1.Research progress on carrier-free and carrier-supported supramolecular nanosystems of traditional Chinese medicine anti-tumor star molecules
Zi-ye ZANG ; Yao-zhi ZHANG ; Yi-hang ZHAO ; Xin-ru TAN ; Ji-chang WEI ; An-qi XU ; Hong-fei DUAN ; Hong-yan ZHANG ; Peng-long WANG ; Xue-mei HUANG ; Hai-min LEI
Acta Pharmaceutica Sinica 2024;59(4):908-917
Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.
2.Improvement Effect and Its Mechanism of Marmesin on Cognitive Impairment in Mice with Alzheimer's Disease
Zhuang-Zhuang LIU ; Shi-Jie SU ; Hong-Ying YANG ; Hai-Xia DING ; Ya-Ru PAN ; Han CAI ; Lei-Jie LIN ; Wei-Rong LI ; Qi WANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(10):2758-2768
Objective To investigate the improvement effect and mechanism of marmesin on cognitive impairment in Alzheimer's disease(AD)mice.Methods Fifty mice were randomly divided into five groups:blank group,model group,low-and high-dose marmesin groups and donepezil(positive drug)group,with 10 mice in each group.After 21 days of continuous administration,except for the blank group,the mice in other groups were given intraperitoneal injection of scopolamine to establish the AD model.Network pharmacology was used to construct the protein-protein interaction(PPI)network of common targets of marmesin in the treatment of AD,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed to provide further research direction.The cognitive function of AD model mice was evaluated by Morris water maze,open field test and new object recognition test.Nissl staining was used to observe the damage of hippocampal neurons.The levels of acetylcholine(Ach),acetylcholine transferase(ChAT),acetylcholinesterase(AChE),reactive oxygen species(ROS),malondialdehyde(MDA)and catalase(CAT)in hippocampus of mice were detected by kit.The protein expression levels of interleukin 6(IL-6),interleukin 1β(IL-1 β),tumor necrosis factor α(TNF-α),nuclear factor E2-related factor 2(NRF2),silent information regulator homologous protein 3(SIRT3),Kelch-like ECH-associated protein 1(KEAP1),quinone oxidoreductase 1(NQO1)and heme oxygenase 1(HO-1)in hippocampus were detected by Western Blot.Results Compared with the model group,the latency of Morris water maze test was significantly shortened in the high-dose marmesin group,the time of entering the target area in the open field new object test and the movement distance in the central area of the open field were prolonged,the number of neurons in the hippocampal CA1 and CA3 regions was significantly increased,the levels of ChAT and Ach in the hippocampus were significantly increased,AChE level was significantly decreased,CAT level was significantly increased,ROS and MDA levels were significantly decreased,TNF-α expression level was decreased,SIRT3 and HO-1 expression levels were increased,and KE AP1 protein expression level was decreased,the differences being statistically significant(P<0.05 or P<0.01 or P<0.001).Conclusion Marmesin can effectively improve the learning and memory impairment of AD mice,and its mechanism may be related to the activation of NRF2/SIRT3 signaling pathway,thereby alleviating oxidative stress level and neuroinflammation,and repairing cholinergic neuron function.
3.Activity evaluation and mechanism study of antibacterial-anti-inflammatory bifunctional Dioscoreae Nipponicae Rhizoma natural components targeting regulatory protein posttranslational modification
Ru-xu SHEN ; Zi-chen YE ; Jia-qi ZHAO ; Qian ZHANG ; Hai-feng TANG ; Di QU
Acta Pharmaceutica Sinica 2024;59(11):2981-2989
The phenomenon of bacterial drug resistance is becoming more and more serious. Natural products, as an important resource for drug discovery, can play a role by regulating protein post-translational modifications related to bacterial infection and inflammatory responses. This provides a valuable compound library for the research and development of new antibacterial drugs. In this present research, dioscin and diosgenin were isolated and identified from
5. The protective effect of Dexrazoxane on onco-Cardiology induced by anticancer agents other than anthracyclines
Jing-Wen LUN ; Yu-Jing LU ; Qi-Rong FENG ; Yu-Xi YUAN ; Qiu-Ru LI ; Hai-Shan ZHAO
Chinese Pharmacological Bulletin 2022;38(12):1816-1822
Aim To evaluate the protective effect of Dexrazoxane(Dex)on onco-Cardiology caused by chemotherapeutic drugs other than anthracycline antitumor drugs using zebrafish embryos, including:cisplatin, paclitaxel, vincristine sulfate, 5-fluorouracil and cyclophosphamide. Methods Zebrafish embryos at 24 hpf(hours post-fertilization)were exposed to different concentrations of drugs. The survival rate and the overall animal morphology at 48 hpf, 72 hpf and 96 hpf were observed with a microscope. Heart rate, ventricular contraction fraction, ventricular volume, and cardiac output were measured and calculated by video recordings made with a VCD system. The protective effect of Dex was evaluated using the established model of onco-Cardiology induced by anti-tumor drugs other than anthracyclines. Results In terms of acute toxicity, cisplatin, vincristine sulfate, 5-fluorouracil and cyclophosphamide all significantly reduced the survival rate of zebrafish embryos. The LC50 value was 437.655, 25.538, 65.606 and 19.021 mmol·L-1, respectively. In addition to paclitaxel, the other four anti-tumor drugs all showed significant changes in overall animal morphology and cardiac function indicators. In the study of the protective effect of Dex on four kinds of tumor heart diseases except anthracyclines, only cisplatin had a significant protective effect, which could improve the cardiotoxicity caused by cisplatin. The optimal concentration of Dex was 80 μmol·L-1. Conclusions Zebrafish models of drug toxicity caused by cisplatin, vincristine sulfate, 5-fluorouracil, and cyclophosphamide is established, which proves that Dex only has a protective effect on the toxicity caused by cisplatin.
6.Risk assessment of malignancy in solitary pulmonary nodules in lung computed tomography: a multivariable predictive model study.
Hai-Yang LIU ; Xing-Ru ZHAO ; Meng CHI ; Xiang-Song CHENG ; Zi-Qi WANG ; Zhi-Wei XU ; Yong-Li LI ; Rui YANG ; Yong-Jun WU ; Xiao-Ju ZHANG
Chinese Medical Journal 2021;134(14):1687-1694
BACKGROUND:
Computed tomography images are easy to misjudge because of their complexity, especially images of solitary pulmonary nodules, of which diagnosis as benign or malignant is extremely important in lung cancer treatment. Therefore, there is an urgent need for a more effective strategy in lung cancer diagnosis. In our study, we aimed to externally validate and revise the Mayo model, and a new model was established.
METHODS:
A total of 1450 patients from three centers with solitary pulmonary nodules who underwent surgery were included in the study and were divided into training, internal validation, and external validation sets (n = 849, 365, and 236, respectively). External verification and recalibration of the Mayo model and establishment of new logistic regression model were performed on the training set. Overall performance of each model was evaluated using area under receiver operating characteristic curve (AUC). Finally, the model validation was completed on the validation data set.
RESULTS:
The AUC of the Mayo model on the training set was 0.653 (95% confidence interval [CI]: 0.613-0.694). After re-estimation of the coefficients of all covariates included in the original Mayo model, the revised Mayo model achieved an AUC of 0.671 (95% CI: 0.635-0.706). We then developed a new model that achieved a higher AUC of 0.891 (95% CI: 0.865-0.917). It had an AUC of 0.888 (95% CI: 0.842-0.934) on the internal validation set, which was significantly higher than that of the revised Mayo model (AUC: 0.577, 95% CI: 0.509-0.646) and the Mayo model (AUC: 0.609, 95% CI, 0.544-0.675) (P < 0.001). The AUC of the new model was 0.876 (95% CI: 0.831-0.920) on the external verification set, which was higher than the corresponding value of the Mayo model (AUC: 0.705, 95% CI: 0.639-0.772) and revised Mayo model (AUC: 0.706, 95% CI: 0.640-0.772) (P < 0.001). Then the prediction model was presented as a nomogram, which is easier to generalize.
CONCLUSIONS
After external verification and recalibration of the Mayo model, the results show that they are not suitable for the prediction of malignant pulmonary nodules in the Chinese population. Therefore, a new model was established by a backward stepwise process. The new model was constructed to rapidly discriminate benign from malignant pulmonary nodules, which could achieve accurate diagnosis of potential patients with lung cancer.
Humans
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Lung
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Lung Neoplasms/diagnostic imaging*
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Multiple Pulmonary Nodules
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Risk Assessment
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Solitary Pulmonary Nodule/diagnostic imaging*
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Tomography, X-Ray Computed
7. Influence of intravascular ultrasound on the prognosis of patients after rotational atherectomy
Zhan-ru QI ; Zhong-hai WEI ; Jing-mei ZHANG ; Qing DAI ; Jun XIE ; Kun WANG ; Li-na KANG ; Lian WANG ; Jie SONG
Journal of Medical Postgraduates 2020;33(6):613-617
ObjectiveThe development of new endovascular imaging techniques has optimized surgical treatment strategies. In this paper, we investigated the effect of rotational atherectomy (RA) guided by intravascular ultrasound (IVUS) on long-term postoperative follow-ups.MethodsClinical data of 211 patients who underwent RA in the Department of Cardiology, Nanjing Drum Tower Hospital from November 2011 to December 2018 were retrospectively analyzed, and they were divided into IVUS Group (116 patients) and Non-IVUS Group (95 patients) according to whether they underwent the guidance of intravascular ultrasound or not. Basic information of all patients, coronary artery lesions and details of operation and other clinical data were collected. The long-term prognosis of the patients was collected and compared by telephone or outpatient follow-ups.ResultsThe head diameter, average stent diameter and total hospitalization expenses of the IVUS Group were significantly higher than those of the Non-IVUS Group, and the differences were statistically significant [(1.53±0.19) mm vs (1.46±0.14) mm, P=0.001; (3.09±0.48) mm vs (2.87±0.30) mm, P<0.001; (57,300±18,300) yuan vs (49,300±16,600) yuan, P=0.001]. The all-cause case fatality rate and cardiogenic case fatality rate of the IVUS Group were lower than those of the Non-IVUS Group (7.5% vs 16.7%, P=0.048; 1.9% vs 11.9%, P=0.005); There were no significant differences in the incidence of long-term major adverse cardiovascular events (MACE), myocardial infarction, target vessel revascularization and non-fatal stroke between the two groups (P>0.05). Multivariate COX regression analysis showed that the cardiogenic mortality was significantly reduced in the IVUS Group (HR=0.10, 95%CI: 0.02~0.63, P=0.014), but there was no statistically significant difference between the two groups in the incidence of all-cause death and long-term MACE (P>0.05).ConclusionCompared with the Non-IVUS Group, IVUS-guided RA can significantly reduce the incidence of long-term cardiogenic death and total hospitalization expenses.
8.Effect of fresh Gastrodia elata on gut microbiota in mice.
Zhong-Yi HUA ; Hong-Mei LI ; Jian-Hui SUN ; Hai-Ru HUO ; Xiao-Qin LI ; Lu-Qi HUANG ; Yuan YUAN
China Journal of Chinese Materia Medica 2019;44(5):1004-1009
Gastrodia elata B1.,a traditional Chinese medicine,was frequently applied as a cure for headache or migraine. Its effects include suppressing hyperactive liver,calming endogenous wind,dredging collateralsand relieving spasm. There has been a proportion that G. elata should be added to The List of Substances That Are Traditionally Both Food and Chinese Medicinal Materials. The dry G. elata was commonly used in clinic,which have some fundamental study on efficacy and mechanism. However,fresh G. elata,which was added to herbal cuisine very often,lacks corresponding research. The interaction of diet,microbiota and human is a hot issue and lots of scholars are focusing on it. This research sequenced the 16 S rRNA of mouse cecal contents on Mi Seq platform to understand the effect of taking fresh G. elata. As the results showing,multiple probiotics grew after taking fresh G. elata extract,including Ruminiclostridium,Butyricicoccus,and Parvibacter. To contrast,some pathogens or potential pathogens,such as Escherichia/Shigella,Parasutterella,decreased. This manifests that fresh G. elata performs a positive regulation on mouse gut microbiota,especially the low-dose fresh G. elata extraction could restructure the microbiota apparently. Our result reveals that microbiota might be a new target for G. elata extract and provides an important basis for further research on the interaction between gut microbiota and pharmacological activity of G. elata.
Animals
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Drugs, Chinese Herbal
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pharmacology
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Gastrodia
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chemistry
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Gastrointestinal Microbiome
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drug effects
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Medicine, Chinese Traditional
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Mice
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Plant Extracts
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pharmacology
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Plants, Medicinal
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chemistry
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RNA, Ribosomal, 16S
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genetics
9.Modern research progress of traditional Chinese medicine based on integrative pharmacology.
Ping WANG ; Shi-Huan TANG ; Jin SU ; Jia-Qi ZHANG ; Ru-Yi CUI ; Hai-Yu XU ; Hong-Jun YANG
China Journal of Chinese Materia Medica 2018;43(7):1297-1302
Integrative pharmacology (IP) is a discipline that studies the interaction, integration and principle of action of multiple components with the body, emphasizing the integrations of multi-level and multi-link, such as "whole and part", " and ", " process and activity evaluation". After four years of development and practice, the theory and method of IP has received extensive attention and application.In order to better promote the development of IP, this paper systematically reviews the concepts, research contents, research methods and application fields about IP.

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