1.Dimethylated arsenics-promoted skin and lung tumorigenesis through the induction of oxidative stress in mice
Yan, AN ; Hua, YIN ; Zhen, LI ; San-xiong, WANG ; Zheng-hui, WANG ; Bu-lin, HAN ; Xian-zhen, KONG
Chinese Journal of Endemiology 2009;28(1):10-13
Objective To examine the possibility that a candidate causal species of the skin and lung tumor promotion induced by exposure to dimethylarsinic acid(DMAv)and dimethylarsinous acid(DMAⅢ),caused by the induction of oxidative stress in mice.Methods Two stages lung tumotigensis animal model induced by lung tumor initiator(4-nitroquinoline 1-oxide,4NQO)and promoter(DMAv)in ddY mice,was used to examine the effect of(-)epigallocatechin gallate(EGCG)on DMAv promoting lung tumorigenesis.Two stages skin tumorigenesis animal model induced by skin tumor initiator[dimethylbenz(α)anthracene,DMBA]and promoter(DMAⅢ)in hairless mice.was used to examine the effects of DMAⅢ in skin tumorigenesis and histopathology.The goxo-2'-deoxyguanosine (8-oxodG)in lung and epidermis were analyzed by HPLC.Results The incidence of lung tumors and 8-oxodG level of lung tissue decreased significantly in 4NQO+DMAv+EGCG group.compared with 4NQO+DMAv group (0.89±0.30 vs 4.00±0.82,1.21±0.09 vs 1.53±0.32,P<0.01).The incidence of severe keratosis in DMBA+ DMIⅢ group was more than that in DMBA group(25 vs 10,P<0.05).An significant elevation of 8-oxodG in epidermis was observed in 0.5 h[(1.67±0.17)/105 dG],1.0 h[(1.62±012)/105 dG],2.0 h[(1.66±023)/105dG], 3.0 h[(1.60±0.15)/105 dG],compared with 0 h[(1.25±0.11)/105 dG],being significant(P<0.05).Conclusion tumor promotion due to DMAv administration is mediated by DMAⅢ through the induction of oxidative stress.
2.Relationship between 18F-FDG PET/CT Semi-Quantitative Parameters and International Association for the Study of Lung Cancer, American Thoracic Society/European Respiratory Society Classification in Lung Adenocarcinomas
Lihong BU ; Ning TU ; Ke WANG ; Ying ZHOU ; Xinli XIE ; Xingmin HAN ; Huiqin LIN ; Hongyan FENG
Korean Journal of Radiology 2022;23(1):112-123
Objective:
To investigate the relationship between 18F-FDG PET/CT semi-quantitative parameters and the International Association for the Study of Lung Cancer, American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) histopathologic classification, including histological subtypes, proliferation activity, and somatic mutations.
Materials and Methods:
This retrospective study included 419 patients (150 males, 269 females; median age, 59.0 years;age range, 23.0–84.0 years) who had undergone surgical removal of stage IA–IIIA lung adenocarcinoma and had preoperative PET/CT data of lung tumors. The maximum standardized uptake values (SUVmax), background-subtracted volume (BSV), and background-subtracted lesion activity (BSL) derived from PET/CT were measured. The IASLC/ATS/ERS subtypes, Ki67 score, and epidermal growth factor/anaplastic lymphoma kinase (EGFR/ALK) mutation status were evaluated. The PET/CT semiquantitative parameters were compared between the tumor subtypes using the Mann–Whitney U test or the Kruskal–Wallis test. The optimum cutoff values of the PET/CT semi-quantitative parameters for distinguishing the IASLC/ATS/ERS subtypes were calculated using receiver operating characteristic curve analysis. The correlation between the PET/CT semi-quantitative parameters and pathological parameters was analyzed using Spearman’s correlation. Statistical significance was set at p < 0.05.
Results:
SUVmax, BSV, and BSL values were significantly higher in invasive adenocarcinoma (IA) than in minimally IA (MIA), and the values were higher in MIA than in adenocarcinoma in situ (AIS) (all p < 0.05). Remarkably, an SUVmax of 0.90 and a BSL of 3.62 were shown to be the optimal cutoff values for differentiating MIA from AIS, manifesting as pure ground-glass nodules with 100% sensitivity and specificity. Metabolic-volumetric parameters (BSV and BSL) were better potential independent factors than metabolic parameters (SUVmax) in differentiating growth patterns. SUVmax and BSL, rather than BSV, were strongly or moderately correlated with Ki67 in most subtypes, except for the micropapillary and solid predominant groups. PET/CT parameters were not correlated with EGFR/ALK mutation status.
Conclusion
As noninvasive surrogates, preoperative PET/CT semi-quantitative parameters could imply IASLC/ATS/ERS subtypes and Ki67 index and thus may contribute to improved management of precise surgery and postoperative adjuvant therapy.
3.Antisense oligonucleotide targeting endostatin enhances hematopoiesis reconstitution in BMT mice.
Ning WU ; Jie-lin QI ; De-rong HU ; Xi-qin ZHANG ; Bing BU ; Zhi-fang LIU ; Han-ying SUN ; Wen-li LIU
Chinese Journal of Hematology 2006;27(8):534-537
OBJECTIVETo explore the effect of antisense oligonucleotide targeting endostatin (endostatin-ASON) transfecting bone marrow stromal cells ( BMSC) on hematopoiesis reconstitution in BMT mice.
METHODSInhibition of endostatin / VCAM-1 protein and mRNA expression was investigated by transfection of antisense oligonucleotide targeting endostatin with confocal microscopy, Western blot and RT-PCR. Bone marrow stromal cells were cultured and divided into 4 groups: group (1) without any treatment; group (2) BMT only; group (3) BMT + endostatin-ASON transfection; group (4) BMT + endostatin scrambled sequence transfection.
RESULTS(1) Endostatin-ASON was successfully introduced into BMSC in vitro, and the transfecting rate was 86% ;(2) After Endostatin-ASON transfected into BMSC, the expression of Endostatin mRNA and its protein on the BMSC was signficantly inhibited at different time point after BMT [the grey value of Endostatin was (0.09 +/- 0.03) - (1.44 +/- 1.19) and (0.02 + 0.02) - (0.14 +/- 0.05), respectively] (P < 0.01 and P < 0.05); (3) Transfecting with Endostatin-ASON effectively promoted the expression of VCAM-1 mRNA and its protein on the BMSC [the gray value of VCAM-1 was (1.60 +/- 0. 92) - (8.05 +/- 0.87) and (0.07 +/- 0.02) - (0.67 +/- 0.09) , respectively] (P <0.01 and P <0.05) ; (4) There was no effects of transfecting Endostatin scrambled sequence on the expression of Endostatin and VCAM-1 on the BMSC (P > 0.05).
CONCLUSIONEndostatin-ASON could inhibit Endostatin expression and enhance VCAM-1 expression in BMSC after syngeneic-BMT in mice, which might be one of the mechanisms underlying the endostatin-ASON accelerating hematopoiesis reconstitution after allogeneic-BMT.
Animals ; Bone Marrow Cells ; drug effects ; metabolism ; Bone Marrow Transplantation ; Dose-Response Relationship, Drug ; Endostatins ; biosynthesis ; genetics ; Female ; Hematopoiesis ; Intercellular Adhesion Molecule-1 ; biosynthesis ; genetics ; Male ; Mice ; Mice, Inbred BALB C ; Oligonucleotides, Antisense ; pharmacology ; RNA, Messenger ; biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection
4.Effect of ligustrazine on the expression of bFGF in bone marrow stromal cells of mice after BMT.
Ning WU ; Deng-Feng ZHOU ; Jie-Lin QI ; Xi-Qin ZHANG ; Bing BU ; Pu-Xia LIU ; Ming-Yu WANG ; Han-Ying SUN ; Wei-Li LIU
Journal of Experimental Hematology 2006;14(5):1004-1007
This study was purposed to investigate the effect of ligustrazine on the expression of bFGF in bone marrow stromal cells (BMSC) and to explore the mechanism of hematopoietic reconstitution after bone marrow transplantation (BMT). The mice were randomly divided into 3 groups: normal group, saline group and ligustrazine group. BMT mouse models were established. The mice of normal group were not treated, the mice of saline group were given normal saline (0.2 ml/mouse, twice a day) through gastric tube, while the mice of ligustrazine group were given ligustrazine (0.2 ml/mouse, twice a day) through gastric tube. On day 7, 14, 21 and 28 after BMT, the femora were taken and the bone marrow mononuclear cell (BMMNC) suspensions were used for the cultivation of bone marrow stromal cells according to Dexter's culture method. The mRNA and protein expressions of bFGF in BMSC were assayed by RT-PCR and Western blot respectively. The results showed that the expression of bFGF in BMSC on the level of mRNA and protein were all reduced significantly after BMT, and increased slowly with the time. On day 7, 14 and 21 after BMT, the expressions of bFGF mRNA and protein in bone marrow stromal cells of ligustrazine group and saline group were lower than that in bone marrow stromal cells of normal group, but the expressions of bFGF mRNA and protein in ligustrazine group were obviously higher than that in saline group (P < 0.01 or P < 0.05). On day 28 after BMT, the expressions of bFGF mRNA and protein in ligustrazine group returned to normal level, while the expressions of bFGF mRNA and protein in saline group not returned to normal level, there was significant difference between these two groups. It is concluded that ligustrazine can enhance bFGF expression level in bone marrow stromal cells after syngeneic bone marrow transplantation in mice, which confirms that ligustrazine can enhance the repair of bone marrow microvessels, improve bone marrow microenvironment and promote hematopoietic reconstitution.
Animals
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Bone Marrow Cells
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metabolism
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Bone Marrow Transplantation
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Cells, Cultured
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Female
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Fibroblast Growth Factor 2
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biosynthesis
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genetics
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Hematopoiesis
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drug effects
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Male
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Mice
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Mice, Inbred BALB C
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Pyrazines
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pharmacology
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RNA, Messenger
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biosynthesis
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genetics
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Random Allocation
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Stromal Cells
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metabolism
5.Intracellular trafficking of TREM2 is regulated by presenilin 1.
Yingjun ZHAO ; Xiaoguang LI ; Timothy HUANG ; Lu lin JIANG ; Zhenqiu TAN ; Muxian ZHANG ; Irene Han Juo CHENG ; Xin WANG ; Guojun BU ; Yun wu ZHANG ; Qi WANG ; Huaxi XU
Experimental & Molecular Medicine 2017;49(12):e405-
Genetic mutations in triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to a variety of neurodegenerative diseases including Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia and Parkinson’s disease. In the brain, TREM2 is highly expressed on the cell surface of microglia, where it can transduce signals to regulate microglial functions such as phagocytosis. To date, mechanisms underlying intracellular trafficking of TREM2 remain elusive. Mutations in the presenilin 1 (PS1) catalytic subunit of the γ-secretase complex have been associated with increased generation of the amyloidogenic Aβ (amyloid-β) 42 peptide through cleavage of the Aβ precursor amyloid precursor protein. Here we found that TREM2 interacts with PS1 in a manner independent of γ-secretase activity. Mutations in TREM2 alter its subcellular localization and affects its interaction with PS1. Upregulation of PS1 reduces, whereas downregulation of PS1 increases, steady-state levels of cell surface TREM2. Furthermore, PS1 overexpression results in attenuated phagocytic uptake of Aβ by microglia, which is reversed by TREM2 overexpression. Our data indicate a novel role for PS1 in regulating TREM2 intracellular trafficking and pathophysiological function.
6.Treatment results and prognostic factors of patients undergoing postoperative radiotherapy for laryngeal squamous cell carcinoma.
Ting JIN ; Wei-Han HU ; Li-Bing GUO ; Wen-Kuan CHEN ; Qiu-Li LI ; Hui LIN ; Xiu-Yu CAI ; Nan GE ; Rui SUN ; Si-Yi BU ; Xin ZHANG ; Meng-Yao QIU ; Wei ZHANG ; Su LUO ; Yi-Xin ZHOU
Chinese Journal of Cancer 2011;30(7):482-489
Postoperative radiotherapy (PRT) is widely advocated for patients with squamous cell carcinomas of the head and neck that are considered to be at high risk of recurrence after surgical resection. The aims of this study were to evaluate the treatment outcomes of PRT for patients with laryngeal carcinoma and to identify the value of several prognostic factors. We reviewed the records of 256 patients treated for laryngeal squamous cell carcinoma between January 1993 and December 2005. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Log-rank test was employed to identify significant prognostic factors for DFS and OS. The Cox proportional hazards model was applied to identify covariates significantly associated with the aforementioned endpoints. Our results showed the 3-, 5-, and 10-year DFS for all patients were 69.9%, 59.5%, and 34.9%, respectively. The 3-, 5-, and 10-year OS rates were 80.8%, 68.6%, and 38.8%, respectively. Significant prognostic factors for both DFS and OS on univariate analysis were grade, primary site, T stage, N stage, overall stage, lymph node metastasis, overall treatment times of radiation, the interval between surgery and radiotherapy, and radiotherapy equipment. Favorable prognostic factors for both DFS and OS on multivariate analysis were lower overall stage, no cervical lymph node metastasis, and using 60Co as radiotherapy equipment. In conclusion, our data suggest that lower overall stage, no cervical lymph node metastasis, and using 60Co as radiotherapy equipment are favorable prognostic factors for DFS and OS and that reducing the overall treatment times of radiation to 6 weeks or less and the interval between surgery and radiotherapy to less than 3 weeks are simple measures to remarkably improve treatment outcome.
Adult
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Aged
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Aged, 80 and over
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Carcinoma, Squamous Cell
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pathology
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radiotherapy
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surgery
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Cobalt Radioisotopes
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therapeutic use
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Combined Modality Therapy
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Disease-Free Survival
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Female
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Follow-Up Studies
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Humans
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Laryngeal Neoplasms
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pathology
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radiotherapy
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surgery
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Laryngectomy
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Lymphatic Metastasis
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Male
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Middle Aged
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Neoplasm Grading
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Neoplasm Staging
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Postoperative Period
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Proportional Hazards Models
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Radioisotope Teletherapy
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Retrospective Studies
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Survival Rate
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Young Adult
7.Surveillance on severe acute respiratory syndrome associated coronavirus in animals at a live animal market of Guangzhou in 2004.
Ming WANG ; Huai-qi JING ; Hui-fang XU ; Xiu-gao JIANG ; Biao KAN ; Qi-yong LIU ; Kang-lin WAN ; Bu-yun CUI ; Han ZHENG ; Zhi-gang CUI ; Mei-ying YAN ; Wei-li LIANG ; Hong-xia WANG ; Xiao-bao QI ; Zhen-jun LI ; Ma-chao LI ; Kai CHEN ; En-min ZHANG ; Shou-yin ZHANG ; Rong HAI ; Dong-zheng YU ; Jian-guo XU
Chinese Journal of Epidemiology 2005;26(2):84-87
OBJECTIVETo study the prevalence of severe acute respiratory syndrome coronavirus (SARS-CoV) like virus in animals at a live animal market of Guanzhou in 2004 before and after culling of wild animal action taken by the local authority, in order to predict the re-emerging of SARS from animal originals in this region.
METHODSAnimals at live animal market were sampled for rectal and throat swabs in triplicate. A single step realtime reverse transcription-polymerase chain reaction (RT-PCR) diagnostic kit was performed for screening SARS-CoV like virus, the manual nested RT- PCR and DNA sequencing were performed for confirmation. Only specimens which tested positive for both of the N and P genes by nested RT-PCR were scored as positive.
RESULTSIn 31 animals sampled in January 5 2004 before culling of wild animals at Guangdong Province, including 20 cats (Felis catus), 5 red fox (Vulpes vulpes) and 6 Lesser rice field rats (Rattus losea), 8 (25.8%) animals were tested positive for SARS-CoV like virus by RT-PCR methods, of which 4 cats, 3 red fox and one Lesser rice field rats were included. However, two weeks after culling of animals and disinfection of the market were implemented, in 119 animals sampled in January 20 2004, including 6 rabbits (Oryctolagus cuniculus), 13 cats, 46 red jungle fowl (Gallus gallus), 13 spotbill duck (Anas platyrhynchos), 10 greylag goose (Anser anser), 31 Chinese francolin (Franclinus pintadeanus), only rectal swab from one greylag goose was tested positive for SARS-CoV like virus. Furthermore, in 102 animals that including 14 greylag gooses, 3 cats, 5 rabbits, 9 spotbill duck (Anaspoecilorhyncha), 2 Chinese francolin (Franclinus pintadeanus), 8 common pheasant (Phasianus colchicus), 6 pigeons, 9 Chinese muntjac (Muntiacus reevesi), 19 wild boar (Sus scrofa), 16 Lesser rice field rats, 5 dogs, 1 mink (Mustela vison), 3 goats, 2 green peafowl (Pavo muticus) sampled in April, May, June, July, August and November, only rectal swab from one pig was tested positive. However, of 12 and 10 palm civets sampled in November and December including five of which had been at the live animals market for 2 days, none of them was tested positive.
CONCLUSIONThis findings revealed that animals being sampled in April, May, June, July, August and November of 2004, only one rectal swab from a pig was tested positive as SARS-CoV like virus, much lower than the results from the previous year, suggesting that the possibility of re-emerging of human infection from animal origins is low for the winter of 2004-2005.
Animals ; Animals, Wild ; virology ; China ; DNA, Viral ; analysis ; Felidae ; virology ; Reverse Transcriptase Polymerase Chain Reaction ; SARS Virus ; isolation & purification
8.Effect of ergosterol peroxide derivatives on the proliferation ,migration and invasion of human triple negative breast cancer cell
Hongyu ZHANG ; Wenkang REN ; Yu ZOU ; Yinglong HAN ; Hongyan YANG ; Ming BU ; Xiaohui DU ; Yu LIN
China Pharmacy 2022;33(11):1355-1360
OBJECT IVE To study the effects of ergosterol peroxide derivatives EP-3P on the proliferation ,migration and invasion of human tripe negative breast cancer cell MDA-MB- 231,and to provide reference for the development of breast cancer related drugs. METHODS MTT assay was adopted to detect the proliferation of MDA-MB- 231 cells after treated with 0(blank control),1.25,2.5,5,10,20,40 μmol/L EP-3P for 24,48 and 72 h. Wound healing assay and Transwell chamber method were adopted to detect the migration and invasion ability of MDA-MB- 231 cells after treated with 0(blank control ),5,10,20 EP-3P for 24 h. The apoptosis and cell cycle distribution were detected by flow cytometry. Western blot assay was used to detect the expressions of B-cell lympho ma-2(Bcl-2),Bcl-2 associated X protein (Bax),caspase-3,cleaved-caspase-3,cytochrome C (Cyt-C),matrix metalloproteinase- 2(MMP-2)and MMP- 9. RESULTS Compared with blank control group ,2.5,5,10,20,40 μmol/L EP-3P could significantly increase the inhibitory rate of cell proliferation (P<0.05 or P<0.01)in a dose and time- dependent manner. After 24 h treatment of EP- 3P(10,20 μmol/L),the rate of cell migration and the number of invasive cells were decreased significantly (P<0.01),and cell was arrested at G 2/M stage (P<0.05 or P<0.01);the apoptotic rate was increased significantly (P<0.05);the protein expressions of Bax ,Cyt-C and cleaved-caspase- 3 were upregulated significantly , while those of Bcl- 2,caspase-3,MMP-2 and MMP- 9 were downregulated significantly (P<0.01). CONCLUSIONS EP-3P can inhibit the proliferation ,migration and invasion of human tripe negative breast cancer cells MDA-MB- 231 through mitochondrial mediated endogenous caspase pathway ,and induce the apoptosis of cells .
9.Transcriptomic analysis in Anemone flaccida rhizomes reveals ancillary pathway for triterpene saponins biosynthesis and differential responsiveness to phytohormones.
Guo-Yan MO ; Fang HUANG ; Yin FANG ; Lin-Tao HAN ; Kayla K PENNERMAN ; Li-Jing BU ; Xiao-Wei DU ; Joan W BENNETT ; Guo-Hua YIN
Chinese Journal of Natural Medicines (English Ed.) 2019;17(2):131-144
Anemone flaccida Fr. Schmidt is a perennial medicinal herb that contains pentacyclic triterpenoid saponins as the major bioactive constituents. In China, the rhizomes are used as treatments for a variety of ailments including arthritis. However, yields of the saponins are low, and little is known about the plant's genetic background or phytohormonal responsiveness. Using one-quarter of the 454 pyrosequencing information from the Roche GS FLX Titanium platform, we performed a transcriptomic analysis to identify 157 genes putatively encoding 26 enzymes involved in the synthesis of the bioactive compounds. It was revealed that there are two biosynthetic pathways of triterpene saponins in A. flaccida. One pathway depends on β-amyrin synthase and is similar to that found in other plants. The second, subsidiary ("backburner") pathway is catalyzed by camelliol C synthase and yields β-amyrin as minor byproduct. Both pathways used cytochrome P450-dependent monooxygenases (CYPs) and family 1 uridine diphosphate glycosyltransferases (UGTs) to modify the triterpenoid backbone. The expression of CYPs and UGTs were quite different in roots treated with the phytohormones methyl jasmonate, salicylic acid and indole-3-acetic acid. This study provides the first large-scale transcriptional dataset for the biosynthetic pathways of triterpene saponins and their phytohormonal responsiveness in the genus Anemone.
Anemone
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drug effects
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genetics
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metabolism
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Biosynthetic Pathways
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drug effects
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genetics
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Cytochrome P-450 Enzyme System
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genetics
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metabolism
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Gene Expression Profiling
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Gene Expression Regulation, Plant
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drug effects
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Glycosyltransferases
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genetics
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metabolism
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Oleanolic Acid
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analogs & derivatives
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metabolism
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Plant Growth Regulators
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pharmacology
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Plant Proteins
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genetics
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metabolism
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Plants, Medicinal
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Rhizome
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drug effects
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genetics
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metabolism
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Saponins
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metabolism
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Triterpenes
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metabolism
10.Chinese Experts Consensus on Immune Checkpoint Inhibitors for Non-small Cell Lung Cancer (2019 version).
Caicun ZHOU ; Jie WANG ; Hong BU ; Baocheng WANG ; Baohui HAN ; You LU ; Zhehai WANG ; Bo ZHU ; Ziping WANG ; Qibin SONG ; Shengxiang REN ; Dongmei LIN ; Yayi HE ; Xiaohua HU ; Hongyun ZHAO ; Shukui QIN
Chinese Journal of Lung Cancer 2020;23(2):65-76
Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, most NSCLC patients are at advanced stage at the time of diagnosis. For patients without sensitive driven-oncogene mutations, chemotherapy is still the main treatment at present, the overall prognosis is poor. Improving outcomes and obtaining long-term survival are the most urgent needs of patients with advanced NSCLC. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs), especially targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), have made a breakthrough in the treatment of NSCLC, beneficial to patients' survival and changed the treatment pattern for NSCLC. It shows more and more important role in the treatment of NSCLC. Led by NSCLC expert committee of Chinese society of clinical oncology (CSCO), relevant experts in this field were organized. On the basis of referring to domestic and foreign literature, systematically evaluating the results of Chinese and foreign clinical trials, and combining the experiences of the experts, the experts group reached an agreement to develop this consensus. It will guide domestic counterparts for better application of ICIs to treat NSCLC.