PHYTOTHERAPY RESEARCH
·
2023
·
IF 7.2
Waimei Si,Xin Li,Bei Jing,Shiquan Chang,Yachun Zheng,Zhenni Chen,Guoping Zhao,Di Zhang
(Switching from the microglial M1 phenotype to the M2 phenotype is a promising therapeutic strategy for neuropathic pain (NP). This study aimed to investigate the potential use of stigmasterol for treating NP. In animal experiments, 32 male Sprague–Dawley rats were randomly divided into the sham operation group, chronic constriction injury (CCI) group, CCI + ibuprofen group, and CCI + stigmasterol group. We performed behavioral tests, enzyme-linked immunosorbent assay, hematoxylin-esoin staining (H&E) staining and immunohistochemistry, immunofluorescence, and Western blotting. In cell experiments, we performed flow cytometry, immunofluorescence, Western blotting, and qRT-PCR. Stigmasterol reduced thermal and mechanical hyperalgesia and serum IL-1β and IL-8 levels and increased serum IL-4 and TGF-β levels in CCI rats. Stigmasterol reduced IL-1β, COX-2, and TLR4 expression in the right sciatic nerve and IL-1β expression in the spinal cord. Stigmasterol reduced the expression of Iba-1, TLR4, MyD88, pNF-κB, pP38 MAPK, pJNK, pERK, COX-2, IL-1β, and CD32 in the spinal cord of CCI rats while increasing the expression of IL-10 and CD206. Stigmasterol decreased M1 polarization markers and increased M2 polarization markers in lipopolysaccharide (LPS)-induced microglia and decreased the expression of Iba-1, TLR4, MyD88, pNF-κB, pP38 MAPK, pJNK, pERK, iNOS, COX-2, and IL-1β in LPS-treated microglia while increasing the expression of Arg-1 and IL-10. Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF-κB pathway to alleviate NP.
研究领域:
药理学
·
神经科学
·
免疫学
·
疼痛研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yan Ma,Wangting Zhou,Huiling Wang,Muci Wu,Sijia Jiang,Yubao Li,Chengjie Ma,Rui Zhang,Jingren He
In this study, a whey protein isolate (WPI)-chitooligosaccharide (COS) stabilized bitter melon ( Momordica charantia L.) seed oil emulsions (WC-BSOE) were prepared using the electrostatic layer-by-layer self-assembly technique, and their modulating effects on ulcerative colitis (UC) were investigated in dextran sulfate sodium (DSS)-induced UC mice model. The stability and releasing ability of WC-BSOE under simulated gastrointestinal digestion condition and their acute toxicity were also investigated. The results showed that WC-BSOE was stable to droplet aggregation in the simulated gastric and intestinal fluids and exhibited sustained release profile during gastrointestinal transit, evidenced by the measurement of particle size, polydispersity index, zeta-potential and released free fatty acids contents. Moreover, WC-BSOE had no toxic effects on BALB/c mice within the dose range of 40,000 mg/kg body weight (BW), and treatment with WC-BSOE at a dosage of 15 mg/kg BW effectively relieved DSS-induced UC symptoms in mice. Furthermore, WC-BSOE could improve the IL-4 and IgA contents in serum, as well as up-regulate the occludin and ZO-1 expressions and down-regulate MPO, MDA and ROS levels in colon tissues of colitis mice, and it also elevated the diversity and relative abundances of Firmicutes, Bacteroides, and Lactobacillus in the intestinal microbiota. These findings indicated that WC-BSOE exerted protective effects in UC through decreasing proinflammatory cytokines, increasing tight junction proteins, suppressing oxidative stress, and regulating intestinal microbiota. Collectively, this study suggested WC-BSOE might be developed as a promising dietary supplement for UC protection.
研究领域:
药学
·
营养学
·
胃肠病学
·
免疫学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Ophthalmology
·
2016
·
IF 1.463
Hongyan Zhou,Wensong Zhang,Xunyi Gao,Hongguang Zhang,Ning Kong
Purpose. The study aimed to evaluate the effect of all-trans retinoic acid-loaded nanostructured lipid carriers (ATRA-NLCs) on the zymosan-induced expression of the cytokines IL-4, IL-10, and IFN-γ and the matrix metalloproteinases/tissue inhibitor of metalloproteinases (MMPs/TIMPs) and TLR2 in rabbit corneal fibroblasts (RCFs). Methods. ATRA-NLCs were prepared by emulsification. RCFs were isolated and harvested after four to seven passages in monolayer culture. Cytokine release (IL-4, IL-10, and IFN-γ) induced by zymosan was analyzed by cytokine release assay, reverse transcription, and real-time polymerase chain reaction (RT-PCR) analysis detection. MMP-1, MMP-3, and MMP-13, TIMP-1 and TIMP-2, and TLR2 expression were analyzed by immunoblotting. Results. ATRA-NLCs were resistant to light and physically stable, and the average size of the ATRA-NLCs was 200 nm. ATRA-NLCs increased the zymosan-induced release of IL-4 and IL-10 and decreased the release of IFN-γ by RCFs. ATRA-NLCs decreased the levels of TLR2 and MMPs/TIMPs above. Conclusions. ATRA may be a potent anti-inflammatory agent for the therapy of fungal keratitis (FK).
研究领域:
药理学
·
眼科学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2022
·Vol. 18
·期 36
·2201656
·
IF 15.153
Yang Sun,Qianrong Zhou,Yawei Du,Jian Sun,Wei Bi,Wenjuan Liu,Ruixue Li,Xingwen Wu,Fei Yang,Liang Song,Ni Li,Wenguo Cui,Youcheng Yu
Bone defect regeneration depends on the population and lifespan of M2 macrophages, which are regulated by dual signals generated by the “physical” spatial configuration of biological tissues and “molecular” chemokines. Herein, inspired by the reprogramming of macrophages, immunoengineered porous microspheres are constructed to accelerate bone repair through the regulation of both “physical” and “molecular” signals. The porous structure of injectable poly ( l -lactic acid) (PLLA) microspheres prepared by the microfluidic technique provides a “physical signal” for osteogenic differentiation. Additionally, interleukin (IL)-4-loaded liposomes (Ls) are modified on PLLA microspheres through amide bonds to produce IL-4/Ls/PLLA microspheres, providing a “molecular signal” in stimulating the differentiation of macrophages to M2 type. It is confirmed that IL-4/Ls/PLLA microspheres could induce M2-macrophages polarization and potentiate osteoblast proliferation and differentiation while coculturing with macrophages and osteoblasts in vitro. Besides, IL-4/Ls/PLLA microspheres are proved to promote bone defect regeneration by inducing the conversion of M1 macrophages to M2 through dual biosignal-functional regulation in both the calvaria defect and maxillary sinus defect models. Overall, the immuno-reprogrammed IL-4/Ls/PLLA microspheres achieve the precise immuno-reprogramming of macrophages by dual biosignal-functional regulation. This immune reengineering strategy paves a way for clinical bone defect treatment.
研究领域:
组织工程
·
生物材料
·
免疫学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROBIAL PATHOGENESIS
·
2024
·
IF 3.3
Tongyu Zhang,Yawen Tian,Xiao Zhang,Wenfeng Wang,Yingkai He,Chongbo Ge,Futing Jia,Zhannan Wang,Yanlong Jiang
The H9N2 avian influenza virus (AIV) is spreading worldwide. Presence of H9N2 virus tends to increase the chances of infection with other pathogens which can lead to more serious economic losses. In a previous study, a regulated delayed lysis Salmonella vector was used to deliver a DNA vaccine named pYL233 encoding M1 protein, mosaic HA protein and chicken GM-CSF adjuvant. To further increase its efficiency, chitosan as a natural adjuvant was applied in this study. The purified plasmid pYL233 was coated with chitosan to form a DNA containing nanoparticles (named CS233) by ionic gel method and immunized by intranasal boost immunization in birds primed by oral administration with Salmonella strain. The CS233 DNA nanoparticle has a particle size of about 150 nm, with an encapsulation efficiency of 93.2 ± 0.12 % which protected the DNA plasmid from DNase I digestion and could be stable for a period of time at 37°. After intranasal boost immunization, the CS233 immunized chickens elicited higher antibody response, elevated CD4 + T cells and CD8 + T cells activation and increased T-lymphocyte proliferation, as well as increased productions of IL-4 and IFN-γ. After challenge, chickens immunized with CS233 resulted in the lowest levels of pulmonary virus titer and viral shedding as compared to the other challenge groups. The results showed that the combination of intranasal immunization with chitosan-coated DNA vaccine and oral immunization with regulatory delayed lytic Salmonella strain could enhance the immune response and able to provide protection against H9N2 challenge.
研究领域:
免疫学
·
病毒学
·
兽医学
✓ 已验证
DOI
PubMed
高影响因子
INFLAMMATION
·
2023
·
IF 5.1
Feng Yong,Hu Jiapeng,Liu Fen,Shang Yunxiao
Asthma is a chronic inflammatory disease characterized by airway remodeling and lung inflammation. Collagen triple helix repeat containing 1 (CTHRC1), a glycoprotein, is involved in multiple pathological processes, including inflammation and fibrosis. However, the function of CTHRC1 in asthma remains unclear. In the present study, the mouse asthma model was successfully generated by sensitizing and challenging mice with ovalbumin (OVA). CTHRC1 expression at both RNA and protein levels was significantly upregulated in lung tissues of asthmatic mice. Asthmatic mice exhibited significant airway remodeling as evidenced by increased bronchial wall and smooth muscle cell layer thickness, goblet cell hyperplasia and collagen deposition, and epithelial-mesenchymal transition (EMT), but those characteristics were reversed by CTHRC1 silencing. The cell model with transforming growth factor-β1 (TGF-β1) induction in bronchial epithelial cells (BEAS-2B) was conducted to verify the effects of CTHRC1 on EMT, a classic mechanism that mediates airway remodeling. The results showed that TGF-β1 stimulation increased CTHRC1 expression, and CTHRC1 knockdown inhibited TGF-β1-induced EMT. OVA-treated mice also showed increased inflammatory cell infiltration and the production of OVA-specific immunoglobulin E (IgE), interleukin (IL)-4, IL-5, and IL-13, which were decreased by CTHRC1 downregulation. The effects of CTHRC1 on OVA-induced airway inflammation were further determined by treating BEAS-2B cells with IL-13, in which CTHRC1 knockdown reduced the IL-13-induced secretion of pro-inflammatory factors, including IL-4 and IL-5. In conclusion, these results indicate that CTHRC1 silencing attenuates asthmatic airway remodeling and inflammation in vivo and in vitro, suggesting that CTHRC1 may be a potential target for asthma treatment. Graphical Abstract
研究领域:
免疫学
·
呼吸医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2024
·
IF 4.3
Yi Chen,Hongjin Qian,Dandan Peng,Yan Jiang,Qiaolin Liu,Yan Tan,Longbao Feng,Biao Cheng,Guilan Li
Wound infection is a major problem faced during wound healing. Therefore, it is necessary to develop wound dressings with excellent antimicrobial properties. Here, a smart response system of PVA-TPE/HA-AMP/SF/ALG wound dressing was prepared by a combination of chemical cross-linking and freeze-drying methods. We grafted AMP onto HA to endow the wound dressing with bacterial resistance and slow release of AMP. At the same time, the system detects bacterial activity in real time for precise antimicrobial activity (through the use of PVA-TPE) and modulates inflammation to reduce bacterial infection (through the use of AMP). In addition, the PVA-TPE/HA-AMP/SF/ALG wound dressing has a good three-dimensional mesh structure, which promotes cell proliferation, enhances collagen deposition and angiogenesis, and thus effectively promotes rapid healing of infected wounds. Moreover, it can induce the expression of inflammatory factors such as VEGF, TNF-α, IFN-γ, IL-4 and TGF-β1 in infected wounds through the Wnt/CAMK/p-PKC signaling pathway, inhibit inflammatory responses, promote wound healing and reduce scar formation. Therefore, the PVA-TPE/HA-AMP/SF/ALG wound dressing smart response system shows great promise in infected wound healing.
研究领域:
材料科学
·
生物医学工程
·
伤口愈合
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2024
·
IF 7.2
Zhaohui Dang,Weihua Huang,Xiayu Cai,Jiandong Ye,Weikang Xu
Most bone filler materials currently achieve bone regeneration by mimicking the natural bone extracellular matrix. However, it is difficult for these materials to replicate the structural functions and bioactivities, including immunomodulation, of natural bone perfectly to reduce inflammation and promote bone regeneration synergistically. Repairing bone defects with scaffolds using a decellularised extracellular matrix (dECM) as a matrix material is an important clinical application and research direction. Here, we processed bovine cancellous bone via an optimised combination of decellularisation methods and preferred dECM, which has the shortest processing time and lowest immunogenicity. Hexagonal mesoporous silica (HMS)/poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with bone morphogenetic protein-2 (BMP-2) were prepared using the complex emulsion method. The HMS/PLGA microspheres had longer cytokine release periods than did the separate HMS and PLGA microspheres. Composite BMP-2/HMS/PLGA microspheres were used to prepare dual-loaded cytokine scaffolds with bone immunomodulatory capacity, which were prepared from composite BMP-2/HMS/PLGA microspheres to increase the osteogenic activity of the dECM and to adsorb interleukin-4 (IL-4) on the surface of the scaffolds. The results showed that the dECM had good cytocompatibility and mechanical strength, and the composite microspheres and IL-4 further endowed the dECM with an ordered spatiotemporally controlled release function, which could release BMP-2 for more than 4 months in the long term and release IL-4 for approximately 10 days in the short term. The composite scaffold not only effectively promoted the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) but also immunomodulated the M1 to M2 polarisation of macrophages (MPs) and mediated the M2 polarisation of MPs, which in turn promoted the osteogenic differentiation of BMSCs, creating a favourable immune microenvironment for bone regeneration. In vivo, the dual drug-loaded scaffolds also exhibited good biocompatibility and significantly superior immunomodulatory bone-enhancing properties compared with those of the other groups. In summary, the combination of dECM scaffolds with cytokine-carrying microspheres and immunomodulatory factors can promote the orderly spatiotemporal release of cytokines, which significantly enhances the bone regeneration and repair effects of dECM scaffolds and is a promising bone filler material for clinical application.
研究领域:
组织工程
·
再生医学
·
生物材料
·
免疫学
·
骨生物学
✓ 已验证
产品关联
DOI
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Mingxin Li,Shugang Li,Chunqing Ai,Wenxiu Zhu,Donglin Sui,Yixuan Li,Binbin Hou,Xiaomeng Ren
The increasing incidence of atopic dermatitis (AD) presents a public health issue, and thus there is an urgent need for safe and effective preventive strategies. In this study, a strategy to reduce the risk of AD in offspring by administering probiotics to the mother was explored. Female mice were given Lactobacillus rhamnosus RL-H3-005 (RL) and Pediococcus acidilactici RP-H3-006 (RP) during pregnancy and lactation period, and their inhibition effects on AD symptoms in offspring mice were evaluated. The results showed that supplementation with RL and RP during pregnancy and lactation period altered not only the gut microbiota community but also microbial community in milk in pregnant mice. Further study showed that pups from RL- and RP-treated pregnant mice had mild symptoms of AD, characterized by reduced epidermal thickness in the ear tissues and numbers of mast cells, which was associated with the reduction in secretory immunoglobulin A (sIgA), immunoglobulin E (IgE), IL-4, IL-5, IL-13, thymic stromal lymphopoietin (TSLP), and eosinophil cationic protein (Ecp). The underlying mechanism of RL and RP on the inhibition of AD symptom in offspring was closely associated with the alterations of the gut microbiota community in offspring, including an increase in Ligilactobacillus and Bacteroides . This study implies that RL and RP hold the potential to reduce the risk of AD in offspring via gut-mammary axis during the pregnancy and lactation period.
研究领域:
微生物学
·
免疫学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Siyang Liu,Liying Yao,Yumeng Wang,Yi Li,Yanju Jia,Yueyue Yang,Na Li,Yuanjing Hu,Deling Kong,Xianhao Dong,Kai Wang,Meifeng Zhu
The inertness of synthetic polymer materials and the insufficient mechanical strength of reprocessed decellularized extracellular matrix (dECM) limited their promotive efforts on tissue regeneration. Here, we prepared a hybrid scaffold composed of PCL microfibers and human placental extracellular matrix (pECM) nanofibers by co-electrospinning, which was grafted with heparin and further absorbed with IL-4. The hybrid scaffold with improved hemocompatibility firstly switched macrophages to anti-inflammatory phenotype (increased by 18.1%) and then promoted migration, NO production, tube formation of endothelial cells (ECs), and migration and maturation of vascular smooth muscle cells (VSMCs), and ECM deposition in vitro and in vivo . ECs coverage rate increased by 8.6% and the thickness of the smooth muscle layer was 1.8 times more than PCL grafts at 12 wks. Our study realized the complementary advantages of synthetic polymer materials and dECM materials, and opened intriguing perspectives for the design and construction of small-diameter vascular grafts (SDVGs) and immune-regulated materials for other tissue regeneration.
研究领域:
生物材料
·
组织工程
·
血管生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
·
IF 8.786
Tian Xiaoying,Fan Rongbo,He Hong,Cui Qingyu,Liang Xi,Liu Qiqi,Liu Tongjie,Lin Kai,Zhang Zhe,Yi Huaxi,Gong Piming,Zhang Lanwei
Food allergy is a serious public health problem because of its high incidence and risk. Probiotics can induce immune regulation in patients with allergic diseases, but its mechanism is not fully clear. In this paper, β-lactoglobulin (β-LG)-sensitized mice were used as models to explore the mechanism of Bifidobacterium animalis KV9 (KV9) and Lactobacillus vaginalis FN3 (FN3) on reducing allergic reactions and regulating immune cell function. The results showed that oral administration of KV9 and FN3 significantly reduced the scores of allergic symptoms, hypothermia symptoms, and serum levels of β-LG-specific immunoglobulins E (β-LG-sIgE), histamine, and mast cell protease in allergic mice. Flow cytometry analysis of intestinal dendritic cells (DCs) showed that the proportion of CD11c+major histocompatibility complex (MHC)-II+DCs, CD11c+CD80+DCs, and CD11c+ CD86+DCs increased after KV9 and FN3 intervention, indicating that the strains induced immature DCs and decreased the antigen-presenting capacity of DCs. Meanwhile, the toll-like receptor 4 (TLR4)-NF-κB signaling pathway was activated in DCs. The secretion of interleukin-12 (IL-12) was significantly increased, while interleukin-4 (IL-4) was decreased by DCs after KV9 and FN3 intervention, indicating that DCs have the potential to promote T-cell differentiation into T helper type 1 (Th1) cells. Furthermore, the proportion of CD3+CD8−IFN-γ+ T cells in the spleen increased, while CD3+CD8−IL-4+T cells decreased after oral administration of KV9 and FN3, correcting the T helper type 2 (Th2)-skewed immune responses. These results indicate that KV9 and FN3 reduce β-LG-induced allergic symptoms in mice, and suggest that the two potential probiotics might be used as an alternative therapeutic agent for mitigating food allergy.
研究领域:
免疫学
·
微生物学
·
过敏学
·
分子生物学
✓ 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）