Harnessing the Potential of FAP-IL12mut TMEkine for Targeted and Enhanced Antitumor Responses.

Although cancer immunotherapy has yielded encouraging outcomes in hematologic malignancies, it has faced challenges in achieving the same level of effectiveness in numerous solid tumors, primarily because of the presence of immunosuppressive tumor microenvironments (TME). The immunosuppressive qualities of the TME have generated considerable interest, making it a focal point for treatments aimed at enhancing immune responses and inhibiting tumor progression. Fibroblast activation protein (FAP), an attractive candidate for targeted immunotherapy, is prominently expressed in the TME of various solid tumors.

A single gene of a commensal microbe affects host susceptibility to enteric infection.

Indigenous microbes inside the host intestine maintain a complex self-regulating community. The mechanisms by which gut microbes interact with intestinal pathogens remain largely unknown. Here we identify a commensal Escherichia coli strain whose expansion predisposes mice to infection by Vibrio cholerae, a human pathogen.

Orotic acid induces hypertension associated with impaired endothelial nitric oxide synthesis.

Orotic acid (OA) is an intermediate of pyrimidine nucleotide biosynthesis. Hereditary deficiencies in some enzymes associated with pyrimidine synthesis or the urea cycle induce OA accumulation, resulting in orotic aciduria. A link between patients with orotic aciduria and hypertension has been reported; however, the molecular mechanisms remain elusive.

Uric acid induces endothelial dysfunction by vascular insulin resistance associated with the impairment of nitric oxide synthesis.

Endothelial dysfunction is defined as impairment of the balance between endothelium-dependent vasodilation and constriction. Despite evidence of uric acid-induced endothelial dysfunction, a relationship with insulin resistance has not been clearly established. In this study, we investigated the role of vascular insulin resistance in uric acid-induced endothelial dysfunction.

Protective effect of resveratrol derivatives on high-fat diet induced fatty liver by activating AMP-activated protein kinase.

Non-alcoholic fatty liver disease is associated with inhibited AMP-activated kinase (AMPK) and activation of sterol regulatory element binding protein 1 (SREBP-1). AMPK phosphorylation inhibits SREBP-1, a major transcription factor of de novo lipogenesis, by inhibiting the liver X receptor (LXR) or by direct phosphorylation. Resveratrol, a polyphenol, has regulatory effects on hepatic lipid metabolism as a potent AMPK activator.

Functional screening of a metagenomic library reveals operons responsible for enhanced intestinal colonization by gut commensal microbes.

Evidence suggests that gut microbes colonize the mammalian intestine through propagation as an adhesive microbial community. A bacterial artificial chromosome (BAC) library of murine bowel microbiota DNA in the surrogate host Escherichia coli DH10B was screened for enhanced adherence capability. Two out of 5,472 DH10B clones, 10G6 and 25G1, exhibited enhanced capabilities to adhere to inanimate surfaces in functional screens.

Effects of Medicinal herb Extracts and their Components on Steatogenic Hepatotoxicity in Sk-hep1 Cells.

Herbal medicines are widely used in many countries for the treatment of many diseases. Although the use of herb extracts as alternative medicine is growing, their toxicological properties have not been thoroughly investigated. In this study, we have investigated the effects of water and ethanol extracts of 18 herbs on the hepatic lipid metabolism and steatogenic hepatotoxicity.