Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke

It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke.Indeed,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue.Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently unclear.To simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke.We found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous acid.Further,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid hydrazide.Our results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation.However,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes.This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury.Lower levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-catenin.By transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear translocation.Altogether,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

Responsive mechanism of three novel hypochlorous acid fluorescent probes and solvent effect on their sensing performance

Optical properties and responsive mechanisms of three newly synthesized fluorescent probes for hypochlorous acid （HOC1） are investigated by employing time-dependent density functional theory. The computational results show that the absorption and emission properties of these probes change obviously when they react with hypochlorous acid. It is found that the probe FHZ has the best performance according to the probing behavior. Moreover, the responsive mechanisms of the probes are studied by analyzing the distributions of molecular orbitals and charge transfer, which are shown as the photon- induced electron transfer （PET） for FHZ and the intramolecular charge transfer OCT） for the other two probes. Specially, solvent effect on optical properties of the probe FHZ before and after reaction is studied within the polarizable continuum model （PCM）. It is shown that performance of the probe depends crucially on the solvent polarity. Our computational results agree well with the experimental measurement, and provide information for design of efficient two-photon fluorescent probes.

A ratiometric near-infrared fluorescent probe for the detection and monitoring of hypochlorous acid in rheumatoid arthritis model and real water samples

Recent studies revealed that the increased level of hypochlorous acid(HOCl)may be deemed to be one of the signs of chronic inflammatory joint disease.Accordingly,the development of effective methods for rapid and accurate detection or monitoring of HOCl in vivo is of great significance for further understanding the role of HOCl in rheumatoid arthritis(RA).Herein,a ratiometric near-infrared(NIR)fluorescent probe(PTA)was reported for the detection and monitoring of HOCl.In the presence of HOCl,the electron-rich S atom and C=C double bond of probe PTA were oxidized in sequence,resulting in the significant hypochromatic shift and decline of absorption spectra.Simultaneously,the intramolecular charge transfer(ICT)process of PTA is inhibited,causing the intrinsic fluorescence emission of PTA shift from 680 to 550 nm.PTA-based test paper strips were successfully prepared and applied to determinate HOCl in actual water samples by“naked eye”colorimetric method.PTA features NIR emission,large Stokes shift(200 nm),low cytotoxicity,high sensitivity(33.9 nM),and short response time(45 s),which enable it to be successfully utilized for imaging endogenous and exogenous HOCl in living zebrafish and mice.More importantly,PTA shows remarkable effectiveness for the monitoring of HOCl-mediated treatment response to RA.Consequently,PTA provides a new approach to further understand the role of HOCl in RA and evaluate the drug treatment efficiency of RA.

Hypochlorous Acid Induces Caspase Dependent Apoptosis in <i>Saccharomyces cerevisiae</i>

Hypochlorous acid (HOCl) is a strong oxidant produced by activated neutrophils via the myeloperoxidase (MPO) enzyme in order to fight against infections. Because of their antimicrobial and antiviral properties, stabilized HOCl solutions were produced to be used as a disinfectant and became a recommended disinfectant against COVID-19 by the US Environmental Protection Agency. Aberrant MPO enzyme activity results in abundant HOCl production which is related to the development and/or progression of several diseases including atherosclerosis, cardiovascular and neurodegenerative diseases. Previous studies investigating the effect of HOCl on the mode of cell death in different cell types reported that HOCl induces both apoptosis and necrosis depending on its concentration. However, the data on the apoptotic pathway triggered by HOCl is controversial. In this study, we investigated the mode of cell death induced by different concentrations of HOCl in Saccharomyces cerevisiae. Our data revealed that HOCl leads to cell death within 1 minute at 170 μM and above. At 340 μM, HOCl causes a rapid necrosis, while 170 μM HOCl leads to apoptosis. HOCl-induced apoptosis is mostly caspase dependent and Aif1 doesn’t have a significant role.

Hypochlorous Acid for Septic Abdominal Processes Using a Unique Negative Pressure Wound Therapy System:A Pilot Study

Background: Septic open abdomens occur in trauma, burn and surgery. Currently, multiple concentrations of hypochlorous acid solutions have effectively decreased the microbiotic burden in wounds. We hypothesized that Vashe?, a neutral hypochlorous acid solution (V-HOCL), would be safe as an intraperitoneal irrigation or washout disinfectant for septic open abdomens utilizing negative pressure wound therapy. Methods: This is a retrospective observational review of patients who required delayed abdominal closures after exploratory laparotomies. Group A (n = 8) had cyclical V-HOCL irrigation to their open abdomens combining AbtheraTM and V.A.C. Dressing System for negative pressure wound therapy with irrigation (NPWT-i) and Group B (n = 9) had intra-abdominal V-HOCL washouts. Results: Fifty percent of both groups had either septic or hemorrhagic shock on admission. Compared to Group B, Group A patients were older (median 50 vs 37 years), and had a median hospitalization of 28 vs 8 days, 4 times as many operations, more acute renal failure and co-morbidities. No statistically significant differences were detected be-tween the two treatment methods with the V-HOCL delivery and removal. Conclusion: There were no episodes of electrolyte imbalance, hypotension, hypertension, anaphylaxis, hemorrhage, visceral injury or systemic toxicity. V-HOCL with/without NPWT-i irrigation was a safe modality and tolerated well in this study.

Role of Lactic Acid Bacteria-Myeloperoxidase Synergy in Establishing and Maintaining the Normal Flora in Man

Lactic acid bacteria (LAB) are incapable of cytochrome synthesis and lack the heme electron transport mechanisms required for efficient oxygen-based metabolism. Consequently, LAB redox activity is flavoenzyme-based and metabolism is fermentative, producing lactic acid, and in many cases, hydrogen peroxide (H2O2). Despite this seeming metabolic limitation, LAB dominate in the normal flora of the mouth, vagina and lower gastrointestinal tract in man. Myeloperoxidase (MPO) is produced by the neutrophil leukocytes and monocytes that provide the innate phagocyte defense against infecting pathogens. MPO is unique in its ability to catalyze the H2O2-dependent oxidation of chloride (Cl-) to hypochlorite (OCl-). In turn, this OCl- directly reacts with a second H2O2 to produce singlet molecular oxygen (), a metastable electronic excitation state of oxygen with a microsecond lifetime that restricts its combustive reactivity within a submicron radius of its point of generation. Each day a healthy human adult produces about a hundred billion neutrophils containing about 4 femtograms MPO per neutrophil. Inflammatory states and G-CSF treatment increase both neutrophil production and the quantity of MPO per neutrophil. After a short circulating lifetime, neutrophils leave the blood and migrate into body spaces including the mouth, vagina, urinary tract, and gastrointestinal tract. Greater than a hundred thousand neutrophils are lavaged from the mouths of healthy humans;the quantity lavaged is proportional to the blood neutrophil count. MPO selectively and avidly binds to most Gram-positive and all Gram-negative bacteria tested, but LAB do not show significant MPO binding. Neutrophils migrating to normal flora sites release MPO into the LAB-conditioned milieu containing adequate acidity and H2O2 to support extra-phagocyte MPO microbicidal action. In combination, LAB plus MPO exert a potent synergistic microbicidal action against high MPO-binding microbes. This LAB-MPO synergy provides a mechanism for the establishment and maintenance of LAB in the normal flora of man.

负载铁系金属氧化物催化次氯酸钠降解酸性大红的实验研究

酸性大红是一种性能良好的染料,也是一种难以治理的工业废水,但由于它在水中溶解度较高,通常难以通过简单方法直接进行处理。次氯酸钠为多功能强氧化剂,安全无毒,但稳定性不高,对氧化活性的利用不够,对酸性大红染料的去除能力有限。通过负载铁系金属氧化物来催化次氯酸钠对酸性大红染料进行降解,从而高效率提供分子反应动能,提高其氧化性;考察pH值、催化剂投入量、反应时间、次氯酸钠用量、负载催化剂量等对酸性大红的降解作用,得出最佳处理条件。结果显示:①采用沉淀—负载法,随着负载量增加,硅藻土图谱上的CoFe_(2)O_(4)峰越来越明显,完成了有效负载;②在pH值为4、反应时间为25 min、催化剂投加量为0.7 g、负载催化剂量达到30%、次氯酸钠溶液为5 mL时,降解酸性大红效果最显著;③对比次氯酸钠和芬顿试剂氧化降解酸性大红发现,次氯酸钠对酸性大红的去除率比芬顿试剂高;④在实际生产废水降解实验中,使用负载铁系金属氧化物催化次氯酸钠降解酸性大红和COD的效果十分显著,用此方法对废水中的酸性大红和COD的去除率分别为90%和83%。

基于Gaussian、ECOSAR模型的紫外/次氯酸体系降解含卤阻燃剂的产物预测与毒性评估

含卤阻燃剂广泛应用于各类电子产品的生产,难降解且具有生物毒性.在生产和使用过程中,部分含卤阻燃剂会残留在水体并排放到水环境造成累积污染,威胁水环境安全,亟需探寻有效的降解去毒方法.本研究通过Gaussian与ECOSAR模型预测了四氯双酚A(TCBPA)、四溴双酚A(TBBPA)、十溴二苯乙烷(DBDPE)等3种典型含卤阻燃剂在紫外/次氯酸(UV/Cl)体系中的光催氧化降解路径与产物毒性.结果表明,UV/Cl体系中的含氯自由基(RCS)与羟基自由基(·OH)易攻击阻燃剂分子结构上键能较低、Fukui指数较高的位点,促使C—Cl键、C—Br键、C—C键等因为受到攻击而断裂,进而降解阻燃剂.同时,利用ECOSAR模型评估发现降解产物的急性毒性LC_(50)-96 h均低于100 mg·L^(-1),佐证了UV/Cl体系对含卤阻燃剂降解的有效性,并降低其环境危害.因此,采用Gaussian计算、ECOSAR模型相结合的分析方法,能够更加便捷地预测阻燃剂降解路径与产物毒性特征,为深入揭示UV/Cl体系光催氧化降解含卤阻燃剂机理提供新思路.

基于苯并噻唑的次氯酸荧光探针的合成及应用

该文以苯并噻唑衍生物和二氨基马来腈为原料,经醛胺缩合制备了一种高选择性的次氯酸(HClO)荧光探针(HADM)。探针HADM在活性氧和活性氮物种的干扰下能对HClO进行快速特异性识别(反应时间<3s)且具有良好的pH稳定性,同时可以观察到明显的绿色荧光。在优化条件下,探针的荧光强度与HClO的浓度呈良好的线性关系,相关系数R~2=0.9969,检测限为2.64×10^(-6)mol/L。红外、核磁、质谱以及荧光光谱研究表明,HClO可氧化探针的HC=N键,生成了醛基化合物,发射绿色的荧光。此外,探针还成功应用于可裸眼识别的HClO试纸和复杂水样的加标回收实验。该探针制备简单、响应快、稳定性及特异性强,可作为实际应用中一种有效的次氯酸检测工具。

次氯酸溶液的稳定性及对口腔组织刺激性的体外研究

目的:研究不同次氯酸(hypochlorous acid,HClO)溶液在模拟临床使用条件下的理化性能及杀灭粪肠球菌的稳定性,并检测HClO对口腔软、硬组织和细胞的相容性。方法:在模拟条件下监测2种不同生产工艺HClO样本的理化指标(有效氯浓度、氧化还原电位和pH值)变化,通过悬液定量杀菌试验测定不同浓度梯度HClO溶液的杀菌对数值。将牙髓组织、舌组织及牙本质块分别浸泡于PBS、100 ppm HClO、200 ppm HClO和3%NaClO 4组溶液中,用称重法和显微硬度仪检测其对软、硬组织的影响。通过CCK-8法检测HClO、NaClO及其10倍稀释液对人牙龈成纤维细胞的毒性作用。采用GraphPad PRIS 8.0软件对数据进行统计学分析。结果:在模拟条件下,HClO溶液的有效氯浓度随时间缓慢衰减,1个月内衰减程度<20 ppm,pH值及氧化还原电位值相对稳定。各样本浓度衰减前后其杀菌对数值均>5.00,HClO处理后的软组织重量及牙本质显微硬度值无显著改变(P>0.05),HClO及其10倍稀释液处理5 min的细胞活性远高于NaClO(P<0.001)。结论:HClO溶液的理化性能及杀菌稳定性良好,能满足临床需求。相比NaClO,HClO细胞毒性低、组织相容性好,有望成为牙髓再生领域安全高效的消毒产品。

基于噻吩环化反应的次氯酸探针的合成与荧光检测研究

次氯酸(HClO)作为体内重要的小分子活性氧(ROS)之一,是细胞内和细胞间的信号分子,同时也是生物体中调节生理和病理过程不可或缺的活性分子,监测其在生物体中的水平对于了解其生物学功能和病理效应至关重要。我们开发了一种用于特异性识别ClO^(-)的新型荧光探针,该探针以四氢-2-萘酮为骨架连接具有较大的斯托克斯位移的二氰基异氟尔酮,对于ClO^(-)的检测是通过ClO^(-)的氧化性作用于γ和δ碳之间的双键部分形成五元噻吩环。探针对于ClO^(-)的荧光响应具有高选择性和快速响应(3 min内),检出限低(0.02 nmol/L)。这项研究为传感ClO^(-)、细胞和活体动物成像提供了一种新的机制,进一步表明了这些探针在生物传感和生物成像中良好的应用前景。

HClO双光子荧光探针研究进展

次氯酸(hypochlorous acid,HClO)由于其高氧化性和反应活性,与神经退行性疾病、炎症、癌症等多种病理生理过程相关。在细胞水平上检测HClO对了解各种疾病的发病机制具有重要意义。因此,科学家设计并合成了多系列的小分子荧光探针用于细胞内HClO成像。本文综述了基于识别机制的双光子荧光探针的代表性案例,为相关工作者提供设计策略参考。

有机硒化合物荧光探针研究进展

荧光探针不仅可以识别目标分析物,而且可以通过荧光信号变化实现定量检测。近年来,含硒有机化合物作为荧光探针已广泛用于检测各种分析物。如金属阳离子和阴离子荧光检测、细胞成像和生物活性监测等。含硒荧光探针与含N-、O-、和S-的荧光探针相比较具有特定优势,其具有高的反应活性,包括氧化、消除以及与亲核试剂和亲电试剂的反应等。此外,含硒的化合物表现出低的氧化还原电位,根据这一性能开发出一系列特定功能的荧光探针,综述了含硒化合物对金属离子、硫醇(RSH)、活性氧物质(ROS)荧光探针的研究进展,并对该领域的发展前景进行了展望。

A ratiometric fluorescent probe for the detection of hypochlorous acid in living cells and zebra fish with a long wavelength emission

A ratiometric fluorescence probe,NClO,for the rapid and selective detection of HClO had been designed and synthesized based on a 1,8-naphthalimide derivative.Probe NClO displayed a red emission(λmax=615 nm).In the presence of HClO,the solution of probe NClO gave off a strong green fluorescence(λem,max=520 nm)with a rapid response(within seconds).This probe had been applied to image HClO in living cells and zebra fish.

次氯酸电解水处理对豆芽生长及品质的影响

为生产不易腐烂、微生物含量少且营养价值更高的绿豆芽和黄豆芽,将有效氯为25 mg/L的次氯酸电解水应用于绿豆、黄豆发芽,研究了次氯酸电解水对豆芽的发芽率、豆茎长、腐烂率、微生物总数及营养成分含量的影响。试验结果表明:次氯酸电解水的杀菌效果明显,与对照相比,次氯酸电解水处理的绿豆芽、黄豆芽表面的菌落总数分别减少10.23%、18.22%,肠杆菌数分别降低了11.39%、19.41%,腐烂率显著降低11.54%、36.05%。次氯酸电解水对豆芽品质无不良影响,相较于对照组,次氯酸电解水处理的绿豆芽与黄豆芽发芽率与豆茎长基本持平。处理组绿豆芽与黄豆芽的抗坏血酸含量分别显著提高了49.85%、49.21%,总酚含量分别提高了23.14%、11.23%。由此可见,次氯酸电解水可一定程度上延缓豆芽的品质劣变,为改善家庭和工业生产的豆芽品质提供了理论支持。

A mitochondria-targeted fluorescent probe for ratiometric detection of hypochlorite in living cells

Hypochlorous acid（HOCl） plays a vital role in many physiological and pathological processes as one of reactive oxygen species（ROS）. Developing highly sensitive and selective methods for HOCl detection is of significant interest. In this work, we developed a benzothiazole based probe 1 for ratiometric fluorescence detection of hypochlorite in living cells. The probe can detect HOCl with high selectivity, fast response（within 30 s） as well as low detection limit（0.18 mmol/L）. Fluorescence co-localization studies demonstrated that probe 1 was a mitochondria-targeted fluorescent probe. Furthermore, confocal fluorescence images of He La cell indicated that probe 1 could be used for monitoring intracellular HOCl in living cells. Finally, test strips experiment suggests that the probe 1 can detect the hypochlorous acid in tap water accompanied by remarkable color change.

Quantifying Hypochlorous Acid Concentration in Environmental Water Using Smartphone Colorimetry

In this study,we developed an eff ective method to detect hypochlorite acid(HClO)by using methylene blue(MB)derivative(BPY1).BPY1 was selectively oxidized through HClO,and the solution color changed from colorless to blue.In the presence of HClO,the ultraviolet–visible(UV–vis)spectra and concentration of HClO had a linear relationship with a detection limit of 0.5μM.Furthermore,a test paper for HClO monitoring was successfully prepared using the BPY1 probe,and the observed detection limit by the naked eye was estimated at 5μM.Additionally,using the BPY1 probe,HClO could also be detected through smartphone colorimetry,and the method showed a good recovery ranging from 98.7 to 104.0%for HClO detection in an actual water sample.Especially for developing countries,such a low-cost and highly sensitive detection method provides a simple and practical method for monitoring HClO in water.

Effect of pyrolysis on Zhaotong lignite oxidation with aqueous sodium hypochlorite

The pyrolysis treatment of lignites could remove thermal-unstable aliphatic structures but enrich aromatic structures in resulting pyrolysis residues,which would facilitate producing benzene polycarboxylic acids(BPCAs).Herein,the demineralized Zhaotong lignite(DZL)was pyrolyzed at 250-550℃ to afford the corresponding pyrolysis residues.Subsequently,DZL and its pyrolysis residues were subjected to oxidation with aqueous sodium hypochlorite.By XRD,FTIR,and element analyses,it was found that the content and polycondensation degree of aromatic structures simultaneously increased with increasing pyrolysis temperature.Furthermore,the yield and selectivity of BPCAs both increased along with raising pyrolysis temperature in resulting products from fully oxidation of DZL and its pyrolysis residues.Based on the distribution of BPCAs,peri-condensed aromatic structures were dominant in DZL and its DPRs,and obviously increased with increasing pyrolysis temperature.More interestingly,good correlation was found between the yield of BPCAs and aromaticity parameters.Meanwhile,the yield of benzenepentacrboxylic acid was well associated with polycondensation degree parameters.

一种可视化次氯酸荧光探针的开发及在环境水样中的应用

针对环境样本特别是生活用水中残留消毒剂成分次氯酸(HOCl)检测方法烦琐这一问题,从经典染料亚甲基蓝入手,开发了可对HOCl进行响应的探针DHUOCl-C。核磁共振氢谱和高分辨质谱的结果表明,已成功制备出DHUOCl-C探针,荧光光谱和吸收光谱等性能测试结果表明,探针不仅响应灵敏(检测限低至1.78 nmol/L),并具备较好的选择性。DHUOCl-C仅专一性地与HOCl响应,不与其他环境水样中可能存在的阴离子、阳离子和氨基酸等物质响应;与HOCl响应后不仅会有明显的荧光变化,5μmol/L的HOCl即可使探针发生肉眼可见的显著颜色变化。在真实环境样本的测试中发现,可通过借助荧光或肉眼直接观察体系的颜色变化,从而对不同来源水样中的HOCl进行识别和检测,结果表明探针可满足生活用水中HOCl便捷化检测的需求。

0.01%次氯酸在白内障超声乳化术前应用的安全性和有效性

目的:评估0.01%次氯酸作为白内障超声乳化术前结膜囊消毒剂的效果和对眼表的影响。方法:随机对照临床试验。285例单眼拟行白内障超声乳化手术的患者随机分为次氯酸组和聚维酮碘组,在消毒前后取结膜囊拭子,使用血琼脂培养基和巧克力琼脂培养基分别进行细菌培养和菌落形成能力(CFUs)测试。所有患者在消毒后2 h,1 d和1 wk接受眼部症状评分、疼痛程度评分的评估,并行角膜荧光素染色、眼红指数、泪河高度和非接触式泪膜破裂时间(NIBUT)检查,记录术后眼内炎的发生率。结果:使用0.01%次氯酸进行结膜囊消毒可显著降低细菌培养阳性率和CFUs,与消毒前相比有差异(均P<0.01),次氯酸消毒能力与聚维酮碘相当(χ2=0.811,P=0.368)。次氯酸组患者眼部症状评分和疼痛程度评分显著低于聚维酮碘组(均P<0.01)。次氯酸组角膜荧光素染色评分、眼红指数均显著低于聚维酮碘组(均P<0.01)。两组患者均无眼内炎发生。结论:0.01%次氯酸作为结膜囊消毒剂安全有效,且患者的不适和对眼表的损伤较小。