmed that NRT reversed the change in the expression of genes related to oxidative stress, lipogenesis, and the endoplasmic reticulum (ER)/unfolded protein response pathway. Network pharmacology and molecular docking analyses identified potential targets of NRT's protective effects and confirmed that NRT regulates the p38 MAPK signaling pathway by targeting mitogen-activated protein kinase 14 (MAPK14). NRT mitigates alcohol-induced liver injury by preventing lipid formation, protecting the antioxidant system, and suppressing ER stress-induced apoptosis through MAPK14 modulation.

N-ethylmaleimide (NEM) inhibits peripheral nerve degeneration (PND) by targeting Schwann cells in a hydrogen sulfide (H₂S)-pathway-dependent manner, but the underlying molecular and pharmacological mechanisms are unclear. We investigated the effect of NEM, an α,β-unsaturated carboxyl compound, on H₂S signaling in in vitro- and ex vivo-dedifferentiated Schwann cells using global proteomics (LC-MS) and transcriptomics (whole-genome and small RNA-sequencing (RNA-seq)) methods. The multi-omics analyses identified several genes and proteins related to oxidative stress, such as Sod1, Gnao1, Stx4, Hmox2, Srxn1, and Edn1. The responses to oxidative stress were transcriptionally regulated by several transcription factors, such as Atf3, Fos, Rela, and Smad2. In a functional enrichment analysis, cell cycle, oxidative stress, and lipid/cholesterol metabolism were enriched, implicating H₂S signaling in Schwann cell dedifferentiation, proliferation, and myelination. NEM-induced changes in the H₂S signaling pathway affect oxidative stress, lipid metabolism, and the cell cycle in Schwann cells. Therefore, regulation of the H₂S signaling pathway by NEM during PND could prevent Schwann cell demyelination, dedifferentiation, and proliferation.

Peripheral nerve degeneration (PND) is a preparative process for peripheral nerve regeneration and is regulated by Schwann cells, a unique glial cell in the peripheral nervous system. Dysregulated PND induces irreversible peripheral neurodegenerative diseases (e.g., diabetic peripheral neuropathy). To develop novel synthetic drugs for these diseases, we synthesized a set of new cinnamaldehyde (CAH) derivatives and evaluated their activities in vitro, ex vivo, and in vivo. The 12 CAH derivatives had phenyl or naphthyl groups with different substitution patterns on either side of the α,β-unsaturated ketone. Among them, 3f, which had a naphthaldehyde group, was the most potent at inhibiting PND in vitro, ex vivo, and in vivo. To assess their interactions with transient receptor potential cation channel subfamily A member 1 (TRPA1) as a target of CAH, molecular docking studies were performed. Hydrophobic interactions had the highest binding affinity. To evaluate the underlying pharmacological mechanism, we performed bioinformatics analysis of the effect of 3f on PND based on coding genes and miRNAs regulated by CAH, suggesting that 3f affects oxidative stress in Schwann cells. The results show 3f to be a potential lead compound for the development of novel synthetic drugs for the treatment of peripheral neurodegenerative diseases.

Aim of the study: We investigated whether nicotinamide adenine dinucleotide kinase (NADK) expression is selectively diminished in alcohol-associated liver cirrhosis (AC), and evaluated its potential as a biomarker for this condition. Material and methods: Human liver samples were obtained...

Background/Objectives: This study compared rocuronium requirements, duration of deep neuromuscular blockade (NMB), and recovery profiles between intermittent bolus and continuous infusion administration. Methods: This prospective, single-center, randomized equivalence trial enrolled 72 adults undergoing elective abdominal cancer surgery under sevoflurane–remifentanil anesthesia. The per-protocol analysis included 67 patients (Group B, n = 34; Group CI, n = 33); five were excluded after neuromuscular monitoring failures precluded primary-outcome calculation. Group B received rocuronium 0.15 mg/kg at post-tetanic count (PTC) ≥ 4. Group CI received 0.3 mg/kg/h after intubation, titrated to maintain PTC ≤ 3. The primary outcome was body weight- and time-normalized total rocuronium requirement, including the intubating dose; the equivalence margin was ±0.13 mg/kg/h. Results: Rocuronium requirements were 0.84 ± 0.21 mg/kg/h in Group B and 0.85 ± 0.26 mg/kg/h in Group CI (mean difference, 0.010; 90% CI, −0.087 to 0.108), within the prespecified equivalence margin. A post hoc sensitivity analysis excluding the intubating dose showed no significant difference (0.38 ± 0.14 vs. 0.37 ± 0.13 mg/kg/h; mean difference, −0.012; 95% CI, −0.075 to 0.051; p = 0.707). Deep NMB duration (127 ± 43 vs. 132 ± 65 min; p = 0.687) and recovery after sugammadex did not differ significantly. Six Group CI patients (18.2%) required rescue boluses. Conclusions: The strategies yielded equivalent normalized total rocuronium requirements within the prespecified margin. Recovery outcomes did not differ significantly; however, the infusion protocol required rescue boluses in some patients. PTC-guided individualization is therefore needed.