MOLECULAR HUMAN REPRODUCTION
·
2018
·Vol. 25
·期 1
·5-16
·
IF 3.449
Sun Huihui,Li Dong,Yuan Ming,Li Qiuju,Zhen Qianwei,Li Ni,Wang Guoyun
STUDY QUESTIONDo exosomes play a role in the pathogenesis of endometriosis in a murine model?SUMMARY ANSWERExosomes from endometriosis (EMS) can alternatively activate macrophages and thus contribute to the development of lesions in mice.WHAT IS KNOWN ALREADYThe pathogenesis of endometriosis, an inflammatory disease, possibly involves peritoneal macrophages. Exosomes are recognized as a new communicator among cells and a key modulator in several inflammatory diseases.STUDY DESIGN, SIZE, DURATIONWe performed in vitr and in vivo experiments to demonstrate the role of exosomes in modulating macrophages. RAW264.7 cells (macrophages) were used to examine the effects of exosomes on macrophages in vitro. An experiment was also conducted in vivo, as follows. Fifty C57BL/6 female mice were randomly allocated to five control and five experimental groups (n = 5/group). The experimental group was injected i.p. with EMS-exosomes derived from eutopic stromal cells, starting on Day-7 then every day for 1 week. The control group received CON-exosomes from mice without endometriosis. Peritoneal macrophages were assessed over the next 6 days. On Day 0, all mice were injected i.p. with endometrium to establish the endometriosis model. On Day 14, all mice were sacrificed, ectopic lesions were counted and measured.PARTICIPANTS/MATERIALS, SETTING, METHODSExosomes were isolated from endometrial stromal cells (ESCs) by ultracentrifugation and characterized through transmission electron microscopy, nanoparticle tracking analysis and western blot. After treatment with exosomes, the polarization and phagocytic ability of the macrophages were detected by flow cytometry analysis, immunofluorescent staining and RT-PCR. C57BL/6 mice were utilized to establish an endometriosis model by i.p. injection of endometrial segments.MAIN RESULTS AND THE ROLE OF CHANCEAfter treatment with EMS-exosomes, the macrophages were polarized into an M2-like phenotype and their phagocytic ability decreased (P < 0.05 versus treatment with CON-exosomes). The total weight and volume of the lesions in mice treated with EMS-exosomes significantly increased compared with those in mice treated with CON-exosomes (P < 0.05). The infiltration of M2-like macrophages was enhanced in the EMS-exosome group (P < 0.001 versus treatment with CON-exosomes).LARGE SCALE DATAN/ALIMITATIONS, REASONS FOR CAUTIONDetection of endometriosis following exosome treatment was only performed in a murine endometriosis model. Clinical data and additional mechanism studies must be conducted to understand the role of exosomes in the pathogenesis of endometriosis.WIDER IMPLICATIONS OF THE FINDINGSThis study emphasizes the importance of EMS-exosomes in the pathogenesis of endometriosis. Further investigations on the exosome signaling pathways may contribute to the development of effective treatments for endometriosis.STUDY FUNDING/COMPETING INTEREST(S)This research was supported by grants (Nos. 81571417 and 81771552) from the National Science Foundation of China. The authors report no conflict of interest.
研究领域:
生殖生物学
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免疫学
·
妇科学
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Ziheng Chen,Hui Chen,Kaiwen Fang,Na Liu,Jiangfan Yu
Magnetic microswarms capable of performing navigation to targeted lesions show great potential for in vivo medical applications. However, using the swarms for lesion cavity filling encounters challenges from precise delivery and sealing. Herein, this work develops a magneto-thermal hydrogel swarm consisting of magnetic hydrogel particles, which can perform phase transition induced by temperature change. The particles are prepared using a temperature-responsive hydrogel matrix, tissue adhesive monomers, and magnetic microparticles. The swarms can be remolded to various shapes, and it can be used to seal perforation in phantom and gastric tissue. The swarms can also serve as drug carriers, and their drug release profiles induced by temperature changes are characterized. Finally, the targeted delivery, adaptive filling, and sealing of a gastric ulcer using the swarms are achieved in ex vivo and in vivo environments.
研究领域:
生物医学工程
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材料科学
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医疗机器人
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组织工程
✓ 已验证
DOI
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2024
·
IF 3.7
Anqi Wang,Yuanyuan Liu,Wugui Xiong,Wei Li,Jin Li,Zhiqiang Yang,Zhongtao Zou,Yinjia Luo,Zhoujiang Chen,Hanmei Li,Chi Teng Vong,Liang Zou
Honokiol (HNK) is one of the bioactive ingredients from the well-known Chinese herbal medicine Magnolia officinalis , and its research interests is rising for its extensive pharmacological activities, including novel therapeutic effect on ulcerative colitis (UC). However, further application of HNK is largely limited by its unique physicochemical properties, such as poor water solubility, low bioavailability, as well as unsatisfied targeting efficacy for inflammatory lesions. In this study, we constructed galactosylation modified PLGA nanoparticles delivery system for efficient target delivery of HNK to the colitic lesions, which could lay a research foundation for the deep development of HNK for the treatment of UC. D-galactose was grafted by chemical coupling reactions with PLGA to prepare Gal-PLGA, which was used as a carrier for HNK (Gal-PLGA@HNK nanoparticles (NPs)). To improve the colon targeting efficiency by oral administration of the NPs, Eudragit S100 was used for wrapping on the surface of Gal-PLGA@HNK NPs (E/Gal-PLGA@HNK NPs). Our results showed that the encapsulation efficiency and drug loading capacity of E/Gal-PLGA@HNK NPs were 90.72 ± 0.54% and 8.41 ± 0.02%, respectively. Its average particle size was 242.24 ± 8.42 nm, with a PDI value of 0.135 ± 0.06 and zeta-potential of -16.83 ± 1.89 mV. The release rate of HNK from E/Gal-PLGA@HNK NPs was significantly decreased when compared with that of free HNK in simulated gastric and intestinal fluids, which displayed a slow-releasing property. It was also found that the cellular uptake of E/Gal-PLGA@HNK NPs was significantly increased when compared with that of free HNK in RAW264.7 cells, which was facilitated by D-galactose grafting on the PLGA carrier. Additionally, our results showed that E/Gal-PLGA@HNK NPs significantly improved colonic atrophy, body weight loss, as well as reducing disease activity index (DAI) score and pro-inflammatory cytokine levels in UC mice induced by DSS. Besides, the retention time of E/Gal-PLGA@HNK NPs in the colon was significantly increased when compared with that of other preparations, suggesting that these NPs could prolong the interaction between HNK and the injured colon. Taken together, the efficiency for target delivery of HNK to the inflammatory lesions was significantly improved by galactosylation modification on the PLGA carrier, which provided great benefits for the alleviation of colonic inflammation and injury in mice.
研究领域:
药学
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纳米技术
·
药物递送系统
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炎症性肠病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Peng He,Sha Yi,Jianzhong Zhang,Chengchao Chu,Xuqi Peng,Changhong Li,Xinfei Sun,Yang Zhang,Hongwei Cheng,Xia Xiong,Gang Liu
Pathological scars, including hypertrophic scars (HTSs) and keloids, are abnormal wound healing responses, and current treatments are often unsatisfactory. Intralesional multi-injection of 5-fluorouracil (5-Fu), a commonly used approach, has raised great concerns due to its short retention time and adverse effects for anti-scar treatments. To address this, we developed a novel formulation of 5-Fu for scar management, carrier-free pure 5-Fu nanoparticles (nano 5-Fu), prepared by a super-stable pure-nanomedicine formulation technology. In vitro tests on keloid fibroblasts and human umbilical vein endothelial cells (HUVECs) showed that nano 5-Fu possessed superior ability to inactivate these cells compared to free 5-Fu. In vivo retention tests on rabbit HTSs and rat normal skin demonstrated that nano 5-Fu could coexist in soft tissues for a longer time, resulting in a more effective dosage in scar lesions. In vivo results on rabbit scars indicated that nano 5-Fu can lead to a significant reduction in scar elevation index (SEI), collagen fiber deposition and microvessels for skin remodeling. Importantly, the results of the first-in-human trial demonstrated that nano 5-Fu could decrease scar height and vascularity with excellent and stable efficacy as well as less topical side effects. Peripheral blood analyses demonstrated the high systemic safety of nano 5-Fu intralesional injection in HTSs. The carrier-free 5-Fu nanoparticle-mediated “domestication” therapy, featuring low dosage, outstanding efficacy and safety, represents a promising strategy for pathological scar treatment.
研究领域:
药剂学
·
皮肤科
·
纳米技术
·
临床试验
✓ 已验证
产品关联
DOI
高影响因子
Food & Function
·
2020
·Vol. 11
·期 11
·9634-9650
·
IF 4.171
Jie Shen,Pei Li,Shuangshuang Liu,Qing Liu,Yue Li,Zheng Zhang,Chengmin Yang,Mengying Hu,Yuhua Sun,Chunnian He,Peigen Xiao
Despite that colorectal cancer (CRC) is a severe global health problem, effective chemopreventive strategies against CRC are still lacking. Huang-qin tea (HQT), a healthy herbal tea, is prepared from the aerial parts of Scutellaria baicalensis Georgi and has been consumed in China for thousands of years. HQT contains abundant flavonoids, which display potent anticancer effects, but no research studies have investigated the cancer-preventive effects of HQT on CRC in vivo. Here, we found that HQT inhibits azoxymethane-induced aberrant crypt foci (ACF) formation in a preneoplastic colonic ACF rat model. The essential role of the gut microbiota in the chemopreventive effect of HQT on CRC in a pseudo-germ-free rat model was confirmed. Besides, HQT modulates inflammatory cytokine expression by significantly decreasing IL-1β, IL-6, IL-10, and TNF-α expression, and elevating IFN-γ production. 16S rDNA sequencing analysis indicated that HQT regulated the gut microbiota by increasing the abundance of beneficial bacteria (Lachnoclostridium, Alistipes, Roseburia, and Lactococcus) and reducing the levels of Bacteroides, Parasutterella, and unidentified_Clostridiales. Fecal metabolomics showed that HQT modulated the AOM-induced metabolomic disorder, and these altered metabolites were almost involved in the lipid metabolic pathways. The Spearman correlation analysis revealed a correlation between the gut microbiota and fecal metabolites. Collectively, these results suggested that HQT exerted beneficial effects on host health by inhibiting inflammation, and by regulating the gut microbiota profile and certain metabolic pathways. In conclusion, HQT inhibits AOM-induced ACF formation by modulating the gut microbiota composition and improving metabolomic disorders, indicating the potential of HQT as a functional beverage candidate for the prevention and treatment of CRC.
研究领域:
肿瘤学
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药理学
·
微生物学
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代谢组学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2023
·
IF 7.2
Yuan Zhu,Wei-feng Yin,Pei Yu,Chao Zhang,Ming-hui Sun,Ling-yi Kong,Lei Yang
Distal metastases from breast cancer, especially bone metastases, are extremely common in the late stages of the disease and are associated with a poor prognosis. EMT is a biomarker of the early process of bone metastasis, and MMP-9 and MMP-13 are important osteoclastic activators. Previously, we found that meso-Hannokinol (HA) could significantly inhibit EMT and MMP-9 and MMP-13 expressions in breast cancer cells. On this basis, we further explored the role of HA in breast cancer bone metastasis. In vivo, we established a breast cancer bone metastasis model by intracardially injecting breast cancer cells. Intraperitoneal injections of HA significantly reduced breast cancer cell metastasis to the leg bone in mice and osteolytic lesions caused by breast cancer. In vitro, HA inhibited the migration and invasion of breast cancer cells and suppressed the expressions of EMT, MMP-9, MMP-13, and other osteoclastic activators. HA inhibited EMT and MMP-9 by activating the ROS/JNK pathway as demonstrated by siJNK and SP600125 inhibition of JNK phosphorylation and NAC scavenging of ROS accumulation. Moreover, HA promoted bone formation and inhibited bone resorption in vitro. In conclusion, our findings suggest that HA may be an excellent candidate for treating breast cancer bone metastasis.
研究领域:
肿瘤学
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药理学
·
细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 29
·5829-5836
·
IF 6.331
Jian Li,Tingting Wang,Feng Jiang,Zhangyong Hong,Xinhui Su,Shuang Li,Shoufa Han
Approaches that could enable precise photodynamic therapy (PDT) are of therapeutic potential. We herein report a trifunctional probe (Glu-RdEB) that could be activated to generate fluorescent rhodamine species to pinpoint tumor foci. The probe contains a γ-glutaminyl moiety cleavable to γ-glutamyl transpeptidase (GGT) overexpressed in multiple tumors, an entity of an ENBS photosensitizer for PDT, and an entity of rhodamine fluorescently quenched by ENBS. Upon activation by tumor-associated GGT, the probe releases highly fluorescent rhodamine that is selectively confined in tumors whereby light irradiation leads to effective tumor regression in mice. These results indicate the feasibility of a fluorescently quenched dye–photosensitizer pair to yield tumor-activatable fluorescence to direct PDT.
研究领域:
癌症治疗
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分子影像
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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
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Ziwei Duan,Jialei Han,Yadong Liu,Xinyu Zhao,Bo Wang,Shuaishuai Cao,Dalin Wu
Magnetic resonance imaging (MRI) has emerged as a pivotal tool in contemporary medical diagnostics, offering non-invasive and high-resolution visualization of internal structures. Contrast agents are essential for enhancing MRI resolution, accurate lesion detection, and early pathology identification. While gadolinium-based contrast agents are widely used in clinical, however, safety concerns have prompted exploration of metal-free alternatives, including fluorine and nitroxide radical-based MRI contrast agents. Fluorine-containing compounds exhibit excellent MRI capabilities, with 19F MRI providing enhanced resolution and quantitative assessment. Nitroxide radicals, such as PROXYL and TEMPO, offer paramagnetic properties for MRI contrast. Despite their versatility, nitroxide radicals suffer from lower relaxivity values (r1) compared to gadolinium. Dual-modal imaging, combining 1H and 19F MRI, has gained prominence for its comprehensive insights into biological processes and disease states. However, existing dual-modal agents predominantly utilize gadolinium-organic ligands without incorporating nitroxide radicals. Here, we introduce a novel dual-modal MRI contrast agent (J-CA) featuring a Janus asymmetric nanostructure synthesized via seeded emulsion polymerization and post-modification. J-CA demonstrates excellent in vitro and in vivo performance in both 19F and 1H MRI, with T2 relaxation time of 5 ms and r1 of 0.31 mM-1·s-1, ensuring dual-modal imaging capability. Moreover, J-CA exhibits superior biocompatibility and organ targeting, making it a promising candidate for precise lesion imaging and disease diagnosis. This work introduces a new avenue for metal-free dual-modal MRI, addressing safety concerns associated with traditional contrast agents.
研究领域:
医学诊断
·
磁共振成像 (MRI)
·
造影剂
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Qilin Li,Jia Liu,Huiling Fan,Lin Shi,Yan Deng,Lei Zhao,Mengxi Xiang,Yunruo Xu,Xulin Jiang,Guobin Wang,Lin Wang,Zheng Wang
Immunogenic chemotherapy (IC) is a type of chemotherapy where certain chemodrugs induce immunogenic cancer cell death (ICD), which in turn arouses T cell antitumor immunity. However, IC concurrently upregulates a key immune suppressor, indoleamine-2,3-dioxygenase (IDO), in both cancer cells and immune cells . IDO-mediated immunosuppression significantly offsets IC's therapeutic benefits in cancer patients , suggesting a necessity of combination with IDO inhibitors. Here, we report an enzyme-, pH-, and redox-triple-sensitive nanosystem using mesoporous silica nanoparticles (MSNs) as a core encapsulating doxorubicin (DOX, an immunogenic chemodrug); the core is coated with a shell ( β -CD-PEI/Ge1MT) for co-delivering 1-methyl-D-tryptophan (1 MT, an IDO inhibitor). By using these responsivenesses sequentially triggering the release of 1 MT into tumor extracellular compartment and DOX into intracellular endo/lysosomal compartment, this nanosystem ( [email protected] ) precisely delivers the drugs to their target cells residing in different compartments. Released 1 MT uptake by IDO-expressing dendritic cells (DCs) and cancer cells suppresses IDO activity, reducing immunosuppressive Tregs' presence; DOX unloaded within cancer cells induces ICD, promoting effector T-cell infiltration . In two preclinical cancer models, [email protected] potentiate both tumor local and systemic antitumor immunity, suppressing primary tumor growth by 78% with an 83% reduction in metastatic foci, as well as extending animal survival, thus strongly demonstrating [email protected] GMTMSNs' clinical translational potential.
研究领域:
癌症研究
·
纳米技术
·
免疫疗法
·
药学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 42
·6604-6611
·
IF 5.047
Ying Xie,Hua Wang,Jinzhu Mao,Yuce Li,Mubashir Hussain,Jinjin Zhu,Yan Li,Lianbin Zhang,Juan Tao,Jintao Zhu
Hypertrophic scarring is a widespread skin disorder that affects a patient's confidence and quality of life. Intralesional injection of bleomycin is one of the most commonly employed treatments for hypertrophic scars, which, however, always brings pain and requires long-term treatment. To overcome these limitations, new methods for bleomycin delivery enabling painlessness, self-administration, the fast onset of action, and good bioavailability are urgently needed. In this study, we developed bleomycin-loaded dissolving microneedles (BMN) made up of hyaluronic acid (HA) with excellent aqueous solubility and enhanced efficacy for inhibiting hypertrophic scars. The as-obtained BMN possesses sufficient mechanical strength to pierce porcine skin ex vivo with an insertion depth of over 300 μm. Moreover, BMN can dissolve rapidly and release 20% of loaded bleomycin within 1 min and 52% within 10 min, and the BMN-treated skin could recover to its original status within 3 h, demonstrating good biocompatibility. Besides, the HA matrix also maintains the stability and activity of bleomycin. Furthermore, we show that BMN consisting of HA and bleomycin can inhibit the proliferation of human hypertrophic scar fibroblasts (hHSFs) and the secretion of transforming growth factor-β (TGF-β1) in vitro. Therefore, bleomycin-loaded dissolving HA microneedles provide a potential route to treat hypertrophic scars in a convenient, efficient, and minimally invasive manner.
研究领域:
皮肤科
·
药剂学
·
生物医学工程
·
伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2023
·
IF 6.7
Peng Chen,Zeng Xiaodie,Cai Jiali,Huang Hanyu,Yang Fang,Jin Shaowen,Guan Xiuhong,Wang Zhiyong
Triple-negative breast cancer is a highly aggressive and metastatic tumor; diagnosing it in the early stages is still difficult, and the prognosis for conventional radio-chemotherapy and immunotreatment is not promising due to cancer’s immunosuppressive microenvironment. The utilization of protein-based nanosystem has proven to be effective in delivering agents with limited adverse effects, yet the combination of diagnosis and treatment remains a difficult challenge. This research took advantage of natural albumin and organic molecules to construct a self-assemble core-shell nanostructure combining with superparamagnetic iron oxide nanocrystals and heptamethine cyanine dye IR780 through non-covalent interactions. This nanocomposite successfully decreased the transverse relaxation time of the magnetic resonance hydrogen nucleus, resulting in outstanding T2 imaging, as well as emitting near-infrared II fluorescence, thereby the resulting dual-modality imaging tool was applied to improve diagnostic competency. It is noteworthy that the nanocomposites exhibited impressive enzyme-like catalytic and photothermal capabilities, resulting in a successful activation of the immune system to efficiently suppress distant metastatic lesions in vivo. Consequently, this nanodrug-based therapy could be an advantageous asset in reinforcing the immune system and hindering the growth and reappearance of the immune-cold breast cancer.
研究领域:
癌症生物学
·
纳米技术
·
成像科学
·
治疗学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Tissue Engineering
·
2024
·
IF 6.7
Yue Zhao,Yinlian Yao,Shilong Fan,Xin Shen,Xingxing Chai,Zimin Li,Jiachun Zeng,Jiang Pi,Zhikun Zhou,Gonghua Huang,Hua Jin
The incidence of ulcerative colitis (UC) is rapidly rising worldwide. Oral drug delivery system is a promising approach for treating UC, but it often fails to accumulate to the inflammatory lesions, thus, it is impressive to develop a colon-targeted oral delivery system for preventing systemic toxicity and maintaining UC therapeutics. Here, a negative-charged PLGA nanoparticle system was designed to encapsulate celastrol (Cel), and then chitosan and mannose were coated on the surface of the nanoparticles (MC@Cel-NPs) to endow these nanoparticles with the mucosal adsorption and macrophage targeting abilities. MC@Cel-NPs demonstrate excellent resist decomposition ability against the strong acidic gastrointestinal environment, and accumulates in the specific inflammatory sites through the affinity of electrostatic reaction. After releasing the payload, MC@Cel-NPs could remarkably alleviate the colon inflammation, which was evidenced by the decrease in pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in both blood and colon sections, and scavenging reactive oxygen species (ROS) in colon cells, including macrophage, neutrophil, T cell, and B cell. This nanoparticle system provided a new approach for treating UC through a Chinese herbal ingredient-related oral delivery manner.
研究领域:
药学
·
纳米技术
·
炎症性肠病
·
药物递送系统
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）