INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Anan Guo,Lvqing Tang,Bing Yang,Niling Xie,Yandong Cui,Wen Sun,Yuan Li,Xiangting Li,Yang Wu,Yingshuai Liu
Adjuvants including aluminum adjuvant (Alum) and oil-water emulsion have been widely used in inactivated pseudorabies virus (PRV) vaccines to improve their performance, however, they are not sufficient to protect from PRV infection because of the weak immune response and poor Th1-type immune response. Divalent manganese ion (Mn 2+ ) has been reported to increase the cellular immune response significantly. In this work, a xanthan gum and carbomer-dispersed Mn 2+ -loaded tannic acid-polyethylene glycol (TPMnXC) nanoparticle colloid is developed and used as an adjuvant to improve the performance of the inactivated PRV vaccine. The good in vitro and in vivo biocompatibility of the developed TPMnXC colloid has been confirmed by the cell viability assay, erythrocyte hemolysis, blood routine analysis, and histological analysis of mouse organs and injection site. The TPMnXC-adjuvanted inactivated PRV vaccine (TPMnXC@PRV) significantly promotes higher and more balanced immune responses indicating with an increased specific total IgG antibody and IgG2a/IgG1 ratio, efficient splenocytes proliferation, and elevated Th1- and Th2-type cytokine secretion than those of control groups. Wild PRV challenge experiment is performed using mice as a model animal, achieving a protection rate of up to 86.67 %, which is much higher than those observed from the commercial Alum. This work not only demonstrates the high potentiality of TPMnXC in practical applications but also provides a new way to develop the Mn 2+ -loaded nanoadjuvant for veterinary vaccines.
研究领域:
兽医学
·
免疫学
·
纳米技术
·
病毒学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2019
·
IF 5.589
Xia Wang,Jianbo Zhu,Baida Kong,Bingnan He,Lai Wei,Yuanxiang Jin,Yudong Shan,Weitao Wang,Chunqiang Pan,Zhengwei Fu
Short-chain chlorinated paraffins (SCCPs, C 10–13 ) were listed as persistent organic pollutants (POPs) by the Stockholm Convention in 2017 and pose extensive exposure risks to humans. To our knowledge, there have been no studies reporting the immmunomodulatory effects of SCCPs until now. C 9 -CPs have also been shown to be present in the environment. In this study, adult male C57BL/6 mice were exposed to 1, 10, or 100 mg/kg/d C 9–13 -CPs by gavage for 28 d. The results showed that compared to those of the controls, exposure to C 9–13 -CPs led to increased spleen weight, delimited germinal centers, enhanced energy metabolism, and elevated glutathione content, but no variation in the malonaldehyde level in the spleen was observed. Exposure to C 9–13 -CPs also increased the populations of splenic lymphocytes, T lymphocytes, NK cells, and the ratio of the CD3 + /CD19 + subsets and CD4 + /CD8 + subsets compared to those of the controls. RNA-seq revealed 424 differentially expressed genes (DEGs) (fold change ≥ 1.5, FDR < 0.05) in the spleen between the control group and the 100 mg/kg/d C 9–13 -CPs-treated group. KEGG analysis demonstrated that folate biosynthesis, pathways in cancer and thyroid hormone signaling were the three most significantly enriched pathways, and despite not reaching statistical significance, some immune-related pathways were also enriched in the KEGG functional enrichment analysis, including the chemokine signaling pathway (FDR < 0.0584), the NF-κB signaling pathway (FDR < 0.0663), Th17 cell differentiation (FDR < 0.0839), and the Jak-STAT signaling pathway. Moreover, compared to those of the controls, exposure to C 9–13 -CPs enhanced the Concanavalin A (Con A)-stimulated cultured splenocyte proliferation, while the exposure showed no effect on the splenocyte proliferation that was stimulated by lipopolysaccharides (LPS). Taken together, these results demonstrated that subacute exposure to C 9–13 -CPs could have immunomodulatory effects in mice. The present study helps to provide an understanding of the comprehensive health risks posed by C 9–13 -CPs.
研究领域:
毒理学
·
免疫学
·
分子生物学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
·
2024
·Vol. 390
·期 1
·116-124
·
IF 3.1
Longbiao Luo,Yi Zhao,Guangji Zhang,Sijing Dong,YinYue Xu,Hehe Shi,Menggai Zhang,Xue Liu,Sicen Wang,Hua Luo,Wanghui Jing
Ulcerative colitis (UC) is an immune-mediated inflammatory disease that can lead to persistent damage and even cancer without any intervention. Conventional treatments can alleviate UC symptoms but are costly and cause various side effects. Tauroursodeoxycholic acid (TUDCA), a secondary bile acid derivative, possesses anti-inflammatory and cytoprotective properties for various diseases, but its potential therapeutic benefits in UC have not been fully explored. Mice were subjected to colitis induction using 3% dextran sulfate sodium (DSS). The therapeutic effect of TUDCA was evaluated by body weight loss, disease activity index (DAI), colon length, and spleen weight ratio. Tissue pathology was assessed using H&E staining, while the levels of pro-inflammatory and anti-inflammatory cytokines in colonic tissue were quantified via ELISA. Tight junction proteins were detected by immunoblotting and intestinal permeability was assessed using fluorescein isothiocyanate (FITC)-dextran. Moreover, the gut microbiota was profiled using high-throughput sequencing of the 16S rDNA gene. TUDCA alleviated the colitis in mice, involving reduced DAI, attenuated colon and spleen enlargement, ameliorated histopathological lesions, and normalized levels of pro-inflammatory and anti-inflammatory cytokines. Furthermore, TUDCA treatment inhibited the downregulation of intestinal barrier proteins, including zonula occludens-1 and occludin, thus reducing intestinal permeability. The analysis of gut microbiota suggested that TUDCA modulated the dysbiosis in mice with colitis, especially for the remarkable rise in Akkermansia. TUDCA exerted a therapeutic efficacy in DSS-induced colitis by reducing intestinal inflammation, protecting intestinal barrier integrity, and restoring gut microbiota balance.
研究领域:
胃肠病学
·
免疫学
·
药理学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2019
·Vol. 20
·期 8
·1-10
·
IF 2.608
Wang Xinxin,Feng Yan,Fu Jijun,Wu Cuishuan,He Bing,Zhang Hua,Wang Xueqing,Dai Wenbing,Sun Yong,Zhang Qiang
Glucocorticoids have been confirmed to be effective in the treatment of a variety of inflammatory diseases. However, their application encounters limitations in terms of tissue distribution and bioavailability in vivo . To address these key issues, we designed and developed a nanopreparation by using egg yolk lecithin/sodium glycocholate (EYL/SGC) and utilize such mixed micelles (MMs) to encapsulate dexamethasone palmitate (DMP) for the treatment of rheumatoid arthritis (RA). The prepared DMP-MMs had an average particle size of 49.18 ± 0.43 nm and were compared with an emulsion-based dexamethasone palmitate. Pharmacokinetic and in vivo fluorescence imaging showed that mixed micelles had higher bioavailability and targeting efficiency in inflammatory sites. An arthritis rat model was established via induction by Complete Freund’s Adjuvant (CFA), followed by the efficacy studies by the observations of paw volume, histology, spleen index, pro-inflammatory cytokines, and CT images. It was confirmed that intravenous injection of DMP-MMs exhibited advantages in alleviating joint inflammation compared with the emulsion system. Composed of pharmaceutical adjuvants only, the nanoscale mixed micelles seem a promising carrier system for the RA treatment with lipophilic drugs.
研究领域:
药剂学
·
药理学
·
纳米技术
·
炎症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Shuang Xie,Yu Li,Wenxiong Cao,Jiawen Peng,Kun Huang,Jie Meng,Xiaohong Li
Intracellular bacteria are the major cause of serious infections including sepsis and peritonitis, but face great challenges in fighting against the stubborn intracellular small colony variants (SCVs). Herein, the authors have developed nanogels (NGs) to destroy both planktonic bacteria and SCVs and eliminate excessive inflammations for peritonitis and sepsis therapies. Free gentamicin (GEN) and hydroxyapatite nanoparticles (NPs) with GEN loading and mannose grafts (mHA G ) are inoculated into ε-polylysine NGs to obtain NG@G1-mHA G2 through crosslinking with phenylboronic acid and tannic acid. The H 2 O 2 consumption after reaction with phenylboronic esters and the elimination of free radicals by tannic acid alleviates the escalated inflammatory status to promote sepsis therapy. After mannose-mediated uptake into macrophages, the acid-triggered degradation of mHA G NPs generates Ca 2+ to destabilize lysosomes and the efficient lysosomal escape leads to reversion of hypometabolic SCVs into normal phenotype and their sensitivity to GEN. In a peritonitis mouse model, NG@G1-mHA G2 treatment provides strong and persistent bactericidal effects against both extracellular bacteria and intracellular SCVs and extends survival of peritonitis mice without apparent hepatomegaly, splenomegaly, pulmonary edema, and inflammatory cell infiltration. Thus, this study demonstrates a concise and versatile strategy to eliminate SCVs and relieve inflammatory storms for peritonitis and sepsis therapies without infection recurrence.
研究领域:
纳米技术
·
药学
·
传染病学
·
生物医学工程
·
药理学
✓ 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）