Synergistic effects of elevated homocysteine level and abnormal blood lipids on the onset of stroke

Hyperhomocysteinemia and abnormal blood lipids are independent risk factors for stroke. However, whether both factors exert a synergistic effect in the onset of stroke remains unclear. The present study is a retrospective analysJs of 2 089 cases of stroke and 2 089 control cases of simple in- tervertebral disk protrusion using a paired multivariate logistic regression method. Adjusting for known confounding variables including the patients＇ age, gender, smoking status, alcohol con- sumption status, patient and family medical history, and clinical biochemical indices, elevated ho- mocysteine level was related to the onset of stroke. Patients with elevated homocysteJne levels and abnormal blood lipids showed a 40.9 % increase in the risk for stroke compared to patients with normal homocysteine levels and blood lipids （odds ratio 1.409; 95% confidence interval 1.127-1.761）. These results indicate that elevated homocysteine and abnormal blood lipids exert synergistic effects in the onset of stroke. Patients with elevated homocysteine levels and abnormal blood lipids are predisposed to stroke.

Investigating the expression profiles of cysteine string proteins(CSPs)in cochlear tissue

Objective:This study aims to explore the expression patterns of cysteine string protein alpha(CSPα)and cysteine string protein beta(CSPβ)in the mammalian inner ear,with an emphasis on their temporal dynamics during the developmental stages of C57BL/6 mice.Methods:We utilized immunofluorescence staining to assess the localization and distribution of CSPαand CSPβwithin the inner ears of C57BL/6 mice and miniature pigs.Additionally,this method facilitated the investigation of their temporal expression profiles.Results:In adult C57BL/6 mice and miniature pigs,CSPαand CSPβwere identified in the cytoplasm of inner hair cells and spiral ganglion cells,yet were absent in outer hair cells.Both proteins were found to colocalize with Ctbp2 on the basal side of the cytoplasm in inner hair cells’basilar membrane.Expression of CSPαwas observed at the nerve fiber termini at the basilar membrane’s base of inner and outer hair cells 10 days postnatally in C57BL/6 mice.Notably,expression of both CSPαand CSPβin the cytoplasm of inner hair cells emerged on the 12th day post-birth,aligning with the timeline for registering cochlear potentials.The expression levels of both proteins increased with age,but were consistently absent in outer hair cells.Contrastingly,expression of CSPαand CSPβwas present in the cytoplasm of inner hair cells in miniature pigs as early as one day post-birth,yet remained absent in the three rows of outer hair cells.Conclusion:CSPαand CSPβexhibit predominant and specific expression in inner hair cells and spiral ganglion cells.A unique expression pattern was observed for CSPα,which was also present at the nerve fiber endings of both inner and outer hair cells.The developmental expression trajectory of CSPαand CSPβin mouse inner hair cells is characterized by an initial absence,followed by a gradual increase.Moreover,the timing of expression onset between mice and miniature pigs indicates distinct temporal dynamics,suggesting a potential role in auditory development.

Cysteine Supplementation to Parenteral Nutrition Improves Red Blood Cell Glutathione Concentrations of Critically Ill Preterm Neonates

Premature neonates have immature antioxidant enzyme systems rendering them more susceptible to oxidative injury. One key antioxidant is glutathione (GSH). The rate limiting amino acid (AA) in GSH production is thought to be cysteine. Critically ill premature neonates who are parenterally fed are often supplemented with additional cysteine, yet the need for cysteine and optimal dose is unknown. This was a prospective, un-blinded, three-group, randomized crossover study aimed to evaluate three doses of cysteine by analyzing red blood cell (RBC) GSH, plasma AA, weight, and nitrogen balance. Neonates were randomized to receive 72 hours of each of the following cysteine doses: 10 mg/g AA, 20 mg/g AA, and 40 mg/g AA. GSH, plasma AAs, weight, and nitrogen balance were evaluated at baseline (after 72 hours of 0 mg/g AA), day three, day six, and day nine. Sixteen patients completed all doses of cysteine, which resulted in significantly increased RBC GSH concentrations over baseline. Plasma concentrations of cystine, total and free cysteine/cystine, glycine and serine increased with cysteine dose. All cysteine doses were associated with adequate weight gain, and positive nitrogen balance. These results are contrary to more recent studies of cysteine effect on RBC GSH concentrations in preterm neonates and infants, but may reflect the severity of illness in our study subjects, where cysteine requirements may be increased.

The Construct of A Neutral Medium Applicable Electrochemiluminescent Sensor Based on the Chemical Modification of Cysteine and Luminol

In the phosphate buffer solution of pH＞7,the cysteine sensitized the electrochemiluminescence (ECL) of luminol.It could be modified on the surface of platinum electrode and furthermore adsorbing the luminol on its exterior to construct an ECL sensor.The ECL intensity of this sensor was strong enough and very stable.There wasn't obvious decrease of ECL intensity for thirty times of using in 48 hours with the relative standard deviation (RSD) of 0.98%.It could be used to determine some quenching effective molecules such as superoxide dismutase (SOD) with negative response upon the concentration range from 4.8 IU/ml to 57.6 IU/ml.

Electrochemical investigation on the film of L-cysteine self-assembled to nanoparticles on a gold electrode

The film contained L-cysteine and gold nanoparticles were provided by self-assembled monolayers (SAMs) and potentiostatic electrodeposition technology on the gold electrode. Two methods were used to study the film: In the first, cyclic voltammetry (CV) was used to inspect the functional groups of the film and the same time hydroquinone was chosen to be a probe molecule in the based solution;secondly, based on analytical technology of scanning electrochemical microscopy (SECM), the heterogeneous rate constant (keff) between solid phase (the modified electrode) and liquid phase (K3Fe(CN)6) was obtained. As a result, the better binary catalysis of hydroquinone was demonstrated and the heterogeneous rate constant (keff) is the greater at 8 h for L-cysteine self-assembled monolayers (SAMs).

Classification and Nomenclature of Plant Metallothionein-like Proteins Based on Their Cysteine Arrangement Patterns

随着植物基因组研究的进展 ,在基因文库和蛋白文库登录的植物类金属硫蛋白基因已超过 5 0个 ,接近金属硫蛋白总数的 1/ 3,而且有不断上升的趋势。鉴于目前植物类金属硫蛋白命名与分类随意性太大 ,很有必要建立一个统一合理的命名与分类法。对植物类金属硫蛋白一级结构进行详细分析后 ,发现该蛋白两端富含半胱氨酸的区域内半胱氨酸的排列方式颇具规律性 ,进而提出了以半胱氨酸排列方式为基础的分类及命名法 ,并阐述了采用这种方法的理由及其可行性。

S-Trityl-L-Cysteine诱导HL-60细胞有丝分裂阻滞和凋亡

目的研究S-三苯甲基-L-半胱氨酸(S-Trityl-L-Cysteine,STLC)对急性白血病HL-60细胞有丝分裂阻滞和凋亡的影响,初步探讨药物作用下HL-60细胞有丝分裂阻滞和凋亡间的因果关系。方法将HL-60细胞分成不加药对照组和不同剂量(1、2.5、5、10、50、100μmol/L)STLC加药组,药物作用一定时间后,台盼蓝染色观察HL-60细胞活性变化,MTT法检测其对HL-60细胞的抑制效应,免疫荧光染色观察细胞及其核的特征,流式细胞术分析细胞周期和亚二倍体峰的变化,Annexin-v/PI双染检测药物处理前后正常骨髓细胞凋亡比率。结果MTT和台盼蓝染色实验显示STLC抑制HL-60细胞生长并致其死亡;免疫荧光染色见核破裂及凋亡小体和细胞体积增大等典型有丝分裂灾变细胞凋亡现象;细胞周期和凋亡分析表明STLC致HL-60细胞凋亡比率与药物浓度和作用时间呈正相关,致G2/M期阻滞比率24h和48h随药物浓度增加而升高,而72h无明显变化,进一步研究发现STLC处理早期即可致G2/M期有丝分裂阻滞和凋亡的同时发生,撤除药物作用后有丝分裂阻滞呈可逆性恢复,STLC作用下正常骨髓细胞凋亡比率无明显变化。结论STLC诱导HL-60细胞阻滞在G2/M期并致其凋亡,显示较强的抗有丝分裂和抗肿瘤效果,药物处理早期有丝分裂阻滞和凋亡同时发生提示尚有该药物作用新机制的存在。

基于CEEMDAN-QPSO-BLS模型的径流预测研究

准确的径流预测是水资源优化配置和高效利用的前提,是制定防洪减灾决策的基础,然而受到人类活动、环境、气候等因素的影响,径流序列呈现出非线性、非稳态、多尺度变化的特点,这为径流的精准预测增加了难度。为提高径流预测的精准度和可信度,结合自适应噪声完备集合经验模态分解(Complete Ensemble Empirical Mode Decomposition with Adaptive Noise,CEEMDAN)方法,量子粒子群优化算法(Quantum Particle Swarm Optimization,QPSO)、宽度学习系统(Broad Learning System,BLS)模型,提出了一种基于CEEMDAN-QPSO-BLS组合式的径流预测模型。该组合模型首先使用CEEMDAN方法对原始径流信号进行分解,得到若干相对平稳的本征模态分量。其次利用QPSO算法对BLS模型的特征层节点组数、增强层节点组数和组内节点数进行寻优,得到最优的宽度学习网络拓扑结构,进而使用最优的QPSOBLS对多个稳态分量进行预测,并对预测分量进行重构,从而获得更高的预测精度。以黄河流域小浪底水库的日径流值为实验数据,将EMD-QPSO-BLS、QPSO-BLS作为CEEMDAN-QPSO-BLS的对比模型,并采用纳什效率系数(NSE)、均方根误差(RMSE)、平均绝对误差(MAE)和平均绝对百分比误差(MAPE)作为模型预测可信度和精准度的评价指标。实验表明,在预见期4天内,与QPSO-BLS、EMD-QPSO-BLS模型相比,CEEMDAN-QPSO-BLS的预测精准度分别提高了79.87%、19.80%,可信度分别提高了131.2%、10.98%,径流预测精度的提高,可为防洪抗旱保护人民生命财产和可持续发展提供决策支持。

Inhibition of cysteine protease papain by metal ions and polysulfide complexes,especially mercuric ion

Aim Cysteine proteases are closely associated with many human and non-human pathological processes and are potential targets for metal ions especially Hg^2＋ and the related species. In the present work, on the basis of to the general study on the effects of some metal ions on the activity of papain, a well-known representative of cysteine protease family, the inhibitory effects of Hg^2＋ and polysulfide complexes were studied. Results All the metal ions tested （Hg^2＋, Cu^2＋, Ag^＋, Au^3＋, Zn^2＋, Cd^2＋, Fe^3＋, Mn^2＋, Pb^2＋, Yb^3＋） inhibit the activity of papain anda good correlation between the inhibitory potency and softness-and-hardness was observed. Among the metals, Hg^2＋ was shown to be a potent inhibitor of papain with a Kiof 2 × 10^-7 mol·L^-1 among. Excessive amounts of glutathione and cysteine could reactivate the enzyme activity of papain deactivated by Hg^2＋. These evidences supported that Hg^2＋ might bind to the catalytic site of papain. Interestingly, Hg （Ⅱ） polysulfide complexes were for the first time found to inhibit papain with a Ki of 7 × 10^-6 mol·L^-1, whose potency is close to a well known mercury compound, thimerosal （Ki=2.7 × 10^-6）. In addition, Hg （Ⅱ） polysulfide complexes exhibit good permeability （ 1.9 × 10-5 cm· s^-1） to caco-2 monolayer. Conclusion These results suggested that mercury polysulfide complexes might be potential bioactive species in the interaction with cysteine proteases and other- SH-content proteins, providing a new clue to understand the mechanism of the toxicological and pharmacological actions of cinnabar and other insoluble mercury compounds.

Modeling the Cysteine Rich Domain of Plant Metallothionein-like Protein

With the progress of plant genome research, more than 50 plant metallothionein_like (MT_L) genes have been found, but only several MT_L proteins have been detected and no experimental structural information for MT_L proteins has been reported so far. Since detailed knowledge of the protein tertiary structure is required to understand its biological function, a method is needed to determine the structure of these proteins. In this study, the structural data of known mammal MT was used to determine the interatomic distance constraints of the CXC and CXXC motifs and the metal_sulfur chelating cluster. Then several possible MT conformations were predicted using a distance geometry algorithm. The statistical analysis was used to select those with much lower target function values and lower conformation energies as the predicted tertiary structural models of the cysteine_rich (CR) domains of these proteins. A suitable prediction method for modeling the CR domain of the plant MT_L protein was constructed. The accurately predicted result for the known structure of an MT protein from blue crab suggests that this method is practicable. The tertiary structures of CR domains of rape MT_L protein LSC54 was then modeled with this method.

Cytoprotective effects of amifostine,ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats

AIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity.

Selectively colorimetric detection of cysteine with triangular silver nanoprisms

Triangular silver nanoprisms were prepared and applied to make colorimetric detection of cysteine based on our findings that cysteine could lead to the blue shift of the dipole plasmon resonance absorption, but other 19 kinds of natural amino acids could not. Cysteine with a concentration 160 nmol/L can result in a color change that can be discerned with naked eyes.

Aberrant methylation of secreted protein acidic and rich in cysteine gene and its significance in gastric cancer

BACKGROUND Aberrant methylation in DNA regulatory regions could downregulate tumor suppressor genes without changing the sequences.However,our knowledge of secreted protein acidic and rich in cysteine(SPARC)and its aberrant methylation in gastric cancer(GC)is still inadequate.In the present research,we performed fundamental research to clarify the precise function of methylation on SPARC and its significance in GC.AIM To investigate promoter methylation and the effects of the SPARC gene in GC cells and tissues and to evaluate its clinical significance.METHODS Plasmids that overexpressed the SPARC gene were transfected into human GC BGC-823 cells;non-transfected cells were used as a control group(NC group).Quantitative real-time polymerase chain reaction and western blotting(WB)were then used to detect the expression of SPARC.Methylation-specific polymerase chain reaction was executed to analyze the gene promoter methylation status.Cell viability was measured by the cell counting kit-8 assay.The migration and invasion ability of cells were detected by scratch assays and transwell chamber assays,respectively.Cell cycle events and apoptosis were observed with a flow cytometer.RESULTS The expression of SPARC mRNA in GC tissues and cells was significantly lower and showed differing degrees of hypermethylation,respectively,than that in normal adjacent tissues and control cells.Treatment with 5-Aza-2’-deoxycytidine(5-Aza-Cdr)was able to restore the expression of SPARC and reverse promoter hypermethylation.Overexpression of the SPARC gene significantly inhibited proliferation,migration,and invasion of GC cells,while also causing cell cycle arrest and apoptosis;the NC group exhibited the opposite effects.CONCLUSION This study demonstrated that SPARC could function as a tumor suppressor and might be silenced by promoter hypermethylation.Furthermore,in GC cells,SPARC inhibited migration,invasion,and proliferation,caused cell cycle arrest at the G0/G1 phase,and promoted apoptosis.

Characterization of Cysteine Coated Magnetite Nanoparticles as MRI Contrast Agent

In this work,a kind of stabilized ferrofluid based on magnetite nanoparticles(mean core and its coating size about 21.9 and 1.6 nm,respectively)was synthesized via coprecipitation method.Cysteine was used as surfactant due to its proper conjunction to the surface of magnetite nanoparticles.Coating density and synthesized ferrofluids were characterized by using transmission electron microscope,thermogravimetry analysis,dynamic light scattering and fourier transform infrared spectroscopy techniques.Magnetic resonance imaging studies show that the synthesized ferrofluid can be used as a potential contrast enhancement agent especially for imaging lymphatic system.

Assay of Cysteine in Human Serum with Quinine-Ce^(4+) Chemiluminescence System

A sensitive and selective chemiluminescence (CL) method was developed for the determination of cysteine. This method is based on that the weak CL of cysteine oxidized with cerium (IV) can be greatly enhanced by quinine, and the total cysteine in human serum can be detected through simply diluting with water, showing a simpler analytical characteristic.

Flow-injection Determination of Cysteine,N-Acetyl Cysteine and Glutathione in Pharmaceuticals via Potassium Ferricyanide-Fe(Ⅲ) Spectrophotometric System

A simple flow injection spectrophotometric method is reported for the determination of cysteine,N-acetyl cysteine and glutathione based on the reduction of Fe（Ⅲ）/ferricyanide,the in situ reduced ions are reacted with unreduced portion of ferricyanide/Fe（Ⅲ） to form soluble Prussian blue,which is monitored at 735 nm.The calibration graphs are linear in the concentration ranges of（1―100）×10-6 mol/L for cysteine and N-acetyl cysteine,and（1―50）×10-6 mol/L for glutathione.The relative standard deviations of 1.8%,2.5% and 1.9% were found for eleven replicate analyses of 5×10-6 mol/L cysteine,N-acetyl cysteine and glutathione.The limits of detection（3σ blank） at 5×10-7 mol/L for cysteine,and 3×10-7 mol/L for N-acetyl cysteine and glutathione were obtained.The proposed method allowed 60 injections/h.The effects of common substances present in pharmaceuticals and human physiological fluids were examined.The method was applied to determining cysteine in pharmaceutical formulations with the recoveries in a range of 97% to 106% and the results obtained are agreed well with labeled values.

C57BL/6小鼠微小三毛滴虫的观察与种系发育分析

为鉴定从某外单位引进的C57BL/6小鼠粪样检测中发现的虫体种类,本试验对虫体进行形态学观察,并进行种系发育分析。取C57BL/6小鼠粪样涂片和瑞士染色后进行显微镜观察,提取粪样总DNA,根据三毛滴虫的16S rRNA进行PCR扩增后测序,运用MEGA11进行种系发育分析。显微镜观察发现,虫体符合微小三毛滴虫的形态学特征,测序发现微小三毛滴虫的基因序列与鼠三毛滴虫高度同源。

A Fluorescence Ratiometric Probe for Cysteine/Homocysteine and Its Application for Living Cell Imaging

A fluorescence ratiometric probe 1 for cysteine (Cys) and homocysteine (Hcy) has been rationally constructed based on intramolecular charge transfer (ICT) mechanism. Upon treatment with Cys/Hcy, probe 1 exhibited a fluorescence ratiometric response, with the emission wavelength displaying a large shift (from 526 nm to 446 nm). When 90 μM Cys were added, the emission ratios (I446/I526) of the probe changed dramatically from 0.01797 to 4.65472. The detection limit was also measured to be 0.18 μM (S/N = 3). The theoretical calculations have confirmed that the ratiometric response of probe 1 to Cys/Hcy is due to the inhibition of ICT process upon the reaction of probe 1 with Cys/Hcy. Furthermore, the fluorescence imaging experiments in living cell demonstrated that probe 1 was favourable for intracellular Cys/Hcy imaging.

An Elevated Dietary Cysteine to Methionine Ratio Does Not Impact on Dietary Methionine Efficiency and the Derived Optimal Methionine to Lysine Ratio in Diets for Meat Type Chicken

Optimal dietary methionine (Met) to lysine (Lys) ratio in presence of elevated dietary cysteine (Cys) levels was derived for meat type growing chicken. Twelve averaged weighed Ross 308 birds (each 50% of male and female per dietary treatment) were utilized in N balance trials. During starter (d10 - 20) and grower period (d25 - 35) five dietary treatments were used. Diets based on uniform mixtures of maize, wheat, soybean meal, potato protein and fish meal were supplemented with crystalline amino acids (AA). In diets 1 - 3, the dietary Cys to Met ratio was set as 85, 95 and 105 to 100, respectively. Diet 4, at a Cys to Met ratio of 105 to 100, was additionally supplemented with betaine (BET) as methyl group donor. Diets 1 - 4 were limiting in Met, diet 5 without L-Lys·HCl addition was limiting in Lys. Individual N-balance data per treatment were utilized for assessing protein quality and efficiency of dietary Met (Diets 1 - 4) or Lys (Diet 5) based on “Goettingen approach”. Elevated dietary Cys supply and supplemented BET failed to improve both dietary protein quality and Met efficiency. The established optimal Met to Lys ratio was on average 34 to 100 for growing chicken during starter and grower period, respectively.

Contribution of lysosomal cysteine proteases in cardiac and renal diseases

Cardiac and renal diseases(CRDs) are characterized by extensive remodeling of the extracellular matrix(ECM)architecture of the cardiorenal system. Among the many extracellular proteolytic enzymes present in cardiorenal cells and involved in ECM remodeling, members of the matrix metalloproteinase family and serine protease family have received the most attention. However, recent findings from laboratory and clinical studies have indicated that cysteine protease cathepsins also participate in pathogenesis of the heart and kidney.Deficiency and pharmacological inhibition of cathepsins have allowed their in vivo evaluation in the setting of pathological conditions. Furthermore, recent studiesevaluating the feasibility of cathepsins as a diagnostic tool have suggested that the serum levels of cathepsins L, S and K and their endogenous inhibitor cystatin C have predictive value as biomarkers in patients with coronary artery disease and heart and renal failure. The goal of this review is to highlight recent discoveries regarding the contributions of cathepsins in CRDs, particularly hypertensive heart failure and proteinuric kidney disease.