Polymers
·
2023
·Vol. 15
·期 5
·1077
·
IF 5
Shuo Li,Li Shi,Ting Ye,Biao Huang,Yuan Qin,Yongkang Xie,Xiaoyuan Ren,Xueqin Zhao
Antibiotic abuse in the conventional treatment of microbial infections, such as inflammatory bowel disease, induces cumulative toxicity and antimicrobial resistance which requires the development of new antibiotics or novel strategies for infection control. Crosslinker-free polysaccharide-lysozyme microspheres were constructed via an electrostatic layer-by-layer self-assembly technique by adjusting the assembly behaviors of carboxymethyl starch (CMS) on lysozyme and subsequently outer cationic chitosan (CS) deposition. The relative enzymatic activity and in vitro release profile of lysozyme under simulated gastric and intestinal fluids were investigated. The highest loading efficiency of the optimized CS/CMS-lysozyme micro-gels reached 84.9% by tailoring CMS/CS content. The mild particle preparation procedure retained relative activity of 107.4% compared with free lysozyme, and successfully enhanced the antibacterial activity againstE. colidue to the superposition effect of CS and lysozyme. Additionally, the particle system showed no toxicity to human cells. In vitro digestibility testified that almost 70% was recorded in the simulated intestinal fluid within 6 h. Results demonstrated that the cross-linker-free CS/CMS-lysozyme microspheres could be a promising antibacterial additive for enteric infection treatment due to its highest effective dose (573.08 μg/mL) and fast release at the intestinal tract.Keywords:lysozyme;carboxymethyl starch;chitosan;layer-by-layer self assembly;enteric infection
研究领域:
药学
·
生物技术
·
材料科学
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产品关联
DOI
PubMed
高影响因子
Cell Reports
·
2025
·
IF 6.9
Zijia Sun,Yingsheng Wang,Shaorui Liu,Hui Li,Danyang He,Heping Xu
Intrinsic enteric neurons (iENs) form a crucial neuronal network within the myenteric and submucosal plexus of the gastrointestinal tract, primarily responsible for regulating gut peristalsis. The mechanisms by which iENs sense and integrate dietary and microbial signals to regulate intestinal homeostasis and inflammation remain unclear. Here, we showed that environmental sensor aryl hydrocarbon receptor (AHR) was expressed in different iEN subsets in the ileum and colon and that AHR ligands differentially modulated iEN activity in these regions. Genetic perturbation of Ahr in neurons increased iEN activation in the ileum but, conversely, decreased it in the colon in response to different intestinal pathogens. Furthermore, neuronal AHR deficiency enhanced the clearance of bacterial pathogens, which was associated with increased proliferation and abundance of group 3 innate lymphoid cells in the ileum. Together, our findings demonstrate the region-specific functions of AHR in neurons in response to infections.
研究领域:
神经科学
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免疫学
·
胃肠病学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Veterinary Science
·
2022
·
IF 3.471
Lu Yixing,Yang Liuye,Zhang Wanying,Li Jie,Peng Xianfeng,Qin Zonghua,Zeng Zhenling,Zeng Dongping
This study aimed to evaluate the antibacterial activity of isopropoxy benzene guanidine (IBG) against C. perfringens based on pharmacokinetics/pharmacodynamics (PK/PD) modeling in broilers. The PK parameters of IBG in the plasma and ileal content of C. perfringens-infected broilers following oral administration at 2, 30, and 60 mg/kg body weight were investigated. in vivo PD studies were conducted over oral administration ranging from 2 to 60 mg/kg and repeated every 12 h for 3 days. The inhibitory Imax model was used for PK/PD modeling. Results showed that the MIC of IBG against C. perfringens was 0.5–32 mg/L. After oral administration of IBG, the peak concentration (Cmax), maximum concentration time (Tmax), and area under the concentration-time curve (AUC) in ileal content of broilers were 10.97–1,036.64 mg/L, 2.39–4.27 h, and 38.31–4,266.77 mg·h/L, respectively. After integrating the PK and PD data, the AUC0 − 24h/MIC ratios needed for the bacteriostasis, bactericidal activity, and bacterial eradication were 4.00, 240.74, and 476.98 h, respectively. For dosage calculation, a dosage regimen of 12.98 mg/kg repeated every 12 h for 3 days was be therapeutically effective in broilers against C. perfringens with MIC ≤ 2 mg/L. In addition, IBG showed potent activity against C. perfringens, which may be responsible for cell membrane destruction. These results can facilitate the evaluation of the use of IBG in the treatment of intestinal diseases in broilers caused by C. perfringens.
研究领域:
兽医学
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微生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Pharmaceutics
·
2021
·Vol. 13
·期 11
·1809
·
IF 6.321
Yanyan Wu,Guang Yang,Henny C. van der Mei,Linqi Shi,Henk J. Busscher,Yijin Ren
Orally administrated probiotic bacteria can aid antibiotic treatment of intestinal infections, but their arrival at their intestinal target site is hampered by killing in the gastrointestinal tract and by antibiotics solely intended for pathogen killing. Carbon-quantum-dots are extremely small nanoparticles and can be derived from different sources, including bacteria. Here, we hypothesize that carbon-quantum-dots inherit antibacterial activity from probiotic source bacteria to fulfill a similar role as live probiotics in intestinal infection therapy. Physico-chemical analyses indicated that carbon-quantum-dots, hydrothermally derived fromBifidobacterium breve(B-C-dots), inherited proteins and polysaccharides from their source-bacteria. B-C-dots disrupted biofilm matrices ofEscherichia coliandSalmonella typhimuriumbiofilms through extensive reactive-oxygen-species (ROS)-generation, causing a decrease in volumetric bacterial-density in biofilms. Decreased bacterial densities leave more open space in biofilms and have enhanced ciprofloxacin penetration and killing potential in anE. colibiofilm pre-exposed to probiotic B-C-dots. Pathogenic carbon-quantum-dots hydrothermally derived fromE. coli(E-C-dots) did not disrupt pathogenic biofilms nor enhanceE. colikilling potential by ciprofloxacin. B-C-dots were biosafe in mice upon daily administration, while E-C-dots demonstrated a decrease in white blood cell and platelet counts and an increase in C-reactive protein levels. Therefore, the way is paved for employing probiotic carbon-quantum-dots instead of viable, probiotic bacteria for synergistic use with existing antibiotics in treating intestinal infections.Keywords:matrix disruption;antibiotics;Bifidobacterium breve;Escherichia coli;reactive oxygen species;intestinal infections;biosafety
研究领域:
微生物学
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药理学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2021
·Vol. 13
·期 5
·602
·
IF 6.321
Kaixiang Zhou,Meixia Huo,Wenjin Ma,Kun Mi,Xiangyue Xu,Samah Attia Algharib,Shuyu Xie,Lingli Huang
Zoonotic intestinal pathogens threaten human health and cause huge economic losses in farming. Enrofloxacin (ENR) shows high antibacterial activity against common intestinal bacteria. However, its poor palatability and low aqueous solubility limit the clinical application of ENR. To obtain an ENR oral preparation with good palatability and high solubility, a granule containing an amorphous ENR solid dispersion (ENR-SD) was prepared. Meanwhile, a PBPK model of ENR in pigs was built based on the physiological parameters of pigs and the chemical-specific parameters of ENR to simulate the pharmacokinetics (PK) of ENR-SD granules in the intestinal contents. According to the results of parameter sensitivity analysis (PSA) and the predicted PK parameters at different doses of the model, formulation strategies and potential dose regimens against common intestinal infections were provided. The DSC and XRD results showed that no specific interactions existed between the excipients and ENR during the compatibility tests, and ENR presented as an amorphous form in ENR-SD. Based on the similar PK performance of ENR-SD granules and the commercial ENR soluble powder suggesting continued enhancement of the solubility of ENR, a higher drug concentration in intestinal contents could not be obtained. Therefore, a 1:5 ratio of ENR and stearic acid possessing a saturated aqueous solubility of 1190 ± 7.71 µg/mL was selected. The predictive AUC24h/MIC90ratios againstCampylobacter jejuni,Salmonella, andEscherichia coliwere 133, 266 and 8520 (>100), respectively, suggesting that satisfactory efficacy against common intestinal infections would be achieved at a dose of 10 mg/kg b.w. once daily. The PSA results indicated that the intestinal absorption rate constant (Ka) was negatively correlated with the Cmaxof ENR in the intestine, suggesting that we could obtain higher intestinal Cmaxusing P-gp inducers to reduce Ka, thus obtaining a higher Cmax. Our studies suggested that the PBPK model is an excellent tool for formulation and dose design.Keywords:intestinal infections;enrofloxacin;solid dispersion;physiologically based pharmacokinetics model;formulation strategies;dose design
研究领域:
兽医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Sheng Wang,Pingping Yuan,Shijie Zhou,Lin Li,Wenjing Peng,Shaoqi Qu
Current antibiotic-based treatments for bacterial enteric infections often disrupt gut microbiota and face reduced efficacy due to gastrointestinal complexity and mucosal barriers. Here, we developed a genistein-loaded nanoparticle using whey protein isolate and prebiotic inulin (Gen_Wi) to improve the gut microbiome health. Gen_Wi nanoparticles mitigated oxidative stress and inflammation in intestinal epithelial cells by activating Nrf2 and suppressing NF-κB pathways, reducing TNF-α and IL-1β levels by nearly 39 and 55.6%, respectively. Remarkably, oral administration of Gen_Wi significantly mitigated Salmonella-induced intestinal damage, reducing bacterial colonization by 1000-fold, restoring goblet cell counts, and enhancing tight junction proteins. Mechanistic analysis revealed that Gen_Wi reshaped gut microbiota composition by promoting beneficial bacteria and increasing production of gut barrier-strengthening short-chain fatty acids, including acetate, propionate, and butyrate. These results highlight Gen_Wi as a prebiotic system that integrates prebiotic functionality with anti-inflammation to combat enteric infections through modulation of host–microbe interactions.
研究领域:
微生物学
·
药剂学
·
免疫学
·
胃肠病学
·
纳米技术
·
营养科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CONTROL
·
2022
·
IF 6.652
Hongli Liu,Wenxiu Zhu,Yu Cao,Jingzhu Gao,Tong Jin,Ningbo Qin,Xiaodong Xia
Vibrio parahaemolyticus is a major food-borne pathogen and the leading cause of seafood-associated enteric infections worldwide. In addition, imprudent use of antibiotics has contributed to increasing antibiotic resistance in V. parahaemolyticus. Therefore, there is an urgent need to develop novel control strategies to reduce V. parahaemolyticus contamination and infection. V. parahaemolyticus could form biofilm on different surfaces and contains several virulence factors, which together contribute to its persistence and pathogenicity. In this study, anti-biofilm and potential anti-virulence effects of punicalagin against V. parahaemolyticus were investigated. Punicalagin at sub-inhibitory concentrations (3.125–12.5 μg/mL) exerted significant anti-biofilm activity (20.9–74.4% reduction). It decreased bacterial motility, and attenuated metabolic activity of cells inside biofilm. Meanwhile, punicalagin inhibited EPS production and caused reduction of exopolysaccharides in biofilms, and decreased Raman peak intensities of different biofilm components. Moreover, punicalagin significantly inhibited V. parahaemolyticus adhesion to Caco-2 cells (23.8–68.1% reduction) and downregulated expression of genes involved in V. parahaemolyticus biofilm formation and virulence. These findings suggest that punicalagin could be potentially developed as an alternative strategy to control V. parahaemolyticus biofilms in food industry and mitigate diseases caused by this pathogen.
研究领域:
微生物学
·
食品安全
·
药理学
·
分子生物学
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产品关联
DOI
高影响因子
Small
·
2021
·Vol. 18
·期 1
·2105530
·
IF 13.281
Xiaofang Zhong,Guangsheng Du,Xuanyu Wang,Yangsen Ou,Hairui Wang,Yining Zhu,Xinyan Hao,Zhiqiang Xie,Yuandong Zhang,Tao Gong,Zhirong Zhang,Xun Sun
Parenteral vaccines typically can prime systemic humoral immune response, but with limited effects on cellular and mucosal immunity. Here, a subcutis-to-intestine cascade for navigating nanovaccines to address this limitation is proposed. This five-step cascade includes lymph nodes targeting, uptaken by dendritic cells (DCs), cross-presentation of antigens, increasing CCR9 expression on DCs, and driving CD103 + DCs to mesenteric lymph nodes, in short, the LUCID cascade. Specifically, mesoporous silica nanoparticles are encapsulated with antigen and adjuvant toll-like receptor 9 agonist cytosine-phosphate-guanine oligodeoxynucleotides, and further coated by a lipid bilayer containing all-trans retinoic acid. The fabricated nanovaccines efficiently process the LUCID cascade to dramatically augment cellular and mucosal immune responses. Importantly, after being vaccinated with Salmonella enterica serovar Typhimurium antigen-loaded nanovaccine, the mice generate protective immunity against challenge of S. Typhimurium . These findings reveal the efficacy of nanovaccines mediated subcutis-to-intestine cascade in simultaneously activating cellular and mucosal immune responses against mucosal infections.
研究领域:
免疫学
·
纳米技术
·
疫苗研发
·
传染病
✓ 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）