Steroids

The cytotoxic dichloromethane-methanol bark extract of Dysoxylum malabaricum was subjected to bioassay-guided fractionation, followed by systematic dereplication to focus on identifying new compounds. From the bark of Dysoxylum malabaricum, two new cycloartane-type triterpenoids were isolated in addition to two previously known triterpenoids. The structuresandabsolute configurations of the isolated compounds were elucidated unambiguously via NMR, HRESIMS data, and electronic circular dichroism calculations...

OBJECTIVES: Glucocorticoids as a drug class are widely used in the treatment of many conditions including more recently as one of the mainstay treatments for the SARS-CoV-2 infection. The physiological adverse effects are well described. However, less is known and understood about the potentially deleterious neuro-cognitive effects of this class of medication. METHODS: We carried out a systematic review of the literature using two separate search strategies. The first focussed on the rates of reporting of adverse cognitive effects of glucocorticoid use in randomised controlled trials...

In this short review we discuss the current view of how the estrogen receptor (ER), a pivotal member of the nuclear receptor superfamily of transcription factors, regulates gene transcription at the single cell and allele level, focusing on in vitro cell line models. We discuss central topics and new trends in molecular biology including phenotypic heterogeneity, single cell sequencing, nuclear phase separated condensates, single cell imaging, and image analysis methods, with particular focus on the methodologies and results that have been reported in the last few years using microscopy-based techniques...

Chronic pain is a worldwide refractory health disease that causes major financial and emotional burdens and that is devastating for individuals and society. One primary source of pain is inflammation. Current treatments for inflammatory pain are weakly effective, although they usually replace available analgesics, such as opioids and non-steroidal anti-inflammatory drugs, which display serious side effects. Emerging evidence indicates that the membrane G protein-coupled estrogen receptor (GPER) may play a crucial role in the regulation of inflammation and pain...

C21 steroidal glycosides are a group of natural compounds with biological activities such as anti-cancer, anti-microbial, and anti-viral properties. In this study, we isolated and determined the structure of a new C21 steroidal glycoside, named Marsdenialongise A from Marsdenia longipes W.T. Wang, using nuclear magnetic resonance spectroscopy and mass spectra data. Marsdenialongise A is a derivative of tenacigenin B and was isolated for the first time from a plant. The inhibitory effect of Marsdenialongise A on cancer cells was evaluated through MTT and cell migration assays, cell cycle, and apoptosis analyses...

OXER1, the receptor for the oxidized arachidonic acid metabolite 5-oxo-ETE has been reported to play a significant role in inflammatory responses, being responsible for leucocyte chemotactic responses. Recently, we have identified OXER1 (GPR170) as a membrane receptor for androgens in prostate and breast cancer cells. Testosterone action via OXER1 induces specific Ca2+ release from intracellular organelles, modifies polymerized actin distribution induces apoptosis and decreases cancer cell migration. These actions are antagonized by 5-oxo-ETE...

BACKGROUND AND AIM: Enhancing vitamin D levels as a crucial modifiable risk factor may provide a critical contribution to prevent susceptibility to various diseases, including musculoskeletal, autoimmune, and inflammatory rheumatic diseases as well as promoting overall health. However, adherence to daily vitamin D supplementation is generally poor, and there are some concerns regarding the high-dose vitamin D supplementation's safety. We aimed to investigate whether a single oral dose of 300,000 IU or consecutive two-day dosing of 300,000 IU each day of cholecalciferol could sufficiently and safely elevate vitamin D levels...

Anti-Müllerian hormone (AMH) is produced exclusively by granulosa cells of ovarian follicles and is an indicator of ovarian reserve which declines with age. Seasonality in AMH levels have been reported to be correlated with variations in Vitamin D levels, which is dependent on sunlight exposure. However, the effects of age and its association with solar radiation intensity with respect to AMH was never studied before. In this study, we investigated the relationship between AMH levels with season and with solar radiation intensity in a cohort of 2235 women aged 19-40 years undergoing hormonal work-up over a four-year period...

Androgens are a class of steroid hormones primarily associated with male sexual development and physiology, but exert pleiotropic effects in either sex. They have a crucial role in various physiological processes, including the regulation of skeletal muscle and adipose tissue homeostasis. The effects of androgens are mainly mediated through the androgen receptor (AR), a ligand-activated nuclear receptor expressed in both tissues. In skeletal muscle, androgens via AR exert a multitude of effects, ranging from increased muscle mass and strength, to the regulation of muscle fiber type composition, contraction and metabolic functions...

The kidney is considered to be one of the most estrogen-responsive, not reproductive organs in the body. Different estrogen receptors (ERs) show sex-specific differences in expression along the nephron and the expression of different ERs also changes with the estrous cycle of the female. The kidney becomes more estrogen-sensitive when estradiol levels are at their highest, just prior to ovulation. This review discusses the different mechanisms by which estradiol can modify the salt and water conservation processes of the kidney through transporter regulation to support the fluid and electrolyte homeostasis changes required in mammalian reproduction...

6β-Hydroxytestosterone is a biomarker for the activity of human cytochrome P450 3A4 (P450 3A4), the major drug metabolizing cytochrome P450 enzyme. Despite its significance, efficient routes for the chemical synthesis of 6β-hydroxytestosterone are rare. In this study, 6β-hydroxytestosterone was synthesized through the oxidation of a 3,5-diene precursor under the Uemura-Doyle reaction conditions using a dirhodium catalyst in the presence of tert-butylhydroperoxide. Mechanistic studies showed that some oxygen is incorporated from molecular oxygen and C-H abstraction is partially rate-limiting...

Two new withanolides, (17R,20S,22R)-4β-acetoxy-5β,6β-epoxy-27-hydroxy-1-oxo-witha-2,24-dienolide (5) and (17R,20S,22R)-5β,6β-epoxy-27-hydroxy-1,4-dioxo-witha-24-enolide (9), and seven known withanolides with normal structure (3-9) were isolated from aerial parts of Cuatresia colombiana. Several semisynthetic derivatives were prepared from the natural metabolites withaferin A and jaborosalactone 38. The compounds were fully characterized by a combination of spectroscopic methods (1D and 2D NMR and MS)...

Salmonella is a Gram-negative bacterium that causes gastrointestinal diseases in 20 to 40 million people globally. Stemmoside C is a steroidal glycoside isolated from Argel, although its antibacterial and antibiofilm properties have not been studied. The antibacterial activity of Stemmoside C against Salmonella enterica was revealed, where MIC of the compound was 16 μg/mL (0.15 µM). Biofilm-associated Stemmoside C treatment destroyed S. typhi cells and reduced viable S. typhi numbers below detectable levels...

Several clinical studies have shown an association between vitamin D deficiency and painful diabetic peripheral neuropathy (DPN). However, it is still unclear whether vitamin D status and inflammatory markers correlate in patients with painful DPN. In this context, we aimed to investigate the associations between serum vitamin D levels and inflammatory status in Kurdish type 2 diabetes patients (T2DM) with painful DPN and without painful DPN. A clinical case-control study was conducted on 86 Kurdish patients with T2DM...

Substantial progress has been made in our understanding of the nongenomic actions, ligand binding, intracellular signaling pathways, and functions of membrane progesterone receptors (mPRs) in reproductive and nonreproductive tissues since their discovery 20 years ago. The five mPRs are members of the progestin adipoQ receptor (PAQR) family which also includes adiponectin receptors (AdipoRs). However, unlike AdipoRs, the 3-D structures of mPRs are unknown, and their structural characteristics remain poorly understood...

Mineralocorticoid receptor (MR) antagonists have shown remarkable benefits in the treatment of cardiovascular disease. However, their underutilization in clinical practice may be attributed to concerns regarding the risk of hyperkalemia. An ideal selective MR modulator would inhibit the detrimental effects of MR in these non-epithelial cells while sparing its physiological function in kidney epithelial cells, thereby reducing the risk of adverse events. To address this issue, a new generation of non-steroidal MR antagonists, including esaxereneone, balcinrenone, ocedurenone, and finerenone, has been developed with distinct molecular structures and pharmacology...

An active form of vitamin D3 (1,25-dihydroxyvitamin D3 ) acts through vitamin D receptor (VDR) initiating genomic response, but several studies described also non-genomic actions of 1,25-dihydroxyvitamin D3 , implying the role of PDIA3 in the process. PDIA3 is a membrane-associated disulfide isomerase involved in disulfide bond formation, protein folding, and remodeling. Here, we used a transcriptome-based approach to identify changes in expression profiles in PDIA3-deficient squamous cell carcinoma line A431 after 1,25-dihydroxyvitamin D3 treatment...

Endocrine disrupting Chemicals (EDCs) are substances that interfere with hormones by several mechanisms including receptor activation or antagonism, changes in gene and protein expression, modification of signal transduction, and/or epigenetic modifications in hormone-producing cells. A survey conducted by the European Union in a Northern Italian region led to the discovery of a large environmental contamination of drinking water by perfluoroalkyl substances (PFAS). As the exposed population showed a high prevalence of arterial hypertension and cardiovascular disease, we decided to investigate if PFAS could enhance the biosynthesis of aldosterone...

Four previously undescribed steroidal saponins named govanosides C-F (1-4) and nine known compounds (5-13) were isolated from the rhizomes of Trillium govanianum Wall. ex D.Don. Govanosides C-E contained a rare sugar moiety i.e., 6-deoxy allose, while govanoside F has acetylated rhamnose moiety in its glycan part. Also, this is the first report on the isolation of feruloyl sucrose derivatives (11-12) and (E)-4-hydroxy-dodec-2-enedioic acid (13) from the Trillium genus. The structure of isolated compounds was deduced using 1D and 2D NMR, HRESIMS, LC-MS/MS, GC-MS, and saccharide linkage analysis...

Glucocorticoids are stress hormones that play central roles in the immediate and slower adaptive responses of the brain and body to new behavioral experience. The exact mechanisms by which the rapid and slow processes underlying glucocorticoid mnemonic effects unfold are under intensive scrutiny. It is possible that glucocorticoids rapidly modify memory representations in the brain by interfering with synaptic functions between inhibitory and excitatory neurons in a timing and context dependent manner. In particular, activity-dependent trans-synaptic messengers appear to have all the necessary attributes to engage in the rapid signaling by glucocorticoids and regulate the brain and behaviors...