eLife
·
2019
·
IF 7.551
Xuefei Yan,Beibei Tang,Biao Chen,Yongli Shan,Huajun Yang,Reproducibility Project: Cancer Biology,Elizabeth Iorns,Rachel Tsui,Alexandria Denis,Nicole Perfito,Timothy M Errington
As part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Li et al., 2015), that described how we intended to replicate selected experiments from the paper ‘The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44’ (Liu et al., 2011). Here we report the results. We found the microRNA, miR-34a, was expressed at twice the level in CD44+ prostate cancer cells purified from xenograft tumors (LAPC4 cells) compared to CD44- LAPC4 cells, whereas the original study reported miR-34a was underexpressed in CD44+ LAPC4 cells (Figure 1B; Liu et al., 2011). When LAPC4 cells engineered to express miR-34a were injected into mice, we did not observe changes in tumor growth or CD44 expression; however, unexpectedly miR-34a expression was lost in vivo. In the original study, LAPC4 cells expressing miR-34a had a statistically significant reduction in tumor regeneration and reduced CD44 expression compared to control (Figure 4A and Supplemental Figures 4A,B and 5C; Liu et al., 2011). Furthermore, when we tested if miR-34a regulated CD44 through binding sites in the 3’UTR we did not find a statistically significant difference, whereas the original study reported miR-34a decreased CD44 expression that was partially abrogated by mutation of the binding sites in the CD44 3’UTR (Figure 4D; Liu et al., 2011). Finally, where possible, we report meta-analyses for each result.
研究领域:
肿瘤学
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分子生物学
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癌症生物学
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PubMed
高影响因子
Frontiers in Immunology
·
2026
·
IF 7
Di Wang,Jiawei Zhu,Qingzhi Wang,Lingyun Shi,Yehua He,Zili Jin,Wenjun Chen,Xiaocong Chen,Shenjun Chen,Hong Li,Ce Zhang,Rui Zhu
Introduction Spontaneous abortion (SA) is closely associated with immune homeostasis of decidual natural killer (dNK) cells at the maternal-fetal interface, yet how decidual stromal cells (DSCs) educate NK cells remains incompletely understood. Here, we showed that DSC-derived hyaluronic acid (HA) shapes NK cell residency and cytotoxicity in early pregnancy. Methods Reanalysis of single-cell RNA sequencing data and functional assays identified DSCs as the major source of HAS2-dependent HA. We assessed dNK phenotypes and functions in SA versus normal pregnancies, and tested HA -CD44 effects using high-molecular-weight HA (HMW-HA) stimulation, HAS2 knockdown in DSCs, and CD44 blockade, with partial rescue by exogenous HMW-HA. Canonical Wnt activation and FOSL2 upregulation were further evaluated by western blotting to examine downstream signaling. Results Our findings revealed a reduced proportion of dNK cells, impaired adhesion molecule expression, and increased cytotoxicity in SA compared with normal pregnancies. HMW-HA from DSCs, via engagement of CD44 on NK cells, promoted the phenotypic transition of peripheral NK cells into CD49a + tissue-resident dNK-like cells, increased adhesion, and shifted cytokine production toward an immune-tolerant profile. HAS2 knockdown in DSCs or CD44 blockade reduced CD49a expression, expanded highly cytotoxic CD44 high subset, and disrupted the balance among dNK1/dNK2/dNK3-like subsets, effects that were partially rescued by exogenous HMW-HA. Mechanistically, HA/CD44 signaling activated canonical Wnt pathways and upregulated the dNK1-associated transcription factor FOSL2 , driving differentiation toward a low-cytotoxic dNK1-like phenotype. Discussion These findings define a DSC-centered HA/HAS2 -CD44 -Wnt - FOSL2 axis that remodels NK cells and supports maternal-fetal immune tolerance, providing potential targets for preventing SA and related pregnancy complications.
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高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
·
IF 2.5
Ruifan Ma,Liguo Hao,Jianing Cheng,Jun He,Qiangqiang Yin,Zhongtao Li,Guiqiang Qi,Xiaoyang Zheng,Dongxu Wang,Tianyu Zhang,Houyi Cong,Zheng Li,Haifeng Hu,Yuguang Wang
Rupture of vulnerable plaque and secondary thrombosis caused by atherosclerosis are one of the main causes of acute cardiovascular and cerebrovascular events, and it is urgent to develop an in-situ, noninvasive, sensitive and targeted detection method at molecular level. We chose CD44, a specific receptor highly expressed on the surface of macrophages, as the target of the molecular probe, and modified the CD44 ligand HA onto the surface of Gd 2 O 3 @MSN, constructing the MRI imaging nanoprobe HA-Gd 2 O 3 @MSN for targeted recognition of atherosclerosis. The fundamental properties of HA-Gd 2 O 3 @MSN were initially investigated. The CCK-8, hemolysis, hematoxylin-eosin staining tests and blood biochemical assays confirmed that HA-Gd 2 O 3 @MSN possessed excellent biocompatibility. Laser confocal microscopy, cellular magnetic resonance imaging, flow cytometry and immunohistochemistry were used to verify that the nanoprobes had good targeting properties. The in vivo targeting performance of the nanoprobes was further validated by employing a rabbit atherosclerosis animal model. In summary, the synthesized HA-Gd 2 O 3 @MSN nanoprobes have excellent biocompatibility properties as well as good targeting properties. It could provide a new technical tool for early identification of atherosclerosis.
研究领域:
医学影像学
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纳米医学
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心血管病学
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高影响因子
COLLOID AND POLYMER SCIENCE
·
2020
·Vol. 299
·期 1
·129-136
·
IF 1.536
Xie Xin,Yuan Zhen,Yuan Qinglan,Huang Yuyou,Yu Qunying,Ren Jin,Liang Liang,Jin Hongguang,Yu Jingmou
Novel chondroitin sulfate A conjugated doxorubicin (CSA-DOX) was synthesized and characterized. The mean diameter of CSA-DOX was 152 nm analyzed by dynamic light scattering (DLS). Further, DOX was physically encapsulated into the CSA-DOX nanoparticles. Total amounts of DOX in three kinds of DOX-loaded CSA-DOX (CSA-DOX/DOX) nanoparticles were from 21.8 to 24.2%. The mean diameters of three CSA-DOX/DOX nanoparticles were in the range of 167–177 nm. The shape of CSA-DOX/DOX nanoparticles was almost spherical. DOX released from DOX-loaded nanoparticles exhibited a biphasic way in phosphate buffered saline (PBS, pH 7.4). Cellular uptake studies exhibited that CSA-DOX and CSA-DOX/DOX nanoparticles could enhance the uptake of DOX into CD44 receptor-positive A549 cells. Moreover, the cytotoxicity of CSA-DOX/DOX nanoparticles against A549 cells significantly improved in contrast with free DOX and CSA-DOX nanoparticles. These results suggested that CSA-DOX copolymer could be a potential carrier for antitumor drug delivery.
Graphical abstract
研究领域:
药学
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生物医学工程
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肿瘤学
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Journal of Materials Chemistry B
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2015
·Vol. 3
·期 18
·3767-3776
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IF 4.726
Bang-Ping Jiang,Li Zhang,Yang Zhu,Xing-Can Shen,Shi-Chen Ji,Xue-You Tan,Lei Cheng,Hong Liang
The construction of advanced phototherapy systems with high therapeutic efficacy toward cancer and low side effects, especially targeted species, is highly desirable. Herein, we developed one kind of water-soluble hyaluronic acid–hybridized polyaniline nanoparticles (HA–PANI NPs) as a nanoplatform for photothermal therapy (PTT) with targeted specificity of a CD44-mediated cancer cell. The water-soluble HA–PANI NPs were fabricated by one-step oxidative polymerization using aniline as a polymerizable monomer and HA as a stabilizer and targeted agent, where non-covalent electrostatic interaction between the negatively charged polymer HA and the cationic polymer PANI drives the formation of HA–PANI NPs. It was demonstrated that approximately spherical HA–PANI NPs are well-dispersed in aqueous solutions, with average hydrodynamic diameters of around 100 nm. Besides, HA–PANI NPs have negligible cytotoxicity in vitro, which facilitates biomedical applications with low toxicity. We studied the in vitro photothermal cell-killing efficacy of HA–PANI NPs by MTT assay and confocal microscopy measurement. The results reveal that HA–PANI NPs can selectively kill the cancer cells of HeLa and HCT-116 cells rather than normal cells of HFF cells upon exposure to a NIR 808 nm laser. The efficient intracellular intake of the HA–PANI NPs by both HeLa and HCT-116 cells are observed, confirming their targeting ability for CD44-overexpressing cancer cells. Furthermore, the results of in vivo photothermal ablation of tumors show excellent treatment efficacy, indicating that the HA–PANI NPs can be considered as an extremely promising nanoplatform for targeted PTT of cancer.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2017
·
IF 7.786
Yingying Chi,Xuelei Yin,Kaoxiang Sun,Shuaishuai Feng,Jinhu Liu,Daquan Chen,Chuanyou Guo,Zimei Wu
This study aimed to develop redox-sensitive and CD44-targeted liposomes to improve chemotherapy of osteosarcoma . Cationic liposomes were prepared and stabilized with a novel detachable polyethylene glycol (PEG 2000 ) conjugated with cholesterol through a bio-reducible disulfide linker (Chol-SS-mPEG). Hyaluronic acid (HA, MW 20–40 kDa), a ligand to CD44, was non-covalently coated on the cationic liposomes. Doxorubicin (DOX) was actively loaded in the liposomes as a model drug. The roles of HA and Chol-SS-mPEG on intracellular drug delivery efficiency, and antitumor efficacy were studied. The structure of Chol-SS-mPEG was confirmed with Fourier-transform infrared and nuclear magnetic resonance ( 1 H NMR). The liposomes, Chol-SS-mPEG/HA-L had a mean diameter of 165 nm, zeta potential − 28.9 mV, and destabilized in reducing or acidic (pH 5–6) conditions. In vitro release of DOX was well-controlled at physiological conditions, but a burst release of 60% was observed in the presence of 10 mM glutathione (GSH), in contrast to non-redox sensitive liposomes (Chol-mPEG/HA-L and Chol-mPEG-L). MTT cell viability assay showed that the dual-functional Chol-SS-mPEG/HA-L with a drug loading of 15.0% (w/w) had significantly higher cytotoxicity to MG63 osteosarcoma cells compared with non-reduction sensitive or non-HA coated liposomes (p < 0.01), consistent with the cellular uptake and intracellular trafficking studies using confocal microscopy and flow cytometry. Furthermore, the HA-coated GSH-responsive liposomes preferentially internalized to MG63 over human liver cells LO2. In rats, liposomes stabilized with either Chol-SS-mPEG or Chol-mPEG, with or without HA, increased the half-life of DOX by > 10-fold. In a MG63 xenograft mouse model, Chol-SS-mPEG/HA-L showed the most effective tumor suppression with minimal uptake by the liver compared with other liposomes. All animals treated with liposomal formulations survived, in contrast to those free-DOX treated. In conclusion, the easily prepared Chol-SS-mPEG/HA-L was demonstrated as an excellent CD44-mediated intracellular delivery system capable of long-circulation and GSH-triggered cytoplasmic drug release. Further translational and multidisciplinary research is required to make it real clinical benefits to cancer patients.
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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高影响因子
GLYCOBIOLOGY
·
2017
·Vol. 27
·期 9
·861-867
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IF 3.112
Qiu Yuanhao,Hou Yilin,Sun Feifei,Chen Peng,Wang Dongdong,Mu Haibo,Zhang Xiaoli,Ding Kan,Duan Jinyou
Antibiotics such as β-lactams and aminoglycosides are often subtherapeutic to intracellular infections due to their high hydrophilicity, resulting in low effectiveness against intracellular pathogens and the emergence of antibiotic resistance. Here we reported that an endogenous aminoglycan, hyaluronic acid could be an effective carbohydrate carrier of the aminoglycoside antibiotic, streptomycin against intracellular pathogens. This conjugation could enhance phagocytic activity, and facilitated the entry of streptomycin into host cells via a CD44-mediated pathway. It appeared that this conjugate could clear intracellular bacteria in phagocytic or nonphagocytic cells in a short-term therapy (4 h) at a lower effective dose. In addition, this conjugate was more efficient in reducing bacteria burden in an in vivo acute infection model than streptomycin did. Interestingly, subcutaneous injection of this conjugate at an excess amount had undetectable side effects such as nephrotoxicity. These results suggested that hyaluronic acid might be an efficient Trojan horse for the delivery of hydrophilic antibiotics to deal with intracellular infections.
研究领域:
药理学
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微生物学
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药物递送系统
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PubMed
高影响因子
ANNALS OF CLINICAL AND LABORATORY SCIENCE
·
2023
·Vol. 53
·期 2
·278-292
·
IF 0.8
Gairang Song,Jianghong Ren,Yan Li,Jinquan Cui
Objective Cancer stem cells (CSCs) are responsible for cervical cancer progression and decreased radiosensitivity of tumor cells. Thepresent work is meant to illuminate the impacts of exportin 1 (XPO1) on the aggressive behaviors and radiosensitivity of cervicalcancer stemness cells and make a deeper inquiry into its regulatory mechanism despite that XPO1 has been supported to elicitsignificant activities on multiple malignancies. Methods XPO1 and Rad21 expression in HeLa (CD44+) cells was tested by RT-qPCR and western blot. Cell viability was estimated via CCK-8 assay. Cell stemness was examined viasphere formation assay and western blot. Following radiation treatment, cell proliferation was judged by CCK-8 assay, westernblot as well as EdU staining whereas TUNEL assay, RT-qPCR and western blot analysis appraised cell apoptosis. Cell radiosensitivitywas assessed through clonogenic survival assay. The levels of DNA damage markers were tested by western blot and related kits.STRING database and Co-IP assay respectively predicted and testified the binding of XPO1 with Rad21. RT-qPCR and western blotalso examined the expression of XPO1 cargoes. Results The experimental data corroborated that XPO1 and Rad21 were overexpressed in cervical cancer tissues and cells. XPO1 inhibitorKPT-330 impeded the stemness while elevated the radiosensitivity of HeLa (CD44+) cells. XPO1 bond to Rad21 and positively modulated Rad21 expression. Moreover, Rad21 elevation reversed the impacts of KPT-330on the behaviors of cervical cancer stemness cells. Conclusion To sum up, XPO1 might impact the aggressive behavior and radioresistance of cervical cancer stemness cells through bindingwith Rad21.
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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放射生物学
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高影响因子
Discover Nano
·
2026
·Vol. 21
·期 1
·334
·
IF 6.7
Xuan Shaoyan,Yang Shenglei,Mao Yuqin,Chen Zhiyong,Zhu Yue,Zhou Ying,Huang Jie,Zhu Xiuliang,Wang Zuhua
Lung cancer remains one of the most prevalent and lethal malignancies worldwide. Oridonin (ORI) exhibits remarkable anti-lung cancer activity. Nevertheless, its clinical application in lung cancer therapy is severely hindered by poor solubility, fast metabolism, insufficient tumor penetration, and low selectivity. In this study, we developed a redox-responsive polymeric micelle (HA-cys-TOS) targeting the CD44 receptor to improve ORI bioavailability and tumor targeting. The polymer was synthesized via esterification and verified by 1 H NMR. Our data showed that ORI@HA-cys-TOS exhibited good stability, biosafety and redox-responsive sustained release. Compared to HepG2 cells, ORI@HA-cys-TOS exhibited significantly enhanced internalization ability in A549 cells, likely due to HA binding to the CD44 receptor overexpressed on A549 cells. Unexpectedly, the enhanced targeted accumulation of ORI@HA-cys-TOS micelles in vivo was also observed in both subcutaneous and in situ lung cancer tissues. In vivo and in vitro antitumor studies demonstrated that ORI@HA-cys-TOS micelles exhibited significantly greater antitumor activity compared to free ORI. Notably, no side-effects were observed during the 21 days experimental period. This study provides an experimental basis for advancing ORI toward clinical personalized lung cancer therapy by targeting CD44 and responding to the tumor redox microenvironment.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2026
·
IF 5.2
Yuling Wang,Jingru Li,Epiphane K. Silli,Fan Tang,Shujing Ren,Wei Liu,Huixia Lv
Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by immune dysregulation, oxidative stress, and epidermal barrier dysfunction. Current therapies often provide incomplete long-term control and may cause adverse effects. Baicalin (BAI), a natural flavonoid with potent anti-inflammatory and antioxidant activities, is a promising candidate for AD treatment; however, its topical application is limited by poor solubility, weak skin penetration, and insufficient retention. To address these challenges, we developed a hyaluronic acid-baicalin conjugate (HA-BAI) that combines enhanced aqueous dispersibility with CD44-associated targeting and intrinsic barrier-supportive properties. HA-BAI exhibited excellent aqueous dispersibility (>220 mg/mL) across different formulation media, whereas free BAI remained poorly soluble (∼0.05 mg/mL). In vitro , HA-BAI exhibited excellent cytocompatibility, suppressed nitric oxide and pro-inflammatory cytokines, enhanced IL-10 expression, and promoted barrier-related proteins in keratinocytes. Ex vivo permeation studies demonstrated enhanced skin accumulation and prolonged retention, with 3.28-fold greater skin-associated fluorescence than the free fluorescent probe at 12 h. In a DNFB-induced AD mouse model, HA-BAI markedly alleviated dermatitis severity, reduced splenomegaly, improved histopathological features, and restored epidermal barrier homeostasis, showing superior therapeutic performance compared with the dose-normalized HA and BAI physical mixture. Collectively, HA-BAI represents a bioactive macromolecular platform that integrates targeted delivery with intrinsic therapeutic functionality for localized treatment of AD. Download: Download high-res image (409KB) Download: Download full-size image
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Interdisciplinary Medicine
·
2025
·
IF 13.6
Liping Yang,Fangli Liao,Yanran Tong,Tong Huang,Yan-e Du,Siyang Wen,Linshan Jiang,Lanlang Peng,Hua Sun,Gaoli Zhang,Weixian Chen
Cancer stem cells exhibit flexible metabolic profiles. However, the underlying mechanisms for differential metabolic pathways affecting stemness maintenance in gastric cancer are poorly understood. Here, we reveal the role of serine hydroxymethyltransferase-2 (SHMT2)/serine-mediated crosstalk between one-carbon metabolism and lipid metabolism in the stemness maintenance of gastric cancer. Clinically, SHMT2 was significantly highly expressed in Gastric cancer cells (GCs) and gastric cancer stem cells, and was associated with clinical malignant features and poor prognosis in gastric cancer patients. Mechanistically, inhibition of SHMT2 expression resulted in diminished serine levels in one-carbon metabolism, which subsequently modified the composition and fluidity of membrane phospholipids, leading to a reduction in lipid rafts within cellular membranes. The remodeling of membrane phospholipids hindered the localization of γ-secretase to lipid rafts, thereby inhibiting the cleavage of CD44 and the subsequent production of CD44-ICD. Consequently, the transcriptional regulation of c-Myc and KLF4 by CD44-ICD was reduced, ultimately disrupting the maintenance of stemness in gastric cancer cells. Together, these results provide compelling evidence for the metabolic adaptability of cancer stem cells, and the SHMT2/serine/lipid rafts signaling axis holds promise as a potential biomarker for the diagnosis and prognosis of gastric cancer. Furthermore, we synthesized HA-Exo-si SHMT2 to investigate targeted therapy for GC, offering a novel approach for the clinical treatment of gastric cancer.
研究领域:
生物化学
·
分子生物学
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肿瘤学
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高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Zhang Weijie,Zhang Zhongyue,Lou Shitong,Chang Zhiwei,Wen Baohong,Zhang Tao
The use of iron oxide (Fe3O4) nanoparticles as novel contrast agents for magnetic resonance imaging (MRI) has attracted great interest due to their high r2 relaxivity. However, both poor colloidal stability and lack of effective targeting ability have impeded their further expansion in the clinics. Here, we reported the creation of hyaluronic acid (HA)-stabilized Fe3O4 nanoparticles prepared by a hydrothermal co-precipitation method and followed by electrostatic adsorption of HA onto the nanoparticle surface. The water-soluble HA functions not only as a stabilizer but also as a targeting ligand with high affinity for the CD44 receptor overexpressed in many tumors. The resulting HA-stabilized Fe3O4 nanoparticles have an estimated size of sub-20 nm as observed by transmission electron microscopy (TEM) imaging and exhibited long-term colloidal stability in aqueous solution. We found that the nanoparticles are hemocompatible and cytocompatible under certain concentrations. As verified by quantifying the cellular uptake, the Fe3O4@HA nanoparticles were able to target a model cell line (HeLa cells) overexpressing the CD44 receptor through an active pathway. In addition, we showed that the nanoparticles can be used as effective contrast agents for MRI both in vitro in HeLa cells and in vivo in a xenografted HeLa tumor model in rodents. We believe that our findings shed important light on the use of active targeting ligands to improve the contrast of lesion for tumor-specific MRI in the nano-based diagnosis systems.
研究领域:
生物医学工程
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纳米医学
·
影像学
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PubMed
高影响因子
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