Journal of Neuroinflammation
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2025
·Vol. 22
·期 1
·1-22
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IF 10.1
Zhou Yanjie,Chen Wu,Zhang Yu,Yang Liu,Lu Fu,Yan Wen,Xie Qingfang,Huang Ying,Huang Wanbin,Wang Lintao,Zeng Ziming,Xiao Zheman
Background Caveolin-1 (CAV1), a scaffolding protein critical for caveolae formation, regulates G-protein-coupled receptor (GPCR) signaling via caveolae-mediated endocytosis. The calcitonin receptor-like receptor (CLR), a GPCR and core subunit of the calcitonin gene-related peptide (CGRP) receptor, is a therapeutic target for migraine. However, the role of CAV1 in CLR regulation and migraine remains unclear.Methods A migraine model was established in female mice via dural inflammatory soup (IS) application. Migraine-like behaviors were assessed using Von Frey filament, spontaneous pain behavior counts, light/dark box, and acetone test. CAV1 was overexpressed by lentivirus and downregulated by small interfering RNA (siRNA) technology. Methyl-β-cyclodextrin (MβCD) was used to inhibit caveolae-mediated endocytosis. The molecular mechanism of CAV1 on CLR and neuroinflammation was investigated using biochemistry, multiplex immunohistochemistry staining, internalization assay, and co-immunoprecipitation.Results Repeated IS stimulation elevated CLR expression and internalization in the trigeminal nucleus caudalis (TNC), concurrently activating ERK/CREB signaling, promoting microglial activation, and increasing inflammatory cytokines (TNFα, IL-1β). CAV1 directly interacted with CLR, promoting its degradation. CAV1 knockdown in the TNC exacerbated migraine pathology, characterized by CLR accumulation, enhanced ERK/CREB phosphorylation, and amplified neuroinflammation. Conversely, CAV1 overexpression or MβCD-mediated caveolae disruption normalized CLR levels, reduced signaling hyperactivity, and reversed nociceptive behaviors.Conclusion CAV1 negatively regulates CLR stability, suppressing ERK/CREB signaling and microglial inflammation in a preclinical female migraine model. These findings suggest that CAV1 contributes to migraine-related hyperalgesia and may represent a novel therapeutic target for migraine treatment.
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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产品关联
DOI
PubMed
高影响因子
CLINICAL ORAL IMPLANTS RESEARCH
·
2014
·Vol. 26
·期 3
·332-341
·
IF 3.123
Nicolas Villard,Chaminda Seneviratne,James Kit Hon Tsoi,Markku Heinonen,Jukka Matinlinna
Objectives The aim of the present study was to evaluate the effect of novel silane system coatings on zirconia and titanium implant surfaces and the attachment of the fungal pathogen Candida albicans . Materials and methods Titanium and zirconia specimens were silica-coated and silanized either with a commercial silane primer (RelyX Ceramic Primer™, 3M ESPE) or a novel silane system primer. The novel silane system primer was a blend of 1.0 vol% 3-acryloxypropyltrimethoxysilane and 0.3 vol% bis-1,2-(triethoxysilyl)ethane diluted in acidified ethanol-water solvent. The surface roughness (R a ), the surface free energy and the chemical composition of substrate surfaces after treatments were evaluated. C. albcans biofilms were developed on silica-coated + silanized surfaces during 48 h of incubation time. Colony forming units (CFU) and real-time PCR (RT-PCR) quantified the cells on the material surfaces. Statistical analyses were carried out by 1-way ANOVA, Tukey post hoc and Games Howell post hoc test at 5% significance level (p) . Results On zirconia and titanium surfaces, the R a and the chemical composition of the specimens were equal ( P < 0.05). The surface free energy was decreased on titanium specimens and increased on zirconia specimen after silanization. CFU of C. albicans was significantly lower on zirconia coated with RelyX Ceramic Primer™, ( P < 0.001) and on titanium coated with both silanes ( P = 0.002). RT-PCR revealed no differences between the mean quantities of C. albicans ( P ≥ 0.067). Conclusion Silica-coating and silanization had modified the titanium and zirconia surfaces significantly. Both the control and experimental silane primers might inhibit the biofilm formation of C. albicans .
研究领域:
口腔医学
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微生物学
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材料科学
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产品关联
DOI
PubMed
高影响因子
CLINICAL ORAL IMPLANTS RESEARCH
·
2025
·
IF 5.3
Minghao Zuo,Heng Zhang,Jialu Lv,Yanyan Zhou,Zhijian Xie,Yiqun Zhou
Objectives This study aimed to develop a novel self-glazed zirconia (SZr) dental implant featuring micro/nano-roughened thread and polished neck, and to examine its properties both in vitro and in vivo. Material and Methods The micro/nano-roughened SZr surfaces (SZr-MN) were manufactured using sandblasting and chemical vapor deposition. Surface topography, elemental composition, roughness, and contact angle were systematically characterized. Streptococcus mutans and Porphyromonas gingivalis were used to evaluate bacterial adhesion. Bone marrow mesenchymal stem cells (BMSCs) and human immortalized keratinocytes were used to assess cell adhesion, proliferation, and osteogenic differentiation. The sandblasting large-grit acid-etching treated titanium (Ti) surfaces (Ti-SLA) served as the control. Ti and SZr implants were inserted into the mandibles of Beagle dogs, followed by radiological, fluorescent, and histomorphometric analyses after 8 and 12 weeks of healing. Results The SZr-MN surface exhibited micro-scale ravines and gullies densely covered with curled, sheet-like nano-structures, which led to suitable roughness and improved hydrophilicity. Compared to the Ti-SLA surface, the SZr-MN surface demonstrated significantly reduced bacterial adhesion, along with increased adhesion and osteogenic differentiation of BMSCs. Consequently, the SZr implant achieved more extensive and denser surrounding bone tissue and enhanced osseointegration compared to the Ti implant, while both showed comparable dimensions of peri-implant soft and hard tissues. Conclusions The novel SZr implant surfaces demonstrated excellent antibacterial activity, biocompatibility, and proosteogenic effect, leading to enhanced osseointegration and satisfactory soft tissue sealing. Our findings offer a unique perspective on improving the biological activity of zirconia dental implants.
研究领域:
牙科
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生物材料
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生物医学工程
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微生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
CLINICAL ORAL IMPLANTS RESEARCH
·
2019
·Vol. 30
·期 10
·1038-1048
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IF 3.825
Ying-juan Yu,Wen-qing Zhu,Li-na Xu,Pan-pan Ming,Shui-yi Shao,Jing Qiu
Objective This study aims to investigate the influence of fluoride exposure on implant osseointegration. Methods A total of 24 male New Zealand white rabbits were randomly divided into the control group and the fluoride exposure group. Rabbits in the control group were fed with tap water, while those in the fluoride exposure group were given 200 mg/L sodium fluoride solution. After 2-month feeding, implants were inserted into the extraction socket immediately after extraction of rabbit mandibular anterior teeth. Four rabbits in each group were sacrificed to collect the implants samples at 1, 2, and 3 months post-implantation, respectively. Radiographic and histomorphometry examinations were performed to evaluate the condition of implant osseointegration. Results Bone volume around the implants increased in a time-dependent manner in both groups. Micro-CT images illustrated that the bone mineral density (BMD) in the fluoride exposure group was significantly lower than that in the control group after implantation for 2 and 3 months. The bone–implant contact ratio (BIC) in the fluoride exposure group was much lower than that of the control group at 3 months post-implantation according to histomorphometry examination. Conclusions In rabbit animal model, high fluoride exposure affected the quality of bone surrounding the implant and significantly reduced bone integration of the implant, especially in the late stage of osseointegration.
研究领域:
口腔医学
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生物材料学
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DOI
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Jinpeng Yao,Yu Chen,Liang Zhang,Yuancun Cheng,Zheng Chen,Yanhui Zhang,Xiaoyi Zheng,Yanwei Lv,Shige Wang,Zhaoshen Li,Jiulong Zhao
The clinical treatment of inflammatory bowel disease (IBD) is challenging. We developed copper sulfate (CuS)/disulfiram (DSF)/methacrylic acid-ethyl acrylate copolymer (EL)/polyvinylpyrrolidone (PVP) nanoplatform (CuS/DSF/EL/PVP) and evaluated its efficiency for treating IBD. After oral administration, the pH-sensitive EL protected the CuS/DSF/EL/PVP against degradation by acidic gastric juices. Once the colon was reached, EL was dissolved, releasing DSF and Cu 2+ . Further, the main in vivo metabolite of DSF can bind to Cu 2+ and form copper (II) N, N-diethyldithiocarbamate (CuET), which significantly alleviated acute colitis in mice. Notably, CuS/DSF/EL/PVP outperformed CuS/EL/PVP and DSF/EL/PVP nanoplatforms in reducing colonic pathology and improving the secretion of inflammation-related cytokines (such as IL-4 and IL-10) in the colonic mucosa. RNA-seq analysis revealed that the nanoplatform reduced colonic inflammation and promoted intestinal mucosal repair by upregulating C-type lectin receptor (CLR)-related genes and signaling pathways. Furthermore, CuS/DSF/EL/PVP showed potential for improving colitis Th1/Th17 cells through innate immunity stimulation, down-regulation of inflammatory cytokines, and upregulation of anti-inflammatory cytokines. Additionally, the intervention with CuS/DSF/EL/PVP led to increased intestinal flora diversity, decreased Escherichia–Shigella abundance, and elevated levels of short-chain fatty acid (SCFA)-producing bacteria Prevotella, Lactobacillus , and Bifidobacterium , indicating their potential to modulate the dysregulated intestinal flora and suppress inflammation. Statement of Significance Our study introduces the CuS/DSF/EL/PVP nanoplatform as a therapeutic strategy for treating inflammatory bowel disease (IBD). This approach demonstrates significant efficacy in targeting the colon and alleviating acute colitis in mice. It uniquely modulates gut immunity and microbiota, exhibiting a notable impact on inflammation-related cytokines and promoting intestinal mucosal repair. The nanoplatform's ability to regulate gut flora diversity, combined with its cost-effective and scalable production, positions it as a potentially transformative treatment for IBD, offering new avenues for personalized medical interventions.
研究领域:
药学
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纳米技术
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胃肠病学
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免疫学
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微生物学
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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）