Morin is a natural polyphenol that was originally isolated from members of the Moraceae family and can be extracted from leaves, fruits, stems and branches of numerous plants. Several evidences demonstrated that Morin could have a benefical effect on several human diseases. In fact, Morin possesses antioxidant, antidiabetic, anti-inflammatory, antitumoral, antihypertensive, antibacterial, hypouricemic, and neuroprotective activity, by modulating the activity of many enzymes. In some cases, Morin exerts a systemic protective action, reducing negative side effects of several drugs, without interfere with their function. In addition, in vitro and in vivo studies, demonstrated that Morin exhibits very low toxicity levels and its chronic administration is well tolerated. All these findings suggest that Morin is a non-toxic, natural compound that could be used, either alone or in combination with other drugs, to prevent many human pathologies.

Type 2 diabetes mellitus (T2DM) is the most prevalent disease and becoming a serious public health threat worldwide. It is a severe endocrine metabolic disorder that has the ability to induce serious complications in all kinds of organs. Although mechanisms of anti-diabetics have been described before, we focus here on the cellular and physiological mechanisms involved in the modulation of insulin and glucose blood levels. As obesity and inflammation are intimately associated with the development of T2DM, their possible relationships are also described. The effects of gut microbiota on insulin resistance have been recently investigated in clinical trials, and we discuss the potential mechanisms by which gut microbiota may improve glucose handling, especially via the metabolism of ingested phytochemicals. Among the historically supported effects of phytochemicals, their therapeutic potential for T2DM leads to consider these natural products as an important pool for the identification of novel anti-diabetic drug leads. This current research extends the descriptions of anti-diabetic effects of plants that are used in traditional medicines or as nutraceuticals. The objective of the present review is to make a systematic report on glucose metabolism in T2DM as well as to explore the relationships between natural phytochemicals and glucose handling.

5-Fluorouracil resistant colon cancer cells are addicted to OXPHOS to survive and enhance stem-like traits

5-Fluorouracil (5-FU) is a key component of chemotherapy for colorectal cancer (CRC). 5-FU efficacy is established by intracellular levels of folate cofactors and DNA damage repair strategies. However, drug resistance still represents a major challenge. Here, we report that alterations in serine metabolism affect 5-FU sensitivity in in vitro and in vivo CRC models. In particular, 5-FU-resistant CRC cells display a strong serine dependency achieved either by upregulating endogenous serine synthesis or increasing exogenous serine uptake. Importantly, regardless of the serine feeder strategy, serine hydroxymethyltransferase-2 (SHMT2)-driven compartmentalization of one-carbon metabolism inside the mitochondria represents a specific adaptation of resistant cells to support purine biosynthesis and potentiate DNA damage response. Interfering with serine availability or affecting its mitochondrial metabolism revert 5-FU resistance. These data disclose a relevant mechanism of mitochondrial serine use supporting 5-FU resistance in CRC and provide perspectives for therapeutic approaches.