isothiocyanates

异硫氰酸酯
  • 文章类型: Journal Article
    有毒金属(镉(Cd),铅(Pb),汞(Hg)和砷(As))和增塑剂(邻苯二甲酸二(2-乙基己基)酯(DEHP),邻苯二甲酸二丁酯(DBP))和双酚A(BPA))已被建议有助于大肠癌(CRC)的发展。萝卜硫素(SFN),来自十字花科蔬菜的异硫氰酸盐,减少化学致癌易感性,但已被证明是一个朋友或敌人,这取决于各种因素。通过进行机械毒理学数据挖掘方法,这项研究旨在确定SFN是否可以在基因水平上减轻有毒金属和/或邻苯二甲酸盐/BPA混合物诱导的CRC。比较毒性基因组学数据库,ToppGeneSuite门户,Cytoscape软件,使用InteractVenn和基因表达综合(GEO)数据库(GEO2R工具)。在所有被研究物质的相互基因中,SFN仅通过PTGS2产生保护性影响。其他建议的保护SFN目标包括ABCA1,ALDH2,BMP2,DPYD,MYC,SLCO2A1和SOD2,仅在邻苯二甲酸酯/BPA暴露的情况下。与针对有毒金属混合物诱导的CRC的SFN保护相关的唯一额外基因是ABCB1。此外,提取的前15个分子途径中的大多数用于研究SFN对邻苯二甲酸盐和BPA混合相关CRC发展的影响与癌症发展直接相关,有毒金属混合物的情况并非如此。目前的研究表明,与有毒金属混合物相比,SFN是一种更有效的针对邻苯二甲酸酯/BPA混合物诱导的CRC的化学保护剂。它还提出了计算方法作为指导进一步研究的简单工具的价值,选择合适的生物标志物并探索毒性机制。
    Toxic metals (cadmium (Cd), lead (Pb), mercury (Hg) and arsenic (As)) and plastificators (bis (2 - ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP)) and bisphenol A (BPA)) have been suggested to aid in colorectal carcinoma (CRC) advancement. Sulforaphane (SFN), isothiocyanate from cruciferous vegetables, diminishes chemical carcinogenesis susceptibility, but has been shown to act as a friend or a foe depending on various factors. By conducting the mechanistic toxicogenomic data mining approach, this research aimed to determine if SFN can alleviate toxic-metal and/or phthalate/BPA mixture-induced CRC at the gene level. Comparative Toxicogenomics Database, ToppGene Suite portal, Cytoscape software, InteractiVenn and Gene Expression Omnibus (GEO) database (GEO2R tool) was used. Among the mutual genes for all the investigated substances, SFN had a protective impact only through PTGS2. Other proposed protective SFN-targets included ABCA1, ALDH2, BMP2, DPYD, MYC, SLCO2A1, and SOD2, only in the case of phthalates/BPA exposure. The only additional gene relevant for SFN protection against the toxic metal mixture-induced CRC was ABCB1. Additionally, the majority of the top 15 molecular pathways extracted for SFN impact on phthalate and BPA mixture-linked CRC development were directly linked with cancer development, which was not the case with the toxic metal mixture. The current research has indicated that SFN is a more effective chemoprotective agent against CRC induced by phthalates/BPA mixture than by toxic-metal mixture. It has also presented the value of computational methods as a simple tool for directing further research, selecting appropriate biomarkers and exploring the mechanisms of toxicity.
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  • 文章类型: Case Reports
    Intralymphatic histiocytosis (ILH) is a rare skin benign condition observed in a variety of inflammatory settings. It is characterized by the presence of ectatic dermal lymphatic vessels containing aggregates of histiocytes. Associated conditions that have been identified include rheumatoid arthritis, metallic orthopedic implants, inflammatory bowel disease, and malignancies of the breast, skin, and colon. Some cases with no attributable underlying cause have been described. The pathophysiology of ILH is not well understood. It has been proposed that it may represent macrophage migration during immune activation. Herein, we present the first description of ILH observed in the healing phase of cellulitis on the skin of the breast. Awareness of this possibility is important when the diagnosis of intravascular carcinomatosis is being considered.
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  • 文章类型: Journal Article
    Cruciferous vegetables contain high levels of glucosinolates (GSL) and isothiocyanates (ITC). ITC are known to induce glutathione S-transferases (GST) and thus exert their anticarcinogenic effects. This study explored the combined effects of cruciferous vegetable, GSL and ITC intake and GST polymorphisms on breast cancer risk. A total of 737 breast cancer cases and 756 controls were recruited into this case-control study. OR and 95 % CI were assessed by multivariable logistic regression. Higher cruciferous vegetable, GSL and ITC intakes were inversely associated with breast cancer risk, with adjusted OR of 0·48 (95 % CI 0·35, 0·65), 0·54 (95 % CI 0·40, 0·74) and 0·62 (95 % CI 0·45, 0·84), respectively. Compared with women carrying the GSTP1 rs1695 wild AA genotype and high cruciferous vegetable, GSL or ITC intake, carriers of the AA genotype with low cruciferous vegetable, GSL and ITC intake had greater risk of breast cancer, with adjusted OR of 1·43 (95 % CI 1·01, 1·87), 1·34 (95 % CI 1·02, 1·75) and 1·37 (95 % CI 1·05, 1·80), respectively. Persons with the GSTM1-null genotype and lower intake of cruciferous vegetables, GSL and ITC had higher risk of breast cancer than those with the GSTM1-present genotype and higher intake, with OR of 1·42 (95 % CI 1·04, 1·95), 1·43 (95 % CI 1·05, 1·96) and 1·45 (95 % CI 1·06, 1·98), respectively. Among women possessing the GSTT1-present genotype, low intake of cruciferous vegetables, GSL or ITC was associated with higher risk of breast cancer. But these interactions were non-significant. This study indicated that there were no significant interactions between cruciferous vegetable, GSL or ITC intake and GST polymorphisms on breast cancer risk.
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  • 文章类型: Journal Article
    Objective: To investigate the association between consumption of cruciferous vegetables (CV), level of urinary isothiocyanates (ITC) and the risk of lung cancer among man in urban Shanghai. Methods: A nested case-control study was conducted within the Shanghai Men\'s Health Study. Using incidence density sampling with a 2∶1 control to case selection ratio, 885 controls were selected to match 443 lung cancer cases diagnosed prior December 31, 2010. A food-frequency questionnaire was administered to estimate CV consumption. The high performance liquid chromatography method was applied to measure urinary ITC level. The CV intake and urinary ITC level were divided into quartiles according to distribution of control group. The lowest quartile was as a reference group. Conditional logistic regression model was used to analyze the relationship between CV intake, urinary ITC level and the risk of lung cancer. Results: The cruciferous vegetables intake median (P(25), P(75)) in cases and controls were 80.05 (46.89, 129.04) and 97.68 (55.25, 151.72) g/d (Z=-3.93, P<0.001). The urinary ITC level were 1.256 (0.474, 3.836) and 1.244 (0.484, 3.004) μmol/g Cr (Z=-0.39, P=0.697). After adjusting for potential confounding factors such as age, education level, smoking and alcohol consumption, for urinary ITC level, the OR(95%CI) for the highest quartile(≥3.004 μmol/g Cr) was 1.25 (0.87-1.80) compared with the lowest quartile(<0.484 μmol/g). For CV intake, the OR(95%CI) for the highest quartile(≥151.71 g/d) was 0.66 (0.43-1.02) compared with the lowest quartile(<55.25 g/d). Conclusion: No association was found between the CV intake, urinary ITC level and lung cancer risk in men.
    目的: 探讨饮食十字花科蔬菜(CV)摄入、尿液中异硫氰酸盐(ITC)水平与男性肺癌发病风险的关系。 方法: 在上海男性健康队列的基础上开展巢式病例-对照研究,选择随访时间2010年12月31日之前经确诊的新发肺癌病例443例,利用密度抽样法按1∶2的比例抽取对照885名。采用食物频率问卷调查饮食CV的摄入情况,使用高效液相色谱法测定对象尿液中的ITC代谢量。按照对照组的CV摄入量、尿液ITC代谢量进行四分位数分组,以最低组为参照组,采用条件Logistic回归模型分析CV摄入、尿中ITC代谢水平和男性肺癌的关系。 结果: 病例组、对照组CV摄入量的M(P(25),P(75))分别为80.05(46.89,129.04)、97.68(55.25,151.72)g/d(Z=-3.93,P<0.001);尿液ITC代谢量的M(P(25),P(75))分别为1.256(0.474,3.836)、1.244(0.484,3.004)μmol/g肌酐(Z=-0.39,P=0.697)。调整年龄、教育程度、吸烟、饮酒等混杂因素后,与尿液中ITC水平最低组(<0.484 μmol/g肌酐)相比,最高组(≥3.004 μmol/g肌酐)肺癌的OR(95%CI)值为1.25(0.87~1.80);与十字花科蔬菜摄入水平最低组(<55.25 g/d)相比,最高组(≥151.71 g/d)肺癌的OR(95%CI)值为0.66(0.43~1.02)。 结论: 未发现CV摄入量、尿液中ITC代谢水平与男性肺癌的发病风险差异有统计学意义。.
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  • 文章类型: Journal Article
    尽管以前的研究已经调查了十字花科蔬菜消费与乳腺癌风险的关系,很少有研究集中在十字花科蔬菜中生物活性成分之间的关联,芥子油苷(GSL)和异硫氰酸酯(ITC),和乳腺癌的风险。这项研究旨在根据中国人群的GSL和ITC含量,研究十字花科蔬菜的消费与乳腺癌风险之间的关系。从2007年6月至2017年3月,共招募了1485例病例和1506例对照纳入本病例对照研究。使用经过验证的FFQ评估十字花科蔬菜的消费量。饮食GSL和ITC是通过使用两个食物组成数据库来计算的,该数据库将十字花科蔬菜中的GSL和ITC含量与对FFQ的响应联系起来。在调整潜在的混杂因素后,通过非条件逻辑回归评估OR和95%CI。在十字花科蔬菜的消费之间发现了显着的负相关,GSL和ITC与乳腺癌的风险。十字花科蔬菜最高四分位数与最低四分位数的校正OR为0·51(95%CI0·41,0·63),GSL为0·54(95%CI0·44,0·67),ITC为0·62(95%CI0·50,0·76),分别。在绝经前和绝经后妇女中也观察到这些负相关。通过激素受体状态的亚组分析发现十字花科蔬菜之间的负相关,GSL和ITC与激素受体阳性或激素受体阴性乳腺癌。这项研究表明,食用十字花科蔬菜,在中国女性中,GSL和ITC与乳腺癌风险呈负相关。
    Although previous studies have investigated the association of cruciferous vegetable consumption with breast cancer risk, few studies focused on the association between bioactive components in cruciferous vegetables, glucosinolates (GSL) and isothiocyanates (ITC), and breast cancer risk. This study aimed to examine the association between consumption of cruciferous vegetables and breast cancer risk according to GSL and ITC contents in a Chinese population. A total of 1485 cases and 1506 controls were recruited into this case-control study from June 2007 to March 2017. Consumption of cruciferous vegetables was assessed using a validated FFQ. Dietary GSL and ITC were computed by using two food composition databases linking GSL and ITC contents in cruciferous vegetables with responses to the FFQ. The OR and 95 % CI were assessed by unconditional logistic regression after adjusting for the potential confounders. Significant inverse associations were found between consumption of cruciferous vegetables, GSL and ITC and breast cancer risk. The adjusted OR comparing the highest with the lowest quartile were 0·51 (95 % CI 0·41, 0·63) for cruciferous vegetables, 0·54 (95 % CI 0·44, 0·67) for GSL and 0·62 (95 % CI 0·50, 0·76) for ITC, respectively. These inverse associations were also observed in both premenopausal and postmenopausal women. Subgroup analysis by hormone receptor status found inverse associations between cruciferous vegetables, GSL and ITC and both hormone-receptor-positive or hormone-receptor-negative breast cancer. This study indicated that consumption of cruciferous vegetables, GSL and ITC was inversely associated with breast cancer risk among Chinese women.
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  • 文章类型: Journal Article
    Self-emulsifying drug delivery systems (SEDDS) have been used as a formulation strategy to overcome the challenges in formulating poorly water soluble drugs. The objective of the present study was to report on the solubilizing capacity of sulforaphane (SFN) and its utilization to formulate SEDDS of poorly water soluble drugs. A set of 24 drugs was tested for their solubility in SFN of which Cyclosporine A, Celecoxib, Paclitaxel, Docetaxel, and Curcumin were selected for subsequent SEDDS formulation development utilizing SFN as common solubilizer. SFN-SEDDS formulations were developed utilizing a step-wise screening method that enabled the selection of the most efficient surfactants and co-surfactants to yield transparent microemulsions by microscopic analysis and absorbance data. The optimized SEDDS formulation for curcumin was selected for further investigation by DSC and FTIR, and was subjected to a dissolution study where more than 95% of the drug was found to dissolve within 10 min in both simulated gastric and intestinal fluids. The physical stability of the SEDDS was also confirmed in both media when monitored at three different temperatures (4, 25 and 37 °C) up to 30 days. This study introduced a new approach to formulating SEDDS by utilizing the solubilizing capacity of SFN and introduced high throughput screening approach to formulation development and stability study.
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  • 文章类型: Journal Article
    Glucosinolates (GLSs) are dietary plant secondary metabolites occurring in the order Brassicales with potential health effects, in particular as anti-carcinogenic compounds. GLSs are converted into a variety of breakdown products (BPs) upon plant tissue damage and by the gut microbiota. GLS biological activity is related to BPs rather than to GLSs themselves.
    we have reviewed the most recent scientific literature on the metabolic fate and the biological effect of GLSs with particular emphasis on the epidemiological evidence for health effect and evidence from clinical trials. An overview of potential molecular mechanisms underlying GLS biological effect is provided. The potential toxic or anti-nutritional effect has also been discussed.
    Epidemiological and human in vivo evidence point towards a potential anti-cancer effect for sulforaphane, indole-3-carbinol and 3,3-diindolylmethane. A number of new human clinical trials are on-going and will likely shed further light on GLS protective effect towards cancer as well as other diseases. BPs biological effect is the results of a plurality of molecular mechanisms acting simultaneously which include modulation of xenobiotic metabolism, modulation of inflammation, regulation of apoptosis, cell cycle arrest, angiogenesis and metastasis and regulation of epigenetic events. BPs have been extensively investigated for their protective effect towards cancer but in recent years the interest also includes other diseases.
    It appears that certain BPs may protect against and may even represent a therapeutic strategy against several forms of cancer. Whether this latter effect can be achieved through diet or supplements should be investigated more thoroughly.
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  • 文章类型: Case Reports
    BACKGROUND: B-cell prolymphocytic leukemia (B-PLL) is a rare, aggressive leukemia distinct from chronic lymphocytic leukemia, with median survival of only 3 years. B-PLL is resistant to most chemotherapy and newer targeted therapies such as alemtuzumab and thalidomide. Phenylethyl isothiocyanate (PEITC) is a natural compound from horseradish with evidence for therapeutic potential in multiple leukemia types.
    METHODS: Here we present a case report of a 53-year-old man whose chronic lymphocytic leukemia transformed to end-stage B-PLL, disqualifying him for allogenic stem cell transplantation. He was treated with PEITC followed by salvage R-CHOP (Rituximab, Cyclophosphamide, Hydroxydaunorubicin [doxorubicin hydrochloride], Oncovin [vincristine sulfate], Prednisone or Prednisolone) chemotherapy, which led to normalized white blood cell count and disease stabilization that requalified him for allogenic peripheral stem-cell transplant therapy. We conducted a systematic review to analyze and interpret the potential contribution of PEITC to his unexpectedly favorable R-CHOP response. Following sequential 8 weeks of PEITC/pentostatin and 6 cycles of R-CHOP, the patient received allogenic peripheral blood stem cell transplant on an outpatient basis and remains well at the time of this publication, with no evidence of CD20+ small B-cells.
    CONCLUSIONS: Given the limited data for R-CHOP in B-PLL, this patient\'s recovery suggests presensitization of B-PLL cells toward R-CHOP, potentially justifying further investigation.
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  • 文章类型: Journal Article
    (1)H and (13)C NMR spectra of allyl isothiocyanate (AITC) were measured, and the exchange dynamics were studied to explain the near-silence of the ITC carbon in (13)C NMR spectra. The dihedral angles α = ∠(C1-C2-C3-N4) and β = ∠(C2-C3-N4-C5) describe the conformational dynamics (conformation change), and the bond angles γ = ∠(C3-N4-C5) and ε = ∠(N4-C5-S6) dominate the molecular dynamics (conformer flexibility). The conformation space of AITC contains three minima, Cs-M1 and enantiomers M2 and M2\'; the exchange between conformers is very fast, and conformational effects on (13)C chemical shifts are small (νM1 - νM2 < 3 ppm). Isotropic chemical shifts, ICS(γ), were determined for sp, sp(x), and sp(2) N-hybridization, and the γ dependencies of δ(N4) and δ(C5) are very large (10-33 ppm). Atom-centered density matrix propagation trajectories show that every conformer can access a large region of the potential energy surface AITC(γ,ε,...) with 120° < γ < 180° and 155° < ε < 180°. Because the extreme broadening of the (13)C NMR signal of the ITC carbon is caused by the structural flexibility of every conformer of AITC, the analysis provides a general explanation for the near-silence of the ITC carbon in (13)C NMR spectra of organic isothiocyanates.
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  • 文章类型: Journal Article
    Experimental studies have provided evidence that isothiocyanates (ITCs) from cruciferous vegetables may modulate carcinogen metabolism and facilitate carcinogen detoxification and reduce cancer risk. However, no epidemiological studies on liver cancer were reported. This study investigates the association between urinary ITCs levels and liver cancer risk among men and women in Shanghai, China. A nested case-control study of 217 incident cases of liver cancer and 427 matched controls identified from the Shanghai Women\'s Health Study and Shanghai Men\'s Health Study was conducted. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) summarizing the association between urinary ITCs levels and liver cancer risk. Compared to those with undetectable ITCs, nonsignificantly inverse association was observed among detectable (OR = 0.80; 95% CI = 0.51-1.26), below-median (OR = 0.76; 95% CI = 0.47-1.24), and above-median concentration (OR = 0.86; 95% CI = 0.52-1.41) with liver cancer risk. Similar patterns were observed when urinary ITCs levels were categorized into tertiles or quartiles. Although our study firstly focused on the association between urinary ITCs exposure and liver cancer risk, we did not find significant results. Future multicenter prospective, different population studies are warranted to validate our findings.
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