Continuous development of personalized treatments is undoubtedly beneficial for oncogenic patients’ comfort and survival rate. Mutant TP53 is associated with a worse prognosis due to the occurrence of metastases, increased chemoresistance, and tumor growth. Currently, numerous compounds capable of p53 reactivation or the destabilization of mutant p53 are being investigated. Several of them, APR-246, COTI-2, SAHA, and PEITC, were approved for clinical trials. This review focuses on these novel therapeutic opportunities, their mechanisms of action, and their significance for potential medical application.
Forty years of research has proven beyond any doubt that p53 is a key regulator of many aspects of cellular physiology. It is best known for its tumor suppressor function, but it is also a regulator of processes important for maintenance of homeostasis and stress response. Its activity is generally antiproliferative and when the cell is damaged beyond repair or intensely stressed the p53 protein contributes to apoptosis. Given its key role in preventing cancer it is no wonder that it is the most frequently mutated gene in human cancer. Surprisingly, a subset of missense mutations occurring in p53 (gain-of-function) cause it to lose its suppressor activity and acquire new functionalities that turn the tumor suppressor protein into an oncoprotein. A solid body of evidence exists demonstrating increased malignancy of cancers with mutated p53 in all aspects considered “hallmarks of cancer”. In this review, we summarize current findings concerning the cellular processes altered by gain-of-function mutations in p53 and their influence on cancer invasiveness and metastasis. We also present the variety of molecular mechanisms regulating these processes, including microRNA, direct transcriptional regulation, protein–protein interactions, and more.
The study aimed to examine samples of different market original sheep cow and goat cheeses, in respect of the content and profile of FA with special emphasis on health-promoting FA. The content of fatty acids in the examined cheeses was highly differentiated and depended on the sort and type of cheese. The content of fatty acid groups in milk fat varied within the limits: SFA, 55.2–67.2%; SCSFA, 10.9–23.4%; BCFA, 1.6–2.9%; MUFA, 15.2–23.4%; PUFA, 1.9–4.3%; trans-MUFA, 1.8–6.0%; and CLA, 1.0–3.1%. From among the examined cheeses, the seasonal sheep cheeses (Oscypek) and mountain cow cheeses were characterized by the highest content of health-promoting fatty acids. The content of health-promoting fatty acids in the fat fraction of these cheeses was CLA 2.1–3.1%, trans-MUFA 3.5–6%, BCFA 2.7–2.9%, and SCSFA 12–18%.
Intrauterine growth restricted (IUGR) pigs are characterized by high perinatal mortality and dysfunction of internal organs, adipose, and muscle tissues. However, little is known about the post-weaning performance and meat quality of the IUGR pigs. The aim of this study was to compare normal pigs and pigs with IUGR from birth until slaughter, also with respect to their meat quality. Pigs with the IUGR achieved lower slaughter weight but did not differ significantly from normal pigs in terms of their meat content. The IUGR did not negatively affect the culinary quality of the obtained meat, including its content of basic chemical components and energy value, as well as hardness, chewiness, cohesiveness, elasticity, and penetration force. The meat of the IUGR pigs, when compared to the meat of normal pigs, was characterized by higher pH, lower EC (Electrical Conductivity) and drip loss; it was also tenderer and obtained higher scores in sensory evaluation of taste, smell, and general desirability. Therefore, such raw material can be appreciated by the consumers and can be used for the production of culinary portions similarly to the raw material obtained from normal pigs.
1 November 2020 in Journal of Inflammation Research
The stress of surgery is characterized by an inflammatory response with immune suppression resulting from many factors, including the type of surgery and the kind of anesthesia, linked with the drugs that are used and the underlying disease of the patient. The trauma of surgery triggers a cascade of reactions involving the immune response and nociception. As strong analgesics, opioids provide the analgesic component of general anesthesia with bi-directional effect on the immune system. Opioids influence almost all aspects of the immune response in regards to leukocytes, macrophages, mast cells, lymphocytes, and NK cells. The suppressive effect of opioids on the immune system is limiting their use, especially in patients with impaired immune response, so the possibility of using multimodal anesthesia without opioids, known as opioid-free anesthesia (OFA), is gaining more and more sympathizers. The idea of OFA is to eliminate opioid analgesia in the treatment of acute pain and to replace it with drugs from other groups that are assumed to have a comparable analgesic effect without affecting the immune system. Here, we present a review on the impact of anesthesia, with and without the use of opioids, on the immune response to surgical stress.