INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Xueting Wang,Jing Yang,Qimeng Zhao,Xianchang Xie,Fuling Deng,Ziyi Wang,Kunpeng Jiang,Xiaoming Li,Hu Liu,Zhenhao Shi,Xu Zhu,Lei Chen,Dalun Lv
Macromolecule hydrogels made from natural extracts have received much attention because of their favorable biocompatibility and wound healing properties. However, their clinical applications are limited by their insufficient mechanical strength and low adhesion properties. To overcome these limitations, we developed a novel injectable Aloe vera hydrogel (PDMA-GelMA@AV). By integrating gelatin methacrylate (GelMA) and polydopamine methacrylamide (PDMA), we significantly improved the mechanical and adhesion properties of the hydrogel. The PDMA-GelMA@AV hydrogel degraded in a simulated wound environment, which was synchronized with the sustained release of the bioactive components of A. vera . In vitro and in vivo analyses revealed that this hydrogel has good biocompatibility. In vitro studies also revealed that the sustained release of the active ingredients of A. vera promoted fibroblast proliferation and migration and increased the expression of key proteins and mRNAs required for wound healing. In addition, it modulated LPS-stimulated macrophages and decreased the expression of TNF-α, IL-1β and iNOS while increasing the expression of TGF-β and ARG. In vivo experiments further confirmed the efficacy of hydrogels in wound healing applications. These findings offer a novel perspective on the application of natural macromolecules as hydrogel-based delivery vehicles in wound care.
研究领域:
生物医学工程
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材料科学
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伤口愈合
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药剂学
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生物材料
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产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2023
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IF 6.2
Xue-Yun Chen,Si-Ning Feng,Yin Bao,Yu-Xin Zhou,Fang Ba
Parkinson's disease (PD) is a neurodegenerative disease. Repetitive transcranial magnetic stimulation (rTMS) is a therapeutic tool in PD. High-throughput sequencing was performed to screen potential therapeutic targets in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. The candidate gene, Clec7a, was screened out and validated. Clec7a is a pattern recognition receptor involved in neuroinflammation. The higher expression of Clec7a was observed in the substantia nigra (SN) and striatum of PD rats with dopaminergic neurons damage and was mainly localized in the microglial. Adeno-associated virus (AAV)-mediated specific knockdown of Clec7a in microglial alleviated 6-OHDA induced motor deficits and nigrostriatal dopaminergic neuron damage of rats, as evidenced by the increase of tyrosine hydroxylase (TH) -positive neurons in SN, as well as dopaminergic nerve fibers in the striatum. Clec7a knockdown restrained the neuroinflammation by suppressing inflammatory factors (IFN-γ, TNF-α, IL-1β, IL-18, and IL-6) release in SN, which might result from enhanced Arg-1 expression (M2 polarization) and defective inducible nitric oxide synthase (iNOS) expression (M1 polarization). The same phenomena were also observed in the LPS inflammatory rat model of PD. In vitro, α-synuclein fibrils induced upregulation of Clec7a expression and microglia polarization to a pro-inflammatory state of BV2 cells, leading to increased release of cytokines. However, Clec7a knockdown reversed those changes and induced a shift to an anti-inflammatory phenotype in BV2 cells. In conclusion, our study suggested that Clec7a was involved in PD pathogenesis, and its inhibition might protect rats from PD by depressing neuroinflammation through microglial polarization.
研究领域:
神经科学
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神经退行性疾病
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治疗干预
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炎症
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Translational Oncology
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2023
·
IF 5
Jiale Cai,Guiping Hu,Lihua Hu,Junge Chen,Dan Chen,Dan Liu,Xiaolei Wang,Boxian Hu,Cheng Li
Introduction Sonodynamic therapy (SDT) has potential clinical applications for cancer therapy, and is yet restricted by complex tumor microenvironmental (TME) factors. Thus, the research problem of TME modulation as well as efficient tumor treatment still needs to be clarified. Method In this study, a calcium carbonate (CaCO 3 ) nanoplatform was designed for ultrasound (US) and TME response-triggered, which encapsulated Ag 2 S and loaded with l -Arg, and further wrapped with RBC/Platelet membrane, named as QD@Ca/M L-Arg . Results Non-invasive US-triggered SDT by Ag 2 S and acidic environment-responsive drug release were achieved. In vitro experiments validated the efficacy of SDT, Ca-ion interference and nitric oxide (NO) gas therapy as combined therapy for cancer treatment. By means of RNA sequencing, the cancer therapeutic mechanism of SDT in redox-related pathways was elucidated. The immunosuppressive TME was simulated with a M2-macrophage/cancer cell co-culture system to confirm the immune activating effect of immunogenic cell death (ICD). Conclusion Accordingly, the potential of QD@Ca/M L- Arg- was demonstrated for in vitro TME modulation, cancer therapeutic efficacy and clinical translation.
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2025
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IF 9.6
Yuanqi Chen,Kezheng Lei,Yinxi Li,Zhixiang Mu,Tengda Chu,Jiajun Hu,Bairui Zeng,Yi Wang,Jianliang Shen,Xiaojun Cai,Tianpeng Shi,Hui Deng
Oral mucosal wounds are more prone to inflammation due to direct exposure to various microorganisms. This can result in pain, delayed healing, and other complications, affecting patients' daily activities such as eating and speaking. Consequently, the overall quality of life for patients is significantly reduced. To address these challenges, we developed a multifunctional therapeutic nanoplatform, DATS@Arg-EA-SA, through the self-assembly of guanidinated dendritic peptides (Arg-EA-SA) that encapsulate diallyl trisulfide (DATS), a hydrogen sulfide (H 2 S) donor. The guanidine-rich surface of DATS@Arg-EA-SA efficiently neutralizes reactive oxygen species (ROS) in the ulcer microenvironment, generating nitric oxide (NO), which acts as the primary antimicrobial agent by disrupting bacterial membranes. Concurrently, the presence of glutathione triggers the release of H 2 S from DATS, providing supplementary antibacterial support. DATS@Arg-EA-SA effectively kills all bacteria, achieving results comparable to those of penicillin, a classical antibiotic. Moreover, it demonstrates superior sterilization efficacy against drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), significantly outperforming penicillin. Following the initial antimicrobial phase, the nanoplatform transitions into an anti-inflammatory stage. H 2 S, in synergy with NO, facilitates the conversion of M1 macrophages to M2 macrophages, thereby reducing the expression of inflammatory factors. Importantly, the combination of H 2 S and NO provides effective analgesia by downregulating the expression of TRPV1 and TRPV4, thus restoring normal dietary behaviors and improving the overall quality of life. This system ultimately promotes collagen fiber deposition and accelerates the re-epithelialization of the ulcer wound, positioning DATS@Arg-EA-SA as a promising gas-delivery nanoplatform for rapid wound repair in the clinical treatment. Statement of Significance Oral mucosal wounds are highly susceptible to microbial infections, leading to inflammation, pain, delayed healing, and a significant decline in quality of life. We developed a multifunctional therapeutic nanoplatform (DATS@Arg-EA-SA) via the self-assembly of guanidinated dendritic peptides encapsulating the H 2 S donor DATS, which exhibited antibacterial, anti-inflammatory, and analgesic properties. In the oral ulcer microenvironment, DATS@Arg-EA-SA generates substantial NO under elevated ROS levels, while glutathione triggers the controlled release of H 2 S. NO disrupts bacterial membranes as the primary antibacterial agent, with H 2 S providing synergistic antibacterial effects. Furthermore, H 2 S and NO synergistically promote the transformation of M1 to M2 macrophages, attenuating inflammation. Importantly, the combined action of H 2 S and NO alleviates pain by downregulating TRPV1 and TRPV4, supporting the restoration of normal dietary behavior and improving quality of life.
研究领域:
药学
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纳米技术
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生物材料
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医学
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牙科
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炎症研究
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伤口愈合
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DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
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2023
·Vol. 29
·期 4
·1000-1011
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IF 5.5
Di Zhang,Bei Jing,Zhen-ni Chen,Xin Li,Hui-mei Shi,Ya-chun Zheng,Shi-quan Chang,Li Gao,Guo-ping Zhao
Introduction Sciatica causes intense pain. No satisfactory therapeutic drugs exist to treat sciatica. This study aimed to probe the potential mechanism of ferulic acid in sciatica treatment. Methods Thirty-two SD rats were randomly divided into 4 groups: sham operation, chronic constriction injury (CCI), mecobalamin, and ferulic acid. We conducted RNA sequencing, behavioral tests, ELISA, PCR, western blotting, and immunofluorescence analysis. TAK-242 and JSH23 were administered to RSC96 and GMI-R1 cells to explore whether ferulic acid can inhibit apoptosis and alleviate inflammation. Results RNA sequencing showed that TLR4/NF-κB pathway is involved in the mechanism of sciatica. CCI induced cold and mechanical hyperalgesia; destroyed the sciatic nerve structure; increased IL-1β, IL-6, TNF-α, IL-8, and TGF-β protein levels and IL-1β, IL-6, TNF-α, TGF-β, TLR4, and IBA-1 mRNA levels; and decreased IL-10 and INF-γ protein levels and IL-4 mRNA levels. Immunohistochemistry showed that IBA-1, CD32, IL-1β, iNOS, nNOS, COX2, and TLR4 expression was increased while S100β and Arg-1 decreased. CCI increased TLR4, IBA-1, IL-1β, iNOS, Myd88, p-NF-κB, and p-p38MAPK protein levels. Treatment with mecobalamin and ferulic acid reversed these trends. Lipopolysaccharide (LPS) induced RSC96 cell apoptosis by reducing Bcl-2 and Bcl-xl protein and mRNA levels and increasing Bax and Bad mRNA and IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK protein levels, while ferulic acid inhibited cell apoptosis by decreasing IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK levels and increasing Bcl-2 and Bcl-xl levels. In GMI-R1 cells, Ferulic acid attenuated LPS-induced M1 polarization by decreasing the M1 polarization markers IL-1β, IL-6, iNOS, and CD32 and increasing the M2 polarization markers CD206, IL-4, IL-10 and Arg-1. After LPS treatment, IL-1β, iNOS, TLR4, Myd88, p-p38MAPK, and p-NF-κB levels were obviously increased, and Arg-1 expression was reduced, while ferulic acid reversed these changes. Conclusion Ferulic acid can promote injured sciatic nerve repair by reducing neuronal cell apoptosis and inflammatory infiltration though the TLR4/NF-κB pathway.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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