Dietary Lactiplantibacillus plantarum KX041 attenuates colitis-associated tumorigenesis and modulates gut microbiota

Colorectal cancer(CRC)is one of the most common cancers and supplementation of probiotics may be a promising intervention method. The present study aimed to investigate the anti-CRC effects of Lactiplantibacillus plantarum KX041 on a CRC mouse model. The CRC mice were induced by 10 mg/kg azoxymethane and 2% dextran sulfate sodium. L. plantarum KX041 was orally administrated once daily(1 × 10^(9) CFU/mouse). Results showed that L. plantarum KX041 could significantly inhibit inflammation, tumor formation, and induce tumor cells apoptosis. Moreover, this probiotic could ameliorate the damage of intestinal barrier by recovering tight junction protein expression(like Occludin, Claudin-1, and ZO-1)and preventing goblet cell loss. Furthermore, the oxidative stress was alleviated by increasing the level of antioxidant mediators(like GSH and SOD)and reducing the level of oxidative mediators(like MDA and MPO). In addition, treatment with L. plantarum KX041 could directly regulate gut microbiota, thereby increasing the abundance of beneficial bacteria(like SCFAs-producing bacteria, Akkermansia)and decreasing the abundance of harmful bacteria(like pro-inflammatory bacteria, Parasutterella), which in turn raised SCFAs levels and lowered LPS levels. In conclusion, L. plantarum KX041 could effectively ameliorate CRC via reshaping intestinal microenvironment, alleviating inflammation, maintaining intestinal permeability, and attenuating oxidative stress.

Remodeling the tumor microenvironment by vascular normalization and GSH-depletion for augmenting tumor immunotherapy

Remodeling tumor microenvironment(TME)is a very promising and effective strategy to enhance the effects of chemotherapy,photodynamic therapy,and immunotherapy.Normalization of tumor vasculature as well as depletion of glutathione(GSH)can improve the TME.Here,we developed a novel therapeutic nanoparticle functional enzyme ultra QDAU5 nanoparticles(FEUQ Nps)based on a fluorescence-on and releasable strategy by combining a vascular normalization inducer,a GSH depleting agent,and an activated fluorophore.In which the cleavage of disulfide bonds releases active molecules that induce vascular normalization and improve the hypoxic microenvironment.In addition,it may deplete GSH in cancer cells,thus inducing the production of reactive oxygen species(ROS)and lipid peroxide(LPO)and promoting iron toxicity.It may also lead to endoplasmic stress and release of calmodulin,which activates the immune system.Meanwhile,quenched fluorophores are turned on in the presence of galactosidase(GLU)for tumor-specific labeling.In summary,we developed novel therapeutic agent nanoparticles with the function of vascular normalization inducers to achieve specific labeling of hepatocellular carcinoma while exerting efficient antitumor effects in vivo.