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Indications for an antidepressive effect of thymosin alpha-1 in a small open-label proof of concept study in common variable immune deficiency patients with depression.
Brain Behav Immun Health
Daniël G Aynekulu Mersha, Sarah E Fromme, Frank van Boven +7 more
A considerable proportion (21%) of patients with common variable immunodeficiency (CVID) suffers from depression. These subjects are characterized by reduced naïve T cells and a premature T cell senescence similar to that of patients with major depressive disorder (MDD). It is known that T cells are essential for limbic system development/function. Treatment with thymosin α1 (Tα1) is capable to increase the thymus output of naïve T cells.
Apelinergic System Affects Electrocardiographic Abnormalities Induced by Doxorubicin.
Biomedicines
Kasper Buczma, Hubert Borzuta, Katarzyna Kamińska +6 more
Background/Objectives: Anthracyclines remain a pivotal element of numerous tumor management regimens; however, their utilization is associated with a range of adverse effects, the most significant of which is cardiotoxicity. Research is constantly being conducted to identify substances that could be incorporated into ongoing cancer chemotherapy to mitigate anthracycline-induced cardiotoxicity. Recently, the apelinergic system has received a lot of attention in this field due to its involvement in cardiovascular regulation. Therefore, the aim of our study was to investigate the ability of the apelinergic system to inhibit the cardiotoxic effects of anthracycline-doxorubicin (DOX). Methods: In this study, 54 Sprague-Dawley rats were divided into seven groups and received intraperitoneal injections with DOX once a week for 4 consecutive weeks. The osmotic pumps provided a continuous release of NaCl (control groups), apelin-13 and elabela at two different doses, and the apelin receptor (APJ) antagonist ML221. Electrocardiography (ECG) and transthoracic echocardiography (TTE) with assessment of left ventricular (LV) systolic parameters were conducted on the first and last days of the experiment. Results: Lower doses of APJ agonists prevented the prolongation of QT and QTc intervals induced by DOX, while higher doses of these drugs exerted no such effect. The TTE examination confirmed DOX-induced LV systolic dysfunction. Moreover, the TTE examination revealed an improvement in the LV systolic parameters in the DOX-treated groups that were simultaneously administered APJ agonists. Conclusions: Our findings support the use of apelin and elabela as potential cardioprotective agents against anthracycline-induced cardiotoxicity.
Kisspeptin control of hypothalamus-pituitary-ovarian functions.
Vitam Horm
K P Joy, R Chaube
The discovery of Kisspeptin (Kiss) has opened a new direction in research on neuroendocrine control of reproduction in vertebrates. Belonging to the RF amide family of peptides, Kiss and its cognate receptor Gpr54 (Kissr) have a long and complex evolutionary history. Multiple forms of Kiss and Kissr are identified in non-mammalian vertebrates, with the exception of birds, and monotreme mammals. However, only a single form of the ligand (KISS1/Kiss1) and receptor (KISS1R/Kiss1r) is retained in higher mammals. Kiss1 is distributed in the hypothalamus-pituitary-gonadal (HPG) axis and its primary function is to stimulate gonadotropin-releasing hormone (GnRH) secretion. Kiss1 neurons are distributed in the rostral periventricular area of the third ventricle (RP3V) and arcuate/infundibular nucleus (ARN/IFN). The ARN/IFN is considered the GnRH pulse generator controlled by steroid negative feedback, and the RP3V neurons is concerned with GnRH surge induced by steroid positive feedback in females. The Kiss1-Kiss1r signaling is important in all aspects of reproduction: puberty onset, maintenance of adult gonadal functions and reproductive aging, and hence assumes therapeutic potentials in the treatment of reproductive dysfunctions and induction of artificial reproduction. This chapter reviews involvement of Kiss1 in the control of the HPG axis functions in female mammals.
Cerebrolysin treatment improved short-term memory deficits while simultaneously increasing hippocampal spine density in hypertensive female rats.
Behav Brain Res
Ivette Espinoza, Ma de Jesús Gómez-Villalobos, Leonardo Aguilar-Hernández +2 more
Hypertension, if untreated, can disrupt the blood-brain-barrier (BBB) and reduce cerebral flow in the central nervous system (CNS) inducing hippocampal atrophy, potentially leading to cognitive deficits and vascular dementia. Spontaneous hypertensive rats (SHR) demonstrated neuroplastic alterations in the hippocampus, hyperlocomotion and memory deficits in males. Cerebrolysin (CBL), a neuropeptide preparation, induces synaptic and neuronal plasticity in various populations of neurons and repairs the integrity of the BBB. This research aims to investigate the behavioral outcomes in locomotion and recognition memory in the Novel Object Recognition Test (NORT) and assess the neuroreparative effect of CBL on the cytoarchitecture of neurons and the spine density in pyramidal neurons of the prefrontal cortex (PFC), the entorhinal cortex (EC) and the CA1 region of the dorsal hippocampus, as well as spheroidal neurons of the dentate gyrus (DG). Our findings indicate that SHR exhibited elevated diastolic and systolic pressures, and increased locomotion. Importantly, CBL treatment improved recognition memory in SHR strain. Hypertension led to reduced arborization in the EC, CA1, and DG regions. Moreover, CBL treatment increased arborization in both normotensive and hypertensive rats in the CA1, and DG regions of hippocampus and EC and selectively increased spine density in the hippocampus of hypertensive rats. These findings suggest that CBL neurotrophic treatment enhances recognition memory and promotes dendritic growth or spine density, depending on the neurochemical environment within the brain.
Injectable Therapeutic Peptides-An Adjunct to Regenerative Medicine and Sports Performance?
Arthroscopy
Mikalyn T DeFoor, Travis J Dekker
High-level athletes and bodybuilders are constantly seeking novel therapies to enhance recovery and expedite return from injury-injectable peptides are a new and trending therapy that may be the wave of the future in the realm of regenerative medicine research in treating joint injuries and osteoarthritis. Very early in vivo research on pharmacokinetics indicates the possibility that body protection compound 157 (BPC-157) is at the forefront of therapeutic peptides, with early demonstrations of this experimental peptide optimizing endurance training, metabolism, recovery, and tissue repair. Although unregulated and yet readily available for purchase over the internet, there is scarce orthopaedic literature investigating the clinical use and outcomes of such therapeutic peptides in tendon, muscle, and cartilage injury. However, this has not slowed the recent exponential growth of the multi-billion-dollar industry in the development of therapeutic peptides. As orthopaedic surgeons and team physicians, we should stay up to date with the latest pharmacokinetic, safety, ethical, and legal profiles and regulations regarding synthetic peptide supplementation for injury recovery and sports performance optimization in our patients, from elite athletes to fitness fanatics, because they will continue to seek the latest and greatest in treatment options and will be approaching us with questions on their results, risks, and benefits.
Novel Pharmacologic Treatments of Female Sexual Dysfunction.
Clin Obstet Gynecol
Andrew How, Christopher Jowdy, Elli Novatcheva +1 more
This review evaluates pharmacologic treatments for female sexual dysfunction (FSD), focusing on hypoactive sexual desire disorder (HSDD). We provide clinically relevant applications for Food and Drug Administration (FDA)-approved medications (flibanserin and bremelanotide) and investigational therapies (Lorexys and testosterone combinations). Detailed study outcomes, safety profiles, and clinical strategies guide clinicians in appropriate diagnosis, patient selection, expectation setting, side effect management, and patient education, improving treatment outcomes and patient satisfaction.
Gastrointestinal hormones and subjective ratings of appetite after low-carbohydrate vs low-fat low-energy diets in females with lipedema - A randomized controlled trial.
Clin Nutr ESPEN
Julianne Lundanes, Gunnhild Eggen Storliløkken, Marte Siwsdotter Solem +7 more
Ketosis seems to attenuate, or prevent, the rise in both ghrelin concentrations and subjective hunger ratings that follow weight loss. However, most of the previous studies have employed very-low energy diets (VLED) and are therefore limited in terms of generalizability.
Magnetic Nanoactuator-Protein Fiber Coated Hydrogel Dressing for Well-Balanced Skin Wound Healing and Tissue Regeneration.
ACS Nano
Chenlong He, Ming Yin, Han Zhou +8 more
Despite significant progress in skin wound healing, it is still a challenge to construct multifunctional bioactive dressings based on a highly aligned protein fiber coated hydrogel matrix for antifibrosis skin wound regeneration that is indistinguishable to native skin. In this study, a "dual-wheel-driven" strategy is adopted to modify the surface of methacrylated gelatin (GelMA) hydrogel with highly aligned magnetic nanocomposites-protein fiber assemblies (MPF) consisting of photothermal responsive antibacteria superparamagnetic nanocomposites-fibrinogen (Fg) complexes as the building blocks. Whole-phase healing properties of the modified hydrogel dressing, GelMA-MPF (GMPF), stem from the integration of Fg protein with RGD peptide activity decorated on the surface of the antibacterial magnetic nanoactuator, facilitating facile and reproducible dressing preparation by self-assembly and involving biochemical, morphological, and biophysical cues. Payload and substantial release of copper ions for in situ catalytic production of nitric oxide (NO) from the fiber inorganic skeleton adsorbed by Fg molecules collectively regulate the proliferation, migration, reorganization, and transdifferentiation behavior of fibroblasts and fulfill antifibrosis in the process of skin wound healing and subcutaneous appendage regeneration. In full-thickness skin lesion mouse models, the complete regeneration of skin tissue with regenerated hair follicle cells and capillary blood vessels is realized in a temporally and spatially ordered manner.
Compounded glucagon-like peptide-1 receptor agonists for weight loss: the direct-to-consumer market in Colorado.
J Pharm Policy Pract
Michael J DiStefano, Mouna Dardouri, Gina D Moore +2 more
High prices and other access barriers have contributed to the rise of a market for compounded glucagon-like peptide-1 receptor agonists for weight loss in the United States. This market has not been systematically studied. We conducted a pilot study to assess the prevalence, characteristics, and advertising content of direct-to-consumer providers of compounded glucagon-like peptide-1 products for weight loss in Colorado.
ACTH-like Peptides Compensate Rat Brain Gene Expression Profile Disrupted by Ischemia a Day After Experimental Stroke.
Biomedicines
Ivan B Filippenkov, Yana Yu Shpetko, Vasily V Stavchansky +6 more
Background: Ischemic stroke results from a disruption of cerebral blood flow. Adrenocorticotropic hormone (ACTH) serves as the basis for the creation of synthetic peptides as neuroprotective agents for stroke therapy. Previously, using RNA-Seq we first revealed differential expressed genes (DEGs) associated with ACTH(4-7)PGP (Semax) and ACTH(6-9)PGP peptides under cerebral ischemia conditions. Analysis was carried out at 4.5 h after transient middle cerebral artery occlusion (tMCAO) model in the ipsilateral frontal cortex of a rat brain. Methods: Here, we analyzed the penumbra-associated frontal cortex of rats and actions under the same peptides at 24 h after tMCAO using RNA-Seq. Results: 3774 DEGs (fold change > 1.5 and Padj < 0.05) were identified under ischemia conditions, whereas 1539 and 2066 DEGs were revealed under Semax and ACTH(6-9)PGP peptides at 24 h after tMCAO. Furthermore, both peptides significantly reduced expression distortions caused by ischemia for 1171 genes associated with immune and neurosignaling pathways. Concomitantly, there were 32 DEGs under ACTH(6-9)PGP versus Semax administration at 24 h after tMCAO. Besides, neurogenesis-, angiogenesis-, protein kinase- and growth factor-related DEGs were revealed under peptides action. Previously, we observed the neuroprotective effect of peptides at the histological level in rat brains at 24 h after tMCAO. Thus, here we demonstrate the transcriptome manifestation of this histological effect. Furthermore, comparison with previous data at the 4.5 h post-tMCAO time point showed that the pattern of peptide action on the transcriptome depends on the time elapsed after tMCAO. Conclusions: We revealed that the effect of ACTH(6-9)PGP was more similar to Semax than different from it a day after tMCAO. At this time point, ACTH-like peptides compensated rat brain gene expression profiles disrupted by ischemia. Thus, our results may be useful for selecting more effective structures for future anti-stroke drugs and appropriate post-stroke time points for their testing.
Effects of Illumination Color on Hypothalamic Appetite-Regulating Gene Expression and Glycolipid Metabolism.
Nutrients
Qi Wang, Qianru Li, Tuo Quan +6 more
Irregular illumination is a newly discovered ambient factor that affects dietary and metabolic processes. However, the effect of the modulation of long-term light exposure on appetite and metabolism remains elusive. Therefore, in this current study, we systematically investigated the effects of up to 8 weeks of exposure to red (RL), green (GL), and white light (WL) environments on appetite, food preferences, and glucose homeostasis in mice on both high-fat and low-fat dietary patterns. It was found that the RL group exacerbated high-fat-induced obesity in mice compared with GL- or WL-treated mice. RL-exposed mice exhibited worsened metabolic profiles, including impaired glucose tolerance/insulin sensitivity, elevated lipid levels, and reduced serum insulin levels. Serological analyses showed that RL exposure resulted in decreased leptin levels and increased levels of orexigenic and hunger hormones in mice. Further qPCR analysis showed that the expression levels of the hypothalamic appetite-related genes NPY and AgRP mRNA were upregulated in RL-treated mice, while the expression level of the appetite suppressor gene POMC mRNA was downregulated. The results of this study will be instructive for the regulation of appetite and metabolism from the perspective of illumination colors.
Effects of Isoflavone Intake on Energy Requirement, Satiety, and Body Composition of Neutered Adult Cats.
Animals (Basel)
Ana Lúcia Yoshida da Silva Yamada, Mônica Estela Zambon Merenda, Layne Carolina Pereira +9 more
Isoflavones are composed of phytoestrogens (genistein and daidzein), which can be metabolized by cats. These compounds can promote the maintenance of lean body mass and control food intake. These effects are desirable in neutered animals, as they are predisposed to obesity. The objective of this study was to evaluate the effects of dietary supplementation of 1.0% isoflavone on the metabolizable energy intake, serum concentrations of satiety-related hormones and peptides, and body composition of neutered cats. Sixteen neutered adult cats were blocked by gender and divided into two groups (n = 8): the control group (CG) received a commercial diet, while the isoflavone group (IG) received the same diet supplemented by 1% of isoflavone for 99 days. Computed tomography was performed on the first and last experimental days to assess the animals' body composition. Satiety challenges were conducted on days 19 and 44. In the last day of the study, blood samples were collected to determine the concentration of insulin, ghrelin, leptin, peptide YY, and GLP-1. A statistical analysis was conducted using R software 3.5.2, considering both the interaction and individual effects of group and time (p < 0.05). The average intake of genistein in the IG was 0.75 ± 0.10 mg/kg body weight, and daidzein intake was 51.73 ± 7.05 mg/kg. No significant individual or interaction effects were observed for any of the analyzed variables. Therefore, the inclusion of 1.0% isoflavone in the diet did not affect the energy requirements, satiety responses, or body composition of neutered adult cats.
Dissociative Identity Disorder Cotreated With Zinc and L-carnosine: A Case Report.
Cureus
Kensaku Sakae, Machi Suka, Hiroyuki Yanagisawa
Little is known about the effectiveness of pharmacotherapy in dissociative identity disorder (DID). Zinc is essential for proper brain function. Its deficiency can lead to mental health symptoms, possibly contributing to dissociation. L-carnosine is an endogenous dipeptide with a neuroprotective effect. We report on the case of a 30-year-old woman with DID and comorbid bipolar I disorder who had zinc deficiency and was successfully cotreated with zinc and L-carnosine. She displayed three alternate identities and exhibited signs of emotional/mood instability, flashbacks, binge eating, and self-harm. The patient also displayed several physical symptoms of zinc deficiency. She did not respond to aripiprazole (0.75 mg/d) and clonazepam (1.5 mg/d), but responded marginally to five months of zinc (50 mg/d) supplementation. Simultaneous administration of L-carnosine, gradually increased from 0.5 g/d to 2 g/d over four months, markedly improved her symptoms. Five months after adding 2 g/d L-carnosine, the patient's pronounced alternate identities that people around her could notice no longer appeared. However, the identities that were not noticeable to the people remained. They disappeared completely two years later and reappeared only when zinc and L-carnosine were discontinued during the subsequent three-year follow-up. The patient's severity scores for dissociation and depression were reduced. Furthermore, signs of emotional/mood instability, flashbacks, binge eating, and self-harm improved. The physical symptoms of zinc deficiency eventually resolved. Further investigation of cotreatment with zinc and L-carnosine for DID and related conditions, particularly the contribution of zinc deficiency to dissociation, is necessary.
Adrenomedullin in pulmonary hypertension.
Dan Med J
Toshio Nishikimi, Hideyuki Kinoshita, Hideaki Inazumi +4 more
Adrenomedullin (AM) exerts strong pulmonary vasodilatory effects. These effects are mediated in part by nitric oxide. Plasma AM levels are increased in patients with pulmonary hypertension and correlate with disease severity and poor outcomes. Acute administration of AM improves the haemodynamics in patients with pulmonary hypertension, while chronic administration prevents the onset of pulmonary hypertension in animal models and delays its progression. Thus, AM is closely related to the pathophysiology of pulmonary hypertension and may be a promising therapeutic target.
Novel chimeric peptides based on endomorphins and ghrelin receptor antagonist produced supraspinal antinociceptive effects with reduced acute tolerance in mice.
Biochimie
Bing Wu, Songxia Cheng, Fuyan Liu +6 more
It is widely recognized that developing bi- or multifunctional opioid compounds could offer a valuable approach to pain management with fewer side effects compared to single-target compounds. In this study, we designed and characterized two novel chimeric peptides, EM-1-DLS and EM-2-DLS, incorporating endomorphins (EMs) and the ghrelin receptor antagonist [D-Lys3]-GHRP-6 (DLS). Functional assays demonstrated that EM-1-DLS and EM-2-DLS acted as κ-opioid receptor (κ-OR)-preferring agonists, weak μ-opioid receptors (μ-OR) and ghrelin receptor (GHSR) agonists. Upon intracerebroventricular (i.c.v.) administration in mice, both EM-1-DLS and EM-2-DLS exhibited dose- and time-dependent antinociceptive effects in the tail withdrawal test. EM-1-DLS demonstrated the highest antinociceptive potency among the peptides, with an ED50 approximately 8-fold greater than EM-1, while EM-2-DLS showed comparable effects to EM-2. The antinociceptive actions of EM-1-DLS involved activation of GHS-R1α, μ-OR, and κ-OR, whereas EM-2-DLS acted via GHS-R1α, δ-OR, and κ-OR pathways. Additionally, acute antinociceptive tolerance was investigated, revealing that EM-1-DLS induced a tolerance ratio of 2.33-fold, significantly lower than the 5.19-fold ratio induced by EM-1. Cross-tolerance ratios between the chimeric peptides and EMs ranged from 0.92 to 1.76, indicating reduced tolerance compared to EMs alone. These findings highlight the potential of these chimeric peptides to mitigate pain with diminished tolerance development, suggesting a promising strategy for the development of new analgesic therapies with improved safety profiles.
Copper-coordination driven brain-targeting nanoassembly for efficient glioblastoma multiforme immunotherapy by cuproptosis-mediated tumor immune microenvironment reprogramming.
J Nanobiotechnology
Yang Chen, Hailong Tian, Xiaodian Zhang +4 more
Limited drug accumulation and an immunosuppressive microenvironment are the major bottlenecks in the treatment of glioblastoma multiforme (GBM). Herein, we report a copper-coordination driven brain-targeting nanoassembly (TCe6@Cu/TP5 NPs) for site-specific delivery of therapeutic agents and efficient immunotherapy by activating the cGAS-STING pathway and downregulating the expression of PD-L1. To achieve this, the mitochondria-targeting triphenylphosphorus (TPP) was linked to photosensitizer Chlorin e6 (Ce6) to form TPP-Ce6 (TCe6), which was then self-assembled with copper ions and thymopentin (TP5) to obtain TCe6@Cu/TP5 NPs. This nanoassembly effectively accumulated in tumor sites through the copper transport mechanism. Meanwhile, TCe6@Cu/TP5 could induce mitochondrial impairment by photodynamic therapy (PDT) mediated reactive oxygen species (ROS) accumulation and Cu2+ triggered cuproptosis, resulting in evoking the AMP-activated protein kinase (AMPK) pathway to degrade PD-L1, and activating the cGAS-STING pathway to enhance anti-tumor immunity. Moreover, TP5 significantly promoted the proliferation and differentiation of dendritic cells (DCs) and T lymphocytes to further amplify the cancer immunity cycle. Collectively, our TCe6@Cu/TP5 NPs effectively facilitate drug accumulation and activate systemic antitumor immunity in vitro and in vivo, providing an innovative solution across the BBB that potentiates GBM immunotherapy.
Apelin/APJ signaling in IGF-1-induced acute mitochondrial and antioxidant effects in spontaneously hypertensive rat myocardium.
J Physiol Biochem
Alejandra M Yeves, Joshua Godoy Coto, Erica V Pereyra +4 more
IGF-1 and apelin are released in response to exercise training with beneficial effects. Previously we demonstrated that a swimming routine is effective to convert pathological into physiological cardiac hypertrophy, and that IGF-1 improves contractility and the redox state, in spontaneously hypertensive rats (SHR). Now, we hypothesize that the apelinergic pathway is involved in the cardioprotective effects of IGF-1 in the SHR. We assessed the redox state and mitochondrial effects of IGF-1 or apelin in the presence/absence of AG1024 or ML221 [pharmacological antagonists of IGF1 (IGF1R) and apelin (APJ) receptors, respectively] in SHR isolated cardiomyocytes or perfused hearts. Acute IGF-1 (10 nmol/L) significantly: -reduced H2O2 production (IGF-1:62 ± 6; control:100 ± 8.1, %), -increased the activity of superoxide dismutase (IGF-1:193 ± 17, control: 100 ± 13,%), -prevented H2O2-induced ΔΨm loss (TMREF10min/F0 min: IGF-1:0.93 ± 0.017, control: 0.72 ± 0.029), -reduced mitochondrial permeability transition pore (mPTP) opening estimated by the calcium retention capacity (nmol/mg protein, IGF-1:251 ± 34, control:112 ± 5), and -increased P-AMPK (IGF-1:129 ± 0.9, control: 100 ± 2%) and P-AKT (IGF-1:143 ± 17 control:100 ± 6, %). These effects were suppressed not only by the antagonism of IGF1R but also of APJ. Moreover, IGF-1 significantly increased APJ (IGF-1:198 ± 29 control:100 ± 15,%) and apelin mRNAs (IGF-1:251 ± 48, control:100 ± 6,%). On the other hand, an equipotent dose of exogenous apelin (50 nmol/L) emulated IGF-1 effects being cancelled by the antagonism of APJ however not by AG1024. IGF-1/IGF1R stimulates the apelinergic pathway, improving the redox balance and mitochondria status in the pathologically hypertrophied myocardium of the SHR.
KPV and RAPA Self-Assembled into Carrier-Free Nanodrugs for Vascular Calcification Therapy.
Adv Healthc Mater
Li Zhang, Dongze Li, Yierpani Aierken +7 more
Cardiovascular disease (CVD) is a leading cause of death globally, and vascular calcification (VC) is an important independent risk factor for predicting CVD. Currently, there are no established therapeutic strategies for the treatment of VC. Although recognized combination therapies of nanomedicines can provide effective strategies for disease treatment, the clinical application of nanomedicines is limited because of their complex preparation processes, low drug loading rates, and unpredictable safety risks. Thus, developing a simple, efficient, and safe nanodrug to simultaneously regulate inflammation and autophagy may be a promising strategy for treating VC. Herein, an anti-inflammatory peptide (lysine-proline-valine peptides, KPV) and the autophagy activator rapamycin (RAPA) are self-assembled to form new carrier-free spherical nanoparticles (NPs), which shows good stability and biosafety. In vivo and in vitro, KPV-RAPA NPs significantly inhibit VC in mice compared to the other treatment groups. Mechanistically, KPV-RAPA NPs inhibit inflammatory responses and activated autophagy. Therefore, this study indicates that the new carrier-free KPV-RAPA NPs have great potential as therapeutic agents for VC combination therapy, which can promote the development of nanodrugs for VC.
Discovery of MT-7117 (Dersimelagon Phosphoric Acid): A Novel, Potent, Selective, and Nonpeptidic Orally Available Melanocortin 1 Receptor Agonist.
J Med Chem
Atsushi Sato, Kenji Morokuma, Takashi Adachi +8 more
Activation of the melanocortin 1 receptor (MC1R) mediates melanogenesis in melanocytes, anti-inflammatory effects in inflammatory cells, and antifibrotic effects in fibroblasts. Thus, MC1R agonists are expected to be beneficial for treating skin, autoimmune, inflammatory, and fibrotic diseases. Afamelanotide, an α-melanocyte-stimulating hormone (α-MSH) analogue MC1R agonist, is used clinically for treating erythropoietic protoporphyria (EPP) as a subcutaneous implant formulation. We explored nonpeptidic small-molecule MC1R agonists with the aim of identifying more convenient oral drugs. By exploring the structure of previously reported compound 5, we discovered compound 11 (MT-7117: dersimelagon phosphoric acid). This compound exhibited strong MC1R agonistic activity, good pharmacokinetic properties, and excellent safety profiles. Furthermore, compound 11 was effective in animal pigmentation evaluation and skin fibrosis model studies. Compound 11 is currently in clinical trials for the treatment of EPP, X-linked protoporphyria (XLP), and systemic sclerosis (SSc). Proof of concept was obtained in phase 2 clinical studies on EPP and XLP.
Acute effect of exercise on appetite-related factors in males with obesity: A pilot study.
Physiol Rep
Sogand Asri, Farhad Rahmani-Nia, Payam Saidie +2 more
To investigate the role of appetite-related factors, including interleukin 6 (IL-6), irisin, interleukin 7 (IL-7), neuropeptide Y (NPY), and leptin, on appetite perception in males with obesity. Eleven males (BMI 35.3 ± 4.2 kg/m2, V̇O2peak 29 ± 3.1 mL/kg/min) participated in two experimental trials (MICE: 60 min of cycling at 60% of V̇O2peak; CTRL: 60 min of quiet resting) using a crossover design. Appetite parameters, including IL-6, IL-7, irisin, and leptin, were measured. Additionally, appetite perception was assessed. IL-6 concentration increased significantly immediately post-exercise (95% CI: [2.207-12.192] pg/mL, p = 0.007) and remained elevated 1 hour post-exercise (95% CI: [2.326-11.855] pg/mL, p = 0.006) compared to CTRL. Irisin also rose significantly immediately post-exercise (95% CI: [0.084-3.061] ng/mL, p = 0.039). NPY decreased significantly 1 h post-exercise (95% CI: [(-20.601) - (-1.380)] ng/L, p = 0.027). No significant differences were observed for IL-7 (p = 0.748, η p 2 $$ {\eta}_p^2 $$ = 0.077) and leptin (p = 0.285, η p 2 = 0.061 $$ {\eta}_p^2=0.061 $$ ). Appetite perceptions were suppressed immediately post-exercise (95% CI: [3.407-19.547] mm, p = 0.008) compared to CTRL. Sixty minutes of MICE increased IL-6 and irisin concentrations while suppressed NPY and appetite perceptions in males with obesity.