- |||||||||| Reasanz (serelaxin) / Novartis
Clinical, Journal: Relaxin and the Cardiovascular System: From Basic Science to Clinical Practice. (Pubmed Central) - Jun 10, 2021
We summarize the most updated clinical data and discuss future directions of serelaxin for the treatment of acute heart failure. This should encourage additional work to determine how can relaxin's beneficial effects be exploited for the treatment of cardiovascular disease.
- |||||||||| Reasanz (serelaxin) / Novartis
Journal: Pulmonary myeloid cell uptake of biodegradable nanoparticles conjugated with an anti-fibrotic agent provides a novel strategy for treating chronic allergic airways disease. (Pubmed Central) - May 28, 2021
The acute heart failure drug, serelaxin (recombinant human gene-2 relaxin, RLX), has potential anti-remodeling and anti-fibrotic effects but only when continuously infused or injected to overcome its short half-life...Furthermore, NP-RLX ameliorated the chronic AAD-induced AI, pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), chemokines (CCL2, CCL11) and the pro-fibrotic TGF-β1/IL-1β axis on AWR and resulting AHR, as well as human myofibroblast-induced collagen gel contraction, to a similar extent as unconjugated RLX. Hence, NP-RLX represents a novel strategy for treating the central features of asthma.
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Journal: Identification of Potent and Long-Acting Single-Chain Peptide Mimetics of Human Relaxin-2 for Cardiovascular Diseases. (Pubmed Central) - May 5, 2021
Recombinant relaxin-2 (serelaxin) has shown beneficial effects in acute heart failure, but its full therapeutic potential has been hampered by its short half-life and the need for intravenous administration limiting its use to intensive care units...Modifications in the B-chain of relaxin, such as the introduction of specific mutations and the trimming of the sequence to an optimal size, resulted in potent, structurally simplified peptide agonists of the relaxin receptor Relaxin Family Peptide Receptor 1 (RXFP1) (e.g., 54). Introduction of suitable spacers and fatty acids led to the identification of single-chain lipidated peptide agonists of RXFP1, with sub-nanomolar activity, high subcutaneous bioavailability, extended half-lives, and in vivo efficacy (e.g., 64).
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Preclinical, Journal: B7-33, a Functionally Selective Relaxin Receptor 1 Agonist, Attenuates Myocardial Infarction-Related Adverse Cardiac Remodeling in Mice. (Pubmed Central) - Mar 9, 2021
Its recombinant formulation (serelaxin) has been demonstrated to reduce infarct size and prevent excessive scar formation in animal models of cardiac ischemia-reperfusion injury...Subsequently, B7-33 (100 nmol/L) reduced tunicamycin (2.5 μg/mL) induced upregulation of GRP78 in an extracellular signal-regulated kinase 1/2-dependent manner. Conclusions B7-33 confers acute cardioprotection and limits myocardial infarction-related adverse remodeling in mice by attenuating cardiomyocyte death and endoplasmic reticulum stress as well as preserving cardiac function.
- |||||||||| Reasanz (serelaxin) / Novartis
Clinical, P2 data, Journal: A phase 2 randomised controlled trial of serelaxin to lower portal pressure in cirrhosis (STOPP). (Pubmed Central) - Dec 30, 2020
P2
Due to its preferential improvement of cortical CBF, serelaxin might reduce cognitive impairments associated with these emergencies. In a small randomised, phase 2, proof-of-concept study in patients with cirrhosis and CSPH, serelaxin infusion was safe and well-tolerated but had a neutral effect on HVPG.
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Journal: RLN3/RXFP3 Signaling in the PVN Inhibits Magnocellular Neurons via M-like Current Activation and Contributes to Binge Eating Behavior. (Pubmed Central) - Nov 28, 2020
Various neuropeptides play important roles in the regulation of feeding behavior, including relaxin-3 (RLN3), which stimulates food intake in rats through the activation of the relaxin-family peptide-3 receptor (RXFP3)...Moreover, we elucidated the neuronal mechanism of RLN3/RXFP3 signaling in PVN in male and female rats and characterized sex differences in the RLN3 innervation of the PVN. These findings increase our understanding of the brain circuits and neurotransmitters involved in binge-eating disorder pathology and identify RXFP3 as a therapeutic target for binge-like eating disorders.
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Journal: Effects of C-Terminal B-Chain Modifications in a Relaxin 3 Agonist Analogue. (Pubmed Central) - Nov 22, 2020
As expected, the C-terminal amide form of A2 showed lower binding affinity for RXFP3 while ester and alcohol substitutions also demonstrated lower affinity. However, while these analogues showed slightly lower binding affinity, there was no significant difference in activation of RXFP3 compared to A2 bearing a C-terminal carboxylic acid, suggesting the binding pocket is able to accommodate additional atoms.
- |||||||||| Reasanz (serelaxin) / Novartis
Journal: Engineering of chimeric peptides as antagonists for the G protein-coupled receptor, RXFP4. (Pubmed Central) - Nov 21, 2020
In a recent study, we were able to engineer a simplified INSL5 analogue 13 which is a relaxin family peptide receptor 4 (RXFP4)-specific agonist...Importantly, analogue 17 has a simplified structure which is more amenable to chemical synthesis. Therefore, analogue 17 is an ideal template for further development into a specific high affinity RXFP4 antagonist which will be an important tool to probe the physiological role of RXFP4/INSL5 axis.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Growth and Maturation in Development: A Fly's Perspective. (Pubmed Central) - Nov 21, 2020
In this review, we will present an overview of the significant advancements in the coordination mechanisms ensuring developmental robustness in Drosophila. We will include (i) the characterization of feedback mechanisms between maturation and growth hormones, (ii) the recognition of a relaxin-like peptide Dilp8 as a central processor coordinating juvenile regeneration and time of maturation, and (iii) the identification of a novel coordinator mechanism involving the AstA/KISS system.
- |||||||||| Reasanz (serelaxin) / Novartis
Journal: Administration study of recombinant human relaxin-2 in horse for doping control purpose. (Pubmed Central) - Nov 19, 2020
rhRLX-2 could be detected and confirmed in the plasma and urine samples collected 105 h and 80 h respectively after the last dose of administration. For doping control purpose, rhRLX-2 ELISA could be used as a screening test to identify potential positive samples for further investigation using the nano-LC/HRMS methods.
- |||||||||| Reasanz (serelaxin) / Novartis
Journal: Relaxin reverses maladaptive remodeling of the aged heart through Wnt-signaling. (Pubmed Central) - Nov 14, 2020
In isolated fibroblasts, relaxin blocked TGFβ-induced collagen elevation in a Wnt dependent manner. These findings demonstrate a close interplay between relaxin and Wnt-signaling resulting in myocardial remodeling and reveals a fundamental mechanism of great therapeutic potential.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Potential Molecular Mechanisms of Plantain in the Treatment of Gout and Hyperuricemia Based on Network Pharmacology. (Pubmed Central) - Nov 6, 2020
The core targets of plantain for hyperuricemia are RELA, MAPK1, NFKBIA, CASP3, CASP8, and TNF, and the main pathways are pathways in cancer, apoptosis, hepatitis B, IL-17 signaling pathway, and toxoplasmosis. This study explored the related targets and mechanisms of plantain for the treatment of gout and hyperuricemia from the perspective of network pharmacological analysis, reflecting the characteristics of multiple components, multiple targets, and multiple pathways, and it provides a good theoretical basis for the clinical application of plantain.
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Journal: Relaxin-2 May Suppress Endometriosis by Reducing Fibrosis, Scar Formation, and Inflammation. (Pubmed Central) - Nov 5, 2020
In the endometriosis mouse model, administration of RLX-2 significantly decreased the area of the endometriotic-like lesion with decreasing fibrotic component compared to non-treated control (p = 0.01). RLX-2 may contribute to the control of endometriotic lesion by suppressing fibrosis, scar formation, and inflammation.
- |||||||||| Reasanz (serelaxin) / Novartis
Journal: H3 relaxin protects against calcium oxalate crystal-induced renal inflammatory pyroptosis. (Pubmed Central) - Nov 1, 2020
RLX-2 may contribute to the control of endometriotic lesion by suppressing fibrosis, scar formation, and inflammation. Our results provide previously unidentified mechanistic insights into CaOx crystal-induced inflammatory pyroptotic damage and H3 relaxin-mediated anti-inflammatory protection and thus suggest a series of potential therapeutic targets and methods for but not limited to nephrocalcinosis.
- |||||||||| irinotecan / Generic mfg.
Journal, BRCA Biomarker: The RXFP3 receptor is functionally associated with cellular responses to oxidative stress and DNA damage. (Pubmed Central) - Oct 27, 2020
RXFP3 expression increased in response to DNA damage, overexpression, and Relaxin 3-mediated stimulation of RXFP3 reduced phosphorylation of DNA damage marker H2AX, and repair protein BRCA1, moderating DNA damage. Our data suggests an RXFP3-GIT2 system that could regulate cellular degradation after DNA damage, and could be a novel mechanism for mitigating the rate of age-related damage accumulation.
- |||||||||| Reasanz (serelaxin) / Novartis
Preclinical, Journal: Intranasal administration of a stapled relaxin-3 mimetic has anxiolytic- and antidepressant-like activity in rats. (Pubmed Central) - Sep 24, 2020
Therefore, the present study suggested that the THSWT formula has an action mechanism involving multiple compounds and network targets for the treatment of ONFH. Our preclinical findings demonstrate that targeting the relaxin-3/RXFP3 system via intranasal delivery of an i,i+7 stapled relaxin-3 mimetic may represent an effective treatment approach for depression, anxiety, and related neuropsychiatric disorders.
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Preclinical, Journal: Effects of chronic silencing of relaxin-3 production in nucleus incertus neurons on food intake, body weight, anxiety-like behaviour and limbic brain activity in female rats. (Pubmed Central) - Sep 16, 2020
Furthermore, NI RLN3 depletion disrupted corticosterone regulation, increased oxytocin and arginine-vasopressin, but not corticotropin-releasing factor, mRNA, in PVN, and decreased basal levels of c-fos mRNA in parvocellular and magnocellular PVN, bed nucleus of stria terminalis and the lateral hypothalamic area, brain regions involved in stress and feeding. These findings support a role for NI RLN3 neurons in fine-tuning stress and neuroendocrine responses and food intake regulation in female rats.
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Journal, Oncolytic Virus: Systemic administration of human mesenchymal stromal cells infected with polymer-coated oncolytic adenovirus induces efficient pancreatic tumor homing and infiltration. (Pubmed Central) - Sep 13, 2020
To overcome the poor delivery of oAd into hMSCs, a relaxin (RLX)-expressing oncolytic Ad (oAd/RLX), which degrades dense tumor extracellular matrix of highly desmoplastic pancreatic cancer, was complexed with biodegradable polymer (poly (ethyleneimine)-conjugated poly(CBA-DAH); PCDP), generating oAd/RLX-PCDP complex...This potent antitumor effect of systemically administered oAd/RLX-PCDP-treated hMSCs was achieved by superior viral replication in tumor tissues than any other treatment group. In conclusion, these results demonstrate that hMSCs are effective carriers for the systemic delivery of oAd to tumor sites and treatment of pancreatic cancer.
- |||||||||| Reasanz (serelaxin) / Novartis
Journal: Expanding the evolutionary explanations for sex differences in the human skeleton. (Pubmed Central) - Sep 5, 2020
Evolutionary explanations for skeletal sex differences (aka sexual dimorphism) that focus too narrowly on big competitive men and broad birthing women must account for the adaptive biology of skeletal growth and its dependence on the developmental physiology of reproduction. In this case, dichotomizing evolution into proximate-ultimate categories may be impeding the progress of human evolutionary science, as well as enabling the popular misunderstanding and abuse of it.
- |||||||||| norethindrone / Generic mfg.
Journal: The Effect of Oral Contraceptive Hormones on Anterior Cruciate Ligament Strength. (Pubmed Central) - Sep 4, 2020
OC formulations with higher progestin-to-estrogen ratios may be more protective for the ACL than formulations with lower ratios. OC formulations with high progestin-to-estrogen ratios may benefit female athletes by reducing their ACL injury risk by decreasing the effects of relaxin on the ACL.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Anti-fibrotic mechanisms of angiotensin AT -receptor stimulation. (Pubmed Central) - Sep 2, 2020
The article further discusses intracellular signalling mechanisms mediating the AT -receptor coupled anti-fibrotic effect, including activation of phosphatases and subsequent interference with pro-fibrotic signalling pathways, induction of matrix-metalloproteinases, and hetero-dimerisation with the AT -receptor, the TGF-βRII-receptor or the RXFP1-receptor for relaxin. Knowledge of the anti-fibrotic effects of the AT -receptor is of particular relevance, because drugs targeting this receptor have entered clinical development for indications involving fibrotic diseases.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Signalling in response to sub-picomolar concentrations of active compounds: pushing the boundaries of G protein-coupled receptor sensitivity. (Pubmed Central) - Aug 23, 2020
We have recently shown that such ultra-sensitivity is also demonstrated by a wide range of prototypical GPCRs, and we have determined the molecular mechanisms behind these responses for three family A GPCRs: the relaxin receptor, RXFP1; the β -adrenoceptor; and the M muscarinic ACh receptor...These occur through a diverse range of signalling pathways and produce modulation of important physiological processes, including neuronal transmission, chemotaxis, gene transcription, protein/ion uptake and secretion, muscle contraction and relaxation, and phagocytosis. Here we summarise the accumulating evidence of ultra-sensitive receptor signalling to show that this is a common, though currently underappreciated, property of GPCRs.
- |||||||||| Reasanz (serelaxin) / Novartis
[VIRTUAL] Local delivery of relaxin-2 as a novel treatment for shoulder arthrofibrosis (On Demand Oral) - Aug 20, 2020 - Abstract #ACSFall2020ACS-Fall_2391;
Major problems with the current treatment strategies include being invasive, having varying degrees of success and they do not target the underlying causes of fibrosis development. We report that intra-articular injections of the natural antifibrotic peptide hormone relaxin-2 alleviates fibrosis in the shoulder joint space by remodeling the ECM and reducing levels of collagen-I in vitro and in vivo, as well as restores glenohumeral ROM in an in vivo rat shoulder contracture model, demonstrating its potential use as an innovative antifibrotic therapeutic.
- |||||||||| Reasanz (serelaxin) / Novartis
Journal: RXFP2 as novel potential biomarker for abnormal differentiation induced by diethylstilbestrol in the gubernaculum of fetal mice. (Pubmed Central) - Aug 11, 2020
In vitro and in vivo experiments were performed to examine the expression level and mechanism of relaxin family peptide receptor 2 (RXFP2) in the gubernaculum of fetal mice following diethylstilbestrol (DES) treatment...These data demonstrate that DES is toxic to gubernaculum in fetal mice, and that RXFP2 is associated with the abnormal gubernaculum morphology induced by DES. Taken together, these data suggest that RXFP2 may be a novel potential biomarker for abnormal differentiation of the gubernaculum.
- |||||||||| Reasanz (serelaxin) / Novartis
Journal: Priming with oxytocin and relaxin improves cardiac differentiation of adipose tissue-derived stem cells. (Pubmed Central) - Jul 25, 2020
In our experiment, oxytocin-relaxin combination increased the population of cardiac troponin I-expressing cells to 6.84% as compared with 2.36% for the untreated ADSCs, 3.7% for oxytocin treatment and 3.41% for relaxin treatment groups. In summary, the results of this study indicated that oxytocin and relaxin hormones individually and in combination can improve cardiac differentiation of ADSCs, and treatment of the ADSCs and possibly other mesenchymal stem cells with these hormones may enhance their cardiogenic differentiation and survival after transplantation into the ischemic heart tissue.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: From sensory circumventricular organs to cerebral cortex: neural pathways controlling thirst and hunger. (Pubmed Central) - Jul 25, 2020
The subfornical organ and OVLT respond to circulating angiotensin II, relaxin and hypertonicity to drive thirst-related neural pathways, whereas circulating amylin, leptin and possibly glucagon-like peptide-1 act at the area postrema to influence neural pathways inhibiting food intake...For thirst, the median preoptic nucleus initially, and thereafter the thalamic paraventricular nucleus and lateral hypothalamus have been identified as likely sites of synaptic links in pathways from subfornical organ and OVLT to the cortex. The challenge remains to identify the links in the neural pathways that relay signals originating in sensory CVOs to cortical sites subserving either thirst or hunger.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Frozen-thawed embryo transfer: the potential importance of the corpus luteum in preventing obstetrical complications. (Pubmed Central) - Jul 24, 2020
The CL produces not only E and P, but also vasoactive products, such as relaxin and vascular endothelial growth factor, which are not replaced in a programmed FET cycle and which are hypothesized to be important for initial placentation...Despite the widespread use of FET, the optimal protocol with respect to live birth rate, maternal health, and perinatal outcomes has yet to be determined. Future practice regarding FET should be based on high-quality evidence, including rigorous controlled trials.
- |||||||||| Reasanz (serelaxin) / Novartis
[VIRTUAL] Unrevealed Structural, Functional and Immunological Pulmonary Changes Induced by Metabolic Syndrome in Elderly (Channel 2) - Jul 15, 2020 - Abstract #ERS2020ERS_5095;
Since these changes in R5Hz, R20Hz and R5Hz-R20Hz may occurs due to airway inflammation and remodeling, the analysis of pro-inflammatory (leptin; IL-1beta; IL-8, p<0.0001; TNF-alpha, p<0.04), anti-inflammatory cytokines (adiponectin; IL-1ra; IL-10; p<0.0001), anti-fibrotic (relaxin 1; relaxin 3; Klotho, p<0.0001) and pro-fibrotic (VEGF, p<0.0001) factors, revealed that MS induces a pulmonary pro-inflammatory and pro-fibrotic response. IOS is an important tool to differentiates the lung function and mechanics of elderly with MS, who present increased airway resistance involving increases in pulmonary pro-inflammatory and pro-fibrotic mediators.
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