From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?

Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host’s metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host’s immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.

     

Climatic influences on cardiovascular diseases

Classical risk factors only partially account for variations in cardiovascular disease incidence; therefore, also other so far unknown features, among which meteorological factors, may influence heart diseases (mainly coronary heart diseases, but also heart failure, arrhythmias, aortic dissection and stroke) rates. The most studied phenomenon is ambient temperature. The relation between mortality, as well as cardiovascular diseases incidence, and temperature appears graphically as a ‘‘U’’ shape. Exposure to cold, heat and heat waves is associated with an increased risk of acute coronary syndromes. Other climatic variables, such as humidity, atmospheric pressure, sunlight hours, wind strength and direction and rain/snow precipitations have been hypothesized as related to fatal and non-fatal cardiovascular diseases incidence. Main limitation of these studies is the unavailability of data on individual exposure to weather parameters. Effects of weather may vary depending on other factors, such as population disease profile and age structure. Climatic stress may increase direct and indirect risks to human health via different, complex pathophysiological pathways and exogenous and endogenous mechanisms. These data have attracted growing interest because of the recent earth’s climate change, with consequent increasing ambient temperatures and climatic fluctuations. This review evaluates the evidence base for cardiac health consequences of climate conditions, and it also explores potential further implications.     

Synthesis of 5,6‐dihydro‐4H‐benzo[d]isoxazol‐7‐one and 5,6‐dihydro‐4H‐isoxazolo[5,4‐c]pyridin‐7‐one Derivatives as Potential Hsp90 Inhibitors

A novel class of 5,6‐dihydro‐4H‐benzo[d]isoxazol‐7‐ones and 5,6‐dihydro‐4H‐isoxazolo[5,4‐c]pyridin‐7‐ones was designed, synthesized, and assayed to investigate the affinity toward Hsp90 protein. The synthetic route was based on a 1,3‐dipolar cycloaddition of nitriloxides, generated in situ from suitable benzaldoximes, with 2‐bromocyclohex‐2‐enones or 3‐bromo‐5,6‐dihydro‐1H‐pyridin‐2‐ones. Whereas all the compounds bearing a benzamide group on the bicyclic scaffold were devoid of activity, the derivatives carrying a resorcinol‐like fragment showed a remarkable inhibitory effect on Hsp90. Docking calculations were performed to investigate the orientation of the new compounds within the binding site of the enzyme.