作者机构：
[Wang, Zhu; Hu, Jinyang; Wang, Z; Niu, Junjie] Hunan Acad Tradit Chinese Med, Affiliated Hosp, Dept Med Oncol, 58 Lushan Rd, Changsha 410000, Hunan, Peoples R China.
通讯机构：
[Wang, Z ] H;Hunan Acad Tradit Chinese Med, Affiliated Hosp, Dept Med Oncol, 58 Lushan Rd, Changsha 410000, Hunan, Peoples R China.
关键词：
triple negative breast cancer;RhoA;ROCK1;Ezrin;scutellaria barbata D.Don extract
摘要：
BACKGROUND: Triple-negative breast cancer (TNBC) lacks effective therapeutic targets. Scutellaria barbata D.Don (SB) has been revealed to have anti-breast cancer (BC) effect, but the effect of SB extract in TNBC is still unclear. Herein, this research delves into the underlying mechanism. METHODS: SB was extracted by solvent extraction, and the main components were identified using an Agilent 6,520 HPLC-Chip/Q-TOF (Chip/Q-TOF) MS system. In vitro cell experiments were conducted. The effects of SB extract alone, SB extract plus EGF, GSK alone, GSK plus Ezrin overexpression, or SB extract plus Ezrin overexpression on cell viability, invasion, migration, and apoptosis were examined by cell function experiments. The apoptosis- and RhoA/ROCK1 pathway-related protein levels were analyzed by western blot assay. RESULTS: Mass spectrometry analysis exhibited that SB extract mainly contains long-chain fatty acids and ursolic acid. SB extract mitigated TNBC cell biological phenotypes, apoptosis- and RhoA/ROCK1 pathway-related marker expressions, which were reversed by EGF. The further results found that GSK obviously weakens TNBC cell biological behaviors, apoptosis- and RhoA/ROCK1 signaling-related protein levels, while oe-Ezrin treatment reverses the effect of GSK on TNBC cells. Moreover, SB extract regulated Ezrin-mediated function of TNBC cells by impeding the RhoA/ROCK1 pathway. CONCLUSION: Our findings demonstrated that SB extract regulated Ezrin-mediated proliferation, migration, invasion, and apoptosis of TNBC cells via suppressing the RhoA /ROCK1 signaling. Our results offer the experimental foundation for further investigation of the anti-cancer role of SB in TNBC cells. HIGHLIGHTS: SB extract inhibits the biological phenotypes of TNBC cells.SB extract inhibits the biological behaviors of TNBC cells through the RhoA/ROCK1 pathway.SB extract modulates Ezrin-mediated TNBC cell proliferation, migration, invasion, and apoptosis via restraining the RhoA/ROCK1 signaling.
通讯机构：
[Tan, Y; Pei, G ] H;Hunan Univ Chinese Med, Coll Pharm, Changsha 410000, Peoples R China.;Educ Dept Hunan Prov, Key Lab Modern Res TCM, Changsha 410000, Peoples R China.
关键词：
H3K18la;LDHA;histone lactylation;liver injury;macrophages;salvianolic acid B
摘要：
Salvianolic acid B (Sal B) is the primary water-soluble bioactive constituent derived from the roots of Salvia miltiorrhiza Bunge. This research was designed to reveal the potential mechanism of Sal B anti-liver injury from the perspective of macrophages. In our lipopolysaccharide-induced M1 macrophage model, Sal B showed a clear dose-dependent gradient of inhibition of the macrophage trend of the M1 type. Moreover, Sal B downregulated the expression of lactate dehydrogenase A (LDHA), while the overexpression of LDHA impaired Sal B's effect of inhibiting the trend of macrophage M1 polarization. Additionally, this study revealed that Sal B exhibited inhibitory effects on the lactylation process of histone H3 lysine 18 (H3K18la). In a ChIP-qPCR analysis, Sal B was observed to drive a reduction in H3K18la levels in the promoter region of the LDHA, NLRP3, and IL-1β genes. Furthermore, our in vivo experiments showed that Sal B has a good effect on alleviating CCl(4)-induced liver injury. An examination of liver tissues and the Kupffer cells isolated from those tissues proved that Sal B affects the M1 polarization of macrophages and the level of histone lactylation. Together, our data reveal that Sal B has a potential mechanism of inhibiting the histone lactylation of macrophages by downregulating the level of LDHA in the treatment of liver injury.
摘要：
Abstract: Objective: To explore the relationship among depression, anxiety and self-concept in college students. Methods: 2200 college students were selected. Beck Depression Rating Scale (BDI), Trait Anxiety Inventory (T-AI) and Tennessee Self-Concept Scale (TSCS) were adopted to measure the college students’ depression, anxiety and self-concept, respectively. Results: The total score of TSCS and scores of moral self-concept, family self-concept, self-identification and self-action of female college students were significantly higher than those of male college students (P < 0.01), and self-criticism was significantly lower than that of male college students (P < 0.05). The BDI and T-AI scores of non-only child college students were significantly higher than those of only child (P < 0.05), and the self-identification scores were significantly lower than those of only child (P < 0.05). The social self-concept scores of urban college students were significantly higher than those of rural college students (P < 0.05). The total score of TSCS in control group was the highest, followed by depression group, anxiety group, depression and anxiety group (P < 0.001). The self-criticism scores of the control group were significantly lower than those of the other three groups (P < 0.001). BDI and T-AI scores of college students were positively correlated (r = 0.58, P < 0.01). The scores of BDI and T-AI were negatively correlated with the total score of TSCS and positive factors (r = −0.39~−0.52, P < 0.01; r = −0.52~−0.70, P < 0.01), was positively correlated with negative factor self-criticism (r = 0.24, P < 0.01; r = 0.31, P < 0.01). Both physiological and psychological self-concept of college students negatively predicted BDI and T-AI scores, and their explanatory quantities were 31.1% and 53.7%, respectively. Self-criticism has a positive predictive effect, and its explanatory volume is 0.5% and 0.7%. Conclusion: Depression and anxiety of college students are negatively affected by their self-concept and its positive factors, and positively affected by its negative factors self-criticism.#@#@#摘要: 目的：探讨大学生抑郁、焦虑与自我概念的关系。方法：选取2200名大学生，采用贝克抑郁自评量表(BDI)、特质焦虑问卷(T-AI)、田纳西自我概念问卷(TSCS)分别测量其抑郁、焦虑及自我概念现状。结果：女大学生TSCS总分及道德伦理自我、家庭自我、自我认同、自我行动上的得分都显著高于男大学生(P < 0.01)，自我批评显著低于男大学生(P < 0.05)；非独生子女大学生的BDI和T-AI得分显著高于独生子女(P < 0.05)，自我认同得分显著低于独生子女(P < 0.05)；城市大学生社会自我得分显著高于农村大学生(P < 0.05)。对照组TSCS总分最高，之后依次为抑郁组、焦虑组和抑郁焦虑组(P < 0.001)；对照组自我批评得分显著低于其他三组(P < 0.001)。大学生BDI和T-AI得分呈正相关(r = 0.58, P < 0.01)；BDI和T-AI得分与TSCS总分及各正向因子呈负相关(r = −0.39~−0.52, P < 0.01; r = −0.52~−0.70, P < 0.01)，与负向因子自我批评呈正相关(r = 0.24, P < 0.01; r = 0.31, P < 0.01)。大学生的心理自我和生理自我都对BDI和T-AI得分有负向预测作用，其解释量分别为31.1%和53.7%；自我批评有正向预测作用，其解释量为0.5%和0.7%。结论：大学生抑郁和焦虑受其自我概念及正向因子的负面影响，受其负向因子自我批评的正向影响。
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Anxiety disorders leads to a decline in quality of life and increased risk of morbidity and mortality. The Baihe Dihuang decoction (BDD) is a classic Chinese medical formula that has been widely used to treat anxiety disorders for thousands of years in China. However, the pharmacodynamic material that is responsible for the antianxiety of BDD remains unclear. AIM OF THE STUDY: To screen the main ingredients of anti-anxiety in BDD based on the establishment of spectrum-effect relationship and verified experiment. METHODS: The UPLC-Q-TOF/MS technique was utilized to establish fingerprints of various fractions of BDD and identify the main compounds. The anti-anxiety effects of BDD were comprehensively evaluated through multiple assessments, including the open field test, elevated plus maze test, and neurotransmitters tests. Then, the spectrum-effect relationship was established through Pearson correlation analysis, gray correlation analysis, orthogonal partial least squares regression analysis. The spectrum-effect relationship results were confirmed through various measures on an anxiety condition cell model, induced by a corticosterone and lipopolysaccharide intervention. These measures included assessing neuronal cell viability, morphology, apoptosis, synaptic damage, and the expression of neurotransmitters and inflammatory factors. RESULTS: In the UPLC-Q-TOF-MS fingerprint, 46 common peaks were identified. The pharmacological results indicated that different fractions of BDD have strong effects on improving anxiety-like behavior and regulating neurotransmitters. Among them, butanol fraction has the highest comprehensive evaluation score of anti-anxiety efficacy, which is main active fraction of BDD for anti-anxiety. The analysis of the spectrum-effect relationship revealed that the 46 peaks exhibited varying degrees of correlation with the anti-anxiety efficacy indicators of BDD. Among them, 14 components have a high correlation with the anti-anxiety efficacy indicators, which may be the potential anti-anxiety efficacy components of BDD. The in vitro activity verification of active components verified our prediction, regaloside A, B, C, D, H, acteoside, and isoacteoside improved neuronal cell viability, cell morphology, apoptosis, and synaptic damage. Additionally, regaloside A, B, C, D, H and acteoside regulated the neurotransmitter levels, while regaloside A, B, C, D, acteoside and isoacteoside inhibited the levels of inflammatory cytokines. CONCLUSION: The butanol fraction was found to be the main active fraction of BDD, and 14 compounds were the major anxiolytic active components. The results of verifying the major active components were consistent with the predicted results of the spectrum-effect analysis. The developed spectrum-effect analysis in this study demonstrates high accuracy and reliability for screening active components in TCMs.
关键词：
Acute toxicity;Behavioral analysis;Danggui Shaoyao San;Danio rerio;Histopathological alteration index
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Although the Traditional Chinese Medicine (TCM) prescription of Danggui Shaoyao San (DSS) presents substantial clinical efficacy and promising clinical prospects, the safety of DSS and its extracts have been inadequately investigated. The larva-adult duality of the zebrafish model offers a more efficient approach for evaluating the safety of herbal preparations in the fields of toxicology and pharmacology. AIM OF THE STUDY: To investigate the acute toxicity of the extract derived from Danggui Shaoyao San, a traditional Chinese medicine preparation, on both Danio rerio embryos and adult organisms. MATERIALS AND METHODS: The components of DSS were identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The hatching rate of Danio rerio juveniles with different concentrations of DSS was calculated and the morphological changes of juveniles after administration were observed through a microscope. The behavioral trajectory of the adult fish was recorded by the observation tower of the automated Danio rerio analysis system, and DSS's effects on the behavior was analyzed. The pathological changes of Danio rerio gills, livers, kidneys, intestines and spermaries were examined using HE staining. RESULTS: Compared with the control group, 25, 50 and 100mg/L of DSS did not elicit any significant impacts on the hatching rate and morphology. Both 200mg/L and the propylene glycol 2% reduced the hatching rate and caused the morphological teratogenic changes of the juvenile fish. The dosage of DSS below 100mg/L had no discernible effect on the behavior of the adult fish, whereas the application of propylene glycol 2% was found to stimulate the adult fish, resulting in a notable increase in high-speed movement distance. 100mg/L DSS group was not observed to cause any noticeable damage to the gills, livers, intestines and spermaries of Danio rerio, only mild nephrotoxicity was detected. The propylene glycol 2% group was found to result in pathological changes such as hyperplasia of epithelial cells on secondary lamellae, liver cell outline loss or atypia, tubal disorganization, goblet cell hypertrophy and irregularly arranged spermatozoa. CONCLUSION: A viable approach for conducting toxicological studies on TCM preparations was developed and tested in this research. The findings showed that Danggui Shaoyao San has minimal acute toxicity to embryos and adult organisms at concentrations up to 100mg/L. These results indicate that Danggui Shaoyao San is a safe TCM preparation.
