Neutrophil-inspired photothermo-responsive drug delivery system for targeted treatment of bacterial infection and endotoxins neutralization

Chengnan Li,Yingying Gan,Zongshao Li,Mengjing Fu,Yuzhen Li,Xinran Peng,Yongqiang Yang,Guo‑bao Tian,Yi Yan Yang,Peiyan Yuan,Xin Ding 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Background P. aeruginosa, a highly virulent Gram-negative bacterium, can cause severe nosocomial infections, and it has developed resistance against most antibiotics. New therapeutic strategies are urgently needed to treat such bacterial infection and reduce its toxicity caused by endotoxin (lipopolysaccharide, LPS). Neutrophils have been proven to be able to target inflammation site and neutrophil membrane receptors such as Toll-like receptor-4 (TLR4) and CD14, and exhibit specific affinity to LPS. However, antibacterial delivery system based on the unique properties of neutrophils has not been reported. Methods A neutrophil-inspired antibacterial delivery system for targeted photothermal treatment, stimuli-responsive antibiotic release and endotoxin neutralization is reported in this study. Specifically, the photothermal reagent indocyanine green (ICG) and antibiotic rifampicin (RIF) are co-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP-ICG/RIF), followed by coating with neutrophil membrane to obtain antibacterial delivery system (NM-NP-ICG/RIF). The inflammation targeting properties, synergistic antibacterial activity of photothermal therapy and antibiotic treatment, and endotoxin neutralization have been studied in vitro. A P. aeruginosa-induced murine skin abscess infection model has been used to evaluate the therapeutic efficacy of the NM-NP-ICG/RIF. Results Once irradiated by near-infrared lasers, the heat generated by NP-ICG/RIF triggers the release of RIF and ICG, resulting in a synergistic chemo-photothermal antibacterial effect against P. aeruginosa (~ 99.99% killing efficiency in 5 min). After coating with neutrophil-like cell membrane vesicles (NMVs), the nanoparticles (NM-NP-ICG/RIF) specifically bind to inflammatory vascular endothelial cells in infectious site, endowing the nanoparticles with an infection microenvironment targeting function to enhance retention time. Importantly, it is discovered for the first time that NMVs-coated nanoparticles are able to neutralize endotoxins. The P. aeruginosa murine skin abscess infection model further demonstrates the in vivo therapeutic efficacy of NM-NP-ICG/RIF. Conclusion The neutrophil-inspired antibacterial delivery system (NM-NP-ICG/RIF) is capable of targeting infection microenvironment, neutralizing endotoxin, and eradicating bacteria through a synergistic effect of photothermal therapy and antibiotic treatment. This drug delivery system made from FDA-approved compounds provides a promising approach to fighting against hard-to-treat bacterial infections.

Purification, characterization and action mechanism of plantaricin JY22, a novel bacteriocin against Bacillus cereus produced by Lactobacillus plantarum JY22 from golden carp intestine

Xinran Lv,Luhuan Miao,Huanhuan Ma,Fengling Bai,Yang Lin,Mengtong Sun,Jianrong Li 한국식품과학회 2018 Food Science and Biotechnology Vol.27 No.3

A novel bacteriocin-producing strain, Lactobacillus plantarum JY22 isolated from golden carp intestine, was screened and identified by its physiobiochemical characteristics and 16S rRNA gene sequence analysis. This bacteriocin, named plantaricin JY22, was purified using ethyl acetate extraction and gel filtration. Its molecular weight was approximately 4.1 kDa by SDS-PAGE analysis. The partial amino acid sequence of plantaricin JY22 was DFGFDIPDEV. It was highly heat-stable and remained active at pH range from 2.5 to 5.5, but was sensitive to protease. Plantaricin JY22 had a bactericidal mode. Scanning electron microscope analysis indicated that plantaricin JY22 damaged the morphology of cells and spores for Bacillus cereus. Moreover, the plantaricin JY22 destroyed cell membrane integrity as confirmed by the leakage of electrolytes, the losses of Na?K?-ATP, AKP, nucleic acids (OD260nm) and proteins. SDS-PAGE of B. cereus proteins further demonstrated that plantaricin JY22 had a remarkable effect on bacterial proteins.

Purification, characterization and action mechanism of plantaricin JY22, a novel bacteriocin against Bacillus cereus produced by Lactobacillus plantarum JY22 from golden carp intestine

Lv, Xinran,Miao, Luhuan,Ma, Huanhuan,Bai, Fengling,Lin, Yang,Sun, Mengtong,Li, Jianrong 한국식품과학회 2018 Food Science and Biotechnology Vol.27 No.3

A novel bacteriocin-producing strain, Lactobacillus plantarum JY22 isolated from golden carp intestine, was screened and identified by its physiobiochemical characteristics and 16S rRNA gene sequence analysis. This bacteriocin, named plantaricin JY22, was purified using ethyl acetate extraction and gel filtration. Its molecular weight was approximately 4.1 kDa by SDS-PAGE analysis. The partial amino acid sequence of plantaricin JY22 was DFGFDIPDEV. It was highly heat-stable and remained active at pH range from 2.5 to 5.5, but was sensitive to protease. Plantaricin JY22 had a bactericidal mode. Scanning electron microscope analysis indicated that plantaricin JY22 damaged the morphology of cells and spores for Bacillus cereus. Moreover, the plantaricin JY22 destroyed cell membrane integrity as confirmed by the leakage of electrolytes, the losses of $Na^+K^+$-ATP, AKP, nucleic acids ($OD_{260nm}$) and proteins. SDS-PAGE of B. cereus proteins further demonstrated that plantaricin JY22 had a remarkable effect on bacterial proteins.

Composite Materials : EFFECT OF LIQUID NITROGEN TREATMENT ON DEFORMATION OF ALUMINA PARTICULATE REINFORCED ALUMINUM COMPOSITE

Huan Xi Li,Xinran Xiao,Jason Lo 대한금속재료학회 ( 구 대한금속학회 ) 1995 Advanced Material and Processing Vol.3 No.-

Changes in growth performance, nutrient digestibility, immune blood profiles, fecal microbial and fecal gas emission of growing pigs in response to zinc aspartic acid chelate

Jiao, Yang,Li, Xinran,Kim, In Ho Asian Australasian Association of Animal Productio 2020 Animal Bioscience Vol.33 No.4

Objective: This study was conducted to investigate the effect of zinc aspartic acid chelate (Zn-ASP) on growth performance, nutrient digestibility, blood profiles, fecal microbial and fecal gas emission in growing pigs. Methods: A total of 160 crossbred ([Landrace×Yorkshire]×Duroc) growing pigs with an initial body weight (BW) of 25.56±2.22 kg were used in a 6-wk trial. Pigs were randomly allocated into 1 of 4 treatments according to their sex and BW (8 replicates with 2 gilts and 3 barrows per replication pen). Treatments were as follows: i) CON, basal diet, ii) TRT1, CON+0.1% Zn-ASP, iii) TRT2, CON+0.2% Zn-ASP, and iv) TRT3, CON+0.3% Zn-ASP. Pens were assigned in a randomized complete block design to compensate for known position effects in the experimental facility. Results: In the current study, BW, average daily gain, and gain:feed ratio showed significant improvement as dietary Zn-ASP increased (p<0.05) in growing pigs. Apparent total tract digestibility (ATTD) of dry matter was increased linearly (p<0.05) in pigs fed with Zn-ASP diets. A linear effect (p<0.05) was detected for the Zn concentration in blood with the increasing levels of Zn-ASP supplementation. Lactic acid bacteria and coliform bacteria were affected linearly (p<0.05) in pigs fed with Zn-ASP diets. However, no significant differences were observed in the ATTD of nitrogen, energy and Zn. And dietary Zn-ASP supplementation did not affect fecal ammonia, hydrogen sulfide and total mercaptans emissions in growing pigs. Conclusion: In conclusion, dietary supplementation with Zn-ASP of diet exerted beneficial effects on the growth performance, nutrient digestibility, blood profiles and fecal microbes in growing pigs.

Design Method for the LCL Filters of Three-phase Voltage Source PWM Rectifiers

Guo, Xizheng,You, Xiaojie,Li, Xinran,Hao, Ruixiang,Wang, Dewei The Korean Institute of Power Electronics 2012 JOURNAL OF POWER ELECTRONICS Vol.12 No.4

A new design method for the LCL filters of three-phase voltage source PWM rectifiers is presented in this paper. Based on the single-phase harmonic equivalent model, the harmonic voltage of the rectifier side is calculated to design the LCL filter parameters by an iterative algorithm, in which the resonance frequency $f_{res}$ and the ratio r between the grid-side inductance and the rectifier-side inductance are selected as known constants. The design criteria and process are introduced and the influence on the design result by the value of the resonance frequency $f_{res}$, ratio r is analyzed. Finally an example (600V, 500kW) is tested by simulation and experiment to verify the validity of the new design method.

Bavachin Suppresses Alpha-Hemolysin Expression and Protects Mice from Pneumonia Infection by Staphylococcus aureus

( Ye Tao ),( Dazhong Sun ),( Xinran Ren ),( Yicheng Zhao ),( Hengjian Zhang ),( Tao Jiang ),( Jiyu Guan ),( Yong Tang ),( Wu Song ),( Shuqiang Li ),( Li Wang ) 한국미생물생명공학회 2022 Journal of microbiology and biotechnology Vol.32 No.10

Staphylococcus aureus (S. aureus) infection causes dramatic harm to human health as well as to livestock development. As an important virulence factor, alpha-hemolysin (hla) is critical in the process of S. aureus infection. In this report, we found that bavachin, a natural flavonoid, not only efficiently inhibited the hemolytic activity of hla, but was also capable of inhibiting it on transcriptional and translational levels. Moreover, further data revealed that bavachin had no neutralizing activity on hla, which did not affect the formation of hla heptamers and exhibited no effects on the hla thermal stability. In vitro assays showed that bavachin was able to reduce the S. aureus-induced damage of A549 cells. Thus, bavachin repressed the lethality of pneumonia infection, lung bacterial load and lung tissue inflammation in mice, providing potent protection to mice models in vivo. Our results indicated that bavachin has the potential for development as a candidate hla inhibitor against S. aureus.

Design Method for the LCL Filters of Three-phase Voltage Source PWM Rectifiers

Xizheng Guo,Xiaojie You,Xinran Li,Ruixiang Hao,Dewei Wang 전력전자학회 2012 JOURNAL OF POWER ELECTRONICS Vol.12 No.4

A new design method for the LCL filters of three-phase voltage source PWM rectifiers is presented in this paper. Based on the single-phase harmonic equivalent model, the harmonic voltage of the rectifier side is calculated to design the LCL filter parameters by an iterative algorithm, in which the resonance frequency fres and the ratio r between the grid-side inductance and the rectifier-side inductance are selected as known constants. The design criteria and process are introduced and the influence on the design result by the value of the resonance frequency fres, ratio r is analyzed. Finally an example (600V, 500kW) is tested by simulation and experiment to verify the validity of the new design method.

USP15 promotes pulmonary vascular remodeling in pulmonary hypertension in a YAP1/TAZ-dependent manner

Wu Zhuhua,Zhu Li,Nie Xinran,Wei Li,Qi Yong 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Pulmonary hypertension (PH) is a life-threatening cardiopulmonary disease characterized by pulmonary vascular remodeling. Excessive growth and migration of pulmonary artery smooth muscle cells (PASMCs) are believed to be major contributors to pulmonary vascular remodeling. Ubiquitin-specific protease 15 (USP15) is a vital deubiquitinase that has been shown to be critically involved in many pathologies. However, the effect of USP15 on PH has not yet been explored. In this study, the upregulation of USP15 was identified in the lungs of PH patients, mice with SU5416/hypoxia (SuHx)-induced PH and rats with monocrotaline (MCT)-induced PH. Moreover, adeno-associated virus-mediated functional loss of USP15 markedly alleviated PH exacerbation in SuHx-induced mice and MCT-induced rats. In addition, the abnormal upregulation and nuclear translocation of YAP1/TAZ was validated after PH modeling. Human pulmonary artery smooth muscle cells (hPASMCs) were exposed to hypoxia to mimic PH in vitro, and USP15 knockdown significantly inhibited cell proliferation, migration, and YAP1/TAZ signaling in hypoxic hPASMCs. Rescue assays further suggested that USP15 promoted hPASMC proliferation and migration in a YAP1/TAZ-dependent manner. Coimmunoprecipitation assays indicated that USP15 could interact with YAP1, while TAZ bound to USP15 after hypoxia treatment. We further determined that USP15 stabilized YAP1 by inhibiting the K48-linked ubiquitination of YAP1. In summary, our findings reveal the regulatory role of USP15 in PH progression and provide novel insights into the pathogenesis of PH.

Baseline Total Metabolic Tumor Volume and Total Lesion Glycolysis Measured on 18F-FDG PET-CT Predict Outcomes in T-Cell Lymphoblastic Lymphoma

Xiaoyan Feng,Xin Wen,Ling Li,Zhenchang Sun,Xin Li,Lei Zhang,Jingjing Wu,Xiaorui Fu,Xinhua Wang,Hui Yu,Xinran Ma,Xudong Zhang,Xinli Xie,Xingmin Han,Mingzhi Zhang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.3

Purpose There is no optimal prognostic model for T-cell lymphoblastic lymphoma (T-LBL). Here, we discussed the predictive value of total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) measured on 18F-fluorodeoxyglucose positron emission tomography–computed tomography (PET-CT) in T-LBL.Materials and Methods Thirty-seven treatment naïve T-LBL patients with PET-CT scans were enrolled. TMTV was obtained using the 41% maximum standardized uptake value (SUVmax) threshold method, and TLG was measured as metabolic tumor volume multiplied by the mean SUV. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier curves and compared by the log-rank test.Results The optimal cutoff values for SUVmax, TMTV, and TLG were 12.7, 302 cm3, and 890, respectively. A high SUVmax, TMTV, and TLG indicated a shorten PFS and OS. On multivariable analysis, TMTV ≥ 302 cm3, and central nervous system (CNS) involvement predicted inferior PFS, while high SUVmax, TLG and CNS involvement were associated with worse OS. Subsequently, we generated a risk model comprising high SUVmax, TMTV or TLG and CNS involvement, which stratified the population into three risk groups, which had significantly different median PFS of not reached, 14 months, and 7 months for low-risk group, mediate-risk group, and high-risk group, respectively (p < 0.001). Median OS were not reached, 27 months, and 13 months, respectively (p < 0.001).Conclusion Baseline SUVmax, TMTV, and TLG measured on PET-CT are strong predictors of worse outcome in T-LBL. A risk model integrating these three parameters with CNS involvement identifies patients at high risk of disease progression.