ACS Applied Materials & Interfaces
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2024
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IF 8.3
Jinzhi Shi,Kai Shi,Qi Dong,Junfeng Yang,Yingshan Zhou,Peng Ma,Sha She,Fan Yang,Zuojiong Gong
Enriching erythrocytes and platelets in seconds and providing a fast seal in bleeding sites is vital to fatal hemorrhage control. Herein, hydrophilic chitosan fibrous mats (CECS-D mats) are fabricated by introducing hydrophilic carboxyethyl groups and subsequent catechol groups onto chitosan fibers. Due to strong hydrophilicity, CECS-D mats exhibit rapid liquid-absorption capacity, especially instantaneous absorptivity to the rabbit blood, which can achieve erythrocyte and platelet aggregations quickly by concentrating blood, thus promoting the formation of blood clots. Furthermore, the mats are self-oxidated to form quinone-amine adducts or quinone multimers by adjusting pH conditions, which not only provides tissue adhesion but also induces erythrocyte aggregation and platelet adhesion, further enhancing the seal and triggering quick closure to achieve fast hemostasis. Therefore, the mats reveal superior hemostatic performance in rabbit liver and spleen models over CECS mats and gauze. Especially in the fatal femoral artery injury model of rabbits, the mats reduce the blood loss by ∼75% and shortened the bleeding time by ∼50% compared with CECS mats, which have been reported to have the same hemostatic effect as commercialized Celox products in a swine femoral artery injury model. Besides, the mats are cytocompatible and degradable as well as antibacterial. This chitosan mat is a promising hemostatic material for fatal hemorrhage control.
研究领域:
生物材料
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止血
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组织工程
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Nano Today
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2024
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IF 13.2
Jinghui Wang,Rongrong Jia,Wei Wei,Mingli Hu,Feng Li,Wenjing Wang,Peng Ye,Jiawei Zhao,Ling Xu,Shuang Wang,Yugang Wang,Min Shi,Guanghui Ma
Liver fibrosis (LF) afflicts millions of patients worldwide, yet a universally accepted standard therapy remains elusive. Notably, an elevation of profibrotic monocytes is observed in peripheral blood of LF patients. Inspired by the spleen’s reported “accomplice” role in LF development and its monocyte reservoir function, the mechanism of spleen-liver co-morbidity is further explored, unveiling an innovative therapy strategy for LF. In detail, exosomes are prepared from macrophages with low expression of lymphocyte antigen 6 complex locus C (ly6c low Exo), showcasing a distinctive ability to accumulate simultaneously in both spleen and liver. The ly6c low Exo treatment reduces profibrotic monocyte proportion in spleen, decreases the circulating profibrotic monocytes, and reshapes hepatic immune microenvironment including macrophages, T cells, and natural killer cells. Such synergistic modulation culminates in the reduction of extracellular matrix, achieving satisfying therapeutic outcomes in LF model. Furthermore, the exosome therapeutic is iterated via loading pirfenidone into ly6c low Exo. A cooperation of two distinct mechanisms is thus achieved by combining the ly6c low Exo immunoregulation with pirfenidone-mediated transforming growth factor-β pathway inhibition, resulting in an enhanced antifibrotic effect in severe LF model. The ly6c low Exo platform described, with its remarkable capacity for dual-accumulation, multifunctional immunoregulatory capabilities, and drug-loading property, presents extensive clinical application prospects for LF treatment.
研究领域:
肝病学
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免疫学
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药理学
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细胞生物学
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DOI
高影响因子
Journal of Functional Foods
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2021
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IF 4.451
Xiaoyan Su,Ming Zhao,Xinyu Fu,Xiaodan Ma,Wei Xu,Songhua Hu
Polysaccharides from Rubus chingii Hu fruits (RFPs) were extracted, purified, characterized and investigated for immunomodulatory activity. Results indicated that RFPs were heteropolysaccharides with molecular weight of 51.7 kDa and contained carbohydrate contents of 96.83%. RFPs with characteristic absorptive peaks of polysaccharide structure and α-configuration were composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose and fucose with a molecular ratio of 0.08:0.17:0.16:0.48:5.73:1.00:1.79:0.03. RFPs promoted splenocyte proliferation, NO release, cytokine production and intracellular Ca 2+ concentration. The mechanism underlying splenocyte activation by RFPs was elucidated by RNA-Seq, in which 2214 differentially expressed genes (DEGs), 2030 GO terms and 92 KEGG pathways were identified. RFPs were further proved to induce a balanced Th1/Th2/Th17 response pattern through MAPK, NF-κB, Jak-STAT and Calcium signaling pathways in splenocytes. These findings provided a fundamental basis for the further application of RFPs as immunomodulators in food and medicine.
研究领域:
免疫学
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药理学
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分子生物学
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生物化学
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DOI
高影响因子
Journal of Functional Foods
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2021
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IF 4.451
Xiaolan Chen,Bingyan Cai,Jing Wang,Zhicun Sheng,Haifeng Yang,Dada Wang,Jiahao Chen,Qingqing Ning
Mulberry leaf polysaccharide (MLP) possess many biological characteristics, such as immunomodulatory and antioxidant properties, but whether MLP can impact the distribution and characteristics of the gut microbiota is not yet clear. In this study, the effects of MLP on diversity- and immune-related factors and short-chain fatty acids (SCFAs) of the gut microbiota in mice were investigated. The results showed that MLP could restore the indexes of the thymus and spleen, the damaged intestinal barrier and levels of inflammatory cytokines in cyclophosphamide (CTX)-treated mice, and alleviate oxidative damage to the liver. Additionally, MLP were associated with a relatively higher abundance of Bacteroidetes but lower levels of Firmicutes, Butyricimonas and Eubacterium in CTX-treated mice. Moreover, MLP restored the levels of acetic acid, propionic acid, and n-butyric acid reduced by CTX. These results indicated that MLP, as a special ingredient, might regulate the immune response by altering the spatial structure of the gut microbiota and the production of SCFAs.
研究领域:
免疫学
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微生物学
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药理学
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DOI
高影响因子
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
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2016
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IF 1.617
Dongfang Hu,Ziqiang Han,Chunling Li,Lin Lv,Zilong Cheng,Sidang Liu
Amphenicols are effective, broad-spectrum antibiotics that function by inhibiting the peptidyl transferase activity of bacteria, while the drugs can also inhibit mitochondrial protein synthesis in eukaryotes through the same mechanism, which leads to multi-organ toxicity. Some side effects of each drug have been studied, while differences in the severity of the hemotoxicities and immunotoxicities of amphenicols have not been reported. Thus, it is important to identify, evaluate, and compare the potential hemotoxicities and immunotoxicities to guide their proper use in humans and animals, which will guarantee food safety and animal welfare. Ovalbumin-immunized Kunming mice were gavaged daily with amphenicols for seven days. Blood samples were collected for hematology analysis, and measuring anti-ovalbumin antibody levels and serum intereukin-2 concentrations. The bone marrow, spleen and thymus were collected for histopathology and apoptosis analyzes. Bone marrow nucleated cells (BMNCs) and splenocytes were harvested to determine their cell cycle stages and to analyze lymphocyte proliferation. The results demonstrated that amphenicols, especially florfenicol (FLO), induced cell cycle arrest and apoptosis of hematopoietic cells, and it changed the bone marrow hematopoietic microenvironment by decreasing the number of peripheral blood cells. Moreover, amphenicols, especially FLO, induced hypoplasia and atrophy of the spleen and thymus, induced cell cycle arrest, as well as splenocyte apoptosis, and decreased the proliferation and viability of lymphocytes and the humoral and cellular immunity of the treated mice. These results suggest that amphenicols induce hemotoxicity and immunotoxicity to some extent, and that FLO induces more severe toxicity than equal doses of chloramphenicol (CAP) and thiamphenicol (TAP).
研究领域:
药理学
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毒理学
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免疫学
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血液学
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产品关联
DOI
PubMed
高影响因子
Food & Function
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2017
·Vol. 8
·期 3
·1020-1027
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IF 3.247
Xiaotong Sheng,Jingmin Yan,Yue Meng,Yuying Kang,Zhen Han,Guihua Tai,Yifa Zhou,Hairong Cheng
This study was aimed at investigating the immunomodulating activity of Hericium erinaceus polysaccharide (HEP) in mice, by assessing splenic lymphocyte proliferation (cell-mediated immunity), serum hemolysin levels (humoral immunity), phagocytic capacity of peritoneal cavity phagocytes (macrophage phagocytosis), and NK cell activity. ELISA of immunoglobulin A (SIgA) in the lamina propria, and western blotting of small intestinal proteins were also performed to gain insight into the mechanism by which HEP affects the intestinal immune system. Here, we report that HEP improves immune function by functionally enhancing cell-mediated and humoral immunity, macrophage phagocytosis, and NK cell activity. In addition, HEP was found to upregulate the secretion of SIgA and activate the MAPK and AKT cellular signaling pathways in the intestine. In conclusion, all these results allow us to postulate that the immunomodulatory effects of HEP are most likely attributed to the effective regulation of intestinal mucosal immune activity.
研究领域:
免疫学
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分子生物学
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胃肠病学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2021
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IF 4.36
Li-na Ji,Shan Wu,Dan-qing Fu,Si-jia Fang,Guan-qun Xie,Yong-sheng Fan,Jie Bao
Ethnopharmacological relevance Jieduquyuziyin prescription (JP) is a traditional Chinese medicine (TCM) formula. According to both TCM theory and more than a decade of clinical practice, JP has been testified to be effective for systemic lupus erythematosus (SLE) treatment as an approved hospital prescription in China. Aim of the study To determine the effect of JP on the treatment of SLE by glucocorticoid (GC) and to further examine the molecular mechanisms. Materials and methods We conducted in vivo experiments to estimate the effect of JP on hepatic gluconeogenesis in MRL/lpr mice treated with GC. Additionally, isoproterenol (ISO) induced hepatic gluconeogenesis model and GC-treated MRL/lpr mouse hepatocytes were carried out in vitro experiments to verify the effect of JP on gluconeogenesis. Results The results showed that JP combined with GC could effectively alleviate the lupus symptoms in MRL/lpr mice and improve the pathological changes of the kidney and liver. And the combination of JP reduced the side effects caused by GC, which was related to the inhibition of GC-induced hepatic gluconeogenesis in MRL/lpr mice. Specifically, JP up-regulated the expression of glucocorticoid receptor (GR) α, phosphoinositide-3-kinase (PI3K) and Akt restrained by GC to reduce the production of forkhead box O1 (FoxO1), peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), and the gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). In viv o, the use of JP either alone or with GC could reduce spleen enlargement , high levels of serum antibodies, aggravated urine protein and renal pathological damage in MRL/lpr mice. Furthermore, the glucose content was reduced in the liver of MRL/lpr mice treated with JP, and the liver damage and steatosis were also alleviated. In vitro , the expressions of PI3K and Akt increased and the expressions of FoxO1, PGC-1α, PEPCK and G6Pase decreased after JP treatment in ISO-treated hepatocytes. Compared with MRL/MP mice, we found that JP could significantly inhibit the expression of gluconeogenesis in the hepatocytes of MRL/lpr mice induced by GC to a greater extent. Conclusions The therapeutic effect of JP on GC-induced is likely related to hepatic gluconeogenesis, which provides a new perspective to reveal the positive role of JP in SLE.
研究领域:
药理学
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免疫学
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分子生物学
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中医
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2022
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IF 7.129
Chao Han,Ying Wang,Ruiying Liu,Beibei Ran,Weidong Li
This study aimed to investigate the structure characteristics Lonicera flos polysaccharides (LP) and the protective effects of LP on cyclophosphamide-induced immunosuppression in mice. The results showed the yield and purity of LP was 1.41% and 94.15%, the molecular weight was 53 kDa, and composed of arabinose, rhamnose, ribose, xylose, mannose, fructose, galactose and glucose; and LP had typical polysaccharide structural characteristics via ultraviolet and Fourier transform infrared (FTIR) spectroscopy, 1 H NMR and 13 C NMR spectra, and scanning electron microscopy (SEM) analyses. Furthermore, LP obviously alleviated the injury of spleen and thymus; significantly promoted Interleukin-2 (IL-2), IL-6, tumor necrosis factor α (TNF-α), immunoglobulin (IgA, IgG and IgM) secretion; and improved the richness of gut microbiota and the contents of short-chain fatty acids (SCFAs) in immunosuppressive mice. Taken together, these results suggested that LP possessed strong protective effect on cyclophosphamide-induced immunosuppression in mice via modulating gut microbiota.
研究领域:
药理学
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免疫学
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分子生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Science China-Life Sciences
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2024
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IF 8
Zhang Zhen,Huang Weijun,Zhang Xiaoran,Wang Zhecun,Xie Manting,Xie Bingbing,Wang Yiling,Chen Xiaoyong,Xiang Andy Peng,Xiang Qiuling
Despite substantial advancements in modern medicine, the management of hypertension remains a major challenge. Stem cell-based therapies have recently demonstrated remarkable efficacy in treating cardiovascular diseases, including hypertension. However, the antihypertensive mechanism of mesenchymal stem cells (MSCs) has not been extensively explored. This study aimed to investigate the role of injected MSCs in regulating blood pressure homeostasis. Our previous study demonstrated that human induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC-MSCs) are functional and homogeneous sources for MSC-based therapy. After the injection of hiPSC-MSCs, a significant reduction in blood pressure and end target organ inflammation were observed in spontaneously hypertensive rats (SHRs). Cell tracking assays demonstrated that the injected hiPSC-MSCs accumulated in the spleens of the SHRs. The injected hiPSC-MSCs accumulated adjacent to the splenic nerve, potentially contributing to the antihypertensive effects. Furthermore, the hiPSC-MSCs released abundant glutamate, which acts as a neuromodulator to activate the splenic sympathetic nerve. After inhibition of glutamate synthesis by siRNA, the ability of hiPSC-MSCs to activate sympathetic nerves was significantly diminished. In addition, the antihypertensive effects of hiPSC-MSCs were eliminated after splenic nerve denervation (SND), underscoring the critical role of the splenic nerve. Moreover, activation of the splenic nerve resulted in increased release of norepinephrine (NE), which increased the number of choline acetyltransferase-positive (ChAT + ) cells in the spleen and peripheral blood. Consequently, the acetylcholine (ACh) produced by elevated ChAT + cells could act as a vasodilator, lowering blood pressure and mitigating inflammation in end target organs. In summary, our findings indicate that hiPSC-MSCs effectively lower blood pressure in hypertension by influencing the splenic nerves and regulating ChAT + cells. The connection between blood pressure regulation and the splenic nerve may offer new insights into the treatment of hypertension.
研究领域:
干细胞治疗
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心血管疾病
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高血压
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神经科学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Xu Zhang,Xiaotong Wang,Rui Shi,Xiaoku Ran,Xiahong He,Deqiang Dou
Ethnopharmacological relevance Red ginseng (RG), a processed product of ginseng (GS), is a generally used qi -tonifying medicine in Traditional Chinese Medicine (TCM). According to the TCM principle, RG is also generally applied to spleen-deficiency syndrome (SDS) clinically for its warmer property. However, the effective substances and mechanism of RG on SDS have not been well investigated. Aim of the study The aim of this study was to explore the effective substances and their mechanism of RG on SDS. Materials and methods The SDS model was established with a compound factor method involving an irregular diet, excessive fatigue and sennae folium with a bitter-cold property. The medicine of RG was split by multi-mode separation methods and analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The appearance indexes such as body weight, body temperature, swimming endurance, urine output, and water content of fecal were determined. The biochemical indexes such as D-xylose, SP , VIP and AChE in the digestive system, CRH, ACTH, CORT, E, T3, T4, T, E2 and 5-HT in the endocrine system, CS, NCR , IDH1 , COX and Na + -K + -ATPase in the metabolism of substance and energy, cAMP and cGMP in the cyclic nucleotide system were analyzed by Enzyme-linked immunosorbent assay (ELISA) kits and biochemical kits. The serum metabolites were analyzed by UPLC-QTOF/MS. Furthermore, the gut microbiota and short-chain fatty acids (SCFAs) in feces were analyzed by 16S rRNA sequencing and headspace gas chromatography-mass method. Results The pharmacological experiments showed that total saponin fraction (RGTSF), less polar fraction (RGLPF), and polysaccharides faction (RGPSF) significantly modulated the “brain-gut” axis-related indexes (the levels of VIP, AChE, and 5-HT). Besides, RGTSF also significantly modulated the hypothalamic-pituitary-adrenal (HPA) axis-related indexes as well as the substance and energy metabolism-related indexes (the levels of ACTH, CORT, A, Na + -K + -ATPase, COX, NCR and CS). RGPSF also significantly modulated the hypothalamus-pituitary-thyroid (HPT) axis-related indexes (the levels of T3 and T4). Secondly, metabolomics indicated that RGTSF could significantly regulate the abnormal metabolic pathways associated with the development of SDS, which involved steroid hormone biosynthesis, taurine and hypotaurine metabolism, primary bile acid biosynthesis, and amino acid metabolism. Subsequently, the study of gut microbiota indicated that RGLPF could increase the diversities of the gut microbiota and the relative abundance of Firmicutes in rats with SDS, while RGWEF significantly increased the relative abundance of Bacteroidetes . At the genus level, RGLPF could increase the relative abundance of Lactobacillus in rats with SDS and decrease that of Akkermansia . Meanwhile, the water-eluted fraction (RGWEF) showed a stronger regulation in SCFAs. Conclusion It is for the first time that the effective substances of red ginseng on spleen-deficiency syndrome were studied systematically, and the different mechanisms of the RG fractions involved in substance and energy metabolism as well as the “brain-gut” axis were revealed. The present study demonstrated that RGTSF, RGPSF, and RGLPF were the effective substances of red ginseng for ameliorating spleen-deficiency syndrome, indicating that ginsenosides composed of primary and secondary saponins as well as polysaccharides were the main effective substances for red ginseng in ameliorating spleen-deficiency syndrome.
研究领域:
民族药理学
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中医药学
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药理学
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代谢组学
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微生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD SCIENCE
·
2022
·Vol. 87
·期 7
·3223-3234
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IF 3.693
Youxian Zhou,Yue Gong,Zhengqi Liu,Lilong Wang,Chunqing Ai,Chengrong Wen,Taihai Zhu,Shuang Song
Although numerous polysaccharides have demonstrated potential immunostimulatory activities in in vitro models, only a few of them successfully stimulate the immune system in vivo. In order to explore the possible reasons for the activity loss of polysaccharides in in vivo models, the immunostimulatory activities in vitro and in vivo and the digestion behavior of a polysaccharide from Cyclina sinensis (CSP) were investigated in the present study. CSP showed obvious immunostimulatory activity in a RAW 264.7 cell model. In in vitro experiment, CSP did not exhibit cytotoxicity at concentrations of ≤10 µg/ml, and significantly increased NO production at concentrations of 0.4–10 µg/ml, suggesting CSP processes immunostimulatory activity in vitro. Further investigation using simulated digestion model indicated that CSP could bind with the protein in the digestive fluids to form precipitate in both the stomach and small intestine, and it could be seriously degraded by amylase during the digestion in the small intestine. Furthermore, the in vivo immunostimulatory activity evaluation demonstrated CSP had no effect on immunosuppressed mice as indicated by the body weight, thymus and spleen indexes, and TNF-α, IL-1β, IL-6, and IL-10 mRNA expression. Thus, the present study indicates that the degradation and precipitation of CSP in the digestive tract are the possible reasons for the activity loss of CSP after digestion. Practical Application Cyclina sinensis is the common aquatic shellfish in China and plays an important role in the marine aquaculture industry. Cyclina sinensis polysaccharide (CSP) is the main active component of C. sinensis . The structure characterization and immunostimulatory activity of a purified fraction of CSP (CSP-1) and the effect of digestion on CSP and its immunostimulatory activity were studied. The result of this study promotes the understanding of the nutritional function effects and provides a scientific reference for the rational development and high-value utilization of C. sinensis .
研究领域:
免疫学
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营养科学
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海洋生物学
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药学
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产品关联
DOI
PubMed
高影响因子
Small Science
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2023
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IF 12.7
Maoze Wang,Ge Yan,Qiyao Xiao,Nan Zhou,Hao-Ran Chen,Wei Xia,Lihua Peng
Transdermal delivery of antigen and chemokine proteins that activates the maturation of skin dendritic cells (DCs) and direct the migration of activated DCs to lymph and spleen is an important alternative to conventional vaccines. However, stratum corneum forms a barrier to skin penetration. The poor cellular uptake of free antigens and chemokines also limits transcutaneous immunization efficacy. In this work, a pair of iontophoresis-driven microneedle patches is constructed, of which, two kinds of outer membrane vesicles (OMVs) derived from Escherichia coli transformed by plasmid encoding gp100 (IPMN-G) and chemokine ligand 21 (IPMN-C) are incorporated within microneedles, respectively. The topical application of IPMN-G and IPMN-C shows the effectiveness of transdermally delivering gp100 and CCL21 secreting vesicles to skin DCs. With iontophoresis as a driving generator, the release and uptake of transgenic OMVs in target cells are significantly enhanced, with transcutaneous immunization initiated. The in vivo applications of IPMN-G and IPMN-C with a 12 h interval retard the progression and prevent the occurrence of tumor spheroids. IPMN-GC is shown as a promising triplatform in engineering transgenic OMV-incorporated microneedles, driven by iontophoresis into a transcutaneous vaccine, providing a noninvasive system for the transdermal delivery of antigen and chemokine proteins for transcutaneous vaccination-meditated immunotherapy.
研究领域:
生物医学工程
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免疫学
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药学
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癌症研究
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）