Background: Ferroptosis is an emerging type of regulated cell death and associated with antitumoral therapy, while some microRNAs have been shown to regulate the tumorigenesis and cancer progression. Meanwhile, polyphyllin I (PPI) has exhibited antitumoral effects by promoting cancer cell apoptosis and ferroptosis. However, it is unclear whether PPI induces cancer cell ferroptosis by regulating microRNAs.Methods: We used two gastric cancer cell lines (AGS and MKN-45) to set up a tumor model of the nude mice, which were then treated daily with PPI to measure the cancer growth in vitro and in vivo. Ferroptosis was measured using immunofluorescence staining and flow cytometric analysis according to levels of intracellular ROS, lipid ROS and ferrous ions. Moreover, NRF2 expression was measured by Western blotting. In some experiments, the mimics or inhibitors of miR-124-3p were used to further confirm its involvement in PPI-induced cancer cell ferroptosis.Results: Here we found that miR-124-3p mediated cancer ferroptosis and tumor repression induced by PPI since PPI increased miR-124-3p expression in gastric cancer cells and promoted their ferroptosis, whereas inhibition of miR-124-3p mostly abolished the effects of PPI on tumor growth, ferroptosis and NRF2 expression. Moreover, miR-124-3p mimics promoted cancer cell ferroptosis by downregulating NRF2 through directly targeting 3′-UTR region of NRF2, confirming a role for miR-124-3p in regulating PPI-induced ferroptosis.Conclusion: PPI exerts its antitumoral effects on the gastric cancer by promoting cell ferroptosis via regulating miR-124-3p. Our findings have clinical implications for cancer chemotherapy.

Kaempferia galanga L. is well known for its use in medicinal and edible homologous application. Various diseases, including those related to oxidation, are commonly treated with it. However, its antioxidant effect is still lacking systematical study. We aimed to screen the most potential antioxidant fraction of the crude ethanolic extract from K. galanga (KG) and evaluate its antioxidant activity and potential mechanism. The ethyl acetate fraction of ethanolic extract from K. galanga (KGEA) was chosen as the most potent antioxidant activity from all the fractions tested. UPLC-Q-TOF-MS/MS was used to determine 43 compounds in KGEA, and 25 potential bioactive compounds were identified by pharmacokinetic analysis. Network pharmacology revealed 174 overlapping targets of chemical and antioxidant targets, and the key targets were identified. Molecular docking and MD simulation revealed a strong binding affinity between the core compounds and their targets. In tests against DPPH and ABTS, KGEA exhibited potent radical scavenging activity. In H₂O₂-induced cells, KGEA could decrease reactive oxygen species (ROS) production; alleviate mitochondrial damage; promote the increase in antioxidant enzymes SOD, CAT, GSH-Px; and reduce the levels of MDA. Mechanistically, KGEA regulated PI3K/Akt and MAPK signaling pathways against oxidative damage. Moreover, in H₂O₂-induced zebrafish, KGEA attenuated ROS generation, cell death, lipid peroxidation, and increased SOD, CAT, GSH-Px activities; it also decreased MDA levels. The antioxidant properties of KGEA were demonstrated in vitro and in vivo, and it should be considered as an antioxidant agent for further profound study.

Lidocaine, an amide-type regional anesthetic, has been an important medication in the field of anesthesia since its clinical approval. Recently, lidocaine has emerged as a powerful immunomodulatory agent beyond its classical anesthetic properties. This review has summarized the recent basic and clinical studies with sufficient evidence on the multifaceted effects of lidocaine on both innate and adaptive immune cells, including macrophages, neutrophils, eosinophils, basophils, natural killer (NK) cells, mast cells, dendritic cells (DCs), monocytes, and T lymphocytes. We have also detailed how lidocaine affects critical cellular processes, such as cellular polarization, cytokine production, phagocytosis, and apoptosis, through multiple signaling pathways, including NF-κB, TLR4/p38 MAPK, voltage-sensitive sodium channels, HIF1α, TGF-β/Smad3, AMPK-SOCS3, TBK1-IRF7, and G protein-coupled receptors. These immunoregulatory effects of lidocaine are dependent on its concentration, duration of action, and the microenvironment. The immunomodulatory actions of lidocaine may contribute to its potential therapeutic value in various settings of diseases, such as cancer, sepsis, acute lung injury, asthma, organ transplantation, ischemia–reperfusion injury (IRI), and diabetes. We propose that lidocaine can be repurposed as an immunomodulator for treating immune-mediated inflammatory diseases. However, future research should define optimal dosing strategies, validate its mechanisms of action in clinical trials, and explore its novel clinical applications as a complementary immunotherapy.

Background: Acetaminophen, a widely used analgesic, has drawn attention for its potential to reduce oxidative stress through inhibiting lipid peroxidation and scavenging free radicals. Emerging evidence indicates that early acetaminophen administration might improve survival outcomes in surgical intensive care unit (SICU) patients. This study aims to explore the relationship between early acetaminophen use and mortality in this patient population.Methods: We conducted a retrospective cohort analysis of adult SICU patients using the Medical Information Mart for Intensive Care (MIMIC-IV) database, which contains data on patients admitted between 2008 and 2019. The intervention cohort received acetaminophen within 48 h of ICU admission, while controls received no early acetaminophen. The primary endpoint was in-hospital mortality. We implemented 1:1 propensity score matching (PSM) to minimize selection bias and balance baseline characteristics between cohorts. Multivariable Cox regression models adjusted for residual confounding.Results: From 5,474 eligible patients, we generated balanced cohorts of 2,740 matched pairs. The acetaminophen group demonstrated significantly lower in-hospital mortality (11.4% vs 14.4%; adjusted HR 0.75, 95% CI 0.62–0.89, P = 0.001) compared to controls. This mortality reduction persisted consistently through sensitivity analyses and subgroup evaluations. Notably, early acetaminophen administration associated with improved survival metrics across multiple timepoints: ICU mortality (adjusted HR 0.63, 0.48–0.82; P = 0.001), 90-day mortality (adjusted HR 0.78, 0.66–0.92; P = 0.004), and 180-day mortality (adjusted HR 0.78, 0.67–0.92; P = 0.002). While no significant differences were observed in ICU or hospital length of stay between groups, early acetaminophen administration was linked to longer ICU-free days through day 28 (β = 0.71; P = 0.022) and longer vasopressor-free days through day 28 (β = 0.77; P = 0.012).Conclusion: Early acetaminophen administration demonstrates independent associations with reduced in-hospital mortality and improved secondary clinical outcomes in surgical ICU populations. These findings highlight the need for prospective trials to confirm therapeutic efficacy and establish causal inference for this readily available pharmacologic intervention.