JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Tiantian Liu,Zehang Zhou,Mengxing Zhang,Puxin Lang,Jing Li,Zhenmi Liu,Zhirong Zhang,Lin Li,Ling Zhang
The cuproptosis cell death pathway brings fresh opportunities for tumor therapy. However, efficient and targeted cuproptosis induction in tumors is still a challenge. Unfortunately, the well-known cuproptosis initiator, disulfiram and copper complex (DSF/Cu 2+ ), also increases PD-L1 level in tumors, which may diminish the final therapeutic outcome. In this study, DSF/Cu 2+ -loading MXene nanosheets are coated with PD-1 overexpressing T cell membrane to generate CuX-P system. CuX-P could recognize and stick to PD-L1 on tumor cells like a patch, which promotes the endocytosis of both CuX-P and PD-L1 by tumor cells. Following internalization and release of DSF/Cu 2+ in the cytoplasm, PD-L1 expression is upregulated. However, due to the presence of CuX-P in the tumor microenvironment , the then supplemented PD-L1 on tumor surface again binds CuX-P for internalization. This feedback loop keeps blocking and consuming the PD-L1 on tumor surface and promotes the enrichment of CuX-P in tumors to induce cuproptosis. After CuX-P treatment with laser irradiation, strong anti-tumor immune responses are stimulated in a mouse model with triple-negative breast cancer. Thus, this study develops a tumor-targeted biomimetic system that offers simultaneous cuproptosis killing, photothermal therapy (PTT) and immunotherapy in mice.
研究领域:
肿瘤学
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免疫治疗
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纳米技术
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癌症生物学
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产品关联
DOI
PubMed
高影响因子
International Journal of Medical Sciences
·
2022
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IF 3.642
Zuofei Chi,Bin Zhang,Ruowen Sun,Ye Wang,Linlin Zhang,Gang Xu
T-cell acute lymphoblastic leukemia (T-ALL) is a common hematologic malignancy. Based on the data from {"type":"entrez-geo","attrs":{"text":"GSE66638","term_id":"66638"}} GSE66638 and {"type":"entrez-geo","attrs":{"text":"GSE141140","term_id":"141140"}} GSE141140 , T-ALL patients depicted a higher USP44 level. However, its role in T-ALL is still unclear. In the present study, we investigated the role of USP44 in T-ALL growth. USP44 overexpression elevated the proliferation of CCRF-CEM cells, while USP44 knockdown suppressed the proliferation of Jurkat and MOLT-4 cells. In addition, USP44 accelerated the cell cycle progression, with boosted cyclinD and PCNA levels. However, USP44 knockdown induced apoptosis in Jurkat and MOLT-4 cells, with an upheaval among cleaved caspase-3 and PARP levels. Mechanistically, USP44 co-localized and interacted with WDR5, leading to the repression of its ubiquitination and degradation. Interestingly, WDR5 overexpression abolished the apoptosis induced by USP44 knockdown. Consistently, the in vivo study revealed that USP44 knockdown restricted the leukemic engraftments in the bone marrow and spleens and reduced the infiltration of T-ALL cells in the livers and lungs. In conclusion, this study indicated that USP44 enhanced the growth of T-ALL through interacting with WDR5 and repressing its ubiquitination. This study highlights the potential use of USP44 as a therapeutic target of T-ALL.
研究领域:
肿瘤学
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血液学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Yan Xu,Jiwei Liu,Zhangya Liu,Guoguang Chen,Xueming Li,Hao Ren
Introduction Limited by tumor vascular barriers, restricted intratumoural T cell infiltration and nanoparticles accumulation remain major bottlenecks for anticancer therapy. Platelets are now known to maintain tumor vascular integrity. Therefore, inhibition of tumor-associated platelets may be an effective method to increase T cell infiltration and drug accumulation at tumor sites. Herein, we designed an ultrasound-responsive nitric oxide (NO) release nanosystem, SNO-HSA-PTX, which can release NO in response to ultrasound (US) irradiation, thereby inhibiting platelet function and opening the tumor vascular barrier, promoting drug accumulation and T cell infiltration.Methods We evaluated the ability of SNO-HSA-PTX to release NO in response to US irradiation. We also tested the effect of SNO-HSA-PTX on platelet function. Plenty of studies including cytotoxicity, pharmacokinetics study, biodistribution, blood perfusion, T cell infiltration, in vivo antitumor efficacy and safety assessment were conducted to investigate the antitumor effect of SNO-HSA-PTX.Results SNO-HSA-PTX with US irradiation inhibited tumor-associated platelets activation and induced openings in the tumor vascular barriers, which promoted the accumulation of SNO-HSA-PTX nanoparticles to the tumor sites. Meanwhile, the damaged vascular barriers allowed oxygen-carrying hemoglobin to infiltrate tumor regions, alleviating hypoxia of the tumor microenvironment. In addition, the intratumoral T cell infiltration was augmented, together with chemotherapy and NO therapy, which greatly inhibited tumor growth.Discussion Our research designed a simple strategy to open the vascular barrier by inhibiting the tumor-associated platelets, which provide new ideas for anti-tumor treatment.
研究领域:
肿瘤学
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药理学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
·
2024
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IF 6.3
Xuxu Wang,Ying Bai,Ruxiu He,Fen Yao,Limin Chang,Ping Nie
Metastable orthorhombic niobium pentoxide (T-Nb 2 O 5 ) with fast lithium storage capability and safe operating voltage is recognized as suitable anode material for high power density lithium-ion batteries (LIBs). While, the T-Nb 2 O 5 also suffers from low electrical conductivity in practical applications. In this work, the electrochemical performance of T-Nb 2 O 5 is enhanced by constructing a free-standing electrode and introducing the N-doped carbon substrate. The free-standing electrode consisting of the network-structured Nb 2 O 5 layer and porous carbon cloth (PCC) avoids the use of binders and benefits the electron transport. In addition, the introduction of N-doped carbon substrate is also beneficial to enhance the electronic conductivity of the Nb 2 O 5 . When used as the anode for LIBs , the PCC@Nb 2 O 5 demonstrates excellent long cycle life and rate performance, with a specific capacity of over 150 mA h g −1 after 3200 cycles at a current density of 1000 mA g −1 . This strategy of constructing free-standing electrodes provides new options for obtaining high-performance Nb 2 O 5 anode electrodes.
研究领域:
材料科学
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电化学
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能源存储
✓ 已验证
产品关联
DOI
高影响因子
BIOELECTROCHEMISTRY
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2012
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IF 3.759
Xiao Liu,Liqiang Luo,Yaping Ding,Zhangping Kang,Daixin Ye
A novel Au-nanoparticles/poly-eriochrome black T film modified glassy carbon electrode (AuNPs/PEBT/GCE) was constructed for the simultaneous determination of l -cysteine (L-Cys) and l -tyrosine (L-Tyr) by differential pulse voltammetry . Fourier transform infrared spectra and electrochemical impedance spectroscopy indicate that the PEBT film was successfully polymerized on the surface of GCE and the film efficiently decreased the charge transfer resistance value of electrode and improved the electron transfer kinetic between analytes and electrode. The scanning electron microscope image shows that the immobilized AuNPs were spherical in shape and enhanced the electrical conductivity of PEBT film. In addition, PEBT film increased the oxidation currents of analytes four times when compared to bare GCE, and the AuNPs separated the oxidation potentials of L-Cys and L-Tyr by 488 mV while bare GCE failed to resolve them. The amperometry results exhibit that the electrocatalytic currents increased linearly with L-Cys concentrations in the range 0.05–100 μM ( r = 0.9981), and the detection limits of L-Cys and L-Tyr were 8 nM and 10 nM ( S / N = 3), respectively. With high sensitivity and selectivity, the proposed electrochemical sensor provides a simple method for simultaneous determination of L-Cys and L-Tyr.
研究领域:
分析化学
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生物医学工程
✓ 已验证
DOI
高影响因子
Bioactive Materials
·
2020
·
IF 8.724
Hong Pan,Wenjun Li,Ze Chen,Yingmei Luo,Wei He,Mengmeng Wang,Xiaofan Tang,Huamei He,Lanlan Liu,Mingbin Zheng,Xin Jiang,Ting Yin,Ruijing Liang,Yifan Ma,Lintao Cai
The adoptive transfer of chimeric antigen receptor-T (CAR-T) cells has shown remarkable clinical responses in hematologic malignancies. However, unsatisfactory curative results and side effects for tumor treatment are still unsolved problems. Herein we develop a click CAR-T cell engineering strategy via cell glycometabolic labeling for robustly boosting their antitumor effects and safety in vivo. Briefly, paired chemical groups (N 3 /BCN) are separately incorporated into CAR-T cell and tumor via nondestructive intrinsic glycometabolism of exogenous Ac 4 GalNAz and Ac 4 ManNBCN, serving as an artificial ligand-receptor. Functional groups anchored on cell surface strengthen the interaction of CAR-T cell and tumor via bioorthogonal click chemistry, further enhancing specific recognition, migration and selective antitumor effects of CAR-T cells. In vivo, click CAR-T cell completely removes lymphoma cells and minimizes off-target toxicity via selective and efficient bioorthogonal targeting in blood cancer. Surprisingly, compared to unlabeled cells, artificial bioorthogonal targeting significantly promotes the accumulation, deep penetration and homing of CAR-T cells into tumor tissues, ultimately improving its curative effect for solid tumor. Click CAR-T cell engineering robustly boosts selective recognition and antitumor capabilities of CAR T cells in vitro and in vivo, thereby holding a great potential for effective clinical cell immunotherapy with avoiding adverse events in patients.
研究领域:
免疫疗法
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肿瘤学
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化学生物学
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细胞工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Ke Gong,Jiangtao Lin,Xiaoyan Chen,Yi Duan,Jiali Zhang,Jian Yu,Jing Wang,Ruifang Sun,Jie Li,Yourong Duan
In esophageal cancer (EC), clinical specimen testing has uncovered a significant increase in BTB and CNC homolog 1 (BACH1) expression and a shift towards an immunosuppressive environment, alongside a notable decrease in p53 protein expression. Therefore, therapeutic strategies focusing on BACH1 inhibition and p53 upregulation appear promising. Traditional oral treatments for EC lack precision and efficacy. Here, we propose a novel approach employing tumor-targeted nanoparticles (NPs) for drug delivery. However, the formation of a drug reservoir at the esophageal site, crucial for the sustained release of therapeutics, presents significant challenges in nano-delivery systems for EC treatment. To address this, we developed a thermosensitive hydrogel composed of F127 and tannic acid, serving as a vehicle for NP loading. These NPs, synthesized through the emulsion/volatization methods of mPEG-PLGA-PLL-cRGD, facilitate in situ drug delivery. Upon contacting esophageal tissue, the hydrogel transitions to a gel, adhering to the lining and enabling sustained release of encapsulated therapeutics. The formulation encompasses NPs laden with small interfering RNA targeting BACH1 (siBACH1) and the p53 activator PRIMA-1, creating a cohesive gel-nano system. Preliminary biological assessments demonstrate that this injectable, thermosensitive gel-nano system adheres effectively to esophageal tissue and targets EC cells. For better modeling clinical outcomes, a patient-derived organoid xenograft (PDOX) model was innovated, involving transplantation of EC-derived organoids into humanized mice, reconstructed with peripheral blood mononuclear cells (PBMCs). Post-treatment analysis showed substantial EC growth inhibition (89.51% tumor inhibition rate), significant BACH1 level reduction, restored anti-tumor immune responses, and pronounced tumor apoptosis. In summary, our study introduces a thermosensitive gel-nano system for EC treatment via restoring p53 activity and boosting T-cell immunity, with potential for clinical application.
研究领域:
肿瘤学
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药学
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生物技术
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE MEDICAL JOURNAL
·
2025
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IF 7.3
Li Na,Mao Jingwei,Tang Haiying,Tan Xiaoyan,Bi Jian,Wu Hao,Chen Xiuli,Wang Yingde
Background: Regulatory dendritic cell (DCreg) subset exhibits a unique capacity for inducing immune tolerance among the variety subsets of dendritic cells (DCs) within gut-associated lymphoid tissues (GALTs). Fms-like tyrosine kinase 3 ligand (FLT3L) is involved in the differentiation of DCregs and the subsequent expansion of regulatory T-cells (Tregs) mediated by DCregs, though the precise mechanism remains poorly understood. This study aimed to explore the expansion mechanism of Treg induced by DCreg and the role of FLT3L in this process. Methods: DCregs were distinguished from other DC subsets isolated from GALTs of BALB/c mice through a mixed lymphocyte reaction assay. The functions and mechanisms by which FLT3L promoted Treg expansion via DCregs were investigated in vitro through co-culture experiments involving DCregs and either CD4 + CD25 − T-cells or CD4 + CD25 + T-cells. Additionally, an in vivo experiment was conducted using a dextran sulfate sodium (DSS)-induced colitis model in mice. Results: CD103 + CD11b + DC exhibited DCreg-like functionality and was identified as DCreg for subsequent investigation. Analysis of Foxp3 + Treg percentages within a co-culture system of CD4 + CD25 − T-cells and DCregs, with or without FLT3L, demonstrated the involvement of the FLT3/FLT3L axis in driving the differentiation of precursor T-cells into Foxp3 + Tregs induced by DCregs. Cell migration and co-culture assays revealed that the FLT3/FLT3L axis enhanced DCreg migration toward Tregs via the Rho pathway. Additionally, it was observed that DCregs could promote Treg proliferation through the Notch pathway, as inhibition of Notch signaling by DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) suppressed Treg expansion within the co-culture system of DCregs and CD4 + T-cells or CD4 + CD25 + T-cells. Furthermore, the FLT3/FLT3L axis influenced JAG1 expression in DCregs, indirectly modulating Treg expansion. In vivo experiments further established that FLT3L promoted DCreg expansion and restored Treg balance in DSS-induced colitis models, thereby ameliorating colitis symptoms in mice. Conclusion: The FLT3/FLT3L axis is integral to the maintenance of DCreg function in Treg expansion.
研究领域:
免疫学
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分子生物学
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医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLACENTA
·
2025
·
IF 2.5
Caiqun Huang,E Fen Cheng,Jinping Ni,Ying Lyu
Introduction Unexplained recurrent spontaneous abortion (URSA) involves multifactorial etiologies, with regulatory T cells (Tregs) playing a pivotal role in maintaining immune tolerance during pregnancy. Baicalein, a flavonoid from Scutellaria baicalensis, exhibits anti-inflammatory and immunomodulatory properties. This study evaluates baicalein's therapeutic potential in mitigating URSA via the TLR4/NF-κB signaling pathway. Methods A URSA mouse model was used, and baicalein was administered intraperitoneally. Pregnancy outcomes, abortion rates, and placental morphology were assessed on gestational day 14 (G14). Treg cells were quantified via flow cytometry, and gene/protein expression levels were analyzed by immunohistochemistry, Western blotting, and real-time PCR. In vitro experiments on ihESCs further investigated the role of the TLR4/NF-κB pathway. Results Baicalein reduced abortion rates from 33.3 % in URSA mice to 21.6 % (low dose) and 14.8 % (high dose), improved embryonic development by altering placental structure and decidual morphology, and reduced inflammation at the maternal-fetal interface. It expanded Treg cells and enhanced the expression of IGFBP-1 and PRL, markers of endometrial decidualization, and decreased TLR4, p-P65, and P65 expression. In vitro, baicalein's effects were abrogated by TLR4 inhibition, confirming pathway specificity. Discussion Baicalein improved pregnancy outcomes by enhancing Treg function and promoting decidualization via TLR4/NF-κB pathway inhibition. These findings highlight baicalein's potential as a therapeutic agent for URSA.
研究领域:
生殖医学
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免疫学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
·
2024
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IF 3.7
Shenglu Liu,Haoxian Gou,Hui Wei,Shengdeng Chen,Shijie Zhuo,Ming Luo,Shu Qin,Mengyu Zhang,Jiatong Chen,Zhiwei Huang,Xianming Xia,Xiaoli Yang,Kai He
Background and Aim The impact of cholecystectomy, which blocks the cholecystohepatic shunt pathway (CHSP), on the prognosis of patients with hepatocellular carcinoma (HCC) is unclear. Hepatic secondary bile acids (BAs) inhibit natural killer T (NKT) cell-mediated immunity against HCC, and the regulation of homeostasis of hepatic secondary BAs is controlled by the CHSP. However, the influence of CHSP on NKT cell-mediated immunity against HCC remains unclear. Methods The clinical data of hospitalized patients undergoing HCC resection were collected. Meanwhile, an in situ HCC mouse model was established, and the CHSP was augmented using oleanolic acid (OA). Results After 1:1 propensity score matching, Cox regression analysis revealed that cholecystectomy was an independent risk factor for HCC recurrence after hepatectomy ( P = 0.027, hazard ratio: 1.599, 95% confidence interval: 1.055–2.422). Experimentally, when OA enhanced CHSP, a significant decrease was observed in the accumulation of secondary BAs in the livers of mice. Additionally, a significant increase was observed in the levels of C-X-C ligand 16 and interferon γ in the serum and tumor tissues. Further, the percentage of C-X-C receptor 6 (+) NKT cells in the tumor tissues increased significantly, and the growth of liver tumors was inhibited. Conclusions This clinical study revealed that cholecystectomy promoted the recurrence after radical hepatectomy in patients with HCC. Preserving the normal-functioning gallbladder as much as possible during surgery may be beneficial to the patient's prognosis. Further investigation into the mechanism revealed that CHSP enhanced NKT cell-mediated immunity against HCC by reducing the hepatic accumulation of secondary BAs.
研究领域:
胃肠病学
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肝病学
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免疫学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL LETTERS
·
2016
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IF 1.088
Juan Wang,Zhihua Li,Yaling Yang
Vortex-assisted liquid–liquid microextraction is reported for the preconcentration of chloramine-T before determination by high-performance liquid chromatography with a diode array detector. Magnetite nanoparticles were used to remove hydrophobic additives in cosmetics by physical adsorption. The method used sonication for 30 min at 45°C in 40% hydrochloric acid to convert the analyte to p-toluenesulfonamide. 1-Hexanol was the extraction solvent with vortex mixing. The extraction conditions were optimized to provide a linear dynamic range from 0.5 to 500.0µg/mL. The recovery of chloramine-T was from 90.8 to 100.9% with a relative standard deviation from 3.7 to 6.5%. The limit of detection was 8.2 mg/kg and the enrichment factor (EF) was 100. Good repeatability, quantitative recovery, and a high EF demonstrated the suitability of the procedure for the determination of chloramine-T in cosmetics.
研究领域:
分析化学
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化妆品科学
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 35
·19659-19667
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IF 2.936
Bhavani P. Nenavathu,Syam Kandula,Swati Verma
Photocatalysts suffer from a lack of separation of photogenerated excitons due to the fast recombination of charge carriers, so a strong synergistic effect exhibited by photocatalysts is promising for effective photocatalysis. Herein, we have synthesized efficient visible light functionalized graphene oxide nanosheet (FGS)/ZnO nanocomposite photocatalysts via a simple and economical approach with large scale production for practical applications. A series of nanocomposites (FGS/ZnO NCs) with different amounts by weight of graphene oxide (GO) have been synthesized via a facile solution route followed by calcination under environmental conditions. The phase, purity and morphological studies of the synthesized FGS/ZnO NCs were carried out using powder X-ray diffraction (XRD) and transmission electron microscopy (TEM). The optical properties were studied using UV-visible diffuse reflectance spectroscopy (DRS) and photoluminescence spectroscopy (PL). XRD results confirm the formation of a pure phase of ZnO in the FGS/ZnO NCs and TEM results show strongly adhered ZnO NPs on the surface of the FGS. DRS results confirm the extension of light absorption in the visible region while PL results confirm the effective separation of charge carriers in 0.09 wt% FGS/ZnO NCs. The synthesized photocatalyst efficiently degrades carcinogenic safranin-T dye under visible light illumination which is reported for the first time using FGS/ZnO nanocomposites. Photocatalytic studies confirm the higher photocatalytic activity of 0.09 wt% FGS/ZnO NCs (about 94.5%) towards the photodegradation of safranin-T dye in aqueous solution under visible light. The improved photocatalytic activity of 0.09 wt% FGS/ZnO NCs can be ascribed to the integrative synergistic effects of the enhanced adsorption capacity of safranin-T dye, effective separation of photogenerated excitons and effective interfacial hybridization of FGS and ZnO NCs. The generation of reactive oxygen species was confirmed using terephthalic acid as a probe molecule and a scavenger test was conducted in presence of histidine.
研究领域:
材料科学
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环境科学
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化学工程
✓ 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）