Prevalence and Related Factors of Attention Deficit Hyperactivity Disorder in School-age Children With Atopic Dermatitis.

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.

Identification and characterization of a novel tyrosine aminotransferase gene (SmTAT3-2) promotes the biosynthesis of phenolic acids in Salvia miltiorrhiza Bunge.

Rosmarinic acid (RA) and salvianolic acid B (SAB) are main phenolic acids in Salvia miltiorrhiza Bunge have been widely used in the treatment of cardiovascular and cerebrovascular diseases due to their excellent pharmacological activity. RA is a precursor of SAB, and tyrosine transaminase (TAT, EC 2.6.1.5) is a crucial rate-limiting enzyme in their metabolism pathway. This study identified a novel TAT gene, SmTAT3-2, and found that it is a new transcript derived from unconventional splicing of SmTAT3. We used different substrates for enzymatic reaction with SmTAT1, SmTAT3 and SmTAT3-2. Subcellular localization of SmTAT1 and SmTAT3-2 was completed based on submicroscopic techniques. In addition, they were overexpressed and CRISPR/Cas9 gene edited in hairy roots of S. miltiorrhiza. Revealed SmTAT3-2 and SmTAT1 showed a stronger affinity for L-tyrosine than SmTAT3, localized in the cytoplasm, and promoted the synthesis of phenolic acid. In overexpressed SmTAT3-2 hairy roots, the content of RA and SAB was significantly increased by 2.53 and 3.38 fold, respectively, which was significantly higher than that of overexpressed SmTAT1 strain compared with EV strain. These findings provide a valuable key enzyme gene for the phenolic acids metabolism pathway and offer a theoretical basis for the clinical application.

Integrated Multiomics and Synergistic Functional Network Revealed the Mechanism in the Tolerance of Different Ecotypes of Salvia miltiorrhiza Bge. to Doxycycline Pollution.

Tetracycline pollution in soil irreversibly damages the biosafety of plants by inhibiting the mitochondrial function. Some traditional Chinese medicine (TCM) plants, such as Salvia miltiorrhiza Bunge, have a strong tolerance to mitochondrial damage. We comprehensively compared the doxycycline (DOX) tolerances of two ecotypes of S. miltiorrhiza in the Sichuan and Shandong provinces and found that the Sichuan ecotype had a lower yield reduction, more stable accumulation of medicinal ingredients, higher mitochondrial integrity, and a more robust antioxidant system. The synergetic response networks under DOX pollution of both ecotypes were constructed using RNA sequencing and ultrahigh-performance liquid chromatography-tandem mass spectrometry. The differentiation of the downstream pathways of aromatic amino acids (AAAs) produced variations in the DOX tolerance of S. miltiorrhiza in different regions. The Sichuan ecotype maintained redox homeostasis and xylem development by activating salvianolic acid and indole biosynthesis, while the Shandong ecotype balanced chemical and mechanical defenses by regulating the flavonoid biosynthesis. Rosmarinic acid, a downstream AAA molecule, maintains the mitochondrial homeostasis of plant seedlings under DOX pollution by targeting the ABCG28 transporter. We also highlight the significance of downstream AAA small molecules in guiding the development of bio-based environmental pollution remediation agents.

Bidirectional regulatory effects of Cordyceps on arrhythmia: Clinical evaluations and network pharmacology.

Background: Cordyceps is a precious Chinese herbal medicine with rich bio-active ingredients and is used for regulating arrhythmia alongside routine treatments. However, the efficacy and potential mechanisms of Cordyceps on patients with arrhythmia remain unclear. Methods: Randomized controlled trials of bradycardia treatment with Cordyceps were retrieved from diverse databases and available data. Dichotomous variables were expressed as a risk ratio (RR) with a 95% confidence interval (CI). Continuous variables were expressed as a standardized mean difference (SMD) with a 95% CI. Network pharmacology was used to identify potential targets of Cordyceps for arrhythmia. Metascape was used for gene ontology (GO) and genome (KEGG) pathway enrichment analysis. Results: Nineteen trials included 1,805 patients with arrhythmia, of whom 918 were treated with Ningxinbao capsule plus routine drugs, and, as a control, 887 were treated with only routine drugs. Six trials reported on bradycardia and the other 13 on tachycardia. Treatment with Cordyceps significantly improved the total efficacy rate in both bradycardia (RR = 1.24; 95% CI, 1.15 to 1.35; Pz <0.00001) and tachycardia (RR = 1.27; 95% CI, 1.17 to 1.39; Pz <0.00001). Cordyceps also had beneficial secondary outcomes. No serious adverse events occurred in patients treated with Cordyceps. The results of KEGG pathway enrichment analysis were mainly connected to adrenergic signaling in cardiomyocytes and the PI3K-Akt signaling pathway. IL6, TNF, TP53, CASP3, CTNNB1, EGF, and NOS3 might be key targets for Cordyceps in the treatment of arrhythmia. Conclusion: This study confirmed that Cordyceps has a certain positive effect on the treatment of arrhythmia and that its main mechanism may be through the regulation of adrenergic signaling in cardiomyocytes and the PI3K-Akt signaling pathway.

Evolutionary research on the expansin protein family during the plant transition to land provides new insights into the development of Tartary buckwheat fruit.

BACKGROUND: Plant transitions to land require robust cell walls for regulatory adaptations and to resist changing environments. Cell walls provide essential plasticity for plant cell division and defense, which are often conferred by the expansin superfamily with cell wall-loosening functions. However, the evolutionary mechanisms of expansin during plant terrestrialization are unclear. RESULTS: Here, we identified 323 expansin proteins in 12 genomes from algae to angiosperms. Phylogenetic evolutionary, structural, motif gain and loss and Ka/Ks analyses indicated that highly conserved expansin proteins were already present in algae and expanded and purified after plant terrestrialization. We found that the expansion of the FtEXPA subfamily was caused by duplication events and that the functions of certain duplicated genes may have differentiated. More importantly, we generated space-time expression profiles and finally identified five differentially expressed FtEXPs in both large and small fruit Tartary buckwheat that may regulate fruit size by responding to indoleacetic acid. CONCLUSIONS: A total of 323 expansin proteins from 12 representative plants were identified in our study during terrestrialization, and the expansin family that originated from algae expanded rapidly after the plants landed. The EXPA subfamily has more members and conservative evolution in angiosperms. FtEXPA1, FtEXPA11, FtEXPA12, FtEXPA19 and FtEXPA24 can respond to indole-3-acetic acid (IAA) signals and regulate fruit development. Our study provides a blueprint for improving the agronomic traits of Tartary buckwheat and a reference for defining the evolutionary history of the expansin family during plant transitions to land.

Docosahexenoic acid treatment ameliorates cartilage degeneration via a p38 MAPK-dependent mechanism.

Osteoarthritis (OA) is a common chronic inflammatory disease, characterized by cartilage degradation. The aberrant expression of matrix metalloproteinase-13 (MMP-13) plays a vital role in the pathogenesis of OA. The anti­inflammatory property of docosahexenoic acid (DHA) was previously revealed and showed that DHA retards the progress of many types of inflammatory disease. To evaluate the prophylactic function of DHA in OA, the effect of DHA on cartilage degeneration was assessed in interleukin­1ß (IL­1ß) stimulated human chondrosarcoma SW1353 cells or a rat model of adjuvant­induced arthritis (AIA). The safe concentration range (0­50 µg/ml in vitro) of DHA was determined by flow cytometry and MTT assay. The inhibitory effects of DHA on MMP­13 mRNA and protein expression were confirmed by RT­qPCR, ELISA and western blotting. Furthermore, findings of an in vivo study showed that DHA can increase the thickness of articular cartilage and decrease MMP­13 expression in cartilage matrix in a rat AIA model. We also revealed the mechanism by which DHA ameliorates cartilage degeneration from OA. The DHA-mediated inhibition of MMP­13 expression was partially attributed to the inactivation of the p38 mitogen­activated protein kinases pathway by suppressing p­p38 in IL-1ß-stimulated SW1353 cells and a rat AIA model. Our findings suggested that DHA is a promising therapeutic agent that may be used for the prevention and treatment of OA.

A low ratio of n-6/n-3 polyunsaturated fatty acids suppresses matrix metalloproteinase 13 expression and reduces adjuvant-induced arthritis in rats.

Increased expression of matrix metalloproteinase 13 (MMP13) in chondrocytes contributes to the development of osteoarthritis. The hypothesis of this study was that diet with a low ratio of n-6/n-3 polyunsaturated fatty acids (PUFAs) is associated with reduced MMP13 expression in inflammatory chondrocytes in vitro and in vivo. Human chondrocytes were cultured with different ratios of linoleic acid (LA, n-6 PUFA) to α-linolenic acid (n-3 PUFA) from 1:1 to 10:1. Proliferation of chondrocytes, MMP13 protein and mRNA levels were detected, respectively. Sprague-Dawley rats (n=30) were fed diets containing different ratios of n-6/n-3 PUFA. Freund's complete adjuvant was injected to make the model of arthritis. Paw swelling rate was measured and all rats were euthanized after 6 weeks of treatment. Serum MMP13 and IL-1 were measured by enzyme-linked immunosorbent assay. Joint histological sections were stained with safranin-O Fast Green to evaluate cartilage damage. Low ratio of LA/α-linolenic acid decreased the mRNA and protein levels of MMP13 but did not affect chondrocytes proliferation. Ratios of PUFA such as 1:1 and 2:1 significantly reduced paw swelling rate, and serum MMP13 and IL-1 levels in a rat model. Histological staining showed that ratios of 1:1 and 2:1 PUFA significantly alleviated cartilage damage in adjuvant-induced arthritis. A ratio of n-6/n-3 PUFA of 1:1 showed the strongest inhibitory effect on MMP13. Our results indicate that a low ratio of n-6/n-3 PUFA at 1:1 significantly suppressed MMP13 expression both in vitro and in vivo and reduced adjuvant-induced arthritis in rats could be a means to control and reduce the symptoms of osteoarthritis.