摘要：
通过网络药理学及动物试验探讨抗纤灵方治疗肝纤维化的作用机制。采用TCMSP、PubChem等数据库筛选出抗纤灵方的有效成分和潜在的相关靶点；利用GeneCards数据库检索肝纤维化的相关靶点；根据药物和疾病匹配的共同靶点，利用STRING数据库进行蛋白质互作分析；构建蛋白质网络，拓扑分析关键靶点；利用Metascape平台对共有靶点进行GO（Gene Ontology）及KEGG（Kyoto Encyclopedia of Genes and Genomes）富集分析以探讨其可能的机制。建立四氯化碳诱导小鼠肝纤维化模型，利用HE染色及Masson染色分析肝组织的病理变化及纤维化程度；试剂盒检测小鼠血清中ALT、AST的表达水平；ELISA检测抗纤灵方对炎性因子TNF、IL-6、IL-1的表达水平。肝组织匀浆检测抗纤灵方对纤维化标志物的影响。抗纤灵方抗肝纤维化的核心活性成分为橘皮素、儿茶素、表小檗碱、黄连碱等。核心靶点有TNF、IL-6、AKT1、TP53等，核心通路包括癌症通路、TNF、流体剪切力与动脉粥样硬化、IL-17、糖尿病并发症中的AGE-RAGE信号通路等。动物试验表明，抗纤灵方可以减少小鼠肝脏炎症细胞浸润及胶原产生，降低炎性因子TNF、IL-6、IL-1水平，抑制肝星状细胞活化指标-SMA等的表达。抗纤灵方可能通过降低炎性因子的水平，抑制肝星状细胞活化从而发挥抗肝纤维化的作用。
期刊：
Journal of Ethnopharmacology,2024年326:117972 ISSN：0378-8741
通讯作者：
Liu, Lumei;Zhang, Wei;He, Qinghu
作者机构：
[Fu, Xinying; He, Qinghu; Li, Wanyu] College of Integrated Chinese and Western Medicine, Hunan Provincial Key Laboratory for Prevention and Treatment of Heart and Brain Diseases with Integrated Traditional Chinese and Western Medicine, Hunan University of Traditional Chinese Medicine, Hunan, 410208, China;[Fu, Xinying; He, Qinghu] College of Integrated Chinese Medicine, Hunan University of Traditional Chinese Medicine, Hunan, 410208, China;[Fu, Xinying] Hunan University of Medicine, Huaihua, Hunan, 418000, China;[Yan, Siyang] The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan, 410007, China;[Sheng, Wen; Kuang, Shida; Hu, Zongren] College of Integrated Chinese Medicine, Hunan University of Traditional Chinese Medicine, Hunan, 410208, China
通讯机构：
[He, Qinghu] H;[Zhang, Wei; Liu, Lumei] C;College of Integrated Chinese and Western Medicine, Hunan Provincial Key Laboratory for Prevention and Treatment of Heart and Brain Diseases with Integrated Traditional Chinese and Western Medicine, Hunan University of Traditional Chinese Medicine, Hunan, 410208, China. Electronic address:;Hunan University of Medicine, Huaihua, Hunan, 418000, China. Electronic address:
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Guhan Yangsheng Jing (GHYSJ) is a traditional Chinese patent medicine, that has the function of nourishing the kidney and replenishing the essence, invigorating the brain and calming the mind. It is often used to treat dizziness, memory loss, sleep disorders, fatigue, and weakness, etc. However, its mechanism for improving sleep has not yet been determined. AIM OF THE STUDY: This study aims to explore the effects of GHYSJ on Sleep Deprivation (SD)-induced hippocampal neuronal pyroptotic injury, learning and cognitive abilities, and sleep quality in mice. METHODS: In this study, a PCPA-induced SD mouse model was established. We assessed the influence of GHYSJ on sleep quality and mood by using the pentobarbital-induced sleep test (PIST) and sucrose preference test (SPT). The pharmacological effects of GHYSJ on learning and memory impairment were evaluated by the Morris Water Maze (MWM) and Open Field Test (OFT). Pathological changes in the hippocampal tissue of the SD rats were observed via HE staining and Nissl staining. The severity of neuronal damage was evaluated by detecting the expression of the neuronal marker Microtubule-associated protein 2 (MAP2), via immunohistochemistry and immunofluorescence. Furthermore, the levels of neurotransmitter 5-hydroxytryptophan (5-HTP), 5-hydroxy tryptamine (5-HT), γ-aminobutyric acid (GABA), and Glutamic acid (Glu) in hippocampal tissues, as well as the expression of inflammatory factors Interleukin-1β (IL-1β) and Interleukin-18 (IL-18) in serum, were determined by ELISA. The expressions of mRNA and protein NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Cysteinyl aspartate specific proteinase1 (Caspase1), High mobility group box-1 protein (HMGB1) and Apoptosis-associated speck-like protein containing CARD (ASC) related to the cellular ferroptosis pathway were tested and analyzed by RT-PCR and WB respectively. RESULTS: PCPA significantly diminishes the sleep span of experimental animals by expediting the expenditure of 5-HT, consequently establishing an essentially direct SD model. The intervention of GHYSJ displays remarkable efficacy in mitigating insomnia symptoms, encompassing difficulties in initiating sleep and insufficient sleep duration. Likewise, it ameliorates memory function impairments induced by sleep deprivation, along with symptoms such as fatigue and depletion of vitality. GHYSJ exerts a protective influence on hippocampal neurons facilitated by inhibiting the down regulation of MAP2 and maintaining the equilibrium of neurotransmitters (5-HTP, 5-HT, GABA, and Glu). It diminishes the expression of intracellular pyroptosis-associated inflammatory factors (IL-1β and IL-18) and curbs the activation of the NLRP3/Caspase1/GSDMD pyroptosis-related signaling pathways, thereby alleviating the damage caused by hippocampal neuronal pyroptosis.
期刊：
BRIEFINGS IN BIOINFORMATICS,2024年25(2) ISSN：1467-5463
通讯作者：
Changning Liu
作者机构：
[Zexin Zhang; Jing Li; Changning Liu] CAS Key Laboratory of Tropical Plant Resources and Sustainable Use , Yunnan Key Laboratory of Crop Wild Relatives Omics, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Kunming 650223 , China;[Wen Chen] Hunan Provincial Key Laboratory of Vascular Biology and Translational Medicine , School of Medicine, Hunan University of Chinese Medicine, Changsha 410208 , China;College of Life Sciences, University of Chinese Academy of Sciences , Beijing 100049 , China;[Zitian Yang] CAS Key Laboratory of Tropical Plant Resources and Sustainable Use , Yunnan Key Laboratory of Crop Wild Relatives Omics, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Kunming 650223 , China<&wdkj&>College of Life Sciences, University of Chinese Academy of Sciences , Beijing 100049 , China
通讯机构：
[Changning Liu] C;CAS Key Laboratory of Tropical Plant Resources and Sustainable Use , Yunnan Key Laboratory of Crop Wild Relatives Omics, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Kunming 650223 , China
关键词：
CRISPR/Cas9;machine learning;lncRNA;sgRNA
摘要：
CRISPR/Cas9 is a promising RNA-guided genome editing technology, which consists of a Cas9 nuclease and a single-guide RNA (sgRNA). So far, a number of sgRNA prediction softwares have been developed. However, they were usually designed for protein-coding genes without considering that long non-coding RNA (lncRNA) genes may have different characteristics. In this study, we first evaluated the performances of a series of known sgRNA-designing tools in the context of both coding and non-coding datasets. Meanwhile, we analyzed the underpinnings of their varied performances on the sgRNA’s specificity for lncRNA including nucleic acid sequence, genome location and editing mechanism preference. Furthermore, we introduce a support vector machine-based machine learning algorithm named CRISPRlnc, which aims to model both CRISPR knock-out (CRISPRko) and CRISPR inhibition (CRISPRi) mechanisms to predict the on-target activity of targets. CRISPRlnc combined the paired-sgRNA design and off-target analysis to achieve one-stop design of CRISPR/Cas9 sgRNAs for non-coding genes. Performance comparison on multiple datasets showed that CRISPRlnc was far superior to existing methods for both CRISPRko and CRISPRi mechanisms during the lncRNA-specific sgRNA design. To maximize the availability of CRISPRlnc, we developed a web server (http://predict.crisprlnc.cc) and made it available for download on GitHub.
作者机构：
[Li, Hua; Chen, Xinhao; Li, H] Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha, Peoples R China.
通讯机构：
[Li, H ] H;Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha, Peoples R China.
摘要：
BACKGROUND: Breast cancer is one of the most common female malignancies. This study explored the underlying mechanism through which the two plant compounds (Brucaine D and Narclasine) inhibited the proliferation of breast cancer cells. OBJECTIVE: The purpose of this study was to explore the effect of Brucaine D and Narclasine on breast cancer development and their potential drug targets. METHODS: GSE85871 dataset containing 212 samples and the hallmark gene set "h.all.v2023.1.Hs.symbols.gmt" were downloaded from the Gene Expression Omnibus (GEO) database and the Molecular Signatures Database (MSigDB) database, respectively. Principal component analysis (PCA) was applied to classify clusters showing similar gene expression pattern. Single sample gene set enrichment analysis (ssGSEA) was used to calculate the hallmark score for different drug treatment groups. The expressions of genes related to angiogenesis, glycolysis and cell cycle were detected. Protein-protein interaction (PPI) network analysis was performed to study the interaction of the hub genes. Then, HERB database was employed to identify potential target genes for Narclasine and Bruceine D. Finally, in vitro experiments were conducted to validate partial drug-target pair. RESULTS: PCA analysis showed that the significant changes in gene expression patterns took place in 6 drugs treatment groups (Narciclasine, Bruceine D, Japonicone A, 1beta-hydroxyalatolactone, Britanin, and four mixture drugs) in comparison to the remaining drug treatment groups. The ssGSEA pathway enrichment analysis demonstrated that Narciclasine and Bruceine treatments had similar enriched pathways, for instance, suppressed pathways related to angiogenesis, Glycolysis, and cell cycle, etc.. Further gene expression analysis confirmed that Narciclasine and Bruceine had a strong ability to inhibit these cell cycle genes, and that MYC, CHEK2, MELK, CDK4 and EZH2 were closely interacted with each other in the PPI analysis. Drug target prediction revealed that Androgen Receptor (AR) and Estrogen Receptor 1 (ESR1) were the targets for Bruceine D, and Cytochrome P450 3A4 enzyme (CYP3A4) was the target for Narciclasine. Cell experiments also confirmed the connections between Narciclasine and CYP3A4. CONCLUSION: The present study uncovered that Narciclasine and Bruceine D could inhibit the growth of breast cancer and also predicted the potential targets for these two drugs, providing a new therapeutic direction for breast cancer patients.
摘要：
Early adolescent smartphone dependence has emerged as a significant social and public health issue. Previous research showed that multiple ecological risks including family, school, and peer risk factors played important roles in early adolescent smartphone dependence. However, these studies have examined risk factors individually rather than examining the cumulative risk effect. Based on the Ecological Systems Theory and Risk-Protective Factor Theory, the present study focused on the longitudinal association between cumulative ecological risk and early adolescent smartphone dependence. We tested two mediating mechanisms of this association, namely social anxiety and self-compassion, and examined possible gender differences in these mediation processes. The study adopted a three-wave longitudinal design spanning one year, with a six-month interval between each wave. 357 secondary school students (Mage = 12.58 years, SD = 0.61, 52.1% girls) from two middle schools in China participated in this study. As expected, cumulative ecological risk positively predicted smartphone dependence one year later, and social anxiety and self-compassion were parallel mediators of this longitudinal association. Meanwhile, there were gender differences in the mediation model. The results provide a theoretical and empirical basis for the development of prevention and intervention strategies and public health policies to reduce the likelihood of early adolescents' smartphone dependence.
作者机构：
[Liu, Shi-Jun; Hou, Shi-Yi; Xia, Bo-Hou; Ge, Yu-Ying; Xie, Ming-Xia; Lu, Yu-Ai] Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, Hunan University of Chinese Medicine, Changsha 410208, PR China
摘要：
In managing unique complexities associated with Chinese medicinal quality assessment, metabolomics serves as an innovative tool. This study proposes an analytical approach to assess differing qualities of Scrophularia ningpoensis （S. ningpoensis）Hemsl by identifying potential biomarker metabolites and their activity with the corresponding secondary metabolites. The methodology includes four steps; first, a GC-MS based metabolomics exploration of the Scrophularia ningpoensis Hemsl. Second, a multivariate statistical analysis (PCA, PLS-DA, OPLS-DA) for quality assessment and biomarker identification. Third, the application of ROC analysis and pathway analysis based on identified biomarkers. Finally, validation of the associated active ingredients by HPLC. The analysis showed distinct metabolite profiles across varying grades of S. ningpoensis Hemsl, establishing a grading dependency relationship. Select biomarkers (gluconic Acid, d-xylulose, sucrose, etc.) demonstrated robust grading performances. Further, the Pentose Phosphate Pathway, deemed as most influential in grading, was tied to the synthesis of key constituents (iridoids, phenylpropanoids). HPLC validation tests affirm a decreasing trend in harpagoside and cinnamic acid levels between first and third-grade samples. In conclusion, this GC-MS based metabolomics combined HPLC method offers a sound approach to assess and distinguish quality variations in S. ningpoensis Hemsl samples.
摘要：
Objective To observe the effectiveness and safety of the Chinese herbal medicine Mingshi Granules(明视方颗粒)for low myopia in children with heart yang insufficiency.Methods A multicentre,prospective,double-blind randomised controlled study was conducted,in which 290 children with low myopia from 8 centres were ran-domly divided into 145 cases in the treatment group and 145 cases in the control group,and the treatment group was given education,dispensing glasses,and Chinese herbal medicine Mingshi Granules,while the control group was given education,dispensing glasses,and granules placebo.Both Mingshi Granules and placebo granules were taken orally,1 bag each time,twice daily,4 weeks of oral intake and 2 weeks of rest as 1 course of treatment,a total of 4 courses of treatment(24 weeks).Equivalent spherical lenses,best naked-eye distance visual acuity,ocular axis,corneal cur-vature K1,adjustment amplitude,traditional Chinese medicine(TCM)symptom scores,calculate the amount of pro-gression of equivalent spherical lenses,were observed at the 12th and the 24th week of treatment,at the 36th week and 48th week of follow-up,resectively,the control rate of myopia progression was evaluated at the 24th week,and safety indexes were observed before treatment.Results The amount of progression of equivalent spherical lenses was lower in the treatment group than in the control group at the 48-week follow-up(P＜0.05).The control rate of myopia progression at 24 weeks after treatment in the treatment group was higher(57.60％,72/125)than that in the control group(44.63％,54/121)(P＜0.05).The best naked-eye distance visual acuity at 36-week follow-up in the treatment group was higher than that in the control group(P＜0.05).Equivalent spherical lenses were significantly lower in both groups at all observation time points compared with pre-treatment(P＜0.05),and were higher in the treatment group than in the control group at the 48-week follow-up(P＜0.05).The ocular axes of both groups were significantly higher at each observation time point after treatment and at follow-up compared with before treatment(P＜0.05).The amount of eye axis growth in the treatment group was lower than that in the control group at 24 weeks after treatment and at the 48-week follow-up(P＜0.05).Corneal curvature K1 was significantly lower in the treatment group at the 24th week of treatment compared to pre-treatment(P＜0.05).The magnitude of adjustment in the treatment group was significantly higher at the 36-week follow-up and at the 48-week follow-up than before treat-ment(P＜0.05).The scores of white/dark complexion,white coating thin pulse,fatigue and total TCM symptom scores of children in both groups at the 12th,24th,36th and 48th weeks of follow-up were significantly lower than those before treatment(P＜0.05);the scores of blurred vision at the 24th and 36th weeks of follow-up were signifi-cantly lower than those before treatment(P＜0.05);and the scores of blurred vision in the treatment group at the 48th week of follow-up were signi-ficantly lower than those before treatment(P＜0.05).In the treatment group,the score of fatigue was higher than that of the control group at the 36-week follow-up,and the score of blurred vision was lower than that of the control group at the 48-week follow-up(P＜0.05).No adverse reactions or obvious abnormali-ties of the safety indexes were observed of the two groups during the treatment.Conclusion Chinese herbal medicine Mingshi Granules showed the effect of controlling the progression of low myopia,improving the best naked eye dis-tance visual acuity,slowing down the growth of the eye axis,improving some of the TCM symptoms,with good safety.
