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The development of an intelligent nanomotor system holds great promise for enhancing the efficiency and effectiveness of antitumor therapy. Leveraging the overexpressed substances in the tumor microenvironment as propellants and chemotactic factors for enzyme-powered nanomotors represents a versatile and compelling approach. Herein, a plasma amine oxidase (PAO)-based chemotactic nanomotor system has been successfully developed, with the ability to enzymatically produce toxic acrolein and H 2 O 2 from the upregulated polyamines (PAs) in the tumor microenvironment for active tumor therapy. Zwitterionic polymeric nanoparticles with superior biocompatibility are synthesized, followed by PAO modification via electrostatic interactions. As expected, the resulting nanomotor system exhibits positive chemotaxis toward PAs concentration gradient. Upon reaching the tumor region, our nanomotors, actuated by the tumor microenvironmental PAs, effectively enhance diffusion and enable deep penetration into the tumor site. This leads to the induction of tumor apoptosis and simultaneous inhibition of tumor invasion and migration by decomposing PAs into toxic products. By smartly utilizing the consumption of these local chemotactic factors and their enzymatic products, our nanomotor system provides a versatile and intelligent platform for active and enhanced tumor therapy. Chemotactic nanomotor shows intelligent positive chemotaxis toward tumor microenvironmental polyamines concentration gradient and enzymatically produces toxic acrolein and H2O2 for product-based cancer therapy. [Display omitted] • Nanomotor effectively enhances the diffusion and enables deep penetration into the tumor cells by enzymatic reaction. • Enzymatic nanomotor induces tumor cell apoptosis by in situ decomposing tumorpolyamines into toxic products • Nanomotor exhibits positive chemotaxis toward polyamines concentration gradient. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOXO) is a widely used anti-cancer agent, yet the precise mechanism underlying the induction of tumor cell death remains unclear. This study aimed to elucidate new mechanisms by which doxorubicin induces apoptosis in the EMT6 mouse breast carcinoma cell line. The role of doxorubicin was assessed using the XTT assay. The assessment of oxidative stress markers, alongside the analysis of SIRT2 and NF-κB p65 (RelA) phosphorylation inhibition, was conducted. In silico studies, including density functional theory (DFT) calculations and molecular docking simulations, were employed to characterize the molecular interactions between doxorubicin and SIRT2. Additionally, doxorubicin was assessed for its capacity to modulate gene expression and associated pathways using multiple bioinformatics tools and web-based platforms. Our finding indicates that Doxorubicin induced apoptosis in EMT6 cells with an IC50 of 8,32 μM. At lower concentrations, doxorubicin enhances the oxidative balance and promotes cell viability. At high concentrations, doxorubicin inhibits SIRT2. Furthermore, an experimental investigation revealed that doxorubicin inhibits RelA phosphorylation. The results also showed that doxorubicin modulated the expression of 19 genes involved in different pathways and several transcription factors. The results of implementing the gene set with SIRT2 and RELA consolidated the experimental results. In conclusion, Doxorubicin was observed to induce EMT6 apoptosis through the inhibition of SIRT2 and RelA proteins. The outcomes of both experimental and bioinformatic studies provide a novel perspective on the biological effects of doxorubicin and underscore the potential of inhibiting the SIRT2-RelA axis as a promising biological target for cancer therapy. Legend: Doxorubicin inhibits SIRT2 and NF- k B p65 phosphorylation and induces EMT6 cell death. [Display omitted] • Doxorubicin induces tumor cell death with an IC50 value of 8,32 μM. • Doxorubicin inhibited SIRT2 and the NF- k B p65 (RelA) proteins leading to the carcinoma cell death. • Doxorubicin modulates expression of 19 genes and more. Implementation of the gene set by SIRT2 and RELA consolidates the experimental finding. • I nhibition of the Sirt2-RelA axis appears as a promising target for breast carcinoma treatment. [ABSTRACT FROM AUTHOR]

Iron overload leads to apoptosis and increased expression of receptor activator of nuclear factor kappa‐Β ligand (RANKL) in osteocytes, which in turn accelerates osteoclastogenesis. Since osteocytes are the main RANKL producers, we hypothesized that apoptotic osteocytes increase RANKL expression in osteocytes, which in turn stimulates osteoclastogenesis and bone resorption. In this study, alendronate or IG9402, a bisphosphonate (BP) analog which does not inhibit bone resorption, inhibited iron overload-induced osteocyte apoptosis and increased RANKL expression. Both BPs also prevented osteoblast apoptosis but did not inhibit the increase in osteoblastic RANKL. Alendronate, but not IG9402, prevented the increase in osteoclastogenesis and serum levels of the bone resorption marker C-telopeptide of type I collagen (CTX) in iron-overloaded mice. Alendronate also prevented the iron overload-induced reduction in femoral bone mineral density, disruption of bone microstructure, and weakness of bone strength. Although IG9402 did not prevent bone loss due to iron overload, it partially prevented reduction of strength, suggesting that osteocyte viability contributes to the maintenance of bone strength. In conclusion, although osteocyte apoptosis in the presence of iron overload leads to an increase in osteocytic RANKL production. However, blocking these events was not sufficient to inhibit iron overload-induced osteoclastogenesis and bone loss. • Bisphosphonates inhibit iron overload-induced osteocyte and osteoblast apoptosis. • Blocking osteocyte apoptosis does not decrease excess iron-induced osteoclastogenesis. • Blocking osteocyte apoptosis does not prevent iron overload-induced bone loss. • Blocking osteocyte apoptosis prevents impaired bone strength due to iron overload. [ABSTRACT FROM AUTHOR]

[Display omitted] • The synergistic anti-hepatoma effect of gallic acid combined with exosomes has been observed. • Exosomes are known to modulate inflammatory, oxidative stress, and glycolytic pathways. • The combination therapy of Gallic acid and exosomes affect Selenocompound, Cysteine and methionine metabolism. Clinically, hepatoma patients are more frequently encountered in the intermediate and advanced stages. Consequently, the majority of patients miss out on the chance to undergo liver transplantation or radical surgery. Radiotherapy and chemotherapy often fall short of delivering satisfactory outcomes. The incidence and mortality rates for liver cancer approach nearly 100%. In recent years, both exosomes (Exos) and natural chemical compounds have demonstrated robust anti-cancer properties; however, the synergistic effect of their combination remains unexplored. Exos were extracted from human umbilical cord mesenchymal stem cells (hUC-MSCs). The impact of gallic acid (GA), hUC-MSCs-Exos, and their combined administration on the proliferation inhibition rate and apoptosis of SMMC-7721 hepatoma cells was assessed to ascertain the efficacy differences before and after the combined treatment. A combination of cells metabolomics and network pharmacology techniques was employed to investigate the underlying mechanisms of action. The pivotal targets associated with glycolysis, inflammation, and oxidative stress pathways were confirmed through ELISA assays. The findings elucidate that GA profoundly impedes the proliferation of SMMC-7721 hepatoma cells and instigates apoptotic processes therein. While the impact of hUC-MSCs-Exos alone was inconspicuous, a notable augmentation in effect ensued upon their combined application. Concomitantly, a marked reduction was observed in the expressionlevels of key enzymes including HK, PFK, PK, LDH, TNF-α, IL-1β, CAT, SOD and GSH-Px in the malignant hepatocytes, while IL-6 and MDA exhibited heightened expression. Pathway enrichment analysis underscored selenocompound metabolism and cysteine and methionine metabolism as pivotal pathways. The potentiated efficacy of GA conjunction with hUC-MSCs-Exos may be attributed to their synergistic modulation of anti-inflammatory, antioxidant, and glycolytic functions, thereby influencing selenocompound metabolism and cysteine and methionine metabolism. This study reveals the efficacy and mechanism of Exos and GA combined therapy for hepatoma, providing new methods and ideas for the clinical treatment of hepatoma. [ABSTRACT FROM AUTHOR]

• BspE, a Brucella T4SS effector, promotes bacterial growth, survival in macrophages, and impacts inflammatory factor release. • It interacts with host PCBP1 in the nucleus, influencing P53 signaling, apoptosis inhibition, and Brucella replication. Brucella T4SS secretes numerous effector proteins to disrupt host immune responses and apoptosis, enabling long-term survival. One such effector protein is BspE, whose role remains largely unknown. In this study, we demonstrated that BspE promotes the growth of Brucella , enhances its survival in macrophages, and affects the release of macrophage inflammatory factors. Furthermore, BspE facilitates Brucella colonization and pathological damage in mice. Our findings reveal that BspE can be translated in the host cell nucleus, where it interacts with the host RNA-binding protein PCBP1 to promote Brucella replication in macrophages. Knockdown of PCBP1 affects BspE-mediated proliferation of Brucella in macrophages. Furthermore, the BspE-PCBP1 interaction hinders P53 signaling and inhibits macrophage apoptosis. Although this interaction affects inflammatory cytokines, it does not significantly involve the NF-κB pathway. These findings contribute to a better understanding of how the Brucella effector protein BspE regulates host immune responses and apoptosis to influence its own survival. [ABSTRACT FROM AUTHOR]