Pharmaceutics
·
2020
·Vol. 12
·期 2
·111
·
IF 4.421
Weinan Li,Jialin Sun,Xiaoyu Zhang,Li Jia,Mingxi Qiao,Xiuli Zhao,Haiyang Hu,Dawei Chen,Yanhong Wang
PEG-poly(β-amino ester) (PEG-PBAE), which is an effective pH-responsive copolymer, was mainly synthesized by Michael step polymerization. Thioridazine (Thz), which was reported to selectively eliminate cancer stem cells (CSCs), was loaded into PEG-PBAE micelles (PPM) prepared by self-assembly at low concentrations. The critical micelle concentrations (CMC) of PPM in water were 2.49 μg/mL. The pH-responsive PBAE segment was soluble due to protonated tertiary amine groups when the pH decreased below pH 6.8, but it was insoluble at pH 7.4. The Thz-loaded PEG-PBAE micelle (Thz/PPM) exhibited a spherical shape, and the drug loading was 15.5%. In vitro release of Thz/PPM showed that this pH-sensitivity triggered the rapid release of encapsulated Thz in a weakly acidic environment. The in vitro cytotoxicity and cellular uptake of various formulations at pH 7.4 and 5.5 were evaluated on the mammospheres (MS), which were sorted by MCF-7 human breast cancer cell lines and identified to be a CD44+/CD24−phenotype. The results of the cytotoxicity assay showed that blank micelles were nontoxic and Thz/PPM exhibited a similar anti-CSC effect on MS compared to Thz solution. Stronger fluorescence signal of Coumarin-6 (C6) was observed in MS treated by C6-loaded PPM (C6/PPM) at pH 5.5. The tumor inhibition rate and tumor weight of the free DOX and Thz/PPM groups were significantly different from those of the other groups, which free DOX and Thz/PPM effectively suppressed breast tumor growth in vivo. The above experimental results showed that Thz/PPM is an ideal and effective pH-responsive drug delivery carrier to a targeted therapy of CSCs.Keywords:poly(β-amino ester);polymeric micelles;pH-responsive;cancer stem cells;thioridazine
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2020
·Vol. 109
·期 2
·207-218
·
IF 3.525
Jing Zhang,Irene ShuPing Zhao,Ollie YiRu Yu,QuanLi Li,May Lei Mei,ChengFei Zhang,Chun Hung Chu
Cyclic adenosine monophosphate (cAMP) is a second messenger involved in the dental regeneration. However, efficient long-lasting delivery of cAMP that is sufficient to mimic the in vivo microenvironment remains a major challenge. Here, cAMP was loaded in stem cells from apical papilla (SCAPs) using layer-by-layer self-assembly with gelatin and alginate polyelectrolytes (LBL-cAMP-SCAPs). LBL-cAMP-SCAPs expressed cAMP and increased the phosphorylation level of cAMP-response element-binding protein (CREB) which were evaluated by immunofluorescence and western blotting (WB). Enzyme-linked immunosorbent assay (ELISA) demonstrated that a sustained release of cAMP and vascular endothelial growth factor (VEGF) were present up to 14 days. Scanning electron microscopy (SEM) found LBL-coated SCAPs exhibited a spheroid-like morphology. CCK8 and live/dead staining showed that LBL treatment had no significant effect on cell proliferation and viability. LBL-cAMP-SCAPs enhanced mineralized nodule formation and up-regulated the mRNA levels of the osteogenesis-related genes, as well as related transcription factor-2 protein level which were revealed by Alizarin red staining, RT-PCR and WB, respectively. In conclusion, LBL self-assembly loaded with cAMP promoted the osteo/odontogenic differentiation of SCAPs, thereby providing a potential strategy for bioactive molecular delivery in dental regeneration.
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Journal of Future Foods
·
2026
·
IF 10.6
Zhen Zhang,Jia Liu,Wei Li,Lin Shen,Chengxu Liu,Jun Sheng,Cunchao Zhao,Ya Wang
Differential pressure explosion puffing regulated fiber structure from DPSR. • Puffing converted insoluble dietary fiber from a compact structure to a porous architecture. • Treatment at 1.0 MPa achieved optimal balance between structural disruption and functionality. • Modified insoluble dietary fiber showed improved hydration and nitrite and cholesterol adsorption. • Electronic structure analysis revealed pressure-induced weakening of intermolecular interactions. This study investigated the modification of insoluble dietary fiber (IDF) from Dendrobium devonianum Paxt stem residues (DPSR) using differential pressure explosion puffing (DPEP). IDF samples were treated at different puffing pressures (0.6, 0.8, 1.0, 1.2, and 1.4 MPa), and their structural characteristics, physicochemical properties, and functional adsorption capacities were systematically evaluated. DPEP transformed the compact IDF matrix into a loose and porous structure, accompanied by reductions in particle size, molecular weight, and crystallinity, while preserving the basic polysaccharide backbone. These structural changes improved the water-holding and swelling capacities of IDF. Among the tested pressures, 1.0 MPa provided the best balance between structural disruption and functional enhancement, reducing the median particle size (D50) from 197.65 μm to 82.01 μm and increasing the water-holding capacity to 8.52 g/g. The functional adsorption properties were also enhanced. IDF-1.0 showed the highest nitrite ion adsorption capacity at pH 2.0 (6.49 μg/g), the strongest cholesterol adsorption capacity at pH 7.0 (0.11 mg/mL), and a glucose adsorption capacity of 22.77 mmol/g. Electronic structure analysis further showed that the degree of electron sharing and integrated crystal orbital Hamilton population of xylose reached their minimum values at 1.0 MPa, indicating that pressure-induced weakening of intermolecular interactions was associated with structural loosening. These findings indicate that DPEP is a promising physical strategy for improving the functionality of plant-derived IDF and provides a new route for the high-value utilization of medicinal-edible plant by-products in functional food applications. Download: Download high-res image (339KB) Download: Download full-size image
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Nanoscience and Nanotechnology Letters
·
2017
·Vol. 9
·期 1
·77-80
·
IF 1.889
Chen Cong,Tang Shijia,Hu Ke
Tumor stem cell (TSC) was one of the research hotspots in tumor diagnostics. However, cells with high expression of TSCs-related markers were rare when they were cultured in 2D models. It is important to build in vitro tumor models to enhance the proliferation of cells with TSCs
related markers. In this study, the magnetic hydrogel based on magnetic nanoparticle assemblies was applied as the substrate for glioma tumor cell (U251) culture. Tumor cells on the surface of this composite material preferred to form multicellular spheroids through adhesion, migration and
emergence. The enhanced expression of TSCs markers indicated the enrichment of TSCs and the stem cell characters of U251 cells cultured on magnetic hydrogel which were further confirmed by drug resistance assay. This composite might provide a valuable platform for TSCs-relative mechanism research
and anti-cancer treatment.
研究领域:
生物材料学
·
肿瘤学
·
细胞生物学
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Immunity Inflammation and Disease
·
2024
·Vol. 12
·期 2
·e1177
·
IF 3.1
Nannan Pang,Shabaaiti Tudahong,Yuejie Zhu,Jiang He,Chunxia Han,Gang Chen,Weiguo Wang,Jing Wang,Jianbing Ding
Background Acute graft-versus-host disease (aGVHD) arises from the imbalance of host T cells. Galectin-9 negatively regulates CD4 effector T cell (Th1 and Th17) function by binding to Tim-3. However, the relationship between Galectin-9/Tim-3 and CD4 + T subsets in patients with aGVHD after Haplo-HSCT (haploidentical peripheral blood hematopoietic stem cell transplantation) has not been fully elucidated. Here, we investigated the role of Galectin-9 and CD4 + T subsets in aGVHD after haplo-HSCT. Methods Forty-two patients underwent Haplo-HSCT (26 without aGVHD and 16 with aGVHD), and 20 healthy controls were included. The concentrations of Galectin-9, interferon-gamma (IFN-γ), interleukin (IL)-4, transforming growth factor (TGF)-β, and IL-17 in the serum and culture supernatant were measured using enzyme-linked immunosorbent assay or cytometric bead array. The expression levels of Galectin-9, PI3K, p-PI3K, and p-mTOR protein were detected by western blot analysis. Flow cytometry was used to analyze the proportions of CD4 + T cell subsets. Bioinformatics analysis was performed. Results In patients with aGVHD, regulatory T (Treg) cells and Galectin-9 decreased, and the Th1, Th17, and Treg cells were significantly imbalanced. Moreover, Treg and Galectin-9 were rapidly reconstituted in the early stage of patients without aGVHD after Haplo-HSCT, but Th17 cells were reconstituted slowly. Furthermore, Tim-3 upregulation on Th17 and Th1 cells was associated with excessive activation of the PI3K/AKT pathway in patients with aGVHD. Specifically, in vitro treatment with Galectin-9 reduced IFN-γ and IL-17 production while augmenting TGF-β secretion. Bioinformatics analysis suggested the potential involvement of the PI3K/AKT/mTOR pathway in aGVHD. Mechanistically, exogenous Galectin-9 was found to mitigate aGVHD by restoring the Treg/Teffs (effector T cells) balance and suppressing PI3K. Conclusion Galectin-9 may ameliorate aGVHD after haplo-HSCT by modulating Treg/Teffs balance and regulating the PI3K/AKT/mTOR pathway. Targeting Galectin-9 may hold potential value for the treatment of aGVHD.
研究领域:
免疫学
·
血液学
·
移植学
·
分子生物学
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高影响因子
JOURNAL OF PINEAL RESEARCH
·
2023
·
IF 10.3
Chao Gu,Quan Zhou,Xiayu Hu,Xiaoyang Ge,Mingzhuang Hou,Wenhao Wang,Hao Liu,Qin Shi,Yong Xu,Xuesong Zhu,Huilin Yang,Xi Chen,Tao Liu,Fan He
Osteoporotic bone defects, a severe complication of osteoporosis, are distinguished by a delayed bone healing process and poor repair quality. While bone marrow-derived mesenchymal stem cells (BMMSCs) are the primary origin of bone-forming osteoblasts, their mitochondrial function is impaired, leading to inadequate bone regeneration in osteoporotic patients. Melatonin is well-known for its antioxidant properties and regulation on bone metabolism. The present study postulated that melatonin has the potential to enhance the repair of osteoporotic bone defects by restoring the mitochondrial function of BMMSCs. In vitro administration of melatonin at varying concentrations (0.01, 1, and 100 μM) demonstrated a significant dose-dependent improvement in the mitochondrial function of BMMSCs obtained from ovariectomized rats (OVX-BMMSCs), as indicated by an elevation in mitochondrial membrane potential, adenosine triphosphate synthesis and expression of mitochondrial respiratory chain factors. Melatonin reduced the level of mitochondrial superoxide by activating the silent information regulator type 1 (SIRT1) and its downstream antioxidant enzymes, particularly superoxide dismutase 2 (SOD2). The protective effects of melatonin were found to be nullified upon silencing of Sirt1 or Sod2 , underscoring the crucial role of the SIRT1-SOD2 axis in the melatonin-induced enhancement of mitochondrial energy metabolism in OVX-BMMSCs. To achieve a sustained and localized release of melatonin, silk fibroin scaffolds loaded with melatonin (SF@MT) were fabricated. The study involved the surgical creation of bilateral femur defects in OVX rats, followed by the implantation of SF@MT scaffolds. The results indicated that the application of melatonin partially restored the mitochondrial energy metabolism and osteogenic differentiation of OVX-BMMSCs by reinstating mitochondrial redox homeostasis. These findings suggest that the localized administration of melatonin through bone implants holds potential as a therapeutic approach for addressing osteoporotic bone defects.
研究领域:
药理学
·
干细胞生物学
·
骨再生
·
组织工程
·
骨质疏松
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高影响因子
Science Signaling
·
2026
·Vol. 19
·期 948
·
IF 7
Qian Zhang,Yuedan Zhu,Yi Chen,Wenhao Hou,Aolong Sun,La Yan,Xingzhu Liu,Yu Yuan,Chaoxin Gao,Junfeng Xie,Rui Zhang,Haiyang Chen
Aging impairs intestinal stem cell (ISC) function, disrupting epithelial homeostasis and regenerative repair. Loss of ISC quiescence promotes intestinal dysfunction and contributes to organismal aging. Here, we report an epitranscriptomic mechanism through which a decrease in adenosine-to-inosine (A-to-I) RNA editing by the adenosine deaminase ADAR in ISCs during aging disrupts a conserved signaling axis that maintains ISC quiescence. In Drosophila melanogaster , ISC-specific loss of dADAR triggered hyperproliferation and tissue aging, whereas dADAR overexpression reduced age-related gut dysfunction and extended life span. Intestinal injury induced a decrease in dADAR, which was necessary for tissue regeneration, and in the zinc finger protein dZn72D, which stabilized dADAR to support intestinal homeostasis during aging. dADAR edited transcripts encoding the RNA binding protein Pumilio (dPUM) to generate an isoform that inhibited translation of two components of the mitogen-activated protein kinase (MAPK), dEGFR and dERK, thereby maintaining ISC quiescence. The abundance of ADAR2 and of the dZn72D ortholog ZFR decreased in human colonic crypts with aging and in mouse colon after injury, suggesting that attenuation of ADAR activity may play a conserved role in ISC aging and in facilitating colonic regeneration. Our work identifies a conserved mechanism of epitranscriptomic regulation that safeguards tissues and the decay of ADAR-mediated RNA editing as a form of age-related epigenetic information loss that disrupts ISC homeostasis.
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高影响因子
INTERNATIONAL ENDODONTIC JOURNAL
·
2026
·
IF 6.4
Yongjie Cai,Xiaoting Peng,Beichen Chen,Yiqing Zhao,Waruna Lakmal Dissanayaka,Yiwen Zhang,Shengyan Yang,Qiong Xu
Aim To delineate the mechanisms underlying the role of lactate-related lactylation, a novel post-translational modification, in the odontogenic differentiation of human dental pulp stem cells (hDPSCs). Methodology Dynamic levels of key glycolytic enzymes and histone lactylation along odontogenic differentiation in hDPSCs were evaluated by Western Blot and quantitative PCR (qPCR). Odontogenic differentiation was assessed via Alkaline Phosphatase and Alizarin Red S staining after treatment with sodium lactate, both with and without p300 knockdown. CUT&Tag sequencing of histone H3K18 lactylation (H3K18la) was performed, and genes identified through this analysis were subjected to pathway enrichment. WNT5A-knockdown hDPSCs were generated to elucidate the impact of both WNT5A and WNT5A/Ca 2+ signalling axis in odontogenesis. Finally, we validated the critical function of lactylation in dentine regeneration using a subcutaneous ectopic transplantation model in nude mice with and without sodium lactate via intraperitoneal injection. Results The similar dynamic trends were observed in glycolytic enzyme expression, intracellular lactate and lactylation levels in hDPSCs. Exogenous lactate dose-dependently increased H3K18 lactylation and significantly promoted hDPSC odontogenic differentiation. Mechanistically, the key lactyltransferase p300 was demonstrated to be a regulator that enhanced lactate-induced H3K18la modification and odontogenic differentiation in hDPSCs. CUT&Tag sequencing identified WNT5A as a target gene whose promoter exhibited increased H3K18la enrichment upon lactate treatment. Lactate upregulated WNT5A expression and activated the WNT5A/Ca 2+ signalling pathway via p300-mediated H3K18la, consequently accelerating the odontogenic differentiation. Further in vivo evidence revealed that lactate administration promoted pulp-like tissue regeneration, accompanied by increased hDPSC odontogenic marker expression and H3K18la levels in nude mice with subcutaneously transplanted dentine slices. Conclusions The lactate-driven mechanism acts through the p300-mediated H3K18la-WNT5A/Ca 2+ signalling axis to promote the odontogenic differentiation of hDPSCs. The crosstalk between metabolism, epigenetic modifications and signalling pathways of hDPSCs might offer novel strategies for dental pulp regeneration.
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高影响因子
Journal of Materials Chemistry B
·
2026
·
IF 5.7
Yunhui Fu,Yuxi Li,Chenlu Wu,Yiying Chen,Xikui Tong,Chen Zhang,Meiyan Wang,yue Shen,Wenyun Zheng,Xingyuan Ma
Mesenchymal stem cell (MSC) transplantation has emerged as an effective approach for treating articular cartilage damage. However, unintended hypertrophy and fibrosis of the regenerated cartilage tissue markedly undermine the therapeutic effect. Herein, a two-factor delivery system, E60TK, based on the elastin-like protein ELP (VPGIG60, E60), co-delivering transforming growth factor β1 (TGF-β1) and kartogenin (KGN), was established to regulate stem cells from human exfoliated deciduous teeth (SHED)-directed cartilage differentiation and prevent cartilage hypertrophy and fibrosis. MTT and Alcian blue staining outcomes demonstrated that the fusion protein E60T composed of E60 and TGF-β1 was capable of effectively facilitating the proliferation and chondrogenic differentiation of SHED cells. Transmission electron microscope (TEM) and DLS findings revealed that the recombinant protein E60T could load KGN at physiological temperature to form nanoparticles E60TK, with particle sizes 241.2 ± 46.1 nm. The results of immunofluorescence and immunohistochemistry following chondrogenic differentiation suggested that E60TK could efficiently induce the chondrogenic differentiation of SHED and significantly suppress the expression of type X collagen. The hyaluronic acid methacrylamide (HAMA) hydrogel loading E60TK, E60TK-HAMA, exhibited excellent biocompatibility, presented an interconnected porous architecture, and was completely degraded within 2 weeks in vitro. In vivo experiments indicated that the E60TK-HAMA hydrogel with SHED encapsulated could effectively promote the formation of new cartilage and inhibit hypertrophy. All these results signified that E60TK was an effective system for regulating the directed chondrogenic differentiation of SHED.
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Stem Cells International
·
2026
·Vol. 2026
·期 1
·6997518
·
IF 3.6
Fengshan Gan,Fan Zheng,Qingzhu Zhou,Boyan Liu,Bin Yang,Lianzhu Ou,Wenli Huang,Xinxin Yang,Zhuo Gong,Yunyu Xiong,Xian Zhao,Jia He
Background Soft tissue defects refer to defects in or damage to human soft tissue, which may affect the appearance, function, and health of the human body and cause physical and psychological distress to the patient. Hyaluronic acid (HA), a fillable material in the field of plastic medicine, could play a crucial role in reconstructing soft tissues and enhancing the adipogenic differentiation of adipose-derived stem cells (ADSCs). Methods We isolated ADSCs from human subcutaneous adipose tissue and cultured them in HA hydrogel at a density of 2.1 × 10 6 /mL, followed by subcutaneous injections of ADSCs (0.2 mL, 1 × 10 7 cells/mL with 0.2 mL of DMEM) and HA hydrogel (0.2 mL) into the dorsal side of nude mice. The expression of related genes and proteins was detected using RT‒qPCR and western blotting. The adipogenic differentiation of ADSCs and adipogenesis in nude mice were assessed using CCK-8, Oil Red O, and HE staining. Results The results revealed an increase in the levels of miR-181a-5p and adipocyte differentiation-related proteins (PPARγ, C/EBPα, FABP4, and adiponectin) and a decrease in the levels of autophagy-related proteins (LC3II/I, Beclin-1, and ATG5) in ADSCs cocultured with HA hydrogel. The adipogenic differentiation ability of ADSCs was enhanced. From a mechanistic standpoint, HA hydrogel inhibited the expression of ATG5 by promoting the expression of miR-181a-5p, thus inhibiting autophagy, promoting the adipogenic differentiation of ADSCs, and promoting the formation of adipose tissue in vivo. Conclusions Our findings suggest that a combined culture of ADSCs and HA hydrogel may be a new method to enhance the adipogenic differentiation of ADSCs.
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Research
·
2023
·
IF 11
Qiang Wang,Tian Yang,Shiyou Li,Chen Xu,Chong Wang,Yuxuan Xiong,Xing Wang,Jiangling Wan,Xiangliang Yang,Zifu Li
Photodynamic therapy with reactive oxygen species production is a prospective treatment to combat cancer stem cells (CSCs). However, the innate drawbacks, including short lifetime and diffusion distance of reactive oxygen species and hypoxia within solid tumors, have become bottlenecks for clinical applications of photodynamic therapy. Here, we develop a mitochondria-targeting hemicyanine–oleic acid conjugate (CyOA), which can self-assemble into supramolecular nanoparticles (NPs) without any exogenous excipients. CyOA is also shown for targeting the mitochondrial complex II protein succinate dehydrogenase to inhibit oxidative phosphorylation and reverse tumor hypoxia, resulting in 50.4-fold higher phototoxicity against breast cancer stem cells (BCSCs) compared to SO3-CyOA NPs that cannot target to mitochondria. In 4T1 and BCSC tumor models, CyOA NPs achieve higher tumor inhibition and less lung metastasis nodules compared to the clinically used photosensitizer Hiporfin. This study develops a self-assembled small molecule that can serve as both oxidative phosphorylation inhibitor and photosensitizer for eradication of CSCs and treatment of solid tumors.
研究领域:
肿瘤学
·
药理学
·
纳米技术
·
生物医学工程
·
化学
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高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Zhiyuan Wang,Renfeng Liu,Youjun Liu,Yuqi Zhao,Yuhao Wang,Botao Lu,Hui Li,Cheng Ju,Weidong Wu,Xinlin Gao,Hailiang Xu,Shixiang Cheng,Yulin Cao,Shuaijun Jia,Chunping Hu,Lei Zhu,Dingjun Hao
Spinal cord organoids are of significant value in the research of spinal cord-related diseases by simulating disease states, thereby facilitating the development of novel therapies. However, the complexity of spinal cord structure and physiological functions, along with the lack of human-derived inducing components, presents challenges in the in vitro construction of human spinal cord organoids. Here, we introduce a novel human decellularized placenta-derived extracellular matrix hydrogel (DPECMH) and, combined with a new induction protocol, successfully construct human spinal cord organoids. The human placenta-sourced decellularized extracellular matrix (dECM), verified through hematoxylin and eosin staining, DNA quantification, and immunofluorescence staining, retained essential ECM components such as elastin, fibronectin, type I collagen, laminin, and so forth. The temperature-sensitive hydrogel made from human placenta dECM demonstrated good biocompatibility and promoted the differentiation of human induced pluripotent stem cell (hiPSCs)-derived spinal cord organoids into neurons. It displayed enhanced expression of laminar markers in comparison to Matrigel and showed higher expression of laminar markers compared to Matrigel, accelerating the maturation process of spinal cord organoids and demonstrating its potential as an organoid culture substrate. DPECMH has the potential to replace Matrigel as the standard additive for human spinal cord organoids, thus advancing the development of spinal cord organoid culture protocols and their application in the in vitro modeling of spinal cord-related diseases.
研究领域:
干细胞生物学
·
神经科学
·
组织工程
·
再生医学
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高影响因子
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