ACS Chemical Biology
·
2017
·
IF 4.995
Jun Xiong,Xiaona Liu,Qing-Yun Cheng,Shan Xiao,Lai-Xin Xia,Bi-Feng Yuan,Yu-Qi Feng
Toxic heavy metals have been considered to be harmful environmental contaminations. The molecular mechanisms of heavy-metals-induced cytotoxicity and carcinogenicity are still not well elucidated. Previous reports showed exposures to toxic heavy metals can cause a change of DNA cytosine methylation (5-methylcytosine, 5-mC). However, it is still not clear whether heavy metals have effects on the recently identified new epigenetic marks in both DNA and RNA, i.e., 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and 5-carboxylcytosine (5-caC). Here, we established a chemical labeling strategy in combination with liquid chromatography–electrospray ionization–mass spectrometry (LC-ESI-MS/MS) analysis for highly sensitive detection of eight modified cytidines in DNA and RNA. The developed method allowed simultaneous detection of all eight modified cytidines with improved detection sensitivities of 128–443-fold. Using this method, we demonstrated that the levels of 5-hmC, 5-foC, and 5-caC significantly decreased in both the DNA and RNA of mouse embryonic stem (ES) cells while exposed to arsenic (As), cadmium (Cd), chromium (Cr), and antimony (Sb). In addition, we found that treatments by heavy metals induced a decrease of the activities of 10–11 translocation (Tet) proteins. Furthermore, we revealed that a content change of metabolites occurring in the tricarboxylic acid cycle may be responsible for the decline of the derivatives of 5-mC. Our study shed light on the epigenetic effects of heavy metals, especially for the induced decline of the derivatives of 5-mC in both DNA and RNA.
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International Journal of Hepatology
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2016
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IF 0
Yunxia Tang,Qiongshu Li,Fanwei Meng,Xingyu Huang,Chan Li,Xin Zhou,Xiaoping Zeng,Yixin He,Jia Liu,Xiang Hu,Ji-Fan Hu,Tao Li
Human umbilical cord-derived mesenchymal stem cells (UCMSCs) are particularly attractive cells for cellular and gene therapy in acute liver failure (ALF). However, the efficacy of this cell therapy in animal studies needs to be significantly improved before it can be translated into clinics. In this study, we investigated the therapeutic potential of UCMSCs that overexpress hepatocyte growth factor (HGF) in an acetaminophen-induced acute liver failure mouse model. We found that the HGF-UCMSC cell therapy protected animals from acute liver failure by reducing liver damage and prolonging animal survival. The therapeutic effect of HGF-UCMSCs was associated with the increment in serum glutathione (GSH) and hepatic enzymes that maintain redox homeostasis, including γ-glutamylcysteine synthetase (γ-GCS), superoxide dismutase (SOD), and catalase (CAT). Immunohistochemical staining confirmed that HGF-UCMSCs were mobilized to the injured areas of the liver. Additionally, HGF-UCMSCs modulated apoptosis by upregulating the antiapoptotic Bcl2 and downregulating proapoptotic genes, including Bax and TNFα. Taken together, these data suggest that ectopic expression of HGF in UCMSCs protects animals from acetaminophen-induced acute liver failure through antiapoptosis and antioxidation mechanisms.
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eLife
·
2024
·
IF 6.4
Junjun Yao,Shaoxing Dai,Ran Zhu,Ju Tan,Qiancheng Zhao,Yu Yin,Jiansen Sun,Xuewei Du,Longjiao Ge,Jianhua Xu,Chunli Hou,Nan Li,Jun Li,Weizhi Ji,Chuhong Zhu,Runrui Zhang,Tianqing Li
While accumulated publications support the existence of neurogenesis in the adult human hippocampus, the homeostasis and developmental potentials of neural stem cells (NSCs) under different contexts remain unclear. Based on our generated single-nucleus atlas of the human hippocampus across neonatal, adult, aging, and injury, we dissected the molecular heterogeneity and transcriptional dynamics of human hippocampal NSCs under different contexts. We further identified new specific neurogenic lineage markers that overcome the lack of specificity found in some well-known markers. Based on developmental trajectory and molecular signatures, we found that a subset of NSCs exhibit quiescent properties after birth, and most NSCs become deep quiescence during aging. Furthermore, certain deep quiescent NSCs are reactivated following stroke injury. Together, our findings provide valuable insights into the development, aging, and reactivation of the human hippocampal NSCs, and help to explain why adult hippocampal neurogenesis is infrequently observed in humans.
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2024
·Vol. 28
·期 20
·e70127
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IF 4.3
Ming Zhang,Guan-Chun Dai,Yuan-Wei Zhang,Pan-Pan Lu,Hao Wang,Ying-Juan Li,Yun-Feng Rui
Diabetic calcific tendinopathy is the leading cause of chronic pain, mobility restriction, and tendon rupture in patients with diabetes. Tendon stem/progenitor cells (TSPCs) have been implicated in the development of diabetic calcified tendinopathy, but the molecular mechanisms remain unclear. This study found that diabetic tendons have a hyperoxic environment, characterized by increased oxygen delivery channels and carriers. In hyperoxic environment, TSPCs showed enhanced osteogenic differentiation and increased levels of reactive oxygen species (ROS). Additionally, hypoxia-inducible factor-1a (HIF-1a), a protein involved in regulating cellular responses to hyperoxia, was decreased in TSPCs by the ubiquitin-proteasome system. By intervening with antioxidant N-acetyl-L-cysteine (NAC) and overexpressing HIF-1a, we discovered that blocking the ROS/HIF-1a signalling axis significantly inhibited the osteogenic differentiation ability of TSPCs. Animal experiments further confirmed that hyperoxic environment could cause calcification in the Achilles tendon tissue of rats, while NAC intervention prevented calcification. These findings demonstrate that hyperoxia in diabetic tendons promotes osteogenic differentiation of TSPCs through the ROS/HIF-1a signalling axis. This study provides a new theoretical basis and research target for preventing and treating diabetic calcified tendinopathy.
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JOURNAL OF CONTROLLED RELEASE
·
2024
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IF 10.5
Xiaochuan Wu,Xiajie Huang,Qi Zhu,Jucong Zhang,Jiahao Hu,Yanling Song,Yuchan You,Luwen Zhu,Jingyi Lu,Xinyi Xu,Minjiang Chen,Wei Wang,Xiuzu Song,Jiansong Ji,Yongzhong Du
Androgenetic alopecia (AGA) is a non-fatal disease prevalent worldwide. However, mixed efficacy has been observed among different therapies for hair regrowth in AGA patients. Thus, a nano-platform with synergistic treatments based on a hybrid extracellular vesicle encapsulating gold nanoparticles (AuNPs) and finasteride (Hybrid/Au@Fi) was constructed through membrane fusion between hair follicle stem cell (HFSC)-derived extracellular vesicles and liposomes. These hybrid vesicles (HVs) not only fuel hair regrowth by providing cellular signals in extracellular vesicles, but also improve storage stability, follicle retention, and drug encapsulation efficiency (EE%) for finasteride inhibiting 5α-reductase, and nano-size AuNPs that simulate low-level laser therapy (LLLT) with similar photothermal effects in vitro. The EE% of finasteride in these HVs reached 45.33%. The dual administration of these extracellular vesicles and finasteride showed a strong synergistic effect on HFSCs in vitro. In an AGA mouse model, once-daily topical Hybrid/Au@Fi (115.07 ± 0.32 nm, −7.50 ± 1.68 mV) gel led to a faster transition of hair follicles (HFs) from the catagen to the anagen, increased hair regrowth coverage, and higher quality of regrowth hair, compared to once-daily 5% minoxidil treatment. Compared to topical minoxidil, the multifaceted synergistic therapy of Hybrid/Au@Fi through topical administration offers a new option for intractable AGA patients with low side effects.
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BIOMATERIALS
·
2024
·
IF 12.8
Yujie Zhang,Yuan Zhao,Chuanfeng An,Yiyang Guo,Yubin Ma,Fei Shao,Yonggang Zhang,Kai Sun,Fang Cheng,Changle Ren,Lijun Zhang,Bingbing Sun,Yang Zhang,Huanan Wang
Recent progress in stem cell therapy has demonstrated the therapeutic potential of intravenous stem cell infusions for treating the life-threatening lung disease of pulmonary fibrosis (PF). However, it is confronted with limitations, such as a lack of control over cellular function and rapid clearance by the host after implantation. In this study, we developed an innovative PF therapy through tracheal administration of microfluidic-templated stem cell-laden microcapsules, which effectively reversed the progression of inflammation and fibrotic injury. Our findings highlight that hydrogel microencapsulation can enhance the persistence of donor mesenchymal stem cells (MSCs) in the host while driving MSCs to substantially augment their therapeutic functions, including immunoregulation and matrix metalloproteinase (MMP)-mediated extracellular matrix (ECM) remodeling. We revealed that microencapsulation activates the MAPK signaling pathway in MSCs to increase MMP expression, thereby degrading overexpressed collagen accumulated in fibrotic lungs. Our research demonstrates the potential of hydrogel microcapsules to enhance the therapeutic efficacy of MSCs through cell-material interactions, presenting a promising yet straightforward strategy for designing advanced stem cell therapies for fibrotic diseases.
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CHEMICAL ENGINEERING JOURNAL
·
2024
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IF 13.3
Yingbo Shen,Rui Liu,Xiangyi Wu,Ying Lu,Bin Kong,Yuanjin Zhao
Mesenchymal stem cells (MSCs) loaded hydrogels have shown positive therapeutic effects in skin wound treatment, while their application is still impractical on the wound bed. Here, we propose novel MSCs-loaded self-healing hydrogel microfiber fragments from microfluidic bubbles interrupted spinning for wound healing. The hydrogel microfibers are composed of sodium alginate, gelatin, polyvinyl alcohol, and borax, vesting them with good biocompatibility and self-healing ability. Their fragments with adjustable length are generated by introducing bubbles into microfluidic channels. We have demonstrated that the self-healing microfibers can promote the proliferation of MSCs, which are seeded alongside fragments’ surfaces to further facilitate the wound healing process. In addition, these MSCs laden self-healing hydrogel microfibers (MSG-fibers) showed obvious healing effect in rat wound model, which significantly promoted granulation tissue formation, collagen deposition and vascular construction at the wound site. Thus, we believe that our proposed MSC-laden microfiber fragments are valuable in promoting wound healing and have promising prospect in becoming new options for wound management.
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ACS Applied Materials & Interfaces
·
2025
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IF 8.2
Hongxiu Yuan,Gang Wang,Fangbo Zou,Peifen Lu,Noshin Afshan,Jianwei Jiao,Jin Jiao
Therapeutic strategies that can target multilevel immunoregulatory pathways in inflammatory bowel disease (IBD) and efficiently target the site of inflammation are expected to greatly enhance the therapeutic efficacy. Here, we have developed a DNA nanorobot-armed bidirectional resistant mesenchymal stem cell (MSC) for IBD treatment, which blocks lymphocyte infiltration at the site of inflammation by bidirectional inhibition of integrin-ligand inter-recognition via resistant aptamer-hands. And this strategy can induce MSC homing for immunomodulation and tissue repair. Herein, in this nanorobot, tetrahedral DNA (TDN) serves as a communication bridge, Integrin α4 and VCAM 1 aptamers are equipped to two vertices of TDN, and the other two cholesterol vertices of TDN are used for immobilization on MSC. In murine colitis models, tail vein-injected resistant MSC preferentially and rapidly accumulated in the inflamed colon and have been more effective in reducing colonic inflammation than pure MSC or aptamers bidirectional inhibitors. The therapeutic strategy proposed in this work has minimal systemic side effects and holds therapeutic promise for a subgroup of IBD patients who do not respond to single anti-inflammatory therapies.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-24
·
IF 10.6
Lai Huasheng,Yip Hon-Chi,Gong Yu,Chan Kai-Fung,Leung Kevin Kai-Chung,Chan Melissa Shannon,Xia Xianfeng,Chiu Philip Wai-Yan
Background Endoscopic submucosal dissection (ESD) is the current standard treatment for early-stage esophageal neoplasms. However, the postoperative esophageal stricture after extensive mucosal dissection remains a severe challenge with limited effective treatments available. In this study, we introduced a chitosan/gelatin (ChGel) sponge encapsulating the adipose mesenchymal stem cells (ADMSCs)-derived exosomes (ChGel MSC−Exo ) for the prevention of esophageal stenosis after ESD in a porcine model. Results Pigs were randomly assigned into (1) ChGel MSC−Exo treatment group, (2) ChGel PBS group, and (3) the controls. Exosome treatments were applied immediately on the day after ESD as well as on day 7. Exosome components crucial for wound healing were investigated by liquid chromatography-tandem mass spectrometry (LC–MS/MS) and small RNA sequencing. ChGel MSC−Exo treatment significantly reduced mucosal contraction on day 21, with less fiber accumulation and inflammatory infiltration, and enhanced angiogenesis when compared with the control and ChGel PBS groups. The anti-fibrotic effects following MSC-Exo treatment were further found to be associated with the anti-inflammatory M2 polarization of the resident macrophages, especially within the M2b subset characterized by the reduced TGFβ1 secretion, which sufficiently inhibited inflammation and prevented the activation of myofibroblast with less collagen production at the early stage after ESD. Moreover, the abundant expression of exosomal MFGE8 was identified to be involved in the transition of the M2b-macrophage subset through the activation of MFGE8/STAT3/Arg1 axis. Conclusions Our study demonstrates that exosomal MFGE8 significantly promotes the polarization of the M2b-macrophage subset, consequently reducing collagen deposition. These findings suggest a promising potential for MSC-Exo therapy in preventing the development of esophageal stricture after near-circumferential ESD. Graphical Abstract
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Artificial Cells Nanomedicine and Biotechnology
·
2018
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IF 3.026
Shunxiu Cao,Jiamin Guo,Yujing He,Murad Alahdal,Shanshan Tang,Yuekui Zhao,Zhaocong Yang,Huashan Gao,Wenjun Hu,Hulin Jiang,Lianju Qin,Liang Jin
The main challenge of anticancer drugs is poor tumor targeting. Now cellular carriers are widely investigated to deliver anticancer agents. As an ideal cellular candidate, human umbilical cord derived mesenchymal stem cells (hUC-MSCs) possess inherent tropism potential to tumor. Here, we constructed hUC-MSCs carrying transferrin-inspired-nanoparticles that contain doxorubicin(hUC-MSCs-Tf-inspired-NPs) to achieve enhanced anti-tumor efficacy and made an evaluation. Results represented that hUC-MSCs-Tf-inspired-NPs not only exhibit the controlled-release property of Tf-inspired-NPs, but also integrate tumor tropism and penetrative abilities of MSCs. The tumor volume of nude mice bearing breast cancer MCF-7 treated with hUC-MSCs-Tf-inspired-NPs, was remarkably reduced compared to those treated with free drug or Tf-inspired-NPs. Thus, Tf-inspired-NPs loaded hUC-MSCs have a potential to deliver anticancer drugs.
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COMPOSITES PART B-ENGINEERING
·
2024
·
IF 12.7
Weiguang Zhao,Yin Yang,Yutong Liu,Yang Wu,Renjie Wang,Shiyi Cao,Haoxin Cai,Zijie Xu,Jun Fang,Hongbing Deng,Zhihong Liu
The complications of enterocystoplasy have challenged traditional bladder reconstruction methods. Tissue engineering scaffolds, involving stem cells implantation and vascularization strategies, emerge as promising alternatives. However, their applications are hindered by issues regarding the source of stem cells and the rapid loss of bioactive factors in a urinary environment. Here, a multilayer biomimetic scaffold consisting of polycaprolactone (PCL) nanofibrous mats and oxidized dextran/carboxymethyl chitosan hydrogel has been synthesized. Bone marrow homing peptide (BMHP) and vascular endothelial growth factor-mimicking peptide (VP) were incorporated into the hydrogel to recruit endogenous stem cells and promote vascularization, respectively. The results indicated that PCL mats not only reinforced the mechanical properties of composite scaffolds but also prolonged the retention of peptides via the hydrophobic surface. In vivo experiments demonstrated that BMHP and VP had crosstalk effects, amplifying their functions to accelerate bladder regeneration, enhance contractility of smooth muscle cells, inhibit fibrosis, and improve innervation. Overall, the novel functionalized scaffolds are potentially viable for urologic tissue reconstruction.
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BIOMATERIALS
·
2024
·
IF 12.8
Yuanyuan Jin,Jiabin Zhang,Xiaodie Chen,Fenfang Li,Tiantian Xue,Ke Yi,Yanteng Xu,Haixia Wang,Yeh-Hsing Lao,Hon Fai Chan,Dan Shao,Mingqiang Li,Yu Tao
Acute liver failure (ALF) is a highly fatal disease, necessitating the advancement and optimization of alternative therapeutic strategies to benefit patients awaiting liver transplantation. In this study, we innovatively established the antioxidant nanozyme-hepatocyte-like cells (HLCs) microtissue sheets (HS/N–Au@composite) for ALF therapy. We first prepared a 3D-printed hyaluronic acid/gelatin/sodium alginate scaffold with N-acetylcysteine (NAC)-capped gold nanoclusters (NAC-Au NCs), forming the N–Au@hydrogel. For the encapsulation of HLC spheroids, we used a biocompatible hybrid hydrogel composed of decellularized extracellular matrix (dECM), thrombin, and fibrinogen, resulting in the HS@dECM hydrogel. Utilizing 3D printing technology, we integrated the N–Au@hydrogel with the HS@dECM hydrogel to create the HS/N–Au@composite for in situ transplantation to treat ALF. Our results demonstrated that NAC-Au NCs effectively mitigated reactive oxygen species (ROS)-induced liver necrosis in ALF. Additionally, the N–Au@hydrogel provided mechanical support, ensuring the proper landing and effective functioning of the transplanted HLC spheroids. The HS/N–Au@composite synergistically decreased serum transaminase levels, reduced the accumulation of pro-inflammatory cytokines, accelerated liver function recovery, and promoted liver regeneration in ALF treatment. This combination of HLC spheroids and NAC-Au NCs nanozymes via 3D-printed composite scaffolds represents a promising strategy for enhancing hepatocyte transplantation and advancing stem cell regenerative medicine in ALF therapy.
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