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
FASEB JOURNAL
·
2025
·Vol. 39
·期 9
·e70561
·
IF 4.2
Haocong Zhang,Xianyun Qin,Hong Yuan,Liangbi Xiang,Hailong Yu
Neuronal inflammation and apoptosis aggravate the secondary injury after spinal cord injury (SCI). Cathepsin L (CTSL) is a lysosomal cysteine protease with effects on the regulation of inflammation, but its role in SCI remains unclear. The in vivo T10 mouse spinal cord contusion model was established. The results showed that CTSL expression was increased following SCI and then gradually decreased. Moreover, CTSL was mainly expressed in microglia. To detect the function of CTSL, after contusive injury, the mice were immediately injected with lentiviruses carrying CTSL shRNA. The results showed that CTSL depletion promoted functional recovery, accompanied by increased locomotor ability. CTSL deficiency reduced lesion cavity areas by inhibiting neuronal apoptosis and neuroinflammation. Indeed, CTSL deficiency decreased the secretion of TNF-α, IL-6, and MCP-1 and M1 microglia polarization in the spinal cord. CTSL depletion inhibited the expression and assembly of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome. In vitro, CTSL expression was increased in LPS-treated BV2 cells. CTSL silencing repressed LPS-induced M1 polarization, as evidenced by the reduction in TNF-α, IL-6, and MCP-1 expression in the supernatant of BV2 cells. CTSL knockdown induced the downregulation of NLRP3 expression and activation. The inhibition role of CTSL knockdown in microglial inflammation and M1 polarization was reversed by NLRP3 agonist. Collectively, the study suggests that CTSL induces the microglia M1 polarization-mediated inflammation via promoting NLRP3 activation and thereby inhibits functional recovery after SCI. Graphical The inhibition of CTSL improves functional recovery and alleviates neuroinflammation through microglial polarization after spinal cord injury. Mechanically, CTSL knockdown inhibited NLRP3 expression and activation, which repressed the production of pro-inflammatory cytokines in M1 microglia, thereby inhibiting spinal cord injury-induced neuroinflammation.
研究领域:
神经科学
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免疫学
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PubMed
高影响因子
CLINICAL SCIENCE
·
2025
·
IF 7.7
Renzi Zhang,Yuhua Zhong,Qiudie Liu,Mengqi Zhang,Daoxin Wang,Sheng Li,Di Qi
Acute respiratory distress syndrome (ARDS) is an acute and severe disease with a high mortality rate. The outbreak of immune inflammation in the lung is an important pathogenic mechanism of ARDS. Notably, an imbalance in macrophage polarization is an important link in the occurrence and development of this inflammatory response. Recently, neuropeptides have been shown to regulate inflammation, but the role of neuropeptides in ARDS remains unclear. The aim of this study was to investigate the regulatory effect of calcitonin gene-related peptide (CGRP) on the inflammatory response in ARDS. We found that CGRP expression was increased in the serum of ARDS patients and in both in vitro and in vivo models of ARDS. CGRP can regulate the polarization of macrophages by targeting its receptor (receptor activity-modifying protein 1); reduce the proportion of M1 macrophages; increase the proportion of M2 macrophages; and reduce pathological injury, inflammation, oxidative stress, and apoptosis in lung tissue in LPS-induced ARDS both in vitro and in vivo . Additionally, we performed transcriptome sequencing and found that hypoxia-inducible factor-1α (HIF-1α) is involved in the above process and that CGRP can alleviate ARDS-related pathological damage, inflammation, and oxidative stress by inhibiting the HIF-1α pathway to regulate macrophage polarization balance. These results indicate that CGRP has good potential for clinical translation in the treatment of pulmonary infection in ARDS. Furthermore, this study provides new ideas for the treatment of inflammatory bursts in ARDS.
研究领域:
免疫学
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分子生物学
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病理学
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PubMed
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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PubMed
高影响因子
Small
·
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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PubMed
高影响因子
BIOLOGICAL PROCEDURES ONLINE
·
2024
·Vol. 26
·期 1
·1-18
·
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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PubMed
高影响因子
FEBS Journal
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2024
·
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
Cancer Communications
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2025
·
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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PubMed
高影响因子
American Journal of Cancer Research
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2021
·
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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PubMed
高影响因子
iScience
·
2025
·
IF 4.1
Yani Hui,Bing Li,Shan He,Haiyan Jiang,Yanlan Xie,Mingzhu Lv,Chuan Zhang,Xiaoxue Xu,Yuan Yong,Hanfeng Yang
Computed tomography (CT)-guided percutaneous microwave ablation (MWA) serves as a standard approach for hepatocellular carcinoma (HCC) treatment, yet faces challenges of higher recurrence rates when treating tumors in special anatomical locations. This study evaluated tungsten disulfide (WS 2 ) nanosheets combined with CT-guided MWA for treating rabbit VX2 liver tumors. WS 2 nanosheets were synthesized and demonstrated excellent microwave thermal effects and CT imaging capability in vitro. In animal studies, the combination therapy significantly enhanced tumor necrosis and apoptosis rates compared to MWA alone, while also activating systemic antitumor immunity as evidenced by increased Cytotoxic Tlymphocyte (CD8 + T-cell) infiltration. The findings suggest WS 2 nanosheets improve MWA efficacy through enhanced energy absorption and immune activation, offering a promising combinatorial strategy for hepatocellular carcinoma treatment.
研究领域:
肿瘤学
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纳米医学
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介入放射学
·
癌症治疗
·
生物医学工程
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PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2017
·Vol. 233
·期 9
·6714-6721
·
IF 4.08
Haihong Zhou,Congli Jin,Lili Cui,Huaijie Xing,Jun Liu,Wang Liao,Haojie Liao,Yangsheng Yu
This study aimed to investigate whether HMGB1 (high mobility group box-1 protein) and receptor for advanced glycation end products (RAGE) were involved in the irradiation-induced endothelial barrier damage and their mechanism. We constructed the damage model of endothelium barrier model with bEnd.3 cells. The permeability of endothelial barrier was detected by sodium fluorescein (Na-F) permeation test, and the irradiation dose which could induce permeability transition was determined by being exposed to different irradiation doses (5, 10, 15, 20 Gy). MTT assay was applied to detect cell viability under different concentrations of HMGB1 , glycyrrhizic acid (GA, a specific inhibitor of HMGB1 ), and FPS-ZM1 (a blood-brain-barrier permeant blocker of RAGE V domain-mediated ligand binding). The expression of HMGB1 , RAGE, and related molecules involved in MAPK signaling pathway, MMP-2, MMP-9, ZO-1, and claudin 5 of differently treated groups were measured by qRT-PCR, western blot, and immunofluorescence. Cells possessed stable endothelial barrier function on 4–7 days after seeded on transwell plates. The permeability of endothelial barrier would change under at least 10 Gy radiation. Both radiation and HMGB1 treatment alone could improve the permeability. After irradiation, the expressions of HMGB1 and RAGE increased and MAPK signal pathway was activated. Meanwhile, MMP-2 and MMP-9 were overexpressed, while the expression of tight junction proteins ZO-1 and claudin 5 was decreased. Radiation could activate MAPK signaling pathway through promoting the expression of HMGB1 and RAGE, which further led to endothelial barrier injury and changed its permeability.
研究领域:
细胞生物学
·
分子生物学
·
医学研究
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PubMed
高影响因子
International Journal of Nanomedicine
·
2018
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IF 4.37
Wentao Deng,Juhui Qiu,Shaoting Wang,Zhi Yuan,Yuefeng Jia,Hailin Tan,Jiru Lu,Ruqiang Zheng
In this study, we performed the characterization and synthesis of biocompatible and targeted albumin and graphene oxide (GO) dual-carrier paclitaxel (PTX) nanoparticles for photothermal-triggered tumor therapy. PTX absorbed on GO nanosheets as cores were coated with human serum albumin (HSA), following surface conjugation with monoclonal antibodies (mAb) against vascular endothelial growth factor (VEGF; denoted as mAbVEGF) via polyethylene glycol linker to form targeted nanoparticles (PTX-GHP-VEGF). The spherical nanoparticles were 191±5 nm in size with good stability and biocompatibility. GO functioned as the first carrier and a near infrared absorber that can generate photothermal effects under 5-minute 808-nm laser irradiation to thermal trigger the release of PTX from the second carrier HSA nanoparticles. The mechanism of thermal-triggered drug release was also investigated preliminarily, in which the heat generated by GO induced swelling of PTX-GHP-VEGF nanoparticles which released the drugs. In vitro studies found that PTX-GHP-VEGF can efficiently target human SW-13 adrenocortical carcinoma cells as evaluated by confocal fluorescence microscopy as well as transmission electron microscopy, and showed an obvious thermal-triggered antitumor effect, mediated by apoptosis. Moreover, PTX-GHP-VEGF combined with near infrared irradiation showed specific tumor suppression effects with high survival rate after 100 days of treatment. PTX-GHP-VEGF also demonstrated high biosafety with no adverse effects on normal tissues and organs. These results highlight the remarkable potential of PTX-GHP-VEGF in photothermal controllable tumor treatment.
研究领域:
药学
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纳米技术
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癌症研究
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生物医学工程
·
药物递送系统
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PubMed
高影响因子
危险品化学品经营许可证（带存储）