Experimental and Therapeutic Medicine
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2015
·Vol. 9
·期 6
·2072-2080
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IF 1.269
Yang Li,Jiefang Wang,Guangming Chen,Shuiwang Feng,Panpan Wang,Xiaofeng Zhu,Ronghua Zhang
The aim of the present study was to investigate the effects of quercetin on the mitogen-activated protein kinase (MAPK) signaling pathway in the osteogenic differentiation of rat mesenchymal stem cells (MSCs). A 3-(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay and an alkaline phosphatase (ALP) assay were used to determine the effects of quercetin (concentrations of 0.1, 1 and 10 µmol/l) on the proliferation and differentiation of MSCs and the expression of ALP, respectively. In addition, through the introduction of inhibitors of p38 MAPK, extracellular signal‑regulated kinase (ERK)1/2 and c‑Jun NH2‑terminal kinase (JNK), the effects of quercetin on the proteins, ALP, collagen type I (COL I) and bone γ‑carboxyglutamate protein (BGP), which are indicators of osteogenic differentiation, were investigated. Immunoblotting was performed to determine the phosphorylation levels of p38 MAPK, ERK1/2 and JNK, while fluorescent quantitative polymerase chain reaction was used to determine the mRNA expression levels of transforming growth factor (TGF)‑β1, bone morphogenetic protein (BMP)‑2 and core binding factor (CBF)α1. At all the concentrations tested, the concentrations of 10, 1 and 0.1 µmol/l quercetin were shown to promote the differentiation of MSCs and the expression of ALP, in which the concentration of 10 µmol/l was optimal. When compared with the control group, the phosphorylation levels of p38 MAPK, ERK1/2 and JNK, the protein expression levels of ALP, COL I and BGP, and the mNRA expression levels of TGF‑β1, BMP‑2 and Cbfα1 were increased in the quercetin‑treated group. However, with the introduction of inhibitors, the levels of phosphorylated p38 MAPK, ERK1/2 and JNK, and the protein expression levels of ALP, COL I and BGP decreased. Furthermore, the mRNA expression levels of TGF‑β1, BMP‑2 and CBFα1 decreased in the quercetin + SP600125 (inhibitor of JNK) and quercetin + PD98059 (inhibitor of ERK1/2) groups. Therefore, quercetin was demonstrated to promote the osteogenic differentiation of MSCs by activating the MAPK signaling pathway. The ERK1/2 and JNK signaling pathways regulate the expression of TGF‑β1, BMP‑2 and CBFα1. Thus, activation of the ERK1/2 and JNK signaling pathways may play a leading role in the quercetin‑promoted osteogenic proliferation and differentiation of MSCs.
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ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Kexin Zhang,Chenyu Zhang,Huanxin Zhou,Yan Yang,Yanzhen Wen,Xiangyu Jiao,Mingze Yao,Yongqiang Wen
Diabetic wounds that do not heal for a long time challenge global healthcare. Mesenchymal stem cell (MSC) therapy has positive significance in promoting diabetic wound healing. However, traditional MSC therapy involves exogenous MSCs, which brings many limitations and unsatisfactory treatment. Moreover, the maintenance of MSC viability and function is difficult because of the high level of reactive oxygen species (ROS) in diabetic wounds. Therefore, we developed a nanofibrous dressing to recruit and protect endogenous MSCs while avoiding the inherent disadvantages of exogenous MSCs. Ceria nanoparticles capable of ROS scavenging are integrated into the nanofibrous dressings, together with Apt19S, a DNA aptamer with affinity and selectivity for MSCs. In addition, the homogenization and freeze-drying technology give the nanofibrous dressings good elasticity, which protects the wound from external pressure. Further experiments in diabetic mice show that the dressing has excellent endogenous MSC recruitment and anti-inflammatory properties, thereby synergistically promoting diabetic wound healing. This study is expected to explore an efficient method of stem cell therapy, providing a new way to construct high-performance wound dressings.
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FOOD AND CHEMICAL TOXICOLOGY
·
2024
·
IF 3.9
Xiu Wang,Kai Zou,Yu Xiong,Yongwang Zheng,Jiale Zheng,Yong Liu,Ting Zhong,Xincheng Zhao
Intestinal health is closely linked to intestinal stem cells (ISCs), which are highly sensitive to the harmful substances in the lumen. However, there is limited knowledge regarding the effects of food additives on ISCs. This study aims to investigate the impact of dietary titanium dioxide nanoparticles (TiO 2 NPs) compared with titanium dioxide microparticles (TiO 2 MPs) on intestinal health associated with ISCs in response to dextran sodium sulfate (DSS)-induced enteritis in mice, as well as the related mechanism. We found that exposure to 1% (w/w) TiO 2 NPs aggravated DSS-induced enteritis in mice, while this effect could not be observed under exposure to TiO 2 MPs. Additionally, 1% (w/w) TiO 2 NPs exposure under DSS-induced enteritis worsened the ISC-mediated regeneration of intestinal epithelium by decreasing the epithelial cell proliferation and epithelial turnover rate while increasing epithelial cell death. Meanwhile, using a 3D intestinal organoid model, we discovered that 20 μg/mL TiO 2 NPs impaired ISC function and disrupted ISC fate specification both ex vivo and in vitro . Furthermore, TiO 2 NPs hindered the nuclear translocation of β-catenin, reducing the overall output of Wnt signaling. Together, TiO 2 NPs deteriorated the intestinal epithelial regeneration of mice with DSS-induced enteritis by perturbating ISC function and fate specification through a mechanism involving Wnt signaling. These findings highlight the adverse effect of dietary TiO 2 NPs on ISCs and shed light on the particle size optimization of TiO 2 food additive.
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ECOTOXICOLOGY
·
2024
·
IF 2.4
Wang Jie,Huang Hexi,Yang Hailin,Wang Su,Li Mengnan,Zhu Zhengyang,Trumble John T.,Di Ning,Zang Liansheng
Cadmium (Cd), a widely distributed environmental pollutant in agroecosystems, causes negative effects on crops and herbivores through bottom-up processes. The gut microbial community of an insect can play a critical role in response to metal stress. To understand how microbiota affect the stress responses of organisms to heavy metals in agroecosystems, we initially used 16S rRNA sequencing to characterize the larval gut microbiota of Chilo suppressalis , an important agricultural pest, exposed to a diet containing Cd. The species richness, diversity, and composition of the gut microbial community was then analyzed. Results revealed that while the richness (Chao1 and ACE) of gut microbiota in larvae exposed to Cd was not significantly affected, diversity (Shannon and Simpson) was reduced due to changes in species distribution and relative abundance. Overall, the most abundant genus was Enterococcus , while the abundance of the genera Micrococcaceae and Faecalibaculum in the control significantly superior to that in Cd-exposed pests. Phylogenetic investigation of microbial communities by the reconstruction of unobserved states (PICRUSt) showed that the intestinal microorganisms appear to participate in 34 pathways, especially those used in environmental information processing and the metabolism of the organism. This study suggests that the gut microbiota of C. suppressalis are significantly impacted by Cd exposure and highlights the importance of the gut microbiome in host stress responses and negative effects of Cd pollution in agroecosystems.
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JOURNAL OF MOLECULAR NEUROSCIENCE
·
2024
·Vol. 74
·期 1
·1-20
·
IF 2.8
Fan Yubao,Huang Shanshan,Li Fugui,Zhang Xiyu,Huang Xueying,Li Weiqiang,Zeng Jixiao,Wang Weijia,Liu Jia
The sympathetic nervous system (SNS) is a crucial branch of the autonomic nervous system (ANS) that is responsible for regulating visceral function and various physiological processes. Dysfunction of the SNS can lead to various diseases, such as hypertension and metabolic disorders. However, obtaining sympathetic neurons from human tissues for research is challenging. The current research aimed at recapitulating the process of human sympathetic neuron development and achieved the successful establishment of a stepwise, highly efficient in vitro differentiation protocol. This protocol facilitated the generation of functional and mature sympathetic neurons from human pluripotent stem cells (hPSCs) using a chemical-defined induction medium. Initially, each differentiation stage was refined to derive sympathoadrenal progenitors (SAPs) from hPSCs through neural epithelial cells (NECs) and trunk neural crest stem cells (NCSCs). hPSC-derived SAPs could be expanded in vitro for at least 12 passages while maintaining the expression of SAP-specific transcription factors and neuronal differentiation potency. SAPs readily generated functional sympathetic neurons (SymNs) when cultured in the neuronal maturation medium for 3–4 weeks. These SymNs expressed sympathetic markers, exhibited electrophysiological properties, and secreted sympathetic neurotransmitters. More importantly, we further demonstrated that hPSC-derived SymNs can efficiently regulate the adipogenesis of human adipose–derived stem cells (ADSCs) and lipid metabolism in vitro. In conclusion, our study provided a simple and robust protocol for generating functional sympathetic neurons from hPSCs, which may be an invaluable tool in unraveling the mechanisms of SNS-related diseases.
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ACS Omega
·
2025
·
IF 4.3
Jie Wang,Fan Yang,Ruting Chen,Xinyue Yang,Jingjing Wang,Hongyan Zhang
Fast reconstruction of the pulpal vasculature is crucial for effective pulp regeneration. Dental pulp stem cells (DPSCs) are promising candidates for pulp regeneration because of their potential for multilineage differentiation and vasculogenic properties. Deferoxamine (DFO) has been shown to stimulate angiogenesis during wound healing and bone regeneration; however, the effects of DFO on the angiogenic potential of DPSCs remain unknown. Moreover, its usefulness is restricted by a limited half-life and challenges in achieving localized tissue enrichment. This study aimed to develop a sustained-release injectable hydrogel composite as a drug delivery system and to investigate its influence on DPSCs. Herein, gelatin-based microspheres (GMSs) were loaded with DFO, and temperature-sensitive injectable hydrogels incorporating collagen and chitosan were synthesized to enable controlled DFO release. The experimental findings demonstrated that the DFO-loaded GMSs (DFO-GMSs) hydrogel composite possessed favorable physical properties and biocompatibility, enabling sustained DFO delivery for up to 15 days. DFO effectively stimulated DPSC migration, promoted the secretion of angiogenesis-related factors, and induced tube formation in vitro. These results suggest that the DFO-GMSs hydrogel composite significantly increased the migration and angiogenic potential of DPSCs, highlighting its promise for tissue regeneration applications.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Boqi Li,Yufeng Gao,Xiaohu Luo,Chuanzhi Hu,Mingyu Deng,Jinghua Chen,Gao Min
Natural extracellular matrices (ECM) provide a more accurate simulation of the cellular growth environment, making them excellent substrate materials for in vitro cell culture. The porcine small intestinal submucosa (SIS) is one of the most widely used natural ECM that display superior bioactivity. However, decellularization operations often result in fiber breakage and failure to recover mechanical strength in the SIS. In the current study, 2,3-dialdehyde cellulose (DAC) was synthesized and cross-linked with SIS gel to form hydrogels. The introduction of DAC into the SIS matrix resulted in a tunable increase in stiffness, which was instrumental in promoting stem cell adhesion and spreading, crucial factors for osteogenic differentiation. The cytotoxicity assessment confirmed the biocompatibility of the SIS-DAC hydrogels indicating their suitability for prolonged cell culture. Moreover, the degradation rate of the hydrogel could be effectively controlled by adjusting the DAC content, addressing the rapid degradation issue associated with SIS gels. This work confirmed the feasibility of using cellulose derivatives to modulate the mechanical properties of matrix gels and influence cell differentiation which offers a valuable experimental foundation for the development of advanced matrix gels tailored for cell culture and regenerative medicine applications.
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Advanced Healthcare Materials
·
2025
·
IF 9.6
Rui Chang,Pei Wang,Hongrui Chen,Shih-Jen Chang,Qianyi Chen,Lei Chang,Yajing Qiu,Xiansong Wang,Xiaoxi Lin
Diabetes-associated skin defects represent a significant global health challenge. While flap grafts have been a preferred treatment for soft-tissue injuries in diabetic patients, their survival is often compromised by impaired vascularization, infection, and the adverse diabetic pathological microenvironment. To address these limitations, a hybrid photo-crosslinkable hydrogel (HPC) integrated hemangioma stem cell-derived nanovesicle (HemV)-loaded dual-metal-polyphenol network (dMPN) (HemV@dMPN/HPC) is developed. HemVs, derived from highly vascularized infantile hemangioma tissues, play a key role in promoting cell proliferation and angiogenesis. The dMPN facilitates the gradual release of copper (Cu 2+ ) and magnesium ions (Mg 2+ ), stimulating angiogenesis and mitigating inflammation. The HPC further sustains ion release while preserving the therapeutic efficacy of HemVs. Moreover, both HPC and Cu 2+ act to confer antibacterial properties, further accelerating wound healing. This multifunctional HemV@dMPN/HPC platform offers a promising therapeutic strategy for treating large diabetic skin defects and can potentially improve flap graft survival.
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FOOD CHEMISTRY
·
2024
·
IF 8.5
Lihui Xiang,Chen Zhu,Jiajia Qian,Xiaochen Zhou,Miao Wang,Zhenshuo Song,Changsong Chen,Wenquan Yu,Lin Chen,Lanting Zeng
Most teas, including white tea, are produced from tender shoots containing both leaf and stem. However, the effect of the stem on white tea quality remains unclear, especially during withering, an essential process. Therefore, this study investigated the withering-induced changes in the leaves and stems of Camellia sinensis cv. ‘Fudingdabai’ by multi-group analysis. During withering, the levels of catechin and theobromine (i.e., major flavor-related compounds) decreased slightly, mainly in the leaves. The abundance of some proteinaceous amino acids related to fresh taste increased in stems due to increased protein hydrolysis. In addition, changes in biosynthetic pathways caused a decrease in theanine (a major non-proteinaceous amino acid) and an increase in gamma-aminobutyric acid in stems. Terpenes, mainly in the stems, were partially affected by withering. Phenylacetaldehyde, a major contributor to white tea aroma, increased mainly in the stems. These findings reflect the positive contribution of the stem to white tea quality.
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KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
·
2025
·
IF 3.1
Jian Wang,Jun Peng,Ling Gao,Jun He,Long Lin,Jia-Meng Li,Ying Xia
Subarachnoid hemorrhage (SAH) can lead to significant acute neuroinflammation, with treatment outcomes often being inadequate. Olfactory mucosa mesenchymal stem cells (OM-MSCs) have promising therapeutic potential in nerve regeneration and functional recovery. This investigation sought to elucidate the functional mechanisms through which exosomes derived from OM-MSCs provide protection against neuroinflammation following SAH. Mouse OM-MSCs and their exosomes were isolated and characterized using various techniques, including transmission electron microscopy, immunofluorescence staining, Western blotting, flow cytometry, and nanoparticle tracking analysis. Hemin-induced HT22 cells were subsequently utilized to assess the impact of OM-MSC-derived exosomes on the inflammatory response, apoptosis, and mitophagy through ELISAs, Western blotting, qPCR, flow cytometry, and immunofluorescence staining. The impacts of exosomes on neuroinflammation and neuronal damage in SAH model mice were assessed using qPCR, ELISAs, Western blotting, immunofluorescence staining, and TUNEL staining. Exosomes derived from OM-MSCs had the capacity to reduce the levels of proinflammatory factors (IL-6, IL-1 β , and TNF- α ) and promote apoptosis in hemin-induced HT22 cells. Exosomes alleviated neuroinflammation and neuronal injury post-SAH, as evidenced by the increase in modified Garcia scores, reduction in the brain water content, decrease in blood–brain barrier permeability, decreases in inflammatory marker levels, and reduction in apoptosis rates. Notably, the protective effects of exosomes derived from OM-MSCs on neuroinflammation and apoptosis, both in vitro and in vivo, were mediated via the activation of mitophagy. These findings provide a fresh perspective for subsequent clinical research in the domain of prevention and treatment strategies.
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PHYTOMEDICINE
·
2024
·
IF 6.7
Ying Liu,Xinran Wang,Chenrong Jin,Juhui Qiao,Chenxi Wang,Leilei Jiang,Shiting Yu,Daian Pan,Daqing Zhao,Siming Wang,Meichen Liu
Background Disruption of stem cell and microbial homeostasis accelerates the aging process. Hence, maintaining these balances effectively delays aging and alleviates the symptoms of age-related diseases. Recent research indicates that targeting endoplasmic reticulum (ER) stress and immune deficiency (IMD) signalling may play a positive role in maintaining homeostasis in aging intestinal stem cells (ISC) and microbial equilibrium. Previous research has suggested that total ginsenosides (TG) derived from Panax ginseng C. A. Meyer may exhibit potential anti-aging properties by mitigating ER stress and mediating the IMD pathway. Nevertheless, it remains unclear whether TG improve ISC and microbial homeostasis by modulating ER stress and the IMD pathway to promote healthy aging. Purpose To elucidate whether TG promotes healthspan in Drosophila and its underlying molecular mechanisms, focusing on its role in regulating ER stress and the IMD pathway to maintain ISC and intestinal microbiota homeostasis. Methods High performance liquid chromatography was performed to detect the main saponin monomer in TG. Survival rate, gut length, barrier function, and feeding/excretion behaviour assays were used to evaluate the effects of TG on the lifespan and gut health of Drosophila . At the stem cell level, “esg-luciferase” reporter system, esg-GFP/delta stem cell fluorescent labelling, and phospho-histone H3+ mitotic activity assays were employed to determine whether TG prevented natural aging or oxidative stress-associated ISC over-proliferation in Drosophila . Immunofluorescence staining was used to detect the effects of TG on ER stress during aging. Overexpression or interference of ER stress target genes and their related c-Jun N-terminal kinase (JNK) gene was manipulated using gene editing technology to verify the molecular mechanism by which TG maintains age-related ISC proliferation homeostasis. Molecular docking and isothermal titration calorimetry were used to verify the direct interactions between TG and ER stress target genes. In addition, at the intestinal flora level, 16S rDNA sequencing was used to analyse the effect of TG on the diversity and abundance of Drosophila intestinal flora and the possible functional pathways involved. RT-qPCR was performed to determine whether TG mediated the expression of target genes in the IMD pathway. A dominant bacterial species-specific mono-association analysis were performed to verify whether the effects of TG on IMD target genes and ISC proliferation depended on the direct control of the dominant bacterial species. Results Our results suggest that administration of TG delays the decline in gut morphology and function in aging Drosophila . TG prevents age-associated ISC hyperproliferation by inhibiting ER stress IRE1-mediated JNK signaling. Furthermore, oral TG prevented aging-associated ISC and gut microbiota dysbiosis by remodelling the gut microbiota and inhibiting Acetobacter -mediated activation of IMD target genes. Conclusion TG promotes healthy aging by inhibiting the excessive proliferation of ISC and alleviating intestinal microbial imbalance, thereby providing new insights for the research and development of anti-aging TG products.
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Stem Cell Research & Therapy
·
2025
·Vol. 16
·期 1
·1-20
·
IF 7.3
Liu Yonghao,Zhou Heng,Pang Pengcheng,Liu Ye,Situ Jieying,Wang Junnan,He Yan,Ye Qingsong
Background Mesenchymal stem cell exosomes are the most extensively researched type of Extracellular vesicles (EVs) that offer novel avenues for hair regeneration. However, their use in the field of hair regeneration was limited by their poor production of exosomes. It has been discovered that intracellular vesicles (IVs), which are produced at a higher rate than exosomes, play a comparable biological purpose. As a result, we developed HTMI-MN, a microneedle that uses tremella, a type of Tremella polysaccharide (TPS), and hyaluronic acid (HA) as matrix materials. It has magnetic intracellular vesicles (Mag-IVs), which work in concert to treat androgenic alopecia (AGA) and encourage hair growth.Methods After characterization of the Mag-IVs, we evaluated the effect on angiogenesis by scratch assay, angiogenesis assay, Western Blot and ELISA assay. In addition, we tested the protective effect of Human hair papillary cells (HHDPCs) by CCK-8 method, Western Blot and flow cytometry. Finally, the effects of tremella polysaccharide on M1/M2 polarization of macrophages were detected by fluorescence staining, Western Blot and flow cytometry. AGA model was established in vivo by DHT, and treatment was given by microneedle injection.Results Our study found that Mag-IVs have greater power to promote angiogenesis and protect HHDPCs from apoptosis compared to other vesicles. Besides, tremella polysaccharide can make the transformation of macrophages to anti-inflammatory phenotype. Taken together, in vivo experiments showed that hair regeneration was faster in HTMI-MN-treated mice.Conclusion These results indicate that Mag-IVs and tremella polysaccharide can synergistically improve the hair microenvironment, which has a promising future for AGA treatment.
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