An integrated network pharmacology and molecular docking approach to reveal the role of Arctigenin against Cutibacterium acnes-induced skin inflammation by targeting the CYP19A1.

Acne caused by inflammation of hair follicles and sebaceous glands is a common chronic skin disease. Arctigenin (ATG) is an extract of Arctium lappa L., which has significant anti-inflammatory effects. However, the effect and mechanism of ATG in cutaneous inflammation mediated by Cutibacterium acnes (C. acnes) has not been fully evaluated. The purpose of this study was to explore the effect and potential mechanism of ATG in the treatment of acne through network pharmacology and experimental confirmation. An acne model was established by injected live C. acnes into living mice and treated with ATG. Our data showed that ATG effectively improved acne induced by live C. acnes, which was confirmed by determining ear swelling rate, estradiol concentration and hematoxylin and eosin (H&E) staining. In addition, ATG inhibited the NLRP3 inflammasome signaling pathway in mice ear tissues and reduced the secretion of pro-inflammatory cytokines IL-1ß to relieve inflammation. The results of network pharmacology and molecular docking confirmed that ATG can regulate 17ß-Estradiol (E2) levels through targeted to CYP19A1, and finally inhibited skin inflammation. Taken together, our results confirmed that ATG regulated E2 secretion by targeting CYP19A1, thereby inhibiting the NLRP3 inflammasome signaling pathway and improving inflammation levels in acne mice. This study provides a basis for the feasibility of ATG in treating acne in clinical practice.

Beneficial effect of residential greenness on sperm quality and the role of air pollution: A multicenter population-based study.

BACKGROUND: Poor sperm quality is a major cause of male infertility. However, evidence remains scarce on how greenness affects male sperm quality. OBJECTIVES: To assess the associations of residential greenness with male sperm quality and the modification effect of air pollution exposure on the relationship. METHODS: A total of 78,742 samples from 33,184 sperm donors from 6 regions across China during 2014-2020 were included and analyzed. Individual residential greenness exposures of study subjects were estimated using the Normalized Difference Vegetation Index (NDVI) during the entire (0-90 lag days) and two key stages (0-37, and 34-77 lag days) of sperm development. Contemporaneous personal exposure levels to air pollutants were estimated using a spatio-temporal deep learning method. Linear mixed models were employed to assess the impact of greenspace in relation to sperm quality. The modification effect of air pollution on the greenspace-sperm quality relationship was also estimated. RESULTS: Per IQR increment in NDVI exposure throughout spermatogenesis were statistically associated with increasing sperm count by 0.0122 (95 % CI: 0.0007, 0.0237), progressive motility by 0.0162 (95 % CI: 0.0045, 0.0280), and total motility by 0.0147 (95 % CI: 0.0014, 0.0281), respectively. Similar results were observed when the model added air pollutants (PM1, PM2.5 or O3) for adjustment. Additionally, specific air pollutants, including PM1, PM2.5, and O3, were found to modify this association. Notably, the protective effects of greenness exposure were more pronounced at higher concentrations of PM1 and PM2.5 and lower concentrations of O3 (all Pinteraction < 0.05). Statistically significant positive effects of NDVI were observed on sperm motility in early spermatogenesis and sperm count in late spermatogenesis. CONCLUSIONS: Exposure to residential greenness may have beneficial effects on sperm quality and air pollution modifies their relationship. These findings highlight the importance of adopting adaptable urban greenspace planning and policies to safeguard male fertility against environmental factors.

Shorter telomere length in children with autism spectrum disorder is associated with oxidative stress.

Objective: Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder caused by a complex interaction between genetic and environmental risk factors. The balance between antioxidant capacity and oxidative stress (OS) induced free radicals may be crucial during the pathophysiological development of ASD. Methods: In this study, 96 children with ASD who met the diagnostic and statistical manual of mental disorders were collected, and the number of children in the typical development (TD) group was matched by 1:1. Digital PCR (dPCR) for telomere length (TL) expression in ASD in peripheral blood leukocytes. Urine levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) content were measured by tandem triple quadrupole mass spectrometry and corrected by urinary creatinine levels. The levels of superoxide dismutase (SOD), catalase (CAT), and capacity (AOC) were detected by kits. Results: The TL of the ASD group was shorter than the TD group (p < 0.01) and had some accurate predictive significance for the identification of ASD (AUC = 0.632, 95% CI: 0.533-0.710, p = 0.002). Both 8-OHdG content and SOD activity in the ASD group were significantly higher than those in the TD group (p < 0.05). Shortened TL (Monofactor: 2.20 (1.22, 3.96), p = 0.009; Multifactor: 2.22 (1.22, 4.00), p = 0.008) and reduced CAT activity (Monofactor: 2.31 (1.28, 4.17), p = 0.006; Multifactor: 2.31 (1.28, 4.18), p = 0.006) are risk factors for the development of ASD, while reduced 8-OHdG content (Monofactor: 0.29 (0.14, 0.60), p = 0.001; Multifactor: 0.27 (0.13, 0.57), p = 0.001) and reduced SOD activity (Monofactor: 0.55 (0.31, 0.98), p = 0.042; Multifactor: 0.54 (0.30, 0.98), p = 0.042) are protective factors for the development of ASD. Conclusion: In this study, TL and OS were significantly different between the ASD group and the TD group. As guanine-rich telomere sequences were likely damaged by oxygen free radicals, creating OS, which is a factor in the incidence and progression of ASDs. In conclusion, oxidative damage occurs in the bodies of children with ASD, which may lead to sustained disease progression and severe clinical manifestations. We assume that timely supplementation of antioxidants is very likely to be a potential treatment for early intervention in children with ASD. Identification and detection of OS-related biomarkers may contribute to early diagnosis and timely interventions in young patients with ASD.

Development and Application of Gas Production Measurement System of Coal-Rock under Temperature-Pressure Coupling.

In this study, a measurement system for gas generation of coal-rock under temperature-pressure coupling was developed by adding gas extraction, collection, and flow-monitoring devices to the original stainless-steel liquid seepage pipeline of an MTS-815 rock triaxial testing machine, which can be used to study the production mechanism of coalbed methane in a real geological environment. The system has the functions of axial loading, confining pressure loading, continuous heating, gas gathering, etc., and has the advantages of good air tightness, high accuracy and stability, long-term loading and heating, and controllable single variables. The preliminary test for the gas production of anthracite in the Shaanxi Formation of the Qinshui Basin under temperature-pressure coupling was carried out by the developed test system. The results show that the test system can provide accurate and effective measurement means for the study of gas production by coal-rock deformation and is expected to provide effective help for the control and exploitation of coalbed methane.