PHARMACOLOGIC INDUCTION OF THE MELANOCOTIN 1 RECEPTOR (MC1R) PATHWAY PROVIDES PROTECTION AGAINST SUNBURN AND ENHANCES EXPRESSION OF ANTIOXIDANT ENZYMES IN THE SKIN

The inability to tan properly after sun exposure strongly correlates with increased incidence of skin cancer. The melanocortin 1 receptor (MC1R) is a transmembrane Gs-coupled cell surface receptor found on epidermal melanocytes that transmits pro-survival and pro-differentiation signals mediated by the second messenger cAMP. Humans carrying loss-of-function polymorphisms in MC1R signaling exhibit higher incidences of skin cancers including melanoma. This study focused on the physiologic effects of topical application of forskolin, an adenylate cyclase activator, in extension (Mc1re/e) K14-SCF animals, which model the fair-skinned UV-sensitive human. Twice daily application of the drug promoted accelerated pigmentation, increased skin darkening due to epidermal deposition of melanin pigment, and induced epidermal melanin, which protected the skin against UV injury as judged by “minimal erythematous dose” (MED). Moreover, MC1R signaling regulated the expression of antioxidant enzymes at the transcriptional level. The human melanoma cell line A375, known to harbor a loss-of-function signaling mutation in MC1R, was used to determine effects of cAMP stimulation on the expression of antioxidant enzymes. We observed increases in expression of genes that control the biosynthesis and regulation of glutathione including the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), glutathione peroxidase, GPX, and glutathione reductase GSR. In addition, there is an increase in manganese superoxide dismutase (MnSOD) at the protein level. There was accumulation of MnSOD in the mitochondria after pharmacologic induction of cAMP with forskolin. Addition of the oxidative agent H2O2 enhanced the expression of MnSOD at the protein level as early as one hour after MC1R stimulation. Oxygen consumption rate on mitochondria was measured using Seahorse analysis; pharmacologic activation of MC1R/cAMP signaling did not affect mitochondrial metabolism. In addition, topical application of a crude extract of Solidago inhibited UV-induced inflammation in K14-SCF mice. Several UV-induced cytokines, including TNF-α, were down-regulated at the transcriptional level after topical application of Solidago extract. Together, these results indicate that MC1R signaling protects melanocytes from UV damage by regulating antioxidant enzyme expression and suggest that pharmacologic cAMP induction may be a useful preventive mechanism against UV-mediated skin sunburn and oxidative injury

Ultraviolet Radiation, Aging and the Skin: Prevention of Damage by Topical cAMP Manipulation

Being the largest and most visible organ of the body and heavily influenced by environmental factors, skin is ideal to study the long-term effects of aging. Throughout our lifetime, we accumulate damage generated by UV radiation. UV causes inflammation, immune changes, physical changes, impaired wound healing and DNA damage that promotes cellular senescence and carcinogenesis. Melanoma is the deadliest form of skin cancer and among the malignancies of highest increasing incidence over the last several decades. Melanoma incidence is directly related to age, with highest rates in individuals over the age of 55 years, making it a clear age-related disease. In this review, we will focus on UV-induced carcinogenesis and photo aging along with natural protective mechanisms that reduce amount of realized solar radiation dose and UV-induced injury. We will focus on the theoretical use of forskolin, a plant-derived pharmacologically active compound to protect the skin against UV injury and prevent aging symptoms by up-regulating melanin production. We will discuss its use as a topically-applied root-derived formulation of the Plectranthus barbatus (Coleus forskolii) plant that grows naturally in Asia and that has long been used in various Aryuvedic teas and therapeutic preparations

UV Radiation and the Skin

UV radiation (UV) is classified as a complete carcinogen because it is both a mutagen and a non-specific damaging agent and has properties of both a tumor initiator and a tumor promoter. In environmental abundance, UV is the most important modifiable risk factor for skin cancer and many other environmentally-influenced skin disorders. However, UV also benefits human health by mediating natural synthesis of vitamin D and endorphins in the skin, therefore UV has complex and mixed effects on human health. Nonetheless, excessive exposure to UV carries profound health risks, including atrophy, pigmentary changes, wrinkling and malignancy. UV is epidemiologically and molecularly linked to the three most common types of skin cancer, basal cell carcinoma, squamous cell carcinoma and malignant melanoma, which together affect more than a million Americans annually. Genetic factors also influence risk of UV-mediated skin disease. Polymorphisms of the melanocortin 1 receptor (MC1R) gene, in particular, correlate with fairness of skin, UV sensitivity, and enhanced cancer risk. We are interested in developing UV-protective approaches based on a detailed understanding of molecular events that occur after UV exposure, focusing particularly on epidermal melanization and the role of the MC1R in genome maintenance

Sociabilidades da morte em Zacatecas. A cooperativa mútua “Obreros Libres” e o apoio às mortes de seus membros, 1902-1910

The objective of this work is to analyze the labor sociabilities that workers (artisans, mining workers and manufacturing workers) adopted and implemented, through mutual aid societies, established in Zacatecas at the end of the 19th century and the beginning of the 20th century. The mutual-cooperative “Obreros Libres” is addressed, established in the city of Zacatecas and directed by Antonio Chávez Ramírez, a Freemason lawyer who moved, through the mutual, between the benefit of workers and political participation. In this context, the sociabilities of death arise in “Obreros Libres”, that is, the sociocultural actions that refer to funeral processions, civic-funeral rites carried out in recognition of active members, sick and deceased protectors. Like other actions and cultural practices in the world of work, it was part of a broader and more heterogeneous universe, instituted by the popular classes.El objetivo de este trabajo es analizar las sociabilidades laborales que adoptaron e implementaron los trabajadores (artesanos, operarios mineros y operarios de las manufacturas), a través de las sociedades de socorros mutuos, establecidas en Zacatecas a finales del siglo XIX y principios del siglo XX. Se aborda la mutuo-cooperativista “Obreros Libres”, establecida en la ciudad de Zacatecas y que fue dirigida por Antonio Chávez Ramírez, un abogado masón que se movió, a través de la mutualista, entre la beneficencia de los trabajadores y la participación política. En este contexto surgen las sociabilidades de la muerte en “Obreros Libres”, es decir, las acciones socioculturales que hacen referencia a los cortejos fúnebres, los ritos cívico-funerarios efectuados en reconocimiento a los socios activos, protectores enfermos y fallecidos. Al igual que otras acciones y prácticas culturales del mundo laboral que formaba parte de un universo más amplio y heterogéneo, instituido por las clases populares. O objetivo deste trabalho é analisar as capacidades trabalhistas adotadas e implementadas pelos trabalhadores (artesãos, trabalhadores da mineração e trabalhadores da indústria), por meio das sociedades de ajuda mútua, estabelecidas em Zacatecas no final do século XIX e início do século XX. Trata-se da cooperativa mútua “Obreros Libres”, estabelecida na cidade de Zacatecas e dirigida por Antonio Chávez Ramírez, advogado maçom que moveu, através do mutualista, entre a beneficência dos trabalhadores e a participação política. Nesse contexto surgem as sociabilidades da morte em “Trabalhadores Livres”, ou seja, as ações socioculturais que remetem às procissões fúnebres, os ritos cívico-fúnebres realizados em reconhecimento aos parceiros ativos, protetores doentes e falecidos. Como outras ações culturais e práticas do mundo do trabalho que fazia parte de um universo mais amplo e heterogêneo, instituído pelas classes populares.&nbsp

Ordres de protecció i drets de les dones que han patit violència de gènere : obstacles per a una efectiva protecció

El objetivo de esta investigación es comprender los mecanismos de aplicación/efectividad de las órdenes de protección relativas a las mujeres que han sufrido violencia de género que solicitan una orden de protección en Cataluña y qué factores inciden en el otorgamiento o la denegación. Los objetivos específicos han sido: 1. Identificar y analizar qué elementos se tienen en cuenta en el otorgamiento de las órdenes de protección; 2. Describir la percepción de seguridad de las mujeres; 3. Analizar la percepción de riesgo por parte de los cuerpos policiales; 4. Entender en el discurso de las/los operadoras/res jurídicos qué elementos son ponderados para otorgar o denegar la orden de protección

Young women's use of a microbicide surrogate: The complex influence of relationship characteristics and perceived male partners' evaluations

This is the post-print version of the article. The official published version can be found at the link below.Currently in clinical trials, vaginal microbicides are proposed as a female-initiated method of sexually transmitted infection prevention. Much of microbicide acceptability research has been conducted outside of the United States and frequently without consideration of the social interaction between sex partners, ignoring the complex gender and power structures often inherent in young women’s (heterosexual) relationships. Accordingly, the purpose of this study was to build on existing microbicide research by exploring the role of male partners and relationship characteristics on young women’s use of a microbicide surrogate, an inert vaginal moisturizer (VM), in a large city in the United States. Individual semi-structured interviews were conducted with 40 young women (18–23 years old; 85% African American; 47.5% mothers) following use of the VM during coital events for a 4 week period. Overall, the results indicated that relationship dynamics and perceptions of male partners influenced VM evaluation. These two factors suggest that relationship context will need to be considered in the promotion of vaginal microbicides. The findings offer insights into how future acceptability and use of microbicides will be influenced by gendered power dynamics. The results also underscore the importance of incorporating men into microbicide promotion efforts while encouraging a dialogue that focuses attention on power inequities that can exist in heterosexual relationships. Detailed understanding of these issues is essential for successful microbicide acceptability, social marketing, education, and use.This study was funded by a grant from National Institutes of Health (NIHU19AI 31494) as well as research awards to the first author: Friends of the Kinsey Institute Research Grant Award, Indiana University’s School of HPER Graduate Student Grant-in-Aid of Research Award, William L. Yarber Sexual Health Fellowship, and the Indiana University Graduate and Professional Student Organization Research Grant

Policy Recommendations for Meeting the Grand Challenge to Achieve Equal Opportunity and Justice

This brief was created forSocial Innovation for America’s Renewal, a policy conference organized by the Center for Social Development in collaboration with the American Academy of Social Work & Social Welfare, which is leading theGrand Challenges for Social Work initiative to champion social progress. The conference site includes links to speeches, presentations, and a full list of the policy briefs

No evidence of brown adipose tissue activation after 24 weeks of supervised exercise training in young sedentary adults in the ACTIBATE randomized controlled trial

Exercise modulates both brown adipose tissue (BAT)metabolismand white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129) was therefore conducted to study the effects of a 24-week supervised exercise intervention, combining endurance and resistance training, on BAT volume and activity (primary outcome). The study was carried out in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada (Spain). One hundred and forty-five young sedentary adults were assigned to either (i) a control group (no exercise, n = 54), (ii) a moderate intensity exercise group (MOD-EX, n = 48), or (iii) a vigorous intensity exercise group (VIG-EX n = 43) by unrestricted randomization. No relevant adverse events were recorded. 97 participants (34 men, 63 women) were included in the final analysis (Control; n = 35, MOD-EX; n=31, and VIG-EX; n=31).We observed no changes in BAT volume (Δ Control: −22.2 ± 52.6ml; Δ MOD-EX: −15.5 ± 62.1ml, Δ VIG-EX: −6.8 ± 66.4 ml; P = 0.771) or 18F-fluorodeoxyglucose uptake (SUVpeak Δ Control: −2.6 ± 3.1ml; Δ MOD-EX: −1.2 ± 4.8, Δ VIG-EX: −2.2 ± 5.1; p = 0.476) in either the control or the exercise groups. Thus, we did not find any evidence of an exercise-induced change on BAT volume or activity in young sedentary adults.Spanish Government PI13/01393Retos de la Sociedad DEP2016-79512-R PTA-12264IEuropean CommissionSpanish Government FPU13/04365 FPU14/04172 FPU15/04059 FPU16/03653 FPU19/01609Consejo Nacional de Ciencia y Tecnologia (CONACyT) 440575Fundacion Iberoamericana de Nutricion (FINUT)Redes Tematicas de Investigacion Cooperativa RETIC Red SAMID RD16/0022AstraZenecaUniversity of Granada Plan Propio de Investigacion 2016 -Excellence actions: Unit of Excellence on Exercise and Health (UCEES)Plan Propio de Investigacion 2018 -Programa Contratos-PuentePrograma Perfecionamiento de DoctoresJunta de Andalucia Consejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGRJunta de Andalucia P18-RT-4455Fundacion Alfonso Martin EscuderoMaria Zambrano fellowship by the Ministerio de Universidades y la Union Europea-NextGenerationEU RR_C_2021_04Novo Nordisk FoundationNovocure Limited NNF18OC003239