Drug resistance and new therapies in colorectal cancer

Chemokines are a large family mediating a lot of biological behaviors including chemotaxis, tumor growth, angiogenesis and so on. As one member of this family, CXC subfamily possesses the same ability. CXC chemokines can recruit and migrate different categories of immune cells, regulate tumor’s pathological behaviors like proliferation, invasion and metastasis, activate angiogenesis, etc. Due to these characteristics, CXCL subfamily is extensively and closely associated with tumors and inflammatory diseases. As studies are becoming more and more intensive, CXCLs’ concrete roles are better described, and CXCLs’ therapeutic applications including biomarkers and targets are also deeply explained. In this review, the role of CXCL family members in various diseases is summarized.

Multidrug resistance is a major challenge to cancer chemotherapy. The multidrug resistance phenotype is associated with the overexpression of the adenosine triphosphate (ATP)-driven transmembrane efflux pumps in cancer cells. Here, we report a lipid membrane-coated silica-carbon (LSC) hybrid nanoparticle that targets mitochondria through pyruvate, to specifically produce reactive oxygen species (ROS) in mitochondria under near-infrared (NIR) laser irradiation. The ROS can oxidize the NADH into NAD ⁺ to reduce the amount of ATP available for the efflux pumps. The treatment with LSC nanoparticles and NIR laser irradiation also reduces the expression and increases the intracellular distribution of the efflux pumps. Consequently, multidrug-resistant cancer cells lose their multidrug resistance capability for at least 5 days, creating a therapeutic window for chemotherapy. Our in vivo data show that the drug-laden LSC nanoparticles in combination with NIR laser treatment can effectively inhibit the growth of multidrug-resistant tumors with no evident systemic toxicity.

Kaempferol, also known as kaempferol‑3 or kaempferide, is a flavonoid compound that naturally occurs in tea, as well as numerous common vegetables and fruits, including beans, broccoli, cabbage, gooseberries, grapes, kale, strawberries, tomatoes, citrus fruits, brussel sprouts, apples and grapefruit. The present review mainly summarizes the application of kaempferol in treating diseases and the underlying mechanisms that are currently being studied. Due to its anti‑inflammatory properties, it may be used to treat numerous acute and chronic inflammation‑induced diseases, including intervertebral disc degeneration and colitis, as well as post‑menopausal bone loss and acute lung injury. In addition, it has beneficial effects against cancer, liver injury, obesity and diabetes, inhibits vascular endothelial inflammation, protects the cranial nerve and heart function, and may be used for treating fibroproliferative disorders, including hypertrophic scar

Gut dysbiosis has been linked to type 1 diabetes (T1D); however, microbial capacity in T1D remains unclear. Here, we integratively profiled gut microbial functional and metabolic alterations in children with new-onset T1D in independent cohorts and investigated the underlying mechanisms. In T1D, the microbiota was characterized by decreased butyrate production and bile acid metabolism and increased lipopolysaccharide biosynthesis at the species, gene, and metabolite levels. The combination of 18 bacterial species and fecal metabolites provided excellently discriminatory power for T1D. Gut microbiota from children with T1D induced elevated fasting glucose levels and declined insulin sensitivity in antibiotic-treated mice. In streptozotocin-induced T1D mice, butyrate and lipopolysaccharide exerted protective and destructive effects on islet structure and function, respectively. Lipopolysaccharide aggravated the pancreatic inflammatory response, while butyrate activated Insulin1 and Insulin2 gene expression. Our study revealed perturbed microbial functional and metabolic traits in T1D, providing potential avenues for microbiome-based prevention and intervention for T1D.

In this study, the secondary sequencing was used to profile circRNA expression in the tissue samples from three CRC patients with liver metastasis and three matched CRC patients. After verified some candidates in another 40 CRC and CRC-m samples by qRT-PCR, we further demonstrated that circRNA_0001178 and circRNA_0000826 were significantly upregulated in CRC-m tissues, and both of them had the potential for diagnosing liver metastases from colorectal cancer. Finally, the networks of circRNA-miRNA-mRNA base on these two circRNAs were constructed respectively. This study showed that differentially expressed circRNAs were existed between the tissue samples from colorectal cancer patients with and without liver metastasis. And also suggested that circRNA_0001178 and circRNA_0000826 may serve as a potential diagnostic biomarker for liver metastases from colorectal cancer.