TOXICOLOGY AND APPLIED PHARMACOLOGY
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2025
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IF 3.4
Huanqing Song,Qingfei Hao,Jingjing Li,Yuanyuan Liu,Zhifang Huo,Ranran Si,Xiaoxia Feng,Chuan Zhou,Xiuyong Cheng
Bone marrow-derived mesenchymal stem cell (BMSCs) delivery is a promising therapeutic strategy for bronchopulmonary dysplasia (BPD); however, its efficacy remains suboptimal. Recent studies have reported that extracellular vesicles derived from peroxiredoxin 6 (PRDX6)-downregulated mesenchymal stem cells (MSCs) exhibit diminished anti-inflammatory and anti-oxidant effects through a paracrine mechanism. Nevertheless, whether PRDX6 participates in BPD progression via paracrine signaling remains unclear. Herein, rat BMSCs were first isolated and characterized. The GFP-labeled lentivirus was used to overexpress PRDX6 in BMSCs. PRDX6-overexpressing BMSCs exhibited improved proliferation and migration abilities. Notably, mesencephalic astrocyte-derived neurotrophic factor (MANF) secretion was significantly increased (~2.5-fold, p < 0.05) in PRDX6-overexpressed BMSCs. Further mechanistic studies revealed that PRDX6 bound to MANF, reducing its endoplasmic reticulum retention by displacing glucose-regulated protein 78, thereby promoting MANF secretion. Silencing MANF expression markedly attenuated the effects of PRDX6 overexpression. PRDX6-modified BMSCs were delivered intratracheally into BPD rat model, which was established by exposing rats in 85 % oxygen for 21 days. PRDX6 overexpression enhanced BMSCs recruitment to injured lung tissues, and significantly reduced apoptosis, inflammation, vascular loss, and pulmonary arterial remodeling. Concurrently, MANF levels in lung tissues, bronchoalveolar lavage fluid, and serum were elevated post-administration. These results suggest that PRDX6-mediated MANF secretion in BMSCs may not only enhance their proliferative and migratory capacities but also directly protect against lung injury. These findings provide a new strategy for amplifying the in vivo efficacy of BMSCs delivery on BPD.
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Human Cell
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2024
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IF 3.4
Chen Die,Su Jimei,Huang Xueying,Chen Hongyu,Jiang Tiejia,Zhi Chunchun,Zhou Zuolin,Zhang Bing,Yu Lan,Jiang Xiaoling
Pathogenic variants of the KCNH1 gene can cause dominant-inherited Temple–Baraitser/Zimmermann–Laband syndrome with severe mental retardation, seizure, gingival hyperplasia and nail hypoplasia. This study established an induced pluripotent stem cell (iPSC) line using urinary cells from a girl with KCNH1 recurrent/hotspot pathogenic variant c.1070G > A (p.R357Q). The cell identity, pluripotency, karyotypic integrity, absence of reprogramming virus and mycoplasma contamination, and differential potential to three germ layers of the iPSC line, named as ZJUCHi003, were characterized and confirmed. Furthermore, ZJUCHi003-derived neurons manifested slower action potential repolarization process and wider action potential half-width than the normal neurons. This cell line will be useful for investigating the pathogenic mechanisms of KCNH1 variants-associated symptoms, as well as for evaluating novel therapeutic approaches.
研究领域:
干细胞生物学
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遗传学
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神经科学
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2026
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IF 6.6
Haitao Zhang,Chaofeng Chen,Dayu Wang,Yiwei Huang,Yang Liu,Zhiyuan Wang,Furui Fu,Hongyu Wang,Senjie Shi,Yijin Li,Jianchun Zeng,Caiping Shen,Chudan Zhong,Xiaozhou Liu,Jinlun Chen,Jie Li,Shufen Liu,Jin Huang,Yirong Zeng,Wenjun Feng
As an emerging environmental contaminant, N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-Q) poses a potential threat to public health. However, the potential link between 6PPD-Q exposure and bone health remains largely unexplored. This study aims to systematically investigate the toxic effects of 6PPD-Q on bone metabolism and elucidate the underlying mechanisms by integrating transcriptomic sequencing, network toxicology, single-cell RNA, Molecular docking, molecular dynamics with both in vivo and in vitro experiments. Integrative analysis converged on mitophagy as a central mechanism in 6PPD-Q-induced osteoporosis, with single-cell sequencing identifying bone marrow-derived mesenchymal stem cells (BMSCs) as the key cell type and revealing CX43, MMP2, PDGFRB, and FYN as the principal targets. Molecular docking and MD simulations confirmed the targeted binding of 6PPD-Q to CX43. RNA-seq analysis of rat tibiae validated the differential expression of CX43 and the critical role of mitophagy. Both in vivo and in vitro experiments demonstrated that 6PPD-Q-induced bone loss was associated with the downregulation of CX43 and concomitant mitophagy dysregulation. In conclusion, this study elucidates that 6PPD-Q induces bone loss was associated with the downregulation of CX43 and concomitant mitophagy dysregulation. Our work establishes a comprehensive mechanistic framework for 6PPD-Q-induced bone damage and offers novel insights for future research into its bone toxicity. The 1 or 10 mg/kg dose used in this study, although higher than the typical environmental exposure level, is consistent with the effects observed in cadmium exposure and is close to the 8 mg/kg dose used in studies on mouse bone toxicity. Additionally, the 5 ng/mL concentration of 6PPD-Q used in the in vitro experiments is comparable to the concentration detected in freshwater, indicating its environmental relevance.
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International Journal of Nanomedicine
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2021
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IF 6.4
Guoxin Jing,Kun Li,Feiyue Sun,Jintong Niu,Rongrong Zhu,Yechang Qian,Shilong Wang
Introduction Embryonic stem cells (ESCs) possess great application prospects in biological research and regenerative medicine, so it is important to obtain ESCs with excellent and stable cellular states during in vitro expansion. The feeder layer culture system with the addition of leukemia inhibitory factor (LIF) is currently applied in ESC cultures, but it has a series of disadvantages that could influence the culture efficiency and quality of the ESCs. With the development of nanotechnology, many studies have applied nanomaterials to optimize the stem cell culture system and regulate the fate of stem cells. In this study, we investigated the layer-number-dependent biofunction of graphene oxide (GO) on the pluripotency of ESCs from mice (mESCs). Methods Single-layer GO (SGO) and multi-layer GO (MGO) were characterized and their effects on the cytotoxicity and self-renewal of mESCs were detected in vitro. The differentiation potentials of mESCs were identified through the formation of embryoid bodies and teratomas. The regulatory mechanism of GO was verified by blocking the target receptors on the surface of mESCs using antibodies. Results Both SGO and MGO were biocompatible with mESCs, but only MGO effectively sustained their self-renewal and differentiation potential. In addition, GO influenced the cellular activities of mESCs by regulating the interactions between extracellular matrix proteins and integrins. Conclusion This work demonstrates the layer-number-dependent effects of GO on regulating the cell behavior of mESCs and reveals the extracellular regulatory mechanism of this process.
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Advanced Healthcare Materials
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2023
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IF 10
Nan Luo,Yu-Wei Deng,Jin Wen,Xiao-Chen Xu,Rui-Xue Jiang,Jing-Yu Zhan,Yu Zhang,Bing-Qiang Lu,Feng Chen,Xi Chen
Pulp exposure often leads to pulp necrosis, root fractures, and ultimate tooth loss. The repair of the exposure site with pulp capping treatment is of great significance to preserving pulp vitality, but its efficacy is impaired by the low bioactivity of capping materials and cell injuries from the local accumulation of oxidative stress. This study develops a Wnt3a-loaded hydroxyapatite nanowire@mesoporous silica (Wnt3a-HANW@MpSi) core−shell nanocomposite for pulp capping treatments. The ultralong and highly flexible hydroxyapatite nanowires provide the framework for the composites, and the mesoporous silica shell endows the composite with the capacity of efficiently loading/releasing Wnt3a and Si ions. Under in vitro investigation, Wnt3a-HANW@MpSi not only promotes the oxidative stress resistance of dental pulp stem cells (DPSCs), enhances their migration and odontogenic differentiation, but also exhibits superior properties of angiogenesis in vitro. Revealed by the transcriptome analysis, the underlying mechanisms of odontogenic enhancement by Wnt3a-HANW@MpSi are closely related to multiple biological processes and signaling pathways toward pulp/dentin regeneration. Furthermore, an animal model of subcutaneous transplantation demonstrates the significant reinforcement of the formation of dentin–pulp complex-like tissues and blood vessels by Wnt3a-HANW@MpSi in vivo. These results indicate the promising potential of Wnt3a-HANW@MpSi in treatments of dental pulp exposure.
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JOURNAL OF NANOPARTICLE RESEARCH
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2015
·Vol. 17
·期 10
·1-10
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IF 2.184
Chen Daquan,Wang Guohua,Song Weiguo,Zhang Qiang
Most anticancer drugs cannot kill cancer stem cells (CSCs) effectively, which lead to the failure of anticancer chemotherapy, such as relapse and metastasis. In this study, we prepared a multifunctional oligosaccharides of hyaluronan (oHA) conjugates, oHA-histidine-menthone 1,2-glycerol ketal (oHM). The oHM conjugates possess pH-sensitive menthone 1,2-glycerol ketal (MGK) as hydrophobic moieties and oHA as the target of CD44 receptor. Anticancer drugs, curcumin(Cur) and paclitaxel(PTX), were loaded into oHM micelles via self-assembly. Then, oHM micelles were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method to fabricate the “nano-eggs.” The formed nano-eggs had a smaller size (120.6 ± 4.5 nm) than oHM micelles (158.6 ± 6.4 nm), indicating that mineralization made the appearance of compact nanoparticles. Interestingly, when the nano-eggs were put into the acidic conditions (pH 6.5), their outer shell(inorganic minerals) will be destroyed with the larger size, while the “nano-eggs” were stable under pH 7.4. For both nano-eggs and oHM micelles, the Cur and PTX were released in a sustained manner depending on the pH of the solution. However, the nano-eggs showed much lower released than the oHM micelles due to the dissolution of the inorganic minerals and pH-sensitive ketal at mildly acidic environments (pH 6.5). In vivo study, the nano-eggs could get to the tumor site more effectively than oHM micelles. CSCs were sorted by a side population assay from MDA-MB-231 breast cancer cell lines over-expressing CD44 receptors. Antitumor activity was also evaluated on MDA-MB-231 xenografts in nude mice. The antitumor efficacy indicated that nano-eggs with co-delivery of Cur and PTX produced the strongest antitumor efficacy, and nano-eggs showed strong activity against cancer stem cells. These double pH-sensitive nano-eggs may provide a promising strategy for drug delivery to both cancer cells and cancer stem cells.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2024
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IF 4.5
Jianfeng OuYang,Bingquan Li,Kangsheng Yang,Wenyi Gan,Xiaogang Miao,Bo Bai,Caiqin Lin,Jiewei Peng,Xiaofei Zheng
Modern developments in bone tissue engineering focus on designing biomimetic materials that exhibit suitable mechanical and physiochemical properties. In this study, we present the development of a new biomaterial scaffold using a newly constructed polymer that contains bisphosphonate in combination with gelatin (GAT). To achieve scaffolding, a chemical grafting technique was used to develop risedronate (RS)-functionalized polycaprolactone (PCL-RS). The freeze-casting process was used to construct the porous PCL-RS/GAT scaffold after incorporating gelatin into the PCL-RS polymer solution. A scaffold with pores that are in perfect position and a porosity of 81.84% was successfully acquired. The biodegradability assessment, 48% of its early weight was lost after five weeks. The PCL-RS/GAT scaffold exhibited an elastic modulus of 32.01 MPa and a tensile strength of 3.9 MPa. The MTT analysis showed the PCL-RS/GAT favorable cytocompatibility with rat bone marrow-derived mesenchymal stem cells (BM-MSC). In addition, the cells cultured in the PCL-RS/GAT scaffold exhibited the greatest ALP activity and mineralization. The RT-PCR test results indicated that the PCL-RS/GAT scaffold had a high RUNX2, COL 1A1, and OCN gene expression, suggesting a strong osteoinductive capacity. The results indicate that the PCL-RS/GAT scaffold is a suitable biomimetic platform for tissue engineering in bone.
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ENVIRONMENTAL SCIENCE & TECHNOLOGY
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2025
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IF 11.3
Wei Zhang,LianRui Duan,JiaYi Liang,Ziyan Liu,GuangYu Jiang,Ziyan Wang,Huiwen Kang,Danyang Huang,Ai Gao
The global annual output of liquid crystal monomers (LCMs) continues to increase, yet associated environmental and health risks remain poorly characterized. Assessing the toxic effects of the LCM mixture and individual components is critical for risk evaluation. Organoid models, characterized by highly biomimetic crypt-villus structures and cellular heterogeneity, serve as the preferred in vitro platforms for risk assessments. Our results reveal that exposure to the LCM mixture inhibits organoid expansion rates and induces abnormal crypt branching. Specifically, four machine learning models predicted that 4-cyano-4′-ethoxybiphenyl (EBCN) significantly contributes to intestinal toxicity. Exposure to EBCN alone reduces the proportion of viable cells, impairs intestinal barrier function, and disrupts stem cell homeostasis. Specifically, upregulated expression of the intestinal stem cell marker olfactomedin 4 (OLFM4) aligns with molecular signatures of inflammatory bowel disease patients in the Gene Expression Omnibus (GEO) data set. Additionally, the application of the Adverse Outcome Pathway framework identifies complement component C3 as the initial event, with downstream immunosuppression mediating EBCN-induced intestinal toxicity. In conclusion, this study highlights potential adverse effects of LCMs on gut physiology and emphasizes the urgent need for comprehensive health risk assessments for both the LCM mixture and individual LCM constituents.
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Stem Cell Research & Therapy
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2025
·Vol. 16
·期 1
·1-18
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IF 7.3
Mao Shihui,Lan Ting,Sun Yimei,Li Lin,Jiang Weifeng,Xu Jiadong,Feng Yan,Hu Huiqin,Fang Yan,Xu Lanxi,Chu Lisheng
Background Bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) show therapeutic promise for ischemic stroke (IS). Preconditioning MSCs with drugs can modulate the cargo composition and function of their derived EVs. This study investigated the therapeutic effects and underlying mechanisms of EVs derived from tetramethylpyrazine (TMP)-preconditioned BMSCs (TMP-BMSC-EVs) in IS.Methods EVs were isolated from BMSCs pretreated with or without TMP by differential centrifugation. The therapeutic efficacy of EVs was evaluated in a rat model of middle cerebral artery occlusion (MCAO) through neurological function assessments and infarct volume quantification. The expression of miR-486 and its roles in regulating microglia/macrophage polarization and neurogenesis, as well as the mechanistic targets, were examined by real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence staining, and Western blotting.Results TMP-BMSC-EVs exerted superior therapeutic efficacy compared to BMSC-EVs. Mechanistically, TMP-BMSC-EVs were enriched with miR-486, which promoted microglia/macrophage M2 polarization and neurogenesis, while downregulating phosphatase and tensin homolog (PTEN) and phosphorylated NF-κB (p-NF-κB) protein levels, and upregulating phosphorylated Akt (p-Akt) expression. Transfection with a miR-486 inhibitor abolished the beneficial effects of TMP-BMSC-EVs, which could be counteracted by the PTEN inhibitor bisperoxovanadium (bpV).Conclusion sTMP-BMSC-EVs could significantly promote neural repair by driving microglia/macrophage M2 polarization and enhancing neurogenesis through miR-486-mediated PTEN inhibition, thereby offering a promising treatment strategy for IS.
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Neural Regeneration Research
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2024
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IF 5.9
Li Tong,Xing Hui-Min,Qian Hai-Dong,Gao Qiao,Xu Sheng-Lan,Ma Hua,Chi Zai-Long
Several studies have found that transplantation of neural progenitor cells (NPCs) promotes the survival of injured neurons. However, a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application. Small extracellular vesicles (sEVs) contain bioactive molecules for neuronal protection and regeneration. Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases. In this study, we intravitreally transplanted sEVs derived from human induced pluripotent stem cells (hiPSCs) and hiPSCs-differentiated NPCs (hiPSC-NPC) in a mouse model of optic nerve crush. Our results show that these intravitreally injected sEVs were ingested by retinal cells, especially those localized in the ganglion cell layer. Treatment with hiPSC-NPC derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration, and regulated the retinal microenvironment by inhibiting excessive activation of microglia. Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells, which had protective effects on RGCs after optic nerve injury. These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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IF 6.2
Bo Luo,Mengxing Liu,Rongrong Li,Mengnan Zhou,Fengjia Zhang,Miao Wang,Yuqing Guo,Qingsi Zhang,Xinyi Liu,Yanbing Wu,Kun Fang,Rong Wang
In the search for novel succinate dehydrogenase inhibitors (SDHIs) fungicides for managing rice sheath blight (RSB) and sclerotinia stem rot (SSR), 28 pyrazole-4-carboxamides incorporating stilbene or diphenylacetylene scaffolds were synthesized and evaluated for antifungal activities. The results showed that compound 7m exhibited the most promising antifungal efficacy against Rhizoctonia solani and Sclerotinia sclerotiorum with EC50 (half maximal effective concentration) values of 0.004 and 0.028 μg/mL, outperforming Boscalid and Fluxapyroxad. Furthermore, the detached leaf assay showed that 7m showed remarkable protective and curative efficacies against R. solani and significant inhibition of S. sclerotiorum growth on oilseed rape leaves, indicating that it had a promising application prospect for RSB and SSR management. Further SDH enzymatic inhibition assay, scanning electron microscopy (SEM), molecular docking studies, and molecular dynamics (MD) simulations revealed that compound 7m shared an antifungal mechanism similar to that of Fluxapyroxad, which was further validated by density functional theory (DFT) and electrostatic potential (ESP) calculations. These findings suggested that 7m held significant promise as a novel SDHI for the effective management of RSB and SSR, warranting further investigation.
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Advanced Healthcare Materials
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2025
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IF 9.6
Yanrong Qin,Bo Chen,Yubin Hu,Xiyu Zhang,Zihan Wang,Chengjie Ma,Ruishan Yang,Bang Wang,Fan Li,Shiwei Niu,Yi Han,Di Lu
Efficient repairment of peripheral nerve injury (PNI) remains a severe clinical challenge worldwide, and recovering the regenerative capability of neurons in peripheral nervous system is hindered by the slow rate and inaccurate direction of axonal elongation. Schwann cells (SCs) loaded nerve guidance conduit has been proven to improve PNI repair, but the low cell survival rate and incomplete differentiation of SCs limited its practical application. To address these hurdles, a biophysically optimized nanofiber-hydrogel scaffold composite (APML@PC) is prepared in this study, the “bio”bonsai“”inspired strategy integrates topological and biological cues to promote adipose-derived mesenchymal stem cells (ADSCs) adhesion, proliferation, and Schwann-like cell differentiation. In vitro and in vivo experiments confirmed the favorable biocompatibility and reasonable biodegradation behavior of this inducible platform, and the robust capability to promote axonal growth, remyelination regeneration, as well as nerve function recovery. This novel composite can serve as a promising candidate for the development of advanced stem cell-based peripheral nerve regeneration, thereby paving a new avenue for clinically effective PNI therapy.
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