Myosin light chain kinase (MLCK) induces contraction of the perijunctional apical actomyosin ring in response to phosphorylation of the myosin light chain. Abnormal expression of MLCK has been observed in respiratory diseases, pancreatitis, cardiovascular diseases, cancer, and inflammatory bowel disease (IBD). The signaling pathways involved in MLCK activation and triggering of endothelial barrier dysfunction are discussed in this review. The pharmacological effects of regulating MLCK expression by inhibitors such as ML-9, ML-7, microbial products, naturally occurring products, and microRNAs are also discussed. The influence of MLCK in inflammatory diseases starts with endothelial barrier dysfunction. The effectiveness of anti-MLCK treatment may depend on alleviation of that primary pathological mechanism. This review summarizes evidence for the potential benefits of anti-MLCK agents in the treatment of inflammatory disease and the importance of avoiding treatment-related side effects, as MLCK is widely expressed in many different tissues.

Background: Colorectal cancer (CRC) incidence is increasing in recent years due to intestinal flora imbalance, making oral probiotics a hotspot for research. However, numerous studies related to intestinal flora regulation ignore its internal mechanisms without in-depth research. Results: Here, we developed a probiotic microgel delivery system (L.r@(SA-CS)₂) through the layer-by-layer encapsulation technology of alginate (SA) and chitosan (CS) to improve gut microbiota dysbiosis and enhance anti-tumor therapeutic effect. Short chain fatty acids (SCFAs) produced by L.r have direct anti-tumor effects. Additionally, it reduces harmful bacteria such as Proteobacteria and Fusobacteriota, and through bacteria mutualophy increases beneficial bacteria such as Bacteroidota and Firmicutes which produce butyric acid. By binding to the G protein-coupled receptor 109A (GPR109A) on the surface of colonic epithelial cells, butyric acid can induce apoptosis in abnormal cells. Due to the low expression of GPR109A in colon cancer cells, MK-6892 (MK) can be used to stimulate GPR109A. With increased production of butyrate, activated GPR109A is able to bind more butyrate, which further promotes apoptosis of cancer cells and triggers an antitumor response. Conclusion: It appears that the oral administration of L.r@(SA-CS)₂ microgels may provide a treatment option for CRC by modifying the gut microbiota.

Polypyrrole nanoparticles (PPy NPs) have been extensively studied for photothermal therapy (PTT) of tumors because they can generate heat upon near-infrared (NIR) irradiation. Developing non-toxic, self-targeting and long-circulating PPy biomaterials to maximize photothermal effects remains challenging. Here, we show that PPy NPs camouflaged with fusing red blood cells (RBC) and platelet (PLT) membranes can kill tumor cells under direct near infrared irradiation (NIR). The resulting RBC–PLT hybrid membrane-coated PPy NPs (PPy@[R–P] NPs) possess characteristics of both RBC and PLT, exhibiting long circulation times and self-targeting properties. After administration of PPy@[R–P] NPs via tail vein, tumor vessels were injured by photothermal stimulation under NIR laser exposure, which induced a large amount of microthrombosis. Due to the existence of PLT membranes, a large number of PPy@[R–P] NPs were successfully recruited to the microthrombosis sites. As a result, the distribution of nanomaterials in the tumor tissues was improved, and excellent photothermal treatment was achieved. The resulting PPy@[R–P] NPs may contribute to anti-tumor PTT.

To investigate gut microbial diversity and the interventional effect of Xiaoyaosan (XYS) in a rat model of functional dyspepsia (FD) with liver depression-spleen deficiency syndrome. The FD with liver depression-spleen deficiency syndrome rat model was established through classic chronic mild unpredictable stimulation every day. XYS group rats received XYS 1 h before the stimulation. The models were assessed by parameters including state of the rat, weight, sucrose test result and open-field test result. After 3 wk, the stools of rats were collected and genomic DNA was extracted. PCR products of the V4 region of 16S rDNA were sequenced using a barcoded Illumina paired-end sequencing technique. The primary composition of the microbiome in the stool samples was determined and analyzed by cluster analysis. Rat models were successfully established, per data from rat state, weight and open-field test. The microbiomes contained 20 phyla from all samples. Firmicutes, Bacteroidetes, Proteobacteria, Cyanobacteria and Tenericutes were the most abundant taxonomic groups. The relative abundance of Firmicutes, Proteobacteria and Cyanobacteria in the model group was higher than that in the normal group. On the contrary, the relative abundance of Bacteroidetes in the model group was lower than that in the normal group. Upon XYS treatment, the relative abundance of all dysregulated phyla was restored to levels similar to those observed in the normal group. Abundance clustering heat map of phyla corroborated the taxonomic distribution. The microbiome relative abundance of FD rats with liver depression-spleen deficiency syndrome was significantly different from the normal cohort. XYS intervention may effectively adjust the gut dysbacteriosis in FD.