Hongyu Li

Realgar (As4S4) has long been used in traditional medicine, yet its clinical application remains limited due to poor bioavailability and toxicity. Realgar transforming solution (RTS), a bioleached product generated through microbial transformation of realgar, exhibits enhanced anti-tumor activity; however, its underlying mechanism remains unclear. This study investigated whether ferroptosis contributes to the anti-leukemic effects of RTS in NB4 cells, focusing on iron homeostasis and the solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) antioxidant axis. NB4 cells were treated with RTS, arsenic trioxide (ATO), or realgar, and cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Transcriptomic profiling, biochemical assays, fluorescence probes, flow cytometry, and Western blotting were employed to evaluate ferroptosis-related changes. RTS inhibited NB4 cell viability more effectively than ATO or realgar at comparable arsenic concentrations. Transcriptomic analysis indicated significant enrichment of ferroptosis-related pathways. RTS decreased glutathione and superoxide dismutase levels, increased malondialdehyde accumulation and lipid peroxidation, disrupted mitochondrial membrane potential, and elevated intracellular total iron and mitochondrial Fe2+ levels. Additionally, RTS downregulated SLC7A11 and GPX4 and altered the expression of iron metabolism-related proteins, including transferrin receptor protein 1, nuclear receptor coactivator 4, ferritin heavy chain 1, ferroportin 1, iron-responsive element-binding protein 2, and heme oxygenase 1. Moreover, ferrostatin-1 and deferoxamine mesylate partially rescued RTS-induced cytotoxicity and alleviated oxidative damage and iron overload. These results indicate that RTS induces ferroptosis-associated cell death in NB4 cells by disrupting iron homeostasis and inhibiting the SLC7A11/GPX4 axis, supporting further investigation of RTS as a modernized arsenic-based anti-leukemic formulation.

Chinese Kushui Rose ( Rosa sertata × Rose rugosa ) is widely recognized for its medicinal and edible properties, and Chinese Kushui Rose Essential Oil (KREO) has attracted growing attention due to its potential anxiolytic and sedative‐hypnotic effects. This study aims to systematically evaluate the preventive effects of KREO against depression‐like behaviors and explore its underlying mechanisms. We identified 57 volatile compounds from KREO using gas chromatography–mass spectrometry (GC–MS), with the major constituents being citronellol, geraniol, and citronellyl acetate. In mice with chronic unpredictable mild stress (CUMS)‐induced depression, administration of KREO facilitated body weight recovery, alleviated depressive‐like behaviors, and improved voluntary locomotor activity and exploratory behavior. Mechanistic investigations revealed that KREO increased hippocampal levels of serotonin (5‐HT) and brain‐derived neurotrophic factor (BDNF), reduced serum corticosterone (Cort) concentrations, and upregulated the expression of tyrosine receptor kinase B (TrkB) as well as the phosphorylation of extracellular signal‐regulated kinase 1/2 (p‐ERK1/2) in the hippocampus. Thus, KREO prevents depression‐like behavior by enhancing monoaminergic neurotransmission and attenuating hypothalamic–pituitary–adrenal (HPA) axis hyperactivity, with these effects associated with activation of the BDNF signaling pathway. These findings support the potential of KREO as a therapeutic intervention for depression and as a functional dietary ingredient.

Parkinson’s disease (PD) is the second most progressive degenerative disorder of the brain due to dopaminergic (DA) neuron degenerations and alpha-synuclein (α-Syn) accumulations. At present, the disease has no effective treatment. Therefore, the current study objective is to identify a novel anti-PD formula (Zhi-Shi-Huang-Wu Formula, F-2) computed at 8:4:2:1 ratio from HSP 70 promoter activators Valeriana jatamansi (V), Acori talarinowii (A), Scutellaria baicalensis (S), Fructus Schisandrae (F). Traditionally, V is used to cure memory impairments, A treats mental disorders, and chronic mild stress, S for neuroprotection, and F showed multiple therapeutic actions to treat insomnia. This study investigated the neuroprotective potential of the V, A, S, F, formula F-2 and its underlying molecular mechanisms in transgenic Caenorhabditis elegans models. A, S, F, and F-2 successfully restored 6-hydroxydopamine intoxicated DA neuron degenerations, reduced food-sensing behavior disabilities, and attenuated α-Syn aggregations. Moreover, activates the lipid deposition and proteasome expressions to confirm α-Syn degradations at the cellular level. Reactive oxygen species (ROS) cause oxidative stress, and A, S, F, and F-2 repressed ROS and raised SOD -3 expressions. Overall, these data indicate that V, A, S, F combined into F-2 (22.3%) are more effective against PD progression-like symptom than individual drugs V (0.7%), A (11.4%), S (9.6%), and F (12.6%). These improved neuroprotective actions of F-2 possibly due to following the antioxidative pathway. Graphical

Primary immune thrombocytopenia (ITP) is a condition marked by immune-mediated inadequate platelet production or excessive destruction. This study investigates the effects of Lienal polypeptide injection (LP) on T lymphocyte subgroups in the spleen and thymus, megakaryocyte counts in the bone marrow, and cytokine levels related to megakaryocyte development in mice with antibody-induced ITP, aiming to elucidate potential therapeutic mechanisms. We first assessed the effects of LP on Meg-01 megakaryocytic cells regarding proliferation, apoptosis, and differentiation using Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assays, Western blot analysis, and flow cytometry for apoptosis and CD41 expression as a differentiation marker. Following this, LP was administered intraperitoneally at 60 mg/(kg·d) for 11 days to ITP mice. We quantified peripheral blood platelets and bone marrow megakaryocytes, measured spleen and thymus indices, and assessed serum levels of stem cell factor (SCF), interleukin-3 (IL-3), interleukin-6 (IL-6), and platelet factor-4 (PF-4) via enzyme-linked immunosorbent assay (ELISA). Flow cytometry quantified T-helper cells (CD4⁺), cytotoxic T cells (CD8⁺), and regulatory T cells (Tregs). LP significantly induced apoptosis in Meg-01 cells while not markedly affecting differentiation. In ITP mice, LP effectively prevented platelet decline without affecting megakaryocyte counts or maturity. Increased SCF, IL-3, and IL-6 levels, alongside decreased PF-4 levels, correlated with enhanced platelet production. Moreover, CD4⁺/CD8⁺ ratios and Treg populations increased, contributing to reduced platelet destruction. In conclusion, LP exerts a protective effect in ITP by modulating SCF, IL-3, IL-6, and PF-4 levels and restoring the balance of T cell subtypes, elucidating its therapeutic potential.