AMB Express
·
2022
·Vol. 12
·期 1
·1-15
·
IF 4.126
Liu Shasha,She Pengfei,Li Zehao,Li Yimin,Yang Yifan,Li Linhui,Zhou Linying,Wu Yong
According to a 2019 report from the Centers of Disease Control and Prevention (CDC), methicillin-resistant Staphylococcus aureus (MRSA) was listed as one of the “serious threats” that had become a global public challenge in hospitals and community. Biofilm-associated infections and refractory persisters of S. aureus also impede the effectiveness of conventional antibiotics that have greatly increased difficulty in clinical therapy. There is an urgent need to develop new antimicrobials with antibiofilm and anti-persister capacities, and drug repurposing is the most effective and most economical solution to the problem. The present study profiles the antimicrobial activity of ceritinib, a tyrosine kinase inhibitor, against S. aureus in vitro and in vivo. We investigated the antimicrobial efficacy of ceritinib against planktonic and persistent S. aureus by a time-killing kinetics assay. Then, antibiofilm effect of ceritinib was assessed by crystal violet staining and laser confocal microscope observation. Ceritinib showed biofilm inhibition and mature biofilm eradication, and possesses robust bactericidal activity against S. aureus persisters. We also evaluated antimicrobial efficacy in vivo using a subcutaneous abscess infection model. Ceritinib ameliorated infection in a subcutaneous abscess mouse model and only showed negligible systemic toxicity in vivo. Mechanism exploration was conducted by transmission electron microscopy, fluorescently labeled giant unilamellar vesicle assays, and a series of fluorescent dyes. In conclusion, we find ceritinib represents potential bactericidal activity against MRSA by disrupting cell membrane integrity and inducing reactive oxygen species production, suggesting ceritinib has the potential to treat MRSA-related infections.
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Frontiers in Medicine
·
2023
·
IF 3.9
Ding Ying,Liu Yu,Zhang Li,Deng Yinqian,Chen Huanyu,Lan Xiaoli,Jiang Dawei,Cao Wei
Background: Early detection of kidney diseases can be challenging as conventional methods such as blood tests or imaging techniques (computed tomography (CT), magnetic resonance imaging (MRI), or ultrasonography) may be insufficient to assess renal function. A single-photon emission CT (SPECT) renal scan provides a means of measuring glomerular filtration rates (GFRs), but its diagnostic accuracy is limited due to its planar imaging modality and semi-quantification property. In this study, we aimed to improve the accuracy of GFR measurement by preparing a positron emission tonometry (PET) tracer 68Ga-Ethylenediaminetetraacetic acid (68Ga-EDTA) and comprehensively evaluating its performance in healthy mice and murine models of renal dysfunction.Methods: Dynamic PET scans were performed in healthy C57BL/6 mice and in models of renal injury, including acute kidney injury (AKI) and unilateral ureter obstruction (UUO) using 68Ga-EDTA. In a 30-min dynamic scan, PET images and time-activity curves (TACs) were acquired. Renal function and GFR values were measured using renograms and validated through serum renal function parameters, biodistribution results, and pathological staining.Results: 68Ga-EDTA dynamic PET imaging quantitatively captured the tracer elimination process. The calculated GFR values were 0.25 ± 0.02 ml/min in healthy mice, 0.01 ± 0.00 ml/min in AKI mice, and 0.25 ± 0.04, 0.29 ± 0.03 and 0.24 ± 0.01 ml/min in UUO mice, respectively. Furthermore, 68Ga-EDTA dynamic PET imaging and GFRPET were able to differentiate mild renal impairment before serum parameters indicated any changes.Conclusions: Our findings demonstrate that 68Ga-EDTA dynamic PET provides a reliable and precise means of evaluating renal function in two murine models of renal injury. These results hold promise for the widespread clinical application of 68Ga-EDTA dynamic PET in the near future.
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Journal of Neuroinflammation
·
2021
·Vol. 18
·期 1
·1-19
·
IF 8.322
Jiang Li,Zhang Yixin,Jing Feng,Long Ting,Qin Guangcheng,Zhang Dunke,Chen Lixue,Zhou Jiying
Background Central sensitization is an important pathophysiological mechanism of chronic migraine (CM). According to our previous studies, microglial activation and subsequent inflammation in the trigeminal nucleus caudalis (TNC) contribute to the central sensitization. The P2X7 receptor (P2X7R) is a purinergic receptor expressed in microglia and participates in central sensitization in chronic pain, but its role in CM is unclear. Numerous studies have shown that P2X7R regulates the level of autophagy and that autophagy affects the microglial activation and inflammation. Recently, autophagy has been shown to be involved in neuropathic pain, but there is no information about autophagy in CM. Therefore, the current study investigated the role of P2X7R in CM and its underlying mechanism, focusing on autophagy regulation.Methods The CM model was established by repeated intraperitoneal injection of nitroglycerin (NTG) in mice. A Von Frey filament and radiant heat were used to assess the mechanical and thermal hypersensitivity. Western blotting and immunofluorescence assays were performed to detect the expression of P2X7R, autophagy-related proteins, and the cellular localization of P2X7R. To determine the role of P2X7R and autophagy in CM, we detected the effects of the autophagy inducer, rapamycin (RAPA) and P2X7R antagonist, Brilliant Blue G (BBG), on pain behavior and the expression of calcitonin gene-related peptide (CGRP) and c-fos. In addition, the effect of RAPA and BBG on microglial activation and subsequent inflammation were investigated.Results The expression of P2X7R was increased and was mainly colocalized with microglia in the TNC following recurrent NTG administration. The autophagic flux was blocked in CM, which was characterized by upregulated LC3-II, and accumulated autophagy substrate protein, p62. RAPA significantly improved the basal rather than acute hyperalgesia. BBG alleviated both basal and acute hyperalgesia. BBG activated the level of autophagic flux. RAPA and BBG inhibited the activation of microglia, limited the inflammatory response, and reduced the expression of CGRP and c-fos.Conclusion sOur results demonstrate the dysfunction of the autophagic process in CM. Activated autophagy may have a preventive effect on migraine chronification. P2X7R contributes to central sensitization through mediating autophagy regulation and might become a potential target for CM.
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Nanoscale Research Letters
·
2014
·Vol. 9
·期 1
·1-8
·
IF 2.481
Liu Zhong-Tao,Xiong Li,Liu Zhi-Peng,Miao Xiong-Ying,Lin Liang-Wu,Wen Yu
This study aimed to compare the inhibitory effects of photosensitizers loaded in hollow silica nanoparticles and conventional photosensitizers on HepG2 human hepatoma cell proliferation and determine the underlying mechanisms. Photosensitizers (conventional Photosan-II or nanoscale Photosan-II) were administered to in vitro cultured HepG2 hepatoma cells and treated by photodynamic therapy (PDT) with various levels of light exposure. To assess photosensitizers' effects, cell viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, apoptotic and necrotic cells were measured by flow cytometry and the expression of caspase-3 and caspase-9 evaluated by western blot. Finally, the in vivo effects of nanoscale and conventional photosensitizers on liver cancer were assessed in nude mice. Nanoscale Photosan-II significantly inhibited hepatoma cell viability in a concentration-dependent manner and this effect was more pronounced with high laser doses. Moreover, nanoscale photosensitizers performed better than the conventional ones under the same experimental conditions (p < 0.05). Flow cytometry data demonstrated that laser-induced cell death was markedly increased after treatment with nanoscale Photosan-II in comparison with free Photosan-II (p < 0.05). Activated caspase-3 and caspase-9 levels were significantly higher in cells treated with Photosan-II loaded in silica nanoparticles than free Photosan-II (p < 0.05). Accordingly, treatment with nanoscale photosensitizers resulted in improved outcomes (tumor volume) in a mouse model of liver cancer, in comparison with conventional photosensitizers. Hollow silica nanoparticles containing photosensitizer more efficiently inhibited hepatoma cells than photosensitizer alone, through induction of apoptosis, both in vivo and in vitro.
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RSC Advances
·
2019
·Vol. 9
·期 35
·19973-19982
·
IF 3.049
Yusif Mohammed Mukhtar,Kaili Wang,Ran Li,Wenwen Deng,Michael Adu-Frimpong,Huiyun Zhang,Kangyi Zhang,Chenlu Gu,Ximing Xu,Jiangnan Yu
Hepatocellular carcinoma (HC) and glioblastoma (GBA) are the most commonly aggressive malignant liver and brain tumors. Based on an established method for the synthesis of amide, two novel analogues (4 and 5) of (S)-perillic acid were synthesized and their structures were affirmed using nuclear magnetic resonance spectroscopic analysis. An MTT cytotoxic assay showed that our derivatives (4 and 5) demonstrated a substantial anti-proliferative effect against HC (HepG2) and GBA (U251) cell lines. Particularly, compound 5 showed growth inhibitory (IC50) effects on U251 (IC50 = 3.10 ± 0.12 μg mL−1) and HepG2 cells (IC50 = 1.49 ± 0.43 μg mL−1), which fall within the acceptable standard recommended by the National institute of cancer (Bethesda, MD, USA) for the selection of anticancer drug candidates. Consequently, we assessed the in vivo antitumor and organ/tissue toxicity of 4, 5 and 5-fluorouracil (5-FU) in hepatoma H22-inoculated mice. The results obtained indicated remarkable tumor growth inhibition with no substantial toxicological effects on the mice and the organs/tissues in the treated groups compared well with the control.
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MOLECULES
·
2019
·Vol. 24
·期 10
·2024
·
IF 3.06
Yi He,Hongli Li,Xiangyu Zheng,Mingwei Yuan,Renyu Yang,Minglong Yuan,Cui Yang
In order to enrich the types ofPanax notoginsengsaponins (PNS) sustained-release preparations and provide a new research idea for the research and development of traditional Chinese medicine sustained-release formulations, a series ofPanax notoginseng saponinsmicrospheres was prepared by a double emulsion method using a series of degradable amphiphilic macromolecule materials polyethylene glycol monomethyl ether-polymandelic acid (mPEG-PMA) as carrier. The structure and molecular weight of the series of mPEG-PMA were determined by nuclear magnetic resonance spectroscopy (1HNMR) and gel chromatography (GPC). The results of the appearance, particle size, drug loading and encapsulation efficiency of the drug-loaded microspheres show that the mPEG10000-PMA (1:9) material is more suitable as a carrier for loading the total saponins ofPanax notoginseng. The particle size was 2.51 ± 0.21 μm, the drug loading and encapsulation efficiency were 8.54 ± 0.16% and 47.25 ± 1.64%, respectively. The drug-loaded microspheres were used for in vitro release and degradation experiments to investigate the degradation and sustained release behaviour of the drug-loaded microspheres. The biocompatibility of the microspheres was studied by haemolytic, anticoagulant and cytotoxicity experiments. The pharmacological activity of the microspheres was studied by anti-inflammatory and anti-tumour experiments. The results showed that the drug-loaded microspheres could be released stably for about 12 days and degraded within 60 days. At the same time, the microspheres had good biocompatibility, anti-inflammatory and anti-tumour activities.Keywords:Panax notoginseng saponins;microspheres;sustained-release;biocompatibility;anti-inflammatory;anti-cancer
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Huiling Ye,Yongguan Liu,Wenqiang Xie,Xing Lin,Haibo Pan
An electrochemical sensor based on loading molecularly imprinted polymers (MIP) on the material surface can improve the specificity towards the object. In this work, a T-shaped PbTiO 3 with a high active-exposed (110) facet was prepared by a hydrothermal process. Then, Ag nanoparticles (Ag NPs) modified T-shaped PbTiO 3 was obtained by in-situ photocatalytic reduced method under UV irradiation , where a hetero-junction was formed with a well lattice matching between the (111) facet of Ag 0 and the (110) facet of PbTiO 3 . A MIPs modified by Ag nanoparticles (NPs)/PbTiO 3 (MAP) electrodes was prepared via electro polymerization process by o-Phenylenediamine (o-PD) in the presence of the template molecule, bovine hemoglobin (BHb), i.e., the detected molecule. The response peak current and concentration of BHb is demonstrated with a good linear relationship in the range of 0.00294–0.41 nM (R 2 =0.98), and the detection limit at 0.23 pM (S/N = 3). A heterojunction between Ag NPs and high- active facet of PbTiO 3 is beneficial to oxidizing electroactive material ([Fe (CN) 6 ] 3-/4- ), generating more BHb-imprinting cavities on the modified electrode and improving the sensitivity of sensor. The electrochemical sensor is with a simple, stable structure and high sensitivity to BHb detection. Furthermore, the sensor was successfully applied to detect BHb in the bovine serum samples.
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FOOD RESEARCH INTERNATIONAL
·
2020
·
IF 4.972
Xin Liu,Peng Wang,Yu-Xiao Zou,Zhi-Gang Luo,Tamer Mahmoud Tamer
Vitamin C (VC) and β -Carotene ( β C) were selected to produce co-encapsulated liposomes using hydrophilic and hydrophobic cavities simultaneously by ethanol injection method. The results of liposomal structure characterized by particle size, polydispersity index, zeta-potential and transmission electron microscope showed that the microstructure of all liposomal samples was spherical without adhesion or break and the size of VC- β C-loaded liposome (L-VC- β C) was bigger than VC-loaded liposome (L-VC) or β C-loaded liposome (L- β C). The encapsulation efficiency (EE) of VC in L-VC- β C was significantly higher than that in L-VC, and the EE of β C in L-VC- β C had no significant change compared with that in L- β C. The free radical scavenging rate of L-VC- β C was significantly higher than that of L- β C, while it had no significant change compared with that of L-VC. In addition, the storage stability of β C in L-VC- β C improved greatly compared with that in L- β C. Furthermore, the zero order model was applied to understand the release kinetics of β C from L- β C and L-VC- β C in the stomach, whereas the Korsmeyr-Peppas model was chosen to describe the release of β C from two types of liposome in small intestine and their release mechanisms were mainly dominated by Fickian diffusion. It was significant to provide a new idea for using hydrophilic and hydrophobic cavities simultaneously in liposomes to design the multicomponent nutrient delivery system.
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Nanoscale
·
2020
·Vol. 12
·期 14
·7651-7659
·
IF 6.895
Xujuan Guo,Bing Cao,Congyu Wang,Siyu Lu,Xianglong Hu
Bacterial infection has caused a serious threat to human public health. Methicillin-resistant Staphylococcus aureus (MRSA) is a representative drug-resistant bacterium, which is difficult to eradicate completely, resulting in high infection probability with severe mortality. Herein, pathogen-targeting phototheranostic nanoparticles, Van-OA@PPy, are developed for efficient elimination of MRSA infection. Van-OA@PPy nanoparticles are fabricated from the in situ templated formation of polypyrrole (PPy) in the presence of ferric ions (Fe3+) and a polymer template, hydrophilic poly(2-hydroxyethyl methacrylate-co-N,N-dimethyl acrylamide), P(HEMA-co-DMA). PPy nanoparticles are further coated with vancomycin conjugated oleic acid (Van-OA) to afford the resultant pathogen-targeting Van-OA@PPy. A high photothermal conversion efficiency of ∼49.4% is achieved. MRSA can be efficiently killed due to sufficient nanoparticle adhesion and fusion with MRSA, followed by photothermal therapy upon irradiation with an 808 nm laser. Remarkable membrane damage of MRSA is observed, which contributes greatly to the inhibition of MRSA infection. Furthermore, the nanoparticles have high stability and good biocompatibility without causing any detectable side effects. On the other hand, residual Fe3+ and PPy moieties in Van-OA@PPy endow the nanoparticles with magnetic resonance (MR) imaging and photoacoustic (PA) imaging potency, respectively. The current strategy has the potential to inspire further advances in precise diagnosis and efficient elimination of MRSA infection in biomedicine.
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BIOSENSORS & BIOELECTRONICS
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2020
·
IF 10.257
Rui Han,Guixiang Wang,Zhenying Xu,Leyao Zhang,Qun Li,Yinfeng Han,Xiliang Luo
An antifouling electrochemical biosensing platform was constructed based on conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) planted with designed peptides. The designed peptides containing doping and antifouling sequences were anchored to an electrode surface , followed by the electrochemical polymerization of PEDOT. The negatively charged doping sequence of the peptide was gradually doped into the PEDOT during the polymerization process, and by controlling the polymerization time, it was able to exactly dope the whole doping sequence into the PEDOT film, leaving the antifouling sequence of the peptide stretched out of the PEDOT surface. Therefore, an excellent conducting and antifouling platform was constructed just like planting a peptide tree in the PEDOT soil. With antibodies immobilized on the peptide, an antifouling electrochemical biosensor for the detection of a typical biomarker CA15-3 was developed. Owing to the unique properties of the conducting polymer PEDOT and the antifouling peptide, the electrochemical biosensor exhibited high sensitivity and long-term stability, and it was capable of detecting CA15-3 in serum of breast cancer patients without suffering from biofouling. The strategy of planting designed antifouling peptides in conducting polymers offered an effective way to develop electrochemical sensors for practical biomarkers assaying in complex biological samples.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2013
·
IF 3.458
Xiaofen Xu,Yanggong Li,Feihu Wang,Li Lv,Jieying Liu,Mingna Li,Aijie Guo,Jinjun Jiang,Yuanyuan Shen,Shengrong Guo
New norcantharidin-conjugated hydroxypropyltrimethyl ammonium chloride chitosan derivatives (NCTD-HACCs) were synthesized and characterized by 1 H NMR, Fourier-transform infrared spectroscopy (FT-IR), and wide-angle X-ray diffraction (WAXD). Two NCTD-HACCs with different degrees of substitution ( DS ) (12.2% and 24.8%) were obtained, which had good water solubility. NCTD was released from the NCTD-HACCs via hydrolysis, faster in pH 5.0 than pH 7.4 and presenting one biphasic drug release pattern with rapid release at the initial stage and slow release later. Fluorescence microscope and flow cytometry analysis demonstrated that the NCTD-HACC was endocytosized into MGC80-3 cells and the uptaken amount increased as incubation time . Compared with free NCTD, the NCTD-HACCs showed lower in vitro anti-tumor activity against human gastric cancer MGC80-3 cells, but higher in vivo tumor growth inhibition in S180 tumor-bearing mice. The in vivo near-infrared (NIR) fluorescence real-time imaging result showed the fluorescence intensity in tumor was much higher than that in heart, liver, spleen and lung (except kidney) after i.v. injection of the FITC-labeled NCTD-HACC2, indicating specific accumulation of the NCTD-HACC in tumor.
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ANALYTICAL CHEMISTRY
·
2018
·
IF 6.042
Hui Wang,Ke Xue,Ping Li,Yuyun Yang,Zixu He,Wei Zhang,Wen Zhang,Bo Tang
Severe atmospheric haze caused by industrial pollution has severely affected human health and led to the increasing incidence of cardiopulmonary diseases, including pneumonia. Conventional methods for diagnosis of pneumonia are complicated and tedious, and current clinical imaging techniques might cause organ injuries to some extent. Therefore, an accurate, fast, and intact imaging method must be developed to diagnose pneumonia in the early stages. In this study, we propose a new two-photon fluorescence probe, named as ASPC, for detection of the activity of the inflammatory biomarker LTA4H through specific recognition and cleavage of amides containing the unnatural amino acid l-AspBzl. The activity of LTA4H in the lung tissues of mice was rapidly and accurately monitored for the first time and could be an indicator for diagnosis of pneumonia. The severity of pneumonia in mice caused by haze particulate was determined through imaging the activity of LTA4H as biomarker and confirmed using a commercial ELISA kit of interleukin-1β. This work provides a promising method for clinical detection of pneumonia and for screening specific depressors of LTA4H as potential drug candidates.
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