RESUMO
Resistin is one of the most important adipokines, and its role lies mainly in controlling insulin sensitivity and inflammation. However, over the last years, the study of resistin gained increased popularity since it was proved that there is a considerable relationship between high levels of resistin and obesity as well as obesity-induced diseases, including diabetes, cardiovascular disorders, and cancer. Regarding cancer risk, circulating resistin levels have been correlated with several types of cancer, including colorectal, breast, lung, endometrial, gastroesophageal, prostate, renal, and pancreatic cancer. Colorectal cancer is regarded as a multi-pathway disease. Several pathophysiological features seem to promote colorectal cancer (CRC) such as chronic inflammation, insulin resistance, and obesity. Even though the molecular mechanisms involved in CRC development remain rather vague, it is widely accepted that several biochemical factors promote CRC by releasing augmented pro-inflammatory cytokines, like IGF-I, insulin, sex-steroid hormones, and adipokines. A wide range of research studies has focused on evaluating the impact of circulating resistin levels on CRC risk and determining the efficacy of chemotherapy in CRC patients by measuring resistin levels. Moreover, significant outcomes have emerged regarding the association of specific single nucleotide polymorphisms (SNPs) in the resistin gene and CRC risk. The present study reviewed the role of circulating resistin levels in CRC development and shed light on specific resistin gene SNPs implicated in the disease's development. Finally, we analyzed the impact of resistin levels on the effectiveness of chemotherapy and further discussed whether resistin can be regarded as a valuable biomarker for CRC prognosis and treatment. Resistin is one of the most important adipokines, and its role lies mainly in controlling insulin sensitivity and inflammation. However, over the last years, the study of resistin gained increased popularity since it was proved that there is a considerable relationship between high levels of resistin and obesity as well as obesity-induced diseases, including diabetes, cardiovascular disorders, and cancer. This review discusses the aberrant expression of resistin and its receptors, its diverse downstream signaling, and its impact on tumor growth, metastasis, angiogenesis, and therapy resistance to support its clinical exploitation in biomarker and therapeutic development.
RESUMO
Introduction Liver regeneration is an exceptionally complex process, orchestrated by a multitude of growth factors and cytokines. Tumor necrosis factor-alpha (TNF-a) and interleukin-6 (Il-6) have a pivotal role in the initiation of the regenerative response. Ursodeoxycholic acid (UDCA) exhibits a liver protective effect that enhances liver growth after injury. The aim of the present study is to evaluate the effect of UDCA in the circulating levels of TNF-a and Il-6 in rats undergoing extended 80% hepatectomy. Materials and methods Twenty-two male Sprague Dawley rats were randomly assigned in an experimental (UDCA group) and a control group. Mice in the UDCA-group received oral pretreatment of UDCA for two weeks preoperatively at a dosage of 25 mg/kg/day. An 80% hepatic resection was performed in both groups by resecting the middle, inferior right, and left lateral liver lobes. The experiment ended 48 hours postoperatively. Results UDCA pretreatment significantly depressed circulating levels of both TNF-a and Il-6 after the conclusion of the experiment as compared to the control group (p=0.001 and p=0.01, respectively). Furthermore, TNF-a levels were significantly reduced before the institution of liver injury (p=0.02). Mice in the UDCA-group exhibited better liver growth as demonstrated by significantly increased Ki-67 and mitotic rate (p=0.04 and p=0.02, respectively). Finally, the liver regeneration rate (LRR) was significantly elevated in the experimental group (UDCA group, 54.5% vs control group, 35.8%; p=0.002) signifying enhanced liver growth kinetics. Conclusion UDCA reduces the expression of TNF-a and Il-6 during the priming phase of liver regeneration. An 80% hepatectomy model of acute liver failure exhibited enhanced liver regeneration in the experimental group, plausibly due to the immunomodulatory effects of UDCA.