The AP-2 Family of Transcription Factors-Still Undervalued Regulators in Gastroenterological Disorders.

Activating enhancer-binding protein 2 (AP-2) is a family of transcription factors (TFs) that play crucial roles in regulating embryonic and oncogenic development. In addition to splice isoforms, five major family members encoded by the TFAP2A/B/C/D/E genes have been identified in humans, i.e., AP-2α/ß/γ/δ/ε. In general, the first three TFs have been studied more thoroughly than AP-2δ or AP-2ε. Currently, there is a relatively limited body of literature focusing on the AP-2 family in the context of gastroenterological research, and a comprehensive overview of the existing knowledge and recommendations for further research directions is lacking. Herein, we have collected available gastroenterological data on AP-2 TFs, discussed the latest medical applications of each family member, and proposed potential future directions. Research on AP-2 in gastrointestinal tumors has predominantly been focused on the two best-described family members, AP-2α and AP-2γ. Surprisingly, research in the past decade has highlighted the importance of AP-2ε in the drug resistance of gastric cancer (GC) and colorectal cancer (CRC). While numerous questions about gastroenterological disorders await elucidation, the available data undoubtedly open avenues for anti-cancer targeted therapy and overcoming chemotherapy resistance. In addition to gastrointestinal cancers, AP-2 family members (primarily AP-2ß and marginally AP-2γ) have been associated with other health issues such as obesity, type 2 diabetes, liver dysfunction, and pseudo-obstruction. On the other hand, AP-2δ has been poorly investigated in gastroenterological disorders, necessitating further research to delineate its role. In conclusion, despite the limited attention given to AP-2 in gastroenterology research, pivotal functions of these transcription factors have started to emerge and warrant further exploration in the future.

Senescent adipocytes and type 2 diabetes - current knowledge and perspective concepts.

Among civilization diseases, the number of individuals suffering from type 2 diabetes (T2DM) is expected to increase to more than a billion in less than 20 years, which is associated with, e.g., populational aging, poor diet, sedentary lifestyle, genetic predispositions, and immunological factors. T2DM affects many organs and is characterized by insulin resistance, high glucose levels, and adipocyte dysfunction, which are related to senescence. Although this type of cellular aging has beneficial biological functions, it can also act unfavorable since senescent adipocytes resist apoptosis, enhance cytokine secretion, downregulate cell identity genes, and acquire the senescence-associated secretory phenotype that renders a more oxidative environment. Opposing T2DM is possible via a wide variety of senotherapies, including senolytics and senomorphics; nevertheless, further research is advised to expand therapeutic possibilities and benefits. Consequences that ought to be deeply researched include secretory phenotype, chronic inflammation, increasing insulin resistance, as well as impairment of adipogenesis and functioning of adipocyte cells. Herein, despite reviewing T2DM and fat tissue senescence, we summarized the latest adipocyte-related anti-diabetes solutions and suggested further research directions.