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学者姓名：马雪梅
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Abstract ：
Background: Wound healing is a complex and intricate biological process that involves multiple systems within the body and initiates a series of highly coordinated responses to repair damage and restore integrity and functionality. We previously identified that breathing hydrogen can significantly inhibit early inflammation, activate autologous stem cells, and promote the accumulation of extracellular matrix (ECM). However, the broader functions and downstream targets of hydrogen-induced ECM accumulation and tissue remodeling are unknown in the wound-healing process. Methods: Consequently, this thesis developed a hydrogen sustained-release dressing based on a micro storage material and reveals the mechanism of hydrogen in treating wound healing. Upon encapsulating the hydrogen storage materials, magnesium (Mg), and ammonia borane (AB), we found that SiO2@Mg exhibits superior sustained-release performance, while SiO2@AB demonstrates a higher hydrogen storage capacity. We used a C57/BL6 mouse full-thickness skin defect wound model to analyze and compare different hydrogen dressings. Results: It was identified that hydrogen dressings can significantly improve the healing rate of wounds by promoting epithelialization, angiogenesis, and collagen accumulation in wound tissue, and that the effect of slow-release dressings is better than of non-slow-release dressings. We also found that hydrogen dressing can promote transcriptome-level expression related to cell proliferation and differentiation and ECM accumulation, mainly through the Wnt1/beta-catenin pathway and TGF-beta 1/Smad2 pathway. Conclusions: Overall, these results provide a novel insight into the field of hydrogen treatment and wound healing.
Keyword ：
angiogenesis angiogenesis hydrogen-releasing micromaterial hydrogen-releasing micromaterial wound healing wound healing molecular mechanism molecular mechanism extracellular matrix deposition extracellular matrix deposition
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| GB/T 7714 | Zhao, Pengxiang , Li, Yufei , Guo, Boyuan et al. Hydrogen-Releasing Micromaterial Dressings: Promoting Wound Healing by Modulating Extracellular Matrix Accumulation Through Wnt/β-Catenin and TGF-β/Smad Pathways [J]. | PHARMACEUTICS , 2025 , 17 (3) . |
| MLA | Zhao, Pengxiang et al. "Hydrogen-Releasing Micromaterial Dressings: Promoting Wound Healing by Modulating Extracellular Matrix Accumulation Through Wnt/β-Catenin and TGF-β/Smad Pathways" . | PHARMACEUTICS 17 . 3 (2025) . |
| APA | Zhao, Pengxiang , Li, Yufei , Guo, Boyuan , Liu, Ziyi , Zhang, Xujuan , Liu, Mengyu et al. Hydrogen-Releasing Micromaterial Dressings: Promoting Wound Healing by Modulating Extracellular Matrix Accumulation Through Wnt/β-Catenin and TGF-β/Smad Pathways . | PHARMACEUTICS , 2025 , 17 (3) . |
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The emergence of sorafenib resistance has become a predominant impediment and formidable dilemma in the therapeutic approach for hepatocellular carcinoma (HCC). Although the approval of next-generation drugs as alternatives to sorafenib is a significant development, the concurrent use of inhibitors that target additional key molecular pathways remains an effective strategy to mitigate the acquisition of resistance. Here, we identified Glutathione S-Transferase Alpha 1 (GSTA1) as a critical modulator of sorafenib resistance (SR) in hepatocellular carcinoma (HCC) based on our findings from experiments conducted on recurrent liver cancer tissues, xenograft mouse models, organoids, and sorafenib-resistant cells. Elevated GSTA1 levels are strongly associated with adverse clinical prognoses. The knockout of GSTA1 reinstates sorafenib sensitivity, whereas its overexpression attenuates drug efficacy. Mechanistically, GSTA1 enhances the accumulation of lipid peroxides and suppresses ferroptosis by exerting its peroxidase function to regulate the SR. Notably, the upregulation of GSTA1 expression is mediated by the transcription factor CTNNB1 (beta-catenin), resulting in the formation of a cytoplasmic complex between GSTA1 and CTNNB1. This complex facilitates the nuclear translocation of CTNNB1, establishing a positive feedback loop. The combined use of GSTA1 and CTNNB1 inhibitors demonstrated synergistic antitumour effects through the induction of ferroptosis both in vitro and in vivo. Our findings reveal a novel regulatory role of the GSTA1/CTNNB1 axis in ferroptosis, suggesting that targeting GSTA1 and CTNNB1 could be a promising strategy to circumvent sorafenib resistance in HCC.
Keyword ：
Ferroptosis Ferroptosis Sorafenib Sorafenib Drug resistance Drug resistance GSTA1 GSTA1 Hepatocellular carcinoma (HCC) Hepatocellular carcinoma (HCC)
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| GB/T 7714 | Ma, Shiwen , Xie, Fei , Wen, Xiaohu et al. GSTA1/CTNNB1 axis facilitates sorafenib resistance via suppressing ferroptosis in hepatocellular carcinoma [J]. | PHARMACOLOGICAL RESEARCH , 2024 , 210 . |
| MLA | Ma, Shiwen et al. "GSTA1/CTNNB1 axis facilitates sorafenib resistance via suppressing ferroptosis in hepatocellular carcinoma" . | PHARMACOLOGICAL RESEARCH 210 (2024) . |
| APA | Ma, Shiwen , Xie, Fei , Wen, Xiaohu , Adzavon, Yao Mawulikplimi , Zhao, Ruping , Zhao, Jinyi et al. GSTA1/CTNNB1 axis facilitates sorafenib resistance via suppressing ferroptosis in hepatocellular carcinoma . | PHARMACOLOGICAL RESEARCH , 2024 , 210 . |
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Ischemic stroke, prevalent among the elderly, necessitates attention to reperfusion injury post treatment. Limited drug access to the brain, owing to the blood-brain barrier, restricts clinical applications. Identifying efficient drug carriers capable of penetrating this barrier is crucial. Blood-brain barrier transporters play a vital role in nutrient transport to the brain. Recently, nanoparticles emerged as drug carriers, enhancing drug permeability via surface-modified ligands. This article introduces the blood-brain barrier structure, elucidates reperfusion injury pathogenesis, compiles ischemic stroke treatment drugs, explores nanomaterials for drug encapsulation and emphasizes their advantages over conventional drugs. Utilizing nanoparticles as drug-delivery systems offers targeting and efficiency benefits absent in traditional drugs. The prospects for nanomedicine in stroke treatment are promising.
Keyword ：
ischemic stroke ischemic stroke blood-brain barrier blood-brain barrier reperfusion injury reperfusion injury nanoparticles nanoparticles
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| GB/T 7714 | Li, Jun , Xie, Fei , Ma, Xuemei . Advances in nanomedicines: a promising therapeutic strategy for ischemic cerebral stroke treatment [J]. | NANOMEDICINE , 2024 , 19 (9) : 811-835 . |
| MLA | Li, Jun et al. "Advances in nanomedicines: a promising therapeutic strategy for ischemic cerebral stroke treatment" . | NANOMEDICINE 19 . 9 (2024) : 811-835 . |
| APA | Li, Jun , Xie, Fei , Ma, Xuemei . Advances in nanomedicines: a promising therapeutic strategy for ischemic cerebral stroke treatment . | NANOMEDICINE , 2024 , 19 (9) , 811-835 . |
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Failures of wound healing have been a focus of research worldwide. With the continuous development of materials science, electrospun nanofiber scaffolds loaded with metal-based nanoparticles provide new ideas and methods for research into new tissue engineering materials due to their excellent antibacterial, anti-inflammatory, and wound healing abilities. In this review, the stages of extracellular matrix and wound healing, electrospun nanofiber scaffolds, metal-based nanoparticles, and metal-based nanoparticles supported by electrospun nanofiber scaffolds are reviewed, and their characteristics and applications are introduced. We discuss in detail the current research on wound healing of metal-based nanoparticles and electrospun nanofiber scaffolds loaded with metal-based nanoparticles, and we highlight the potential mechanisms and promising applications of these scaffolds for promoting wound healing.
Keyword ：
extracellular matrix extracellular matrix electrospinning electrospinning metal-based nanoparticles metal-based nanoparticles nanostructure nanostructure wound healing wound healing nanofiber scaffolds nanofiber scaffolds
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| GB/T 7714 | Dang, Zheng , Ma, Xuemei , Yang, Zihao et al. Electrospun Nanofiber Scaffolds Loaded with Metal-Based Nanoparticles for Wound Healing [J]. | POLYMERS , 2024 , 16 (1) . |
| MLA | Dang, Zheng et al. "Electrospun Nanofiber Scaffolds Loaded with Metal-Based Nanoparticles for Wound Healing" . | POLYMERS 16 . 1 (2024) . |
| APA | Dang, Zheng , Ma, Xuemei , Yang, Zihao , Wen, Xiaohu , Zhao, Pengxiang . Electrospun Nanofiber Scaffolds Loaded with Metal-Based Nanoparticles for Wound Healing . | POLYMERS , 2024 , 16 (1) . |
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As a novel antioxidant, a growing body of studies has documented the diverse biological effects of molecular hydrogen (H-2) in a wide range of organisms, spanning animals, plants, and microorganisms. Although several possible mechanisms have been proposed, they cannot fully explain the extensive biological effects of H-2. Mitochondria, known for ATP production, also play crucial roles in diverse cellular functions, including Ca2+ signaling, regulation of reactive oxygen species (ROS) generation, apoptosis, proliferation, and lipid transport, while their dysfunction is implicated in a broad spectrum of diseases, including cardiovascular disorders, neurodegenerative conditions, metabolic disorders, and cancer. This review aims to 1) summarize the experimental evidence on the impact of H-2 on mitochondrial function; 2) provide an overview of the mitochondrial pathways underlying the biological effects of H-2, and 3) discuss H-2 metabolism in eukaryotic organisms and its relationship with mitochondria. Moreover, based on previous findings, this review proposes that H-2 may regulate mitochondrial quality control through diverse pathways in response to varying degrees of mitochondrial damage. By combining the existing research evidence with an evolutionary perspective, this review emphasizes the potential hydrogenase activity in mitochondria of higher plants and animals. Finally, this review also addresses potential issues in the current mechanistic study and offers insights into future research directions, aiming to provide a reference for future studies on the mechanisms underlying the action of H-2.
Keyword ：
molecular hydrogen (H-2) molecular hydrogen (H-2) mitochondria mitochondria hydrogenase hydrogenase complex I complex I mitochondrial quality control mitochondrial quality control
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| GB/T 7714 | Zhang, Xiaoyue , Xie, Fei , Ma, Shiwen et al. Mitochondria: one of the vital hubs for molecular hydrogen's biological functions [J]. | FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY , 2023 , 11 . |
| MLA | Zhang, Xiaoyue et al. "Mitochondria: one of the vital hubs for molecular hydrogen's biological functions" . | FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 11 (2023) . |
| APA | Zhang, Xiaoyue , Xie, Fei , Ma, Shiwen , Ma, Chen , Jiang, Xue , Yi, Yang et al. Mitochondria: one of the vital hubs for molecular hydrogen's biological functions . | FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY , 2023 , 11 . |
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BackgroundDespite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. H-2 has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how H-2 functions in wound healing remains unknown, especially for the link between H-2 and extracellular matrix (ECM) deposition and epidermal stem cells (EpSCs) activation.MethodsHere, we established a cutaneous aseptic wound model and applied a high concentration of H-2 (66% H-2) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, digital spatial profiler analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging.ResultsWe revealed that a high concentration of H-2 (66% H-2) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. The effect was not dependent on O-2 or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the H-2 group. ECM components early (3 days post-wounding) deposition were found in the H-2 group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. H-2 accelerated early autologous EpSCs proliferation (1-2 days in advance) and then differentiation into myoepithelial cells. These epidermal myoepithelial cells could further contribute to ECM deposition. Other beneficial outcomes include sustained moist healing, greater vascularization, less T-helper-1 and T-helper-17 cell-related systemic inflammation, and better tissue remodelling.ConclusionWe have discovered a novel pattern of wound healing induced by molecular hydrogen treatment. This is the first time to reveal the direct link between H-2 and ECM deposition and EpSCs activation. These H-2-induced multiple advantages in healing may be related to the enhancement of cell viability in various cells and the maintenance of mitochondrial functions at a basic level in the biological processes of life.
Keyword ：
Molecular hydrogen Molecular hydrogen Epidermal stem cell proliferation Epidermal stem cell proliferation Wound care Wound care Re-epithelialization Re-epithelialization Extracellular matrix deposition Extracellular matrix deposition
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| GB/T 7714 | Zhao, Pengxiang , Dang, Zheng , Liu, Mengyu et al. Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition [J]. | INFLAMMATION AND REGENERATION , 2023 , 43 (1) . |
| MLA | Zhao, Pengxiang et al. "Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition" . | INFLAMMATION AND REGENERATION 43 . 1 (2023) . |
| APA | Zhao, Pengxiang , Dang, Zheng , Liu, Mengyu , Guo, Dazhi , Luo, Ruiliu , Zhang, Mingzi et al. Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition . | INFLAMMATION AND REGENERATION , 2023 , 43 (1) . |
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Purpose: Lacrimal gland benign lymphoepithelial lesion (LGBLEL) is an IgG4related disease of unknown etiology with a risk for malignant transformation. Estrogen is considered to be related to LGBLEL onset. Methods: Seventy-eight LGBLEL and 13 control clinical samples were collected and studied to determine the relationship between estrogen and its receptors and LGBLEL development. Results: The serological analysis revealed no significant differences in the levels of three estrogens be-tween the LGBLEL and control groups. However, immunohistochemical analyses indicated that the expression levels of ERb and its downstream receptor RERG were relatively lower in LGBLEL samples than in control samples, with higher expression in the lacrimal gland and lower expression in the lymphocyte infiltration region. However, low expression of ER a was detected. The transcriptome sequence analysis revealed upregulated genes associated with LGBLEL enriched in lymphocyte proliferation and activation function; downregulated genes were enriched in epithelial and vascular proliferation functions. The key genes and gene networks were further analyzed. Interactions between B cells and epithelial cells were analyzed due to the identified involvement of leukocyte subsets and epithelial cells. B cell proliferation was found to potentially contribute to lacrimal gland apoptosis. Conclusion: Therefore, the tissue-heterogeneous expression pattern of ER b is potentially related to the clinical manifestations and progression of LGBLEL, although further investigations are required to confirm this finding.
Keyword ：
ER beta ER beta B lymphocyte proliferation B lymphocyte proliferation tumor development tumor development lacrimal gland apoptosis lacrimal gland apoptosis LGBLEL LGBLEL clinical manifestations clinical manifestations
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| GB/T 7714 | Zhang, Xujuan , Zhao, Pengxiang , Ma, Mingshen et al. Missing link between tissue specific expressing pattern of ER & beta; and the clinical manifestations in LGBLEL [J]. | FRONTIERS IN MEDICINE , 2023 , 10 . |
| MLA | Zhang, Xujuan et al. "Missing link between tissue specific expressing pattern of ER & beta; and the clinical manifestations in LGBLEL" . | FRONTIERS IN MEDICINE 10 (2023) . |
| APA | Zhang, Xujuan , Zhao, Pengxiang , Ma, Mingshen , Wu, Hao , Liu, Rui , Liu, Ziyi et al. Missing link between tissue specific expressing pattern of ER & beta; and the clinical manifestations in LGBLEL . | FRONTIERS IN MEDICINE , 2023 , 10 . |
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The heterogeneous and highly plastic cell populations of macrophages are important mediators of cellular responses during all stages of wound healing, especially in the inflammatory stage. Molecular hydrogen (H-2), which has potent antioxidant and anti-inflammatory effects, has been shown to promote M2 polarization in injury and disease. However, more in vivo time series studies of the role of M1-to-M2 polarization in wound healing are needed. In the current study, we performed time series experiments on a dorsal full-thickness skin defect mouse model in the inflammatory stage to examine the effects of H-2 inhalation. Our results revealed that H-2 could promote very early M1-to-M2 polarization (on days 2-3 post wounding, 2-3 days earlier than in conventional wound healing), without disturbing the functions of the M1 phenotype. Time series analysis of the transcriptome, blood cell counts, and multiple cytokines further indicated that peripheral blood monocytes were a source of H-2-induced M2 macrophages and that the functions of H-2 in macrophage polarization were not only dependent on its antioxidant effects. Therefore, we believe that H-2 could reduce inflammation in wound care by shifting early macrophage polarization in clinical settings.
Keyword ：
wound healing wound healing in vivo time series study in vivo time series study anti-ROS independent anti-ROS independent inflammation stage inflammation stage M2 macrophage polarization M2 macrophage polarization molecular hydrogen molecular hydrogen
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| GB/T 7714 | Zhao, Pengxiang , Cai, Zisong , Zhang, Xujuan et al. Hydrogen Attenuates Inflammation by Inducing Early M2 Macrophage Polarization in Skin Wound Healing [J]. | PHARMACEUTICALS , 2023 , 16 (6) . |
| MLA | Zhao, Pengxiang et al. "Hydrogen Attenuates Inflammation by Inducing Early M2 Macrophage Polarization in Skin Wound Healing" . | PHARMACEUTICALS 16 . 6 (2023) . |
| APA | Zhao, Pengxiang , Cai, Zisong , Zhang, Xujuan , Liu, Mengyu , Xie, Fei , Liu, Ziyi et al. Hydrogen Attenuates Inflammation by Inducing Early M2 Macrophage Polarization in Skin Wound Healing . | PHARMACEUTICALS , 2023 , 16 (6) . |
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Abstract ：
Molecular hydrogen (H-2) has emerged as a new therapeutic option in several diseases and is widely adopted by healthy people. However, molecular data to support therapeutic functions attributed to the biological activities of H-2 remain elusive. Here, using transcriptomic and metabolomic approaches coupled with biochemistry and micro-CT technics, we evaluated the effect of long-term (6 months) and daily use of H-2 on liver function. Rats exposed 2 h daily to H-2 either by drinking HRW (H-2 dissolved in H2O) or by breathing 4% H-2 gas showed reduced lipogenesis and enhanced lipolysis in the liver, which was associated with apparent loss of visceral fat and brown adipose tissue together with a reduced level of serum lipids. Both transcripts and metabolites enriched in H-2-treated rats revealed alteration of amino acid metabolism pathways and activation of purine nucleotides and carbohydrate biosynthesis pathways. Analysis of the interaction network of genes and metabolites and correlation tests revealed that NADP is the central regulator of H-2 induced metabolic alterations in the liver, which was further confirmed by an increase in the level of components of metabolic pathways that require NADP as substrate. Evidence of immune response regulation activity was also observed in response to exposure to H-2. This work is the first to provide metabolomic and transcriptomic data to uncover molecular targets for the effect of prolonged molecular hydrogen treatment on liver metabolism.
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| GB/T 7714 | Adzavon, Yao Mawulikplimi , Xie, Fei , Yi, Yang et al. Long-term and daily use of molecular hydrogen induces reprogramming of liver metabolism in rats by modulating NADP/NADPH redox pathways [J]. | SCIENTIFIC REPORTS , 2022 , 12 (1) . |
| MLA | Adzavon, Yao Mawulikplimi et al. "Long-term and daily use of molecular hydrogen induces reprogramming of liver metabolism in rats by modulating NADP/NADPH redox pathways" . | SCIENTIFIC REPORTS 12 . 1 (2022) . |
| APA | Adzavon, Yao Mawulikplimi , Xie, Fei , Yi, Yang , Jiang, Xue , Zhang, Xiaokang , He, Jin et al. Long-term and daily use of molecular hydrogen induces reprogramming of liver metabolism in rats by modulating NADP/NADPH redox pathways . | SCIENTIFIC REPORTS , 2022 , 12 (1) . |
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The potential for preventive and therapeutic applications of H-2 have now been confirmed in various disease. However, the effects of H-2 on health status have not been fully elucidated. Our previous study reported changes in the body weight and 13 serum biochemical parameters during the six-month hydrogen intervention. To obtain a more comprehensive understanding of the effects of long-term hydrogen consumption, the plasma metabolome and gut microbiota were investigated in this study. Compared with the control group, 14 and 10 differential metabolites (DMs) were identified in hydrogen-rich water (HRW) and hydrogen inhalation (HI) group, respectively. Pathway enrichment analysis showed that HRW intake mainly affected starch and sucrose metabolism, and DMs in HI group were mainly enriched in arginine biosynthesis. 16S rRNA gene sequencing showed that HRW intake induced significant changes in the structure of gut microbiota, while no marked bacterial community differences was observed in HI group. HRW intake mainly induced significant increase in the abundance of Lactobacillus, Ruminococcus, Clostridium XI, and decrease in Bacteroides. HI mainly induced decreased abundances of Blautia and Paraprevotella. The metabolic function was determined by metabolic cage analysis and showed that HI decreased the voluntary intake and excretions of rats, while HRW intake did not. The results of this study provide basic data for further research on hydrogen medicine. Determination of the effects of hydrogen intervention on microbiota profiles could also shed light on identification of mechanism underlying the biological effects of molecular hydrogen.
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| GB/T 7714 | Xie, Fei , Jiang, Xue , Yi, Yang et al. Different effects of hydrogen-rich water intake and hydrogen gas inhalation on gut microbiome and plasma metabolites of rats in health status [J]. | SCIENTIFIC REPORTS , 2022 , 12 (1) . |
| MLA | Xie, Fei et al. "Different effects of hydrogen-rich water intake and hydrogen gas inhalation on gut microbiome and plasma metabolites of rats in health status" . | SCIENTIFIC REPORTS 12 . 1 (2022) . |
| APA | Xie, Fei , Jiang, Xue , Yi, Yang , Liu, Zi-Jia , Ma, Chen , He, Jin et al. Different effects of hydrogen-rich water intake and hydrogen gas inhalation on gut microbiome and plasma metabolites of rats in health status . | SCIENTIFIC REPORTS , 2022 , 12 (1) . |
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