Rheumatoid arthritis (RA) is a chronic autoimmune disease that is primarily characterized by synovial inflammation. Our previous studies demonstrated that the lymphatic system is critical for the development and maintenance of RA disease, and sufficient lymph drainage helps to improve joint inflammation. In this study, we found that NG-R1, the main active component in the traditional Chinese medicinal herb Sanchi, activating lymphatic function can attenuate synovial inflammation. According to histopathological staining of ankle sections, NG-R1 significantly decreased the area of inflammation and reduced bone destruction of ankle joints in TNF-Tg mice. Near infrared-indocyanine green (NIR-ICG) lymphatic imaging system has shown that NG-R1 significantly improved the lymphatic drainage function. However, the molecular mechanism of its activity is not properly understood. Our in-depth study demonstrates that NG-R1 reduced the inflammatory cytokine production of lymphatic endothelial cells (LECs) stimulated by TNF-α, and the mechanism ameliorated the phosphorylation of IKKα/β and p65, and the translocation of p65 into the nucleus. In summary, this study proved that NG-R1 promoted lymphatic drainage function to ameliorating rheumatoid arthritis in TNF-Tg mice by suppressing NF-κB signaling pathway.

Krüppel-like factors (KLFs) are a group of DNA-binding transcriptional regulators with multiple essential functions in various cellular processes, including proliferation, migration, inflammation, and angiogenesis. The aberrant expression of KLFs is often found in tumor tissues and is essential for tumor development. At the molecular level, KLFs regulate multiple signaling pathways and mediate crosstalk among them. Some KLFs may also be molecular switches for specific biological signals, driving their transition from tumor suppressors to promoters. At the histological level, the abnormal expression of KLFs is closely associated with tumor cell stemness, proliferation, apoptosis, and alterations in the tumor microenvironment. Notably, the role of each KLF in tumors varies according to tumor type and different stages of tumor development rather than being invariant. In this review, we focus on the advances in the molecular biology of KLFs, particularly the regulations of several classical signaling pathways by these factors, and the critical role of KLFs in tumor development. We also highlight their strong potential as molecular targets in tumor therapy and suggest potential directions for clinical translational research.

Kidney dysfunction is particularly important in systemic organ injuries caused by aging. Metabolomics are utilized in this study to explore the mechanism of kidney dysfunction during aging by the identification of metabolites and the characterization of metabolic pathways. We analyzed the serum biochemistry and kidney histopathology of male Kunming mice aged 3 months and 24 months and found that the aged mice had inflammatory lesions, aggravated fibrosis, and functional impairment. A high-resolution untargeted metabolomics analysis revealed that the endogenous metabolites in the kidneys and urine of the mice were significantly changed by 25 and 20 metabolites, respectively. A pathway analysis of these differential metabolites revealed six key signaling pathways, namely, D-glutamine and D-glutamate metabolism, purine metabolism, the citrate cycle [tricarboxylic acid (TCA) cycle], histidine metabolism, pyruvate metabolism, and glyoxylate and dicarboxylate metabolism. These pathways are involved in amino acid metabolism, carbohydrate metabolism, and nucleotide metabolism, and these can lead to immune regulation, inflammatory responses, oxidative stress damage, cellular dysfunction, and bioenergy disorders, and they are closely associated with aging and kidney insufficiency. We also screened nine types of sensitive metabolites in the urine as potential biomarkers of kidney dysfunction during the aging process to confirm their therapeutic targets in senior-induced kidney dysfunction and to improve the level of risk assessment for senile kidney injury.