The Journal of steroid biochemistry and molecular biology
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J. Steroid Biochem. Mol. Biol. · Apr 2021
DHEA inhibits proliferation, migration and alters mesenchymal-epithelial transition proteins through the PI3K/Akt pathway in MDA-MB-231 cells.
Cancer is one of the leading causes of death worldwide, and breast cancer is the most common among women. Dehydroepiandrosterone (DHEA), the most abundant steroid hormone in human serum, inhibits proliferation and migration of breast cancer cells, modulating the expression of proteins involved in mesenchymal-epithelial transition (MET). However, the underlying molecular mechanisms are not fully understood. ⋯ However, wortmannin and LY294002, inhibitors of the PI3K/Akt pathway, abolished the up- and down-regulation of E- and N-cadherin expression respectively, and inhibition of migration induced by DHEA in MDA-MB-231 cells. The siRNA that blocks the PI3K pathway, abolished the effects of DHEA on proliferation, migration, MET proteins expression and the growth of tumors in nude mice. In conclusion, these results suggest that PI3K/Akt pathway participates in the effects of DHEA on breast cancer cells.
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J. Steroid Biochem. Mol. Biol. · Jan 2021
Cholesterol metabolites and plant sterols in cerebrospinal fluid are associated with Alzheimer's cerebral pathology and clinical disease progression.
Altered cholesterol metabolism is associated with increased risk of neurodegeneration and in particular with the development of Alzheimer's disease (AD). Here, we investigate whether non-cholesterol sterols and oxysterols in the central nervous system are associated with (i) the presence of cerebral AD pathology, (ii) distinct aspects of AD pathology, i.e. amyloid pathology, neuronal injury, and tau pathology, and (iii) cognitive decline over time. ⋯ We show the importance of CSF levels of several non-cholesterol sterols and oxysterols to AD and core AD biomarkers. The plant sterols campesterol and sitosterol appear to be involved in tau pathology and neurodegeneration. CSF desmosterol level indicates CNS cholesterol synthesis and might be of relevance for clinical disease severity. Therefore these non-cholesterol sterols may represent intervention targets to slow down disease progression.
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J. Steroid Biochem. Mol. Biol. · Oct 2020
Randomized Controlled Trial Comparative Study"Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study".
The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19. ⋯ Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer.
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J. Steroid Biochem. Mol. Biol. · Sep 2020
ReviewVitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166.
Coronavirus infection is a serious health problem awaiting an effective vaccine and/or antiviral treatment. The major complication of coronavirus disease 2019 (COVID-19), the Acute Respiratory Distress syndrome (ARDS), is due to a variety of mechanisms including cytokine storm, dysregulation of the renin-angiotensin system, neutrophil activation and increased (micro)coagulation. ⋯ Based on a pilot study, oral calcifediol may be the most promising approach. These studies are expected to provide guidelines within a few months.
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J. Steroid Biochem. Mol. Biol. · Apr 2020
Randomized Controlled TrialPrincipal results of the VITamin D and OmegA-3 TriaL (VITAL) and updated meta-analyses of relevant vitamin D trials.
Whether supplemental vitamin D reduces risk of cancer or cardiovascular disease (CVD) is relatively unexplored in randomized trial settings. The VITamin D and OmegA-3 TriaL (VITAL) was a nationwide, randomized, placebo-controlled, 2 × 2 factorial trial of daily vitamin D3 (2000 IU) and marine omega-3 fatty acids (1 g) in the primary prevention of cancer and CVD among 25,871 U. S. men aged ≥50 and women aged ≥55, including 5106 African Americans. ⋯ Vitamin D did not significantly reduce the co-primary endpoint of major CVD events (HR = 0.97 [0.85-1.12]), other cardiovascular endpoints, or all-cause mortality (HR = 0.99 [0.87-1.12]). Updated meta-analyses that include VITAL and other recent vitamin D trials indicate a significant reduction in cancer mortality but not in cancer incidence or CVD endpoints. Additional research is needed to determine which individuals may be most likely to derive a net benefit from vitamin D supplementation. (VITAL clinicaltrials.gov identifier: NCT01169259).