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https://www.readbyqxmd.com/read/29146972/specific-targeting-of-melanotic-cells-with-peptide-ligated-photosensitizers-for-photodynamic-therapy
#1
Paul Lorenz Bigliardi, Bhimsen Rout, Aakanksha Pant, Viknish Krishnan-Kutty, Alex N Eberle, Ramasamy Srinivas, Brendan Adrian Burkett, Mei Bigliardi-Qi
A strategy combining covalent conjugation of photosensitizers to a peptide ligand directed to the melanocortin 1 (MC1) receptor with the application of sequential LED light dosage at near-IR wavelengths was developed to achieve specific cytotoxicity to melanocytes and melanoma (MEL) with minimal collateral damage to surrounding cells such as keratinocytes (KER). The specific killing of melanotic cells by targeted photodynamic therapy (PDT) described in this study holds promise as a potentially effective adjuvant therapeutic method to control benign skin hyperpigmentation or superficial melanotic malignancy such as Lentigo Maligna Melanoma (LMM)...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138870/insig2-rs7566605-single-nucleotide-variant-and-global-dna-methylation-index-levels-are-associated-with-weight-loss-in-a-personalized-weight-reduction-program
#2
Francesca Pirini, Sebastian Rodriguez-Torres, Bola Grace Ayandibu, María Orera-Clemente, Alberto Gonzalez-de la Vega, Fahcina Lawson, Roland J Thorpe, David Sidransky, Rafael Guerrero-Preston
Single nucleotide polymorphisms associated with lipid metabolism and energy balance are implicated in the weight loss response caused by nutritional interventions. Diet‑induced weight loss is also associated with differential global DNA methylation. DNA methylation has been proposed as a predictive biomarker for weight loss response. Personalized biomarkers for successful weight loss may inform clinical decisions when deciding between behavioral and surgical weight loss interventions. The aim of the present study was to investigate the association between global DNA methylation, genetic variants associated with energy balance and lipid metabolism, and weight loss following a non‑surgical weight loss regimen...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29124692/ultraviolet-radiations-skin-defense-damage-mechanism
#3
Dheeraj Mohania, Shikha Chandel, Parveen Kumar, Vivek Verma, Kumar Digvijay, Deepika Tripathi, Khushboo Choudhury, Sandeep Kumar Mitten, Dilip Shah
UV-radiations are the invisible part of light spectra having a wavelength between visible rays and X-rays. Based on wavelength, UV rays are subdivided into UV-A (320-400 nm), UV-B (280-320 nm) and UV-C (200-280 nm). Ultraviolet rays can have both harmful and beneficial effects. UV-C has the property of ionization thus acting as a strong mutagen, which can cause immune-mediated disease and cancer in adverse cases. Numbers of genetic factors have been identified in human involved in inducing skin cancer from UV-radiations...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29121414/stress-induced-suppression-of-neuropeptide-y-induced-hunger-in-anorexic-chicks-involves-corticotropin-releasing-factor-signaling-and-the-paraventricular-nucleus-of-the-hypothalamus
#4
Jinxin Wang, Jiaqing Yi, Paul B Siegel, Mark A Cline, Elizabeth R Gilbert
The Virginia lines of chickens have been selected for low (LWS) or high (HWS) juvenile body weight and have different severities of anorexia and obesity, respectively. The LWS that are exposed to stressors at hatch are refractory to neuropeptide Y (NPY)-induced food intake and the objective was to elucidate the underlying mechanisms. Chicks were exposed to a stressor (-20°C for 6 minutes, and 22°C and delayed access to food for 24 hours) after hatch and hypothalamic nuclei, including the lateral hypothalamus (LH), paraventricular nucleus (PVN), ventromedial hypothalamus (VMH), and arcuate nucleus (ARC), were collected 5 days later...
November 9, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/29113896/neuroinflammation-produced-by-heavy-alcohol-intake-is-due-to-loops-of-interactions-between-toll-like-4-and-tnf-receptors-peroxisome-proliferator-activated-receptors-and-the-central-melanocortin-system-a-novel-hypothesis-and-new-therapeutic-avenues
#5
Osvaldo Flores-Bastías, Eduardo Karahanian
Excessive alcohol intake induces an inflammatory response in the brain, via TNFα, TLR4 and NF-κB signaling pathways. It has been proposed that neuroinflammation would play a very important role in the development of alcohol addiction. In addition to stimulating the synthesis of inflammatory mediators such as IL-6, IL-1β and TNFα, NF-κB is capable of reducing the anti-inflammatory activity of PPARα and PPARγ. Reciprocally, PPARα, PPARγ and melanocortin 4 receptor (MC4R) can decrease the proinflammatory activity of NF-κB, establishing an interplay of inactivations between such nuclear factors and receptors...
November 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29099963/activity-of-the-hypothalamic-melanocortin-system-decreases-in-middle-aged-and-increases-in-old-rats
#6
Nóra Füredi, Alexandra Mikó, Balázs Gaszner, Diána Feller, Ildikó Rostás, Judit Tenk, Margit Solymár, Márta Balaskó, Erika Pétervári
Appearance of middle-aged obesity and aging anorexia both in humans and rodents suggests a role for regulatory alterations. Hypothalamic melanocortin agonist, alpha-melanocyte-stimulating hormone (alpha-MSH) produced in the arcuate nucleus (ARC) reduces body weight via inducing hypermetabolism and anorexia mainly through melanocortin 4 receptors (MC4R) in the paraventricular nucleus (PVN). Orexigenic ARC-derived agouti-related protein (AgRP) is an inverse agonist on MC4R in the PVN. Previously we demonstrated that characteristic age-related shifts in the catabolic effects of alpha-MSH may contribute both to middle-aged obesity and aging anorexia...
November 1, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29097517/neuropeptides-in-obesity-and-metabolic-disease
#7
REVIEW
Agatha A van der Klaauw
BACKGROUND: The global rise in the prevalence of obesity and associated comorbidities such as type 2 diabetes, cardiovascular disease, and cancer represents a major public health concern. CONTENT: Studies in rodents with the use of global and targeted gene disruption, and mapping of neurocircuitry by using optogenetics and designer receptors exclusively activated by designer drugs (DREADDs) have greatly advanced our understanding of the neural control of body weight...
November 2, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/29094944/design-of-mc1r-selective-%C3%AE-msh-analogues-with-canonical-amino-acids-leads-to-potency-and-pigmentation
#8
Yang Zhou, Saghar Mowlazadeh Haghighi, Ioanna Zoi, Jonathon R Sawyer, Victor J Hruby, Minying Cai
Melanoma is a lethal form of skin cancer. Skin pigmentation, which is regulated by the melanocortin 1 receptor (MC1R), is an effective protection against melanoma. However, the endogenous MC1R agonists lack selectivity for the MC1R and thus can have side effects. The use of noncanonical amino acids in previous MC1R ligand development raises safety concerns. Here we report the development of the first potent and selective hMC1R agonist with only canonical amino acids. Using γ-MSH as a template, we developed a peptide, [Leu(3), Leu(7), Phe(8)]-γ-MSH-NH2 (compound 5), which is 16-fold selective for the hMC1R (EC50 = 4...
November 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29059347/sim1-neurons-are-sufficient-for-mc4r-mediated-sexual-function-in-male-mice
#9
Erin Semple, Jennifer W Hill
Sexual dysfunction is a poorly understood condition that affects up to one-third of men around the world. Existing treatments that target the periphery do not work for all men. Previous studies have shown that central melanocortins, which are released by pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus, can lead to male erection and increased libido. Several studies specifically implicate the melanocortin 4 receptor (MC4R) in the central control of sexual function, but the specific neural circuitry involved is unknown...
October 19, 2017: Endocrinology
https://www.readbyqxmd.com/read/29058865/melanocortin-1-receptor-targeting-ultrasmall-silica-nanoparticles-for-dual-modality-human-melanoma-imaging
#10
Feng Chen, Xiuli Zhang, Kai Ma, Brian Madajewski, Miriam Benezra, Li Zhang, Evan Phillips, Melik Ziya Turker, Fabio Gallazzi, Michael Overholtzer, Mohan Pauliah, Mithat Gonen, Pat Zanzonico, Ulrich B Wiesner, Michelle S Bradbury, Thomas Quinn
The poor prognosis associated with malignant melanoma has not changed substantially over the past 30 years. Targeted molecular therapies, such as immunotherapy have shown promise, but suffer from resistance and off-target toxicities, underscoring the need for alternative therapeutic strategies that can be used in combination with existing protocols. Moreover, peptides targeting melanoma-specific markers, like the melanocortin-1 receptor (MC1-R), for imaging and therapy exhibit high renal uptake that limits clinical translation...
October 23, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29058194/characterization-of-mc4r-regulation-of-the-kir7-1-channel-using-the-tl-flux-assay
#11
Michael J Litt, Roger D Cone, Masoud Ghamari-Langroudi
The family of inward rectifying potassium channels (Kir channels) plays crucial roles in the regulation of heart rhythms, renal excretion, insulin release, and neuronal activity. Their dysfunction has been attributed to numerous diseases such as cardiac arrhythmia, kidney failure and electrolyte imbalance, diabetes mellitus, epilepsy, retinal degeneration, and other neuronal disorders. We have recently demonstrated that the melanocortin-4 receptor (MC4R), a Gαs-coupled GPCR, regulates Kir7.1 activity through a mechanism independent of Gαs and cAMP...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29056149/the-role-of-the-melanocortin-system-in-drug-and-alcohol-abuse
#12
Montserrat Navarro
The melanocortin (MC) system is composed of different peptides centrally produced by proopiomelanocortin neurons in the arcuate nucleus of the hypothalamus (N.Arc) and the medulla. These peptides act through five subtypes of melanocortin receptors (MCRs) that belong to the family of seven-transmembrane G-protein-coupled receptors that are coupled through Gαs signaling pathways. MC3R and MC4R are the predominant MCR subtypes in the brain, and they are widely expressed in brain regions thought to modulate drug self-administration, including the nucleus accumbens, the hypothalamus, and the ventral tegmental area...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/29044987/sticky-fingers-at-work-palmitoylation-dependent-mc1r-activation
#13
Jose Carlos Garcia-Borron, Celia Jimenez-Cervantes
No abstract text is available yet for this article.
October 17, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29044715/bayesian-genome-wide-association-analysis-for-body-weight-in-farmed-atlantic-salmon-salmo-salar-l
#14
G M Yoshida, J P Lhorente, R Carvalheiro, J M Yáñez
We performed a genome-wide association study to detect markers associated with growth traits in Atlantic salmon. The analyzed traits included body weight at tagging (BWT) and body weight at 25 months (BW25M). Genotypes of 4662 animals were imputed from the 50K SNP chip to the 200K SNP chip using fimpute software. The markers were simultaneously modeled using Bayes C to identify genomic regions associated with the traits. We identified windows explaining a maximum of 3.71% and 3.61% of the genetic variance for BWT and BW25M respectively...
October 17, 2017: Animal Genetics
https://www.readbyqxmd.com/read/29031731/evaluation-of-a-melanocortin-4-receptor-mc4r-agonist-setmelanotide-in-mc4r-deficiency
#15
Tinh-Hai Collet, Béatrice Dubern, Jacek Mokrosinski, Hillori Connors, Julia M Keogh, Edson Mendes de Oliveira, Elana Henning, Christine Poitou-Bernert, Jean-Michel Oppert, Patrick Tounian, Florence Marchelli, Rohia Alili, Johanne Le Beyec, Dominique Pépin, Jean-Marc Lacorte, Andrew Gottesdiener, Rebecca Bounds, Shubh Sharma, Cathy Folster, Bart Henderson, Stephen O'Rahilly, Elizabeth Stoner, Keith Gottesdiener, Brandon L Panaro, Roger D Cone, Karine Clément, I Sadaf Farooqi, Lex H T Van der Ploeg
OBJECTIVE: Pro-opiomelanocortin (POMC)-derived peptides act on neurons expressing the Melanocortin 4 receptor (MC4R) to reduce body weight. Setmelanotide is a highly potent MC4R agonist that leads to weight loss in diet-induced obese animals and in obese individuals with complete POMC deficiency. While POMC deficiency is very rare, 1-5% of severely obese individuals harbor heterozygous mutations in MC4R. We sought to assess the efficacy of Setmelanotide in human MC4R deficiency. METHODS: We studied the effects of Setmelanotide on mutant MC4Rs in cells and the weight loss response to Setmelanotide administration in rodent studies and a human clinical trial...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031713/peripheral-cannabinoid-1-receptor-blockade-restores-hypothalamic-leptin-signaling
#16
Joseph Tam, Gergő Szanda, Adi Drori, Ziyi Liu, Resat Cinar, Yoshihiro Kashiwaya, Marc L Reitman, George Kunos
OBJECTIVE: In visceral obesity, an overactive endocannabinoid/CB1 receptor (CB1R) system promotes increased caloric intake and decreases energy expenditure, which are mitigated by global or peripheral CB1R blockade. In mice with diet-induced obesity (DIO), inhibition of food intake by the peripherally restricted CB1R antagonist JD5037 could be attributed to endogenous leptin due to the rapid reversal of hyperleptinemia that maintains leptin resistance, but the signaling pathway engaged by leptin has remained to be determined...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031712/mitochondrial-uncoupling-in-the-melanocortin-system-differentially-regulates-npy-and-pomc-neurons-to-promote-weight-loss
#17
Natalie Jane Michael, Stephanie Elise Simonds, Marco van den Top, Michael Alexander Cowley, David Spanswick
OBJECTIVE: The mitochondrial uncoupling agent 2,4-dinitrophenol (DNP), historically used as a treatment for obesity, is known to cross the blood-brain-barrier, but its effects on central neural circuits controlling body weight are largely unknown. As hypothalamic melanocortin neuropeptide Y/agouti-related protein (NPY/AgRP) and pro-opiomelanocortin (POMC) neurons represent key central regulators of food intake and energy expenditure we investigated the effects of DNP on these neurons, food intake and energy expenditure...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031711/lorcaserin-improves-glycemic-control-via-a-melanocortin-neurocircuit
#18
Luke K Burke, Emmanuel Ogunnowo-Bada, Teodora Georgescu, Claudia Cristiano, Pablo B Martinez de Morentin, Lourdes Valencia Torres, Giuseppe D'Agostino, Christine Riches, Nicholas Heeley, Yue Ruan, Marcelo Rubinstein, Malcolm J Low, Martin G Myers, Justin J Rochford, Mark L Evans, Lora K Heisler
OBJECTIVE: The increasing prevalence of type 2 diabetes (T2D) and associated morbidity and mortality emphasizes the need for a more complete understanding of the mechanisms mediating glucose homeostasis to accelerate the identification of new medications. Recent reports indicate that the obesity medication lorcaserin, a 5-hydroxytryptamine (5-HT, serotonin) 2C receptor (5-HT2CR) agonist, improves glycemic control in association with weight loss in obese patients with T2D. Here we evaluate whether lorcaserin has an effect on glycemia without body weight loss and how this effect is achieved...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29030576/genetic-induction-of-hypometabolism-by-ablation-of-mc4r-does-not-suppress-als-like-phenotypes-in-the-g93a-mutant-sod1-mouse-model
#19
Shachee Doshi, Preetika Gupta, Robert G Kalb
Dysfunction and death of motor neurons leads to progressive paralysis in amyotrophic lateral sclerosis (ALS). Recent studies have reported organism-level metabolic dysfunction as a prominent but poorly understood feature of the disease. ALS patients are hypermetabolic with increased resting energy expenditure, but if and how hypermetabolism contributes to disease pathology is unknown. We asked if decreasing metabolism in the mutant superoxide dismutase 1 (SOD1) mouse model of ALS (G93A SOD1) would alter motor function and survival...
October 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29020973/the-%C3%AE-melanocyte-stimulating-hormone-peroxisome-proliferator-activated-receptor-%C3%AE-pathway-down-regulates-proliferation-in-melanoma-cell-lines
#20
Enrica Flori, Eleonora Rosati, Giorgia Cardinali, Daniela Kovacs, Barbara Bellei, Mauro Picardo, Vittoria Maresca
BACKGROUND: The α-Melanocyte Stimulating Hormone (αMSH)/Melanocortin-1 receptor (MC1R) interaction promotes melanogenesis through the cAMP/PKA pathway. The direct induction of this pathway by Forskolin (FSK) is also known to enhance melanocyte proliferation. αMSH acts as a mitogenic agent in melanocytes and its effect on proliferation of melanoma cells is less known. We previously identified the αMSH/Peroxisome Proliferator Activated Receptor (PPARγ) pathway as a new pathway on the B16-F10 mouse melanoma cell line...
October 11, 2017: Journal of Experimental & Clinical Cancer Research: CR
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