1.Advances in anti-tumor research of HDAC inhibitors and combination with PI3K inhibitors
Lei HUANG ; Xiao-guang CHEN ; Fang-fang LAI
Acta Pharmaceutica Sinica 2022;57(12):3557-3563
Histone deacetylase (HDAC) is usually abnormally overexpressed, which mainly leads to the transcriptional repression of tumor suppressor genes. Histone deacetylase inhibitors (HDIs) exert anti-tumor biological effects by regulating nucleosome structure, inhibiting HDAC activity, and controlling the expression of tumor suppressor genes. There are currently 5 drugs on the market, but only for peripheral T-cell lymphoma and cutaneous T-cell lymphoma. In solid tumors, most of the HDAC inhibitors used have failed to achieve effective therapeutic effects. Phosphoinositide 3-kinase (PI3K) is the starting node of the PI3K-AKT-mTOR signaling pathway, which plays a very important role in the proliferation, migration, invasion, and differentiation of tumor cells. The abnormal activation of PI3K is closely related to the occurrence and development of tumors, and the combined use of HDAC and PI3K inhibitors and HDAC/PI3K dual-target inhibitors show synergistic anticancer activity. This article introduces the anti-tumor clinical and preclinical research progress of representative HDAC inhibitors and PI3K inhibitors, as well as HDAC/PI3K dual-target inhibitors.
2.Some Thoughts on Medical Humanistic Care from the Perspective of Humanistic Psychology and Maslow's Hierarchy of Needs
Ming FANG ; Ping WU ; Lei XIAO ; Huan ZHANG
Chinese Medical Ethics 1994;0(06):-
The article analyzes patients' needs from humanistic psychology to find out shortages existing in current medical service.The values and importance of medical humanistic care are also discussed from the perspective of medical humanism.
3.Observation of corneal endothelial cells after femtosecond laser in situ keratomileusis
Xiao-Lei, LU ; Fang-Lie, YANG ; Yu-Zhi, BAO
International Eye Science 2015;(2):208-210
To observe the morphology of corneal endothelial cells after femtosecond laser in situ keratomileusis ( Femto-LASlK) .METHODS:From May to September in 2013, 88 eyes of 45 patients with myopia who accepted Femto-LASlK were enrolled in this study. The morphology of central corneal endothelial cells was measured by a non-contact corneal endothelial cell analyzer before, 1mo and 1a after surgery. The number, density, average size, size standard deviation, size coefficient of variation and hexagonality of the corneal endothelial cells were observed. All the measurements were analyzed by statistical analysis.RESULTS: All patients underwent operation smoothly, and no complication was observed during and after surgery;One month after surgery, the endothelial cell density (ECD) was 2815. 34±297. 07/mm2, which had a 2. 64% decrease compared with preparative ECD (t=4. 60, P= 0. 00), there was no statistical significance between ECD measurements of 1mo and 1a after surgery ( P>0. 05 ); One month after surgery, the size standard deviation ( SSD ) was 118. 47 ± 31. 58μm2 , which increased significantly compared with the preoperative SSD(t=-3. 87, P=0. 03), there was no statistical significance between SSD measurements of 1mo and 1a after surgery ( P>0. 05 );After surgery, the number, hexagonality, average size and size coefficient of variation of the corneal endothelial cells didn't change statistically(P>0. 05).CONCLUSlON: ln the early period after Femto-LASlK, the ECD decreased slightly, however this kind of surgery did not have significant harm to the function of corneal endothelial cells, and the surgery didn't cause the progressive loss of corneal endothelial cells.
4.Rapid Detection of Active Pharmaceutical Ingredients in Weak Active Pharmaceutical Ingredient Signal Drugs by Paper Substrate-Surface Enhanced Raman Scattering Spectrometry
Xiao LI ; Yun MENG ; Lei WANG ; Qian QIAN ; Fang FANG ; Li MIAO
Chinese Journal of Analytical Chemistry 2015;(11):1735-1742
A rapid detection method of active pharmaceutical ingredients( API) in weak API signal drugs by surface enhanced Raman scattering ( SERS) technology combined with paper substrate was established in this work. By soaking the filter paper in silver nanoparticles solution ( Ag NPs) to synthesize Ag NPs-paper as the substrate, and then the sample solution was dropping on the substrate with SERS detection. On the basis of strengthen ability of Ag NPs-paper, result of SERS detection and optimal preparation conditions, the fast identification method of weak API signal drugs was established. In this case, the SERS spectra of weak API signal drugs and their standards SERS spectra were obtained, where the correlation coefficient of weak API signal drug SERS spectra and its standard was more than 0. 9. The result showed that by this method, the low content API in weak API signal drugs could be well investigated, and the deficiencies of the normal Raman spectroscopy efficiently was also overcome. In conclusion, the synthesize method of Ag NPs-paper was simple, and the strengthen effect of this Ag NPs-paper on the intensity was obviously observed. Paper substrate-SERS method was simple, rapid and sensitive, and could be used to detect weak API signal drugs, presenting broad application prospects in the rapid detection of weak API signal drugs.
5.Inhibitory effect of curcumin on corneal keratocytes fibrosis
Xiao-lei, LI ; Xiu-jun, SONG ; Jian-min, LU ; Hui-fang, WANG ; Xiao-rong, ZHANG
Chinese Journal of Experimental Ophthalmology 2011;29(5):402-406
Background The injury or surgery of cornea cause the proliferation of corneal stromal cells and scar formation.Recent research showed that cureumin can obviously reduce the degree of fibrosis of tissue.But if curcumm play inhibitory effect on corneal keratocytes fibrosis is rarely reported.Objecttve This studv was to investigate the effect of curcumin on the transformation of corneal keratocytes into fibroblasts in vitro and further explore the antifibrotic effect of curcumin on corneal keratocytes.Methods The murine corneal keratocytes from 150 BALB/c mice were isolated and primary culture in DMEM culture medium containing 10% fetal bovine serum and then divided into blank control group(inducer group,CG),low-dose group(CG+7.5 mg/L curcumin),mediumdose group(CG+10.0 mg/L curcumin),high-dose group(CG+12.5 mg/L curcumin),non-inducer group.Seven days following intervention,the expression of cell markers such as keratocan,aldehyde dehydrogenase(ALDH),decorin and fibronectin-1 in keratocytes were analyzed by RT-PCR.The effect of curcumin on cultured murine corneal keratocytes proliferation was evaluated by MTS technique.The expression of fibronectin-1 in murine cornea was investigated by immunofluorescence assay.Results The primarily cultured keratocytes showed tlIe fusiform-like shape with the abundant cytoplasm and big nuclei.In the presence of curcumin,the mRNA levels of keratocan and ALDH were down-regulated and those of CD90 and decorin were up-regulated,showing the significantly differences with the increase of dose(P<0.05),but the expression pf fibronectin-i was not obviously changed with the alteration of dose of curcumin. MTS showed that the inhibitory rates of curcumin on keratocytes in 10.0 mg/L and 2. 5 mg/L groups were enhanced in comparison with 7.5 mg/L group, showing statistically significant difference among three groups( F = 956.00, P<0.05). The expression of fibronectin-1 was found in the corneal keratocytes with the red fluorescence in stroma. Conclusion Curcumin can inhibit the fibrosis of corneal keratoeytes in a dose-dependent manner. These results offer a preliminary theoretical basis for the application of curcumin in controlling corneal scar formation during wound healing.
6.Effects of plant-derived smoke water on accumulation of biomass and active substance of Salvia miltiorrhiza f. alba.
Jie ZHOU ; Lin ZOU ; Jia LI ; Xiao WANG ; Wei LIU ; Lei FANG ; Qiang LI ; Fang ZHANG ; Yong-Qing ZHANG
China Journal of Chinese Materia Medica 2014;39(13):2460-2463
To study the effect of plant-derived smoke water on the accumulation of biomass and active substance of Salvia miltiorrhiza f. alba, seedlings of S. miltiorrhiza were treated with different concentrations of smoke water (1:500, 1: 1 000, 1: 2 000). The fresh weight and dry weight of underground part, the number of split-root, maximum root diameter, average root diameter, average root length, the content of lipophilic components and water-soluble components were measured. Results showed that fresh weight and dry weight of underground part were respectively improved by 98.01%, 44.32% and 85.71%, 28.57% with significant difference by smoke water treatment with concentration of 1: 500 and 1: 1 000. Maximum root diameter and dry weight of underground part were respectively enhanced by 58.44% and 85.71% by smoke water with concentration of 1:500. The content of tanshinone I and tanshinone II(A) were improved by smoke water treatment, however there were no significantly difference on the content of cryptotanshinone and dihydrotan shinone. This study indicates that smoke water treatment could be used to improve the accumulation of biomass and active substance content of S. miltiorrhiza f. alba, which could provide new ideas for its green cultivating.
Agriculture
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methods
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Biomass
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Drugs, Chinese Herbal
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analysis
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metabolism
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Salvia miltiorrhiza
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chemistry
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growth & development
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metabolism
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Smoke
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analysis
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Water
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chemistry
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metabolism
7.Comparison on surface ultrastructure characteristic and drought resistance of different Trichosanthes kirilowii strains.
Jie ZHOU ; Lin ZOU ; Li-Hua BIAN ; Lei FANG ; Wei LIU ; Yong-Qing ZHANG ; Jia LI ; Fang ZHANG ; Xiao WANG
China Journal of Chinese Materia Medica 2014;39(9):1564-1568
Trichosanthes kirilowii has been widely cultivated as its medicinal use, health care and food value. Drought resistance of seedlings is an important feature in breeding. Seeds of two T. kirilowii strains were used to research the difference of surface ultrastructure characteristic and drought resistance. Scanning electron microscope was used to identify the surface ultrastructure characteristic of seeds and PEG was used to simulate drought stress. The seeds germination rate, MDA content, chlorophyll content and the antioxidant enzymes activity were measured under the drought stress. The results showed that the seed surface colour of KXY-001 was lighter than that of KXY-005. The testa cobwebbing of KXY-001 was more intensive than that of KXY-005. The germination rate of KXY-001 was higher than that of KXY-005 under drought stress. The MDA content was increased and the chlorophyll content was decreased with the increasing of drought degree. The SOD activity of KXY-001 was higher than that of KXY-005, while the activity of POD and CAT was also increased firstly and decreased later. Surface reticulate of seeds and hilar traits can be used as identification points to identify the investigated strains. SOD and POD are activated to resist drought in T. kirilowii seedlings and the drought resistance of KXY-001 is superior than that of KXY-005.
Adaptation, Physiological
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drug effects
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Catalase
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metabolism
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Chlorophyll
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metabolism
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Droughts
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Germination
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Malondialdehyde
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metabolism
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Microscopy, Electron, Scanning
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Peroxidase
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metabolism
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Polyethylene Glycols
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pharmacology
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Seedlings
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metabolism
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Seeds
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growth & development
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metabolism
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ultrastructure
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Species Specificity
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Superoxide Dismutase
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metabolism
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Trichosanthes
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classification
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growth & development
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metabolism
8.Astragalus polysaccharides improved the cardiac function in Sjögren's syndrome model rats based on keap 1-Nrf2/ARE signaling pathway: a mechanism exploration.
Fang WANG ; Jian LUI ; Ying-Fa YE ; Xiao-Jun ZHANG ; Lei WAN ; Zheng LI
Chinese Journal of Integrated Traditional and Western Medicine 2014;34(5):566-574
OBJECTIVETo explore the mechanism of Astragalus polysaccharides (APS) for improving the cardiac function of Sjogren's syndrome (SS) model rats based on Keapl-Nrf2/ARE signaling pathway.
METHODSTotally 48 male Wistar rats were randomly divided into four groups by random digit table, i.e., the blank control group,the model control group,the APS group, and the hydroxychloroquine group, 12 in each group. Except those in the blank control group, 0. 1 mL mixed antigen protein of sufficiently emulsified Freund's complete adjuvant and submandibular gland protein was injected from two feet plantar to induce SS model. The intervention was started from 19th day after inflammation induction. Equal volume of normal saline was given to rats in the blank control group (1 mL/100 g), APS was administered to those in the APS group (1 mg/100 g), and hydroxychloroquine (0.03 125 g/kg) was administered to those in the hydroxychloroquine group. All rats were intervened once per day for 30 consecutive days. Changes of rats' body mass and drinking water quantity, submandibular gland index, spleen index, histological changes of glands were observed. Changes of the heart function were monitored using invasive hemodynamics. Serum reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (TAC), tumor necrosis factor alpha (TNF-alpha), and interleukin-35 (IL-35)were detected using ELISA method. The pathological changes were observed using HE staining. The protein expression of ROS, reactive nitrogen species (RNS), glutathione (GSH), and thioredoxin (TRX) were observed by immunohistochemical staining. The mRNA expression of Keap1, Nrf2, and ARE was detected using real time fluorescent quantitative PCR. The protein expression levels of gamma-glutamic acid and a half long glycine synthetase (gamma-GCS) and heme oxygenase 1 (HO-1) in the myocardial tissue were determined by Western blot method. Results Compared with the blank control group, the quantity of drinking water, submandibular gland index, spleen index, heart rate (HR), cardiac index (HI), left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVEDP), MDA, ROS, TNF-alpha, ROS protein expression, RNS protein expression, Keap 1 mRNA expression, Maf mRNA expression, Nfr2 mRNA expression, and HO-1 protein expression, and gamma-GCS protein expression significantly increased (P <0.01); body mass, +/-dp/dtmax, SOD, TAC, IL-35, GSH, and TRX significantly decreased (P <0.01) in the model group. Compared with the model group, the quantity of drinking water, submandibular gland index, spleen index, LVEDP, MDA, ROS, TNF-alpha, ROS protein expression, RNS protein expression, Keap1 mRNA expression, Maf mRNA expression, Nfr2 mRNA expression, and HO-1 protein expression, and gamma-GCS protein expression significantly decreased (P<0.05); body mass, +/-dp/dtmax, SOD, TAC, IL-35, GSH protein expression, and TRX protein expression significantly increased (P < 0.05, P <0.01) in the AR group and the hydroxychloroquine group. In the hydroxychloroquine group HR increased (P <0.05). In the AR group HR and LVSP decreased (P <0. 05, P <0. 01). Compared with the hydroxychloroquine group, HR, LVEDP, - dp/dtmax, y-GCS protein expression significantly decreased (P <0. 05, P <0. 01); SOD, TAC, GSH, TRX, HO-1 protein expression increased (P <0.01 )in the AR group. HI was positively correlated with ROS (P <0. 05). LVSP and LVEDP were positively correlated with Keap1 -Nrf2/ARE signaling pathways (P <0. 01) , and negatively correlated with TAC (P <0. 05, P <0. 01 ). +/-dp/dtmax was negatively correlated with Keap1-Nrf2/ARE signaling pathways(P <0.05), and positively correlated with TNF alpha (P <0. 05).
CONCLUSIONSDeclined heart function exists in SS rats. The mechamechanism of APS for improving the heart function might be closely correlated with activating Keap1-Nrf2/ARE signaling pathway.
Animals ; Astragalus Plant ; Blotting, Western ; Carboxylic Ester Hydrolases ; metabolism ; Heme Oxygenase-1 ; metabolism ; Hydroxychloroquine ; Male ; Malondialdehyde ; metabolism ; Myocardium ; enzymology ; NF-E2-Related Factor 2 ; metabolism ; Plant Extracts ; therapeutic use ; Polysaccharides ; metabolism ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism ; Signal Transduction ; Sjogren's Syndrome ; Submandibular Gland ; Superoxide Dismutase ; metabolism ; Thioredoxins ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism
9.Microcystic adnexal carcinoma: report of two cases.
Wei FANG ; Dong CHEN ; Jian-feng SHANG ; Fu WANG ; Lei XIAO
Chinese Journal of Pathology 2009;38(1):59-60
Adult
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Arm
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Carcinoembryonic Antigen
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metabolism
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Carcinoma, Basal Cell
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pathology
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Carcinoma, Skin Appendage
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metabolism
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pathology
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surgery
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Diagnosis, Differential
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Head and Neck Neoplasms
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metabolism
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pathology
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surgery
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Humans
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Male
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Middle Aged
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Mucin-1
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metabolism
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Skin Neoplasms
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metabolism
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pathology
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surgery
10.Studies on sesquiterpenes from Solanum septemlobum.
Xiu-ping NIE ; Lei ZHANG ; Fang YAO ; Kai XIAO ; Sheng-jun DAI
China Journal of Chinese Materia Medica 2015;40(8):1514-1517
By means of preparative HPTLC and column chromatography over silica gel and Sephadex LH-20, ten sesquiterpenes were isolated and purified from the whole plants of Solanum septemlobum Bunge. Based on the physico-chemical properties and spectral data, their structures were elucidated and identified as: lyratol D(1), solajiangxin B(2), 1 ,2-dehydrocyperone(3), solanerianone A (4), dehydrocarissone(5), ligucyperonol(6), nardoeudesmol A(7), solajiangxin F(8), and lyratol B(9), solajiangxin D(10). For the first time, compounds 1-10 were isolated from Solanum septemlobum, and compounds 5-7 were obtained from the genus Solanum.
Drugs, Chinese Herbal
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chemistry
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isolation & purification
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Mass Spectrometry
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Molecular Structure
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Sesquiterpenes
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chemistry
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isolation & purification
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Solanum
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chemistry