Steroid Molecule Research Articles

New Paradigms in Brassinosteroids, Strigolactones, Sphingolipids, and Nitric Oxide Interaction in the Control of Lateral and Adventitious Root Formation.

The root system is formed by the primary root (PR), which forms lateral roots (LRs) and, in some cases, adventitious roots (ARs), which in turn may produce their own LRs. The formation of ARs is also essential for vegetative propagation in planta and in vitro and for breeding programs. Root formation and branching is coordinated by a complex developmental network, which maximizes the plant's ability to cope with abiotic stress. Rooting is also a response caused in a cutting by wounding and disconnection from the donor plant. Brassinosteroids (BRs) are steroid molecules perceived at the cell surface. They act as plant-growth-regulators (PGRs) and modulate plant development to provide stress tolerance. BRs and auxins control the formation of LRs and ARs. The auxin/BR interaction involves other PGRs and compounds, such as nitric oxide (NO), strigolactones (SLs), and sphingolipids (SPLs). The roles of these interactions in root formation and plasticity are still to be discovered. SLs are carotenoid derived PGRs. SLs enhance/reduce LR/AR formation depending on species and culture conditions. These PGRs possibly crosstalk with BRs. SPLs form domains with sterols within cellular membranes. Both SLs and SPLs participate in plant development and stress responses. SPLs are determinant for auxin cell-trafficking, which is essential for the formation of LRs/ARs in planta and in in vitro systems. Although little is known about the transport, trafficking, and signaling of SPLs, they seem to interact with BRs and SLs in regulating root-system growth. Here, we review the literature on BRs as modulators of LR and AR formation, as well as their crosstalk with SLs and SPLs through NO signaling. Knowledge on the control of rooting by these non-classical PGRs can help in improving crop productivity and enhancing AR-response from cuttings.

Production of 11α-Hydroxysteroid Derivatives by Corynebacterium glutamicum Expressing the Rhizopus oryzae Hydroxylating System.

Hydroxylation of steroids has acquired special relevance for the pharmaceutical industry. Particularly, the 11α-hydroxylation of steroids is a process of biotechnological importance currently carried out at industrial scale for the production of contraceptive drugs and glucocorticoids. This process is performed by several fungal species including Rhizopus nigricans, Aspergillus ochraceus, Aspergillus niger, and Rhizopus oryzae that are used to produce by biotransformation hydroxylated steroids for pharmaceutical purposes (Wang et al., J Steroid Biochem Mol Biol 171:254-261, 2017). However, the development of more efficient biotransformation processes is essential since the steroidal derivatives obtained by the in vivo hydroxylation are often a mixture of hydroxylated compounds in different positions of the steroid molecule. This phenomenon is due to the large number of different CYPs contained in the fungal strains.The genes responsible for the 11α-hydroxylase activity in R. oryzae consisting in the cytochrome CYP509C12 and its redox partner, the reductase RoCPR1, have been chemically synthetized forming a synthetic operon named FUN optimized to be expressed in bacteria. To express this operon, we have selected the strain Corynebacterium glutamicum R31 that is a robust and GRAS bacterial strain widely used for industrial purposes. The synthetic operon has been cloned in the pECXK-99E vector, yielding pXKFUN plasmid, and transformed C. glutamicum R31 to generate C. glutamicum R31 (pXKFUN) strain. This strain is not a steroid degrader and can efficiently transport C19 and C21 steroids across the cytoplasmic membrane (García-Fernandez et al. Catalysts 316:1-12, 2017). C. glutamicum can be used as a clean host for steroid biotransformation, because it does not introduce additional undesired side reactions on the steroids, thus reducing the contamination of the final products (Felpeto-Santero et al., Microbiol Biotechnol 12:856-868, 2019). Here we show a proof of concept that C. glutamicum can be used as a suitable chassis to perform steroid biotransformation expressing eukaryotic cytochromes. The protocol below provides detailed information on steroid 11α-hydroxylations by Corynebacterium recombinant strain.

Biocatalysis of Steroids by Mycobacterium sp. in Aqueous and Organic Media.

Mycobacterium sp. can convert steroids such as β-sitosterol, campesterol, and cholesterol, by selective side-chain cleavage and oxidation of the C3 hydroxyl group to a ketone, into key intermediates that can be easily functionalized to yield commercially interesting pharmaceutical products. In aqueous systems, the biocatalysis is limited by the low solubility of the steroids in water. Several strategies have been introduced to tackle this limitation, e.g., formation of cyclodextrin-steroid complexes and generation of aqueous microdispersions with steroid particle size in the range of hundreds of nanometers. Still, the introduction of an organic phase acting as a substrate and/or product reservoir is a well-established and relatively easy to implement strategy to overcome the sparing water solubility of steroid molecules. However, the organic phase has to be carefully chosen to prevent tampering with the activity/viability of microbial cells.In this chapter, we describe the methodology for the biocatalysis of β-sitosterol to 4-androstene-3,17-dione (AD) and 1,4-androstadiene-3,17-dione (ADD), both in aqueous and organic:aqueous systems. In the latter case, both traditional organic solvents and green solvents are proposed.

The Role of Glucocorticoids in Breast Cancer Therapy.

Glucocorticoids (GCs) are anti-inflammatory and immunosuppressive steroid molecules secreted by the adrenal gland and regulated by the hypothalamic-pituitary-adrenal (HPA) axis. GCs present a circadian release pattern under normal conditions; they increase their release under stress conditions. Their mechanism of action can be via the receptor-independent or receptor-dependent pathway. The receptor-dependent pathway translocates to the nucleus, where the ligand-receptor complex binds to specific sequences in the DNA to modulate the transcription of specific genes. The glucocorticoid receptor (GR) and its endogenous ligand cortisol (CORT) in humans, and corticosterone in rodents or its exogenous ligand, dexamethasone (DEX), have been extensively studied in breast cancer. Its clinical utility in oncology has mainly focused on using DEX as an antiemetic to prevent chemotherapy-induced nausea and vomiting. In this review, we compile the results reported in the literature in recent years, highlighting current trends and unresolved controversies in this field. Specifically, in breast cancer, GR is considered a marker of poor prognosis, and a therapeutic target for the triple-negative breast cancer (TNBC) subtype, and efforts are being made to develop better GR antagonists with fewer side effects. It is necessary to know the type of breast cancer to differentiate the treatment for estrogen receptor (ER)-positive, ER-negative, and TNBC, to implement therapies that include the use of GCs.

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements.

Overcoming the challenges of poor aqueous solubility of active pharmaceutical ingredients (APIs) is necessary to render them bioavailable. This study addresses the poor solubility of two potent steroid hormones, 17β-estradiol (BES) and progesterone (PRO), via their complexation with two water-soluble native cyclodextrins (CDs) namely β-CD and γ-CD. The hydrated inclusion complexes β-CD·BES, β-CD·PRO, γ-CD·BES and γ-CD·PRO were prepared via kneading and co-precipitation, and 1H NMR spectroscopic analysis of solutions of their pure complex crystals yielded the host-guest stoichiometries 2:1, 2:1, 1:1 and 3:2, respectively. Both powder X-ray diffraction (PXRD) and single-crystal X-ray diffraction (SCXRD) were employed for focused studies of the isostructurality of the CD complexes with known complexes and structural elucidation of the new complexes, respectively. SCXRD analyses of β-CD·BES, β-CD·PRO and γ-CD·PRO at 100(2) K yielded the first crystal structures of CD complexes containing the hormones BES and PRO, while the complex γ-CD·BES was readily shown to be isostructural with γ-CD·PRO by PXRD. Severe disorder of the encapsulated steroid molecules in the respective channels of the CD molecular assemblies was evident, however, preventing their modelling, but combination of the host-guest stoichiometries and water contents of the four hydrated inclusion complexes enabled accurate assignment of the chemical formulae of these ternary systems. Predicted electron counts for the complexed molecules BES and PRO correlated reasonably well with the complex compositions indicated by 1H NMR spectroscopy. Subsequent measurements of the aqueous solubilities of the four complexes confirmed significant solubility improvements effected by encapsulation of the steroids within the CDs, yielding solubility enhancement factors for BES and PRO in the approximate range 5-20.

Assessment of Phytochemical and Antimicrobial Activity of Withania somnifera (Ashwagandha)

Withania somnifera L. (Dunal), a member of the Solanaceae family, has been used by Ayurvedicpractitioners for thousands of years. The root of Withania somnifera contains flavonoids,alkaloids, steroids, and other useful functional components. It contains a high concentration ofbioreactors, or secondary metabolites, such as steroidal lactones, alkaloids, and flavonoids, all ofwhich have beneficial properties and are used in ninety Ayurvedic formulations. Ashwagandhahas long been recognized as a potent rejuvenator, general health tonic, and treatment for awide range of ailments. It is a sedative, diuretic, and anti-inflammatory herb that is well knownfor increasing energy and endurance while also acting as an adaptogen with high immunestimulatory and anti-stress properties. Ashwagandha is used to treat colds, cough, emaciation,diabetes, conjunctivitis, epilepsy, insomnia, senile dementia, leprosy, Parkinson’s disease,mental disorders, rheumatic, arthritis, intestinal infections, bronchitis, asthma, impotence, andalso used as HIV/AIDS suppressant. According to the Indian Herbal System, ashwagandha isone of the most important herbs and the best adaptogenic (Ayurveda). Withanolide is made upof steroidal molecules that are supposed to help with inflammation. Ashwagandha boosts theimmune system, reduces inflammation, improves cognition, and promotes overall health andwell-being. Ashwagandha is a shrub that promotes bone marrow and sperm production, as wellas acting as an anti-aging. By using the agar well diffusion method, the antibacterial activity ofdifferent solvent extracts of Withania somnifera stem was assessed against the gram-negativebacteria Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. When testedagainst several test microorganisms, all of the extracts showed strong antibacterial activity. E.coli was the investigation’s most vulnerable bacterium, and all of the plant extracts displayedzones of inhibition when used against it. The methanol extract of W. somnifera stem and leafhad the strongest antibacterial effect against E.coli, followed by S. aureus and Pseudomonas.All bacterial strains were least inhibited by DH2O extract. The MIC of the extracts that wererecorded ranged from 8 mm to 26 mm. In the current experiment, methanol extract had thelowest MIC value (8 mm) against S. aureus and Pseudomonas. Different phytochemicals werefound in different extracts of Withania according to qualitative phytochemical analysis. Severalstudies have found that Ashwagandha has anti-tumor and anti-inflammatory properties. It has asignificantly greater steroidal than hydrocortisone, which is a typical cancer treatment.

Evaluation of action of steroid molecules on SARS-CoV-2 by inhibiting NSP-15, an endoribonuclease.

Many countries in the world have recently experienced an outbreak of COVID-19, turned out to be a pandemic which significantly affected the world economy. Among many attempts to treat/control infection or to modulate host immunity, many small molecules including steroids were prescribed based on their use against other viral infection or inflammatory conditions. A recent report established the possibility of usage of a corticosteroid against the virus through inhibiting NSP-15; an mRNA endonuclease of SARS-CoV-2 and thereby viral replication. This study aimed to identify potential anti-viral agents for the virus through computational approaches and to validate binding properties with the protein target through molecular dynamics simulation. Unlike the conventional approaches, dedicated data base of steroid like compounds was used for initial screening along with dexamethasone and cortisone, which are used in the treatment of COVID-19 affected population in some countries. Molecular docking was performed for three compounds filtered from data base in addition to dexamethasone and Cortisone followed by molecular dynamics simulation analysis to validate the dynamics of binding at the active site. In addition, analysis of ADME properties established that these compounds have favorable drug-like properties. Based on docking, molecular dynamics simulation studies and various other trajectory analyses, compounds that are identified could be suggested as therapeutics or precursors towards designing new anti-viral agents against SARS-CoV-2, to combat COVID-19. Also, this is an attempt to study the impact of steroid compounds on NSP-15 of SARS-CoV-2, since many steroid like compounds are used during the treatment of COVID-19 patients.

(1S,3R)-N-{(3S,10S,12S,13R,17R)-12-Hy-droxy-17-[(R)-5-hy-droxy-pentan-2-yl]-10,13-di-methyl-hexa-deca-hydro-1H-cyclo-penta-[a]phenanthren-3-yl}adamantane-1-carboxamide 0.25-hydrate.

The title compound, C35H57NO3·0.25H2O, was synthesized from de-oxy-cholic acid followed by a protection, a Mitsonobu substitution, a Staudinger reduction, formation of an amide and final reduction in the lateral chain. The compound crystallizes in the P1 space group with four steroid mol-ecules and one water mol-ecule in the triclinic cell unit. The crystal structure features O-H⋯O hydrogen bonding. The crystal studied was refined as a non-merohedral twin.

Structural comparison of the cytochrome P450 enzymes CYP106A1 and CYP106A2 provides insight into their differences in steroid conversion.

Understanding the structural basis of the selectivity of steroid hydroxylation requires detailed structural and functional investigations on various steroid hydroxylases with different selectivities, such as the bacterial cytochrome P450 enzymes. Here, the crystal structure of the cytochrome P450 CYP106A1 from Priestia megaterium was solved. CYP106A1 exhibits a rare additional structural motif of a cytochrome P450, a sixth β-sheet. The protein was found in different unusual conformations corresponding to both open and closed forms even when crystallized without any known substrate. The structural comparison of CYP106A1 with the previously investigated CYP106A2, including docking studies for both isoforms with the substrate cortisol, reveals a completely different orientation of the steroid molecule in the active sites. This distinction convincingly explains the experimentally observed differences in substrate conversion and product formation by the two enzymes.

Bile acid-based advanced drug delivery systems, bilosomes and micelles as novel carriers for therapeutics.

Diabetes mellitus affects almost half a billion patients worldwide and results from either destruction of β-cells responsible for insulin secretion or increased tissue resistance to insulin stimulation and the reduction of glycemic control. Novel drug delivery systems can improve treatment efficacy in diabetic patients. The low aqueous solubility of most oral antidiabetic drugs decreases drug bioavailability; therefore, there is a demand for the use of novel methods to overcome this issue. The application of bile acids mixed micelles and bilosomes can provide an enhancement in drug efficacy. Bile acids are amphiphilic steroidal molecules that contain a saturated tetracyclic hydrocarbon cyclopentanoperhydrophenanthrene ring, and consist of three 6-membered rings and a 5-membered ring, a short aliphatic side chain, and a tough steroid nucleus. This review offers a comprehensive and informative data focusing on the great potential of bile acid, their salts, and their derivatives for the development of new antidiabetic drug delivery system.

In Silico Approach: Effect of the Oxidation Iron State (Heme-Group) in Steroidogenesis Pathways

One of the main design features of enzyme regulators for the CYPs is the presence of a heme-group and different oxidation states in iron atoms. The selective inhibition of a CYP-enzyme can help to reduce the formation of steroidal molecules that causes undesirable disorders and is, therefore a topic of great biochemical-pharmaceutical interest. The present work carried out an analysis of effect on the coupling-energy of the iron core according to its changes from oxidation Fe(II) to Fe(III) state, over inhibitors and substrates, in a particular enzyme. Two crystals from CYP21A2, CYP11A1, CYP17A1 and CYP19A1 enzymes were selected, assigning the oxidation states separately in each case. It was highlighted that for CYP11A1 and CYP19A1 enzymes, no significant difference was observed in coupling energies between Fe oxidation state and crystal stereo-disposition. This last can be used to analyze their congruence towards the reported biological data. For CYP17A1, the ideal crystal for inhibitors design is 6CHI since the crystal with 4NKV presented differences in all the molecules analyzed since the oxidation state of the iron atom changes the molecule's orientation in the enzyme coupling. In contrast, in CYP21A2, no changes were observed. A greater biological congruence with 5BVU was observed because the coupling energies concur with the selectivity of the enzyme towards its endogenous substrates and reported inhibitors. It was concluded that the effect of the oxidation state of iron on the Binding Coupling Energy (BCE) depends directly on the functional groups attached to the steroidal molecule and their stereo-disposition.

Morphological behavior of fullerene‐steroid hybrid derivatives

Over the years, fullerene has been covalently linked to other polar structures, increasing its aqueous solubility, thereby improving its potential use for biological and biomedical applications. Here, we report on the self‐organization characteristics in water of fullerene‐steroid hybrid derivatives with broad structural features. A library of 12 hybrid derivatives was prepared and classified into three groups: (1) mono adducts with only one steroid molecule and one fullerene moiety fused; (2) hybrids bearing wings with one fullerene moiety and two steroid molecules; and (3) a structure with two fullerene moieties linked to one steroid molecule and a mixture of two different monoaducts where C60‐malonate is attached to the A or D ring of steroid moiety. Different spectroscopic techniques characterized all synthesized fullerene derivatives, such as nuclear magnetic resonance (NMR) experiments (1H and 13C), Fourier transform infrared spectroscopy (FTIR), and high‐resolution mass spectrometry (HRMS). The morphology of the derivatives in aqueous solution was determined by transmission electron microscopy (TEM). In general, all the derivatives were organized into spherical nanoscale structures, where the structural characteristics defined the particle size distribution (PSD), showing a broad range of sizes from 6 to over 50 nm, and only a low percentage of larger particles were observed. The presence of dehydroepiandrosterone moieties in fullerene derivatives bearing wings and the increase in lipophilicity conferred by two C60 in the same structure induced more homogeneous and smaller particles, ranging from 6 to 20 nm. A preliminary computational study of the wing aggregates IIb showed that theoretical curve aggregates are more stable than linear ones supporting our TEM and PDS results.

Abstract 3356: Comparative analysis of approved and undertrial SERDs in estrogen receptor-α (ERα): An in-silico approach

Abstract Background: Despite recent advancements in early detection and treatment, breast cancer is the second most common cancer affecting women globally, with 11.7% of total new cases. The disease is the fifth leading cause of cancer mortality worldwide, with 685,000 deaths in 2020. Approximately 75% of all breast cancer are ERα positive and resistant to current therapies like aromatase Inhibitors (AIs) and selective receptors modulators (SERMs). The selective estrogen receptor degrader (SERDs) ability to antagonize and degrade ERα makes them promising therapeutic agents for hormone-refractory breast cancer treatment. Fulvestrant is the only SERD with steroidal core currently approved for ER-positive breast cancer treatment. However, its poor physicochemical properties limit its efficacy. Many non-steroidal SERDs such as Amcenestrant, Elacestrant, Camizestrant, Giredestrant, and LSZ102 are under various advanced development stages. However, their long-term efficacy is yet to be established. Our in- silico studies aim to evaluate and compare multiple SERDs (approved and under trial) in terms of their shape similarity, binding mechanism, and stability with ERα receptor. Methods: Present work focuses on evaluating and comparing the shape similarity and electrostatic potential of various SERDs with respect to ERα endogenous ligand; estradiol (E2). Docking studies were performed to understand the binding mode of selected SERDs within the active site of ERα. Additional parameters like root-mean square-square deviation (RMSD), root-mean square-fluctuation (RMSF), pocket volume fluctuations, and protein-ligand binding energy were calculated using Molecular Dynamics (MD) simulation techniques to understand the stability and binding mechanism of various SERDs. Result: Among various evaluated SERDs, Fulvestrant shares the highest whereas Elacestrant shares the lowest shape similarity with E2. All docked SERDs cores occupy the same binding pocket and tend to bind in a similar fashion as E2, with their tail protruding towards helix 12 (H12). As observed interactions with H12 are mainly responsible for ERα downregulation. However, in MD studies analysis, it was found that non-steroidal core molecules were less stable and showed more fluctuations (within active site) than steroidal core molecule (Fulvestrant). Moreover, protein-ligand binding energy for Fulvestrant was found to be lower which corresponds to its higher stability with ERα. Conclusion: The current study helps us to understand the binding mechanism, antagonism, and downregulation of multiple SERDs, among which Fulvestrant showed the highest binding affinity towards ERα (due to its highest shape similarity with E2) and can interact with and disrupt H12 (due to its long tail) which is a critical component of SERD. This knowledge could further be used to develop novel SERDs for ESR1 mutant and HR-positive breast cancer treatment. Citation Format: Vishal Unadkat, Shishir Rohit, Parva Purohit, Chirag Mehta, Vishal Goswami, Mahesh Barmade, Sonam Sinha, Ganesh Sangle. Comparative analysis of approved and undertrial SERDs in estrogen receptor-α (ERα): An in-silico approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3356.

Isolation, characterizations, and antimicrobial activities of a phytosterol Dendrosterone isolated from plant Dendrobium ochreatum

Background- The present work aimed to isolate one steroidal molecule from Dendrobium ochreatum. From phytochemical analysis, the presence of steroids was observed only in chloroform extracts of the stem, and the antimicrobial activities supported the extracts to be the most significant one, so work was aimed at isolating the chloroform extracts of the stem. MethodAbout 250 gm of each leaf stem and root powder was filled in the thimble and extracted with hexane, chloroform, and ethanol using a Soxhlet extractor for 72 hrs. The extract solution was filtered through Whatman filter paper no.1, then concentrated using a rotary flash evaporator and stored in the refrigerator. All total of nine (9) extracts were prepared, and out of these nine extracts, the phytochemical analysis suggested the presence of phytosterol in the chloroform extract of the stem (SCDO). Therefore, the isolation was carried out for this particular extract. ResultThe isolated compound was subjected to crystallization, and the melting point was found to be 242-244⁰C. The structure of the compound was determined by spectral analysis like U.V., I.R., N.M.R., Mass Spectroscopy, and lastly, X-Ray Crystallography. All the spectral data proved the compound to be a phytosterol/steroids “Dendrosterone” (molecular formula=C29H44O5; molecular weight = 472.66). ConclusionThis isolated steroid was further screened for antimicrobial activity (for the first time) against different gram +ve, and -ve strains of bacteria and other strains of fungi, and this phytosterol was found to be active against B.subtilis, and C. albincas among all the organisms tested.

Discovery of novel rost-4-ene derivatives as potential plant activators for preventing phytopathogenic bacterial infection: Design, synthesis and biological studies.

Gradually aggravated disease caused by phytopathogenic bacteria severely restricts food security and crop yield, and few pesticides can relieve this severe situation. Thus, development and excavation of new agrochemicals with high bioactivity and novel action mechanism may be a feasible strategy to control intractable bacterial diseases. As a privileged molecular framework, steroid molecules exhibit diversiform bioactivities. Herein, a series of novel androst-4-ene derivatives were designed, synthesised and investigated for their antibacterial behaviour to excavate novel agrochemicals on the base of steroid molecules. Bioassay results indicated that target compounds displayed high bioactivities toward three destructive phytopathogenic bacteria, including Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac) and Pseudomonas syringae pv. actinidiae (Psa). Compound III19 displayed excellent in vitro antibacterial profiling (EC50 =2.37 mg L-1 towards Xoo, EC50 =2.10mg L-1 towards Xac, EC50 =9.50 mg L-1 towards Psa). Furthermore, compound III19 showed outstanding in vivo protective activities, with values of 81.81% and 58.75% towards kiwifruit bacterial canker and rice bacterial leaf blight, respectively. Analysis of the antibacterial mechanism disclosed that compound III19 enhanced host defence enzyme activities superoxide dismutase (SOD), peroxidase (POD), phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), and catalase (CAT) and increased the salicylate synthase content to induce host resistance. In addition, compound III19 increased the membrane permeability, destroyed the cell membrane and killed the bacteria. Given these profiles of target compounds, we highlight a new strategy for controlling intractable plant bacterial diseases by inducing plant resistance and targeting the bacterial cell membrane. © 2022 Society of Chemical Industry.

PENGGUNAAN KORTIKOSTEROID PADA SINDROM HELLP

Background: Hypertension in pregnancy is one of the main causes of maternal morbidity and mortality. HELLP syndrome is potentially life-threatening to the mother. Currently the main treatment for HELLP syndrome is symptomatic. Corticosteroids can be used to treat the patient's condition and promote fetal lung maturation. Methods: The research method used is a literature review, namely literature collected from various sources related to the use of corticosteroids in the HELLP syndrome. Results: The typical clinical symptoms of HELLP syndrome were right upper quadrant abdominal pain, nausea, and vomiting. At less than 27 weeks of gestation, conservative therapy is considered. Corticosteroids are important therapeutic agents used to treat allergic and inflammatory disorders or to suppress unwanted immune systems. Steroid molecules diffuse across cell membranes and bind to glucocorticoid receptors, causing a conformational change in the receptor thereby inhibiting transcription factors that control the synthesis of proinflammatory mediators. Another important effect is the inhibition of phospholipase A2, which is responsible for the production of many inflammatory mediators. Several studies showed that there was no difference in outcome between the treatment group and the control group. Other references say the use of corticosteroids in preterm pregnancy has shown beneficial results. Conclusion: The use of corticosteroids in the HELLP syndrome of preterm pregnancy has been shown to be beneficial.Keyword: Corticosteroid, HELLP syndrome, Pregnancy

Bile Acids Transporters of Enterohepatic Circulation for Targeted Drug Delivery.

Bile acids (BAs) are important steroidal molecules with a rapidly growing span of applications across a variety of fields such as supramolecular chemistry, pharmacy, and biomedicine. This work provides a systematic review on their transport processes within the enterohepatic circulation and related processes. The focus is laid on the description of specific or less-specific BA transport proteins and their localization. Initially, the reader is provided with essential information about BAs′ properties, their systemic flow, metabolism, and functions. Later, the transport processes are described in detail and schematically illustrated, moving step by step from the liver via bile ducts to the gallbladder, small intestine, and colon; this description is accompanied by descriptions of major proteins known to be involved in BA transport. Spillage of BAs into systemic circulation and urine excretion are also discussed. Finally, the review also points out some of the less-studied areas of the enterohepatic circulation, which can be crucial for the development of BA-related drugs, prodrugs, and drug carrier systems.

Small molecule RHP1 promotes root hair tip growth by acting upstream of the RHD6-RSL4-dependent transcriptional pathway and ROP signaling in plants.

Root hairs are single-cell projections in the root epidermis. The presence of root hairs greatly expands the root surface, which facilitates soil anchorage and the absorption of water and nutrients. Root hairs are also the ideal system to study the mechanism of polar growth. Previous research has identified many important factors that control different stages of root hair development. Using a chemical genetics screen, in this study we report the identification of a steroid molecule, RHP1, which promotes root hair growth at nanomolar concentrations without obvious change of other developmental processes. We further demonstrate that RHP1 specifically affects tip growth with no significant influence on cell fate or planar polarity. We also show that RHP1 promotes root hair tip growth via acting upstream of the RHD6-RSL4-dependent transcriptional pathway and ROP GTPase-guided local signaling. Finally, we demonstrate that RHP1 exhibits a wide range of effects on different plant species in both monocots and dicots. This study of RHP1 will not only help to dissect the mechanism of root hair tip growth, but also provide a new tool to modify root hair growth in different plant species.

Biochemical characterization of the bile acid synthetic enzyme 3β‐hydroxy‐Δ5‐C27 steroid dehydrogenase/isomerase type VII

Cholesterol is a key biological molecule that is a vital precursor of steroid molecule biosynthesis, including steroid hormones, bile acids and vitamin D3.These processes require 3β‐hydroxysteroid dehydrogenase (3β‐HSD) enzymes, which catalyze dehydrogenation of hydroxysteroids. This family of enzymes catalyzes a wide variety of reaction mechanisms, carrying out a combination of oxidation, isomerization and decarboxylase reactions that result in the formation of cholesterol, steroid hormones and bile acids. 3β‐hydroxy‐Δ5‐C27 steroid dehydrogenase/isomerase type VII (HSD3B7) is responsible for the NAD+ dependent conversion of 7α‐hydroxycholesterol (7‐OHC) to 7α‐hydroxy‐3‐oxo‐4‐cholestenoate (7‐HOC), the second step of the bile acid synthesis pathway, which is vital for nutrient absorption and excretion of excess lipids. This oxidation reaction is one of many steps that increases the solubility of cholesterol for either storage or secretion. HSD3B7 shows substantial functional differences from other family members leaving significant gaps in our understanding of its mode of catalysis and substrate specificity. To this end, I have characterized HSD3B7 using Michaelis‐Menten kinetics, thermal shift assays, and begun x‐ray crystallographic studies. These studies reveal that HSD3B7 displays activity towards multiple bile acid precursors with differing hydrocarbon tail oxidation, with Km values in the low micromolar range. HSD3B7 retains its catalytic efficiency towards these substrates, suggesting that its substrate binding pocket can withstand changes in polarity upon alterations to this hydrocarbon tail. Lastly, HSD3B7 can be crystallized after modification to its membrane associated region, which will result in one of the first structures of a 3β‐HSD enzyme. Together these studies provide key insight into the mechanism of substrate specificity of HSD3B7 and appears amenable for X‐ray crystal structure determination.

Dehydroepiandrosterone Sulfate and Arterial Hypertension

Dehydroepiandrosterone sulfate (DHEAS) is a steroid molecule whose function and mechanism of action in the human body are still inadequately researched. A potential protective function for the cardiovascular system can be explained by activation of nitric oxide production, impact on endothelial and mitochondrial function, and inhibition of proinflammatory cytokine production (IL-6 and TNF-α). Some research shows the beneficial effects of DHEA/DHEAS on many bodily functions, especially in the cardiovascular and the neurological systems. However, we need to be careful with interpretation of the results because of different criteria used for defining arterial hypertension, the race that was observed, and reproductive status of women, as these factors can change the conclusion. Due to a lack of evidence, DHEAS supplementation is still not recommended. We need multicentric prospective and randomized studies on DHEAS to examine its potential impact on blood pressure regulation and cardiovascular risk.