BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2025
·
IF 2.2
Liting Wen,Xiaoxia Zeng,Zengping Lin,Peixiong Chen,Dapeng Zhao,Xianhai Zeng
Background Cholesteatoma is a benign epithelial lesion that affects the middle ear or mastoid process, causing otorrhea and hearing impairment. Currently, the pathogenesis of temporal bone injury in middle ear cholesteatoma remains elusive, hindering the development of effective treatment strategies. Methods and Results We examined the expression of transcription factor AP-2-beta (TFAP2B) and its downstream factor silent mating type information regulation 2 homolog 1 (SIRT1) in clinical samples from patients with middle ear cholesteatoma and analyzed the potential correlation between TFAP2B expression and clinical conditions. The findings revealed a significant down-regulation of TFAP2B and SIRT1 in patients diagnosed with middle ear cholesteatoma ( p < 0.01), and TFAP2B expression was negatively correlated with the clinical manifestations of hearing impairment and bone destruction. We further explored the role of TFAP2B in the differentiation of RAW 264.7 cells into osteoclasts induced by receptor activator of nuclear factor kappa B ligand (RANKL) in vitro . TFAP2B overexpression significantly inhibited, while TFAP2B knockdown promoted osteoclast differentiation of RAW264.7 cells. Further investigation suggested that TFAP2B positively regulated SIRT1 ( p <0.01) and negatively regulated NF-κB activation. Finally, we demonstrated that TFAP2B transcriptionally regulated SIRT, which inhibited the activation of the NF-κB signaling pathway by reducing the acetylation level of the p65 subunit, thereby suppressing osteoclast differentiation. Conclusions TFAP2B/SIRT1 plays a crucial role in regulating osteoclast differentiation in middle ear cholesteatoma. The downregulation of TFAP2B/SIRT1 triggers enhanced osteoclast differentiation, which may contribute to one of the mechanisms underlying bone destruction in middle ear cholesteatoma.
研究领域:
医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Lin Ye,Congcong Yu,Jiechao Xia,Kainan Ni,Yejin Zhang,Xiaozhang Ying,Dingqi Xie,Yang Jin,Rongtai Sun,Ruikang Tang,Shunwu Fan,Shasha Yao
Reactive Oxygen Species (ROS) refers to a highly reactive class of oxidizing species that have the potential to induce cellular apoptosis and necrosis. Cuproptosis, a type of cell death, is primarily associated with the effects of copper ions. However, the specific relationship between ROS, cuproptosis, and osteosarcoma (OS) remains relatively unexplored. Additionally, there is limited research on the use of cuproptosis in conjunction with oxidative stress for treating OS and inhibiting tumor-induced bone destruction. To address these gaps, a novel treatment approach has been developed for OS and neoplastic bone destruction. This approach involves the utilization of glutathione (GSH) and pH-responsive organic-inorganic mesoporous silica nanoparticles@Cu 2 S@oxidized Dextran (short for MCD). The MCD material demonstrates excellent cytocompatibility, osteogenesis, tumor suppression, and the ability to inhibit osteoclast formation. The specific mechanism of action involves the mitochondria of the MCD material inhibiting key proteins in the tricarboxylic acid (TCA) cycle. Simultaneously, the generation of ROS promotes this inhibition and leads to alterations in cellular energy metabolism. Moreover, the MCD biomaterial exhibits promising mild-temperature photothermal therapy in the second near-infrared (NIR-II) range, effectively mitigating tumor growth and OS-induced bone destruction in vivo .
研究领域:
肿瘤学
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生物医学工程
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2023
·
IF 15.1
Huiyun Li,Yusong Yuan,Lingpu Zhang,Chun Xu,Hailin Xu,Zhiwei Chen
Osteoarthritis (OA) is a chronic joint disease characterized by synovitis and joint cartilage destruction. The severity of OA is highly associated with the imbalance between M1 and M2 synovial macrophages. In this study, a novel strategy is designed to modulate macrophage polarization by reducing intracellular reactive oxygen species (ROS) levels and regulating mitochondrial function. A ROS-responsive polymer is synthesized to self-assemble with astaxanthin and autophagy activator rapamycin to form nanoparticles (NP@Poly RHAPM ). In vitro experiments show that NP@Poly RHAPM significantly reduced intracellular ROS levels. Furthermore, NP@Poly RHAPM restored mitochondrial membrane potential, increased glutathione (GSH) levels, and promoted intracellular autophagy, hence successfully repolarizing M1 macrophages into the M2 phenotype. This repolarization enhanced chondrocyte proliferation and vitality while inhibiting apoptosis. In vivo experiments utilizing an anterior cruciate ligament transection (ACLT)-induced OA mouse model revealed the anti-inflammatory and cartilage-protective effects of NP@Poly RHAPM , effectively mitigating OA progression. Consequently, the findings suggest that intra-articular delivery of ROS-responsive nanocarrier systems holds significant promise as a potential and effective therapeutic strategy for OA treatment.
研究领域:
药理学
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生物医学工程
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骨科
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免疫学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
BULLETIN DU CANCER
·
2023
·
IF 1.2
Siyan Zhang,Xingyao Zhang,Dong Zhang,Liang Wei,Bin Xiong,Qi Meng,Shougang Jiang
Summary Introduction Gambogic acid (GA) as an active compound isolated from Gamboge, have been investigated for many years and proved to be a promising natural anticancer agent for clinical treatment . This study aimed to investigate the inhibitory effect of docetaxel (DTX) combined with gambogic acid on bone metastasis of lung cancer. Methods The anti-proliferation effect of the combination of DTX and GA on Lewis lung cancer (LLC) cells was determined by MTT assays . The anticancer effect of the combination of DTX and GA on bone metastasis of lung cancer in vivo was explored. Evaluation of the efficacy of drug therapy was performed by comparing the degree of bone destruction and the pathological section of bone tissue of the treated mice with that of the control mice. Results In vitro cytotoxicity, cell migration, and osteoclast-induced formation assay showed that GA enhanced the therapeutic effect of DTX in Lewis lung cancer cell with a synergistic effect. In an orthotopic mouse model of bone metastasis, the average survival of the DTX + GA combination group (32.61d ± 1.06 d) was significantly increased compared with that of the DTX group (25.75 d ± 0.67 d) or GA group (23.99 d ± 0.58 d), * P < 0.01. Conclusion The combination of DTX and GA has synergistic effect and resulted in more effective inhibition of tumor metastasis , providing a strong preclinical rationale for the clinical development of the DTX + GA combination for treating bone metastasis of lung cancer.
研究领域:
肿瘤学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2024
·
IF 4.7
Kumar Ganesan,Cong Xu,Chunguang Xie,Yue Sui,Chuan Zheng,Fei Gao,Jianping Chen
Breast cancer (BC) is the most common cancer in women and is known for its tendency to spread to the bones, causing significant health issues and mortality. In this study, we aimed to investigate whether cryoprotective isoliquiritigenin-zein phosphatidylcholine nanoparticles (ISL@ZLH NPs) could inhibit BC-induced bone destruction and tumor metastasis in both in vitro and animal models. To evaluate the potential of ISL@ZLH NPs, we conducted various experiments. First, we assessed cell viability, colony formation, transwell migration, and wound healing assays to determine the impact of ISL@ZLH NPs on BC cell behavior. Western blotting, TRAP staining and ALP activity were performed to examine the effects of ISL@ZLH NPs on osteoclast formation induced by MDA-MB-231 cell-conditioned medium and RANKL treated RAW 264.7 cells. Furthermore, we assessed the therapeutic impact of ISL@ZLH NPs on tumor-induced bone destruction using a mouse model of BC bone metastasis. Treatment with ISL@ZLH NPs effectively suppressed BC cell proliferation, colony formation, and motility, reducing their ability to metastasize. ISL@ZLH NPs significantly inhibited osteoclast formation and the expression of factors associated with bone destruction in BC cells. Additionally, ISL@ZLH NPs suppressed JAK-STAT signaling in RAW264.7 cells. In the BCBM mouse model, ISL@ZLH NPs led to a significant reduction in osteolytic bone lesions compared to the control group. Histological analysis and TRAP staining confirmed that ISL@ZLH NPs preserved the integrity of bone structure, preventing invasive metastasis by confining tumor growth to the bone marrow cavity. Furthermore, ISL@ZLH NPs effectively suppressed tumor-induced osteoclastogenesis, a key process in BC-related bone destruction. Our findings demonstrate that ISL@ZLH NPs have the potential to inhibit BC-induced bone destruction and tumor metastasis by targeting JAK-STAT signaling pathways and suppressing tumor-induced osteoclastogenesis. These results underscore the therapeutic promise of ISL@ZLH NPs in managing BC metastasis to the bones.
研究领域:
肿瘤学
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药理学
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纳米技术
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2022
·
IF 9.417
Bo Chen,Jibing Wang,Xing Jin,Xin Wang,Zhangling Fan,Yuxin Zhang,Xuehan Sang,Zhaoxiang Meng
In the macrophage-specific mTORC1 signaling activation model, the synovial macrophages polarized toward M1, thus aggravating synovitis and progression of OA. Therefore, intra-articular injection of rapamycin, a classical mTORC1 inhibitor, may show great potential for alleviating synovitis and delaying cartilage destruction in osteoarthritis (OA). However, the durable retention of drugs in the joint cavity is still a critical issue to be addressed. Herein, we crosslinked the Poloxamer 407 and hyaluronic acid (P-HA) to prepare an injectable and thermo-responsive drug delivery system to durably retain rapamycin and dramatically magnify their therapeutic effects in OA management. The prepared P-HA hydrogel showed excellent biocompatibility with chondrocytes and fibroblasts, as well as possessed sustained rapamycin release profiles for 14 days. Intra-articular injection of this rapamycin-incorporated P-HA hydrogel indicated a positively effect on inducing the polarization of synovial macrophages from M1 to M2 phenotype and reducing synovial inflammation in OA. This strategy significantly decreased the pro-inflammatory cytokines ( e.g. , TNF-α, IL-1β, and IL-6) and increased the anti-inflammatory cytokine ( e.g. , IL-10) expression in the synovial tissues and synovial fluid. As a result, intra-articular injection of rapamycin-incorporated P-HA hydrogel significantly prevented cartilage destruction by inducing cartilage matrix formation, which suggesting a great potential for the management of OA.
研究领域:
药理学
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生物医学工程
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骨科
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免疫学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
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2018
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IF 4.556
Kaili Wang,Chunjing Guo,Xue Dong,Yueming Yu,Bingjie Wang,Wanhui Liu,Daquan Chen
Many cancers, such as human breast cancer and lung cancer, easily metastasize to bones, leading to the formation of secondary tumors in advanced stages. On the basis of the CD44-targeted effect of oHA and the bone-targeted effect of ALN, we prepared a reduction-responsive, CD44 receptor-targeting and bone-targeting nanomicelle, called CUR-loaded ALN-oHA-S-S-CUR micelles. In this study, we aimed to evaluate the antitumor activity and bone-targeting ability of CUR-loaded ALN-oHA-S-S-CUR micelles. The in vivo experiment results showed that a larger number of micelles was gathered in the bone metastatic tumor tissue and reduced the bone destruction. The CUR-loaded ALN-oHA-S-S-CUR micelles markedly inhibited the tumor growth. So the CUR-loaded ALN-oHA-S-S-CUR micelles constitute a promising drug delivery system for bone tumor therapy.
研究领域:
药学
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癌症研究
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纳米技术
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Advances
·
2022
·Vol. 8
·期 40
·
IF 14.957
Bin Zhao,Lingting Zeng,Danyang Chen,Songqing Xie,Zhaokui Jin,Guanglin Li,Wei Tang,Qianjun He
Synovial microenvironment (SME) plays a vital role in the formation of synovial pannus and the induction of cartilage destruction in arthritis. In this work, a concept of the photocatalytic regulation of SME is proposed for arthritis treatment, and monodispersive hydrogen–doped titanium dioxide nanorods with a rutile single-crystal structure are developed by a full-solution method to achieve near infrared–photocatalytic generation of hydrogen molecules and simultaneous depletion of overexpressed lactic acid (LA) for realizing SME regulation in a collagen-induced mouse model of rheumatoid arthritis. Mechanistically, locally generated hydrogen molecules scavenge overexpressed reactive oxygen species to mediate the anti-inflammatory polarization of macrophages, while the simultaneous photocatalytic depletion of overexpressed LA inhibits the inflammatory/invasive phenotypes of synoviocytes and macrophages and ameliorates the abnormal proliferation of synoviocytes, thereby remarkably preventing the synovial pannus formation and cartilage destruction. The proposed catalysis-mediated SME regulation strategy will open a window to realize facile and efficient arthritis treatment.
研究领域:
生物医学工程
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材料科学
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风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Ying Chen,Yonglin Wang,Xianfang Jiang,Jinhong Cai,Yuting Chen,Hanji Huang,Yuan Yang,Li Zheng,Jinmin Zhao,Ming Gao
Excessive cell-free DNA (cfDNA) released by damaged or apoptotic cells can cause inflammation, impacting the progression of rheumatoid arthritis (RA). cfDNA scavengers, such as cationic nanoparticles (NPs), have been demonstrated as an efficient strategy for treating RA. However, most scavengers are limited by unfavorable biocompatibility and poor scavenging efficacy. Herein, by exploiting the favorable biocompatibility, biodegradability and bioadhesion of polydopamine (P), we modified P with dimethylamino groups to form altered charged DPs to bind negatively charged cfDNA for RA therapy. Results showed that DPs endowed with superior binding affinity of cfDNA and little cytotoxicity, which effectively inhibited lipopolysaccharide (LPS) stimulated inflammation in vitro , resulting in the relief of joint swelling, synovial hyperplasia and cartilage destruction in RA rats. Significantly, DPs with higher DS of bis dimethylamino group exhibited higher positive charge density and stronger cfDNA binding affinity, leading to excellent RA therapeutic effect among all of the treated groups, which was even close to normal rats. These finding provides a novel strategy for the treatment of cfDNA-associated diseases.
研究领域:
纳米技术
·
药学
·
风湿病学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Yaping Shen,Yang Zou,Binglin Bie,Chanjuan Dong,Yonggang Lv
Although mild photothermal therapy (mild-PTT) avoids treatment bottleneck of the traditional PTT, the application of mild-PTT in deep and internal tumors is severely restricted due to thermal resistance, limited irradiation area and penetration depth. In addition, bone resorption caused by tumor colonization in distal bone tissue exacerbates tumor progression. Here, a strategy was developed for the treatment of bone metastasis and alleviation of bone resorption, which was based on liquid metal (LM) nanoparticle to resist thermal resistance induced by mild-PTT via autophagy activation. Briefly, LM and autophagy activator (Curcumin, Cur) were loaded into zeolitic imidazolate framework-8 (ZIF-8), which was then functionalized with hyaluronic acid/alendronate (CLALN). CLALN exhibited good photothermal performance, drug release ability under acidic environment, specifical recognition and aggregation at bone metastasis sites. CLALN combined with mild-PPT dramatically inhibited tumor progress by inducing the impaired autophagy and reduced the expression of programmed cell death ligand 1 (PD-L1) protein triggered by mild-PTT, resisting thermal resistance and alleviating the immunosuppression. Besides, CLALN combined with mild-PPT effectively alleviated osteolysis compared with only CLALN or mild-PPT. Our experiments demonstrated that this multi-functional LM-based nanoparticle combined with autophagy activation provided a promising therapeutic strategy for bone metastasis treatment. Statement of significance Due to the limited light penetration, photothermal therapy (PTT) has limited inhibitory effect on tumor cells colonized in the bone. In addition, nonspecific heat diffusion of PTT may accidentally burn normal tissues and damage peripheral blood vessels, which can block the accumulation of drugs in deep tumors. Here, a multifunctional liquid metal based mild-PTT delivery system is designed to inhibit tumor growth and bone resorption by modulating the bone microenvironment and activating autophagy “on demand”. It can overcome the treatment bottleneck of traditional PTT and improve the treatment effect of mild-PTT by resisting photothermal resistance and immune suppression. In addition, it also exhibits favorable heat/acid-responsive drug release performance and can specifically target tumor cells at the site of bone metastases.
研究领域:
癌症治疗
·
纳米技术
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生物医学工程
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药学
·
光热疗法
·
骨转移
✓ 已验证
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）