Journal of Biophotonics
·
2024
·
IF 2
Zengjun Xie,Zhihui He,Zhen Yuan,Miao Wang,Feifan Zhou
Cerebral lymphatic drainage is an important pathway for metabolic waste clearance in the brain, which plays a crucial role in the progression of central nervous system diseases. Recent studies have shown that norepinephrine (NE) is involved in the regulation of cerebral lymphatic drainage function, but the modulation mechanism remains unknown. In this study, we confirmed that NE rapidly reduced glymphatic influx and enhanced meningeal lymphatic clearance. Moreover, the transverse sinus (TS) was the vital region of cerebral lymphatic drainage regulation by NE. Further analysis revealed that NE inhibition could simultaneously enhance glymphatic drainage and dorsal meningeal lymphatic drainage, mainly acting on the TS region. This study demonstrated that the cerebral lymphatic drainage system can be regulated by NE, with the TS region serving as the primary modulating site. The findings provide a potential regulatory target for the amelioration of neurological diseases associated with cerebral lymphatic drainage function.
研究领域:
神经科学
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药理学
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神经病学
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产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2023
·
IF 6.7
Chen Kai,Cai Zhongyuan,Cao Yingzi,Jiang Lingling,Jiang Yuting,Gu Haojie,Fu Shengxiang,Xia Chunchao,Lui Su,Gong Qiyong,Song Bin,Ai Hua
The localization and differential diagnosis of the sentinel lymph nodes (SLNs) are particularly important for tumor staging, surgical planning and prognosis. In this work, kinetically inert manganese (II)-based hybrid micellar complexes (MnCs) for magnetic resonance imaging (MRI) were developed using an amphiphilic manganese-based chelate (C18-PhDTA-Mn) with reliable kinetic stability and self-assembled with a series of amphiphilic PEG-C18 polymers of different molecular weights (C18En, n = 10, 20, 50). Among them, the probes composed by 1:10 mass ratio of manganese chelate/C18En had slightly different hydrodynamic particle sizes with similar surface charges as well as considerable relaxivities (∼13 mM−1 s−1 at 1.5 T). In vivo lymph node imaging in mice revealed that the MnC MnC-20 formed by C18E20 with C18-PhDTA-Mn at a hydrodynamic particle size of 5.5 nm had significant signal intensity brightening effect and shortened T1 relaxation time. At an imaging probe dosage of 125 μg Mn/kg, lymph nodes still had significant signal enhancement in 2 h, while there is no obvious signal intensity alteration in non-lymphoid regions. In 4T1 tumor metastatic mice model, SLNs showed less signal enhancement and smaller T1 relaxation time variation at 30 min post-injection, when compared with normal lymph nodes. This was favorable to differentiate normal lymph nodes from SLN under a 3.0-T clinical MRI scanner. In conclusion, the strategy of developing manganese-based MR nanoprobes was useful in lymph node imaging.
研究领域:
医学影像学
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肿瘤学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
·
2021
·
IF 6.458
Jie Dong,Jinghua Sun,Wenwen Cai,Chunyan Guo,Qian Wang,Xuhui Zhao,Ruiping Zhang
Lymphatic metastasis plays an important role in malignant tumor invasion. Efficient identification of sentinel lymph node (SLN) is extremely significant for designing therapeutic strategies and assessing prognosis. In this work, we developed a natural cuttlefish melanin nanoprobe for the preoperative and intraoperative evaluation of lymphatic metastasis. The cuttlefish melanin nanoparticle could improve the water-solubility and biocompatibility of the near-infrared-II (NIR-II) dye, and extend the retention time of small molecule dye. The NIR-II imaging results verified that the nanoparticles have a high accumulation, high sensitivity, and high signal-to-noise ratio in the lymphatic system . Moreover, the nanoparticles have obvious naked-eye identification potential due to their natural brownish-black color. Additionally, the nanoparticles can combine with Gd ions to achieve preoperative lymphatic magnetic resonance imaging (MRI). The results of this study provide a unique approach to effectively identify and accurately remove lymph nodes before operation and during surgery, exhibiting tremendous potential in clinical translation.
研究领域:
医学影像
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生物医学工程
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肿瘤学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Open Medicine
·
2023
·Vol. 18
·期 1
·
IF 2.1
Yangfa Chao,Wenting Huang,Zhiheng Xu,Ping Li,Shaodong Gu
Lymphocyte apoptosis is a latent factor for immunosuppression in sepsis. Forkhead box protein P3 (FOXP3) can interact with RUNX family transcription factor 1 (RUNX1) in regulatory T cells. Our research was to probe whether RUNX1/FOXP3 axis affects immunosuppression in the process of sepsis by modulating T and B lymphocyte apoptosis. We constructed sepsis model in mice and mouse CD4 + T and CD19 + B lymphocytes. RUNX1 and FOXP3 expressions and apoptosis in cells were assessed by western blot, quantitative real-time PCR, and flow cytometer. Inflammation of serum and pathological damage was assessed by ELISA and H&E staining. Relationship between RUNX1 and FOXP3 was assessed by co-immunoprecipitation. The findings showed that RUNX1 ameliorated the survival rate, pathological damage, and decreased inflammation-related factors, and inhibited apoptosis of CD4 + T and CD19 + B cells in cecal ligation and puncture mice. Furthermore, RUNX1 up-regulated the viability and down-regulated apoptotic rate with the changed expressions of apoptosis-related molecules in lipopolysaccharide (LPS)-mediated CD4 + T and CD19 + B cells. Additionally, FOXP3 interacted with RUNX1, and its silencing decreased RUNX1 expression and reversed the inhibitory effect of RUNX1 on apoptosis of LPS-mediated CD4 + T and CD19 + B cells. In summary, the RUNX1/FOXP3 axis alleviated immunosuppression in sepsis progression by weakening T and B lymphocyte apoptosis.
研究领域:
免疫学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
Separations
·
2024
·Vol. 11
·期 4
·105
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IF 2.5
Dan Yu,Xiaoming Cai,Shuo Wang,Yi Li,Yuguang Du,Zhuo A. Wang,Siming Jiao,Zhenquan Yang
Phlebopus portentosusis an edible and medicinal mushroom with a delicious taste and high nutritional value. The oligosaccharides derived fromP. portentosusmay be the material basis for its biological activity. The degradation of polysaccharide and the maintenance of its activity after degradation are key steps in related research. This study applied an acid degradation method to prepareP. portentosusrefined polysaccharide (PPRP) with a smaller molecular weight, and the optimal hydrolysis conditions determined were a temperature of 80 °C, an acid concentration of 2 mol/L, and a hydrolysis time of 2 h. The polysaccharide structure and immune activity were then further investigated. The results showed that the PPRP comprised two fractions with approximate weights of 61,600 Da and 5500 Da. The monosaccharide composition of PPRP was mannose, rhamnose, glucose, and galactose, with a molar ratio of 1.00: 22.24: 2.93: 1.03. The major functional groups included O-H, C-H, C-O, and C-O-C. The glycosidic bond types were mainly α- and β-glycosidic bonds. Cell experiments demonstrated that PPRP could significantly increase the proliferation of macrophages and enhance the cytotoxicity of NK cells. Moreover, PPRP also significantly promoted the proliferation of B lymphocytes and T lymphocytes, especially at a concentration of 200 μg/mL. This study furnishes scientific evidence underlining the significant potential of PPRP in immune activity, thereby serving as a material basis and scientific bedrock for further investigations into the mechanism ofP. portentosusoligosaccharide activity.
研究领域:
真菌学
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免疫学
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生物化学
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药理学
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产品关联
DOI
高影响因子
BIOMATERIALS
·
2019
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IF 10.273
Wenjuan Zhang,Sichen Song,Hanxun Wang,Qiu Wang,Dan Li,Shunzhe Zheng,Zhuangyan Xu,Haotian Zhang,Jian Wang,Jin Sun
Tumor metastases account for about 90% of cancer-related death, among which lymphatic metastases play a pivotal role . Therefore, high-efficiency sentinel lymph node (SLN) identification is significant for lymph node (LN) metastasis diagnosis in clinic. Herein, a novel in vivo covalent albumin-binding near-infrared (NIR) fluorescent IR820-maleimide conjugate (IR-Mal) is firstly designed as a SLN dual-mode imaging agent. The IR-Mal conjugate exhibits bright blue appearance and its large Stokes shift (over 100 nm) increases the fluorescent imaging resolution effectively. The fluorescence intensity of covalent albumin-binding IR-Mal (BSA-IR-Mal) complex is considerably stronger than that of IR-Mal. In vivo , IR-Mal could rapidly covalently bind the tissue interstitial albumin following subcutaneous administration and BSA-IR-Mal complexes could specifically accumulate on LN, and detect both normal and metastatic SLN through naked-eye and fluorescence imaging with high resolution. Moreover, the light stability and enhanced fluorescence intensity of BSA-IR-Mal complex facilitates its diagnosis accuracy. These findings suggest that such in vivo irreversible albumin-binding fluorescence conjugates could serve as a new agent for dual-mode imaging and have a great potential to be applied in the SLNs imaging and diagnosis.
研究领域:
医学成像
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肿瘤学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Nanomaterials
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2018
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IF 2.207
Mingkai Zhang,Yang Gao,Jialiang Wang,Zhanbo Liu,Zaishun Jin,Jianbo Yu,Yukuan Feng,Qiang Lü
In order to determine a particular tumor cell via nanomaterials, we introduce the preparation of CD20 and CD5 coupled nanoprobes (denoted as CD20 and CD5 nanoprobes for convenience) and an application in identification of mantle cell lymphoma (MCL) from B-cell lymphoma. In this work, CD20 and CD5 nanoprobes were prepared by selectively oxidizing the carbon-carbon double bonds of oleate ligands on the surfaces of NaYF4:Yb3+,Tm3+ and NaYF4:Yb3+,Er3+ nanoparticles and, respectively, coupling carboxyl groups on the particles’ surfaces with CD20 and CD5 monoclonal antibodies through EDC/NHS crosslinking agents. After in situ hybridized Jeko-1 cells and Raji cells as a reference with CD20 and CD5 nanoprobes, in vitro double-color upconversion fluorescence imaging of Jeko-1 cells was demonstrated through visualization of blue and green fluorescence under a 980 nm laser excitation. Moreover, in vivo upconversion fluorescence imaging of the transplanted cancer model was also measured. These experimental results indicate that Jeko-1 cells have been specifically labeled by CD20 and CD5 nanoprobes. It is therefore concluded that CD20 and CD5 nanoprobes could be used to specially differentiate mantle cell lymphoma (MCL) from B-cell lymphoma.
研究领域:
生物医学工程
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癌症研究
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纳米技术
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免疫学
✓ 已验证
产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Kaiping Wang,Yuxuan Liu,Zeming Zhang,Ziming Zheng,Wenqi Tang,Wangtianzi Teng,Xu Mu,Jinglin Wang,Yu Zhang
Lentinan (LNT), a natural polysaccharide, has been reported to exhibit immunomodulatory effects in the intestine after oral administration. Herein, we aimed to investigate the lymphatic transport of LNT in Peyer's patches (PPs) by traceable fluorescent labeling and to explore whether/how LNT contacts related immune cells. Near-infrared imaging confirmed the absorption of LNT in the small intestinal segment and its accumulation within PPs after oral administration. Subsequently, tissue imaging confirmed that M cells are the main cells responsible for transporting LNT to PPs, and an M cell model was established to explore the involvement of Dectin-1 in the absorption process. Systematic in vitro and in vivo studies revealed that the Dectin-1 further mediates the uptake of LNT by mononuclear phagocytes in PPs. Moreover, LNT can promote the proliferation and differentiation of mononuclear phagocytes, thereby activating immune responses. In summary, this study elucidates the pharmacokinetic mechanisms by which LNT exerts oral immunomodulatory effects, providing a theoretical basis for the development and application of other polysaccharides.
研究领域:
免疫学
·
药理学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2022
·Vol. 11
·期 22
·2201166
·
IF 11.092
Yueyang Deng,Caixia Tan,Shuguang Huang,Honghao Sun,Zhaoting Li,Jing Li,Zhanwei Zhou,Minjie Sun
Tumor metastasis contributes to high cancer mortality. Tumor cells in lymph nodes (LNs) are difficult to eliminate but underlie uncontrollable systemic metastasis. The CC chemokine receptor 7 (CCR7) is overexpressed in tumor cells and interacts with CC chemokine ligand 21 (CCL21) secreted from LNs, potentiating their lymphatic migration. Here, a site-specific polyplex is developed to block the CCR7-CCL21 signal and kill tumor cells toward LNs, greatly limiting their lymphatic infiltration. A CCR7-targeting small interfering RNA (siCCR7) is condensed by mPEG-poly-(lysine) with chlorin e6 (Ce6) modification (PPLC) to form PPLC/siCCR7. The knockdown of CCR7 by siCCR7 in tumor cells significantly reduced their response on CCL21 and LN tropism. Additionally, photodynamic therapy-mediated immune activation precisely targets and kills tumor cells released from the primary foci before they reaches the LNs, reducing the number of tumor cells entering the LNs. Consequently, the PPLC/siCCR7 polyplexes inhibited up to 92% of lung metastasis in 4T1 tumor bearing mice and reduced tumor cell migration to LNs by up to 80%. This site-specific strategy optimized anti-metastasis efficacy and promotes the clinical translational development of anti-metastatic therapy.
研究领域:
肿瘤学
·
分子生物学
·
免疫学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Yuling Mao,Shuang Feng,Shuai Li,Qinfu Zhao,Donghua Di,Yanfeng Liu,Siling Wang
Lymphatic transport of oral drugs allows extraordinary gains in bioavailability and efficacy through avoidance of first-pass hepatic metabolism and preservation of drugs at lymphatic tissues against lymph-mediated diseases. Chylomicrons can transport dietary lipids absorbed from the intestine to the tissues through lymphatic circulation . Herein, we engineered for the first time a chylomicron-pretended mesoporous silica nanocarrier that utilizes the digestion, re-esterification, and lymphatic transport process of dietary triglyceride to promote lymphatic transport of oral drugs. Taking lopinavir (LNV) as a model antiretroviral drug with disadvantages such as poor solubility, high first-pass effect and off-target deposition, this vehicle exhibited several properties belonging to ideal nanocarriers, including high drug load, amorphous dispersion and controlled release in the gastrointestinal tract . Additionally, a nano-bio interaction was demonstrated between nanoparticles and a key protein involved in chylomicron assembly; this biochemical reaction in cellular was utilized for the first time to promote lymphatic transport of nanocarriers for oral delivery. As a result, the chylomicron-pretended nanocarrier afforded 10.6-fold higher oral bioavailability compared with free LNV and effectively delivered LNV to gut-associated lymphoid tissues, where HIV persists and actively evolves. This approach not only promises a potential application to HIV-infected individuals but also opens a new avenue to other lymph-mediated pathologies such as autoimmune diseases and lymphatic tumor metastasis.
研究领域:
药剂学
·
纳米医学
·
药物递送系统
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Hong Liu,Zhenfu Wen,Haolin Chen,Zeyu Yang,Zhicheng Le,Zhijia Liu,Yongming Chen,Lixin Liu
Great efforts have been made to manipulate nanoparticles (NPs) with a diameter of 10–100 nm to passively target lymph nodes (LNs) to magnitude anti-tumor activity of T cells . However, no attention has been paid to increasing the retention of NPs with active affinity in order to induce a prolonged release of antigens or molecular adjuvants in the LNs mattering the immune response. Here, we formulated two NPs encapsulated with imiquimod (IMQ), a TLR7/8 agonist, and paclitaxel (PTX) and further modified them with tannic acid (TA), respectively, to generate IMQ NP and PTX NP with a final diameter of approximately 40 nm. Attributing a strong affinity of TA molecules to the elastin of LN conduits, the TA modified IMQ NPs can bypass the gaps in the layer of lymphatic endothelial cells and enter the paracortex through the lymph node capsule-associated (LNC) conduits. Similarly, the TA modified PTX NPs increased delivery of PTX to the metastatic tumor site in LNs, where the tumor-associated antigens were released and presented by conduits-lining dendritic cells to activate T cells. Thus, the NPs with deposition to LN conduits showed excellent performance in preventing lymphovascular invasion of triple-negative breast cancer cells and lung metastasis thereafter. On the contrary, the NPs without TA flowed through the subcutaneous sinus existing LNs directly by efferent lymphatic vessels showing relatively poor therapeutic outcomes. This study reveals that TA may mediate the long retention of antigens and molecular adjuvants to be delivered to deep LNs for developing potent vaccination technology.
研究领域:
癌症研究
·
药学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers of Optoelectronics
·
2023
·Vol. 16
·期 1
·1-12
·
IF 5.4
Li Dongyu,Lin Hao,Sun Silin,Liu Shaojun,Liu Zhang,He Yuening,Zhu Jingtan,Xu Jianyi,Semyachkina-Glushkovskaya Oxana,Yu Tingting,Zhu Dan
Alzheimer’s disease (AD) is an age-related neurodegenerative disorder that poses a significant burden on socio-economic and healthcare systems worldwide. However, the currently available therapy of AD is limited, and new strategies are needed to enhance the clearance of β-amyloid (Aβ) protein and improve cognitive function. Photobiomodulation (PBM) is a non-invasive and effective therapeutic method that has shown promise in treating various brain diseases. Here, we demonstrate that 1267-nm PBM significantly alleviates cognitive decline in the 5xFAD mouse model of AD and is safe as it does not induce a significant increase in cortical temperature. Moreover, with the combination of 3D tissue optical clearing imaging and automatic brain region segmentation, we show that PBM-mediated reductions of Aβ plaques in different subregions of prefrontal cortex and the hippocampus are different. The PBM-induced lymphatic clearance of Aβ from the brain is associated with improvement of memory and cognitive functions in 5xFAD mice. Our results suggest that the modulation of meningeal lymphatic vessels (MLVs) should play an important role in promoting Aβ clearance. Collectively, this pilot study demonstrates that PBM can safely accelerate lymphatic clearance of Aβ from the brain of 5xFAD mice, promoting improvement of neurocognitive status of AD animals suggesting that PBM can be an effective and bedside therapy for AD. Graphical Abstract
研究领域:
神经科学
·
生物医学工程
·
治疗学
✓ 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）