PHARMACEUTICAL CHEMISTRY JOURNAL
·
2024
·Vol. 57
·期 8
·1179-1188
·
IF 0.8
Pan Miao,Yuan Jia,Tang Qin,Wu Yajing,Peng Yu,Zhang Jinyin,Ma Hang,Li Xuegang
Antibiotic resistance is a major problem in the treatment of Helicobacter pylori (H. pylori). Berberine (BBR) has proven to be a promising alternative, though it is less effective than antibiotics. Structurally modified BBR might improve the anti-H. pylori activity. In this study, 8-octyl berberine (OBBR), a BBR derivative, was investigated for the activity and mechanism of action against H. pylori. The results showed that the anti-H. pylori activity of OBBR was significantly higher than that of BBR (about 64 times) and close to amoxicillin. Surprisingly, OBBR was not resistant to H. pylori after 45 generations of induction and showed synergistic effect with amoxicillin in vitro. Regarding the mechanism, OBBR changed the morphological structure of bacteria and caused the outgrowth of phosphatidylserine on the cell membrane, thereby increasing its permeability. Moreover, OBBR inhibited the urease activity, down-regulated the mRNA levels of flagellar genes flaA and flaB, and reduced the motility of H. pylori, thus inhibiting intra-gastric colonization. In an animal model of H. pylori infection, OBBR was found to have a certain effect on the clearance of H. pylori in mice. An excellent anti-H. pylori activity and low drug resistance of OBBR suggest that structural modification of the BBR scaffold may be a favorable approach to the development of promising antibiotics for the treatment of H. pylori.
研究领域:
微生物学
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药理学
·
药物化学
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传染病学
·
分子生物学
✓ 已验证
DOI
高影响因子
TALANTA
·
2020
·
IF 5.339
Jiao Zhou,Lei Han,Yu Ling,Lei Wang,Nian Bing Li,Hong Qun Luo
Relying on the specific coordination of Ag + and mismatched cytosine-cytosine (C–C), the high-efficiency inhibition of urease by Ag + ion, and the rapid and sensitive response of phenol red to pH, a sensitive ratiometric sensor has been designed for visual detection of human immunodeficiency virus gene (HIV DNA). This sensor utilizes the HIV DNA to initiate catalytic hairpin assembly (CHA) process, releasing Ag + to inhibit subsequent urease-catalyzed urea hydrolysis and prevent the pH of the solution from rising. The CHA process and the absorbance ratio of phenol red at different wavelengths (A 559 /A 432 ) amplify the signal, allowing the sensor to detect HIV DNA from 10 to 130 nM in a sensitive and highly selective manner with a low detection limit of 7.8 nM. In addition, this sensor can visually distinguish different concentrations of HIV DNA within a certain range and possesses a good recovery in 1% of serum samples, which will provide new ideas for biosensor design, dipstick test, blood test, and other clinical disease prevention.
研究领域:
生物技术
·
纳米技术
·
分析化学
·
分子生物学
·
医学诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Zili Yang,Liangmeng Wang,Zhixue Gao,Xiaomeng Hao,Ming Luo,Zili Yu,Jianguo Guan
Injectable chemically powered nanomotors may revolutionize biomedical technologies, but to date, it is a challenge for them to move autonomously in the blood circulation system and they are too large in size to break through the biological barriers therein. Herein, we report a general scalable colloidal chemistry synthesis approach for the fabrication of ultrasmall urease-powered Janus nanomotors (UPJNMs) that have a size (100–30 nm) meeting the requirement to break through the biological barriers in the blood circulation system and can efficiently move in body fluids with only endogenous urea as fuel. In our protocol, the two hemispheroid surfaces of eccentric Au−polystyrene nanoparticles are stepwise grafted with poly(ethylene glycol) brushes and ureases via selective etching and chemical coupling, respectively, forming the UPJNMs. The UPJNMs have lasting powerful mobility with ionic tolerance and positive chemotaxis, while they are able to be dispersed steadily and self-propelled in real body fluids, as well as demonstrate good biosafety and a long circulation time in the blood circulation system of mice. Thus, the as-prepared UPJNMs are promising as an active theranostics nanosystem for future biomedical applications.
研究领域:
纳米技术
·
生物医学工程
·
材料科学
·
生物物理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
·
IF 9.9
Wei Liu,Hongmei Nie,He Li,Ya Liu,Maoye Tian,Shuhuai Wang,Yuwei Yang,Wei Long
Design of engineered cells to target and deliver nanodrugs to the hard-to-reach regions has become an exciting research area. However, the limited penetration and retention of cell-based carriers in tumor tissue restricted their therapeutic efficiency. Inspired by the enhanced delivery behavior of mobile micro/nanomotors, herein, urease-powered platelet cell motors (PLT@Au@Urease) capable of active locomotion, tumor targeting, and radiosensitizers delivery were designed for boosting radiosensitization. The engineered platelet cell motors were constructed by in situ synthesis and loading of radiosensitizers gold nanoparticles in platelets, and then conjugation with urease as the engine. Under physiological concentration of urea, thrust around PLT@Au@Urease motors can be generated via the biocatalytic reactions of urease, leading to rapid tumor cell targeting and enhanced cellular uptake of radiosensitizers. Encouragingly, in comparison with engineered PLT without propulsion capability (PLT@Au), the self-propelled PLT@Au@Urease motors could significantly increase intracellular ROS level and exacerbate nuclear DNA damage induced by γ-radiation, resulting in a remarkably high sensitization enhancement rate (1.89) than that of PLT@Au (1.08). In vivo experiments with 4 T1-bearing mice demonstrated that PLT@Au@Urease in combination with radiation therapy possessed good antitumor performance. Such an intelligent cell motor would provide a promising approach to enhance radiosensitization and broaden the applications of cell motor-based delivery systems.
研究领域:
生物医学工程
·
纳米技术
·
癌症治疗
·
放射生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
·
2009
·
IF 3.075
Wen-Jun Mao,Peng-Cheng Lv,Lei Shi,Huan-Qiu Li,Hai-Liang Zhu
Fourteen metronidazole derivatives (compounds 3a – f and 4b – h ) have been synthesized by coupling of metronidazole and salicylic acid derivatives. All of them are reported for the first time. Their chemical structures are characterized by 1 H NMR, MS, and elemental analysis. The inhibitory activities against Helicobacter pylori urease have been investigated in vitro and many compounds have showed promising potential inhibitory activities of H. pylori urease. The effect of compounds 4b (IC 50 = 26 μM) and 4g (IC 50 = 12 μM) was comparable with that of acetohydroxamic acid, a well known H. pylori urease inhibitor used as a positive control. The experimental values of IC 50 showed that inhibitor was potent urease inhibitor. A docking analysis using the autodock 4.0 program could explain the inhibitory activities of compound 4g against H. pylori urease.
研究领域:
药物化学
·
药理学
·
微生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 15
·3373-3386
·
IF 7
Jiru Miao,Xiang Wu,Yue Fang,Mingzhu Zeng,Zhimao Huang,Mi Ouyang,Rong Wang
Catheter-associated urinary tract infections are one of the most common hospital-acquired infections. Encrustation formation results from infection of urease-producing bacteria and further complicates the situation. A typical sign of the initial onset of encrustation formation is the alkalization of the urine (pH up to 9–10). However, effective antibacterial strategies with high antimicrobial loading efficiency and pH-responsiveness of antimicrobial release are still lacking. In this study, we developed a poly(sulfobetaine methacrylate)-tannic acid (polySBMA-TA) hydrogel coating, which served as a universal, efficient, and responsive carrier for antimicrobials on urinary catheters. Common antimicrobials, including poly(vinylpyrrolidone)-iodine, copper ions, and nitrofurazone were loaded into the polySBMA-TA coating in high efficiency (several fold higher than that of the polySBMA coating), via the formation of multiple non-covalent interactions between the antimicrobials and hydrogel coating. The hydrogel coatings maintained good antibacterial properties under neutral conditions. More importantly, the pH-responsive release of antibacterial agents under alkaline conditions further enhanced the antibacterial activity of the coatings, which was advantageous for killing the urease-producing bacteria and preventing encrustation. In vitro and in vivo tests confirmed that the hydrogel coating has good biocompatibility, and could effectively inhibit bacterial colonization and encrustation formation. This study offers new opportunities for the utilization of a simple and universal antimicrobial-loaded hydrogel coating with smart pH-responsive properties to combat bacterial colonization and encrustation formation in urinary catheters.
研究领域:
生物材料
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生物医学工程
·
感染控制
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYST
·
2018
·Vol. 143
·期 12
·2901-2907
·
IF 3.864
Wenyue Xie,Lingli Lei,Meiling Tian,Zeying Zhang,Yingshuai Liu
A high-resolution colorimetric immunoassay platform has been developed based on enzyme-catalyzed multicolor generation and smartphone-assisted signal readout. The multi-color generation is accomplished in this system through the urease-catalyzed urea hydrolysis-induced color change of the pH indicator phenol red, from yellow to orange to red over pH 6.6 to 8.0. The color change is easily tailored by controlling the urease activity via the inhibitor silver ion (Ag+), the amount of which is in turn adjusted by alkaline phosphatase (ALP)-catalyzed ascorbic acid (AA) production. An ALP-linked colorimetric immunoassay is readily realized based on the above urease catalyzed multicolor generation system. Under optimal conditions, a limit of detection (LOD) of 1.73 ng mL−1 and a dynamic range from 0 to 18 ng mL−1 are achieved with rabbit IgG as a model analyte. A colored picture for each test is directly taken using a smartphone and then quantitatively analyzed with the free software ImageJ, eliminating the use of expensive and desktop equipment. The dose-dependent multicolor display is easier to distinguish with the naked eye for qualitative or semiquantitative detection over the traditional one-color system. The developed immunoassay scheme provides a promising platform for on-site testing or applications in resource-poor areas.
研究领域:
分析化学
·
生物传感
·
即时检测
·
移动健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Jue Zhang,Zhenqiang Shi,Chao He,Xin Song,Ye Yang,Shudong Sun,Weifeng Zhao,Changsheng Zhao
Adsorbents are usually used to remove uremic toxins for blood purification. However, the removal of urea is still an intractable problem, since no effective material has been found for urea removal by physical adsorption. Here, urease immobilized graphene oxide core@shell heparin-mimicking polymer (U-GO-HMP) beads were designed, which exhibited good urea removal ability with a removal amount of about 635 mg/g and a removal ratio of about 80% from urea solution. In addition, urea could be removed from collected dialysate and the removal ratio could reach 60% within 480 min. Beyond that, the U-GO-HMP beads also showed good reusability with sustainable relative activity after 5 cycles. Furthermore, the U-GO-HMP beads exhibited good blood compatibility with low hemolysis ratio, suppressed complement activation and contact activation, as well as increased clotting times. It is worthy believing that the U-GO-HMP beads may have great potential in the field of blood purification for urea removal.
研究领域:
生物医学工程
·
材料科学
·
血液透析
·
血液净化
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2024
·
IF 14.7
Yongkang Lai,Tinglin Zhang,Xiaojing Yin,Chunping Zhu,Yiqi Du,Zhaoshen Li,Jie Gao
Helicobacter pylori ( H. pylori) infection remains the leading cause of gastric adenocarcinoma, and its eradication primarily relies on the prolonged and intensive use of two antibiotics. However, antibiotic resistance has become a compelling health issue, leading to H. pylori eradication treatment failure worldwide. Additionally, the powerlessness of antibiotics against biofilms, as well as intracellular H. pylori and the long-term damage of antibiotics to the intestinal microbiota, have also created an urgent demand for antibiotic-free approaches. Herein, we describe an antibiotic-free, multifunctional copper-organic framework (HKUST-1) platform encased in a lipid layer comprising phosphatidic acid (PA), rhamnolipid (RHL), and cholesterol (CHOL), enveloped in chitosan (CS), and loaded in an ascorbyl palmitate (AP) hydrogel: AP@CS@Lip@HKUST-1. This platform targets inflammatory sites where H. pylori aggregates through electrostatic attraction. Then, hydrolysis by matrix metalloproteinases (MMPs) releases CS-encased nanoparticles, disrupting bacterial urease activity and membrane integrity. Additionally, RHL disperses biofilms, while PA promotes lysosomal acidification and activates host autophagy, enabling clearance of intracellular H. pylori . Furthermore, AP@CS@Lip@HKUST-1 alleviates inflammation and enhances mucosal repair through delayed Cu 2+ release while preserving the intestinal microbiota. Collectively, this platform presents an advanced therapeutic strategy for eradicating persistent H. pylori infection without inducing drug resistance.
研究领域:
胃肠病学
·
药学
·
微生物学
·
纳米技术
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2019
·
IF 8.355
Zhoujiang Chen,Tian Xia,Zhanlin Zhang,Songzhi Xie,Tao Wang,Xiaohong Li
The delivery of nanoparticles encounters a series of biological barriers from systemic clearance, tumor accumulation, cellular uptake and intracellular drug release. In this study we propose enzyme-powered nanomotors launched from intratumorally injected local depots to overcome these delivery barriers. Hydroxyapatite-embedded mesoporous silica nanoparticles ( [email protected] ) are prepared by formation of silica layers on CaCO 3 nanoparticles, transformation of CaCO 3 into Hap cores, and camptothecin (CPT) loading. Janus nanoparticles (JPs) are obtained by the selective deposition of gold layer on one side of [email protected] Janus nanomotors (JNMs) are constructed by separately grafting hyaluronic acid (HA) and urease on the opposite sides of JPs as the targeting moiety and power source, respectively. JNMs indicate self-propelled motion under the physiological concentration of urea (5 mM), and the motion is less disturbed in the dense tumor matrix. Despite no influence on the endocytosis mechanism, the self-propelled motion and HA-mediated targeting enhance the cellular uptake and cytotoxicity of JNMs. JNMs rapidly release the encapsulated CPT in the acidic endo/lysosomes of tumor cells (pH 5.0) while maintaining their integrity (CTP release <10%) in physiological conditions (pH 7.4) and tumor matrix (pH 6.5). In addition, JNMs are loaded into electrospun fiber fragments ( [email protected] ) for intratumoral administration to achieve a high retention and gradual release of JNMs in response to the slightly acidic tumor matrix (pH 6.5). The self-propelled motion promotes the deep penetration and even distribution of JNMs in tumors, dramatically enhancing the antitumor efficacy. Therefore, the launching of nanomotors from intratumoral depots is a feasible strategy to boost the antitumor efficacy via promoting the local accumulation, deep tumor penetration, tumor cell capture and intracellular release of chemotherapeutic drugs.
研究领域:
纳米技术
·
药学
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2022
·
IF 10.723
Ming Zhao,Zhenhai Chen,Li Hao,Huayao Chen,Xinhua Zhou,Hongjun Zhou
Inefficient use of traditional pesticides causes serious environmental pollution. Stimuli-responsive pesticide formulations improve the utilization efficiency of target pests and reduce harm to non-target organisms and the environment. Herein, multi-stimuli-responsive avermectin (AVM) polyurea microcapsules ( [email protected] ) are prepared by interfacial polymerization with modified carboxymethyl cellulose CMC-SS-NH 2 as the wall material and hexadecane as the temperature-responsive core. The microcapsules are 3.90 μm in size and the encapsulation efficiency of AVM is 88.23 %. The photostability of [email protected] is 5-times that of AVM solution. The insecticidal effect of AVM solution and AVM emulsifiable concentrate (EC) decreases to 13.3 % and 16.6 %, respectively, after UV irradiation for 180 min, whereas that of [email protected] still remains at 50.0 %. [email protected] has better foliar affinity and releases under the stimuli of temperature, glutathione , pH, cellulase , and urease . Hence, it has high insecticidal activity and biosafety. This smart controlled-release pesticide formulation provides a promising solution for green agriculture.
研究领域:
农业科学
·
环境科学
·
材料科学
·
化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）