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Many progesterone (P4) effects are mediated by its intracellular receptor (PR), which has two isoforms, PR-A and PR-B, each of them with different function and regulation. Differential PR expression in cancer cells has been associated to a PR isoform-specific promoter methylation. In astrocytomas, the most frequent and aggressive brain tumors, PR isoforms expression is directly correlated to the tumor’s...
Imbalanced functions of osteoclasts and osteoblasts are involved in various types of bone damage including postmenopausal osteoporosis. In the present study, we investigated the cellular mechanism by which estrogen interacts in the process of osteoblastic differentiation regulated by BMP-4 using mouse MC3T3-E1 cells that express estrogen receptors (ER) and BMP-4. Estradiol enhanced BMP-4-induced Runx2,...
A series of bufalin 3-nitrogen-containing-ester derivatives (2–6) were designed, synthesized, and evaluated for their proliferation inhibition activities against human cervical epithelial adenocarcinoma (HeLa) and non-small-cell lung cancer (A549) cell lines. The structure–activity relationships (SARs) of this new series were described in this paper. Cytotoxicity data revealed that C3 moiety had important...
In 21-hydroxylase deficiency, urinary metabolites of 21-deoxycortisol, mainly derived from its 11oxo form 21-deoxycortisone, are indicators of intra-adrenal overproduction of 17-hydroxyprogesterone. In affected neonates these metabolites are numerous and most have not been previously described. This work forms the concluding part of a comprehensive study of urinary steroids, aiming to enhance the...
A deproteinized natural cancellous bone mineral (B) was studied in a cell culture model for its anabolic potential using two radiolabelled steroid substrates, 14C-testosterone (14C-T) and 14C-4-androstenedione (14C-4-A) independently; in the presence or absence of the anti-androgen finasteride (F) and minocycline (M). Culture medium was assayed for the biologically active metabolite 5alpha-dihydrotestosterone...
The effects of cholesterol on cell proliferation and adipocytic differentiation have been evaluated for the first time in mouse adipose-derived stromal cells (mASCs). Cholesterol loading by using cholesterol:methyl- β-cyclodextrin (Chol:MβCD) complexes promoted cellular levels of free cholesterol (FC) and cholesteryl ester (CE), induced high cell proliferation of mASCs dose-dependently. Compared with...
The prevalence of Cushing’s syndrome (CS) in at-risk populations in developing countries remains uncertain. Evening urinary cortisol (UFC 22–23 ) and salivary cortisol after treatment with 1-mg DST (SAF dex ) have seldom been used as diagnostic tools in these populations.(1) To establish the prevalence of CS in adults with cortisol-related morbidities using UFC 22–23 and SAF...
A series of final twelve propanoyloxy derivatives of 5β-cholan-24-oic acid (O-propanoyl derivatives of cholic acid) as potential drug absorption modifiers (skin penetration enhancers, intestinal absorption promoters) was generated by multistep synthesis. Structure confirmation of all generated compounds was accomplished by 1 H NMR, 13 C NMR, IR and MS spectroscopy methods. All the...
Synthesis of four novel (4'R)- and (4'S)- 2'-{[(E)-3β-hydroxyandrost-5-en-17-ylidene]-methyl} oxazolines, comprising 4'-hydroxymethyl (1 and 2) and 4'-methoxycarbonyl (3 and 4) substituents is presented. Reaction of 17α-bromo-21-iodo-3β-acetoxypregn-5-en-20-one with either (L)-serine methyl ester, or (D)-serine methyl ester resulted in methyl N-[3β-acetoxy-21-oxopregna-5,17(20)-dien-21-yl]-(L)-serinate...
A simple and practical method for synthesis of the D-ring modified steroidal dienamides (4a–k) from the steroidal α,α-dicyanoalkene 3 and aldehydes via vinylogous aldol reaction was first reported. By using NaOAc as a base, the desired products were obtained in moderate to good yields in ethanol under mild conditions. All the synthesized steroidal dienamides are new and are currently being evaluated...
Increasing resistance of clinically relevant fungi is causing major problems in anti-mycotic therapy. Particularly for immunosuppressed patients fungal infections are of concern and increasing resistance against clinically used antimycotic drugs is hampering successful treatment. In the search for new antifungals ergosterol biosynthesis still is the most prominent target. However, several pitfalls...
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