RESUMEN
Berberine was used as the lead compound in the present study to design and synthesize novel berberine derivatives by splicing bromine bridges of different berberine carbon chain lengths coupled nitric oxide donors, and their lipid lowering activities were assessed in a variety of ways. This experiment synthesized 17 new berberine nitric oxide donor derivatives. Compared with berberine hydrochloride, most of the compounds exhibited certain glycerate inhibitory activity, and compounds 6a, 6b, 6d, 12b and 12d showed higher inhibitory activity than berberine, with 6a, 6b and 6d having significant inhibitory activity. In addition, compound 6a linked to furazolidone nitric oxide donor showed better NO release in experiments; In further mechanistic studies, we screened and got two proteins, PCSK9 and ACLY, and docked two proteins with 17 compounds, and found that most of the compounds bound better with ATP citrate lyase (ACLY), among which there may be a strong interaction between compound 6a and ACLY, and the interaction force was better than the target drug Bempedoic Acid, which meaning that 6a may exert hypolipidemic effects by inhibiting ACLY; moreover, we also found that 6a may had the better performance in gastrointestinal absorption, blood-brain barrier permeability, Egan, Muegge class drug principle model calculation and bioavailability.
RESUMEN
Context: Atopic dermatitis (AD) is a chronic inflammatory skin disease and commonly affects children. AD is associated with a high incidence of ADHD, the most common psychological and neurobehavioral disorder in children and adolescents. If clinicians don't identify ADHD and intervene early, preschool children can experience adverse effects. Objective: The study intended to investigate the prevalence of attention deficit hyperactivity disorder (ADHD) in preschool children with AD, analyze the associated factors, and provide insights for early identification of risk factors and the development of interventions to reduce the likelihood of ADHD occurrence. Design: The research team performed a prospective, observational, case-control study. Setting: The study took place at the Zhoushan branch of Ruijin Hospital at the Shanghai Jiaotong University School of Medicine in Zhoushan, Zhejiang, China. Participants: Participants were 80 school-aged children diagnosed with AD and admitted to the hospital between May 2019 and May 2023. Groups: Based on the presence or absence of ADHD, the research team divided the children into two groups: (1) the Simple AD group with 71 participants with AD only, and the AD + ADHD group, with 9 participants with AD and ADHD. Outcome Measures: The research team: (1) collected and analyzed participants' demographic and clinical data, including an assessment of the AD severity using the SCORing Atopic Dermatitis (SCORAD) scale and the presence of sleep disorders using the Children's Sleep Habits Questionnaire (CSHQ); (2) assessed the presence of ADHD using the Swanson, Nolan, and Pelham-IV rating scales (SNAP-IV); (3) analyzed the factors influencing the occurrence of ADHD in AD children, using univariate and multivariate logistic regression analysis. Results: Among the 80 school-age children with AD, 9 participants (11.25%) had received a diagnosis of ADHD. The AD + ADHD group's age (P < .001); body mass index (BMI), with P < .001; AD severity (P = .013); rate of sleep disorders (P = .001); and levels of serum interleukin 6 (IL-6), with (P < .001), interleukin 4 (IL-4), with (P < .001), and nerve growth factor (NGF), with (P < .001) were all significantly greater than those of the Simple AD group. The univariate logistic regression analysis indicated that age (P = .014), BMI (P = .024), AD severity (P = .022), sleep disorders (P = .042), and levels of IL-6 (P = .044), IL-4 (P = .045), and NGF (P = .046) were all significantly related to the development of ADHD in school-age children with AD. The multivariate logistic regression analysis revealed that sleep disorders (P = .018) and elevated levels of serum IL-6 (P = .032), IL-4 (P = .021), and NGF (P = .016 ) were independent risk factors for ADHD (OR = 2.651, 3.074, 2.686, 3.340). Conclusions: School-aged children with AD are more likely to develop ADHD, which is mainly associated with sleep disorders and elevated levels of serum IL-6, IL-4, and NGF. Clinicians should give attention to these risk factors and implement early interventions to reduce the risk of children with AD developing ADHD.