mineral receptor antagonists

INTRODUCTION: Uterine fibroids, the most prevalent benign tumors among reproductive-age women, pose treatment challenges that range from surgical interventions to medical therapies for symptom control. Progestins and estroprogestins effectively manage uterine bleeding by suppressing dysfunctional endometrium over fibroids. While GnRH agonists represent a crucial milestone in symptom treatment, their prolonged use results in menopausal-like symptoms and irreversible bone mineral density loss...

This study aimed to explore the effects of peroxisome proliferator-activated receptor γ (PPARγ) inhibition on fracture healing of nonunion and the underlying mechanisms. Bone marrow mesenchymal stem cells (BMSCs) were treated with PPARγ antagonist GW9662 (5 μM, 10 μM). Alkaline phosphatase (ALP) staining and Alizarin Red S was used to assess early stage of osteogenesis and osteogenic differentiation. GW9662 (1 mg/kg/day) were administered intraperitoneally into the rats with bone fracture...

An oral fixed-dose combination of relugolix/estradiol/norethisterone (also known as norethindrone) acetate [Myfembree® (USA); Ryeqo® (EU)] (hereafter referred to as relugolix combination therapy) has been approved in the USA for the management of moderate to severe pain associated with endometriosis in premenopausal women and in the EU for the symptomatic treatment of endometriosis in adult women of reproductive age with a history of previous medical or surgical treatment for their endometriosis. The gonadotropin-releasing hormone (GnRH) receptor antagonist relugolix decreases estradiol and progesterone levels, while the addition of estradiol/norethisterone acetate mitigates hypoestrogenic effects including bone mineral density (BMD) loss and vasomotor symptoms...

Prostate cancer is an exemplar of an enhancer-binding transcription factor-driven disease. The androgen receptor (AR) enhanceosome complex comprised of chromatin and epigenetic coregulators assembles at enhancer elements to drive disease progression. The paralog lysine acetyltransferases p300 and CBP deposit histone marks that are associated with enhancer activation. Here, we demonstrate that p300/CBP are determinant cofactors of the active AR enhanceosome in prostate cancer. Histone H2B N-terminus multisite lysine acetylation (H2BNTac), which was exclusively reliant on p300/CBP catalytic function, marked active enhancers and was notably elevated in prostate cancer lesions relative to the adjacent benign epithelia...

INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2Is) have beneficial effects on the renal function of chronic kidney disease (CKD) patients, although the types of patients suitable for this treatment remain unclear. METHODS: A retrospective observational study was conducted on CKD patients who were treated with SGLT2I at our department from 2020 to 2023. The estimated glomerular filtration rate (eGFR) just before treatment was defined as the baseline and the difference between pre-and post-treatment eGFR slopes were used to compare the improvement of renal function...

Mammalian switch/sucrose nonfermentable (mSWI/SNF) ATPase degraders have been shown to be effective in enhancer-driven cancers by functioning to impede oncogenic transcription factor chromatin accessibility. Here, we developed AU-24118, an orally bioavailable proteolysis-targeting chimera (PROTAC) degrader of mSWI/SNF ATPases (SMARCA2 and SMARCA4) and PBRM1. AU-24118 demonstrated tumor regression in a model of castration-resistant prostate cancer (CRPC) which was further enhanced with combination enzalutamide treatment, a standard of care androgen receptor (AR) antagonist used in CRPC patients...

Conn's syndrome, defined as unilateral aldosterone-producing adenoma, accounts for 35-40% of cases of primary hyperaldosteronism. Primary hyperaldosteronism typically occurs in younger patients with poorly controlled arterial hypertension due to extracellular fluid retention, in whom at least a triple combination of antihypertensives, including a diuretic, is needed to maintain normotension. The clinical picture of arterial hypertension may be complemented by symptoms associated with hypokalaemia, such as weakness, fatigue, palpitations, convulsions, polydipsia, or polyuria...

AIMS: Formyl peptide receptor 1 (FPR1), from a G-protein coupled receptor family, was previously well-characterized in immune cells. But the function of FPR1 in osteogenesis and fracture healing was rarely reported. This study, using the FPR1 knockout (KO) mouse, is one of the first studies that try to investigate FPR1 function to osteogenic differentiation of bone marrow-derived stem cells (BMSCs) in vitro and bone fracture healing in vivo. MATERIALS AND METHODS: Primary BMSCs were isolated from both FPR1 KO and wild type (WT) mice...

BACKGROUND: Patients with fibro-calcific aortic valve disease (FCAVD) have lipid depositions in their aortic valve that engender a proinflammatory impetus toward fibrosis and calcification and ultimately valve leaflet stenosis. Although the lipoprotein(a)-autotaxin (ATX)-lysophosphatidic acid axis has been suggested as a potential therapeutic target to prevent the development of FCAVD, supportive evidence using ATX inhibitors is lacking. We here evaluated the therapeutic potency of an ATX inhibitor to attenuate valvular calcification in the FCAVD animal models...

UNLABELLED: Mammalian switch/sucrose non-fermentable (mSWI/SNF) ATPase degraders have been shown to be effective in enhancer-driven cancers by functioning to impede oncogenic transcription factor chromatin accessibility. Here, we developed AU-24118, a first-in-class, orally bioavailable proteolysis targeting chimera (PROTAC) degrader of mSWI/SNF ATPases (SMARCA2 and SMARCA4) and PBRM1. AU-24118 demonstrated tumor regression in a model of castration-resistant prostate cancer (CRPC) which was further enhanced with combination enzalutamide treatment, a standard of care androgen receptor (AR) antagonist used in CRPC patients...

Background and Objectives: Dental caries is one of the most common human pathological conditions resulting from the invasion of bacteria into the dentin. Current treatment options are limited. In many cases, endodontic therapy leads to permanent pulp tissue loss. Dentin-pulp complex regeneration involves dental pulp stem cells (DPSCs) that differentiate into odontoblast-like cells under an inflammatory context. However, limited information is available on how DPSC differentiation processes are affected under inflammatory environments...

Trifloxystrobin (TRI) is a methacrylate fungicide, and fluopyram (FLU) is a new pyridylethylbenzamide fungicide and nematicide. Both are often detected in water bodies and may be highly toxic to many aquatic organisms. Unfortunately, the aquatic biological risks of single FLU or a mixture of trifloxystrobin and fluopyram have not been reported. In this study, zebrafish was selected as the test organism to investigate the combined toxicity of trifloxystrobin and fluopyram to zebrafish. After zebrafish embryos exposed to three pesticide solutions, Alcian-blue staining, Alizarin-red staining and quantitative PCR (qPCR) were performed...

BACKGROUND: Uterine leiomyomas are common for reproductive-aged women and affect women's quality of life due to heavy menstrual bleeding or dysmenorrhea. Leiomyomas grow according to estradiol exposure and decrease after post-menopause. In case serious symptoms are caused by leiomyomas, pharmacotherapy or surgical treatment is proposed. Prior to surgical treatment, pharmacotherapies aimed at the reduction of leiomyoma and uterine volume or improvement of anemia are introduced to conduct minimum invasive surgery (i...

OBJECTIVE: To investigate the relationship between icariin and the osteoblastic differentiation of vascular smooth muscle cells (VSMCs) and the signal pathway involved. METHODS: We applied a universally accepted calcification model of VSMCs induced by β glycerophosphate. Then the VSMCs calcification was observed by treatment with icariin and/or inhibitors of estrogen receptors (ERs) and p38-mitogen-activated protein kinase (MAPK) signaling. RESULTS: Icariin inhibited osteoblastic differentiation and mineralization of VSMCs due to decreased ALP activity and Runx2 expression...

PURPOSE: Acromegaly is a chronic disease characterized by growth hormone (GH) hypersecretion, usually caused by a pituitary adenoma, resulting in elevated circulating levels of insulin-like growth factor type I (IGF-I). Pegvisomant (PEG), the GH-receptor (GHR) antagonist, is used in treating acromegaly to normalize IGF-I hypersecretion. Exposure to increased levels of GH and IGF-I can cause profound alterations in bone structure that are not completely reverted by treatment of GH hypersecretion...

Herbal supplements are widely used to enhance prostate health. These supplements may contain several types of plant sterols, vitamins, and minerals. By weight, however, plant sterols make up an abundant ingredient component, with saw palmetto extract or its primary component, beta-sitosterol, often comprising the most abundant sterol. Saw palmetto extract/beta-sitosterol has been shown to promote anti-tumorigenic processes in prostate cancer cells and rodent models of prostate cancer. It has also been shown to inhibit the 5α-reductase enzyme, thereby behaving similarly to finasteride and dutasteride, which are widely used to treat prostatic enlargement, or benign prostatic hyperplasia (BPH)...

BACKGROUND: Although cannabinoid receptor 1 (CB1R) antagonists can inhibit bone loss in osteoporosis mouse models, different strains of mice show different bone mass phenotypes after knock out the CB1R gene. The relationship between CB1R and bone metabolism is complex, and its regulatory role in bone metabolism and as a therapeutic target for osteoporosis requires further investigation. METHODS: Based on lumbar spine volumetric bone mineral density (vBMD) data of healthy female cynomolgus monkeys aged 1-25 years, naturally aged postmenopausal female osteoporotic monkeys and normal young monkeys were screened by detecting lumbar vertebrae vBMD and estradiol levels in this study...

Osteoporosis is a significant global health concern, linked to reduced bone density and an increased fracture risk, with effective treatments still lacking. This study explored the potential of gamma-aminobutyric acid (GABA) and its receptors as a novel approach to promote osteogenesis and address osteoporosis. GABA concentrations up to 10 mM were well-tolerated by MC3T3-E1 preosteoblast, stimulating osteoblast differentiation and mineralization in a concentration- and time-dependent manner. In vivo experiments with zebrafish larvae demonstrated the ability of GABA to improve vertebral formation and enhanced bone density, indicating the potential therapeutic value for osteoporosis...

We have previously reported that the cortical bone thinning seen in mice lacking the Wnt signaling antagonist Sfrp4 is due in part to impaired periosteal apposition. The periosteum contains cells which function as a reservoir of stem cells and contribute to cortical bone expansion, homeostasis, and repair. However, the local or paracrine factors that govern stem cells within the periosteal niche remain elusive. Cathepsin K (Ctsk), together with additional stem cell surface markers, marks a subset of periosteal stem cells (PSCs) which possess self-renewal ability and inducible multipotency...

Human bone marrow mesenchymal stem cells (hBMSCs) are attractive therapeutic agents for bone tissue regeneration owing to their osteogenic differentiation potential. Notoginsenoside R1 (NGR1) is a novel phytoestrogen with diverse pharmacological activities. Here, we probed whether NGR1 has an effect on the osteogenic differentiation of hBMSCs. EdU, CCK-8 and Transwell assays were used to measure proliferation and migration of hBMSCs after treatment with different doses of NGR1. hBMSCs were treated with osteogenic differentiation induction medium for osteogenesis...