Frontiers in Microbiology
·
2024
·
IF 4
Wang Liping,Liang Aihua,Huang Jukai
Introduction: Diabetic nephropathy (DN) presents a significant therapeutic challenge, compounded by complex pathophysiological mechanisms. Recent studies suggest Exendin-4 (Ex-4) as a potential ameliorative agent for DN, albeit with unclear mechanisms. This research investigates the effects and underlying mechanisms of Ex-4-enriched exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) on DN, focusing on their renoprotective properties and interactions with gut microbiota.Method: Exosomes from hUCMSCs (hUCMSCs-Exo) were loaded with Ex-4 via electroporation. A streptozotocin (STZ) -induced DN mouse model was employed to assess the therapeutic impact of these engineered exosomes. The study further explored immune cell dynamics, mainly CD4+ regulatory T (Treg) cells, using bioinformatics, flow cytometry, and the influence of gut microbiota through antibiotic treatment and specific bacterial reintroduction.Results: Treatment with hUCMSCs-Exo@Ex-4 significantly improved key DN markers, including blood glucose and proteinuria, alleviating kidney damage. A notable decrease in natural Treg cell infiltration in DN was observed, while Ex-4-loaded exosomes promoted CD4+ Treg cell induction. The therapeutic benefits of hUCMSCs-Exo@Ex-4 were diminished upon CD4+ Treg cell depletion, underscoring their role in this context. Notably, CD4+ Treg cell induction correlated with the presence of Prevotella species, and disruption of gut microbiota adversely affected these cells and the therapeutic efficacy of the treatment. However, the reintroduction of Prevotella strains counteracted these adverse effects.Discussion: This study elucidates a novel therapeutic mechanism of Ex-4-loaded hUCMSCs exosomes in DN, highlighting the induction of CD4+ Treg cells mediated by specific gut microbiota components. These findings underscore the potential of leveraging gut microbiota and immune cell interplay in developing effective DN treatments.
研究领域:
糖尿病
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肾病学
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干细胞治疗
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免疫学
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微生物组研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Zhou Ye,Manman Zhu,Shaojie Li,Fan Zhang,Yingqi Ran,Cong Liu,Xiangchang Xu,Shujiao Liu,Xiang Xie,Yingchen Wang,Lan Yao
Cardiac autoimmune injury and oxidative stress play critical roles in the development of myocarditis. Promising approaches for treating this condition include suppressing excessive immune responses and reducing oxidative stress in the myocardium. The programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) axis is known to regulate immune responses and prevent damage caused by T-cell overactivation, while elevated reactive oxygen species (ROS) contribute to the progression of myocarditis. In this study, we developed multifunctional nanoparticles (PMN@EDR) that overexpress PD-L1 and are loaded with edaravone (EDR). The PMN@EDR NPs were successfully synthesized and comprehensively characterized. PMN@EDR effectively targeted inflammation-stimulated CD4 + T cells and damaged myocardial cells, inhibiting CD4 + T-cell proliferation, activation, and the release of pro-inflammatory cytokines via the PD-1/PD-L1 pathway. Additionally, PMN@EDR further suppressed CD4 + T-cell activation and alleviated HL-1 cardiomyocyte damage by releasing EDR to eliminate free radicals. For the in vivo treatment of myocarditis, compared to traditional single-target anti-inflammatory and antioxidant drugs, PMN@EDR not only reduced inflammation and the release of inflammatory mediators but also decreased ROS levels, thereby minimizing cardiomyocyte apoptosis and improving cardiac function. In conclusion, the PMN@EDR-based modulation of immune responses and oxidative stress offers a promising therapeutic strategy for myocarditis.
研究领域:
纳米技术
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免疫学
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心脏病学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2024
·
IF 4.1
Yuan-Xin Qian,Feng-Feng Zhou,Qiang Chen,Fen Dong,Han-Ying Xu,Yu-Long Sun,Ji-Teng Wang,Tao Han
Arginine plays a key role in regulating the immune function of fish. To evaluate the effect of arginine on the immune response of largemouth bass ( Micropterus salmoides ), the effects of arginine on cell viability, NADPH oxidase activity, respiratory burst activity, and NO production of leukocytes were analyzed both in vitro and in vivo . In this study, we found that arginine could promote the respiratory burst activity of leucocytes both in vivo and in vitro . By incubating leukocytes with the combination of LPS and arginine, we found that arginine supplementation inhibited the expression of inflammatory genes ( tumor necrosis factor-alpha , tnfα ; interleukin ( il ) 8 and il10 ) and apoptotic genes ( caspase 3 , caspase 8 , and caspase 9 ) induced by LPS, as well as promoted the arginine metabolism. Arginine supplementation significantly induced ( cd4-like ) cd4 gene expression after LPS challenge. Further studies showed that LPS could significantly increase nucleotide-binding oligomerization domain containing 1 ( nod1 ) gene expression, but decreased the nod2 gene. The arginine supplementation increased nuclear factor kappa-B (NF-κB) protein level. In conclusion, arginine can alleviate LPS-induced inflammatory response and apoptosis as well as induce cd4 gene expression against LPS challenge via adjusting the expression of NODs signaling.
研究领域:
免疫学
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水产养殖
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Cell Reports
·
2024
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IF 7.5
Mingzhi Wu,Xiaojun Zhou,Xinyi Zhou,Genxin Wang,Yiqun Zeng,Jun Li,Edward V. Prochownik,Fubing Wang,Youjun Li
Cholesterol metabolism reprogramming plays essential roles in hepatocellular carcinoma (HCC). However, precisely how cholesterol metabolism is dysregulated is not clear. Here, we show that the palmitoyltransferase ZDHHC3 and depalmitoylase ABHD17A regulate HCC cell cholesterol biosynthesis by dynamically S-acylating SREBP cleavage-activating protein (SCAP). SCAP S-acylation by ZDHHC3 at C264 antagonizes HACE1-mediated SCAP ubiquitination. Intriguingly, SREBP2 transcriptionally upregulates ZDHHC3 to form a positive feedback loop, which explains why negative feedback regulation of SCAP/SREBP2 signaling fails in HCC. Increased cholesterol in the tumor microenvironment (TME) restrains CD4 + T cell cytotoxicity. Hence, the cholesterol metabolism reprogramming and cholesterol level alternation in the TME cooperate to promote HCC development. We identified a small-molecule inhibitor of ZDHHC3 that, combined with anti-PD-1 immunotherapy, inhibited diethyl nitrosamine (DEN)/CCl 4 -induced HCC growth in mice. ZDHHC3-mediated SCAP S-acylation reprograms cholesterol metabolism and promotes HCC immune escape. ZDHHC3 is thus identified as a rational chemotherapy target for HCC.
研究领域:
癌症生物学
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分子生物学
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免疫学
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代谢学
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产品关联
DOI
PubMed
高影响因子
iScience
·
2024
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IF 4.6
Xiang-Xing Kong,Jia-Sheng Xu,Ye-Ting Hu,Yu-Rong Jiao,Sheng Chen,Cheng-Xuan Yu,Si-Qi Dai,Zong-Bao Gao,Xu-Ran Hao,Jun Li,Ke-Feng Ding
Current studies on the immune microenvironment of colorectal cancer (CRC) were mostly limited to the tissue level, lacking relevant studies in the peripheral blood, and failed to describe its alterations in the whole process of adenocarcinoma formation, especially of adenoma carcinogenesis. Here, we constructed a large-scale population cohort and used the CyTOF to explore the changes of various immune cell subsets in peripheral blood of CRC. We found monocytes and basophils cells were significantly higher in adenocarcinoma patients. Compared with early-stage CRC, effector CD4 + T cells and naive B cells were higher in patients with lymph node metastasis, whereas the basophils were lower. We also performed random forest algorithm and found monocytes play the key role in carcinogenesis. Our study draws a peripheral blood immune cell landscape of the occurrence and development of CRC at the single-cell level and provides a reference for other researchers.
研究领域:
肿瘤学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Wenjuan Ma,Junyi Che,Weiwei Chen,Dandan Wang,Huayong Zhang,Yuanjin Zhao
The therapeutic application of mesenchymal stem cells (MSCs) has good potential as a treatment strategy for systemic lupus erythematosus (SLE), but traditional MSC therapy still has limitations in effectively modulating immune cells. Herein, we present a promising strategy based on dexamethasone liposome-integrated MSCs (Dexlip-MSCs) for treating SLE via multiple immunomodulatory pathways. This therapeutic strategy prolonged the circulation time of dexamethasone liposomes in vivo, restrained CD4+T-cell proliferation, and inhibited the release of proinflammatory mediators (IFN-γ and TNF-α) by CD4+T cells. In addition, Dexlip-MSCs initiated cellular reprogramming by activating the glucocorticoid receptor (GR) signaling pathway to upregulate the expression of anti-inflammatory factors such as cysteine-rich secretory protein LCCL-containing domain 2 (CRISPLD2) and downregulate the expression of proinflammatory factors. In addition, Dexlip-MSCs synergistically increased the anti-inflammatory inhibitory effect of CD4+T cells through the release of dexamethasone liposomes or Dex-integrated MSC-derived exosomes (Dex-MSC-EXOs). Based on these synergistic biological effects, we demonstrated that Dexlip-MSCs alleviated disease progression in MRL/lpr mice more effectively than Dexlip or MSCs alone. These features indicate that our stem cell delivery strategy is a promising therapeutic approach for clinical SLE treatment.
研究领域:
免疫学
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干细胞治疗
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风湿病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
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IF 7.7
Yaozhong Lv,Yajun Yang,Ying Chen,Dongfan Wang,Yipeng Lei,Mingyue Pan,Zhenzhong Wang,Wei Xiao,Yujie Dai
In order to investigate the structural characteristics and immunomodulatory effects of Poria cocos polysaccharides , a water-soluble homogeneous polysaccharide (PCP-2) was isolated by water extraction and alcohol precipitation and further purified by Cellulose DEAE-52 and Sephacryl S-100HR column chromatography . PCP-2 is a heteropolysaccharide composed of glucose, galactose , mannose , and fucose in a molar ratio of 42.0: 35.0: 13.9: 9.1. It exhibits a narrow molecular weight distribution at 2.35 kDa with a branching degree of 37.1 %. The main chain types of PCP-2 include 1,3- β -D-Glc and 1,6- β -D-Glc as the backbone glucans and 1,6- α -D-Gal as the backbone heterogalactan. In vitro experiments demonstrate that PCP-2 directly stimulate RAW264.7 cell proliferation and secretion of inflammatory factors such as NO and TNF- α . In cyclophosphamide (CTX)-induced mice, it promotes the development of thymus and spleen immune organs, elevates the blood levels of IgG, IgA, IgM and CD3 + CD4 + T cells , increases the intestinal villus height/ crypt depth ratio and improves gut barrier dysfunctions. These findings suggest that PCP-2 is a natural fungal polysaccharide with broad spectrum of immunoenhancing effects, which can significantly ameliorate the immunocompromised state.
研究领域:
免疫学
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药理学
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生物化学
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真菌学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
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IF 5.7
Zongping Zhu,Yirong Luo,Liting Lin,Tianhui Gao,Qingsong Yang,Yunqiu Fan,Shuyi Wang,Chaomei Fu,Wan Liao
Turmeric, a traditional medicinal herb, is commonly used as a dietary and functional ingredient. This study aimed to investigate the effect of turmeric polysaccharides (TPs) on intestinal immunity and gut microbiota in cyclophosphamide (Cy)-induced immunosuppressed BALB/c mice. We verified that the oral administration of TPs-0 and TPs-3 (200 and 400 mg/kg, bw) improved thymus and spleen indexes, increased the whole blood immune cells (WBC) and lymph count index, and stimulated the secretion of serum immunoglobulin IgG. More importantly, TPs-0 and TPs-3 could repair intestinal immune damage and reduce intestinal inflammation. The specific mechanism is ameliorating the intestinal pathological damage, promoting CD4+ T cell secretion, regulating the expression of related cytokines, and reducing the level of critical proteins in the NF-κB/iNOS pathway. Interestingly, the intake of TPs-0 and TPs-3 significantly increased the content of short-chain fatty acids (SCFAs). Moreover, TPs-0 and TPs-3 relieved the intestinal microbiota disorder via the proliferation of the abundance of Lactobacillus and Bacteroides and the inhibition of Staphylococcus. Cumulatively, our study suggests that TPs-0 and TPs-3 can relieve intestinal immune damage by repairing the immune barrier and regulating intestinal flora disorders. TPs have potential applications for enhancing immunity as a functional food.
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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营养科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Quanjuan Guo,Ailu Yang,Rongrong Zhao,Huajun Zhao,Yongliang Mu,Jian Zhang,Qiuju Han,Yuhang Su
Nimodipine, a calcium antagonist, exert beneficial neurovascular protective effects in clinic. Recently, Calcium channel blockers (CCBs) was reported to protect against liver fibrosis in mice, while the exact effects of Nimodipine on liver injury and hepatic fibrosis remain unclear. In this study, we assessed the effect of nimodipine in Thioacetamide (TAA)-induced liver fibrosis mouse model. Then, the collagen deposition and liver inflammation were assessed by HE straining. Also, the frequency and phenotype of NK cells, CD4 + T and CD8 + T cells and MDSC in liver and spleen were analyzed using flow cytometry. Furthermore, activation and apoptosis of primary Hepatic stellate cells (HSCs) and HSC line LX2 were detected using α-SMA staining and TUNEL assay, respectively. We found that nimodipine administration significantly attenuated liver inflammation and fibrosis. And the increase of the numbers of hepatic NK and NKT cells, a reversed CD4 + /CD8 + T ratio, and reduced the numbers of MDSC were observed after nimodipine treatment. Furthermore, nimodipine administration significantly decreased α-SMA expression in liver tissues, and increased TUNEL staining adjacent to hepatic stellate cells. Nimodipine also reduced the proliferation of LX2, and significantly promoted high level of apoptosis in vitro . Moreover, nimodipine downregulated Bcl-2 and Bcl-xl, simultaneously increased expression of JNK, p-JNK, and Caspase-3. Together, nimodipine mediated suppression of growth and fibrogenesis of HSCs may warrant its potential use in the treatment of liver fibrosis.
研究领域:
药理学
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免疫学
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肝病学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 44
·6924-6933
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IF 5.047
Pei Liu,Weitao Yang,Lei Shi,Haiyan Zhang,Yan Xu,Peiru Wang,Guolong Zhang,Wei R. Chen,Bingbo Zhang,Xiuli Wang
Phototherapy, particularly photothermal therapy (PTT) and photodynamic therapy (PDT), has become a promising therapeutic technique for the treatment of skin cancers because of its minial invasiveness, high efficacy, and low side effects. Nevertheless, single modality therapy, either PTT or PDT, has limited clinical effectiveness in treating skin cancers. Thus, combined applications of PTT and PDT have been frequently reported; however, PTT and PDT often require their respective photoagents and excitation light sources, resulting in challenges in clinical transformation. In this study, to address these issues, we report the use of biocompatible gold nanoclusters Au25(Capt)18 for the concurrent PTT and PDT treatment of cutaneous squamous cell carcinoma (cSCC) using an 808 nm near-infrared (NIR) laser. Utilizing their high light-thermal conversion efficiency, potent generation of singlet oxygen, and strong photothermal stability, Au25(Capt)18 nanoclusters potentiated a significant proliferation suppression of cSCC XL50 cells in vitro and the inhibition of cSCC tumors on SKH-1 mice in vivo. In particular, under 808 nm light irradiation, the tumor-cell-killing contributions of PTT and PDT were estimated to be 28.86% and 71.14%, respectively, by using an ROS scavenger to quench the PDT effect. Tumor-infiltrating CD4+ T and CD8+ T cells were observed after one course of concurrent PTT and PDT. Preliminary toxicity studies indicated low adverse effects of the Au25(Capt)18 nanoclusters. Through this study, we report the use of a simple nanostructure for simultaneous PTT and PDT applications to effectively kill cSCC and to induce anti-tumor immune responses. Our study could lead to the development of effective photoagents for current, synergistic applications of different phototherapies with targeted immunological responses for the treatment of cancers.
研究领域:
肿瘤学
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纳米技术
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光疗
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Xueyan Wu,Jun Peng,Chunyu Zhang,Yifan Liao,Xinran Zhang,Yilin Hou,Tiantang Fan,Tianyun Fan,Jigang Wang
Radix Bupleuri polysaccharides (RBP) are heteropolysaccharides with a molecular weight distribution ranging from 1.10 to 121.21 kDa, extracted from the traditional Chinese medicinal herb Radix Bupleuri . Using DEAE-cellulose column chromatography, one neutral polysaccharide (RBP-1) and two acidic polysaccharides (RBP-2 and RBP-3) were isolated. These polysaccharides exhibited the capability to activate RAW264.7 macrophages, with the acidic fractions demonstrating greater effects than the neutral ones. RNA sequencing revealed that differentially expressed genes (DEGs) were significantly enriched in MAPK and NF-κB signaling pathways following RBP-3 treatment. Mechanistic studies further demonstrated that RBP-3 activates these pathways through toll-like receptors TLR2 and TLR4. Additionally, RBP effectively alleviated immunosuppression by modulating gut microbiota and restoring the integrity of the intestinal mucosal barrier in cyclophosphamide (CTX)-induced immunosuppressed mice. RBP influenced the generation of colonic short-chain fatty acids (SCFAs), regulated CD4+ T cell differentiation, and enhanced intestinal immune function. These findings highlight RBP potential as a natural immunomodulator and establish a theoretical foundation for the formulation of immune-supportive botanical products derived from Radix Bupleuri .
研究领域:
免疫学
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药理学
·
分子生物学
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中医学
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微生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Yang Gao,Shi-Qiao Liu,Jia-Long Wang,Han-Ming Cui,Qiu-Yan Zhang,Lei Wang,Yi-Xin Zhang,Jian Li,Yu Dong,Yuan-Hui Hu
Ethnopharmacological relevance Sanhuang Xiexin Decoction (SHXD), consisting of Coptis chinensis Franch., Scutellaria baicalensis Georgi and Rheum palmatum L. , is t raditionally used for relieving fever, purging fire for removing toxins, eliminating phlegm and haemostasis, eliminating the wetness-evil from the upper warmer, clearing away the heat-evil and expelling superficial evils. Each of the three herbs contained in SHXD has been indicated to have anti-inflammatory effects in vivo , but its effects on rat NK-cell phenotypes remain unexplored, and the comprehensive mechanism of this compound SHXD in curing the inflammation induced by lipopolysaccharides (LPS) remains to be revealed. Aim of the study The study aim was to assess the effect of SHXD on LPS-induced fever and inflammation in a rat model, reduce NLRP3 activation in NK cells expressing specific cell phenotype antibodies and determine the therapeutic value of this approach in vivo . Materials and methods SHXD extract was prepared and analysed by the developed ultra-performance liquid chromatography (UPLC) method for the simultaneous detection of 14 compounds. The main peaks were firstly identified on an Orbitrap via high resolution tandem mass spectrometry (MS). Then, the extract was used in the rat model of LPS-induced inflammation and fever for pharmacologically study the effects of drug treatment. Peripheral blood lymphocyte cells were isolated from the animals, including those subjected to the SHXD extract treatment, and the cell phenotype was determined prior to cell culture and after treating the cell cultures with the extract. The phenotypes of cells harvested using CD3, CD4, CD8a, CD81, CD161 and CD86 antibodies were used to verify the enhanced memory of the peripheral blood lymphocytes cells (PBMC) that were induced into nature killer (NK) cells. Results The SHXD extract was prepared, analysed and identified via quality control equipment and was observed to have pharmacological effects that reduced NLRP3 activation and fever in rats. The production of NK cells and peripheral blood lymphocytes was induced by the SHXD extract, which manifested as increased levels of CD4 + , CD8a+, CD81 + , CD161+ and CD86 + cells. The levels of CD3 + cells were significantly different between the model group and the drug-treated or control groups (p < 0.01) with dose independence, while the levels of CD4 + cells were not significantly different between the drug-treated and control groups, with a trend towards lower levels in the model group with dose independence. The levels of CD4 + cells was significantly different between the drug-treated group and the model groups with dose independence (p < 0.05). The levels of CD86 + cells were not significantly different between the drug-treated group and the model and control groups. The levels of CD8a + cells was significantly different between the model group and the drug and control groups (p < 0.05, dose 2.0 μg/ml), with higher levels in the drug-treated group. The levels of CD3 + , CD4 + , CD8a + cells in the drug treated group have dose dependence with SHXD. Conclusions This experiment revealed that SHXD reduced NLRP3 activation in the blood of LPS-treated rats, which occurred through the activation of NK cells that expressed CD3, CD8a and CD161. SHXD may possess anti-inflammatory effect via activacting the one of major pharmacology effcet of NK cells that expressed CD3, CD8a and CD161 phenotypes expression. This result demonstrates that SHXD may possess ability to enhance the memory of peripheral blood lymphocytes and natural killer cells.
研究领域:
药理学
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免疫学
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分析化学
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中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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