Sepsis is an organ dysfunction caused by an uncontrolled inflammatory response from the host to an infection. Sepsis is the main cause of morbidity and mortality in intensive care units (ICU) worldwide. One of the first organs to suffer from injuries resulting from sepsis is the brain. The central nervous system (CNS) is particularly vulnerable to damage, mediated by inflammatory and oxidative processes, which can cause the sepsis-associated encephalopathy (SAE), being reported in up to 70% of septic patients. This review aims to bring a summary of the main pathophysiological changes and dysfunctions in SAE, and the main focuses of current experimental studies for new treatments and therapies. The pathophysiology of SAE is complex and multifactorial, combining intertwined processes, and is promoted by countless alterations and dysfunctions resulting from sepsis, such as inflammation, neuroinflammation, oxidative stress, reduced brain metabolism, and injuries to the integrity of the blood-brain barrier (BBB). The treatment is limited once its cause is not completely understood. The patient's sedation is far to provide an adequate treatment to this complex condition. Studies and experimental advances are important for a better understanding of its pathophysiology and for the development of new treatments, medicines, and therapies for the treatment of SAE and to reduce its effects during and after sepsis. Keywords Sepsis . Encephalopathy . Experimental studies . Brain Abbreviations SAE Sepsis-associated encephalopathy ICU Intensive care units CNS Central nervous system BBB Blood-brain barrier TNF-α Necrosis factor alpha IL Interleukins CSF Cerebrospinal fluid ROS Reactive oxygen species NO Nitric oxide RNS Reactive nitrogen species H 2 O 2 Hydrogen peroxide O 2 .

No abstract

No abstract

No abstract

Hepatocellular carcinoma (HCC) is the most prevalent type of tumor among primary liver tumors and is the second highest cause of cancer-related deaths worldwide. Current therapies are controversial, and more research is needed to identify effective treatments. A new synthetic compound, potassium 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-olate (CPBMF65), is a potent inhibitor of the human uridine phosphorylase-1 (hUP1) enzyme, which controls the cell concentration of uridine (Urd). Urd is a natural pyrimidine nucleoside involved in cellular processes, such as RNA synthesis. In addition, it is considered a promising biochemical modulator, as it may reduce the toxicity caused by chemotherapeutics without impairing its anti-tumor activity. Thus, the objective of this study is to evaluate the effects of CPBMF65 on the proliferation of the human hepatocellular carcinoma cell line (HepG2). Cell proliferation, cytotoxicity, apoptosis, senescence, autophagy, intracellular Urd levels, cell cycle arrest, and drug resistance were analyzed. Results demonstrate that, after incubation with CPBMF65, HepG2 cell proliferation decreased, mainly through cell cycle arrest and senescence, increasing the levels of intracellular Urd and maintaining cell proliferation reduced during chronic treatment. In conclusion, results show, for the first time, the ability of a hUP1 inhibitor (CPBMF65) to reduce HepG2 cell proliferation through cell cycle arrest and senescence.