1.Discovery of human pancreatic lipase inhibitors from root of Rhodiola crenulata via integrating bioactivity-guided fractionation,chemical profiling and biochemical assay
Ma LI-JUAN ; Hou XU-DONG ; Qin XIAO-YA ; He RONG-JING ; Yu HAO-NAN ; Hu QING ; Guan XIAO-QING ; Jia SHOU-NING ; Hou JIE ; Lei TAO ; Ge GUANG-BO
Journal of Pharmaceutical Analysis 2022;12(4):683-691
Although herbal medicines(HMs)are widely used in the prevention and treatment of obesity and obesity-associated disorders,the key constituents exhibiting anti-obesity activity and their molecular mechanisms are poorly understood.Recently,we assessed the inhibitory potentials of several HMs against human pancreatic lipase(hPL,a key therapeutic target for human obesity),among which the root-extract of Rhodiola crenulata(ERC)showed the most potent anti-hPL activity.In this study,we adopted an integrated strategy,involving bioactivity-guided fractionation techniques,chemical profiling,and biochemical assays,to identify the key anti-hPL constituents in ERC.Nine ERC fractions(retention time=12.5-35 min),obtained using reverse-phase liquid chromatography,showed strong anti-hPL activity,while the major constituents in these bioactive fractions were subsequently identified using liquid chromatography-quadrupole time-of-flight mass spectrometry(LC-Q-TOF-MS/MS).Among the identified ERC constituents,1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose(PGG)and catechin gallate(CG)showed the most potent anti-hPL activity,with pIC50 values of 7.59±0.03 and 7.68±0.23,respectively.Further investigations revealed that PGG and CG potently inhibited hPL in a non-competitive manner,with inhibition constant(Ki)values of 0.012 and 0.082 μM,respectively.Collectively,our integrative analyses enabled us to efficiently identify and characterize the key anti-obesity constituents in ERC,as well as to elucidate their anti-hPL mechanisms.These findings provide convincing evidence in support of the anti-obesity and lipid-lowering properties of ERC.
2. Study of a-Asarone protecting BV2 cells damaged by OGD/R by regulating of NLRP3 pathway
Fei-Fei XU ; Kai GUI ; Li-You WANG ; Ya-Qi GUAN ; Ming LIU ; Qin-Qing LI ; Ya-Juan TIAN ; Wen-Bin HE ; Shi-Feng CHU
Chinese Pharmacological Bulletin 2022;38(8):1209-1218
Aim To evaluate the protective effect of α-asarone on microglials with cerebral ischemia/reperfusion injury by measuring the expression of polar transformation and related inflammatory proteins in BV2 cells in vitro and its mechanisms.Methods The cerebral ischemia/reperfusion injury BV2 cells were pretreated by α-asarone in vitro and simulated by OGD/R model.The effect of α-asarone on the viability of damaged cells in OGD/R model was determined by CCK-8; the morphological changes of cells were observed to analyze the general morphology of cells; the levels of proinflammatory factor IL-1β, IL-18 and anti-inflammatory factor IL-10, IL-4, and ROS activity secreted by BV2 cells were detected by ELISA; the protein expressions of TGF-β, TNF-α and inflammatory related protein NLRP3, caspase 1, p-NF-κB were detected by Western blot.Results The results of in vitro experiments were as follows: the activity of damaged cells in OGD/R model was significantly increased by α-asarone, with the increase of administration dose, the cells in the low, medium and high dose groups of α-asarone decreased, and the "amoeba-like" cells and the cell body were gradually became stereoscopic and full.From the results of cell morphology, it could be seen that α-asarone had a certain proliferative effect on normal cells; the release was significantly reduced of proinflammatory factor IL-1β, IL-18 and TNF-α in OGD/R injured BV2 cells pretreated with α-asarone, also increased the release of IL-10, IL-4 and TGF-β, with a dose-effect relationship, and the high dose(16 μmol·L-1)was the best; the expressions of inflammatory related protein NLRP3, caspase 1, NF-κB and ROS activity in injured cells of OGD/R model were significantly reduced after pretreatment with α-asarone.Conclusions α-asarone has a significant protective effect on cerebral ischemia/reperfusion injury, mainly by regulating ROS activity and inhibiting phosphorylation of NF-κB, in order to reduce the excessive activation of NLRP3 inflammatory corpuscles reducing the secretion of proinflammatory factor IL-1β and IL-18, promoting the secretion of anti-inflammatory factor IL-10 and IL-4, so as to protect cerebral ischemia/reperfusion injury by anti-inflammatory reaction.
3.3- to 24-month Follow-up on COVID-19 with Pulmonary Tuberculosis Survivors after Discharge: Results from a Prospective, Multicenter Study
Ya Jing WANG ; Yu Xing ZONG ; Hui Gui WU ; Lin Yuan QI ; Zhen Hui LI ; Yu Xin JI ; Lin TONG ; Lei ZHANG ; Bo Ming YANG ; Ye Pu YANG ; Ke Ji LI ; Rong Fu XIAO ; Song Lin ZHANG ; Hong Yun HU ; De Hong LIU ; Fang Shou XU ; Sheng SUN ; Wei WU ; Ya MAO ; Qing Min LI ; Hua Hao HOU ; Yuan Zhao GONG ; Yang GUO ; Wen Li JIAO ; Jin QIN ; Yi Ding WANG ; Fang WANG ; Li GUAN ; Gang LIN ; Yan MA ; Ping Yan WANG ; Nan Nan SHI
Biomedical and Environmental Sciences 2022;35(12):1091-1099
Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9%) were men. Among them, nearly two-thirds (62.5%) of the survivors were moderate, three (9.4%) were severe, and more than half (59.4%) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6% at 3 months to 15.8% at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1%) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.
4.Mechanism of Sinisan in Treating Type 2 Diabetes Mellitus Based on Network Pharmacology
Yi-ming BI ; Bei YIN ; Ya-qing XIA ; Guan-jie FAN
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(24):169-177
Objective:To investigate the mechanism of Sinisan in treating type 2 diabetes mellitus(T2DM) based on network pharmacology. Method:Based on electronic databases, active ingredients of Sinisan and target genes of ingredients as well as type 2 diabetes were screened out. Cytoscape software was applied to construct "herb-active ingredient-target-disease" interaction network diagram,respectively. The common genes of ingredients and disease were uploaded to the STRING database, and the protein interaction network map (PPI) was constructed. CytoNCA and Cluster Marker were used to analyze PPI,respectively. Finally,ClueGO was used to analyze gene ontology (GO) enrichment and Kyoto Encyclopedia of genes and genomes (KEGG) pathway enrichment. Result:A total of 137 active components and 110 effective genes of Sinisan in the treatment of type 2 diabetes were screened out. Based on PPI analysis,these effective genes were divided into 4 different clusters, and 12 genes were considered as the most effective targets. GO enrichment analysis showed that cluster 1 mainly involved acute inflammatory response and acetylcholine receptor signaling pathway, cluster 2 mainly involved cellular response to steroid hormone stimulu and xenobiotic stimulus,and cluster 3 was mainly engaged in the metabolism process of protein,fatty and glucose and the response to hypoxia. KEGG analysis was highly correlated with advanced glycation end products-receptor for AGE (AGE-RAGE) pathway,apoptosis pathway,inflammatory pathway,cell cycles and various metabolic pathways. Conclusion:Sinisan has a regulatory effect in pathogenesis and prognosis of T2DM,such as inflammation,cell apoptosis and nutrition metabolism. Moreover,its potential mechanisms on diabetic angiopathies,diabetic cognitive impairment and cancers were reveal,so as to define a direction for the fundamental research of Sinisan.
5.Network Pharmacology-based Mechanism of Xiao Xianxiongtang in Treatment of Coronary Heart Disease
Qing-ya GUAN ; Jie WANG ; Yun ZHANG ; Yong-mei LIU ; Zhen-peng ZHANG ; Xing-jiang XIONG ; Jun-ming HE
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(5):152-161
Objective::To predict Xiao Xianxiongtang's treatment of coronary heart disease (CHD) targets and analyze their function by the network pharmacology method, and build ingredients-targets-channel network pharmacological model, in order to reveal potential pathways and mechanisms of Xiao Xianxiongtang for CHD treatment. Method::Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to obtain components, and CHD targets over Xiao Xianxiongtang were predicted by using Swiss Target Prediction reverse pharmacophore matching method. CHD targets which Food and Drug Administration (FDA) approved were collected from Therapeutic Target Database (TTD), Drugbank and Disease-gene Net databases (DisGeNET). Wenn diagram was used to obtain the correlation intersection.Target characteristics were analyzed with GEO2R online, Reactome FI was used to analyze the enrichment of target pathways, and Cytoscape software was used to construct the " component-target-pathway" network. Result::Network analysis showed that Xiao Xianxiongtang treated CHD by regulating 24 target proteins through 25 therapeutic components, and acting on 21 specific pathways and 4 biological processes.According to the multiple gene chip analysis of GEO2R online, there were up-down-regulated differences in the targets, including 11 up targets and 13 down targets. Conclusion::Xiao Xianxiongtang treats CHD by involving the biological processes through berberine and flavonoid groups of Coptidis Rhizoma, nucleosides and organic acids of
6.Diagnostic value of pyruvate kinase M2 gene for papillary thyroid carcinoma in fine-needle aspiration specimens
Xingyue CAO ; Ya WU ; Ting XU ; Hongyan DENG ; Jing HANG ; Jianxiang WANG ; Xiao LI ; Qing YAO ; Rong RONG ; Meiping SHEN ; Haixia GUAN ; Xiaohong WU
Chinese Journal of Endocrinology and Metabolism 2019;35(4):276-281
Objective To investigate the diagnostic value of pyruvate kinase M2 ( PKM2) gene expression in papillary thyroid carcinoma ( PTC). Methods Quantitative real-time PCR ( RT-qPCR) was used to detect the expression of PKM2 mRNA in benign thyroid nodules, PTC, and normal thyroid cells around nodules of fine-needle aspiration (FNA) specimens. Immunohistochemistry ( IHC) was used to detect the expression of PKM2 protein in thyroid tissue after thyroidectomy. The receiver operating characteristic curve was constructed to evaluate the diagnostic value of PKM2 in PTC. Results The expression of PKM2 mRNA was detectable in FNA specimens of thyroid nodules,higher in PTC than those in normal thyroid tissue and benign thyroid nodules (P<0.01). PKM2 expression level was correlated with diameter of PTC ( P<0.05) , but had no correlation with lymph node metastasis, BRAFV600E mutation, and American Joint Committe on Cancer( AJCC) stage ( P>0.05) . The expression level of PKM2 mRNA in FNA specimens of thyroid nodules was paralleled with the expression level of PKM2 protein in postoperation pathological tissues. The accuracy, sensitivity, specificity of PKM2 gene in the diagnosis of PTC were 62.8%, 46.9%, and 95.7%, respectively. The accuracy and sensitivity of PKM2 combined with BRAFV600E were increased to 87.6%and 83.7%. Conclusion Detection of PKM2 gene in FNA specimens is highly specific in the diagnosis of PTC, making it a valuable molecular marker for preoperative diagnosis. The combination of PKM2 and BRAFV600E detection shows a higher diagnosis efficiency.
7.Effect of acupuncture in different time on nausea and vomiting induced by chemotherapy of lung cancer.
Ya-Ling WANG ; Jin-Xia LI ; Xiao-Qing GUO ; Rui-Yang FU ; Xin-Jun GUAN
Chinese Acupuncture & Moxibustion 2019;39(12):1269-1273
OBJECTIVE:
To observe the effect of acupuncture in different time on nausea and vomiting induced by chemotherapy of lung cancer.
METHODS:
A total of 150 patients with chemotherapy for lung cancer were randomized into a No.1 observation group, a No.2 observation group and a control group, 50 cases in each one. Excluded the dropped-off cases, finally, there were 49 cases in the No.1 observation group, 44 cases in the No.2 observation group and 47 cases in the control group. In the control group, 30 min before chemotherapy, the slow intravenous injection with tropisetron hydrochloride was used, 5 mg each time, once a day for 3 days. In the No.1 observation group, 30 min before chemotherapy, the slow intravenous injection with tropisetron hydrochloride was given combined with acupuncture. The acupoints selected were Zusanli (ST 36), Zhongwan (CV 12) and Neiguan (PC 6). The needles were retained for 30 min. The treatment was given once a day for 3 days totally. In the No.2 observation group, 30 min before chemotherapy, the slow intravenous injection with tropisetron hydrochloride was used, and 30 min after chemotherapy, acupuncture treatment was exerted. The acupoints and needling method were same as those in the No.1 observation group. Before and after treatment, the digestive reaction score, Karnofsky performance status scale (KPS) score and white blood cell count were all observed in the three groups. Additionally, the therapeutic effect and adverse reaction were observed and the therapeutic effect was compared among the treatment with acupuncture in different time.
RESULTS:
On the 2nd day of chemotherapy, the effective rates were 85.7% (42/49) and 75.0% (33/44) in the No.1 observation group and the No.2 observation group respectively, both higher obviously than 68.1% (32/47) in the control group (<0.05), and the effective rate in the No.1 observation group was higher obviously than the No.2 observation group (<0.05). On the 3rd day of chemotherapy, the effective rates were 81.6% (40/49) and 61.4% (27/44) in the No.1 observation group and the No.2 observation group respectively, both higher obviously than 57.5% (27/47) in the control group (<0.05), and the effective rate in the No.1 observation group was higher obviously than the No.2 observation group (<0.05). Compared before treatment, the KPS scores after treatment were obviously lower in the three groups (<0.05), and the decreased value of KPS score in the No.1 observation group was much lower than the control group and the No.2 observation group (<0.05). After 3-day chemotherapy, the white blood cell count was all reduced in each group, but the decreased value was not different statistically among the groups (>0.05).
CONCLUSION
Acupuncture combined with the slow intravenous injection with tropisetron hydrochloride achieve the satisfactory effect of prevention and treatment for vomiting induced by chemotherapy of lung cancer. The acupuncture intervention before chemotherapy greatly improves the effect on the nausea and vomiting induced by chemotherapy of lung cancer.
Acupuncture Points
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Acupuncture Therapy
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Humans
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Lung Neoplasms
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Nausea
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therapy
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Treatment Outcome
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Vomiting
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therapy
8.Anti-Hypertensive Action of Fenofibrate via UCP2 Upregulation Mediated by PPAR Activation in Baroreflex Afferent Pathway.
Jian GUAN ; Miao ZHAO ; Chao HE ; Xue LI ; Ying LI ; Jie SUN ; Wei WANG ; Ya-Li CUI ; Qing ZHANG ; Bai-Yan LI ; Guo-Fen QIAO
Neuroscience Bulletin 2019;35(1):15-24
Fenofibrate, an agonist for peroxisome proliferator-activated receptor alpha (PPAR-α), lowers blood pressure, but whether this action is mediated via baroreflex afferents has not been elucidated. In this study, the distribution of PPAR-α and PPAR-γ was assessed in the nodose ganglion (NG) and the nucleus of the solitary tract (NTS). Hypertension induced by drinking high fructose (HFD) was reduced, along with complete restoration of impaired baroreceptor sensitivity, by chronic treatment with fenofibrate. The molecular data also showed that both PPAR-α and PPAR-γ were dramatically up-regulated in the NG and NTS of the HFD group. Expression of the downstream signaling molecule of PPAR-α, the mitochondrial uncoupling protein 2 (UCP2), was up-regulated in the baroreflex afferent pathway under similar experimental conditions, along with amelioration of reduced superoxide dismutase activity and increased superoxide in HFD rats. These results suggest that chronic treatment with fenofibrate plays a crucial role in the neural control of blood pressure by improving baroreflex afferent function due at least partially to PPAR-mediated up-regulation of UCP2 expression and reduction of oxidative stress.
Afferent Pathways
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drug effects
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Animals
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Antihypertensive Agents
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pharmacology
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Baroreflex
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drug effects
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Blood Pressure
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drug effects
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Fenofibrate
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pharmacology
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Male
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Oxidative Stress
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drug effects
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PPAR gamma
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drug effects
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metabolism
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Rats, Sprague-Dawley
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Signal Transduction
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drug effects
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Transcriptional Activation
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drug effects
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Uncoupling Protein 2
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drug effects
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metabolism
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Up-Regulation
9.Two symmetrical unsaturated acids isolated from Viscum album.
Duo CAO ; Li-Qing WANG ; Xiao-Min HAN ; Hui-Rui GUAN ; Meng LEI ; Ya-Hui WEI ; Liang CHENG ; Pei-Ming YANG ; Zheng-Liang SUN ; Wen GAO ; Jia-Kun DAI
Chinese Journal of Natural Medicines (English Ed.) 2019;17(2):145-148
In the present study, two new acetylene conjugate compounds, dibutyl (2Z, 6Z)-octa-2, 6-dien-4-yne dioate (1), and dibutyl (2E, 6E)- octa-2, 6-dien-4-yne dioate (2), were isolated from the dry stem leaves of Viscum album, along with nine known compounds (3 - 11). Their structures were confirmed on the basis of spectroscopic data. Compounds 1 and 8 showed antioxidant activity against xanthine oxidase (XOD) and 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydroxyl (DPPH), with the IC of 1.22 and 1.33 μmol·L, and the SC of 4.34 and 8.22 μmol·L, respectively.
Acetylene
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chemistry
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Antioxidants
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chemistry
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pharmacology
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Biphenyl Compounds
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chemistry
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Molecular Structure
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Picrates
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chemistry
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Plant Extracts
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chemistry
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pharmacology
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Plant Leaves
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chemistry
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Viscum album
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chemistry
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Xanthine Oxidase
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chemistry
10.An interlaboratory comparison study on the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels.
Ya Zhen QIN ; Li Wen ZHU ; Shang LIN ; Su Xia GENG ; Sheng Wei LIU ; Hui CHENG ; Cheng Ye WU ; Min XIAO ; Xiao Qing LI ; Rui Ping HU ; Li Li WANG ; Hai Yan LIU ; Dao Xin MA ; Tao GUAN ; Yuan Xin YE ; Ting NIU ; Jian Nong CEN ; Li Sha LU ; Li SUN ; Tong Hua YANG ; Yun Gui WANG ; Tao LI ; Yue WANG ; Qing Hua LI ; Xiao Su ZHAO ; Ling Di LI ; Wen Min CHEN ; Ling Yu LONG ; Xiao Jun HUANG
Chinese Journal of Hematology 2019;40(11):889-894
Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People's Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories' results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion: The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.
China
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Core Binding Factor Alpha 2 Subunit
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Humans
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Leukemia, Myeloid, Acute
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RUNX1 Translocation Partner 1 Protein
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Real-Time Polymerase Chain Reaction
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Transcription, Genetic
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WT1 Proteins

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