Acanthosis Nigricans

The epidermis is a dynamic tissue in which keratinocytes proliferate in the basal layer and undergo a tightly controlled differentiation while moving into the suprabasal layers. The balance between keratinocyte proliferation, differentiation, and death is essential, and its perturbation can result in pathological changes. Some common skin diseases, such as psoriasis, are characterized by hyperproliferation accompanied by inflammatory reactions, suggesting that molecules with topical anti-inflammatory and ROS scavenging abilities may be useful for their treatment. Here we investigate the potential of the flavone Luteolin-7-glucoside (LUT-7G) as a treatment for psoriasis. We show that LUT-7G leads to a modification of the cell cycle and the induction of keratinocyte differentiation, with modification of energy, fatty acid, and redox metabolism. LUT-7G treatment also neutralizes the proliferative stimulus induced by the proinflammatory cytokines IL-22 and IL-6 in HEKn. Moreover, in the Imiquimod (IMQ) mouse model of psoriasis, topical administration of LUT-7G leads to a marked reduction of acanthosis and re-expression of epidermal differentiation markers. Dissection of the IL-22 signalling pathway, activated by IMQ treatment, demonstrates that LUT-7G impairs the nuclear translocation of phosphorylated (activated) STAT3, blocking the IL-22 signalling cascade. Thus LUT-7G appears to be a promising compound for the treatment of hyperproliferative and inflammatory skin diseases, such as psoriasis.

ImportancePacific Islanders have among the highest rates of obesity and type 2 diabetes in the world. Targeting children is critical for primary prevention.ObjectivesTo prevent young child overweight and obesity and to improve health in the US-Affiliated Pacific region via the Children's Healthy Living Program.Design, setting, and participantsIn this multijurisdictional, multilevel, multicomponent community randomized clinical trial, where all evaluable children were analyzed according to the random assignment of their community, hierarchical difference-in-difference models accounted for the community randomization, community clustering with jurisdictions, and these models were adjusted for the age and sex distribution of the community. The setting was 27 communities in 5 jurisdictions (Alaska, American Samoa, Commonwealth of the Northern Mariana Islands, Guam, and Hawaii). Participants were 4329 children (time 1) and 4042 children (time 2) aged 2 to 8 years in 27 selected communities from October 7, 2012, to October 25, 2015. Data analysis was completed in June 2018.InterventionsNineteen activities addressed policy, environment, messaging, training, and 6 target behaviors (sleep time, screen time, physical activity, fruits and vegetables, water, and sugar-sweetened beverages).Main outcomes and measuresPrimary outcomes were body size measurements. Secondary outcomes were acanthosis nigricans, sleep quality and duration, dietary intake, physical activity, and other questionnaire reponses.ResultsThe study included 27 communities and 8371 evaluable children (mean [SD] age, 5.4 [1.8] years; 50.9% male [n = 4264]). Data analysis included 952 children in the intervention group and 930 children in the control group aged 2 to 5 years at time 1; 825 children in the intervention group and 735 children in the control group aged 2 to 5 years at time 2; 565 children in the intervention group and 561 children in the control group aged 6 to 8 years at time 1; and 517 children in the intervention group and 560 children in the control group aged 6 to 8 years at time 2. The intervention communities showed significant improvement compared with control communities in overweight and obesity prevalence (effect size [d] = -3.95%; 95% CI, -7.47% to -0.43%), waist circumference (d = -0.71 cm; 95% CI, -1.37 to -0.05 cm), and acanthosis nigricans prevalence (d = -2.28%; 95% CI, -2.77% to -1.57%). Age and sex subgroup analysis revealed greater difference among the intervention communities in acanthosis nigricans prevalence in the group aged 2 to 5 years (-3.99%) vs the group aged 6 to 8 years (-3.40%), and the interaction was significant (d = 0.59%, P Conclusions and relevanceThe intervention reduced the prevalence of young child overweight and obesity and acanthosis nigricans. Comprehensive, effective, and sustainable interventions are needed to improve child health in the US-Affiliated Pacific region.Trial registrationClinicalTrials.gov Identifier: NCT01881373.

IntroductionChildhood obesity leads to early subclinical atherosclerosis and arterial stiffness. Studying biomarkers like trimethylamine N-oxide (TMAO), linked to cardio-metabolic disorders in adults, is crucial to prevent long-term cardiovascular issues.MethodsThe study involved 70 children aged 4 to 18 (50 obese, 20 normal-weight). Clinical examination included BMI, waist measurements, puberty stage, the presence of acanthosis nigricans, and irregular menstrual cycles. Subclinical atherosclerosis was assessed by measuring the carotid intima-media thickness (CIMT), and the arterial stiffness was evaluated through surrogate markers like the pulse wave velocity (PWV), augmentation index (AIx), and peripheral and central blood pressures. The blood biomarkers included determining the values of TMAO, HOMA-IR, and other usual biomarkers investigating metabolism.ResultsThe study detected significantly elevated levels of TMAO in obese children compared to controls. TMAO presented positive correlations to BMI, waist circumference and waist-to-height ratio and was also observed as an independent predictor of all three parameters. Significant correlations were observed between TMAO and vascular markers such as CIMT, PWV, and peripheral BP levels. TMAO independently predicts CIMT, PWV, peripheral BP, and central SBP levels, even after adding BMI, waist circumference, waist-to-height ratio, puberty development and age in the regression model. Obese children with high HOMA-IR presented a greater weight excess and significantly higher vascular markers, but TMAO levels did not differ significantly from the obese with HOMA-IRConclusionOur study provides compelling evidence supporting the link between serum TMAO, obesity, and vascular damage in children. These findings highlight the importance of further research to unravel the underlying mechanisms of this connection.

BackgroundAcanthosis nigricans (AN) is a highly visible cutaneous condition that has been associated with cardiometabolic factors, drugs, or malignancy in various populations. AN can be challenging to treat. Transmasculine patients are a special population, but their AN prevalence, and whether AN associates with demographic factors, co-morbidities and gender affirming care (GAC) treatment types have not been well-studied. Our study explores whether GAC treatment type is associated with AN while controlling for confounders in a large group of transmasculine patients at an academic center.MethodsFollowing Institutional Review Board approval, the Stanford Research Repository (01/01/2016-21/09/2023) was searched to identify transmasculine patients for individual chart review. The primary outcome was AN and its association with demographic factors, co-morbidities, and gender-affirming care (GAC) treatment type by multivariate logistic regression (presented as Odds Ratio (OR) and 95% Confidence Interval (CI)).ResultsOut of 945 transmasculine patients, AN prevalence was 4.55%, an elevated rate compared to the overall database prevalence of 0.3% for the same period. Prevalence of AN in transmasculine patients never exposed to GAC was 4.02% (7/174). Median age was 20.1 years (interquartile range (IQR) 17.2-25.4). On multivariate logistic regression, AN was associated with obesity (OR 9.31, 95% CI 4.40-20.33), metabolic syndrome (OR 4.04, 95% CI 1.09-15.23), prediabetes (OR 3.17, 95% CI 1.10-8.54), hypertension (OR 2.74, 95% CI 0.96-7.18), and Hispanic ethnicity (OR 2.46, 95% CI 1.12-5.25). GAC type (including exogenous testosterone usage) was not associated with AN, despite >99% power to detect a 10% difference in AN prevalence.ConclusionsBecause AN is enriched in transmasculine patients, and precedes co-morbidities in a majority of cases, dermatologists and other physicians should consider examination of common areas for AN in in transmasculine patients, as screening and diagnosis of co-morbidities could lead to improved health outcomes.