Microbiota and its induced inflammation in colorectal mucosa have been considered risk factors for the development of colorectal carcinogenesis. Previous studies demonstrated that the coexisting elements of microbiota in the gut, such as short chain fatty acids (SCFAs) and lipopolysaccharides (LPS), which exhibited regulatory effects on the intestinal epithelial cells individually. Unfortunately, the association between butyrate and the toll-like receptor (TLR) signaling pathway in the development of colon cancer is not fully elucidated. In the present study, by culturing human colon cancer SW480 cells or mouse colon cancer CT26 cells with butyrate and/or TLR4 ligand LPS in vitro, it was identified that butyrate suppressed the growth and promoted apoptosis of these cancer cells. Notably, the expression levels of TLR4 and CD14 were markedly increased on these butyrate-treated cells, but not on LPS-alone treated cells. Additionally, butyrate treatment induced the phosphorylation of extracellular signal-regulated kinase, tumor protein 38, c-Jun NH2-terminal kinase and nuclear factor-κB (NF-κB) p65, and then promoted the pro-inflammatory cytokine tumor necrosis factor-α, but not interleukin 6 secretion in SW480 and CT26 cells. Therefore, butyrate treatment regulates the expression of TLR4, mitogen-activated protein kinase and NF-κB signal pathway activation and pro-inflammatory response in vitro. Although the exact mechanisms have not been fully explored, these results suggested that butyrate and LPS-TLR4 signaling mediated innate immunity in colon cancer cells through two distinct but inter-regulated pathways. Thus, butyrate can further initiate innate immunity against tumor cells by upregulating the TLR4 expression and activation to preserve intestinal homeostasis.
Hepatic ischemia/reperfusion (I/R) injury is a common pathophysiological process that occurs following liver surgery, which is associated with oxidative stress, and can cause acute liver injury and lead to liver failure. Recently, the development of drugs for the prevention of hepatic I/R injury has garnered interest in the field of liver protection research. Previous studies have demonstrated that [D‑Ala2, D‑Leu5]‑Enkephalin (DADLE) exerts protective effects against hepatic I/R injury. To further clarify the specific mechanism underlying the effects of DADLE on hepatic I/R injury, the present study aimed to observe the effects of various doses of DADLE on hepatic I/R injury in mice. The results indicated that DADLE, at a concentration of 5 mg/kg, significantly reduced the levels of alanine aminotransferase and aspartate aminotransferase in the serum, and the levels of malondialdehyde in the liver homogenate. Conversely, the levels of glutathione, catalase and superoxide dismutase in the liver homogenate were increased. In addition, DADLE was able to promote nuclear factor, erythroid 2 like 2 (Nrf2) nuclear translocation and upregulate the expression of heme oxygenase (HO)‑1, which is a factor downstream of Nrf2, thus improving hepatic I/R injury in mice. In conclusion, the present study demonstrated that DADLE was able to significantly improve hepatic I/R injury in mice, and the specific mechanism may be associated with the Nrf2/HO‑1 signaling pathway.
Nanoparticles as drug delivery systems can alter the drugs' hydrophilicity to affect drug uptake and efflux in tissues. They prevent drugs from non-specifically binding with bio-macromolecules and enhance drug accumulation at the lesion sites, improving therapy effects and reducing unnecessary side effects. Metal–organic frameworks (MOFs), the typical nanoparticles, a class of crystalline porous materials via self-assembled organic linkers and metal ions, exhibit excellent biodegradability, pore shape and sizes, and finely tunable chemical composition. MOFs have a rigid molecular structure, and tunable pore size can improve the encapsulation drug's stability under harsh conditions. Besides, the surface of MOFs can be modified with small-molecule ligands and biomolecule, and binding with the biomarkers which is overexpressed on the surface of cancer cells. MOFs formulations for therapeutic have been developed to effectively respond to the unique tumor microenvironment (TEM), such as high H2O2 levels, hypoxia, and high concentration glutathione (GSH). Thus, MOFs as a drug delivery system should avoid drugs leaking during blood circulation and releasing at the lesion sites via a controlling manner. In this article, we will summary environment responsive MOFs as drug delivery systems for tumor therapy under different stimuli.
TRPV1 is a non-selective channel receptor widely expressed in skin tissues, including keratinocytes, peripheral sensory nerve fibers and immune cells. It is activated by a variety of exogenous or endogenous inflammatory mediators, triggering neuropeptide release and neurogenic inflammatory response. Previous studies have shown that TRPV1 is closely related to the occurrence and/or development of skin aging and various chronic inflammatory skin diseases, such as psoriasis, atopic dermatitis, rosacea, herpes zoster, allergic contact dermatitis and prurigo nodularis. This review summarizes the structure of the TRPV1 channel and discusses the expression of TRPV1 in the skin as well as its role of TRPV1 in skin aging and inflammatory skin diseases.
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