Novel Steroid

Bile acids are synthesised in the liver and are essential amphiphilic steroids for maintaining the balance of cholesterol and energy metabolism in livestock and poultry. They can be used as novel feed additives to promote fat utilisation in the diet and the absorption of fat-soluble substances in the feed to improve livestock performance and enhance carcass quality. With the development of understanding of intestinal health, the balance of bile acid metabolism is closely related to the composition and growth of livestock intestinal microbiota, inflammatory response, and metabolic diseases...

INTRODUCTION: There is a paucity of data and therapeutic options nationally and internationally on calcineurin inhibitor (CNI)-resistant forms of focal segmental glomerulosclerosis (FSGS) in children. CNI (tacrolimus or cyclosporine) are proven monotherapy in children with FSGS with a steroid-dependent (SD) or steroid-resistant (SR) course. We analyzed a novel therapeutic option in CNI-resistant FSGS by using the dual therapy of rituximab and mycophenolate to maintain remission. METHODS: This is a retrospective analysis of clinical, therapeutic profile, and treatment outcomes (sustained remission versus no remission) in subjects with CNI-resistant FSGS who received dual rituximab therapy along with mycophenolate as maintenance therapy for a minimum of 1 year...

BACKGROUND: The novel coronavirus disease(corona virus disease 2019: COVID-19)has calmed down worldwide, and the severity of the disease is decreasing. On the other hand, due to the emergence of strain mutations, the number of infected people shows a wavy course. I have experienced a case of gastric cancer that underwent chemotherapy including an immune checkpoint inhibitors(ICI) early after COVID-19, so I will report it including a discussion. CASE: A 71-year-old man...

Cancer cachexia (CC) is a devastating metabolic syndrome characterized by skeletal muscle wasting and body weight loss, posing a significant burden on the health and survival of cancer patients. Despite ongoing efforts, effective treatments for CC are still lacking. Metabolomics, an advanced omics technique, offers a comprehensive analysis of small-molecule metabolites involved in cellular metabolism. In CC research, metabolomics has emerged as a valuable tool for identifying diagnostic biomarkers, unravelling molecular mechanisms and discovering potential therapeutic targets...

The study of intact phase II metabolites of endogenous anabolic androgenic steroids (EAAS) gives important information about metabolism and has the potential to improve the detection of doping with testosterone. For analysis with liquid chromatography-mass spectrometry (LC-MS), chemical derivatization at the steroid moiety is a technique to improve the positive ionization efficiency of glucuronidated/sulfated EAAS under collision-induced dissociation (CID) conditions. However, regarding the chromatographic performance, there are still challenges to address, for example, poor peak shape, which is mainly caused by nondefined adsorption in the chromatographic system...

RATIONALE: X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene leading to very long chain fatty acid (VLCFA) accumulation. The disease demonstrates a spectrum of phenotypes including adrenomyeloneuropathy (AMN). We aimed to identify the genetic basis of disease in a patient presenting with AMN features in order to confirm the diagnosis, expand genetic knowledge of ABCD1 mutations, and elucidate potential genotype-phenotype associations to inform management. PATIENT CONCERNS: A 29-year-old male presented with a 4-year history of progressive spastic paraplegia, weakness of lower limbs, fecal incontinence, sexual dysfunction, hyperreflexia, and positive Babinski and Chaddock signs...

Steroids are an important family of bioactive compounds. Steroid drugs are renowned for their multifaceted pharmacological activities and are the second-largest category in the global pharmaceutical market. Recent developments in biocatalysis and biosynthesis have led to the increased use of enzymes to enhance the selectivity, efficiency, and sustainability for diverse modifications of steroids. This review discusses the advancements achieved over the past five years in the enzymatic modifications of steroid scaffolds, focusing on enzymatic hydroxylation, reduction, dehydrogenation, cascade reactions, and other modifications for future research on the synthesis of novel steroid compounds and related drugs, and new therapeutic possibilities...

The development of novel agents with immunoregulatory effects is a keen way to combat the growing threat of inflammatory storms to global health. To synthesize pseudo-steroidal glycosides tethered by ether bonds with promising immunomodulatory potential, we develop herein a highly effective deoxygenative functionalization of a novel steroidal donor (steroidation) facilitated by strain-release, leveraging cost-effective and readily available Sc(OTf)3 catalysis. This transformation produces a transient steroid-3-yl carbocation which readily reacts with O -, C -, N -, S -, and P -nucleophiles to generate structurally diverse steroid derivatives...

Muscarinic acetylcholine receptors are metabotropic G-protein coupled receptors. Muscarinic receptors in the cardiovascular system play a central role in its regulation. Particularly M2 receptors slow down the heart rate by reducing the impulse conductivity through the atrioventricular node. In general, activation of muscarinic receptors has sedative effects on the cardiovascular system, including vasodilation, negative chronotropic and inotropic effects on the heart, and cardioprotective effects, including antifibrillatory effects...

Amyloidosis presents a diagnostic challenge, particularly when concomitant with severe conditions like acute exacerbations of idiopathic pulmonary fibrosis (IPF). In this report, we detail the case of a 73-year-old patient with acute exacerbation of IPF and simultaneous emergence of cardiac amyloidosis. The patient's clinical journey began with persistent exertional dyspnea, progressing to hypoxemia on admission. Chest CT scans showed extensive ground-glass opacities, consolidations, and pre-existing honeycombing-like cysts and reticular shadows, accompanied by a right-sided pleural effusion...

Aim: The aim of this study was the synthesis of steroid compounds with heterocyclic rings and good anticancer properties. Materials & methods: The synthesis, in silico and in vitro anticancer testing of novel pyridin-2-yl estra-1,3,5(10)-triene derivatives was performed. Results: All synthesized compounds have shown promising results for, antiproliferative activity, relative binding affinities for the ligand binding domains of estrogen receptors α, β and androgen receptor, aromatase binding potential, and inhibition of AKR1C3 enzyme...

Rheumatoid arthritis is a systemic autoimmune disorder related to joint inflammation, bone erosion, and deformity. Numerous studies indicate that the causes and consequences of RA are still being debated, and therapeutic strategies are in the translation stage. Non-steroidal anti-inflammatory drugs continue to be often used to relieve pain. Still, due to their poor efficacy, failure to halt the spread of the disease, and undesirable adverse effects, they are no longer regarded as first-line treatments. The development of biologic DMRDs designed to reduce the inflammatory response led to substantial changes to the strategy for managing this disease...

INTRODUCTION: The clinical evolution of steroid-sensitive forms of pediatric idiopathic nephrotic syndrome (INS) is highly heterogeneous following the standard treatment with prednisone. To date, no prognostic marker has been identified to predict the severity of the disease course starting from the first episode. METHODS: In this monocentric prospective cohort study we set up a reproducible and standardized flow cytometry panel using two sample tubes (one for B-cell and one for T-cell subsets) to extensively characterized the lymphocyte repertoire of INS pediatric patients...

BACKGROUND: Kidney transplantation is an acceptable therapy end-stage kidney disease secondary to antineutrophil cytoplasmic antibody-associated vasculitis with risk of disease recurrence ranging from 3% to 17%. Standard posttransplant immunosuppression is the mainstay of therapy after recurrence. Recently, new medications focused on complement regulation and avoidance of steroids have been shown to be effective in treating antineutrophil cytoplasmic antibody (ANCA) vasculitis with no studies in the pediatric population...

Resistant hypertension (RHT) is characterized by persistently high blood pressure (BP) levels above the widely recommended therapeutic targets of less than 140/90 mmHg office BP, despite life-style measures and optimal medical therapies, including at least three antihypertensive drug classes at maximum tolerated dose (one should be a diuretic). This condition is strongly related to hypertension-mediated organ damage and, mostly, high risk of hospitalization due to hypertension emergencies or acute cardiovascular events...

Chronic kidney disease (CKD) represents an enormous healthcare burden, the management of which has been stagnant for the last couple of decades, with blockade of the renin-angiotensin-aldosterone system (RAAS) the most potent tool available to retard kidney disease progression. In the new cardiometabolic era, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as forerunners in addressing combined cardiorenal risk. This review summarises the evidence for SGLT2i use in diabetic and non-diabetic CKD and examines the risk:benefit profile in this population...

Glucocorticoids (GCs) act through the glucocorticoid receptor (GR) and are commonly used as anti-inflammatory and immunosuppressant medications. Chronic GC use has been linked with unwanted complications such as steroid-induced diabetes mellitus (SIDM), although the mechanisms for these effects are not completely understood. Modification of six GC parent molecules with 2-mercaptobenzothiazole resulted in consistently less promoter activity in transcriptional activation assays using a 3xGRE reporter construct while constantly reducing inflammatory pathway activity...

Neuroinflammation accompanies several brain disorders, either as a secondary consequence or as a primary cause and may contribute importantly to disease pathogenesis. Neurosteroids which act as Positive Steroid Allosteric GABA-A receptor Modulators (Steroid-PAM) appear to modulate neuroinflammation and their levels in the brain may vary because of increased or decreased local production or import from the systemic circulation. The increased synthesis of steroid-PAMs is possibly due to increased expression of the mitochondrial cholesterol transporting protein (TSPO) in neuroinflammatory tissue, and reduced production may be due to changes in the enzymatic activity...

PURPOSE OF REVIEW: This review details the three new agents, including two novel mechanisms of action, approved to treat Crohn's disease in recent years. We review efficacy, safety, prescribing information, and available data on positioning these new therapies. RECENT FINDINGS: Risankizumab and upadacitinib are novel mechanisms of action approved to treat moderate to severe Crohn's disease. Risankizumab targets the cytokine interleukin-23. Upadacitinib is a selective Janus kinase-1 inhibitor approved for use in individuals who have previously failed or are intolerant to an anti-TNF agent...

Maternal exposure to elevated levels of steroid hormones during pregnancy is associated with the development of chronic conditions in offspring that manifest in adulthood. However, the effects of progesterone (P4) administration during early pregnancy on fetal development and subsequent offspring behavior remain poorly understood. In this study, we aimed to investigate the effects of P4 treatment during early pregnancy on the transcript abundance in the fetal brain and assess the behavioral consequences in the offspring during adolescence and adulthood...