Assessment of thiol/disulfide homeostasis for prognostic follow-up of cholangiocarcinoma patients

Background:Cholangiocarcinoma(CCA)is a cancer type that builds in the bile ducts that carry digestive fluid,bile.These ducts connect the liver to the gallbladder and the small intestine.The disease is often diagnosed at an advanced stage,resulting in a low 5-year survival rate.This study aims to evaluate the concentrations of serum thiol/disulfide in CCA patients and healthy volunteers and investigate the association between oxidative activity and clinical and pathological characteristics in CCA patients.By examining the relationship between reduced thiol/disulfide measures and tumorigenesis of the disease,we can potentially identify an unfavourable prognosis in CCA patients.Methods:To assess the status of thiol/disulfide in the blood of Cholangiocarcinoma patients using a novel automated homeostasis assay,we recruited 55 individuals for this study(CCA patients,n=27;healthy volunteers,n=28).We measured the levels of serum total thiol(TT)(–SH+–S-S–),native thiol(NT)(–SH),and disulfide(DD)(–S-S–)in both the CCA group and the control group.Additionally,we calculated the ratio of thiol/disulfide(–SH/–S-S–).Results:We explored the relationship between oxidative activity and clinical and pathological characteristics in CCA patients.The study found no significant differences in age and sex between CCA patients and controls.NT and TT levels were higher in the control group compared to the CCA group.However,the disulfide level did not significantly differ between the two groups.Pearson's correlation matrix analysis revealed positive correlations between TT and NT levels and negative correlations between NT/TT%,DD level,and DD/TT%.Conclusion:Our findings suggest a statistical difference in serum thiol/disulfide parameters.As a marker of total oxidant status,thiol and disulfide levels have decreased in patients with CCA.However,no correlation was found between the tumour markers CEA and CA19-9 and thiol levels.A decrease in blood thiol and disulfide concentrations or the ratio of thiol to disulfide may indicate an increase in oxidative stress and decreased antioxidant capacity.As an indication of the prognosis of cholangiocarcinoma disease in the early period,it may be used to determine the effectiveness of medical interventions.The NT/TT%,disulfide/native thiol percentage,and DD/TT%ratios did not significantly change between the groups.Therefore,measuring serum thiol levels could be a helpful marker for assessing prognosis in the early stages of CCA.Nevertheless,further studies must validate these results and investigate the underlying mechanisms.

The superhydrophobic sponge decorated with Ni-Co double layered oxides with thiol modification for continuous oil/water separation

In this paper, the superhydrophobic polyurethane sponge(SS-PU) was facilely fabricated by etching with Jones reagent to bind the nanoparticles of Ni-Co double layered oxides(LDOs) on the surface, and following modification with n-dodecyl mercaptan(DDT). This method provides a new strategy to fabricate superhydrophobic PU sponge with a water contact angle of 157° for absorbing oil with low cost and in large scale. It exhibits the strong absorption capacity and highly selective characteristic for various kinds of oils which can be recycled by simple squeezing. Besides, the as-prepared sponge can deal with the floating and underwater oils, indicating its application value in handling oil spills and domestic oily wastewater. The good self-cleaning ability shows the potential to clear the pollutants due to the ultralow adhesion to water. Especially, the most important point is that the superhydrophobic sponge can continuously and effectively separate the oil/water mixture against the condition of turbulent disturbance by using our designed device system, which exhibit its good superhydrophobicity, strong stability.Furthermore, the SS-PU still maintained stable absorption performance after 150 cycle tests without losing capacity obviously, showing excellent durability in long-term operation and significant potential as an efficient absorbent in large-scale dispose of oily water.

Glutathione peroxidase mimicry of diphenyl diselenide: Plausible contribution of proteins’ thiols

Organoseleniums are a class of compounds attracting attention across the globe owing to their Glutathione peroxidase(GPx)mimicry,which confers on them a strong antioxidant activity.Diphenyl diselenide(DPDS)is an Organoselenium whose GPx mimetic property has been suggested to rely on the oxidation of non-protein or protein thiols critical to the activities of some sulfhydryl enzymes.This study,therefore investigated the GPx mimic/antioxidant property of DPDS as well as the role of thiols of two key sulfhydryl enzymes,cerebral Na^(+)/K^(+)-ATPase(sodium pump)and hepatic delta-aminolevulinic acid dehydratase(δ-ALAD)in the GPx mimicry of DPDS.Albino Wistar rats were euthanized,and the liver and brain were removed and used to assay for the effect of DPDS on lipid peroxidation induced by two prooxidants[Fe2^(+)(10μM)and H2O2,(1 mM)]as well as the activities of the sulfhydryl enzymes.The results revealed that DPDS profoundly(P<0.05)counteracted Fe2^(+)and H2O2-induced lipid peroxidation in the rats’hepatic and cerebral tissues.Furthermore,the results of assay systems for lipid peroxidation and sodium pump revealed that DPDS inhibited Na^(+)/K^(+)-ATPase and lipid peroxidation in the brain tissue homogenates in the same reaction system.A similar result was obtained in the assay system for lipid peroxidation and hepaticδ-ALAD as DPDS simultaneously inhibited the enzyme’s activity and lipid peroxidation.This suggests that the GPx mimetic property of DPDS may be linked to the enzymes’loss of activity,which further validates the suggestions that the enzymes’inhibition,as well as the antioxidant action of DPDS,rely on the oxidation of critical thiols of the enzymes.However,the GPx mimicry of DPDS should be investigated in the presence of thiol-blocking or oxidizing agents in biological systems in order to further ascertain the role of protein thiols.

Further Analytical Studies on a Mercuri Thiol Adduct Isolated from a Human Prostate Cancer Cell Line (LNCaP)

Thiols play vital roles in cellular metabolism knowledge of which may be important in the design of future anticancer drugs. Previous work on the composition of the thiols present in human cancer cell lines has shown the presence of an unknown low molecular weight species, deemed to be a “Conthiol”, which could be important in this respect. This was prepared and isolated from a human prostate cancer cell line (LNCaP) in the form of an adduct of 2-mercuri-4-nitrophenol;it accounts for 56.5% of the total cellular thiols present in this cell line. Initial LC-MS analysis of this adduct had indicated that the possible molecular weight of the thiol was in the region of 467 daltons. In further analytical studies to identify the thiol, attempts were made to release it from the adduct by passage through a Thiopropyl Sepharose6B column. LC-MS analysis of the column eluate revealed two components yielding negative ion fragments of 427 m/z and 449 m/z. Only the former component contained thiol, indicating that a breakdown and/or possible rearrangement of the Conthiol had occurred. Further investigations of the column thiol eluate using ICP-MS analysis showed that the sulfur content agreed with the spectrophotometric analysis result (Ellman assay) and that the molecule did not contain phosphate. Amino acid analyses of the eluate were negative. In an attempt to prevent the breakdown of the thiol released by the Thiopropyl Sepharose 6B column, the adduct was treated with 5% v/v bromine water prior to applying to the column. In this instance the thiol containing eluate obtained from the column was treated with an equimolar quantity of mercuric chloride forming a fresh adduct, RS-Hg-SR. LC-MS analysis of this mercurial adduct detected a negative ion fragment of 782 m/z which on further ionization gave a ladder like pattern showing loss of mass units of 58 in each rung. This would seem to suggest the presence of a repeat polymer like structure containing 5 monomers, which, plus the thiol atom, gives a possible formula weight of 322;probably revealing only a part of the unknown Conthiol molecule whose properties and formula weight do not correlate with any known cellular thiol. Further analysis of the thiol released from the adduct on the Thiopropyl Sepharose 6B column by Infra-red (FTIR) provided little information except to confirm the presence of the thiol group and C=O stretch bands together with the possibility of a lactam ring at 1651 and 1634 cm·s-1.

Studies on the Thiol Components of Isolated Nuclei

The thiol components of the nonhistone proteins prepared from isolated nuclei from rat liver, regenerating liver and hepatoma 223 cells have been investigated after reaction with radio labelled N-ethylmaleimide and 5-5’-dithiobis-(2-nitrobenzoic acid) (DTNB). The labelled adducts formed were examined by isoelectric focusing analysis in polyacrylamide gel and the distribution of the radiolabels within sliced portions of the gels determined. In the case of the 14C labelled NEM adduct the label was found to be spread amongst numerous protein components within the gel however, in the case of the 35S labelled DTNB adducts, only a small proportion of the label was found in the protein material which was retained in the acidic isoelectric point (pI) region of the gel. The bulk of the 35S labelled adduct (56% - 60%) was found to have migrated into the anode solution (10 mM phosphoric acid). This could be adsorbed onto a hydrophobic resin (XAD2) resin and eluted with methanol. Gel filtration chromatographic analysis of this adduct material on BioGel P2, (exclusion limit 1500 daltons) showed low molecular weight components to be present. Slightly different patterns were obtained for these nuclei, each containing several 35S components with molecular weights greater than the Ellman reagent itself. These 35S labelled thiol components did not contain any protein, peptide or amino acid components indicating strongly that a novel species of thiols could be present in these nuclei bound within the non-histone protein matrices.

Investigation of the Low Molecular Weight Thiol Composition in a Metastatic Prostate Cancer Cell Line (LNCaP) by LC-UV-MS and NMR after Labelling with the Ellman Reagent

The low molecular weight thiols present in the deproteinized extract of a prostate cancer cell line (LNCaP-FGC) were analysed after derivatization with the Ellman reagent (ESSE). The mixed disulphides formed (RSSE) were fractionated, characterized and quantified by liquid chromatography on a C-18 column using UV detection. This revealed the presence, in femtomoles per cell, of glutathione (8.30 ± 0.73), cysteine (2.71 ± 0.04) and cysteinylglycine (0.83 ± 0.10), accounting for the bulk of the thiol present. Further analysis of the cell extracts using a novel and sensitive mass spectrometry technique allowed the detection of low level of an additional derivative which was identified as cysteinylglycerate using NMRspectroscopy.

PEG-thiol修饰对金磁微粒胶体稳定性和抗吞噬能力的影响

目的探讨PEG-thiol修饰对GoldMag的磁学性能、体外悬浮稳定性和抗吞噬能力的影响。方法用PEG-thiol对GoldMag进行表面修饰,采用MR FSE序列T2W、GRE序列T2*W和T2mapping分别检测PEG-GoldMag和GoldMag的磁学性能;以Zeta电位仪检测两种纳米粒溶液的Zeta电位,紫外-可见光分光光度计检测两种纳米粒溶液不同时间点的吸光度,评估其悬浮稳定性。分别用两种纳米粒对小鼠单核巨噬细胞RAW 264.7进行体外标记,以普鲁士蓝染色检测两种纳米粒的细胞标记率,ICP-OES检测两种不同纳米粒标记的RAW 264.7细胞的细胞内铁含量,评估PEG修饰对GoldMag纳米粒体外抗吞噬能力的影响。结果GoldMag和PEG-GoldMag溶液的Zeta电位分别为-18.3mV和-39.5 mV。室温下静置100 min后,GoldMag和PEG-GoldMag溶液的相对吸光度分别为50%和88.5%;静置200min后两种溶液的相对吸光度分别为17%～18%和80%。两种纳米粒均能标记RAW 264.7细胞,GoldMag和PEG-GoldMag对RAW 264.7细胞的标记率分别为(85.3±2.1)%和(23.6±1.3)%。GoldMag和PEG-GoldMag标记的RAW264.7细胞的铁含量分别为(21.6±2.3)pg/细胞和(8.7±1.2)pg/细胞。在T2WI、T2*WI和T2mapping三种图像上,各浓度下PEG-GoldMag和GoldMag纳米粒凝胶的信号强度和T2值差异无统计学意义(P>0.05)。结论PEG-thiol修饰能显著改善GoldMag的悬浮稳定性和抗吞噬清除能力,且对其磁学性能无明显影响。

Thiol-free route to diaryl sulfides by Cu catalyzed coupling of sodium thiosulfate with aryl halides

A method for the synthesis of diaryl sulfides from aryl halides in polyethylene glycol was reported.Inodorous Na2S2O3·5H2O,which is readily available as a stable salt,is an effective source of sulfur in the presence of Cu I as catalyst.

Fe(NO_3)_3·9H_2O/Fe(HSO_4)_3:An efficient reagent system for the oxidation of alcohols,thiols and sulfides in the absence of solvent

Fe（NO3）3-9H2O/Fe（HSO4）3 was used as an efficient reagent system for the oxidation of alcohols to their corresponding carbonyl compounds. All reactions were performed in the absence of solvent in good to high yields. Under the same reaction conditions, thiols and sulfides were also converted to their corresponding disulfides and sulfoxides, respectively. 2007 Farhad Shirini. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Effect of Polyvinyl Alcohol with a Thiol End Group on the Properties of Polyacrylic Dispersions and Spray-dried Powder

The emulsion polymerization of highly shear-stable copolymer dispersions of methyl methacrylate and butyl acrylate were carried out using poly （vinyl alcohol） with a thiol end group （PVA-SH） as protective colloid. The dispersions can be transformed into corresponding redispersible powder via a spray dryingcooling process. On-line FT-IR monitoring shows that grafting polymer of PVA-g-PMMA was formed mainly at the stage-1 of the emulsion polymerization. TEM images show, the PVA-SH shell was fragmentary when adding SDS at initial stage and integrated when adding at particle growing or final stage. The particle size turns to be smaller when delayed adding SDS surfactant. Triethanolamine, a co-regulator of PVA-SH, controlled the M to 50 000-70 000 and reduced the PDI to 1.5-1.7. The acrylic dispersions with 0.8wt%-1.5wt% PVA-SH1 can be spray-dried into super dispersible polymer powder （SDPP）, which can easily disperse in water and form recon- stituted dispersions with an average particle size smaller than 1 micron.

A Mechanism Study of a Novel Acid-Activatable Michael-Type Fluorescent Probe for Thiols

A Michael addition is usually taken as a base-catalysed reaction. However, our synthesized 2-（quinolin-2-ylmethylene） malonic acid （QMA） as a Michael-type thiol fluorescent probe is acid-active in its sensing reaction. In this work, based on theoretic calculation and experimental study on 7-hydroxy-2-（quinolin-2-ylmethylene） malonic acid, we demonstrated that QMA as a Michael acceptor is acid-activatable, i.e., it works only in solutions at pH〈7, and the lower the pH of solutions is, the higher reactivity QMA has. In alkaline solution, the malonate QMA[-2H＋]2- cannot react with both RSand RSH. In contrast, 2-（quinolin-2- ylmethylene） malonic ester （QME）, the ester of QMA, reveal a contrary pH effect on its sensing reaction, that is, it can sense thiols in alkaline solutions but not in acidic solutions, like a normal base-catalysed Michael addition. The values of activation enthalpies from theoretic calculation support the above sensing behavior of two probes under different pH conditions. In acidic solutions, the protonated QMA is more highly reactive towards electrophilic attack over its other ionized states in neutral and alkaline solutions, and so can react with lowly reactive RSH. In contrast, there is a big energy barrier in the interaction of QME with RSH （acidic solutions）, and the reaction of QME with the highly reactive nucleophile RS- is a low activation energy process （in alkaline solutions）. Theoretic calculation reveals that the sensing reaction of QMA undergoes a 1,4-addition process with neutral thiols （RSH）, and a 1,2-addition pathway for the sensing reaction of QME with RS-. Therefore, the sensing reaction of QMA is an acid-catalysed Michael addition via a 1,4-addition, and a normal base-catalysed Michael addition via a 1,2-addition.

Synthesis of thiol-functionalized TiO_2 nanocomposite and photocatalytic degradation for PAH under visible light irradiation

In this paper, a thiol-functionalized nanophotocatalyst MPTES/TiO2 was first synthesized by one-pot method using P123 as a template. X-ray diffraction confirms the complete anatase crystalline of thiol-functionalized TiO2, N2 adsorption-desorption isotherm demonstrated that these materials possess high surface area and mesoporous structure. The results of XPS show that MPTES has been successfully polymerized in mesoporous structured TiO2. The photodegradation of phenanthrene （PHE） was investigated under visible light irradiation （λ 〉 420 nm） to evaluate the photocatalytic activity of these materials. Based the experiment results of GC-Mass analysis, a possible mechanism was proposed.

First Principle Study on the Rectification of Molecular Junctions Based on the Thiol-ended Oligosilane

The electron transport properties of various molecular junctions based on the thiol-ended oligosilane are investigated through density functional theory combined with non-equilibrium Green＇s function formalism. Our calculations show that oligosilanes doped by the phenyl and -C10H6 groups demonstrate better rectifying effect and their rectification ratios are up to 15.41 and 65.13 for their molecular junctions. The current-voltage （I-V） curves of all the Au/ modified oligosilane/Au systems in this work are illustrated by frontier molecular orbitals, transmission spectra and density of states under zero bias. And their rectifying behaviors are analyzed through transmission spectra.

Synthesis and <i>in Vitro</i>Biological Activities of 4,5-Disubstituted 1,2,4-Triazole-3-Thiols

Purpose: The triazole nucleus is an important part of the therapeutically interesting drug candidate as antimicrobial, analgesic, anticancer, anticonvulsant and anti-inflammatory agents. Methods: Therefore, in this study, twelve 4,5-disubstituted-1,2,4-triazole-3-thiols were synthesized by the reaction of substituted isothiocyanates and hydrazides using the common method of base catalysed intramolecular dehydrative cyclization of substituted thiosemicarbazides 3(a-f) and 4(a-f). The structures of these compounds were characterized by means of FT-IR, 1H-NMR, and elemental analysis data. All these compounds were screened for antibacterial, antioxidant, antitumor and cytotoxic activities. Results: Among these compounds: 5c, 5f and 6f were found active against gram positive cocci, the compounds 5a, 5b, 5d, 6a and 6f showed 85% free radical scavenging effect at 3 ppm when tested for antioxidant activity, 75% tumors inhibition was recorded using 5c, 5d and 6a and brine shrimps lethality assay declared 5a, 5b and 6d was 129.62 μg/ml, 161.577 μg/ml and 81.56 μg/ml respectively. Conclusion: Compounds carrying significant bioactivity can be further studied using animal models to establish their safety profile prior to initiating clinical trials.

Dynamic Thiol-Disulphide Homeostasis in Patients with Multiple Sclerosis

Objective: The aim of this study was to evaluate thiol-disulphide homeostasis in patients with Multiple Sclerosis (MS) during attack and remission. Design and Methods: A total of 82 patients admitted to our clinic were divided into 2 groups according to whether they are having an attack or not. Peripheral blood samples were taken from all patients and their native thiol, disulphide and total thiol concentrations were measured by a newly developed automated method. In addition, their disulphide/native thiol, disulphide/total thiol and native thiol/total thiol ratios were calculated. Results: The average disulphide values, disulphide/native thiol and disulphide/total thiol ratios of the patients with MS who were having an attack were found to be significantly higher compared to those in remission (p = 0.001, p = 0.001, p = 0.001, respectively). Conclusion: Our results have shown that thiol-disulphide balance was shifted to the oxidative area during the relapse. These homeostasis parameters, which can be easily measured by this newly developed method at low costs, may be important in terms of showing the disease activity and presenting the underlying mechanisms of the disease.

The Synthesis of Neodymium Complexes with Polymers Containing Thiol and Sulphoxide and Their Catalytic Activities

Introduction Polymers containing thiol and sulphoxide which have active—SH and—SO groups respectively, have wide application to biological, pharmaceutical, industrial and other chemical field and—SH and—SO groups are easy to form complexes with metals, so they have aroused an increasing interest of many authors. A large number of functional resins and corresponding metal complexes have been synthesized.

First Synthesis of 2a-Thiol Ether Analog of Docetaxel

A 2a-phenylthio ether analog 1c of docetaxel was synthesized for the first time from 10-deacetylbaccatin III 3 via double inversion of C-2 configuration. This compound showed very weak cytotoxicity toward several tumor cell lines.

Molecular Cloning of a Thiol Proteinase Inhibitor Gene and Its Expression in E.coli

A cDNA library was constructed with 1.5×10~6 pfu from rice immature seeds,fromwhich a cDNA clone for rice thiol proteinase inhibitor,oryzacystatin(OC),was isolated byscreening with synthesized oligodeoxynucleotide probe,which contained a 309bp open read-ing frame,84bp 5′-end noncoding region and a poly(A)signal AATAAA at the 3′-end fol-lowed by 31Nt poly(A).Then the coding region of OC was amplified and inserted into thedownstream of λP_RP_L promoter for thermal-inducible expression in E.coli.Shifting the cul-ture temperature from 30℃ to 42℃ led to a high level expression of OC,which exhibited adistinct band of 12.0 kDa and accounted for at least 10% of the total soluble proteins fromSDS-PAGE.The papain-inhibitory activity of the expressed OC was further confirmed.

Characterization of Formation Kinetics of Self-Assembled Thiol Monolayers on Gold by Electrochemical Impedance Spectroscopy

Self-assembled monolayers of octadecanethiol (ODT) on gold have been studied by electrochemical impedance spectroscopy (EIS). The fractional coverage has been examined as a function of immersion time of Au in ODT deposition solution. The fractional coverage exhibits two distinct adsorption steps: an initial rapid step followed by a slow one. The fractional coverage of ODT monolayer increases sharply from zero to more than 99% of its maximum within the first minute. However. it takes a day for the fractional coverage to approach its final value.

Resonance Light-Scattering Spectroscopy Study on Interaction between Gold Colloid and Thiol Containing Pharmaceutical

In this paper, we used resonance light\|scatter i ng (RLS) spectroscopy to study the interaction between thiol\|containing pharmac eutical and gold colloid. And for the first time, we proposed that this highly s ensitive, gold colloid\|based assay using RLS technique may have potential appli cation in detecting thiol\|containing substances.