MATERIALS & DESIGN
·
2023
·
IF 8.4
Guichun Wang,Chengjun Peng,Maomao Tang,Yuxiao Wang,Jiaxin Li,Hairong Chen,Xiangwei Chang,Zixuan Shu,Ning He,Jian Guo,Shuangying Gui
Currently, the antibiotics-loaded hydrogels have not shown an over standard of clinical effects on periodontitis treatment. Abnormal crosstalk between macrophages and periodontal ligament stem cells (PDLSCs) is a key factor for unexpected clinical efficacy. Here, we reported a therapeutic strategy for the programmed intervention of macrophages and PDLSCs based on folic acid-modified liposome hydrogel composites loaded with genistein (FA-GEN-Lip@Gel). FA-GEN-Lip@Gel exhibited excellent thermos-sensitivity and injectability, could sustained-release genistein for more than 120 h. Flow cytometry showed that FA-GEN-Lip@Gel shifted macrophages from the M1 to M2 phenotype. We further confirmed the anti-inflammatory mechanisms that FA-GEN-Lip@Gel regulate TLR4/MyD88/NF-κB axis in macrophages. In addition, FA-GEN-Lip@Gel could promote osteogenic differentiation of PDLSCs via remodeling of cytokine secretion of IL-6, IL-17, TNF-α and IL-10 in macrophages, as verified by conditioned culture system. Therefore, FA-GEN-Lip@Gel significantly reduced periodontal inflammation in vivo according to ELISA, H&E and immunofluorescence staining. Meanwhile, FA-GEN-Lip@Gel promoted alveolar bone regeneration by remodeling RANKL/OPG balance and increasing osteogenic markers of ALP, BMP2 and RUNX2. Altogether, this study develops a novel liposome-hydrogel composites that can be efficiently simultaneously boost inflammation resolution and osteogenic differentiation in periodontitis via modulating the crosstalk between macrophages and PDLSCs.
研究领域:
牙科学
·
药学
·
生物医学工程
·
免疫学
✓ 已验证
产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Zhichang Qiu,Lu Xiang,Yanhui Han,Bin Zhang,Xuguang Qiao,Zhenjia Zheng,Hang Xiao
The present study identified the protective effects of garlic oligo/poly-saccharides of different chain lengths against dextran sulfate sodium (DSS)-induced colitis in mice and elucidated the structure-function relationships. The results showed that oral intake of garlic oligo/poly-saccharides decreased disease activity index, reduced colon shortening and spleen enlargement, and ameliorated pathological damage in the mouse colon. The dysregulation of colonic pro-/anti-inflammatory cytokines was significantly alleviated, accompanied by up-regulated antioxidant enzymes, blocked TLR4-MyD88-NF- κ B signaling pathway, enhanced intestinal barrier integrity, and restored SCFA production. Garlic oligo/poly-saccharides also reversed gut microbiota dysbiosis in colitic mice by expanding beneficial bacteria and suppressing the growth of harmful bacteria. High-molecular-weight polysaccharides exhibited stronger alleviating effects on DSS-induced colitic symptoms in mice than low-molecular-weight oligo/poly-saccharides did, probably due to their greater ability to be fermented in the colon. Taken together, this study demonstrated the anti-inflammatory effects of garlic oligo/poly-saccharides and revealed that high-molecular-weight polysaccharide fractions were more effective in alleviating DSS-induced colitis.
研究领域:
药理学
·
免疫学
·
胃肠病学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2022
·
IF 4.622
Yipeng Gu,Kai Chen,Bingwen Xi,Jun Xie,Xuwen Bing
Paeonol, a naturally occurring polyphenol isolated from medical plant , has been known to exhibit anti-oxidative and anti-inflammatory effects. In order to evaluate the effect of paeonol on Carassius auratus gibelio infected by pathogenic bacteria Aeromonas hydriphila . 750 fish were randomly divided into 5 groups, which separately treated with 0.85% sterile saline (blank), A. hydriphila (negative control), A. hydriphila with paeonol (4 mg/kg, 64 mg/kg), and A. hydriphila with enrofloxacin (12 mg/kg, positive control). Fish were anaesthetized with MS-222 (100 mg/L), and samples were collected at 6 and 72 h after A. hydriphila challenge. The results showed that compared with the negative group, the survival in paeonol groups marked increased by 14.75% and 18.94%. The plasma immunoglobulin M (IgM) was notably increased, and low density lipoprotein (LDL) was significantly decreased in paeonol groups at 6 h ( P < 0.05). The antioxidative enzymes catalase (CAT), total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) were significantly increased in paeonol groups at 6 h, while malondialdehyde (MDA) and myeloperoxidase (MPO) contents were lower ( P < 0.05). The inflammatory related genes MyD88 and TLR-5 were significantly downregulated, and the TLR-3 was significantly increased in paeonol groups at 72 h ( P < 0.05). In addition, histopathological analyses showed that the lesion in liver, spleen and caudal kidney were considerably attenuated in paeonol groups. In conclusion, paeonol could increase the survival rate, mitigate oxidative damage, inflammation, tissue lesions, and improve the immunity of gibel carp challenged with A. hydrophila .
研究领域:
水产养殖
·
免疫学
·
微生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
De-yang Huo,Yan-fei Li,Ling-jie Song,Wen-xin Zhang,Xin-dian Li,Jing Zhang,Shen Ren,Zi Wang,Wei Li
Natural plant-derived polysaccharides exhibit substantial potential for treating ulcerative colitis (UC) owing to their anti-inflammatory and antioxidant properties and favorable safety profiles. However, their practical application faces several challenges, including structural instability in gastric acid, imprecise targeting of inflamed regions, and limited intestinal retention times. To address these limitations, pH-responsive, colon-targeting microspheres (pWGPAC MSs) are developed for delivering phosphorylated wild ginseng polysaccharides (pWGP) to alleviate UC. These pWGPAC MSs are fabricated by incorporating pWGP into calcium-crosslinked alginate microspheres with subsequent chitosan surface modification to enhance mucosal adhesion. These pWGPAC MSs demonstrated exceptional stability under acidic conditions while enabling targeted release in the colon. In a mouse model of UC, the pWGPAC MSs effectively mitigated mucosal injury, attenuated inflammation, and restored intestinal barrier function. Further mechanistic investigations revealed that these pWGPAC MSs modulated the TLR4/MYD88 signaling pathway and promoted M2 macrophage polarization. Integrated microbiome and metabolome analyses demonstrated that these pWGPAC MSs regulated the gut microbiota composition and decreased pro-inflammatory metabolite levels. In addition, these microspheres demonstrated promising safety profiles. Collectively, these findings establish pWGPAC MSs as a promising therapeutic strategy for the treatment of UC and provide a solid foundation for future clinical applications.
研究领域:
药学
·
胃肠病学
·
免疫学
·
微生物学
·
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
Wei Liu,Di Liu,Tianyi Cui,Yili Wang,Sufei Zhou,Fangzhen Tian,Ke Yang,Wei Wang,Lewei Bi,Kelong Fan,Lan Li,Hao Wang,Xiao-Dong Zhang
Pneumonia involves complex immunological and pathological processes leading to pulmonary dysfunction, which can be life-threatening yet lacks effective specialized medications. Natural enzymes can be used as biological agents for the treatment of oxidative stress-related diseases, but limiting to catalytic and environmental stability as well as high cost. Herein, an artificial enzyme, gold nanoclusters (Au NCs) with excellent stability, bioactivity, and renal clearance can be used as the next-generation biological agents for acute lung injury (ALI) and allergic lung disease (ALD). The Au 25 clusters can mimic catalase (CAT) and glutathione peroxidase (GPx), and the K m of Au 24 Er 1 with H 2 O 2 reaches 1.28 mM, about 22 times higher than natural CAT (≈28.8 mM). The clusters inhibit the oxidative stress in the mitochondria and promote the synthesis of adenosine triphosphate (ATP). The molecular mechanism shows that the TLR4/MyD88/NF-κB pathway and M1 macrophage-mediated inflammatory response are suppressed in ALI and the Th1/Th2 imbalance in ovalbumin (OVA)-induced ALD is rescued. Further, the clusters can notably improve lung function in both ALI and ALD models which paves the way for immunomodulation and intervention for lung injury and can be used as a substitute for natural enzymes and potential biopharmaceuticals in the treatment of various types of pneumonia.
研究领域:
纳米技术
·
免疫学
·
药理学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Yawen Zhang,Yue Wu,Yuping Yan,Yijing Ma,Linglan Tu,Jingjing Shao,Xuanyu Tang,Lingfeng Chen,Guang Liang,Lina Yin
Conventional oral therapy for ulcerative colitis (UC) is associated with premature release or degradation of drugs in the harsh gastrointestinal environment, resulting in reduced therapeutic effectiveness. Consequently, we aimed to develop a dual-targeted delivery system with a nanoparticle-in-microparticle (nano-in-micro) structure. The prepared Asiatic Acid-loaded delivery system (AA/CDM-BT-ALG) had pH-sensitive properties. Cellular uptake evaluation confirmed that nanoparticles exhibited targeted absorption by macrophages and Caco-2 cells through mannose (Man) receptor and biotin-mediated endocytosis, respectively. Therefore, this mechanism effectively enhances intracellular drug concentration. Additionally, the biodistribution study conducted on the gastrointestinal tract of mice indicated that the colon of the microspheres group showed higher fluorescence intensity with longer duration than the other groups. This finding indicated that the microspheres exhibited selective accumulation in areas of colon inflammation. In vivo experiments in colitis mice showed that AA/CDM-BT-ALG significantly alleviated the histopathological characteristics of the colon, reduced neutrophil and macrophage infiltration, and decreased pro-inflammatory cytokine expression. Furthermore, the effect of AA/CDM-BT-ALG on colitis was validated to be closely related to the TLR4/MyD88/NF-κB signaling pathway. The present findings suggest that the development of a dual-targeted delivery system has been accomplished effectively, with the potential to serve as a drug-controlled release system for treating UC. This article is protected by copyright. All rights reserved
研究领域:
药剂学
·
药理学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Wenbo Ge,Zhun Li,Yajun Yang,Xiwang Liu,Zhaohan Zhu,Lixia Bai,Zhe Qin,Xiao Xu,Jianyong Li,Shihong Li
Pathogenic Escherichia coli ( E. coli ) can cause intestinal diseases in humans and livestock, damage the intestinal barrier, increase systemic inflammation, and seriously threaten human health and the development of animal husbandry. In this study, we designed and synthesized a novel conjugate florfenicol sulfathiazole (FST) based on drug combination principles, and investigated its antibacterial activity in vitro and its protective effect on inflammatory response and intestinal barrier function in E. coli O78-infected mice in vivo . The results showed that FST had superior antibacterial properties and minimal cytotoxicity compared with its prodrugs as florfenicol and sulfathiazole. FST protected mice from lethal E. coli infection, reduced clinical signs of inflammation, reduced weight loss, alleviated intestinal structural damage. FST decreased the expression of inflammatory cytokines IL-1β, IL-6, TNF-α, and increased the expression of claudin-1, Occludin, and ZO-1 in the jejunum, improved the intestinal barrier function, and promoted the absorption of nutrients. FST also inhibited the expression of TLR4, MyD88, p-p65, and p-p38 in the jejunum. The study may lay the foundation for the development of FST as new drugs for intestinal inflammation and injury in enteric pathogen infection.
研究领域:
药理学
·
微生物学
·
免疫学
·
兽医学
✓ 已验证
DOI
PubMed
高影响因子
BIOSCIENCE REPORTS
·
2022
·Vol. 42
·期 2
·
IF 3.976
Wang Xiaoya,Zhang Xinyu,Su Jianqing,Chu Xiuling
Here, we study the therapeutic effect of Acanthopanax senticosus total flavonoids (ASTFs) using a mouse intestinal inflammation model. The inflammation model used in the present study was developed through lipopolysaccharide (LPS) treatment of mice. The experimental mice were divided into a control group, model group (10 mg/kg LPS), dexamethasone group (1 mg/kg DEX) and ASTF low-, medium- and high-dosage groups (200, 400 and 800 mg/kg, respectively). The morphological and structural changes in the ileum, jejunum and duodenum were observed using HE staining. The number of intestinal goblet cells (GCs) was calculated based on PAS staining. The contents of interleukin (IL)-1β, IL-6, prostaglandin E2 (PGE2) and tumor necrosis factor α (TNF-α) were determined using enzyme-linked immunosorbent assay (ELISA) and the related mRNA expression level were measured by RT-PCR. The protein expression levels of Toll-like receptor 4 (TLR4), MyD88, p65 and p-p65 were measured using Western blotting. In addition, the 16S rRNA sequences of bacterial taxa were amplified and analyzed to assess changes in the intestinal microbes of LPS-induced mice and also in response to regulation by ASTF. Following intervention with ASTF, different therapeutic effects were shown according to the various dosages tested, all of which resulted in improved intestinal morphology and an increased number of intestinal GCs, while the contents of IL-1β, IL-6, PGE2 and TNF-α and the related mRNA expression level were significantly reduced. The TLR4, MyD88 and p-p65/p-65 protein expression levels were also significantly reduced. In addition, 16S rRNA sequencing results show that LPS disrupts the structure of mouse gut microbes, though we observed that normal microbial status can be restored through ASTF intervention.
研究领域:
药理学
·
免疫学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2022
·
IF 5.895
Sen Li,Yu Chen,Yu Zhang,Hongyan Lv,Lei Luo,Shuo Wang,Xiao Guan
Coffee cherry husks, the main byproduct of coffee production, contain an abundance of polyphenols. In this study, dextran sodium sulfate (DSS)-induced colitis mice were used to study the protective effects of polyphenolic extracts of coffee cherry husks (CCHP) on inflammation. The results indicated that CCHP administration alleviated the histological changes of DSS-induced colitis in mice and downregulated the mRNA level of TNF-α, IL-1β, IL-6 and Cox-2. Interestingly, CCHP inhibited the activation of microglia and suppressed neural inflammation in the brain. The TLR4/Myd88/NF-κB signaling pathway was examined and found to be inhibited by CCHP. Furthermore, a determination of the gut microbiota showed that an alteration of microbiota induced by DSS was restored by CCHP, including the decrease of the relative abundance of Proteobacteria and the increase of Bacteroidota. In conclusion, our results revealed the great potential of CCHP to alleviate brain inflammation in colitis mice by inhibiting the NF-κB signaling pathway and regulating gut microbiota.
研究领域:
药理学
·
免疫学
·
神经科学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2021
·
IF 6.988
Qiyan Chen,Ruifeng Luo,Xiaoqin Han,Jinming Zhang,Yao He,Shanshan Qi,Xiulan Pu,Wenbiao Nie,Lingling Dong,Haiting Xu,Fang Liu,Meisi Lin,Huiyun Zhong,Chaomei Fu,Fei Gao
In this study, we developed an advanced colitis-targeted nanoparticles (NPs)-into-yeast cell wall microparticles (YPs) drug delivery system for ulcerative colitis (UC) therapy. In brief, YPs entrap hyaluronic acid (HA), and polyethylenimine (PEI) modified rhein (RH)-loaded ovalbumin NPs (HA/PEI-RH NPs) to form HA/PEI-RH NYPs. YPs can make HA/PEI-RH NPs pass through gastric environment stably and be degraded by β-glucanase to promote drug release from HA/PEI-RH NYPs in the colon. Cellular uptake evaluation confirmed that HA/PEI-RH NPs could specifically target and enhance the uptake rate via HA ligands. In biodistribution studies, HA/PEI-RH NYPs were able to efficiently accumulate in the inflammed colon in mice. In vivo experiments revealed that the HA/PEI-RH NYPs could significantly alleviate inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Therefore, HA/PEI-RH NYPs have advantages of good gastric stability, β-glucanase-sensitive release ability, macrophage-targeted ability, and anti-UC effects. These advantages indicate YPs-entrapped multifunctional NPs are a promising oral drug delivery system for UC therapy.
研究领域:
药学
·
生物技术
·
医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Yannan Chen,Wentao Su,Shanshan Tie,Weina Cui,Xiaoting Yu,Lijuan Zhang,Zheng Hua,Mingqian Tan
Orally targeted strategy of anti-inflammatory agents has attracted tremendous attention for reducing highly health-care costs and enhancing the intervention efficiency of ulcerative colitis (UC). Herein, we developed a new kind of sequence-targeted astaxanthin nanoparticles for UC treatment. Astaxanthin nanoparticles were firstly designed by self-assembly method using (3-carboxypentyl) (triphenyl) phosphonium bromide (TPP)-modified whey protein isolate (WPI)-dextran (DX) conjugates. Subsequently, lipoic acid (LA) modified hyaluronic acid (HA) was coated on the surface of the nanoparticles by double emulsion evaporation method. Exhilaratingly, the constructed sequence-targeted astaxanthin nanoparticle exhibited excellent macrophages and mitochondria targeting ability, with a Pearson's correlation coefficient of 0.84 adstnd 0.92, respectively. In vivo imaging elucidated an obvious accumulation of the sequence-targeted nanoparticles in colon tissues in UC mice. Meanwhile, the reduction stimulus release features of astaxanthin were observed in the presence of 10 mM of glutathione (GSH) at pH 7.4. Most importantly, in vivo experiments indicated that sequence-targeted astaxanthin nanoparticles could markedly alleviate inflammation by moderating the TLR4/MyD88/NF-κB signaling pathway . What's more, the composition of gut microbiota and the production of short chain fatty acid were also improved upon the uptake of sequence-targeted astaxanthin nanoparticles. Our results suggested this novel astaxanthin nanoparticles, which showed sequence-targeted ability and reduction response feature, could be exploited as a promising strategy for effective UC treatment.
研究领域:
药学
·
纳米技术
·
炎症性肠病
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
·
2023
·
IF 4.6
Jianghui HU,Jimin NI,Junping ZHENG,Yanlei GUO,Yong YANG,Cheng YE,Xiongjie SUN,Hui XIA,Yanju LIU,Hongtao LIU
Traditionally, Tripterygium hypoglaucum (Levl.) Hutch (THH) are widely used in Chinese folk to treat rheumatoid arthritis (RA). This study aimed to investigate whether the anti-RA effect of THH is related with the gut microbiota. The main components of prepared THH extract were identified by HPLC-MS. C57BL/6 mice with adjuvant-induced arthritis (AIA) were treated with THH extract by gavage for one month. THH extract significantly alleviated swollen ankle, joint cavity exudation, and articular cartilage destruction in AIA mice. The mRNA and protein levels of inflammatory mediators in muscles and plasma indicated that THH extract attenuated inflammatory responses in the joint by blocking TLR4/MyD88/MAPK signaling pathways. THH extract remarkably restored the dysbiosis of the gut microbiota in AIA mice, featuring the increases of Bifidobacterium , Akkermansia , and Lactobacillus and the decreases of Butyricimonas , Parabacteroides , and Anaeroplasma . Furthermore, the altered bacteria were closely correlated with physiological indices and drove metabolic changes of the intestinal microbiota. In addition, antibiotic-induced pseudo germ-free mice were employed to verify the role of the intestinal flora. Strikingly, THH treatment failed to ameliorate the arthritis symptoms and signaling pathways in pseudo germ-free mice, which validates the indispensable role of the intestinal flora. For the first time, we demonstrated that THH extract protects joint inflammation by manipulating the intestinal flora and regulating the TLR4/MyD88/MAPK signaling pathway. Therefore, THH extract may serve as a microbial modulator to recover RA in clincial practice.ver RA in clincial practice.
研究领域:
药理学
·
免疫学
·
微生物学
·
风湿病学
✓ 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）