Yongning Li

This study aimed to investigate the protective effect of curcumin against sepsis‐associated acute kidney injury (SA‐AKI) in vitro and in vivo, and to clarify the role of ferroptosis in this protection. Human renal tubular epithelial cell (RTEC) line HK‐2 was stimulated with lipopolysaccharide (LPS). Ferroptosis was further induced with erastin. In vivo, a rat SA‐AKI model was produced by cecal ligation and puncture (CLP) and allocated to the Sham, sepsis, and curcumin (Cur) + sepsis (Sep) groups. Glutathione (GSH), malondialdehyde (MDA), and pro‐inflammatory cytokines were quantified by ELISA. Western blot analysis was used to evaluate the ferroptosis‐related proteins, including long‐chain acyl‐coenzyme synthetases 4 (ACSL4) and glutathione peroxidase 4 (GPX4). Apoptosis of RTECs was assessed with TUNEL staining, and ultrastructural changes were examined by transmission electron microscopy (TEM). Compared with the Sepsis group, the Cur + Sep group showed significantly lower Paller damage scores, reduced Scr, BUN, TNF‐α, IL‐1β, IL‐6, MDA, Fe ²⁺ levels, and ACSL4 protein expression (all p < 0.05). Conversely, GSH and GPX4 levels were significantly elevated in the Cur + Sep group (both p < 0.05). TUNEL staining revealed fewer apoptotic RTECs in the Cur + Sep group compared with the Sepsis group ( p < 0.05). TEM demonstrated swollen mitochondria with condensed membranes and vanished cristae in the sepsis group, changes that were markedly alleviated by curcumin. In HK‐2 cells, erastin abolished curcumin's protective effect against LPS‐induced injury. Curcumin attenuates SA‐AKI, likely by suppressing inflammation and ferroptosis via the ACSL4/GPX4 signaling pathway.

Sepsis is a systemic inflammatory response syndrome caused by pathogenic microorganisms such as bacteria, fungi, viruses, and parasites invading the body. It is primarily characterized by an immune dysregulation in response to infection, leading to severe complications such as dysfunction of vital organs, shock, and disseminated intravascular coagulation (DIC), thereby threatening the patient’s life. Additionally, approximately 3 million surviving patients suffer from cognitive impairment, severely affecting their quality of life. Curcumin, a monomer of traditional Chinese medicine, has extensive pharmacological activity. Numerous studies have shown that curcumin can counteract the inflammatory response in sepsis and protect against organ damage caused by sepsis, suggesting that curcumin may become a new direction for sepsis treatment. In this review, we summarize the therapeutic effects and detailed mechanisms of curcumin in the treatment of sepsis based on current research.

Sonodynamic therapy (SDT) is effective in treating intimal hyperplasia and promoting plaque stability in animal models. The present study aimed to evaluate the effects of SDT with the sonosensitizer protoporphyrin IX (PpIX) on vascular smooth muscle cell (VSMC) viability and autophagy. Cultured VSMCs cells were divided into the following groups: i) Control, ii) ultrasound, iii) PpIX and iv) SDT. Flow cytometry and laser confocal detection were used to measure Annexin V stained VSMCs following different treatments. Alterations in mitochondrial membrane potential (MMP) were evaluated via JC-1 staining. Autophagosome formation was observed using electron and fluorescence microscopy. Western blotting was used to analyze the expression levels of the autophagy markers light chain 3 (LC3-I) and LC3-II. The results demonstrated that SDT did not trigger apoptosis nor induce a significant decline in MMP of VSMCs. However, SDT significantly increased autophagasome formation and increased the LC3-II/LC3-I ratio. The findings demonstrated that PpIX-SDT increased autophagy without inducing mitochondrial-dependent apoptosis in VSMCs.

Hepatocellular carcinoma (HCC) accounts for 75 % of liver cancers and is the second most lethal cancer, associated with its multiple etiologies, poor prognosis and resistance to chemotherapy drugs. Chemotherapy treatment on HCC suffers low efficacy of drug uptake and can produce a range of side effects. Here we report an investigation on the effect of a combined treatment on human hepatocellular carcinoma BEL-7402 cells using low-intensity ultrasound (US) and 5-fluorouracil (5-FU). The uptake of 5-FU was measured by the high-performance liquid chromatography (HPLC). DNA damage was detected by the comet assay. MTT assay was used to examine cell viability. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (Δψm) were respectively detected by the fluorescent probes DCFH-DA or JC-1. Endogenous apoptosis-associated proteins were analyzed by the western blot and immunohistochemistry. Histopathological changes were evaluated by the hematoxylin and eosin (H&E) staining. Cell apoptosis was evaluated by the TUNEL and flow cytometry assays. Cell proliferation was measured using the immunohistochemical staining of PCNA. Our results showed that low-intensity US (1.1 MHz, 1.0 W/cm2, 10 % duty cycle) significantly enhanced the uptake of 5-FU, 5-FU-mediated DNA damage and reactive oxygen species (ROS) generation. The increased ROS production up-regulated the p53 protein level, which led to the up-regulation of Bax and down-regulation of Bcl-2. The enhancement of ROS generation and the activation of the apoptosis-associated proteins further triggered the collapse of mitochondrial membrane potential, released cytochrome c from mitochondria into cytosol and activated the mitochondria-caspase pathway, and cell apoptosis. Such enhanced effects could be partially blocked by the ROS scavenger N-acetylcysteine (NAC). Overall, low-intensity US combined with 5-FU led to an effective inhibition of tumor growth and prolonged overall survival of BEL-7402 HCC-bearing nude mice by more than 15 % compared with 5-FU treatment alone. Our results showed that low-intensity ultrasound combined with 5-FU produced much enhanced synergistic anti-tumor effects via enhanced ROS production in treating HCC.