CELLULAR AND MOLECULAR LIFE SCIENCES
·
2024
·Vol. 81
·期 1
·1-20
·
IF 6.2
Jiang Yujun,Gao Ruihan,Ying Qiaohui,Li Xiaolin,Dai Yaling,Song Aimei,Liu Hongrui,Hasegawa Tomoka,Li Minqi
Active vitamin D, known for its role in promoting osteoporosis, has immunomodulatory effects according to the latest evidence. Eldecalcitol (ED-71) is a representative of the third-generation novel active vitamin D analogs, and its specific immunological mechanisms in ameliorating diabetic osteoporosis remain unclear. We herein evaluated the therapeutic effects of ED-71 in the context of type 2 diabetes mellitus (T2DM), delving into its underlying mechanisms. In a T2DM mouse model, ED-71 attenuated bone loss and marrow adiposity. Simultaneously, it rectified imbalanced glucose homeostasis and dyslipidemia, ameliorated pancreatic β-cell damage and hepatic glycolipid metabolism disorder. Subsequently, in mice injected with the Treg cell-depleting agent CD25, we observed that the beneficial effects of ED-71 mentioned earlier were partially contingent on the Treg subsets ratio. Mechanistically, ED-71 promoted the differentiation of CD4 + T cells into Treg subsets, facilitating Ca 2+ influx and the expression of ORAI1 and STIM1, pivotal proteins in store-operated Ca 2+ entry (SOCE). The SOCE inhibitor, 2-APB, partially attenuated the positive effects of ED-71 observed in the above results. Overall, ED-71 regulates SOCE-mediated Treg cell differentiation, accomplishing the dual purpose of simultaneously ameliorating diabetic osteoporosis and glucolipid metabolic disorders, showcasing its potential in osteoimmunity therapy and interventions for diseases involving SOCE.
研究领域:
内分泌学
·
免疫学
·
代谢学
·
药理学
·
骨质疏松
✓ 已验证
DOI
PubMed
高影响因子
Materials Advances
·
2022
·Vol. 3
·期 18
·7080-7086
·
IF 0
Xueke Wu,Chenyuan Yan,Lixuan Mu,Yuan Wang,Guangwei She,Wensheng Shi
By assembling fluorophore-marked DNA stem-loops on the surface of gold nanobipyramids (AuNBPs) with an efficient photothermal conversion, we fabricated a multifunctional photothermal reagent (AuNBPs-mPEG/AA-TR). The sgc8 sequences that were embedded inside the DNA stem-loops can specifically target the PTK7, an overexpressed protein located on the surface of CCRF-CEM cells (human acute lymphoblastic leukemia T lymphocyte) to realize an active targeting function. Before the AuNBPs-mPEG/AA-TR bind to the PTK7 proteins, the DNA stem-loops are folded, and the fluorophore linked on the DNA stem-loop will be close to the AuNBPs. In this configuration, the fluorescence from the fluorophore is quenched by the AuNBPs. However, when the AuNBPs-mPEG/AA-TR bound to the PTK7 proteins through the sgc8 sequences, the DNA stem-loops can be opened partially to enable the fluorophore to be far away from the AuNBPs. As a result, the fluorescent signal will be activated. Therefore, the fluorescence can be used as a visual signal to reveal the binding between the AuNBPs-mPEG/AA-TR and CCRF-CEM cells (usually called activatable fluorescence labelling). While under irradiation of an 808 nm laser, the CCRF-CEM cells could be ablated through the photothermal therapy of the AuNBPs-mPEG/AA-TR with a high photothermal efficiency. Applying the AuNBPs-mPEG/AA-TR to Human B lymphoma cells (Ramos cells) and CCRF-CEM cells, we found that only the CCRF-CEM cells can be effectively targeted, actively fluorescently labeled, and readily ablated by the AuNBPs-mPEG/AA-TR. This work provides an alternative photothermal agent for the targeted therapy of tumors.
研究领域:
纳米技术
·
生物医学工程
·
癌症治疗
·
分子生物学
·
光学
✓ 已验证
DOI
JOURNAL OF ANIMAL SCIENCE
·
2014
·Vol. 92
·期 8
·3745-3752
·
IF 1.92
Yin Y.,Zhang W. G.,Zhou G. H.,Guo B.
The objective of this study was to investigate the differences in protein modifications between pale, soft, and exudative (PSE) and red, firm, and nonexudative (RFN) pork during postmortem (PM) aging. Longissimus dorsi (LD) including 8 PSE and 8 RFN muscles were individually removed from 16 carcasses. These 16 LD muscles were vacuum packaged at 24 h after slaughter and stored at 4°C for 1, 3, and 5 d. The centrifugation loss, drip loss, color, protein solubility, protein oxidation, protein degradation including desmin, troponin T, and integrin, and μ-calpain activation were determined. The pH of PSE samples was significantly lower than that of RFN samples at both 1 and 24 h PM (P < 0.05). The L* values of PSE pork were significantly greater than that of RFN pork at different time point during PM storage (P < 0.01). The centrifugation loss of PSE samples at d 1 was extremely greater than samples from RFN pork (P < 0.01). The cumulative drip loss for d 0 to 1, d 0 to 3, and d 0 to 5 in PSE pork were significantly greater than that from RFN pork (P < 0.05). The carbonyl content of myofibrillar proteins was not significantly different between PSE and RFN pork samples (P > 0.05). In addition, PSE pork presented a lower solubility of sarcoplasmic protein, myofibrillar protein, and total protein than RFN pork except the solubility of myofibrillar protein at d 1 (P < 0.05). The intensity of intact desmin and troponin T 2 in PSE pork at d 3 and 5 were significantly greater than that in RFN pork (P < 0.05), whereas no significant difference was detected at d 1. The intensity of intact troponin T 1 in PSE pork at d 5 was greater than that in RFN pork (P < 0.05). However, more degradation products of integrin were detected in PSE pork compared to that of RFN pork at d 1 (P < 0.05). Red, firm, and nonexudative pork presented lower intensity of intact 80 kDa calpain and greater intensity of autolyzed 76 kDa product compared to PSE pork (P < 0.01). The results indicate that the degree of μ-calpain activation, the extent of protein degradation including desmin and integrin, and the level of protein solubility in PSE pork could contribute to its low water holding capacity during PM storage.
研究领域:
肉类科学
·
食品科学
·
生物化学
·
宰后生理学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2024
·
IF 6.1
Xiaopeng Li,Yang Zhong,Pengyuan Qi,Daoming Zhu,Chenglong Sun,Nan Wei,Yang Zhang,Zhanggui Wang
Radiotherapy (RT) is one of the most common treatments for cancer. However, intracellular glutathione (GSH) plays a key role in protecting cancer from radiation damage. Herein, we have developed a platelet membrane biomimetic nanomedicine (PMD) that induces double GSH consumption to enhance tumor radioimmunotherapy. This biomimetic nanomedicine consists of an external platelet membrane and internal organic mesoporous silica nanoparticles (MON) loaded with 2-deoxy-D-glucose (2-DG). Thanks to the tumor-targeting ability of the platelet membranes, PMD can target and aggregate to the tumor site, which is internalized by tumor cells. Within tumor cells overexpressing GSH, MON reacts with GSH to degrade and release 2-DG. This step initially depletes the intracellular GSH content. The subsequent release of 2-DG inhibits glycolysis and adenosine triphosphate (ATP) production, ultimately leading to secondary GSH consumption. This nanodrug combines dual GSH depletion, starvation therapy, and RT to promote immunogenic cell death and stimulate the systemic immune response. In the bilateral tumor model in vivo, distal tumor growth was also well suppressed. The proportion of mature dendritic cells (DC) and CD8 + T cells in the mice was increased. This indicates that PMD can promote anti-tumor radioimmunotherapy and has good prospects for clinical application.
研究领域:
纳米医学
·
癌症治疗
·
免疫治疗
·
辐射生物学
·
药学
✓ 已验证
DOI
PubMed
高影响因子
Life Science Alliance
·
2024
·Vol. 7
·期 4
·e202302375
·
IF 3.3
Jialing Bao,Yunlin Tang,Yebo Chen,Jiangyan Jin,Xue Wang,Guozhen An,Lu Cao,Huarui Zhang,Gong Cheng,Guoqing Pan,Zeyang Zhou
Microsporidia are difficult to be completely eliminated once infected, and the persistence disrupts host cell functions. Here in this study, we aimed to elucidate the impairing effects and consequences of microsporidia on host DCs. Enterocytozoon hellem, one of the most commonly diagnosed zoonotic microsporidia species, was applied. In vivo models demonstrated that E. hellem-infected mice were more susceptible to further pathogenic challenges, and DCs were identified as the most affected groups of cells. In vitro assays revealed that E. hellem infection impaired DCs’ immune functions, reflected by down-regulated cytokine expressions, lower extent of maturation, phagocytosis ability, and antigen presentations. E. hellem infection also detained DCs’ potencies to prime and stimulate T cells; therefore, host immunities were disrupted. We found that E. hellem Ser/Thr protein phosphatase PP1 directly interacts with host p38α (MAPK14) to manipulate the p38α(MAPK14)/NFAT5 axis of the MAPK pathway. Our study is the first to elucidate the molecular mechanisms of the impairing effects of microsporidia on host DCs’ immune functions. The emergence of microsporidiosis may be of great threat to public health.
研究领域:
免疫学
·
微生物学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-21
·
IF 10.6
Xu Wenhao,Ye Shiqi,Liu Wangrui,Guo Huaqi,Zhang Linhui,Wei Shiyin,Anwaier Aihetaimujiang,Chang Kun,Malafaia Guilherme,Zhang Hailiang,Ye Dingwei,Wei Gang
In recent years, the environmental health issue of microplastics has aroused an increasingly significant concern. Some studies suggested that exposure to polystyrene microplastics (PS-MPs) may lead to renal inflammation and oxidative stress in animals. However, little is known about the essential effects of PS-MPs with high-fat diet (HFD) on renal development and microenvironment. In this study, we provided the single-cell transcriptomic landscape of the kidney microenvironment induced by PS-MPs and HFD in mouse models by unbiased single-cell RNA sequencing (scRNA-seq). The kidney injury cell atlases in mice were evaluated after continued PS-MPs exposure, or HFD treated for 35 days. Results showed that PS-MPs plus HFD treatment aggravated the kidney injury and profibrotic microenvironment, reshaping mouse kidney cellular components. First, we found that PS-MPs plus HFD treatment acted on extracellular matrix organization of renal epithelial cells, specifically the proximal and distal convoluted tubule cells, to inhibit renal development and induce ROS-driven carcinogenesis. Second, PS-MPs plus HFD treatment induced activated PI3K-Akt, MAPK, and IL-17 signaling pathways in endothelial cells. Besides, PS-MPs plus HFD treatment markedly increased the proportions of CD8 + effector T cells and proliferating T cells. Notably, mononuclear phagocytes exhibited substantial remodeling and enriched in oxidative phosphorylation and chemical carcinogenesis pathways after PS-MPs plus HFD treatment, typified by alterations tissue-resident M2-like PF4 + macrophages. Multispectral immunofluorescence and immunohistochemistry identified PF4 + macrophages in clear cell renal cell carcinoma (ccRCC) and adjacent normal tissues, indicating that activate PF4 + macrophages might regulate the profibrotic and pro-tumorigenic microenvironment after renal injury. In conclusion, this study first systematically revealed molecular variation of renal cells and immune cells in mice kidney microenvironment induced by PS-MPs and HFD with the scRNA-seq approach, which provided a molecular basis for decoding the effects of PS-MPs on genitourinary injury and understanding their potential profibrotic and carcinogenesis in mammals. Graphical Abstract
研究领域:
环境健康
·
分子生物学
·
免疫学
·
肾病学
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
Science Advances
·
2020
·Vol. 6
·期 36
·
IF 13.117
Lin Qin,Jun Cao,Kun Shao,Fan Tong,Zhihang Yang,Ting Lei,Yazhen Wang,Chuan Hu,Channakeshava Sokke Umeshappa,Huile Gao,Nicholas A. Peppas
Application of cancer vaccines is limited due to their systemic immunotoxicity and inability to satisfy all the steps, including loading of tumor antigens, draining of antigens to lymph nodes (LNs), internalization of antigens by dendritic cells (DCs), DC maturation, and cross-presentation of antigens for T cell activation. Here, we present a combinatorial therapy, based on a α-cyclodextrin (CD)–based gel system, DOX/ICG/CpG-P-ss-M/CD, fabricated by encapsulating doxorubicin (DOX) and the photothermal agent indocyanine green (ICG). Upon irradiation, the gel system exhibited heat-responsive release of DOX and vaccine-like nanoparticles, CpG-P-ss-M, along with chemotherapy- and phototherapy-generated abundant tumor-specific antigen storage in situ. The released CpG-P-ss-M acted as a carrier adsorbed and delivered antigens to LNs, promoting the uptake of antigens by DCs and DC maturation. Notably, combined with PD-L1 blocking, the therapy effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis.
研究领域:
肿瘤学
·
免疫治疗
·
药学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Pei Pan,Xue Dong,Ying Chen,Jing-Jie Ye,Yun-Xia Sun,Xian-Zheng Zhang
Radiotherapy is adopted to obliterate multiple malignant tumors clinically, which might also induce antitumor immune response. However, traditional radiotherapy is not enough to ablate tumors and activate long-term immunological response. Here, we developed a hybrid nanoplatform (MGTe) composed of GTe (glutathione (GSH) decorated Te nanoparticles) and fusing tumor cell membranes (TM) and bacterial outer membranes (BM). In this nanoplatform, GTe was designed for radiotherapy sensitization, concurrently the fusion of TM and BM was expected for amplifying antitumor immune. With a high-Z element, MGTe could enhance radiosensitivity by reactive oxygen species (ROS) production and cancer cell immunogenic death (ICD) under X-ray irradiation, which would also trigger antitumor immune. At meanwhile, TM and BM would further enlarge the immunological effects through antigen presenting cells (APCs) maturation and cytotoxic T lymphocytes (CTLs) stimulation. In this synergistic strategy, the combination of MGTe and X-ray showed significant tumor inhibition by radiation-driven immunotherapy, which will find great potential as an attractive clinical alternative to fight against tumor with reduced side effects.
研究领域:
肿瘤学
·
纳米技术
·
免疫学
·
放射生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Energy Storage
·
2022
·
IF 8.907
Sebastiano Tomassetti,Alessia Aquilanti,Pio Francesco Muciaccia,Gianluca Coccia,Christoph Mankel,Eduardus A.B. Koenders,Giovanni Di Nicola
The increasing use of renewable energy sources has highlighted the importance of energy storages, and in particular of latent heat thermal energy storages (LHTESs). Among the phase change materials (PCMs) that can be used in such systems, sugar alcohols (SAs) are considered potential substances that may lead to interesting applications in the LHTES sector. In this work, a detailed literature review analysis of six SAs (xylitol, sorbitol, erythritol, mannitol, inositol, dulcitol), their thermophysical properties, their thermal stability and their main LHTES applications is presented for the first time. The thermophysical properties under discussion include melting and crystallization temperatures , latent heats of melting and crystallization, specific heat, thermal conductivity , density and dynamic viscosity . Thermal stability was evaluated by taking into account studies of thermal endurance, degradation temperature and cycling stability. Differential scanning calorimetry (DSC), T -history, Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) were considered as measurement techniques. Applications include the use of SAs in solar collectors and cookers, heat exchangers , porous materials, absorption cooling systems, mobilized thermal energy storages (M-TESs). New measurements of phase transition properties and degradation temperature for the studied SAs were also carried out by the authors of the present study. A good agreement between the proposed data and the literature values was found. The analysis reveals that some SAs may be considered suitable for low-to-medium temperature LHTES applications, provided that their drawbacks are adequately evaluated and addressed. To this purpose, the study also highlights the most critical aspects that should be considered when developing both fundamental research and engineering applications related to SAs.
研究领域:
能量存储
·
热能工程
·
材料科学
·
可再生能源
✓ 已验证
DOI
高影响因子
Advanced Science
·
2023
·Vol. 10
·期 33
·2302622
·
IF 15.1
Yifan Ma,Lili Sun,Jingjing Zhang,Chi-ling Chiang,Junjie Pan,Xinyu Wang,Kwang Joo Kwak,Hong Li,Renliang Zhao,Xilal Y. Rima,Chi Zhang,Anan Zhang,Yutong Liu,Zirui He,Derek Hansford,Eduardo Reategui,Changsheng Liu,Andrew S. Lee,Yuan Yuan,Ly James Lee
Regenerative medicine in tissue engineering often relies on stem cells and specific growth factors at a supraphysiological dose. These approaches are costly and may cause severe side effects. Herein, therapeutic small extracellular vesicles (t-sEVs) endogenously loaded with a cocktail of human vascular endothelial growth factor A (VEGF-A) and human bone morphogenetic protein 2 (BMP-2) mRNAs within a customized injectable PEGylated poly (glycerol sebacate) acrylate (PEGS-A) hydrogel for bone regeneration in rats with challenging femur critical-size defects are introduced. Abundant t-sEVs are produced by a facile cellular nanoelectroporation system based on a commercially available track-etched membrane (TM-nanoEP) to deliver plasmid DNAs to human adipose-derived mesenchymal stem cells (hAdMSCs). Upregulated microRNAs associated with the therapeutic mRNAs are enriched in t-sEVs for enhanced angiogenic–osteogenic regeneration. Localized and controlled release of t-sEVs within the PEGS-A hydrogel leads to the retention of therapeutics in the defect site for highly efficient bone regeneration with minimal low accumulation in other organs.
研究领域:
再生医学
·
组织工程
·
干细胞生物学
·
骨修复
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2022
·Vol. 11
·期 12
·2102739
·
IF 11.092
Yanyun Hao,Hui Li,Huajun Zhao,Yutong Liu,Xiaoyan Ge,Xia Li,Hongfei Chen,Ailu Yang,Jing Zou,Xue Li,Xuechun Sun,Xinke Zhang,Xiao Wang,Zepeng Li,Qilu Zhang,Hao Wu,Guan Wang,Jian Zhang,Bruno G. De Geest,Zhiyue Zhang
Cancer immunotherapy is revolutionary in oncology and hematology. However, a low response rate restricts the clinical benefits of this therapy owing to inadequate T lymphocyte infiltration and low delivery efficiency of immunotherapeutic drugs. Herein, an intelligent nanovehicle (folic acid (FA)/1-(4-(aminomethyl) benzyl)-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine (IMDQ)-oxaliplatin (F/IMO)@CuS) armed with multifunctional navigation is designed for the accurate delivery of cargoes to tumor cells and dendritic cells (DCs), respectively. The nanovehicle is based on a near infrared-responsive inorganic CuS nanoparticles, acting as a photosensitizer and carrier of the chemotherapeutic agent oxaliplatin, and enters tumor cells owing to the presence of folic acid on the surface of CuS upon intratumoral injection. Furthermore, a toll-like receptor (TLR) 7/8 agonist-conjugated polymer, anchored on the surface of CuS, is modified with mannose to bind with DCs in the tumor microenvironment. Upon exposure to laser irradiation, nanovehicles disassemble, releasing oxaliplatin, to ablate tumor cells and amplify immunogenic cell death in combination with photothermal therapy. Mannose-modified polymer-TLR7/8 agonist conjugates are subsequently exposed, leading to the activation of DCs and proliferation of T cells. Collectively, these intelligent nanovehicles reduce tumor burden, exert a robust antitumor immune response, and generate long-term immune protection to prevent tumor recurrence.
研究领域:
肿瘤学
·
免疫学
·
纳米技术
·
药学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）