Acta Pharmaceutica Sinica B
·
2025
·
IF 14.6
Xuewen Yang,Yanwei Zhang,Xiaoping Leng,Yanying Wang,Manyu Gong,Dongping Liu,Haodong Li,Zhiyuan Du,Zhuo Wang,Lina Xuan,Ting Zhang,Han Sun,Xiyang Zhang,Jie Liu,Tong Liu,Tiantian Gong,Zhengyang Li,Shengqi Liang,Lihua Sun,Lei Jiao,Baofeng Yang,Ying Zhang
Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.
研究领域:
心脏病学
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分子生物学
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病理学
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药理学
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产品关联
DOI
PubMed
高影响因子
Polymers
·
2025
·Vol. 17
·期 5
·607
·
IF 4.9
Peifen Ma,Jianlong Da,Guanghui Zhao,Feiya Suo,Yan Li,Xiaochun Zhou,Yao Li,Yiheng Han,Mingyang Zou,Xinman Dou
Diabetic wounds are therapeutically challenging because of the complex and adverse microenvironment that impedes healing. Unlike conventional wound dressings, hydrogels provide antibacterial, anti-inflammatory, and repair-promoting functions. In this study, we developed a light-responsive and injectable chitosan methacryloyl (CSMA) hydrogel, incorporating soy isoflavones (SIs) and gold nanoparticles (AuNPs). Transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, and proton nuclear magnetic resonance (1H NMR) spectroscopy analyses confirmed the successful synthesis of the CSMA/SI/AuNP hydrogels. In vitro experiments demonstrated that this hydrogel exhibited exceptional biocompatibility and enhanced the migration of human umbilical vein endothelial cells (p< 0.05), thereby underscoring its potential for promoting angiogenesis. In vivo studies have indicated that hydrogels significantly enhance the rate of wound healing (p< 0.001). Moreover, they facilitate angiogenesis (p< 0.01) and diminish the inflammatory response at the wound site (p< 0.05). Additionally, hydrogels promote collagen deposition and the regeneration of skin appendages. These findings substantiate the hydrogel’s therapeutic potential for diabetic wound care, highlighting its promise for regenerative medicine. CSMA/SI/AuNP represents a significant advancement in diabetic wound treatment, addressing key challenges in wound healing by offering a multifaceted therapeutic approach with broad clinical implications for enhancing patient outcomes in chronic wound management.
研究领域:
生物材料学
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再生医学
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药理学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 33
·6798-6804
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IF 4.726
Shixuan Chen,Min Zhang,Xuebing Shao,Xueer Wang,Lei Zhang,Pengcheng Xu,Wen Zhong,Lu Zhang,Malcolm Xing,Lin Zhang
Angiogenesis and re-epithelialization are critical factors in skin wound healing. Growth factors and stem cells have demonstrated their active roles in promoting these two processes. Peptides show similar effects with growth factors with lower cost and controllable properties. Here we report a biomimetic fragment of the laminin –Ser-Ile-Lys-Val-Ala-Val (SIKVAV)-conjugated chitosan hydrogel that can promote skin regeneration. In vitro we found that this peptide-conjugated hydrogel significantly promoted BMSC adhesion and proliferation. In vivo, this hydrogel accelerated wound contraction. The subcutaneous implantation test and H&E staining results revealed that the peptide-modified chitosan hydrogel dramatically led to the formation of new blood vessels. Moreover, Masson staining showed that many newborn collagen fibers appeared in the peptide hydrogel group, while only a few newborn collagen fibers were found in control and chitosan hydrogel groups. The peptide chitosan hydrogel also re-epithelialized quickly, while the control and chitosan hydrogel took more time to complete. These results suggest that the SIKVAV peptide is an effective motif to significantly improve the function of chitosan in angiogenesis and re-epithelialization of skin.
研究领域:
生物材料学
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再生医学
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皮肤修复
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DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2025
·
IF 2.2
Xiaoyun Yang,Yi Wang,Yujin Feng,Feng Wang,Lijuan Gao,Yueheng Wang
Myocardial infarction is often accompanied by symptoms of myocardial fibrosis, causing myocardial systolic and diastolic dysfunction. High levels of TMAO are considered to be strongly connected to cardiovascular diseases occurrence. The objective of this investigation was to determine whether formal TMAO affects the development of cardiac muscle fibers. The left anterior descending (LAD) coronary artery was ligated to construct myocardial infarction mouse model, while the control group mouse was only operated vessel separation. According to whether or not TMAO intervention is given, mice were divided into control, TMAO, myocardial infarction model(model), and myocardial infarction model + TMAO(model + TMAO). TMAO and model + TMAO group received 0.24 % TMAO in drinking water for one month. After modeling, echocardiography assessed cardiac function, and cardiac tissues were collected for analysis. Masson staining observed collagen deposition, while immunohistochemistry was conducted to identify fibronectin, collagen III, collagen I, and JAK/STAT pathway related proteins levels. In vitro, mouse cardiac fibroblasts were cultured and treated with varying TMAO concentrations (0, 300, 600, 900 μM), and Western blot was carried out to analyse changes in fibronectin, collagen III, and collagen I. Subsequently, the JAK2/STAT3 pathway inhibitor AG490 was utilized to treat cells and further examine the changes of fibronectin and collagen. The in vivo data showed TMAO significantly increases fibrosis and upregulates fibronectin, collagen III, and collagen I. In vitro experiments indicated that TMAO promotes fibronectin, collagen III, and collagen I levels through regulating the JAK2/STAT3 pathway, ultimately accelerating fibrosis.
研究领域:
心血管疾病研究
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2016
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IF 2.551
Xiaochun Luo,Ping Huang,Baohong Yuan,Tao Liu,Fang Lan,Xiaoyan Lu,Liangcheng Dai,Yunjun Liu,Hui Yin
Astragaloside IV (AS-IV), one of the major active compounds extracted from Astragali Radix , has been used experimentally for its potent antiinflammatory and immunoregulatory activities. In this study, we further investigate the potential efficacy of AS-IV on impaired wound healing in streptozotocin-induced diabetic mice. A full-thickness skin wound was produced on the back of diabetic mice and treated with AS-IV or vehicle topically. Our results showed that AS-IV application promoted diabetic wound repair with wounds gaping narrower and exhibiting augmented reepithelialization . AS-IV enhanced the collagen deposition and the expression of extracellular matrix (ECM)-related genes such as fibronectin and collagen IIIa, which implies a direct effect of AS-IV on matrix synthesis. AS-IV also improved the new blood vessel formation in wound tissue with increased numbers of endothelial cells and enhanced expression of VEGF and vWF. Moreover, the beneficial effect of AS-IV was related to the development of polarized alternatively activated macrophages, which involved in resolution of inflammation and facilitation of wound repair. All together, these findings suggest that AS-IV may play a potential effect on maintenance of cutaneous homeostasis and acceleration of diabetic wound healing.
研究领域:
药理学
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免疫学
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糖尿病研究
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DOI
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 27
·6346-6360
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IF 7
Zuqin Dong,Quanying Liu,Xiaowen Han,Xinyue Zhang,Xinyue Wang,Chen Hu,Xing Li,Jie Liang,Yafang Chen,Yujiang Fan
Cutaneous wound healing is a complex process that strives to re-establish the original structure and functions of the skin. With the development of electrospinning technology, nanofibrous membrane biomaterials have emerged as promising pro-regenerative strategies for recapitulating the structure and composition of the natural extracellular matrix (ECM). Herein, a nanofibrous membrane wound dressing material based on recombinant human collagen type III (rhCol III) crosslinked by EDC/NHS (rhCol III EN NF), which incorporated multiple Gly–Glu–Lys (GEK) and Gly–Leu–Ser–Gly–Glu–Arg (GLSGER) integrin receptors, has been developed utilizing green electrospinning technology. The rhCol III EN NF exhibited excellent flexibility, mechanical properties and water absorption. Amino acid analysis showed that rhCol III EN NF retained integrin receptor-associated amino acids to mediate cell activities and then expedite wound healing. Subsequent in vitro experiments confirmed that the rhCol III EN NF effectively promotes cell adhesion, proliferation and migration. On a mouse full-thickness wound model, rhCol III EN NF dressings expedited wound closure and greatly improved collagen deposition, recovering dermal and epidermal structures as well as skin appendages. Altogether, our research demonstrated that rhCol III EN NF prepared by electrospinning technology could efficiently heal wounds and regenerate skin.
研究领域:
生物材料学
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再生医学
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皮肤科学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL & PHARMACEUTICAL BULLETIN
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2024
·Vol. 72
·期 7
·669-675
·
IF 1.5
Xiongwei Deng,Qiang Li,Haitao Yuan,Hejun Hu,Shaoyong Fan
Tendon injury is a prevalent orthopedic disease that currently lacks effective treatment. Galangin (GLN) is a vital flavonoid found abundantly in galangal and is known for its natural activity. This study aimed to investigate the GLN-mediated molecular mechanism of tendon-derived stem cells (TDSCs) in tendon repair. The TDSCs were characterized using alkaline phosphatase staining, alizarin red S staining, oil red O staining, and flow cytometry. The effect of GLN treatment on collagen deposition was evaluated using Sirius red staining and quantitative (q)PCR, while a Western bot was used to assess protein levels and analyze pathways. Results showed that GLN treatment not only increased the collagen deposition but also elevated the mRNA expression and protein levels of multiple tendon markers like collagen type I alpha 1 (COL1A1), decorin (DCN) and tenomodulin (TNMD) in TDSCs. Moreover, GLN was also found to upregulate the protein levels of transforming growth factor β1 (TGF-β1) and p-Smad3 to activate the TGF-β1/Smad3 signaling pathway, while GLN mediated collagen deposition in TDSCs was reversed by LY3200882, a TGF-β receptor inhibitor. The study concluded that GLN-mediated TDSCs enhanced tendon repair by activating the TGF-β1/Smad3 signaling pathway, suggesting a novel therapeutic option in treating tendon repair.
研究领域:
骨科
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干细胞研究
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
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2025
·
IF 3.9
Ying Fan,Chuli Liao,Jie Li,Meiling Wu,Jie Liu,Feng Li,Wen Wu
Nitric oxide (NO) is essential for wound healing, promoting angiogenesis and collagen deposition. This study investigates a novel dual-matrix nanocomposite hydrogel incorporating S-nitrosoglutathione (GSNO), a physiological NO donor, to enhance cutaneous wound healing. GSNO was encapsulated in ammonio methacrylate copolymer nanoparticles and embedded in an alginate-based matrix, achieving controlled NO release. GSNO-loaded nanoparticles were prepared using solvent displacement and solvent evaporation methods, resulting in spherical, well-distributed, and positively charged particles. These nanoparticles were cross-linked with negatively charged alginic acid to form a nanocomposite hydrogel. The hydrophobic nanoparticles protected GSNO from degradation, while the hydrophilic alginate matrix sustained the release of active GSNO for up to 10 hours, promoting hemostasis and maintaining a moist wound environment. The hydrogel exhibited good biocompatibility in human fibroblasts and significantly enhanced wound repair by promoting fibroblast formation, neovascularization, and collagen deposition, as demonstrated by hematoxylin and eosin staining and Masson’s trichrome staining. In conclusion, the GSNO-loaded nanocomposite hydrogel significantly accelerated the healing process by enhancing angiogenesis and collagen deposition, offering a promising strategy for improving wound healing.
研究领域:
生物材料学
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医学
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药剂学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Xin Chen,Sai Zhu,Si-Yu Chen,Jia-Nan Wang,Li-Jiao Sun,Shan-Min Tao,Xiao-Feng Li,Hai-Di Li,Ying-Yin Sun,Chuan-Hui Xu,Xiao-Guo Suo,Ming-Lu Ji,Cheng Huang,Xiao-Ming Meng,Jun Li
Hepatic fibrosis is an essential pathology of multiple chronic liver diseases. The aim of this study was to investigate the role of miR-301a-3p in hepatic fibrosis. We found that miR-301a-3p was upregulated in hepatic fibrosis patients and in culture-activated human hepatic stellate cells (HSCs). Interestingly, miR-301a-3p expression was increased in hepatic fibrosis progression mice while decreased in hepatic fibrosis recovery mice, indicating that miR-301a-3p may participate in the hepatic fibrosis pathology. Functionally, the effects of miR-301a-3p both on hepatic fibrosis progression and regression were assessed in vivo . Inhibiting miR-301a-3p ameliorated mouse liver fibrogenesis and collagen deposition and suppressed HSC activation and fibrogenic factor expression. Whereas, in hepatic fibrosis regression, upregulating miR-301a-3p impaired mouse hepatic fibrosis recovery by inducing HSC activation and triggering inflammation. Consistently, gain-of-function and loss-of-function analysis of miR-301a-3p were performed to evaluate its effects on human HSCs LX-2 cell. We found that suppressing miR-301a-3p inhibited LX-2 cell activation and proliferation, and induced LX-2 cell apoptosis, accompanied by decreased fibrotic mediators expression. Collectively, these findings suggest miR-301a-3p drives liver fibrogenesis and HSC activation in hepatic fibrosis. Mechanistically, we demonstrated miR-301a-3p binds directly to phosphatase and tensin homolog (PTEN) by luciferase reporter analysis, pull-down, and RIP assay. Indicating that miR-301a-3p plays a critical role in promoting liver fibrogenesis via modulating the PTEN/platelet derived growth factor β (PDGFR-β) pathway. In conclusion, our findings demonstrate that miR-301a-3p expression is closely correlated with hepatic fibrosis pathology, and that enhancing miR-301a-3p maintains the HSC profibrogenic phenotype, triggers inflammatory responses, promotes fibrogenic factor production, and further exacerbates liver fibrogenesis. These findings suggest that miR-301a-3p may serve as a promising diagnostic and prognosis biomarker for hepatic fibrosis treatment.
研究领域:
分子生物学
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肝病学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2025
·
IF 4.7
Jicong Lu,Yingying Guo,Zhaoyuan Yang,Mengxia Xie,Shuangyu Zhang,Keji Li,Jingjing Yang,Shanhui Xue,Da Xu,Kanglu Yan,Yuehua Liu
The prevalence of gestational diabetes mellitus (GDM) is currently on the rise globally, which heightens the risk of adverse pregnancy outcomes and subsequently increases the likelihood of cesarean delivery. GDM can induce hyperglycemic conditions in cesarean wounds, leading to delayed wound healing and complications such as itching, pain, and scarring. These complications significantly impact the quality of life and mental health of mothers. Furthermore, there is a lack of effective clinical prevention strategies. Consequently, the need to improve wound healing after cesarean sections in women with GDM is a pressing concern that warrants our attention. To maximize the therapeutic impact and extend the bioavailability of calycosin-7-glucoside (CG), it was integrated into a hybridized hydrogel (GOHA) as a drug carrier to create the GOHACG hydrogel. Bases on our tests, the GOHACG hydrogel demonstrated a strong capacity for water absorption, appropriate pore size, and good biocompatibility to adjust to the in situ surroundings of the wound. GOHACG also promoted epidermal regeneration, collagen deposition, angiogenesis, and the conversion of macrophages from the M1 to M2 phenotype. Indicating a reduction in the inflammatory response, accelerated wound repair, and minimized skin scarring in a postcesarean delivery model involving gestational diabetic mellitus mice. In brief, the GOHACG possesses significant properties that enhance wound healing in GDM model, suggesting its potential effects in treating wound healing of GDM.
研究领域:
医学
·
药理学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
Gels
·
2025
·Vol. 11
·期 4
·226
·
IF 5.3
Jiaqi Li,Yuanli Huang,Yalu Wang,Qianqian Han
Wound healing is a complex biological process involving inflammation, proliferation, and remodeling phases. Effective healing is essential for maintaining skin integrity, driving the need for advanced materials like hydrogels, known for their high water retention and tunable mechanical properties. In this study, we synthesized a biocompatible composite hydrogel composed of γ-polyglutamic acid (γ-PGA) and ε-polylysine (ε-PL) through a Schiff base reaction, forming a stable crosslinked network. Its physicochemical properties, including rheological behavior and swelling capacity, were systematically evaluated. Biocompatibility was assessed via in vitro hemolysis and cytotoxicity assays, and in vivo testing was performed using a full-thickness skin defect model in Sprague Dawley (SD) rats to evaluate wound-healing efficacy. The PGA-PL hydrogel demonstrated excellent physicochemical properties, with a maximum swelling ratio of 65.6%, and biocompatibility as evidenced by low hemolysis rates (<5%) and high cell viability (>80%). It promoted wound healing by inhibiting the inflammatory response, reducing levels of the inflammatory cytokine IL-6, enhancing angiogenesis, and accelerating collagen deposition. The hydrogel showed complete biodegradation within 21 days in vivo without inducing a significant inflammatory response and significantly accelerated wound healing, achieving an 86% healing rate within 7 days compared to 67% in the control group. The PGA-PL composite hydrogel exhibits excellent mechanical strength and biocompatibility, and its effective wound-healing capabilities lay the groundwork for future development and optimization in various tissue engineering applications.
研究领域:
生物材料学
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医学
·
组织工程学
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产品关联
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2024
·
IF 3.8
Ting Liu,Zhentao Cheng,Derong Song,Erpeng Zhu,Hui Li,Rutao Lin,Zhiling Wan,Shunxing Liu,Zeguang Gong,Chunlan Shan
Mycoplasma gallinarum ( MG ) can cause infectious respiratory diseases in poultry that are chronic. Arbutin (AR) possesses anti-inflammatory, bacteriostatic, antitussive, and expectorant pharmacological effects, but whether it exerts regulatory effects on MG -induced pneumonia and fibrosis remains unclear. The study results unveiled that pulmonary connective tissue hyperplasia, pulmonary capillary congestion, and inflammatory cell infiltration, as well as serum levels of cytokines (i.e., TNF-α, IL-1β, IL-6, and IL-10), were elevated after MG infection. Collagen fibers were significantly deposited in the lung tissue from MG -infected chicks. Furthermore, the expression levels of key factors in the JAK2/STAT3 and TGF-β/Smad pathways markedly increased. AR intervention significantly alleviated MG -induced pneumonic injury, and reduced collagen deposition and the expression of fibrosis markers in the lung tissue. AR reduced the degree of pulmonary fibrosis by regulating key factors of the JAK2/STAT3 signaling pathway in the MG -infected HD11 cells. Thus, AR effectively reduced the expression of inflammatory factors by regulating the JAK2/STAT3 signaling pathway, thereby improving lung inflammation and fibrosis.
研究领域:
兽医学
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药理学
·
呼吸系统疾病
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）