1.Discovery of the radio-protecting effect of Ecliptae Herba, its constituents and targeting p53-mediated apoptosis in vitro and in vivo.
Jiang WU ; Wenfeng GOU ; Zhiyun WANG ; Huajie CHANG ; Deguan LI ; Wenbin HOU ; Changxiao LIU
Acta Pharmaceutica Sinica B 2023;13(3):1216-1230
Radiation protection drugs are often accompanied by toxicity, even amifostine, which has been the dominant radio-protecting drug for nearly 30 years. Furthermore, there is no therapeutic drug for radiation-induced intestinal injury (RIII). This paper intends to find a safe and effective radio-protecting ingredient from natural sources. The radio-protecting effect of Ecliptae Herba (EHE) was discovered preliminarily by antioxidant experiments and the mouse survival rate after 137Cs irradiation. EHE components and blood substances in vivo were identified through UPLC‒Q-TOF. The correlation network of "natural components in EHE-constituents migrating to blood-targets-pathways" was established to predict the active components and pathways. The binding force between potential active components and targets was studied by molecular docking, and the mechanism was further analyzed by Western blotting, cellular thermal shift assay (CETSA), and ChIP. Additionally, the expression levels of Lgr5, Axin2, Ki67, lysozyme, caspase-3, caspase-8,8-OHdG, and p53 in the small intestine of mice were detected. It was found for the first time that EHE is active in radiation protection and that luteolin is the material basis of this protection. Luteolin is a promising candidate for RⅢ. Luteolin can inhibit the p53 signaling pathway and regulate the BAX/BCL2 ratio in the process of apoptosis. Luteolin could also regulate the expression of multitarget proteins related to the same cell cycle.
2.Research progress in quality studies and antiviral effect of Qingyan Dropping Pills
Yuli WANG ; Mingrui ZHANG ; Hong ZHOU ; Xuehai ZHOU ; Yubo LI ; Huling LI ; Dandan SHANG ; Jinlei WANG ; He HUANG ; Yitao WANG ; Changxiao LIU
International Journal of Biomedical Engineering 2023;46(3):258-263
Qingyan Dropping Pills have the effects of relieving wind and heat, detoxifying, and promoting the pharynx. It is commonly used in traditional Chinese medicines to treat acute and chronic pharyngitis, as well as sore throats and dry throats caused by surgery. Recently, many studies have shown that Qingyan Dropping Pills have certain effects on bacteriostasis, anti-inflammatory, antioxidant, and antiviral activities. As the coronavirus disease 2019 (COVID-19) pandemic enters the post-epidemic era, the regular use of drugs for COVID-19 pandemic symptoms has become a new trend. Therefore, there is a good market prospect to explore and develop Chinese patent medicines with antiviral effects. A preliminary study on the herbal formula and material basis of Qingyan Dropping Pills revealed that they have potential for antiviral applications. In this paper, the research on the quality study and antiviral effect of Qingyan Dropping Pills was reviewed, and the research direction of its secondary development was discussed to provide ideas and references for the new use of old traditional Chinese medicines.
3.Erratum: Author correction to 'Discovery of the radio-protecting effect of ecliptae herba, its constituents and targeting p53-mediated apoptosis in vitro and in vivo' Acta Pharm Sin B 13 (2023) 1216-1230.
Jiang WU ; Wenfeng GOU ; Zhiyun WANG ; Huajie CHANG ; Deguan LI ; Wenbin HOU ; Changxiao LIU
Acta Pharmaceutica Sinica B 2023;13(6):2815-2816
[This corrects the article DOI: 10.1016/j.apsb.2022.09.003.].
4.Nutritional literacy and influencing factors among students from Nutrition Improvement Program for Rural Compulsory Education Students in Chongqing
LI Shengping, ZENG Mao, XIE Changxiao, XU Qi, ZHAO Yong
Chinese Journal of School Health 2022;43(1):41-44
Objective:
To analyze the nutritional literacy and influencing factors among students from Nutrition Improvement Program for Rural Compulsory Education Students (NIPRCES) in Chongqing, and to provide a scientific basis for improving the nutritional literacy of middle school students in the NIPRCES.
Methods:
Using cross sectional survey, a total of 3 365 students in the grade 7 and 8 were selected from the middle schools in 12 national pilot districts and 2 Chongqing pilot districts by online survey in September 2020. Students filled out a self designed nutritional literacy questionnaire anonymously. The relative evaluation method was used to convert the nutritional literacy of scores into a percentile, and the median score was used as the criterion for qualified nutritional literacy screening.
Results:
The median score of nutritional literacy of participants was 63.5, and 64.2% achieved the qualified level. The results of multivariate Logistic regression analysis showed that boarding school ( OR =1.28, 95% CI =1.08- 1.51 ) and no parents as the primary caregiver ( OR =1.22,95% CI =1.05-1.42) were associated with poor nutritional literacy. Urban residence ( OR =0.75, 95% CI =0.63-0.90), NIPRCES local pilot ( OR =0.83, 95% CI =0.71-0.97) and high paternal education ( OR =0.70, 95% CI =0.52-0.95) were associated with higher nutritional literacy ( P <0.01). Classroom was the main channel for students to obtain nutrition information at present (65.1%) and in the future (72.8%).
Conclusion
The nutritional literacy among students in the NIPRCES in Chongqing needs to be improved. Nutritional literacy level of students can be strengthened by nutritional education in boarding schools, rural areas, national pilot areas, and primary caregivers.
5.Absolute bioavailability,dose proportionality,and tissue distribution of rotundic acid in rats based on validated LC-QqQ-MS/MS method
Haihua SHANG ; Xiaohan DAI ; Mi LI ; Yueyi KAI ; Zerong LIU ; Min WANG ; Quansheng LI ; Yuan GU ; Changxiao LIU ; Duanyun SI
Journal of Pharmaceutical Analysis 2022;12(2):278-286
Rotundic acid(RA),an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb.(Aquifoliaceae),possesses diverse bioactivities.To further study its pharmacokinetics,a simple and sensitive liquid chromatography with triple quadrupole mass spectrometry(LC-QqQ-MS/MS)method was developed and validated to quantify RA concentration in rat plasma and tissue using etofesalamide as an internal standard(IS).Plasma and tissue samples were subjected to one-step protein precipitation.Chromatographic separation was achieved on a ZORBAX Eclipse XDB-C18 col-umn(4.6 mm×50 mm,5 μm)under gradient conditions with eluents of methanol:acetonitrile(1∶1,V/V)and 5mM ammonium formate:methanol(9∶1,V/V)at 0.5mL/min.Multiple reaction monitoring transitions were performed at m/z 487.30 → 437.30 for RA and m/z 256.10 → 227.10 for IS in the negative mode.The developed LC-QqQ-MS/MS method exhibited good linearity(2-500 ng/mL)and was fully validated in accordance with U.S.Food and Drug Administration bioanalytical guidelines.Dose proportionality and bioavailability in rats were determined by comparing pharmacokinetic data after single oral(10,20,and 40 mg/kg)and intravenous(10 mg/kg)administration of RA.Tissue distribution was studied following oral administration at 20 mg/kg.The results showed that the absolute bioavailability of RA after administration at different doses ranged from 16.1%to 19.4%.RA showed good dose proportionality over a dose range of 10-40 mg/kg.RA was rapidly absorbed in a dose-dependent manner and highly distributed in the liver.In conclusion,this study is the first to systematically elucidate the absorption and distribution characteristics of RA in rats,which can provide additional information for further development and evaluation of RA in drug metabolism and pharmacokinetic studies.
6. Taxifolin attenuates inflammation via suppressing MAPK signal pathway in vitro and in silico analysis
Xingyan ZHANG ; Huling LI ; Wenjing ZHAO ; Xin LI ; Fujun ZHOU ; Yutong ZHOU ; Tao CUI ; Yuli WANG ; Changxiao LIU ; Xiaoyan LIAN ; Wenjing ZHAO ; Fujun ZHOU ; Tao CUI ; Changxiao LIU ; Yuli WANG ; Changxiao LIU ; Yuli WANG ; Yuli WANG
Chinese Herbal Medicines 2022;14(4):554-562
Objective: Taxifolin is a natural flavonoid compound that can be isolated from onions, grapes, oranges and grapefruit. It also acts as a medicine food homology with extraordinary antioxidant and anti-inflammatory activity. This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction. Methods: Levels of interleukin (IL)-6, IL-1β and intracellular reactive oxygen species (ROS) were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide (LPS). Subsequently, the mRNA and protein levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α and the phosphorylation expression levels of the MAPK signal pathway were also evaluated. A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway. And then MAPK inhibitors were used to reveal the expression level of iNOS, VEGF, COX-2 and TNF-α in RAW264.7 cells. Results: It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin. Then, the mRNA and protein levels of iNOS, VEGF, COX-2 and TNF-α were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well. In silico analysis, taxifolin could form a relatively stable combination with MAPK signal pathway. MAPK inhibitors showed increasing or decreasing effect in the mRNA levels of iNOS, VEGF, COX-2 and TNF-α, which suggesting that taxifolin down-regulated iNOS, VEGF, COX-2 and TNF-α expressions were not entirely through the MAPK pathway. Conclusion: This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress.
7.Five cases of breast reconstruction with pedicled greater omentum metastasis after mastectomy
Guangxu HAO ; Qing ZHONG ; Changxiao ZHAO ; Li DONG ; Yi REN ; Jing ZHANG
Chinese Journal of Endocrine Surgery 2021;15(2):211-214
Immediate breast reconstruction with pedicle great omentum metasasis is safe,easy to perform, and has extensive clinical indications, less postoperative complications. The shape of reconstructed breast is plump and symmetrical, which is the optimal choice for reconstruction surgery with small and medium-sized breast at present. The surgical methods and effects of breast reconstruction with pedicle great omentum metastasis in 5 patients are reported in this article. Combined with the previous literature, the feasibility and safety of surgery is discussed, which provide a reference to clinicians.
8.Early predictors of Mycoplasma pneumoniae necrotizing pneumonia in children
Shuaishuai LIU ; Jing MA ; Zhongxiao ZHANG ; Changxiao LI ; Linlin HAN ; Chen MENG
Chinese Journal of Applied Clinical Pediatrics 2021;36(8):601-604
Objective:To study the early predictors of Mycoplasma pneumoniae necrotizing pneumonia in children.Methods:Clinical data of 291 children with lobar pneumonia caused by Mycoplasma pneumoniae who were hospitalized in Department of Respiratory Intervention, Qilu Children′s Hospital of Shandong University from August 2016 to September 2018, were retrospectively analyzed.The patients were divided into necrotizing pneumonia group (154 cases) and non-necrotizing pneumonia group (137 cases). After comparing clinical characteristics, laboratory tests, and bronchoscopy findings, multivariate logistic regression analysis was carried out on the indicators with statistical significance to obtain the independent predictive indicators of Mycoplasma pneumoniae necrotizing pneumonia, and then the cutoff value with the maximum diagnostic value of each indicator was found through receiver operating characteristic (ROC) curve analysis.Results:There were no significant differences in gender and age distribution, duration before admission, and platelet count between the 2 groups(all P>0.05). Necrotizing pneumonia group manifested with 11.0(8.3-14.4)×10 9/L of white blood cell count, 0.740±0.115 of neutrophil, 44.2(21.2-72.0) mg/L of C-reactive protein(CRP), 55(35-80) mm/1 h of erythrocyte sedimentation rate, 0.19(0.08-0.60) ng/L of procalcitonin, 2.63(1.62-3.79) mg/L of plasma D-dimer, 456(340-665) U/L of serum lactate dehydrogenase, (35.6±4.3) g/L of serum albumin, 121 cases(78.6%)of bronchoscopic mucosal erosion, 75 cases(48.7%)of purulent lavage, 119 cases(77.3%)of massive secretions embolism; non-necrotizing pneumonia group manifested with 8.7(6.9-11.6)×10 9/L of white blood cell count, 0.660±0.127 of neutrophil percentage, 15.9(7.5-34.3) mg/L of CRP, 45(30-60) mm/1 h of erythrocyte sedimentation rate, 0.10(0.06-0.20) ng/L of procalcitonin, 0.69(0.46-1.24) mg/L of plasma D-dimer, 314(250-419) U/L of serum lactate dehydrogenase, (38.9±3.7) g/L of serum albumin, 53 cases(38.7%)of bronchoscopic mucosal erosion, 20 cases(14.6%)of purulent lavage, and 76 cases(55.5%)of massive secretions embolism.All the above indicators had statistical differences between the 2 groups.Erythrocyte sedimentation rate, serum lactate dehydrogenase, D-dimer, and bronchoscopic mucosal erosion were independent predictors of Mycoplasma necrotizing pneumonia.The area under the ROC curve were 0.643, 0.749, 0.858 and 0.699, respectively, with the cut off point of 53 mm/1 h, 335 U/L, and 1.36 mg/L, respectively. Conclusions:Erythrocyte sedimentation rate≥53 mm/1 h, serum lactate dehydrogenase≥335 U/L, D-dimer≥1.36 mg/L, and bronchoscopic mucosal erosion are early independent predictors of Mycoplasma necrotizing pneumonia in children, among which D-dimer has the highest value.
9.Application of immune checkpoint targets in the anti-tumor novel drugs and traditional Chinese medicine development.
Yuli WANG ; Xingyan ZHANG ; Yuyan WANG ; Wenjing ZHAO ; Huling LI ; Lixing ZHANG ; Xinping LI ; Tiejun ZHANG ; Hongbing ZHANG ; He HUANG ; Changxiao LIU
Acta Pharmaceutica Sinica B 2021;11(10):2957-2972
Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers. In the last few years, extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines (TCMs). The main advantage of TCMs and natural medicine is that they usually contain multiple active components, which can act on multiple targets at the same time, resulting in additive or synergistic effects. The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest. For example,
10.Potential synergic mechanism of Wutou-Gancao herb-pair by inhibiting efflux transporter P-glycoprotein
Yufei HE ; Zihong WEI ; Ying XIE ; Xiulin YI ; Yong ZENG ; Yazhuo LI ; Changxiao LIU
Journal of Pharmaceutical Analysis 2020;10(2):178-186
Wutou-Gancao herb-pair is extensively used to attenuate the toxicity and enhance the efficacy of aconite. In this study, potential synergic mechanism of the herb pair was investigated by utilizing multiple ap-proaches. In silico and in vitro Caco-2 cell models were applied to study the potential binding mode of bioactive ingredients existing in liquorice with P-glycoprotein (P-gp), as well as the inhibition effects on P-gp. Additionally, anti-inflammatory activity of aconitine (AC) combined with active ingredients of liquorice, as well as pharmacokinetic patterns of AC after co-administration was investigated. Anti-inflammatory effect of AC (1 mg/kg) in rats was enhanced in combination with bioactive ingredients of liquorice (10 mg/kg). In the meanwhile, the exposure of AC in vivo was altered, in terms of Cmax and AUC. For instance, the Cmax and AUC were increased to 1.9 and 1.3 folds, respectively, when used in combination with liquiritigenin. The in silico study revealed the potential binding mode with outward facing conformation of P-gp. The resulting data obtained from transport of rhodamine-123 (Rh-123) across Caco-2 cell monolayer further indicated that the function of P-gp was inhibited by chemicals in liquorice. The synergic effect was therefore proposed to be attributed to inhibition of P-gp by liquorice since AC has been demonstrated to be the substrate of P-gp. The resuls revealed that potential synergic mechanism of Wutou-Gancao herb-pair by inhibiting function of key efflux transporter P-gp to enhance the exposure of AC in systematic circulation, and further the anti-inflammatory effect, which helps clarify the compatibility rationale of these two herbs.


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