INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2016
·Vol. 17
·期 11
·1934
·
IF 3.257
Yi Song,Rongxin Qin,Xichun Pan,Qin Ouyang,Tianyu Liu,Zhaoxia Zhai,Yingchun Chen,Bin Li,Hong Zhou
Previously, artesunate (AS) and dihydroartemisinine 7 (DHA7) were found to have antibacterial enhancement activity againstEscherichia colivia inhibition of the efflux pump AcrB. However, they were only effective againstE. colistandard strains. This study aimed to develop effective antibacterial enhancers based on the previous work. Our results demonstrate that 86 new antibacterial enhancers were designed via 3D-SAR and molecular docking. Among them, DHA27 had the best antibacterial enhancement activity. It could potentiate the antibacterial effects of ampicillin against not onlyE. colistandard strain but also clinical strains, and of β-lactam antibiotics, not non-β-lactamantibiotics. DHA27 could increase the accumulation of daunomycin and nile red withinE. coliATCC 35218, but did not increase the bacterial membrane permeability. DHA27 reducedacrB’s mRNA expression ofE. coliATCC 35218 in a dose-dependent manner, and its antibacterial enhancement activity is related to the degree ofacrBmRNA expression inE. coliclinical strains. The polypeptides from AcrB were obtained via molecular docking assay; the pre-incubated polypeptides could inhibit the activity of DHA27. Importantly, DHA27 had no cytotoxicity on cell proliferation. In conclusion, among newly designed antibacterial enhancers, DHA27 had favorable physical and pharmacological properties with no significant cytotoxicity at effective concentrations, and might serve as a potential efflux pump inhibitor in the future.Keywords:antibacterial enhancer;AcrB inhibitor;DHA27;molecular mechanism
研究领域:
微生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Genes & Diseases
·
2025
·
IF 9.4
Rongtian Pan,Renrui Zou,Ying Sui,Fei Wu,Dongfeng Wang,Yuan Zhang,Shaorong Yu
P21-activated kinase 1 (PAK1) plays an oncogenic role in colorectal cancer (CRC). However, the role of PAK1 in CRC progression remains incompletely understood. Here, we showed that PAK1 enhanced the mRNA stability of multiple oncogenic factors. We found that PAK1 promoted CRC initiation and progression as previously reported. Mechanistically, loss of PAK1 promoted mRNA decay and inhibited the expression of CD44, SAA1, MTOR, RPS6KB1, and EIF4G1, the factors involved in tumorigenesis in many cancers. Importantly, our results revealed that the PAK1 inhibitor, PF3758309, exhibited a profound synergistic effect with oxaliplatin in CRC. Collectively, our study unveils a novel function of PAK1 in CRC progression. Thus, these results highlight the potential of targeting PAK1 as a therapeutic strategy in CRC, particularly in combination with oxaliplatin.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Medicine
·
2024
·Vol. 19
·期 1
·1-12
·
IF 5.3
Zhou Hongyan,Hu Dingxin,Zhao Xian,Qin Siyuan,Nong Qiyao,Tian Yuan,Zhang Zunjian,Dong Haijuan,Zhang Pei,Xu Fengguo
Background Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study. Objective This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism. Methods The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics. Results In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 μM, 47 μM, 46.5 μM and 9.8 μM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism. Conclusion The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.
研究领域:
肿瘤学
·
药理学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Virulence
·
2025
·
IF 5.4
Yue Dong,Xiaona Liu,Shanshan Xiong,Mingyu Cao,Haojie Wu,Long Chen,Mengmeng Zhao,Yadan Zheng,Zhiyun Zhang,Yanyan Liu,Yanhua Li,Qianwei Qu,Chunliu Dong
The emergence and rapid development of antibiotic resistance poses a serious threat to global public health. Streptococcus suis (S. suis) is an important zoonotic pathogen, and the development of its antibiotic resistance has made the infections difficult to treat. The combination of non-antibiotic compounds with antibiotics is considered a promising strategy against multidrug-resistant bacteria. However, the mechanism by which metabolites act as antibiotic adjuvant remains unclear. Here, we found that guanosine metabolism was repressed in multidrug-resistant S. suis. Exogenous guanosine promoted the antibacterial effects of ceftiofur sodium (CEF) in vitro and in vivo. Furthermore, we demonstrated that exogenous guanosine promoted the biosynthesis of purine pathway, TCA cycle and bacterial respiration, which make bacteria more sensitive to the killing effect of antibacterial. In addition, the function of the cell membrane is affected by guanosine and the accumulation of antimicrobials in the bacteria increased. Bacterial-oxidative stress and DNA damage induced by guanosine is also one of the mechanisms by which the antibacterial effect is enhanced. These results suggest that guanosine is a promising adjuvant for antibacterial drugs and provide new theoretical basis for the clinical treatment of S. suis infection.
研究领域:
微生物学
·
感染病学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Microbiology
·
2020
·Vol. 5
·期 8
·1040-1050
·
IF 15.54
Song Meirong,Liu Yuan,Huang Xiaoyong,Ding Shuangyang,Wang Yang,Shen Jianzhong,Zhu Kui
The rapid emergence and dissemination of multidrug-resistant (MDR) bacterial pathogens pose a serious threat to global healthcare. One particular concern is the carbapenem-resistant Enterobacteriaceae (CRE), a group of Gram-negative bacteria that have evolved resistance to all or nearly all available antibiotics. Coupled with the fact of barren antibiotic development pipeline nowadays, a critical approach is to revitalize existing antibiotics using antibiotic adjuvants. We found a short linear antibacterial peptide (SLAP)-S25 carrying four non-natural amino acids of 2,4-diaminobutanoic acid (Dab), which solely showed weak antibacterial activity but boosted the efficacy of antibiotics covering all major classes, including cefepime, colistin, ofloxacin, rifampicin, tetracycline and vancomycin, against MDR Gram-negative pathogens. Mechanistic studies showed that SLAP-S25 triggers membrane damage by binding to both lipopolysaccharide (LPS) in the outer membrane and phosphatidylglycerol (PG) in bacterial cytoplasmic membrane, to potentiate antibiotic efficacy through collaborative strategies. Lastly, SLAP-S25 effectively enhanced the activity of colistin against MDR Escherichia coli -associated infections in three animal models. Our findings provide a potential therapeutic option using existing antibiotics in combination with broad-spectrum antibiotic adjuvants, to address the prevalent infections caused by MDR Gram-negative pathogens worldwide.
研究领域:
微生物学
·
感染病学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2015
·
IF 6.723
Yalong Bai,Yan Cui,George C. Paoli,Chunlei Shi,Dapeng Wang,Xianming Shi
Nanomaterials have been widely reported to affect the polymerase chain reaction (PCR). However, many studies in which these effects were observed were not comprehensive, and many of the proposed mechanisms have been primarily speculative. In this work, we used amino-modified silica-coated magnetic nanoparticles (ASMNPs, which can be collected very easily using an external magnetic field) as a model and compared them with gold nanoparticles (AuNPs, which have been studied extensively) to reveal the mechanisms by which nanoparticles affect PCR. We found that nanoparticles affect PCR primarily by binding to PCR components: (1) inhibition, (2) specifity, and (3) efficiency and yield of PCR are impacted. (1) Excess nanomaterials inhibit PCR by adsorbing to DNA polymerase, Mg2+, oligonucleotide primers, or DNA templates. Nanoparticle surface-active groups are particularly important to this effect. (2, a) Nanomaterials do not inhibit nonspecific amplification products caused by false priming as previously surmised. It was shown that relatively low concentrations of nanoparticles inhibited the amplification of long amplicons, and increasing the amount of nanoparticles inhibited the amplification of short amplicons. This concentration phenomenon appears to be the result of the formation of “joints” upon the adsorption of ASMNPs to DNA templates. (b) Nanomaterials are able to inhibit nonspecific amplification products due to incomplete amplification by preferably adsorbing single-stranded incomplete amplification products. (3) Some types of nanomaterials, such as AuNPs, enhance the efficiency and yield of PCR because these types of nanoparticles can adsorb to single-stranded DNA more strongly than to double-stranded DNA. This behavior assists in the rapid and thorough denaturation of double-stranded DNA templates. Therefore, the interaction between the surface of nanoparticles and PCR components is sufficient to explain most of the effects of nanoparticles on PCR.
研究领域:
分子生物学
·
纳米技术
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
RARE METALS
·
2025
·
IF 11
Du Juan,Ye Yong-Long,Xie Chao-Xiang,Luo Jia-Yong,Xu Kai-Wei,Sun Ya-Bing,Lai Liang-Xue,Ren Wen-Zhi,Guo Jun-Ming,Wu Ai-Guo,Liu Kai-Tai
Preoperative radiotherapy is a cornerstone of treatment for locally advanced rectal cancer, but intrinsic tumor cell radio resistance remains a primary obstacle limiting therapeutic efficacy. Herein, for the first time, we successfully constructed Hf 0.7 Ti 0.3 O 2 @PEG (HT) nanoparticles by introducing titanium (Ti) into hafnium dioxide (HfO 2 ). These HT nanoparticles synergistically combined the superior X-ray energy deposition capability of Hf and the efficient radiation-induced ROS generation performance of Ti, leading to a 1.4-fold higher ROS yield compared to HfO 2 . Moreover, HT nanoparticles significantly enhanced radiosensitivity by inducing extensive DNA damage and oxidative stress in tumor cells. This resulted in a tumor inhibition rate of 87.7% ± 2.1% in mouse models. Notably, HT nanoparticles enabled a marked reduction in radiation dose while maintaining therapeutic efficacy and safety, overcoming the major limitation of conventional HfO 2 nanoradiosensitizers in ROS generation. This study presents a promising new approach for rectal cancer radiotherapy and holds significant potential for improving outcomes in radioresistant rectal cancer.
研究领域:
肿瘤学
·
纳米医学
·
放射治疗
·
氧化应激
·
分子生物学
·
转化医学
✓ 已验证
产品关联
DOI
高影响因子
Small
·
2025
·
IF 12.1
Zhenhua Ge,Shengyi Yang,Zhenheng Zhang,Mingdong Hong,Mingzhu Liu,Ayesha Zia,Yurong Jiang,Bingsuo Zou,Libin Tang
High-sensitivity infrared photodetectors have attracted attention due to their broad applications. Photomultiplication is an ideal choice for high-sensitivity photodetectors since it can generate large photogenerated current under incident faint illumination, making them more user-friendly and cost-effective without any extra amplifier circuits. In this work, 2 wt.% acetic acid in methanol is optimized to treat the electron-accumulated ZnO layer in photodetector ITO/ZnO/PbS/Ag by increasing its interfacial oxygen vacancies, thus the interfacial band bends at the ZnO/PbS interface due to the accumulated charges under illumination. In this way, a high-gain photomultiplication-type photodetector ITO/ZnO/PbS/Ag, in which PbS colloidal quantum dots (CQDs) act as the active layer, is presented. As a result, a high responsivity of 524 A/W with a high external quantum efficiency of 66516% is achieved from the photodetector ITO/ZnO/PbS/Ag under 0.2 µW cm −2 980 nm illumination at -1 V. Further, a low turn-on voltage of 2 V is obtained from the upconverters ITO/ZnO/PbS(240 nm)/TAPC(50 nm)/CBP:Ir(ppy) 3 (60 nm)/BCP(20 nm)/LiF(1nm)/Al under 1.637 mW cm −2 980 nm illumination, exhibiting a photon-to-photon conversion efficiency of 11.08%. In addition, upconversion imaging through a single-pixel device and a 16 × 16 display array is demonstrated, implying its potential scalable applications. Therefore, it provides a promising and applicable pathway for high-performance upconverters.
研究领域:
材料科学
·
光电技术
·
纳米科技
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Chengyi He,Tianyue Wu,Jing Li,Xingyu Zhang,Zirui Zheng,Yuxia Gao,Chenhui Zhang,Tingjun Zhong,Yunfei Zhang,Fengpei Du
Pesticides are important agricultural production materials to ensure global food security, but the low utilization rate during pesticide application has caused a large amount of waste and environmental pollution. The use of pesticide carriers to deliver pesticides can help to prevent rapid release, assist in targeted release, and improve pesticide utilization. However, after completing pesticide delivery, less part of pesticide carriers has more functions and may remain in the environment, leading to material waste and environmental burden. Here, we propose that the environment-friendly carrier materials for pesticide delivery can synergistically enhance control efficacy with pesticides. Based on the bio-stimulant polyglutamic acid, amphiphilic polymers (mPEG-b-PLG) were constructed, and they assembled into nano micelle. After encapsulating prothioconazole (PTC) into the nano micelle through hydrogen bonding, electrostatic interactions and hydrophobic interactions through co-assembly, mPEG-b-PLG-PTC nanospheres with a diameter of approximately 120 nm were prepared. The nanospheres exhibit pH responsiveness for targeted release of pesticides, as well as excellent retention capacity, droplet bounce inhibition ability, and deposition capacity. At the same time, compared with commercial formulations, it has long-term antifungal properties and lower EC 50 , while its acute toxicity to human cells is lower, which can reduce cell apoptosis by about 63 %. It is also gratifying that the main root length, plant height, and fresh weight of wheat seedlings treated with mPEG-b-PLG have significantly improved, effectively applying carrier materials for synergistic effects. In summary, this work proposes a promising strategy to synergize pesticide carrier materials as active ingredients, providing new ideas for the integration of pesticide and fertilizer, improving pesticide utilization efficiency, and reducing environmental pollution.
研究领域:
农业科学
·
材料科学
·
环境科学
✓ 已验证
产品关联
DOI
高影响因子
Biosensors-Basel
·
2022
·Vol. 12
·期 11
·1053
·
IF 5.743
Changfei Duan,Yingjie Zhang,Peipei Li,Qiang Li,Wenbo Yu,Kai Wen,Sergei A. Eremin,Jianzhong Shen,Xuezhi Yu,Zhanhui Wang
Combinations of sulfonamides (SAs) and antibacterial synergists (ASGs) are frequently used for treating infectious diseases and promoting growth for animals, which cause potential hazards to food safety and human health. To realize the simultaneous detection of SAs and ASGs in food, a homogeneous and high-throughput screening dual-wavelength fluorescence polarization immunoassay (DWFPIA) was developed. In this study, three SAs tracers and three ASGs tracers were synthesized by fluoresceins with different linkers and paired with their corresponding monoclonal antibodies (mAbs), respectively. To achieve a high sensitivity and broad specificity, the combination of tracers SADMPM-HDF with the longest linker paring mAb 10E6 for SAs and tracer HaptenA-DSCA paring mAb 9C9 for ASGs were chosen for the development of DWFPIA, achieving surprising IC50values for 23 SAs below 100 μg L−1and 5 ASGs below 50 μg L−1. The accuracy of DWFPIA was applied in real milk samples by typical sulfamethazine (SMZ) and trimethoprim (TMP), with recoveries of 81.7–97.2% and 78.6–103.6%, and coefficient of variations (CVs) below 18.9%, which could be completed within 15 min, including sample pretreatment. We firstly developed a simultaneous screening DWFPIA, covering all of the SAs and ASGs used in clinic and providing a great application potential in food safety analysis.Keywords:sulfonamides;antibacterial synergists;dual-wavelength fluorescence polarization immunoassay;homogeneous detection
研究领域:
食品安全
·
免疫学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL LETTERS
·
2020
·
IF 1.467
Jiajia Hong,Xiaotang Hao,Tiantian Liu,Weiting Liu,Meiyi Xie,Mei Wang,Qian Xu,Bingyi Yang
A sensitive method termed rapid synergistic cloud point extraction (RS-CPE) combined with partial least squares (PLS) was developed for the extraction and simultaneous determination of trace amounts of phenol and three detrimental chlorophenols (CPs) via a microplate assay (MPA). In this study, n-pentanol was used as a novel synergistic inducer and the linear nonionic surfactant Tergitol 15-S-7 was used as an extractant. The whole process of RS-CPE was accomplished in a few minutes without the need for the time-consuming water- or ice-bath steps used in traditional cloud point extraction. An automated and high-throughput assay using a 96-well plate allowed for the simultaneous processing of multiple samples with low sample volume requirements (approximately 200 µL). However, synchronized determination of several CPs using MPA method was problematic because of spectral interferences. Fortunately, a multivariate calibration method using PLS was applied to circumvent these limitations. Under the optimum conditions, the linear dynamic concentration ranges were from 0.5 to 15 µg/mL for 2-chlorophenol and 0.5 to 20 µg/mL for the other analytes. The detection limit range was from 0.275 to 0.419 µg/mL. The enrichment factor was up to 15.4 fold. The developed methodology was successfully applied to quantitative analysis of phenol and three CPs in water samples with recoveries from 90.0% to 109%.
研究领域:
分析化学
·
环境科学
✓ 已验证
产品关联
DOI
高影响因子
CELLULOSE
·
2019
·Vol. 27
·期 2
·991-1007
·
IF 3.917
Wang Tingting,Xu Lei,Shen Huiying,Cao Xiuming,Wei Qufu,Ghiladi Reza A.,Wang Qingqing
Abstract With the aim of developing self-disinfecting materials to prevent pathogen transmission from surfaces to new hosts, here we report a simple and eco-friendly way to prepare photodynamic bacterial cellulose (BC) onto which the naturally-occurring photosensitizer hypocrellin (Hc) has been covalently appended. The resultant hypocrellin-grafted BC membrane (Hc-BC) was characterized by both physical (SEM, TGA, XRD) and spectroscopic (IR, diffuse reflectance UV–visible) methods, and the photosensitizer loading was found to be 155 nmol Hc/mg membrane. Indirect cytotoxicity tests employing mouse skin fibroblast (L929) cells showed no changes in cell viability, demonstrating that the Hc-BC membrane lacked any leachable components (e.g., unreacted coupling agent or hypocrellin) that could be cytotoxic to mammalian cells. The photodynamic antibacterial activity of Hc-BC was evaluated against gram-positive S. aureus (ATCC-6538) and gram-negative E. coli strain 8099. Our results demonstrated a 99.5 + % (2.7 log units) reduction in S. aureus upon illumination (Xe lamp, 65 ± 5 mW/cm 2 , 420–780 nm; 30 min), however, no statistically significant inactivation of E. coli was observed. Potentiation with potassium iodide was found to increase the antibacterial efficacy of Hc-BC against S. aureus to 99.997% (4.8 log units) at 10 mM KI, while E. coli was inactivated by 99.1% (2 log units) at 100 mM KI, with the increase in inactivation being attributable to short-lived reactive iodide radicals that are the major biocidal agents in the potentiation of Hc-BC by KI. Taken together, our findings demonstrated that hypocrellin-grafted bacterial cellulose is a sustainable material from which potent photodynamic antibacterial materials may be derived. Graphic abstract
研究领域:
材料科学
·
生物技术
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）