Placental and serum levels of human α-Klotho in preeclampsia & intra-uterine growth retardation: A potential sensitive biomarker?

INTRODUCTION: α-Klotho protein has three isoforms: a transmembrane (mKL), a shed- soluble isoform, and a circulating soluble isoform (sKL). mKL is expressed in the kidney and placenta, while sKL is detectable in blood and urine. It is known that α-Klotho levels fluctuate during pregnancy mainly in women with complications such as preeclampsia (PE) and intra-uterine growth restriction (IUGR). METHODS: Forty-nine participants were divided into two groups: healthy and complicated pregnancy (PE, IUGR or both). Tissue samples (2 cm3) from the maternal side, Blood and urine samples were collected during pregnancy and postpartum. Samples were subjected to biochemical (WB), histological (H&E and IHC) staining as well as genetic analysis (qPCR). RESULTS: Blood αKL levels were preserved in both healthy and complicated pregnancies. Significantly lower blood αKL concentrations were found in PE postpartum (PP) compared to levels during pregnancy, and were significantly lower compared with postpartum of a healthy pregnancy. αKL activity was reduced in complicated pregnancies vs. healthy pregnancies. Placen tal mKL levels (ELISA) and expression (WB) were lowered in complicated pregnancies compared with the healthy pregnancies group. Additionally, we found a significant decline in the expression of mKL mRNA in PE/IUGR placentas compared with the healthy group. DISCUSSION: Several studies have focused on the involvement of αKL in normal placentation during pregnancy. Our results suggest lower function of sKL in complicated pregnancy compared with a control, and present differences in placental mKL levels as well as tissue and gene expression between healthy and complicated pregnancy. In light of our results, we conclude that complicated pregnancy is associated with in decline in mKL.

Active vitamin D supplementation and COVID-19 infections: review.

SARS-CoV-2, causing the lethal disease COVid-19, is a public health emergency in the 2020 global pandemic. The outbreak and fast spreading of SARS-CoV-2 have a high morbidity and mortality specifically in elder patients with chronic diseases such as diabetes mellitus, arterial hypertension, chronic kidney disease, and organ transplanted patients with immunosuppressive therapy. Preliminary results support different treatments such as chloroquine and convalescent plasma infusion in severe cases, with good outcome. On the other hand, the efficacy of supplementation with active vitamin D, an immunomodulator hormone with antiinflammatory and antimicrobial effects, is unproven. A recent study reported that vitamin D attains antiviral effects, via blocking viral replication directly. SARS-CoV-2 primarily uses the immune evasion process during infection via the envelope spike glycoprotein, which is followed by a cytokine storm, causing severe acute respiratory disease syndrome and death. SARS-CoV-2, by using the well-known angiotensin-converting enzyme 2 by the protein spike, as the host receptor to enter into alveolar, myocardial, and renal epithelial cells, can be disrupted by vitamin D. However, the correlation between vitamin D levels and COVID-19 deaths in previous studies was insignificant. Retrospective studies demonstrated a correlation between vitamin D status and COVID-19 severity and mortality, while other studies did not find this correlation. Studies have shown that, vitamin D reduces the risk of acute viral respiratory tract infections and pneumonia via direct inhibition of viral replication, antiinflammatory and immunomodulatory effects. The data available today regarding the beneficial protective effect of vitamin D is unclear and with conflicting results. Large randomized control trials are necessary to test this hypothesis. In this review, we will explain the cross talk between the active vitamin D and the angiotensin-converting enzyme 2, and summarize the data from the literature.

Vitamin E and diabetic nephropathy in mice model and humans.

Diabetes mellitus (DM) is associated with increased oxidative stress due to elevated glucose levels in the plasma. Glucose promotes glycosylation of both plasma and cellular proteins with increased risk for vascular events. Diabetic patients suffer from a higher incidence of cardiovascular complications such as diabetic nephropathy. Haptoglobin (Hp) is an antioxidant plasma protein which binds free hemoglobin, thus preventing heme-iron mediated oxidation. Two alleles exist at the Hp gene locus (1 and 2) encoding three possible Hp genotypes that differ in their antioxidant ability, and may respond differently to vitamin E treatment. Several clinical studies to have shown that Hp 1-1 genotype is a superior antioxidant to the Hp 2-2 genotype and Hp 2-2 genotype is associated with a higher incidence of cardiovascular disease. Vitamin E was found to have beneficial effect in patient and mice with Hp 2-2 genotype. In this review we have summarized the results of our studies in patients with diabetic nephropathy treated with vitamin E and in diabetic mice with different haptoglobin genotypes.