JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2025
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IF 4.9
Yuling Wang,Jun Deng,Xi Wang,Dan Luo,Shujing Ren,Xueping Guo,Dan Chen,Rui Liu,Siyuan Chen,Wei Liu
Adjuvant skincare formulations possessing anti-inflammatory and antibacterial properties can alleviate treatment-related side effects and enhance patient adherence in acne management. Paeonol (PAE), totarol (TOT), and ergothioneine (ERG) demonstrate promising anti-acne activity. However, their clinical translation is hindered by poor solubility, limited stability, and insufficient skin permeation. To address these limitations, we co-encapsulated PAE, TOT, and ERG into hyaluronic acid (HA)-modified nanoliposomes (NLPs). Compared to the NLPs modified with HA with high molecular weights, those formulated with miniHA (3-10 kD a ) exhibited superior skin penetration capability and cellular uptake efficiency. The miniHA modified NLPs co-encapsulated PAE, TOT, and ERG (PTE-NLPs) exhibited excellent biocompatibility in both in vitro cytotoxicity assay and chicken embryo chorionic allantoic membrane irritation assays. Compared to free functional ingredients, PTE-NLPs demonstrated significantly enhanced anti-inflammatory and antibacterial efficacy in cellular assays. Furthermore, in 3D skin models, PTE-NLPs suppressed Transient Receptor Potential Vanilloid 1 (TRPV1) expression, indicating a potential mechanism for attenuating neuronal hyperreactivity. The anti-inflammatory activity was subsequently validated in vivo. These findings collectively demonstrate that miniHA-modified NLPs provide a safe and efficient platform for co-delivering synergistic anti-acne actives, highlighting their strong potential as an adjuvant therapy for acne management.
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高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2024
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IF 4.2
Bin Wang,Wei Wang,Jingyu Li,Jianjun Li
The molecular mechanism underlying the promotion of fracture healing by mechanical stimuli remains unclear. The present study aimed to investigate the role of zinc finger protein 36 like 2 (ZFP36L2)-histone deacetylase 1 (HDAC1) axis on the osteogenic responses to moderate mechanical stimulation. Appropriate stimulation of fluid shear stress (FSS) was performed on MC3T3-E1 cells transduced with ZFP36L2 and HDAC1 recombinant adenoviruses, aiming to validate the influence of mechanical stress on the expression of ZFP36L2-HDAC1 and the osteogenic differentiation and mineralization. The results showed that moderate FSS stimulation significantly upregulated the expression of ZFP36L2 in MC3T3-E1 cells ( p < 0.01). The overexpression of ZFP36L1 markedly enhanced the levels of osteogenic differentiation markers, including bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), Osterix, and collagen type I alpha 1 (COL1A1) ( p < 0.01). ZFP36L2 accelerated the degradation of HDAC1 by specifically binding to its 3’ UTR region, thereby fulfilling its function at the post-transcriptional regulatory gene level and promoting the osteogenic differentiation and mineralization fate of cells. Mechanical unloading notably diminished/elevated the expression of ZFP36L2/HDAC1, decreased bone mineral density and bone volume fraction, hindered the release of osteogenic-related factors and vascular endothelial growth factor in callus tissue ( p < 0.01), and was detrimental to fracture healing. Collectively, proper stress stimulation plays a crucial role in facilitating osteogenesis through the promotion of ZFP36L2 and subsequent degradation of HDAC1. Targeting ZFP36L2-HDAC1 axis may provide promising insights to enhance bone defect healing.
研究领域:
骨科
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分子生物学
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细胞生物学
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生物力学
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DOI
PubMed
高影响因子
Small
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2025
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IF 12.1
Qi Wu,Mingyang Liu,Hui Zhang,Guanghao Li,Ziqing Yang,Xiaodan Wu,Guanghui Tan,Chenfeng Ji,Yingxue Jin
At present, tumor immune escape is a major problem in the treatment of tumors. The complex network of tumor microenvironments significantly impairs the efficacy of immunotherapy. This paper reports the preparation and immunoantitumor activity of a novel multifunctional defect tungsten trioxide@ferrocene-folic acid composite (WO 3-x @Fe-FA) with a high Fenton reaction rate. Ferrocene is modified on the surface of defective trioxide by the covalent coupling method for the first time, and the reaction rate of Fenton is increased by 10 times. WO 3-x @Fe-FA induces immunogenic cell death (ICD) through the powerful synergistic anti-tumor effect of PTT/CDT and decomposes H 2 O 2 to produce oxygen through the Fenton reaction, thus down-regulating the expression of immune checkpoint PD-L1 induced by tumor hypoxia. In vitro and in vivo experiments proved that WO 3-x @Fe-FA reverses the immunosuppressive tumor microenvironment, transforms the immunosuppressive “cold tumor” into the immune “hot tumor”, and activates the immune activity of the system. In vitro and in vivo experiments show that WO 3-x @Fe-FA has excellent immunoantitumor activity, and it is expected to be a candidate drug for immunoantitumor therapy.
研究领域:
肿瘤学
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免疫学
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材料科学
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DOI
PubMed
高影响因子
Cancer Communications
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2025
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IF 24.9
Jie Zhang,Chen Zhang,Ruichen Zang,Weiwu Chen,Yining Guo,Haofei Jiang,Jing Le,Kunyu Wang,Haobo Fan,Xudong Wang,Sisi Mo,Peng Gao,Wenhao Guo,Xinrong Jiang,Fengbin Gao,Junming Jiang,Juyan Zheng,Yuxing Chen,Yicheng Chen,Yanlan Yu,Guoqing Ding
Background: Only a few bladder cancer patients benefit from anti-programmed cell death protein 1/programmed cell death ligand 1 immunotherapy. The cluster of differentiation 47 (CD47) plays an important role in tumor immune evasion. CD47 is a highly glycosylated protein, however, the mechanisms governing CD47 glycosylation and its potential role in immunosuppression are unclear. Therefore, this study aimed to evaluate the function of CD47 glycosylation in bladder cancer. Methods: Western blotting, immunohistochemistry, and flow cytometry were used to measure protein expression, protein-protein interactions, and phagocytosis in bladder cancer. A murine model was employed to investigate the impact of mannosidase alpha class 1B member 1 (MAN1B1) modification of CD47 on anti-phagocytosis in vivo. An ex vivo model, patient-derived tumor-like cell clusters, was used to examine the effect of targeting MAN1B1 on phagocytosis. Results: Our research identified that aberrant CD47 glycosylation was responsible for its immunosuppression. The glycosyltransferase MAN1B1 responsible for CD47 glycosylation was highly expressed in bladder cancer. Abnormal activation of extracellular signal-regulated kinase (ERK) was significantly associated with MAN1B1 stability by regulating the interaction between MAN1B1 and the E3 ubiquitin ligase HMG-CoA reductase degradation 1 (HRD1). Mechanistically, abnormally activated ERK stabilized MAN1B1, resulting in the glycosylation of CD47 and facilitating immune evasion by enhancing its interaction with signal-regulatory protein alpha (SIRP-α). In vitro and in vivo experiments demonstrated that MAN1B1 knockout weakened CD47-mediated anti-phagocytosis. MAN1B1 inhibitors promoted phagocytosis without causing anemia, offering a safe alternative to anti-CD47 therapy. Conclusions: This comprehensive analysis uncovered that ERK activation stabilizes MAN1B1 by regulating the interaction between MAN1B1 and HRD1, facilitates immune evasion via CD47 glycosylation, and presents new potential targets and strategies for cancer immunotherapy that do not cause anemia.
研究领域:
肿瘤学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
American Journal of Cancer Research
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2021
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IF 6.166
Xinwei Liu,Dulei Xiang,Chong Xu,Ruonan Chai
EIF3m is the latest identified subunit of the eukaryotic translation initiation factor 3 (eIF3), however, its function in malignant tumor is rarely reported. In the current work, we observed that EIF3m was aberrant over-expressed in lung adenocarcinoma (LADC) tissues and cell lines, and the increased EIF3m level was closely related to the poor clinical outcomes of the LADC patients. The gain- and loss-of-function assays demonstrated the proto-oncogenetic potential of EIF3m in vitro and in vivo . EIF3m induced-malignant phenotype was partly mediated by the up-regulation of CAPRIN1. The biochemical analysis showed that EIF3m could bind to the 5’UTR of CAPRIN1 and positively modulate its expression at the post-transcription level. Furthermore, we identified the interaction between EIF3m and the deubiquitinase UCHL5, which stabilized and promoted the accumulation of EIF3m in LADC cells. In summary, our findings extended the knowledge about the EIF3m function and highlight the roles of the UCHL5/EIF3m/CAPRIN1 axis during the progression of LADC.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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DOI
PubMed
高影响因子
BIOLOGICAL PROCEDURES ONLINE
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2024
·Vol. 26
·期 1
·1-18
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IF 3.7
Meng Xiangchao,Chen Hongye,Tan Zhihui,Yan Weitao,Liu Yinfeng,Lv Ji,Han Meng
Abstract Breast cancer is the most common female malignancy worldwide. Ubiquitin-specific peptidase 53 (USP53) has been shown to exert cancer-suppressing functions in several solid tumors, but its role and the underlying mechanism in breast cancer has not been clearly elucidated. Therefore, we have carried out a series of detailed studies on this matter at the levels of bioinformatics, clinical tissue, cell function and animal model. We found that USP53 expression was downregulated in breast cancer specimens and was negatively correlated with the clinical stages. Gain- and loss-of-function experiments demonstrated USP53 inhibited proliferation, clonogenesis, cell cycle and xenograft growth, as well as induced apoptosis and mitochondrial damage of breast cancer cells. Co-immunoprecipitation data suggested that USP53 interacted with zinc finger MYND-type containing 11 (ZMYND11), and catalyzed its deubiquitination and stabilization. The 33–50 amino acid Cys-box domain was key for USP53 enzyme activity, but not essential for its binding with ZMYND11. The rescue experiments revealed that the anti-tumor role of USP53 in breast cancer cells was at least partially mediated by ZMYND11. Both USP53 and ZMYND11 were prognostic protective factors for breast cancer. USP53-ZMYND11 axis may be a good potential biomarker or therapeutic target for breast cancer, which can provide novel insights into the diagnosis, treatment and prognosis.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
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DOI
PubMed
高影响因子
FEBS Journal
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2024
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IF 5.5
Yaqing Li,Xiyang Liu,Yulai Li,Jieting Wang,Mengqian Zhang,Weili Xue,Mingzhi Zhang
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and is associated with a poor prognosis. Data from the Gene Expression Profiling Interactive Analysis (GEPIA) database revealed dysregulated expression of several ubiquitin-specific proteases (USPs) in DLBCL tissues (DLBCL vs. non-DLBCL = 47 vs. 337), including USP19 (log 2 fold change = 1.17, P < 0.05). USP19 is closely linked to tumorigenesis, but its role in DLBCL progression remains largely unknown. Here, we investigated the role of USP19 in DLBCL development. Genetic manipulation of USP19 using adenovirus-based vectors was performed in two DLBCL cell lines, SUDHL4 and DB cells. The results showed that USP19 knockdown suppressed the proliferation, anchorage-independent growth and xenograft tumor formation of DLBCL cells and arrested the cell cycle at the G1 stage. In parallel, DLBCL cells overexpressing USP19 acquired a more malignant phenotype. Next, to explore USP19 interactors, we performed co-immunoprecipitation/liquid chromatography–mass spectrometry and identified potential interacting proteins. Among them, Parkinson disease protein 7 (PARK7), a member of the peptidase C56 family known to be involved in carcinogenesis, was further validated to bind with and be stabilized by USP19. Additionally, we found that USP19 induced PARK7 deubiquitylation in both DLBCL cell lines, and PARK7 acted as a downstream effector of USP19 in regulating the growth of DLBCL cells. Collectively, USP19 exerts a tumor-promoting role in DLBCL through interacting with and stabilizing PARK7.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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PubMed
高影响因子
EXPERIMENTAL ANIMALS
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2024
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IF 2.2
Zhi-Hui GUAN,Di YANG,Yi WANG,Jia-Bin MA,Guo-Nian WANG
Ischemia/reperfusion (I/R) is a pathological process that occurs in numerous organs and is often associated with severe cellular damage and death. Ectodysplasin-A2 receptor (EDA2R) is a member of the TNF receptor family that has anti-inflammatory and antioxidant effects. However, to the best of our knowledge, its role in the progression of myocardial I/R injury remains unclear. The present study aimed to investigate the role of EDA2R during myocardial I/R injury and the molecular mechanisms involved. In vitro, dexmedetomidine (DEX) exhibited a protective effect on hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and downregulated EDA2R expression. Subsequently, EDA2R silencing enhanced cell viability and reduced the apoptosis of cardiomyocytes. Furthermore, knockdown of EDA2R led to an elevated mitochondrial membrane potential (MMP), repressed the release of Cytochrome C and upregulated Bcl-2 expression. EDA2R knockdown also resulted in downregulated expression of Bax, and decreased activity of Caspase-3 and Caspase-9 in cardiomyocytes, reversing the effects of H/R on mitochondria-mediated apoptosis. In addition, knockdown of EDA2R suppressed H/R-induced oxidative stress. Mechanistically, EDA2R knockdown inactivated the NF-κB signaling pathway. Additionally, downregulation of EDA2R weakened myocardial I/R injury in mice, as reflected by improved left ventricular function and reduced infarct size, as well as suppressed apoptosis and oxidative stress. Additionally, EDA2R knockdown repressed the activation of NF-κB signal in vivo. Collectively, knockdown of EDA2R exerted anti-apoptotic and antioxidant effects against I/R injury in vivo and in vitro by suppressing the NF-κB signaling pathway.
研究领域:
心脏病学
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分子生物学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
CELLULAR SIGNALLING
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2024
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IF 4.4
Zheng-Ming Cao,Su Fu,Chao Dong,Teng-Yue Yang,Xiao-Kang Liu,Chun-Lin Zhang,Dong-Zhe Li
The progression of osteoarthritis (OA) includes the initial inflammation, subsequent degradation of the extracellular matrix (ECM), and chondrocyte apoptosis. Down syndrome candidate region 1 (DSCR1) is a stress-responsive gene and expresses in varied types of cells, including chondrocytes. Bioinformatics analysis of GSE103416 and GSE104739 datasets showed higher DSCR1 expression in the inflamed cartilage tissues and chondrocytes of OA. DSCR1 had two major isoforms, isoform 1 (DSCR1–1) and isoform 4 (DSCR1–4). We found that DSCR1–1 had a faster ( in vitro ) and higher expression ( in vivo ) response to OA compared to DSCR1–4. IL-1β-induced apoptosis, inflammation, and ECM degradation in chondrocytes were attenuated by DSCR1–1 overexpression. DSCR1–1 triggered the phosphorylation of cAMP response element-binding 1 (CREB1) at 133 serine sites by decreasing calcineurin activity. Moreover, activated CREB1 moved into the cell nucleus and combined in the promoter regions of aldehyde dehydrogenase 2 (ALDH2), thus enhancing its gene transcription. ALDH2 could recover Wnt/β-catenin signaling transduction by enhancing phosphorylation of β-catenin at 33/37 serine sites and inhibiting the migration of β-catenin protein from the cellular matrix to the nucleus. In vivo , adenoviruses (1 × 10 8 PFU) overexpressing DSCR1–1 were injected into the articular cavity of C57BL/6 mice with medial meniscus surgery-induced OA, and it showed that DSCR1–1 overexpression ameliorated cartilage injury. Collectively, our study demonstrates that DSCR1–1 may be a potential therapeutic target of OA.
研究领域:
骨科
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分子生物学
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细胞生物学
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PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
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2024
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IF 4.6
Haocong Zhang,Liangbi Xiang,Hong Yuan,Hailong Yu
Neuroinflammation-caused secondary injury is a key event after spinal cord injury (SCI). Dedicator of cytokinesis 2 (DOCK2) belonging to DOCK-A subfamily has a vital role in microglia polarization and neuroinflammation via mediating Rac activation. However, the role of DOCK2 in SCI is unclear. In the present study, SCI model in mice was established by an impactor at thoracic T10 level. DOCK2 expression was significantly increased in the spinal cord after SCI. After knocking down DOCK2 using a lentivirus-mediated method, SCI mice exhibited improved motor function recovery, as revealed by increased Basso Mouse Scale (BMS) score, angle of incline, and relatively coordinated footprint, and decreased damaged area in the spinal cord. DOCK2 deficiency reduced neuronal apoptosis in the spinal cord after injury. Besides, deficiency of DOCK2 suppressed neuroinflammation after SCI, demonstrated by the reduction in pro-inflammatory mediators including IFN-γ, IL-1β and IL-6 and the increase in IL-4, IL-10 and IL-13, anti-inflammatory factors. The CD86, iNOS and COX-2 were down-regulated in the spinal cord, whereas CD206, Arg-1 and TGF-β were up-regulated by DOCK2 deficiency. Rac activation was prevented by DOCK2 deficiency following SCI. In vitro experiments were conducted for further verification. Treatment of BV-2 microglia with lentivirus-mediated DOCK2 inhibited IFN-γ/LPS-induced pro-inflammatory microglia polarization but increased IL-4-induced anti-inflammatory microglia, through inhibiting Rac activation. In brief, our data reveal that DOCK2 deficiency improves functional recovery in mice after SCI, which is related to Rac activation.
研究领域:
神经科学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2025
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IF 6.5
Yixiao Yang,Tao Ye,Fusheng Shang,Dagui Chen,Kai Wang,Shengli He
Introduction Lung cancer, a deadly malignancy, often employs Docetaxel (DTX) as a chemotherapy option. However, DTX non-selective distribution limits its therapeutic effectiveness due to adverse side effects. This study aims to develop novel folate-targeted albumin polyester nanocarriers (FA-DTX-APs) encapsulating DTX for precise delivery, enhancing lung cancer treatment efficacy.Methods FA-DTX-APs were meticulously crafted utilizing the thin-film dispersion technique and subsequently evaluated for their physicochemical characteristics, encapsulation efficiency, and drug release profiles. To assess their biological properties, anti-tumor efficacy, and biosafety in the context of lung cancer, a comprehensive series of hemolysis assays, cellular studies, and animal experiments were conducted.Results FA-DTX-APs exhibit nanovesicle properties with a size of (223.65 ± 6.83) nm, a potential of (26.76 ± 3.15) mV, and encapsulate DTX with high efficiency (96.19 ± 3.27%) and loading capacity (9.75 ± 0.38%). FA-DTX-APs enable tumor-targeted drug delivery and slow release of the drug over a long period of time, with faster release in acidic environments. By efficiently targeting and entering lung cancer cells, FA-DTX-APs effectively hinder cancer growth (P < 0.05), demonstrating superior anti-tumor effects (P < 0.05), biocompatibility and enhanced biological safety (P < 0.05).Conclusion This study introduces FA-DTX-APs, an innovative nanocarrier characterized by exceptional biocompatibility and safety. It successfully targets lung cancer cells to deliver DTX in a sustained, slow-release manner, ensuring prolonged tumor-killing effects. As such, FA-DTX-APs hold immense promise as a novel nanoagent for lung cancer therapy.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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DOI
PubMed
高影响因子
CARBON
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2024
·
IF 10.5
Lina Bao,Wanchun Luo,Qinying Li,Yu Zhang,Zitong Zhang,Xi Li,Le Wang,Jintao Zhang,Kun Huang,Xu Yu,Li Xu
Metal dyshomeostasis is one of the pathological features of Alzheimer's disease (AD). Cu 2+ is believed to induce the formation of neurotoxic β-amyloid (Aβ) aggregates and aggravate oxidative damage. It is challenging to take effective therapeutic interventions towards the complicated pathogenesis related to Cu 2+ . Herein, chiral carbon dots were proposed for Cu 2+ -related AD therapy. The chiral CDs were prepared based on the ternary carbon sources, using L/ d -cysteine as the chiral carbon source, citric acid as the carbonization source and β-cyclodextrin as the chirality inducer, reserving and enhancing the chirality of CDs. Compared to L-Cys-CDs, D-Cys-CDs exhibited enhanced chirality, stronger affinity towards Cu 2+ and comparable antioxidant ability, but better inhibition on peroxidase-like activity of Cu 2+ or Aβ 42 -Cu 2+ . Thus, D-Cys-CDs performed better to inhibit Cu 2+ -induced Aβ aggregation. Meanwhile, D-Cys-CDs can alleviate the cytotoxicity of Aβ 42 -Cu 2+ with satisfactory anti-inflammation effect and scavenging ability towards intracellular reactive oxygen species. D-Cys-CDs succeeded in reducing Aβ deposits and releasing paralysis for the AD model CL2120 nematodes. D-Cys-CDs with an enantiomeric effect on Cu 2+ -induced Aβ aggregation and the peroxidase-like activity of Cu 2+ was promising as the multifunctional therapeutic agent for Cu 2+ -induced AD therapy.
研究领域:
纳米技术
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神经科学
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治疗学
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材料科学
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DOI
高影响因子
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