According to numerous animal studies, adverse environmental stimuli, including physical, chemical, and biological factors, can cause low‐grade chronic inflammation and subsequent tumor development. Human epidemiological evidence has confirmed the close relationship between chronic inflammation and tumorigenesis. However, the mechanisms driving the development of persistent inflammation toward tumorigenesis remain unclear. In this study, we assess the potential role of reactive oxygen species (ROS) and associated mechanisms in modulating inflammation‐induced tumorigenesis. Recent reports have emphasized the cross‐talk between oxidative stress and inflammation in many pathological processes. Exposure to carcinogenic environmental hazards may lead to oxidative damage, which further stimulates the infiltration of various types of inflammatory cells. In turn, increased cytokine and chemokine release from inflammatory cells promotes ROS production in chronic lesions, even in the absence of hazardous stimuli. Moreover, ROS not only cause DNA damage but also participate in cell proliferation, differentiation, and apoptosis by modulating several transcription factors and signaling pathways. We summarize how changes in the redox state can trigger the development of chronic inflammatory lesions into tumors. Generally, cancer cells require an appropriate inflammatory microenvironment to support their growth, spread, and metastasis, and ROS may provide the necessary catalyst for inflammation‐driven cancer. In conclusion, ROS bridge the gap between chronic inflammation and tumor development; therefore, targeting ROS and inflammation represents a new avenue for the prevention and treatment of cancer.

2,3,5,4′‐Tetrahydroxystilbene‐2‐O‐β‐D‐glucoside (TSG), an important monomer extracted from Polygonum multiflorum, can prevent a number of inflammation associated chronic diseases. However, the mechanism involved in TSG inducing anti‐inflammatory role remains unclear. As an inducible antioxidant enzyme, Heme oxygenase‐1 (HO‐1), is crucial for protecting the mammalian cells against adverse stimuli. Here, we found that the TSG treatment strongly induces the expression of HO‐1 in an NRF2‐depended manner. Meanwhile, TSG increased the mitochondrial mass through upregulation of the mitochondrial biogenesis activators (PGC‐1α, NRF1, and TFAM) as well as the mitochondrial complex IV. Furthermore, TSG attenuated Lipopolysaccharide (LPS) mediated RAW264.7 cells activation and secretion of proinflammatory cytokines, including interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α). Zinc Protoporphyrin (ZnPP), a selective inhibitor of HO‐1 activity, was able to attenuate TSG mediated mitochondrial biogenesis and anti‐inflammatory process. Finally, we observed that LPS induced obvious mtDNA depletion and ATP deficiency, which indicated a severe damage of mitochondria. TSG restored the LPS induced mitochondrial dysfunction via activation of the mitochondrial biogenesis. ZnPP treatment markedly reversed the inhibitory effects of TSG on mitochondrial damage and oxidative stress in LPS stimulated macrophages. Taken together, these findings suggest that TSG enhances mitochondrial biogenesis and function mainly via activation the HO‐1. TSG can be developed as a potential drug for treatment of inflammatory diseases.

Epithelial-to-mesenchymal transition (EMT) is critical to the progression of several disease processes including carcinoma metastasis and organ fibrosis. Recent studies show that reactive oxygen species (ROS) and mitochondrial dysfunction have been associated with EMT. However, the role of mitochondria in the EMT process remains to be elucidated. Through the induction of EMT using TGF-β1, we demonstrated that mitochondrial functions were abnormal by increasing ROS production and reducing mitochondrial membrane potential, ATP content and mitochondrial complex protein expression. Resveratrol, a mitochondria protective agent, was found to prevent EMT by preserving mitochondrial functions during the process. However, the inhibitory effects of resveratrol on EMT were abolished in mitochondrial DNA-depleted cells. These findings suggest a critical role for mitochondria in EMT and implicate the protection of mitochondria as a potential target to prevent EMT to treat tumour metastasis or tissue fibrosis, and other diseases involving with mitochondria.

Objective: Chlorine is a chemical threat agent that can be harmful to humans. Inhalation of high levels of chlorine can lead to acute lung injury (ALI). Currently, there is no satisfactory treatment, and effective antidote is urgently needed. Pentoxifylline (PTX), a methylxanthine derivative and nonspecific phosphodiesterase inhibitor, is widely used for the treatment of vascular disorders. The present study was aimed to investigate the inhibitory effects of PTX on chlorine-induced ALI in rats. Methods: Adult male Sprague-Dawley rats were exposed to 400 ppm Cl₂ for 5 min. The histopathological examination was carried out and intracellular reactive oxygen species (ROS) levels were measured by the confocal laser scanning system. Subsequently, to evaluate the effect of PTX, a dose of 100 mg/kg was administered. The activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG) and lactate dehydrogenase (LDH) were determined by using commercial kits according to the manufacturer’s instructions. Western blot assay was used to detect the protein expressions of SOD1, SOD2, catalase (CAT), hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), occludin, E-cadherin, bcl-xl, LC 3, Beclin 1, PTEN-induced putative kinase 1 (PINK 1) and Parkin. Results: The histopathological examination demonstrated that chlorine could destroy the lung structure with hemorrhage, alveolar collapse, and inflammatory infiltration. ROS accumulation was significantly higher in the lungs of rats suffering from inhaling chlorine (P<0.05). PTX markedly reduced concentrations of MAD and GSSG, while increased GSH (P<0.05). The protein expression levels of SOD1 and CAT also decreased (P<0.05). Furthermore, the activity of LDH in rats treated with PTX was significantly decreased compared to those of non-treated group (P<0.05). Additionally, the results also showed that PTX exerted an inhibition effect on protein expressions of HIF-1α, VEGF and occludin, and increased the level of E-cadherin (P<0.05). While the up-regulation of Beclin 1, LC 3II/I, Bcl-xl, and Parkin both in the lung tissues and mitochondria, were found in PTX treated rats (P<0.05). The other protein levels were decreased when treated with PTX (P<0.05). Conclusion: PTX could ameliorate chlorine-induced lung injury via inhibition effects on oxidative stress, hypoxia and autophagy, thus suggesting that PTX could serve as a potential therapeutic approach for ALI.