Efficacy and safety of prophylactic anticoagulation in patients with primary nephrotic syndrome: a systematic review and meta-analysis.

Background And Aims: Nephrotic syndrome (NS) is associated with an increased incidence of venous thromboembolism (VTE), approximately 10%. We performed a systematic review to evaluate the efficacy and safety of prophylactic anticoagulation in patients with NS.

Methods: Studies evaluating prophylactic anticoagulation in NS were identified by an electronic search of MEDLINE and EMBASE databases until December 2021.

Parentification, distress, and relationship with parents as factors shaping the relationship between adult siblings and their brother/sister with disabilities.

According to parentification theory, when the siblings of a brother/sister with disabilities assume parent-like duties, this role reversal is known as sibling-focused parentification. It has a significant impact on these siblings' distress and the quality of their family relationships; 605 Italian adult siblings (19-26 years) of people with disabilities completed the online survey. Measures of siblings' parentification, distress, quality of family relationships, social support, and perceived benefits of parentification were used.

In silico identification of a β-adrenoceptor allosteric site that selectively augments canonical βAR-Gs signaling and function.

Activation of β-adrenoceptors (βARs) causes airway smooth muscle (ASM) relaxation and bronchodilation, and βAR agonists (β-agonists) are front-line treatments for asthma and other obstructive lung diseases. However, the therapeutic efficacy of β-agonists is limited by agonist-induced βAR desensitization and noncanonical βAR signaling involving β-arrestin that is shown to promote asthma pathophysiology. Accordingly, we undertook the identification of an allosteric site on βAR that could modulate the activity of β-agonists to overcome these limitations.

Characterization of a new WHIM syndrome mutant reveals mechanistic differences in regulation of the chemokine receptor CXCR4.

WHIM syndrome is a rare immunodeficiency disorder that is characterized by warts, hypogammaglobulinemia, infections, and myelokathexis. While several gain-of-function mutations that lead to C-terminal truncations, frame shifts and point mutations in the chemokine receptor CXCR4 have been identified in WHIM syndrome patients, the functional effect of these mutations are not fully understood. Here, we report on a new WHIM syndrome mutation that results in a frame shift within the codon for Ser339 (S339fs5) and compare the properties of S339fs5 with wild-type CXCR4 and a previously identified WHIM syndrome mutant, R334X.

Phenylalanine 193 in Extracellular Loop 2 of the -Adrenergic Receptor Coordinates -Arrestin Interaction.

G protein-coupled receptors (GPCRs) transduce a diverse variety of extracellular stimuli into intracellular signaling. These receptors are the most clinically productive drug targets at present. Despite decades of research on the signaling consequences of molecule-receptor interactions, conformational components of receptor-effector interactions remain incompletely described.

Pharmacological Characterization of Low Molecular Weight Biased Agonists at the Follicle Stimulating Hormone Receptor.

Follicle-stimulating hormone receptor (FSHR) plays a key role in reproduction through the activation of multiple signaling pathways. Low molecular weight (LMW) ligands composed of biased agonist properties are highly valuable tools to decipher complex signaling mechanisms as they allow selective activation of discrete signaling cascades. However, available LMW FSHR ligands have not been fully characterized yet.

Nuclear expression of VDR and AHR is mutually exclusive in glandular cells in endometriosis.

The vitamin D receptor (VDR) and aryl hydrocarbon receptor (AHR) are two nuclear receptors that exert their effects by binding with ligands and forming a molecular complex. These complexes translocate to the nucleus and activate the expression of a series of genes which have a response element to VDR or AHR. Both receptors have been identified in the pathogenesis of endometriosis, a common disease characterized by the formation of endometrium-like tissue in ectopic zones.

Pharmacological Programming of Endosomal Signaling Activated by Small Molecule Ligands of the Follicle Stimulating Hormone Receptor.

Follicle-stimulating hormone receptor (FSHR) is a G protein-coupled receptor (GPCR) with pivotal roles in reproduction. One key mechanism dictating the signal activity of GPCRs is membrane trafficking. After binding its hormone FSH, FSHR undergoes internalization to very early endosomes (VEEs) for its acute signaling and sorting to a rapid recycling pathway.

Membrane Estrogen Receptor (GPER) and Follicle-Stimulating Hormone Receptor (FSHR) Heteromeric Complexes Promote Human Ovarian Follicle Survival.

Classically, follicle-stimulating hormone receptor (FSHR)-driven cAMP-mediated signaling boosts human ovarian follicle growth and oocyte maturation. However, contradicting data suggest a different view on physiological significance of FSHR-mediated cAMP signaling. We found that the G-protein-coupled estrogen receptor (GPER) heteromerizes with FSHR, reprogramming cAMP/death signals into proliferative stimuli fundamental for sustaining oocyte survival.

Direct impact of gonadotropins on glucose uptake and storage in preovulatory granulosa cells: Implications in the pathogenesis of polycystic ovary syndrome.

Background: Polycystic ovary syndrome (PCOS) is often associated with higher levels of LH, and arrested ovarian follicular growth. The direct impact of high LH on FSH mediated metabolic responses in PCOS patients is not clearly understood.

Method: In order to investigate the impact of FSH and LH on glucose metabolism in preovulatory granulosa cells (GCs), we used [UC]-2 deoxyglucose, D-[UC]-glucose or 2-NBD glucose to analyse glucose uptake and its incorporation into glycogen.

Glycosylation Pattern and Bioactivity of Reference Follitropin alfa and Biosimilars.

Recombinant follicle-stimulating hormone (FSH) (follitropin alfa) and biosimilar preparations are available for clinical use. They have specific FSH activity and a unique glycosylation profile dependent on source cells. The aim of the study is to compare the originator (reference) follitropin alfa (Gonal-f®)- with biosimilar preparations (Bemfola® and Ovaleap®)-induced cellular responses .

Biased Signaling and Allosteric Modulation at the FSHR.

Knowledge on G protein-coupled receptor (GPCRs) structure and mechanism of activation has profoundly evolved over the past years. The way drugs targeting this family of receptors are discovered and used has also changed. Ligands appear to bind a growing number of GPCRs in a competitive or allosteric manner to elicit balanced signaling or biased signaling (i.

Workflow Description to Dynamically Model β-Arrestin Signaling Networks.

Dynamic models of signaling networks allow the formulation of hypotheses on the topology and kinetic rate laws characterizing a given molecular network, in-depth exploration, and confrontation with kinetic biological data. Despite its standardization, dynamic modeling of signaling networks still requires successive technical steps that need to be carefully performed. Here, we detail these steps by going through the mathematical and statistical framework.

Inferring biallelism of two FSH receptor mutations associated with spontaneous ovarian hyperstimulation syndrome by evaluating FSH, LH and HCG cross-activity.

Research Question: What is the cumulative effect of two follicle-stimulating hormone receptor (FSHR) mutations in spontaneous ovarian hyperstimulation syndrome (sOHSS) pathogenesis? Are these mutations in the mono- or biallelic state?

Design: Two FSHR mutations were found in a pregnant patient affected by sOHSS with no predisposing conditions. While the p.Asn106His mutation is novel, the p.

β-arrestins and biased signaling in gonadotropin receptors.

Gonadotropin receptors include the follicle stimulating hormone receptor (FSHR) and the luteinizing hormone/choriogonadotropin receptor (LHCGR), both belong to the G protein-coupled receptor (GPCR) superfamily and are essential to reproduction. FSHR is activated by follicle stimulating hormone (FSH) while LHCGR is activated by either luteinizing hormone (LH) or choriogonadotropin (CG). Upon ligand binding, gonadotropin receptors undergo conformational changes that lead to the activation of the heterotrimeric G protein, resulting in the production of different second messengers.

Follicle-Stimulating Hormone Receptor: Advances and Remaining Challenges.

Follicle-stimulating hormone (FSH) is produced in the pituitary and is essential for reproduction. It specifically binds to a membrane receptor (FSHR) expressed in somatic cells of the gonads. The FSH/FSHR system presents many peculiarities compared to classical G protein-coupled receptors (GPCRs).

Genetics of gonadotropins and their receptors as markers of ovarian reserve and response in controlled ovarian stimulation.

Several controlled ovarian stimulation (COS) protocols have been developed to increase the yield of mature oocytes retrieved in assisted reproductive techniques (ARTs). The ovarian reserve (OR) influences the COS response, and it represents the main parameter that helps clinicians in refining clinical treatments in the perspective of a "personalized" ART. This approach is even more needed in particular conditions such as poor OR or polycystic ovary syndrome.

Estrogen Modulates Specific Life and Death Signals Induced by LH and hCG in Human Primary Granulosa Cells In Vitro.

Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are glycoprotein hormones used for assisted reproduction acting on the same receptor (LHCGR) and mediating different intracellular signaling. We evaluated the pro- and anti-apoptotic effect of 100 pM LH or hCG, in the presence or in the absence of 200 pg/mL 17β-estradiol, in long-term, serum-starved human primary granulosa cells (hGLC) and a transfected granulosa cell line overexpressing LHCGR (hGL5/LHCGR). To this purpose, phospho-extracellular-regulated kinase 1/2 (pERK1/2), protein kinase B (pAKT), cAMP-responsive element binding protein (pCREB) activation and procaspase 3 cleavage were evaluated over three days by Western blotting, along with the expression of target genes by real-time PCR and cell viability by colorimetric assay.

β-arrestin signalling and bias in hormone-responsive GPCRs.

G protein-coupled receptors (GPCRs) play crucial roles in the ability of target organs to respond to hormonal cues. GPCRs' activation mechanisms have long been considered as a two-state process connecting the agonist-bound receptor to heterotrimeric G proteins. This view is now challenged as mounting evidence point to GPCRs being connected to large arrays of transduction mechanisms involving heterotrimeric G proteins as well as other players.