Magnesium (Mg2+) deficiency is probably the most underestimated electrolyte imbalance in Western countries. It is frequent in obese patients, subjects with type-2 diabetes and metabolic syndrome, both in adulthood and in childhood. This narrative review aims to offer insights into the pathophysiological mechanisms linking Mg2+ deficiency with obesity and the risk of developing metabolic syndrome and type 2 diabetes. Literature highlights critical issues about the treatment of Mg2+ deficiency, such as the lack of a clear definition of Mg2+ nutritional status, the use of different Mg2+ salts and dosage and the different duration of the Mg2+ supplementation. Despite the lack of agreement, an appropriate dietary pattern, including the right intake of Mg2+, improves metabolic syndrome by reducing blood pressure, hyperglycemia, and hypertriglyceridemia. This occurs through the modulation of gene expression and proteomic profile as well as through a positive influence on the composition of the intestinal microbiota and the metabolism of vitamins B1 and D.

We have previously shown that the signal peptideless cytokine interleukin 1a (IL-la) may play a role as an intracellular regulator of human endothelial cell senescence (J. A. M. Maier, P. Voulalas, D. Roeder, and T. Maciag, Science 249: [1570][1571][1572][1573][1574] 1990). To investigate the potential intracellular function of IL-lot, transformed endothelial cells were transfected with the human cDNAs that code for the two forms of IL-la, the precursor molecule IL-11-27, and the mature protein IL-11.3-271* The subcellular localization of the two different polypeptides was investigated directly or by using chimeric genes constructed by fusion of different fragments of the IL-la gene and the P-galactosidase open reading frames. The IL-1 113-271 protein was cytoplasmic, while IL-11-271 was nuclear. The basic cluster at the NH2 terminus of IL-1, KVLKKRR, has been shown to mediate IL-lot nuclear targeting. Moreover, nuclear localization of IL-la correlates with impaired cell growth and expression of some IL-la-inducible genes. These results suggest that transport of endogenous intracellular IL-lat has been highlighted by the discovery of an intracellular IL-1 receptor antagonist which is expressed in keratinocytes (17). This protein could function as an intracellular competitor of either internalized or endogenously produced IL-la.To determine whether IL-lat represents an intracellular regulatory molecule in endothelial cells, we transfected transformed endothelial cells (tEC) (46) with plasmids containing the cDNAs that code for IL-11-271 and IL-1 113-271 The subcellular localization of the two forms was investigated directly or by using chimeric genes constructed by fusion of the IL-lot and ,B-galactosidase (P-Gal) open reading frames. IL-11_271 was nuclear, while IL-11,3-271 was cytoplasmic. The sequence responsible for the nuclear targeting of IL-1 is contained within seven amino acid residues at positions 79 to 85. We also determined whether or not the activity of endogenous IL-la correlates with its ability to localize to the nucleus. The following data suggest that transport of IL-la into the nucleus is required for it to modulate endothelial cell properties. MATERIALS AND METHODSPlasmid construction. Most plasmids were constructed by PCR amplification of the IL-la cDNA with primers bearing unique sequence and restriction enzyme sites. Plasmid Cfla, containing the full-length cDNA for IL-lat, was kindly provided by R. Gayle (Immunex, Seattle, Wash.).The primers used to clone IL-lot in pMEXneo (29) were IL-11-271 sense (5'-CCG TCG ACC CAC CAT GGC-3'),

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Purpose In less than one and a half year, the COVID-19 pandemic has nearly brought to a collapse our health care and economic systems. The scientific research community has concentrated all possible efforts to understand the pathogenesis of this complex disease, and several groups have recently emphasized recommendations for nutritional support in COVID-19 patients. In this scoping review, we aim at encouraging a deeper appreciation of magnesium in clinical nutrition, in view of the vital role of magnesium and the numerous links between the pathophysiology of SARS-CoV-2 infection and magnesium-dependent functions. Methods By searching PubMed and Google Scholar from 1990 to date, we review existing evidence from experimental and clinical studies on the role of magnesium in chronic non-communicable diseases and infectious diseases, and we focus on recent reports of alterations of magnesium homeostasis in COVID-19 patients and their association with disease outcomes. Importantly, we conduct a census on ongoing clinical trials specifically dedicated to disclosing the role of magnesium in COVID-19. Results Despite many methodological limitations, existing data seem to corroborate an association between deranged magnesium homeostasis and COVID-19, and call for further and better studies to explore the prophylactic or therapeutic potential of magnesium supplementation. Conclusion We propose to reconsider the relevance of magnesium, frequently overlooked in clinical practice. Therefore, magnesemia should be monitored and, in case of imbalanced magnesium homeostasis, an appropriate nutritional regimen or supplementation might contribute to protect against SARS-CoV-2 infection, reduce severity of COVID-19 symptoms and facilitate the recovery after the acute phase.

More and more studies are accumulating about COVID-19. Some aspects of the pathogenesis of the disease recall events occurring in Mg deficiency, such as a drop of T cells, increased plasma concentration of inflammatory cytokines, and endothelial dysfunction. We hypothesize that a low Mg status, which is rather common, might foment the transition from mild to critical clinical manifestations of the disease. Epidemiological, clinical, and fundamental research is needed to clarify the potential role of Mg deficiency in COVID-19.