Ricerc@Sapienza

Necroptosis is a caspases-independent programmed cell death displaying intermediate features between necrosis and apoptosis. Albeit some physiological roles during embryonic development such tissue homeostasis and innate immune response are documented, necroptosis is mainly considered a pro-inflammatory cell death. Key actors of necroptosis are the receptor-interacting-protein-kinases, RIPK1 and RIPK3, and their target, the mixed-lineage-kinase-domain-like protein, MLKL. The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated.

Cancer may complicate the clinical course of non-valvular atrial fibrillation (AF) but its association with cardiovascular events (CVEs) is still unclear. We performed a prospective cohort study including 2092 consecutive AF patients on vitamin K antagonists. Principal endpoint was the occurrence of CVEs including fatal/non-fatal myocardial infarction (MI) and ischemic stroke/TIA and cardiovascular death. Secondary endpoints were major adverse cardiac events (MACE) and thromboembolism (TE).

Hydrogen sulfide (H2S), after nitric oxide (NO) and carbon monoxide (CO), is known as the third gasotransmitter. Involved in antioxidant protection and regulation of different physiological functions, H2S is synthesized by cystathionine β-synthase (CBS) and few other enzymes, and is oxidatively catabolized in the mitochondrion, where H2S-derived electrons are transferred to coenzyme Q by sulfide quinone oxidoreductase (SQR), stimulating respiration and ATP production. Metabolic and oncologic diseases are related to dysregulation of H2S metabolism.

Hydrogen sulfide (H2S) plays key roles in human (patho)physiology. Synthesized endogenously by known enzymatic systems, H2S is mainly metabolized through a mitochondrial sulfide-oxidizing pathway that comprises sulfide:quinone oxidoreductase (SQR) and a few other enzymes. H2S degradation through this pathway is coupled to electron injection into the respiratory chain and, thus, to stimulation of ATP synthesis. In cancer cells, H2S was reported to be synthesized at high levels and to stimulate energy metabolism and cell proliferation.

Hydrogen sulfide (H2S), a known inhibitor of cytochrome c oxidase (CcOX), plays a key signaling role in human (patho)physiology.
H2S is synthesized endogenously and mainly metabolized by a mitochondrial sulfide-oxidizing pathway including sulfide:quinone
oxidoreductase (SQR), whereby H2S-derived electrons are injected into the respiratory chain stimulating O2 consumption and ATP
synthesis. Under hypoxic conditions, H2S has higher stability and is synthesized at higher levels with protective effects for the cell.

Sulfane sulfur species comprise a variety of biologically relevant hydrogen sulfide (H2S)-derived species, including per- and poly-sulfidated low molecular weight compounds and proteins. A growing body of evidence suggests that H2S, currently recognized as a key signaling molecule in human physiology and pathophysiology, plays an important role in cancer biology by modulating cell bioenergetics and contributing to metabolic reprogramming.

PROteolysis TArgeting Chimeras (PROTACs) are heterobifunctional molecules that trigger the poly-ubiquitination of the protein of interest (POI) inducing its degradation via the recruitment of the ubiquitin-proteasome system, thus suppressing the POI's intracellular levels and indirectly all its functions. Recently, one of the fields where the protein knockdown induced by PROTACs has demonstrated to serve as a promising biochemical tool and to provide new opportunities for drug discovery is the epigenetics (epi-PROTACs).

Introduction: Diet may influence various aspects of human health. In fact, it is well known that diet can favour or not the development of various human pathologies, like diabetes, hypertension, and hypercholesterolaemia. Interestingly, diet has an influence in cancer development too (e.g., this relation has been studied for pancreatic, colonic, gastric, and breast cancers). Between the mechanisms that could explain this relation, there is epigenetic.

Cardiovascular diseases, chronic obstructive pulmonary diseases, diabetes, rheumatoid arthritis, and cancer are the most common noncommunicable diseases (NCDs). These NCDs share risk factors with periodontal disease (PD), a preventable risk factor linked to lifestyle. The discussion regarding the association between these chronic diseases is more complex. There is still a significant knowledge gap particularly of the causal relationship between PD and NCDs.