China's realgar/orpiment deposits may be classified into three types, the stratabound, hot-water sedimentary and hydrothermal, according to their mineralizing processes, geological occurrences, tectonic and geoche...China's realgar/orpiment deposits may be classified into three types, the stratabound, hot-water sedimentary and hydrothermal, according to their mineralizing processes, geological occurrences, tectonic and geochemical features. The three types may be further distinguished into seven subtypes, namely, the Xiaguan, Shuiluo, Jiepaiyu, Songpan, Shixia, Wangzhuang and Ninghshan ones. On this basis three minerogenic models are established, and based on studies of their geochemistry and minerogenic mechanisms the prerequisites for prospecting for these types of deposits are given in the paper.展开更多
Formation and dissolution of secondary arsenic minerals often play significant roles in controlling arsenic mobility in contaminated environments, especially in sulfide mines. Weathering of the orpiment and realgar-be...Formation and dissolution of secondary arsenic minerals often play significant roles in controlling arsenic mobility in contaminated environments, especially in sulfide mines. Weathering of the orpiment and realgar-bearing tailings from the Shimen realgar deposit, the largest realgar deposit in Asia, were studied. An integrated mineralogical analysis by using X-ray powder diffraction (XRD), Raman spectrum, scanning electron microscope (SEM) and transmission electron microscope (TEM) reveals four kinds of As-bearing secondary minerals including arsenic oxides, arsenates, As-gypsum, and As-Fe minerals. The precipitation of arsenates is due to interaction of As-bearing run-off waters and the underlying carbonate rocks, or the transformation of gypsum into arsenates or As-bearing gypsum through SO42-/HAsO42- substitution. Ca-arsenates are mainly weilite and pharmacolite with Ca/As atomic ratio of 1. Scanning transmission X-ray microscope (STXM) and X-ray absorption fine structure (XAFS) reveal that the valence of arsenic is mainly +3 and +5.展开更多
Terahertz time-domain spectroscopy(THz-TDS)is an effective nondestructive and noninvasive tool for investigating sulfur-containing pigments.Combined with Raman spectroscopy and vibrational mode analysis,it is signific...Terahertz time-domain spectroscopy(THz-TDS)is an effective nondestructive and noninvasive tool for investigating sulfur-containing pigments.Combined with Raman spectroscopy and vibrational mode analysis,it is significant for artifact identification and conservation.In this work,the terahertz absorption spectra of pararealgar(As_(4)S_(4))and orpiment(As_(2)S_(3))samples mixed with polytetrafluoroethylene(PTFE)are characterized in a range from 0.2 THz to 2.2 THz,and their distinctive peaks are observed,respectively.Meanwhile,qualitative analysis is also implemented by using Raman spectroscopy as a complementary technique.The lattice vibrations are simulated by using solid-state density functional theory(ss-DFT),illustrating different characteristic absorption peaks for specific crystalline structures and dynamic properties.This work provides a reliable database of sulfur-containing pigments for using the THz technology to actually analyze and diagnose cultural relics.展开更多
目的探究雄黄主要成分二硫化二砷(As_(2)S_(2))对三阴性乳腺癌(triple negative breast cancer,TNBC)的作用及表观遗传调控机制。方法采用CCK-8、平板克隆形成和细胞划痕实验探究As_(2)S_(2)对人正常乳腺上皮细胞MCF-10A及TNBC细胞增殖...目的探究雄黄主要成分二硫化二砷(As_(2)S_(2))对三阴性乳腺癌(triple negative breast cancer,TNBC)的作用及表观遗传调控机制。方法采用CCK-8、平板克隆形成和细胞划痕实验探究As_(2)S_(2)对人正常乳腺上皮细胞MCF-10A及TNBC细胞增殖和迁移的影响;4D-label free定量蛋白质组学分析挖掘As_(2)S_(2)抗TNBC的潜在干预靶点酸性核磷蛋白家族成员32A(acidic nuclear phosphoprotein family member 32A,ANP32A);慢病毒感染法构建ANP32A过表达敲低细胞株,探究潜在靶点ANP32A对As_(2)S_(2)抗TNBC作用的影响;蛋白质免疫共沉淀和Western blot实验探究As_(2)S_(2)是否通过ANP32A调控TNBC细胞H3乙酰化。结果As_(2)S_(2)对人正常乳腺上皮细胞MCF-10A影响甚微,但显著抑制TNBC细胞增殖和迁移,且呈剂量依赖性;4D-lable free定量蛋白质组学分析结果显示,促癌因子ANP32A被As_(2)S_(2)显著下调,且ANP32A表达影响As_(2)S_(2)在TNBC中的抗增殖和迁移效果。As_(2)S_(2)能下调ANP32A的蛋白水平,抑制乙酰转移酶抑制剂复合物亚基的招募,增加H3乙酰化水平。结论As_(2)S_(2)通过下调ANP32A蛋白调控TNBC细胞中H3乙酰化,抑制TNBC细胞增殖和迁移。展开更多
The effects of nanometer realgar uterine cervix cancer cell line SiHa cells and suspension on proliferation and apoptosis of human oncogenic genes HPV16E6/E7 were investigated. A "micro-jet effiux" strategy was used...The effects of nanometer realgar uterine cervix cancer cell line SiHa cells and suspension on proliferation and apoptosis of human oncogenic genes HPV16E6/E7 were investigated. A "micro-jet effiux" strategy was used for the preparation of nanometer realgar suspension. SiHa cells were treated with nanometer Realgar suspension in various concentrations (6.25, 12.5, 25 and 50 mg/L) for different durations (12, 24, 48 and 72 h). The inhibitive effect of nanometer realgar suspension on growth of SiHa cells was detected by MTT method. Special morphological changes of apoptosis were observed by transmission electron microscopy (TEM) and DNA fragments electrophoresis. The apoptotic rate was quantified by flow cytometry (FCM). The expression of HPV 16E6/E7 mRNA and protein was assayed by RT-PCR and Western blot respectively. The results showed after being treated with 25--50 mg/L nanometer realgar suspension for 48 h, the survival rate of SiHa cells was decreased, and apoptotic rate markedly increased in a time- and concentration-dependent manner. TEM and DNA electrophoresis revealed the special morphological changes of apoptosis. The apoptotic rate of SiHa cells treated with nanometer realgar suspension was significantly higher than in the control group (P〈0.01), and G0/G1 phase arrest appeared following treatment with nanometer realgar suspension in 25 and 50 mg/L for 48 h. RT-PCR and Western blot assay indicated that nanometer realgar suspension reduced the HPV16E6/E7 gene expression. Nanometer realgar suspension could inhibit the proliferation and induce apoptosis of SiHa cells. The mechanism may be related to the down-regulation of the HPV16E6/E7 gene expression.展开更多
Objective: To observe the effects and mechanisms of nanocrystallized realgar for the treatment of skin cancer. Methods: The clinical part was observing the therapeutic effect for the skin ulceration by externally usin...Objective: To observe the effects and mechanisms of nanocrystallized realgar for the treatment of skin cancer. Methods: The clinical part was observing the therapeutic effect for the skin ulceration by externally using the nanocrystallized realgar. The experimental part was culturing the human squamous cell carcinoma A431 cells (A431) in vitro environment, estimating the effects of proliferation and apoptosis of A431 by MTT method and flow cytometry, and observing the effects on the expression of Survivin, Caspase-3 by RT-PCR method. Results: External treatment with nanocrystallized realgar had a therapeutic effect for the skin ulceration;it can promote the ulcers of skin cancer and skin metastasis healing. The experiments confirmed that nanocrystallized realgar can inhibit the A431 proliferation, induce the cells apoptosis, promote the expression of Caspase-3 and reduce the expression of Survivin. And the experiments also found that the effects were in a concentration-dependent manner, and they have a synergistic effect with cis-Dichlorodiamineplatinum (DDP). Conclusions: External treatment with nanocrystallized realgar for the patients of skin cancer or skin metastasis achieved satisfactory therapeutic effects by inhibiting A431 proliferation and inducing these cells apoptosis. The mechanism might be associated with promoting the expression of Caspase-3 and reducing the expression of Survivin.展开更多
The high-pressure structural,vibrational and electrical properties for realgar were investigated by in-situ Raman scattering and electrical conductivity experiments combined with first-principle calculations up to~30....The high-pressure structural,vibrational and electrical properties for realgar were investigated by in-situ Raman scattering and electrical conductivity experiments combined with first-principle calculations up to~30.8 GPa.It was verified that realgar underwent an isostructural phase transition at~6.3 GPa and a metallization at a higher pressure of~23.5 GPa.The isostructural phase transition was well evidenced by the obvious variations of Raman peaks,electrical conductivity,crystal parameters and the As–S bond length.The phase transition of metallization was in closely associated with the closure of bandgap rather than caused by the structural phase transition.And furthermore,the metallic realgar exhibited a relatively low compressibility with the unit cell volume V_(0)=718.1.4Å^(3)and bulk modulus B_(0)=36.1 GPa.展开更多
Objective To observe the clinical effect of realgar on multiple myeloma and to investigate its mechanism. Methods MTT and double antibody cramped ELISA assay were used to detect the activity of interleukin-6(IL-6) and...Objective To observe the clinical effect of realgar on multiple myeloma and to investigate its mechanism. Methods MTT and double antibody cramped ELISA assay were used to detect the activity of interleukin-6(IL-6) and level of soluble interleukin-6 receptor(sIL-6R) of the bone marrow supernant in 15 multiple myeloma patients treated by realgar or not. Results The activity of interleukin-6 and level of soluble interleukin-6 receptor of multiple myeloma patients were significantly higher than that of control group(P<0.01). They were not apparently decreased after realgar was used for 50 days(P>0.05).The interleukin-6 activity of stage Ⅲ patients were much higher than that of stage Ⅰ or Ⅱ(P<0.05). There was no difference of the level of soluble interleukin-6 receptor between two groups(P>0.05). For the 15 patients who were treated by using realgar, 3 got complete remission(CR), 5 got partial remission(PR), 7 came to not remission(NR). Conclusion Realgar could not decrease the activity of interleukin-6 and level of soluble interleukin-6 receptor so as to inhibit the proliferation of tumor cells.展开更多
Objective: To evaluate whether realgar could down-regulate human telomerase reverse transcriptase (hTERT) gene expression and telomerase activity in acute promyelocytic leukemia cell line-NB4 cells. Methods: The expre...Objective: To evaluate whether realgar could down-regulate human telomerase reverse transcriptase (hTERT) gene expression and telomerase activity in acute promyelocytic leukemia cell line-NB4 cells. Methods: The expression of hTERT-mRNA was analyzed by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Telomerase activity was determined by polymerase chain reaction enzyme-linked immunoassay (PCR-ELISA). Flow cytometry using PI staining was applied to analyze the cell cycle and apoptosis. Results: Treatment of NB4 cells with 155, 300, 600 μg/L realgar reduced telomerase activity significantly accompanying with decrease of hTERT-mRNA and increasing cell apoptosis. G2/M phase arrest appeared when treated with realgar in 300, 600 μg/L. Conclusion: It is suggested that telomerase activity of NB4 cells can be specifically inhibited by realgar through the down-regulation of hTERT gene expression. G2/M phase arrest and apoptosis by realgar in NB4 cells might be related to the reduction of telomerase activity and hTERT-mRNA expression.展开更多
BACKGROUND:The Chinese herbal compound realgar exerts detoxification effects as an adjuvant. It is suggested that realgar exerts detoxification via the following pathways: in the pathological state, realgar corrects...BACKGROUND:The Chinese herbal compound realgar exerts detoxification effects as an adjuvant. It is suggested that realgar exerts detoxification via the following pathways: in the pathological state, realgar corrects the oxidative stress state by increasing stress levels, activating some endogenous protective factors and antagonizing the excessive release of inflammatory factors, as well as inhibiting complement activation. OBJECTIVE: To observe the changes in stress proteins, inflammatory mediators, and complement in the brain tissue and serum of rats with inflammatory brain injury, which have been treated with the Chinese herbal compound Angong Niuhuang, and to compare the efficacy of Angong Niuhuang with that of realgar, to verify the mechanism of action of realgar. DESIGN, TIME AND SETTING: Randomized, controlled, cytological experiment, performed in the Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine in March 2006. MATERIALS: Thirty-six healthy, male, Sprague Dawley rats received 250 U/kg Bordetella pertussis via the common carotid artery within 15 seconds to induce inflammatory brain injury. Reagents and kits were as follows: Realgar and Angong Niuhuang powder (Foshan Second Pharmaceutical Factory, China), Bordetella pertussis diagnostic antigen (National Institute for the Control of Pharmaceutical and Biological Products, China), heat shock protein 70 (HSP70) enzyme-labeled immunosorbent assay (ELISA) kit (Stressgen, USA), tumor necrosis factor-α (TNF-α) ELISA kit (Biosource, USA), nitric oxide synthase (NOS) kit, Coomassie brilliant blue protein kit (Nanjing Jiancheng Bioengineering Co.,Ltd., China), and complements C3 and C4 (Shanghai Kehua Dongling Diagnositic Products Co.,Ltd., China). METHODS: Thirty-six rats were randomly and evenly divided into the following six groups: normal control, model, high-, middle-, and low-dose realgar-treated, and Angong Niuhuang-treated groups. At one hour prior to establishing the model, rats in the high-, middle-, and low-dose realgar-treated groups were administered 300, 150, and 75 mg/kg realgar, respectively; while rats in the Angong Niuhuang group received 1.5 g/kg Angong Niuhuang powder; In the model group, rats were administered Bordetalla pertussis only. MAIN OUTCOME MEASURES: Two hours after the administration of Bordetalla pertussis, the HSP70 level in the brain tissue and serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and TNF-α were determined by ELISA tests, hemooxygenase-1 (HO-1) activity in the brain tissue and serum was determined by dual-wavelength spectrophotometry, NOS and inducible nitric oxide synthase (iNOS) activities in the brain tissue were measured by the Bradford assay method, and serum levels of complement C3 and C4 were determined by immunoturbidimetry. RESULTS: In the high-dose realgar and Angong Niuhuang groups, the HSP70 level in the brain tissue of rats with inflammatory brain injury was increased significantly (P 〈 0.01). In the realgar-treated groups, HO-1 activity in the brain tissue and serum was dose-dependently enhanced with increasing realgar doses. However, no significant difference existed between the realgar groups and the model group (P 〉 0.05). In the Angong Niuhuang group, HO-1 activity in the brain tissue and serum was increased (P 〈 0.05). In the realgar and Angong Niuhuang groups, serum levels of IL-1β, IL-6, and TNF-α were significantly decreased; the serum IL-1β level recovered to the normal level and serum levels of IL-6 and TNF-α dose-dependently decreased in the realgar groups. NOS activity in the brain tissue was lower in the high-dose realgar group than in the model group (P 〈 0.05). iNOS activity was significantly lower in the middle- and high-dose realgar groups than in the model group (P 〈 0.01). NOS and iNOS activities were significantly lower in the Angong Niuhuang group than in the model group (P 〈 0.01). The serum C3 level was significantly decreased in the middle-dose realgar and Angong Niuhuang groups (P 〈 0.01). CONCLUSION: At certain doses, realgar is able to correct the oxidative stress state, by inducing and activating endogenous protective factors, such as HSP70, and inhibiting the excessive release of inflammatory mediators, such as IL-1β, IL-6, and TNF-α. However, it remains unclear whether realgarinhibits the activation of C3 and C4.展开更多
OBJECTIVE To investigate the effect and the mechanisms of realgar transforming solution(RTS)on down-regulating over activated ras.METHODS we used the optimizing technical processes to obtain the RTS,and eval⁃uate the ...OBJECTIVE To investigate the effect and the mechanisms of realgar transforming solution(RTS)on down-regulating over activated ras.METHODS we used the optimizing technical processes to obtain the RTS,and eval⁃uate the mechanisms of RTS on down-regulating overactivated ras in Caenorhabditis elegans.RESULTS We found that the mRNA level of let60 and lin45 significantly decreased following exposure to RTS,but mRNA levels of mpk1 were not statistically significant in let60/ras(gf)mutant.RTS together with sorafenib(RAF inhibitors)significantly enhanced the activity of RTS on down-regulating overactivated ras more than RTS only,but 50μmol·L^-1 PD98059,a specific ERK inhibitor did not.Lin45 gene RNAi decreased the ability of RTS on down-regulating overactivated ras significantly,but mpk1 gene RNAi did not,indicating that the activity of RTS on down-regulating overactivated ras mainly through targeting to lin45/raf.In addition,RTS significantly increased mRNA level of pmk1/p38 and jnk1/jnk in let-60/ras(gf)mutant,50μmol·L^-1 SB203580(p38 inhibitor)and SP600125(JNK inhibitor)significantly attenuated the effects of RTS on down-regulating overactivated ras in some degree,and pmk1,jnk1 gene RNAi displayed the similar results,suggesting that P38 and JNK/MAPK pathways in some degree were involved in the effects of RTS on down-regulating overactivated ras in C.ele⁃gans.CONCLUSION Realgar transforming solution down-regulate the Ras/MAPK pathway through JNK and P38 MAPK pathways.展开更多
In order to inquire into the therapeutic effects of Xiao Shi Xiong Huang San (硝石雄黄散the Nitrum and Realgar Powder), one of the Dunhuang Prescription, on angina pectoris due to coronary heart disease (APCHD), the a...In order to inquire into the therapeutic effects of Xiao Shi Xiong Huang San (硝石雄黄散the Nitrum and Realgar Powder), one of the Dunhuang Prescription, on angina pectoris due to coronary heart disease (APCHD), the authors have treated 61 cases of APCHD by externally applying paste of the powder on Zhiyang (GV 9), with another 30 cases of APCHD treated with the nitroglycerin paste on Zhiyang as the controls. The results showed that the total effective rate was 82% and markedly effective rate 31.2% in the treatment group (the Paste of Nitrum and Realgar Powder), and the total effective rate was 46.6% and markedly effective rate 23.2% in the control group (the nitroglycerin paste). The difference in therapeutic effects between the two groups was very significant (P<0.01), indicating that the therapeutic effect of the former was significantly superior to that of the latter.展开更多
Objective:Realgar is a traditional mineral Chinese medicine with antitumor effects,but it has high toxicity and low efficacy in its crude form.The purpose of this study was to optimize realgar to increase its efficacy...Objective:Realgar is a traditional mineral Chinese medicine with antitumor effects,but it has high toxicity and low efficacy in its crude form.The purpose of this study was to optimize realgar to increase its efficacy and therapeutic potential.Methods:Crude realgar(CR)was mechanically ground to obtain nano-realgar(NR),and then nano-realgar processed products(NRPPs)were obtained using three different traditional Chinese medicine processing methods:grinding in water,acid water,and alkali water,respectively.Results:By analyzing the size distribution of nanoparticles and the content of arsenic trioxide(As_(2)O_(3);ATO),we found that acid water-ground NRPPs had the characteristics of high purity and low toxicity.The effects of CR,NR,and NRPPs on proliferation,cell cycle,and apoptosis of MCF-7 cells were detected,and the ability of NRPPs to induce apoptosis in MCF-7 cells was analyzed.The results showed that the average particle size of acid water-ground NRPPs was 137.7 nm,and the content of ATO was 2.83 mg/g.Acid water-ground NRPPs showed better effects on inhibiting proliferation,cell cycle,and apoptosis of MCF-7 cells than CR and NR.Western blot assays further confirmed that acid water-ground NRPPs upregulated the protein expression of TP53,Bax,cytochrome c,caspase-9,and caspase-3 in MCF-7 cells(P<0.05)and inhibited the expression of Bcl-2(P<0.05).Conclusion:These results suggest that acid water-ground NRPPs can induce apoptosis of MCF-7 cells through regulating mitochondrial-mediated apoptosis,providing evidence for the clinical application of realgar.展开更多
Objective :To investigate PML. gene and protein expression and localization in leukemia cell lines. Methods Cell morphology was assayed by Wright’s stain and fluorescence stain, and PML mRNA expression by RT-PCR, PML...Objective :To investigate PML. gene and protein expression and localization in leukemia cell lines. Methods Cell morphology was assayed by Wright’s stain and fluorescence stain, and PML mRNA expression by RT-PCR, PML protein localization by immuno-fluorescence. Results NB4 and HL-60 cells differentiated morphologically after treatment with anti-retinoic acid (ATRA ) while K562 cells did not differentiate. Typical apoptosis was found in each cell line after treatment with red orpiment. Immuno-fluorescence analysis showed, after treatment with ATRA, the fusion protein disappeared in NB4 cells and the PML protein relocated, while HL-60 and K562 cells had no difference from control cells. After treatment with red orpiment, the fusion protein disappeared in NB4 cells, then degraded, which was also seen in HL-60 cells and K562 cells. The expression of PML mRNA was not changed in all three cell lines after treatment with ATRA or red orpiment. Conclusion PML plays the role of differentiation and apoptosis inducer in leukemia cells at the translational level. PML in POD plays the role of apoptosis inducer and the growth control of leukemia cells.展开更多
文摘China's realgar/orpiment deposits may be classified into three types, the stratabound, hot-water sedimentary and hydrothermal, according to their mineralizing processes, geological occurrences, tectonic and geochemical features. The three types may be further distinguished into seven subtypes, namely, the Xiaguan, Shuiluo, Jiepaiyu, Songpan, Shixia, Wangzhuang and Ninghshan ones. On this basis three minerogenic models are established, and based on studies of their geochemistry and minerogenic mechanisms the prerequisites for prospecting for these types of deposits are given in the paper.
文摘Formation and dissolution of secondary arsenic minerals often play significant roles in controlling arsenic mobility in contaminated environments, especially in sulfide mines. Weathering of the orpiment and realgar-bearing tailings from the Shimen realgar deposit, the largest realgar deposit in Asia, were studied. An integrated mineralogical analysis by using X-ray powder diffraction (XRD), Raman spectrum, scanning electron microscope (SEM) and transmission electron microscope (TEM) reveals four kinds of As-bearing secondary minerals including arsenic oxides, arsenates, As-gypsum, and As-Fe minerals. The precipitation of arsenates is due to interaction of As-bearing run-off waters and the underlying carbonate rocks, or the transformation of gypsum into arsenates or As-bearing gypsum through SO42-/HAsO42- substitution. Ca-arsenates are mainly weilite and pharmacolite with Ca/As atomic ratio of 1. Scanning transmission X-ray microscope (STXM) and X-ray absorption fine structure (XAFS) reveal that the valence of arsenic is mainly +3 and +5.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.61805129 and 11874245)the National Key Research and Development Program of China(Grant No.2021YFB3200100)the Yungang Special Fund of Shanxi Datong University,China(Grant No.2020YGZX005)。
文摘Terahertz time-domain spectroscopy(THz-TDS)is an effective nondestructive and noninvasive tool for investigating sulfur-containing pigments.Combined with Raman spectroscopy and vibrational mode analysis,it is significant for artifact identification and conservation.In this work,the terahertz absorption spectra of pararealgar(As_(4)S_(4))and orpiment(As_(2)S_(3))samples mixed with polytetrafluoroethylene(PTFE)are characterized in a range from 0.2 THz to 2.2 THz,and their distinctive peaks are observed,respectively.Meanwhile,qualitative analysis is also implemented by using Raman spectroscopy as a complementary technique.The lattice vibrations are simulated by using solid-state density functional theory(ss-DFT),illustrating different characteristic absorption peaks for specific crystalline structures and dynamic properties.This work provides a reliable database of sulfur-containing pigments for using the THz technology to actually analyze and diagnose cultural relics.
文摘目的探究雄黄主要成分二硫化二砷(As_(2)S_(2))对三阴性乳腺癌(triple negative breast cancer,TNBC)的作用及表观遗传调控机制。方法采用CCK-8、平板克隆形成和细胞划痕实验探究As_(2)S_(2)对人正常乳腺上皮细胞MCF-10A及TNBC细胞增殖和迁移的影响;4D-label free定量蛋白质组学分析挖掘As_(2)S_(2)抗TNBC的潜在干预靶点酸性核磷蛋白家族成员32A(acidic nuclear phosphoprotein family member 32A,ANP32A);慢病毒感染法构建ANP32A过表达敲低细胞株,探究潜在靶点ANP32A对As_(2)S_(2)抗TNBC作用的影响;蛋白质免疫共沉淀和Western blot实验探究As_(2)S_(2)是否通过ANP32A调控TNBC细胞H3乙酰化。结果As_(2)S_(2)对人正常乳腺上皮细胞MCF-10A影响甚微,但显著抑制TNBC细胞增殖和迁移,且呈剂量依赖性;4D-lable free定量蛋白质组学分析结果显示,促癌因子ANP32A被As_(2)S_(2)显著下调,且ANP32A表达影响As_(2)S_(2)在TNBC中的抗增殖和迁移效果。As_(2)S_(2)能下调ANP32A的蛋白水平,抑制乙酰转移酶抑制剂复合物亚基的招募,增加H3乙酰化水平。结论As_(2)S_(2)通过下调ANP32A蛋白调控TNBC细胞中H3乙酰化,抑制TNBC细胞增殖和迁移。
基金a grant from Hubei Chal-lenging Program of Science and Technology,China(No.2007AA301B38-3)
文摘The effects of nanometer realgar uterine cervix cancer cell line SiHa cells and suspension on proliferation and apoptosis of human oncogenic genes HPV16E6/E7 were investigated. A "micro-jet effiux" strategy was used for the preparation of nanometer realgar suspension. SiHa cells were treated with nanometer Realgar suspension in various concentrations (6.25, 12.5, 25 and 50 mg/L) for different durations (12, 24, 48 and 72 h). The inhibitive effect of nanometer realgar suspension on growth of SiHa cells was detected by MTT method. Special morphological changes of apoptosis were observed by transmission electron microscopy (TEM) and DNA fragments electrophoresis. The apoptotic rate was quantified by flow cytometry (FCM). The expression of HPV 16E6/E7 mRNA and protein was assayed by RT-PCR and Western blot respectively. The results showed after being treated with 25--50 mg/L nanometer realgar suspension for 48 h, the survival rate of SiHa cells was decreased, and apoptotic rate markedly increased in a time- and concentration-dependent manner. TEM and DNA electrophoresis revealed the special morphological changes of apoptosis. The apoptotic rate of SiHa cells treated with nanometer realgar suspension was significantly higher than in the control group (P〈0.01), and G0/G1 phase arrest appeared following treatment with nanometer realgar suspension in 25 and 50 mg/L for 48 h. RT-PCR and Western blot assay indicated that nanometer realgar suspension reduced the HPV16E6/E7 gene expression. Nanometer realgar suspension could inhibit the proliferation and induce apoptosis of SiHa cells. The mechanism may be related to the down-regulation of the HPV16E6/E7 gene expression.
文摘Objective: To observe the effects and mechanisms of nanocrystallized realgar for the treatment of skin cancer. Methods: The clinical part was observing the therapeutic effect for the skin ulceration by externally using the nanocrystallized realgar. The experimental part was culturing the human squamous cell carcinoma A431 cells (A431) in vitro environment, estimating the effects of proliferation and apoptosis of A431 by MTT method and flow cytometry, and observing the effects on the expression of Survivin, Caspase-3 by RT-PCR method. Results: External treatment with nanocrystallized realgar had a therapeutic effect for the skin ulceration;it can promote the ulcers of skin cancer and skin metastasis healing. The experiments confirmed that nanocrystallized realgar can inhibit the A431 proliferation, induce the cells apoptosis, promote the expression of Caspase-3 and reduce the expression of Survivin. And the experiments also found that the effects were in a concentration-dependent manner, and they have a synergistic effect with cis-Dichlorodiamineplatinum (DDP). Conclusions: External treatment with nanocrystallized realgar for the patients of skin cancer or skin metastasis achieved satisfactory therapeutic effects by inhibiting A431 proliferation and inducing these cells apoptosis. The mechanism might be associated with promoting the expression of Caspase-3 and reducing the expression of Survivin.
基金the strategic priority Research Program(B)of the Chinese Academy of Sciences(Grant No.18010401)Key Research Program of Frontier Sciences of CAS(Grant No.QYZDB-SSW-DQC009)+3 种基金Hundred Talents Program of CAS,NSF of China(Grant Nos.41774099 and 41772042)Youth Innovation Promotion Association of CAS(Grant No.2019390)Special Fund of the West Light Foundation of CASthe Supercomputer Center of Fujian Institute of Research on the Structure of Matter(FJIRSM)is acknowledged.
文摘The high-pressure structural,vibrational and electrical properties for realgar were investigated by in-situ Raman scattering and electrical conductivity experiments combined with first-principle calculations up to~30.8 GPa.It was verified that realgar underwent an isostructural phase transition at~6.3 GPa and a metallization at a higher pressure of~23.5 GPa.The isostructural phase transition was well evidenced by the obvious variations of Raman peaks,electrical conductivity,crystal parameters and the As–S bond length.The phase transition of metallization was in closely associated with the closure of bandgap rather than caused by the structural phase transition.And furthermore,the metallic realgar exhibited a relatively low compressibility with the unit cell volume V_(0)=718.1.4Å^(3)and bulk modulus B_(0)=36.1 GPa.
文摘Objective To observe the clinical effect of realgar on multiple myeloma and to investigate its mechanism. Methods MTT and double antibody cramped ELISA assay were used to detect the activity of interleukin-6(IL-6) and level of soluble interleukin-6 receptor(sIL-6R) of the bone marrow supernant in 15 multiple myeloma patients treated by realgar or not. Results The activity of interleukin-6 and level of soluble interleukin-6 receptor of multiple myeloma patients were significantly higher than that of control group(P<0.01). They were not apparently decreased after realgar was used for 50 days(P>0.05).The interleukin-6 activity of stage Ⅲ patients were much higher than that of stage Ⅰ or Ⅱ(P<0.05). There was no difference of the level of soluble interleukin-6 receptor between two groups(P>0.05). For the 15 patients who were treated by using realgar, 3 got complete remission(CR), 5 got partial remission(PR), 7 came to not remission(NR). Conclusion Realgar could not decrease the activity of interleukin-6 and level of soluble interleukin-6 receptor so as to inhibit the proliferation of tumor cells.
基金Supported by Xi'an Foundation of Science and Technology Program(200016)
文摘Objective: To evaluate whether realgar could down-regulate human telomerase reverse transcriptase (hTERT) gene expression and telomerase activity in acute promyelocytic leukemia cell line-NB4 cells. Methods: The expression of hTERT-mRNA was analyzed by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Telomerase activity was determined by polymerase chain reaction enzyme-linked immunoassay (PCR-ELISA). Flow cytometry using PI staining was applied to analyze the cell cycle and apoptosis. Results: Treatment of NB4 cells with 155, 300, 600 μg/L realgar reduced telomerase activity significantly accompanying with decrease of hTERT-mRNA and increasing cell apoptosis. G2/M phase arrest appeared when treated with realgar in 300, 600 μg/L. Conclusion: It is suggested that telomerase activity of NB4 cells can be specifically inhibited by realgar through the down-regulation of hTERT gene expression. G2/M phase arrest and apoptosis by realgar in NB4 cells might be related to the reduction of telomerase activity and hTERT-mRNA expression.
基金the National Natural Science Foundation of China, No. 30672637
文摘BACKGROUND:The Chinese herbal compound realgar exerts detoxification effects as an adjuvant. It is suggested that realgar exerts detoxification via the following pathways: in the pathological state, realgar corrects the oxidative stress state by increasing stress levels, activating some endogenous protective factors and antagonizing the excessive release of inflammatory factors, as well as inhibiting complement activation. OBJECTIVE: To observe the changes in stress proteins, inflammatory mediators, and complement in the brain tissue and serum of rats with inflammatory brain injury, which have been treated with the Chinese herbal compound Angong Niuhuang, and to compare the efficacy of Angong Niuhuang with that of realgar, to verify the mechanism of action of realgar. DESIGN, TIME AND SETTING: Randomized, controlled, cytological experiment, performed in the Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine in March 2006. MATERIALS: Thirty-six healthy, male, Sprague Dawley rats received 250 U/kg Bordetella pertussis via the common carotid artery within 15 seconds to induce inflammatory brain injury. Reagents and kits were as follows: Realgar and Angong Niuhuang powder (Foshan Second Pharmaceutical Factory, China), Bordetella pertussis diagnostic antigen (National Institute for the Control of Pharmaceutical and Biological Products, China), heat shock protein 70 (HSP70) enzyme-labeled immunosorbent assay (ELISA) kit (Stressgen, USA), tumor necrosis factor-α (TNF-α) ELISA kit (Biosource, USA), nitric oxide synthase (NOS) kit, Coomassie brilliant blue protein kit (Nanjing Jiancheng Bioengineering Co.,Ltd., China), and complements C3 and C4 (Shanghai Kehua Dongling Diagnositic Products Co.,Ltd., China). METHODS: Thirty-six rats were randomly and evenly divided into the following six groups: normal control, model, high-, middle-, and low-dose realgar-treated, and Angong Niuhuang-treated groups. At one hour prior to establishing the model, rats in the high-, middle-, and low-dose realgar-treated groups were administered 300, 150, and 75 mg/kg realgar, respectively; while rats in the Angong Niuhuang group received 1.5 g/kg Angong Niuhuang powder; In the model group, rats were administered Bordetalla pertussis only. MAIN OUTCOME MEASURES: Two hours after the administration of Bordetalla pertussis, the HSP70 level in the brain tissue and serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and TNF-α were determined by ELISA tests, hemooxygenase-1 (HO-1) activity in the brain tissue and serum was determined by dual-wavelength spectrophotometry, NOS and inducible nitric oxide synthase (iNOS) activities in the brain tissue were measured by the Bradford assay method, and serum levels of complement C3 and C4 were determined by immunoturbidimetry. RESULTS: In the high-dose realgar and Angong Niuhuang groups, the HSP70 level in the brain tissue of rats with inflammatory brain injury was increased significantly (P 〈 0.01). In the realgar-treated groups, HO-1 activity in the brain tissue and serum was dose-dependently enhanced with increasing realgar doses. However, no significant difference existed between the realgar groups and the model group (P 〉 0.05). In the Angong Niuhuang group, HO-1 activity in the brain tissue and serum was increased (P 〈 0.05). In the realgar and Angong Niuhuang groups, serum levels of IL-1β, IL-6, and TNF-α were significantly decreased; the serum IL-1β level recovered to the normal level and serum levels of IL-6 and TNF-α dose-dependently decreased in the realgar groups. NOS activity in the brain tissue was lower in the high-dose realgar group than in the model group (P 〈 0.05). iNOS activity was significantly lower in the middle- and high-dose realgar groups than in the model group (P 〈 0.01). NOS and iNOS activities were significantly lower in the Angong Niuhuang group than in the model group (P 〈 0.01). The serum C3 level was significantly decreased in the middle-dose realgar and Angong Niuhuang groups (P 〈 0.01). CONCLUSION: At certain doses, realgar is able to correct the oxidative stress state, by inducing and activating endogenous protective factors, such as HSP70, and inhibiting the excessive release of inflammatory mediators, such as IL-1β, IL-6, and TNF-α. However, it remains unclear whether realgarinhibits the activation of C3 and C4.
文摘OBJECTIVE To investigate the effect and the mechanisms of realgar transforming solution(RTS)on down-regulating over activated ras.METHODS we used the optimizing technical processes to obtain the RTS,and eval⁃uate the mechanisms of RTS on down-regulating overactivated ras in Caenorhabditis elegans.RESULTS We found that the mRNA level of let60 and lin45 significantly decreased following exposure to RTS,but mRNA levels of mpk1 were not statistically significant in let60/ras(gf)mutant.RTS together with sorafenib(RAF inhibitors)significantly enhanced the activity of RTS on down-regulating overactivated ras more than RTS only,but 50μmol·L^-1 PD98059,a specific ERK inhibitor did not.Lin45 gene RNAi decreased the ability of RTS on down-regulating overactivated ras significantly,but mpk1 gene RNAi did not,indicating that the activity of RTS on down-regulating overactivated ras mainly through targeting to lin45/raf.In addition,RTS significantly increased mRNA level of pmk1/p38 and jnk1/jnk in let-60/ras(gf)mutant,50μmol·L^-1 SB203580(p38 inhibitor)and SP600125(JNK inhibitor)significantly attenuated the effects of RTS on down-regulating overactivated ras in some degree,and pmk1,jnk1 gene RNAi displayed the similar results,suggesting that P38 and JNK/MAPK pathways in some degree were involved in the effects of RTS on down-regulating overactivated ras in C.ele⁃gans.CONCLUSION Realgar transforming solution down-regulate the Ras/MAPK pathway through JNK and P38 MAPK pathways.
文摘In order to inquire into the therapeutic effects of Xiao Shi Xiong Huang San (硝石雄黄散the Nitrum and Realgar Powder), one of the Dunhuang Prescription, on angina pectoris due to coronary heart disease (APCHD), the authors have treated 61 cases of APCHD by externally applying paste of the powder on Zhiyang (GV 9), with another 30 cases of APCHD treated with the nitroglycerin paste on Zhiyang as the controls. The results showed that the total effective rate was 82% and markedly effective rate 31.2% in the treatment group (the Paste of Nitrum and Realgar Powder), and the total effective rate was 46.6% and markedly effective rate 23.2% in the control group (the nitroglycerin paste). The difference in therapeutic effects between the two groups was very significant (P<0.01), indicating that the therapeutic effect of the former was significantly superior to that of the latter.
基金supported by the Science and Technology_Research Project of Hubei Education Department(No.B2019097).
文摘Objective:Realgar is a traditional mineral Chinese medicine with antitumor effects,but it has high toxicity and low efficacy in its crude form.The purpose of this study was to optimize realgar to increase its efficacy and therapeutic potential.Methods:Crude realgar(CR)was mechanically ground to obtain nano-realgar(NR),and then nano-realgar processed products(NRPPs)were obtained using three different traditional Chinese medicine processing methods:grinding in water,acid water,and alkali water,respectively.Results:By analyzing the size distribution of nanoparticles and the content of arsenic trioxide(As_(2)O_(3);ATO),we found that acid water-ground NRPPs had the characteristics of high purity and low toxicity.The effects of CR,NR,and NRPPs on proliferation,cell cycle,and apoptosis of MCF-7 cells were detected,and the ability of NRPPs to induce apoptosis in MCF-7 cells was analyzed.The results showed that the average particle size of acid water-ground NRPPs was 137.7 nm,and the content of ATO was 2.83 mg/g.Acid water-ground NRPPs showed better effects on inhibiting proliferation,cell cycle,and apoptosis of MCF-7 cells than CR and NR.Western blot assays further confirmed that acid water-ground NRPPs upregulated the protein expression of TP53,Bax,cytochrome c,caspase-9,and caspase-3 in MCF-7 cells(P<0.05)and inhibited the expression of Bcl-2(P<0.05).Conclusion:These results suggest that acid water-ground NRPPs can induce apoptosis of MCF-7 cells through regulating mitochondrial-mediated apoptosis,providing evidence for the clinical application of realgar.
基金Partially supported by the National Natural Science Foundation of China(36970328)
文摘Objective :To investigate PML. gene and protein expression and localization in leukemia cell lines. Methods Cell morphology was assayed by Wright’s stain and fluorescence stain, and PML mRNA expression by RT-PCR, PML protein localization by immuno-fluorescence. Results NB4 and HL-60 cells differentiated morphologically after treatment with anti-retinoic acid (ATRA ) while K562 cells did not differentiate. Typical apoptosis was found in each cell line after treatment with red orpiment. Immuno-fluorescence analysis showed, after treatment with ATRA, the fusion protein disappeared in NB4 cells and the PML protein relocated, while HL-60 and K562 cells had no difference from control cells. After treatment with red orpiment, the fusion protein disappeared in NB4 cells, then degraded, which was also seen in HL-60 cells and K562 cells. The expression of PML mRNA was not changed in all three cell lines after treatment with ATRA or red orpiment. Conclusion PML plays the role of differentiation and apoptosis inducer in leukemia cells at the translational level. PML in POD plays the role of apoptosis inducer and the growth control of leukemia cells.