Mucosal Immunology
·
2024
·
IF 7.9
Jinzhe Tong,Simiao Chen,Xinyue Gu,Xuanqi Zhang,Fang Wei,Yingying Xing
Tissue-resident memory T cells (T RM ) can be induced by infection and vaccination, and play a key role in maintaining long-term protective immunity against mucosal pathogens. Our studies explored the key factors and mechanisms affecting the differentiation, maturation, and stable residence of gastric epithelial CD4 + T RM induced by Helicobacter pylori (Hp) vaccine and optimized Hp vaccination to promote the generation and residence of T RM .CD38 regulated mitochondrial activity and enhanced TGF-β signal transduction to promote the differentiation and residence of gastric epithelial CD4 + T RM by mediating the expression of CD105. Extracellular nucleotides influenced the long-term maintenance of T RM in gastric epithelium by P2RX7. Vitamin D3 and Gram-positive enhancer matrix particles (GEMs)as immune adjuvants combined with Hp vaccination promoted the production of CD69 + CD103 + CD4 + T RM .
研究领域:
免疫学
·
微生物学
·
分子生物学
·
疫苗学
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DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2024
·
IF 3.1
Sun Hui,Wang ZiTong,Tu BingHua,Shao ZiChen,Li YiDan,Han Di,Jiang YinJie,Zhang Peng,Zhang WeiChang,Wu YunYan,Wu XiaoMing,Liu Chi-Ming
Type 2 diabetes mellitus (T2DM) is a metabolic disease. Diabetes increases the risk of benign prostatic hyperplasia (BPH). Capsaicin is extracted from chili peppers and possesses many pharmacological properties, including anti-diabetic, pain-relieving, and anti-cancer properties. This study aimed to investigate the effects of capsaicin on glucose metabolism and prostate growth in T2DM mice and uncover the related mechanisms. Mice model of diabetes was established by administering a high-fat diet and streptozotocin. Oral administration of capsaicin for 2 weeks inhibited prostate growth in testosterone propionate (TP)-treated mice. Furthermore, oral administration of capsaicin (5 mg/kg) for 2 weeks decreased fasting blood glucose, prostate weight, and prostate index in diabetic and TP-DM mice. Histopathological alterations were measured using hematoxylin & eosin (H&E) staining. The protein expression of 5α-reductase type II, androgen receptor (AR), and prostate-specific antigen (PSA) were upregulated in diabetic and TP-DM mice, but capsaicin reversed these effects. Capsaicin decreased the protein expression of p-AKT, insulin-like growth factor-1 (IGF-1), IGF-1R, and the receptor for advanced glycation end products (RAGE) in diabetic and TP-DM mice. Capsaicin also regulated epithelial-mesenchymal transition (EMT) and modulated the expression of fibrosis-related proteins, including E-cadherin, N-cadherin, vimentin, fibronectin, α-SMA, TGFBR2, TGF-β1, and p-Smad in TP-DM mice. In this study, capsaicin alleviated diabetic prostate growth by attenuating EMT. Mechanistically, capsaicin affected EMT by regulating RAGE/IGF-1/AKT, AR, and TGF-β/Smad signalling pathways. These results provide with new therapeutic approach for treating T2DM or T2DM-induced prostate growth.
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产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2018
·Vol. 14
·期 12
·2135-2145
·
IF 5.068
Chen Xiaoyu,Qin Zainen,Zhao Jinmin,Yan Xiaohui,Ye Jing,Ren En,Wang Junqing,Yang Xingchen,Heng Shujun,Zheng Li,Liu Gang
Mesenchymal stem cells (MSCs) have potential uses for cartilage repair due to the potential of chondrogenic differentiation. However, developing effective approaches to regulate chondrogenesis in vivo remains a big challenging. To address the limitations, we propose the application
of magnetic fields, which features excellent performance for tissue penetration, good biocompatibility even at high magnetic strength, and wireless remote control. To test this concept, a pulsed magnetic field (PMF) was used to enhance the chondrogenesis of SPIO-labeled MSCs in a rat model
of cartilage defects. The SPIO labeling not only efficiently strengthens the responsiveness of MSCs to the externally applied PMF but also enables in vivo non-invasive monitoring of MSCs with magnetic resonance imaging (MRI). Importantly, biochemical and gene expression analysis reveal
the upregulation of certain cartilage biomarkers (i.e., SOX9 and COL2A1), showing that the PMF improves the chondrogenesis of MSCs via activation of the TGF-β/SMAD signaling pathways. These results indicate a promising scheme for stem cell-based cartilage repair.
研究领域:
生物医学工程
·
干细胞生物学
·
再生医学
·
骨科
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DOI
PubMed
高影响因子
CHEMOSPHERE
·
2022
·
IF 8.943
Man Qu,He Chen,Hanpeng Lai,Xing Liu,Dayong Wang,Xing Zhang
Nanoplastics represented by nanopolystyrene (NPS) and its chemically modified derivatives are environmentally ecotoxicological hotpots in recent years, but their toxicity and underlying mechanisms have not been fully identified. Here we employed Caenorhabditis elegans as an animal model to systematically compare the toxicity between nanopolystyrene and its 4 chemically modified derivatives (PS-PEG, PS-COOH, PS-SOOOH and PS-NH 2 ) at predicted environmental concentrations. Our study demonstrated that compared with PS exposed group, PS-NH 2 exposure (15 μg/L) caused a significant decline in lifespan by suppressed DAF-16/insulin signaling and shortened body length by inhibiting DBL-1/TGF β signaling. Different from PS-NH 2 exposed group, PS-SOOOH exposure (15 μg/L) could not cause changes in lifespan, but shortened body length by inhibiting DBL-1/TGF β signaling. In addition, PS-COOH, PS-SOOOH or PS-NH 2 exposure (1 μg/L or 15 μg/L) caused more serious toxicity in reducing locomotion behavior and causing gut barrier deficit. Hence the rank order in toxicity of PS-NH 2 ＞PS-SOOOH＞PS-COOH＞PS＞PS-PEG was identified. Furthermore, we also presented evidence to support the contention that the observed toxic effects on nematodes were linked to oxide stress and activation of anti-oxidative molecules for reversing the adverse effects induced by nanopolystyrene and its 4 chemically modified derivatives. Our data highlighted nanoplastics may be charge-dependently toxic to environmental organisms, and the screened low toxic modification may support polystyrene nanoparticles continued application for daily consumer goods and biomedicine.
研究领域:
环境科学
·
毒理学
·
分子生物学
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DOI
PubMed
高影响因子
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
·
2023
·
IF 2.9
Junfu Guo,Shuangyu Lyu,Yanchen Qi,Xuanyi Chen,Lu Yang,Chunhui Zhao,Hao Wang
Ferritin, one of the key regulators of iron homeostasis, is widely present throughout almost all species. The vertebrate ferritin family, which originates from a single gene in the ancestral invertebrates, contains the widest variety of ferritin subtypes among all animal species. However, the evolutionary history of the vertebrate ferritin family remains to be further clarified. In this study, genome-wide identification of the ferritin homologs is performed in lampreys, which are the extant representatives of jawless vertebrates that diverged from the future jawed vertebrates more than 500 million years ago. Molecular evolutionary analyses show that four members of the lamprey ferritin family, L-FT1–4, are derived from a common ancestor with jawed vertebrate ferritins prior to the divergence of the jawed vertebrate ferritin subtypes. The lamprey ferritin family shares evolutionarily conserved characteristics of the ferritin H subunit with higher vertebrates, but certain members such as L-FT1 additionally accumulate some features of the M or L subunits. Expression profiling reveals that lamprey ferritins are highly expressed in the liver. The transcription of L-FT1 is significantly induced in the liver and heart during lipopolysaccharide stimulation, indicating that L-FTs may play a role in the innate immune response to bacterial infection in lampreys. Furthermore, the transcriptional expression of L-FT1 in quiescent and LPS-activated leukocytes is up- and down-regulated by the lamprey TGF-β2, an essential regulator of the inflammatory response, respectively. Our results provide new insights into the origin and evolution of the vertebrate ferritin family and reveal that lamprey ferritins may be involved in immune regulation as target genes of the TGF-β signaling pathway.
研究领域:
分子进化
·
免疫学
·
基因组学
·
生物化学
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DOI
PubMed
高影响因子
Reproductive Sciences
·
2025
·
IF 2.5
Qiu Yingying,Wei Xinjun,Cao Jian,Wang Jindan,Dou Qianru,Zhou Fangfang,Chen Xi,Liu Yongli,Wan Guiping,Huang Meihua,Li Zhenli,Gui Tao
Adenomyosis (AM), a gynecological disorder that severely affects female reproductive health. AM-associated macrophage (AAM) polarization-induced epithelial–mesenchymal transition (EMT) is a key driver of AM progression. In this study, we investigated the role and underlying mechanisms of endometrial mesenchymal stem cell (eMSC)-derived exosomes in regulating AAM polarization and the subsequent EMT of endometrial epithelial cells (EECs). In vitro coculture studies revealed that AM eutopic eMSCs markedly induced M2 macrophage polarization via exosomes and promoted EMT of EECs. Differentially expressed microRNAs (DE-miRNAs) between exosomes derived from normal eMSCs (N-eMSCs) and AM eutopic eMSCs (A-eMSCs) were identified using miRNA sequencing and miR-4669 was found to be the most significantly upregulated miRNA. Internalization of exosomal miR-4669 by macrophages induced their polarization toward the M2 phenotype and promoted the EMT of EECs. Mechanistic analysis using luciferase assay, mRNA sequencing, and rescue experiments revealed that miR-4669 induced M2 macrophage polarization via downregulation of DUSP6 and activation of MAPK/ERK signaling. The polarized M2 macrophages promoted the EMT of ISK cells via TGF-β1 secretion. In an AM xenograft mouse model, miR-4669 depletion inhibited AM progression by targeting the DUSP6/ERK1/2 pathway in macrophages. Overall, AM A-eMSC-derived exosomal miR-4669 facilitates M2 macrophage polarization by targeting the DUSP6/ERK signaling pathway, thereby promoting EMT of EECs via TGF-β1 secretion. These findings open avenues for developing novel preventive and therapeutic strategies for AM. Graphical
研究领域:
妇科学
·
干细胞生物学
·
分子生物学
·
细胞信号传导
·
癌症生物学
·
免疫学
·
microRNA研究
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Liu Bin,Li Faping,Wang Yuxiong,Gao Xin,Li Yunkuo,Wang Yishu,Zhou Honglan
Background: Kidney injuries often carry a grim prognosis, marked by fibrosis development, renal function loss, and macrophage involvement. Despite extensive research on macrophage polarization and its effects on other cells, like fibroblasts, limited attention has been paid to the influence of non-immune cells on macrophages. This study aims to address this gap by shedding light on the intricate dynamics and diversity of macrophages during renal injury and repair.Methods: During the initial research phase, the complexity of intercellular communication in the context of kidney injury was revealed using a publicly available single-cell RNA sequencing library of the unilateral ureteral obstruction (UUO) model. Subsequently, we confirmed our findings using an independent dataset from a renal ischemia-reperfusion injury (IRI) model. We treated two different types of endothelial cells with TGF-β and co-cultured their supernatants with macrophages, establishing an endothelial cell and macrophage co-culture system. We also established a UUO and an IRI mouse model. Western blot analysis, flow cytometry, immunohistochemistry and immunofluorescence staining were used to validate our results at multiple levels.Results: Our analysis revealed significant changes in the heterogeneity of macrophage subsets during both injury processes. Amyloid β precursor protein (APP)-CD74 axis mediated endothelial-macrophage intercellular communication plays a dominant role. In the in vitro co-culture system, TGF-β triggers endothelial APP expression, which subsequently enhances CD74 expression in macrophages. Flow cytometry corroborated these findings. Additionally, APP and CD74 expression were significantly increased in the UUO and IRI mouse models. Immunofluorescence techniques demonstrated the co-localization of F4/80 and CD74 in vivo.Conclusion: Our study unravels a compelling molecular mechanism, elucidating how endothelium-mediated regulation shapes macrophage function during renal repair. The identified APP-CD74 signaling axis emerges as a promising target for optimizing renal recovery post-injury and preventing the progression of chronic kidney disease.
研究领域:
肾病学
·
免疫学
·
分子生物学
·
细胞生物学
·
病理生理学
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DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Zaigang Zhou,Cheng Li,Chao Li,Lei Zhou,Shuo Tan,Weibin Hou,Congying Xie,Long Wang,Jianliang Shen,Wei Xiong
It is newly revealed that collagen works as a physical barrier to tumor immune infiltration, oxygen perfusion, and immune depressor in solid tumors. Meanwhile, after radiotherapy (RT), the programmed death ligand-1 (PD-L1) overexpression and transforming growth factor-β (TGF-β) excessive secretion would accelerate DNA damage repair and trigger T cell exclusion to limit RT efficacy. However, existing drugs or nanoparticles can hardly address these obstacles of highly effective RT simultaneously, effectively, and easily. In this study, it is revealed that inducing mitochondria dysfunction by using oxidative phosphorylation inhibitors like Lonidamine (LND) can serve as a highly effective multi-immune pathway regulation strategy through PD-L1, collagen, and TGF-β co-depression. Then, IR-LND is prepared by combining the mitochondria-targeted molecule IR-68 with LND, which then is loaded with liposomes (Lip) to create IR-LND@Lip nanoadjuvants. By doing this, IR-LND@Lip more effectively sensitizes RT by generating more DNA damage and transforming cold tumors into hot ones through immune activation by PD-L1, collagen, and TGF-β co-inhibition. In conclusion, the combined treatment of RT and IR-LND@Lip ultimately almost completely suppressed the growth of bladder tumors and breast tumors.
研究领域:
肿瘤学
·
免疫疗法
·
纳米技术
·
放射生物学
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DOI
PubMed
高影响因子
Scientific Reports
·
2015
·
IF 5.578
Shixuan Chen,Junbin Shi,Min Zhang,Yinghua Chen,Xueer Wang,Lei Zhang,Zhihui Tian,Yuan Yan,Qinglin Li,Wen Zhong,Malcolm Xing,Lu Zhang,Lin Zhang
The purpose of this study was to permit bone marrow mesenchymal stem cells (BMSCs) to reach their full potential in the treatment of chronic wounds. A biocompatible multifunctional crosslinker based temperature sensitive hydrogel was developed to deliver BMSCs, which improve the chronic inflammation microenvironments of wounds. A detailed in vitro investigation found that the hydrogel is suitable for BMSC encapsulation and can promote BMSC secretion of TGF-β1 and bFGF. In vivo, full-thickness skin defects were made on the backs of db/db mice to mimic diabetic ulcers. It was revealed that the hydrogel can inhibit pro-inflammatory M1 macrophage expression. After hydrogel association with BMSCs treated the wound, significantly greater wound contraction was observed in the hydrogel + BMSCs group. Histology and immunohistochemistry results confirmed that this treatment contributed to the rapid healing of diabetic skin wounds by promoting granulation tissue formation, angiogenesis, extracellular matrix secretion, wound contraction, and re-epithelialization. These results show that a hydrogel laden with BMSCs may be a promising therapeutic strategy for the management of diabetic ulcers.
研究领域:
干细胞生物学
·
伤口愈合
·
糖尿病
·
药剂学
·
生物医学工程
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DOI
PubMed
高影响因子
Genes
·
2024
·Vol. 15
·期 5
·605
·
IF 2.8
Haijun Huang,Yuyan Liu,Qian Wang,Caichao Dong,Le Dong,Jingjing Zhang,Yu Yang,Xiancai Hao,Weijing Li,Ivana F. Rosa,Lucas B. Doretto,Xuebin Cao,Changwei Shao
It is widely known that all-female fish production holds economic value for aquaculture.Sebastes schlegelii, a preeminent economic species, exhibits a sex dimorphism, with females surpassing males in growth. In this regard, achieving all-female black rockfish production could significantly enhance breeding profitability. In this study, we utilized the widely used male sex-regulating hormone, 17α-methyltestosterone (MT) at three different concentrations (20, 40, and 60 ppm), to produce pseudomales ofS. schlegeliifor subsequent all-female offspring breeding. Long-term MT administration severely inhibits the growth ofS. schlegelii, while short term had no significant impact. Histological analysis confirmed sex reversal at all MT concentrations; however, both medium and higher MT concentrations impaired testis development. MT also influenced sex steroid hormone levels in pseudomales, suppressing E2 while increasing T and 11-KT levels. In addition, a transcriptome analysis revealed that MT down-regulated ovarian-related genes (cyp19a1aandfoxl2) while up-regulating male-related genes (amh) in pseudomales. Furthermore, MT modulated the TGF-β signaling and steroid hormone biosynthesis pathways, indicating its crucial role inS. schlegeliisex differentiation. Therefore, the current study provides a method for achieving sexual reversal using MT inS. schlegeliiand offers an initial insight into the underlying mechanism of sexual reversal in this species.
研究领域:
水产养殖
·
内分泌学
·
分子生物学
·
生理学
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DOI
PubMed
高影响因子
PLACENTA
·
2024
·
IF 3
Gaoying Wang,Ruirui Dong,Haijian Zhao,Ningzhen Ye,Jing Wang,Jing Cheng,Xinrui Shi,Liang Luo,Ting Zhang
Background Abnormal bile acid metabolism leading to changes in placental function during pregnancy. To determine whether endoplasmic reticulum protein 29 (ERp29) can mediate the pregnancy effects of cholestasis by altering the level of trophoblast cell apoptosis. Methods ERp29 in serum of 66 intrahepatic cholestasis of pregnancy (ICP) pregnant women and 74 healthy were detected by ELISA. Subcutaneous injection of ethinyl estradiol (E2) was used to induce ICP in pregnant rats. Taurocholic acid (TCA) was used to simulate the ICP environment, and TGF-β1 was added to induce the epithelial mesenchymal transformation (EMT) process. The scratch, migration, and invasion test were used to detect the EMT process. ERp29 overexpression/knockdown vector were constructed and transfected to verify the role of ERp29 in the EMT process. Downstream gene was obtained through RNA-seq. Results Compared with the healthy pregnant women, the expression levels of ERp29 in serum of ICP pregnancy women were significantly increased (P < 0.001). ERp29 in the placenta tissue of the ICP pregnant rats increased significantly, and the level of apoptosis increased. The placental tissues of the ICP had high expression of E-cadherin and low expression of N-cadherin, snail1, vimentin. After HTR-8/SVneo cells were induced by TCA, EMT was inhibited, while the ERp29 increased. Cell and animal experiments showed that, knockdown of ERp29 reduced the inhibition of EMT, the ICP progress was alleviated. Overexpression of FOS salvaged the inhibitory effects of ERp29 on cell EMT. Discussion The high level of ERp29 in placental trophoblast cells reduced FOS mRNA levels, inhibited the EMT process and aggravated the occurrence and development of ICP.
研究领域:
妇产科学
·
分子生物学
·
细胞生物学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
Theranostics
·
2025
·Vol. 15
·期 16
·8587
·
IF 13.3
Wei-Jia Yu,Wen-Xi Jiang,Shu-Jing Liu,Hui-Hua Li,Qiu-Yue Lin
Rationale: Infiltration of immune cells into the heart plays a crucial role in the transition from adaptive hypertrophy to heart failure (HF) following chronic pressure overload. However, the key factors in myeloid cells that regulate this process are still not well defined. Here, we studied the functional role of S100A8/A9 in myeloid cells during this transition. Methods: Cardiac hypertrophy and HF models were induced by transverse aortic constriction (TAC) for 1 to 4 weeks. The heterogeneity of CD45 + immune cells and the cellular sources of S100A8/A9 were analyzed using published single-cell RNA sequencing datasets. The effects of S100A8/A9 on TAC-induced hypertrophy and HF were verified in S100A9 knockout (KO) and bone marrow (BM)-chimeric mice and in an in vitro coculture system. Results: S100A8/A9 levels were significantly increased in HF patients and in TAC-induced HF model mice. Moreover, the TAC-induced transition from adaptive hypertrophy to HF was significantly attenuated in S100A9-KO mice and WT mice transplanted with S100A9-KO BM cells. Mechanistically, TAC-stimulated upregulation of S100A8/A9 in neutrophils induced an early inflammatory response and adaptive hypertrophy through activation of the p38 MAPK/JNK/AP-1 pathway, leading to increased production of IL-1β and chemokines (CCL2 and CCL6). These chemokines promoted the infiltration of CCR2 + macrophages to the damaged heart. Therefore, they exhibited upregulation of S100A8/A9, which led to exacerbation of inflammation, cardiac hypertrophy and fibrosis via activation of the NF-κB/NLRP3, AKT/Calcineurin A and TGF-β/Smad2 signaling pathways. Additionally, treating WT mice with the S100A9 inhibitor ABR-238901 prevented TAC-induced cardiac hypertrophy-related dysfunction. Conclusion: The present findings establish an S100A8/A9-related axis between myeloid cells and cardiac cells that drives the pressure overload-induced transition from hypertrophy to HF, suggesting that S100A8/A9 is a promising therapeutic target for this disease.
研究领域:
心脏病学
·
免疫学
·
分子生物学
·
基因组学
·
生物医学研究
✓ 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）