ACTA PHARMACOLOGICA SINICA
·
2020
·Vol. 42
·期 7
·1190-1194
·
IF 5.064
Shen Zhu-qing,Wang Juan,Tan Wen-fu,Huang Tao-min
Hedgehog plays an important role in a wide range of physiological and pathological conditions. Paracrine activation of Hedgehog pathway in stromal cells increases the expression of VEGF, which promotes neovascularization in colorectal cancer and ultimately the growth of colorectal cancer. Berberine (BBR) has anticancer activity. In this study we investigated whether BBR inhibited the growth of colon cancer through suppressing the paracrine sonic hedgehog (SHH) signaling in vitro and in vivo. We showed that BBR (1–10 μM) dose-dependently inhibited the secretion and expression of SHH protein in HT-29 and SW480 cells. BBR did not influence the transcription of SHH, but promoted the degradation of SHH mRNA, thus decreased the SHH mRNA expression in the colorectal cancer cells. In nude mice bearing HT-29 xenograft, oral administration of BBR (100 mg · kg − 1 · d −1 ) or a positive control drug GDC-0449 (100 mg · kg −1 · d −1 ) for 4 weeks markedly suppressed the growth of HT-29 tumor with BBR exhibiting a better antitumor efficacy. The tumor growth inhibition caused by BBR or GDC-0449 was comparable to their respective inhibitory effect on the mouse-specific Gli mRNA expression in the tumor. However, BBR (20 μM) did not affect the expression of human transcription factor Gli1 mRNA in HT-29 and SW480 cells. In conclusion, BBR promotes the degradation of SHH mRNA in colorectal cancer cells, interrupting the paracrine Hedgehog signaling pathway activity thus suppresses the colorectal cancer growth. This study reveals a novel molecular mechanism underlying the anticancer action of BBR.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 5
·1277-1287
·
IF 6.331
Gao-Jian Huang,Han-Ping Yu,Xue-Lian Wang,Bing-Bing Ning,Jing Gao,Yi-Qin Shi,Ying-Jie Zhu,Jun-Li Duan
Hydroxyapatite (HAP) is promising for the clinical treatment of bone defects because of its excellent biocompatibility and osteo-conductivity. However, highly porous HAP scaffolds usually exhibit high brittleness and poor mechanical properties, thus organic constituents are usually added to form composite materials. In this work, a highly porous and elastic aerogel made from ultralong HAP nanowires with ultrahigh porosity (∼98.5%), excellent elasticity and suitable porous structure is prepared as the high-performance scaffold for bone defect repair. The highly porous structure of the as-prepared aerogel is beneficial to bone ingrowth and matter/fluid transfer, and the high elasticity can ensure the structural integrity of the scaffold during bone regeneration. Therefore, the HAP nanowire aerogel scaffold can promote the adhesion, proliferation and migration of rat bone marrow derived mesenchymal stem cells (rBMSCs), and elevate the protein expression of osteogenesis and angiogenesis related genes. The in vivo experimental results demonstrate that the HAP nanowire aerogel scaffold is favorable for the ingrowth of new bone and blood vessels, and thus can greatly accelerate bone regeneration and neovascularization. The as-prepared HAP nanowire aerogel scaffold shows promising potential for biomedical applications such as bone defect repair.
研究领域:
生物材料
·
组织工程
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Qian Zhang,Yansha Qiao,Chaojing Li,Jing Lin,Hui Han,Xiaoli Li,Jifu Mao,Fujun Wang,Lu Wang
The inferior tendon healing after surgery is inextricably linked to the surgical suture. Poor load transfer along the suture often results in a high tendon re-tear rate. Besides, the severe inflammation and infection induced by sutures even cause a second surgery. Herein, to alleviate the above-mentioned issues, a multifunctional suture was fabricated by decorating chitosan/gelatin-tannic acid (CS/GE-TA) on the porous tape suture. The porous tape suture ensured the required mechanical properties and sufficient space for tissue integration. Compared to the pristine suture, the CS/GE-TA decorated suture (TA100) presented a 332% increase in pull-out force from the tendon, indicating potentially decreased re-tear rates. Meanwhile, TA100 showed superior anti-inflammatory and antibacterial performances. In vivo experiments further proved that TA100 could not only reduce inflammatory action but also facilitate collagen deposition and blood vessel formation . These results indicate that the multifunctional sutures are promising candidates for accelerating tendon healing.
研究领域:
生物医学工程
·
组织工程
·
手术材料
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2014
·
IF 8.312
Serge Ostrovidov,Xuetao Shi,Ling Zhang,Xiaobin Liang,Sang Bok Kim,Toshinori Fujie,Murugan Ramalingam,Mingwei Chen,Ken Nakajima,Faten Al-Hazmi,Hojae Bae,Adnan Memic,Ali Khademhosseini
Engineering functional muscle tissue requires the formation of densely packed, aligned, and mature myotubes. To enhance the formation of aligned myotubes with improved contractibility, we fabricated aligned electrospun gelatin multi-walled carbon nanotubes (MWNTs) hybrid fibers that were used as scaffolds for the growth of myoblasts (C2C12). The MWNTs significantly enhanced myotube formation by improving the mechanical properties of the resulting fibers and upregulated the activation of mechanotransduction related genes. In addition, the fibers enhanced the maturation of the myotubes and the amplitude of the myotube contractions under electrical stimulation (ES). Such hybrid material scaffolds may be useful to direct skeletal muscle cellular organization, improve cellular functionality and tissue formation.
研究领域:
组织工程
·
生物材料
·
细胞生物学
·
肌肉骨骼研究
✓ 已验证
DOI
PubMed
高影响因子
Aggregate
·
2025
·
IF 13.7
Yijing Du,Xue Zheng,Yanli Gao,Zetao Dang,Yuewei Zhang,Shoujun Zhu
Concurrent imaging of skin inflammation and neovascularization is crucial for diagnosing and monitoring skin conditions, especially in flap transplantation. However, current imaging modalities in the clinic are often non-intuitive, have low resolution, or lack the ability to specifically target skin inflammation. Given that albumin can serve as a biomarker for the disruption of skin-vessel barrier (SVB), probes targeting skin inflammation typically need to specifically bind to endogenous albumin, which often results in high background signals. In this study, we screen a series of near-infrared (NIR) dyes for their in vivo covalent binding capabilities with endogenous albumin, and identify the optimal dye for achieving high-contrast imaging of skin inflammation in models of SVB disruption, with minimal interference from other tissues or organs (e.g., skin and muscle). Moreover, by utilizing an albumin-targeting dye with another albumin-escaping NIR-II dye with a non-overlapping emission wavelength, this work explores the concurrent imaging of skin inflammation and neovascularization after flap transplantation, affording to simultaneously assess skin inflammation and the restoration of blood supply.
研究领域:
生物医学成像
·
生物化学
·
皮肤病学
·
外科移植
·
分子探针
·
生物光子学
✓ 已验证
DOI
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2025
·
IF 3.5
Xiaodan Chu,Xuan Chen,Man Guo,Xinyue Li,Zhihai Qu,Peiling Li
Insufficient trophoblast cell infiltration is implicated in the progression of preeclampsia (PE). The immunoglobulin superfamily member 8 (IGSF8) has been shown to promote cell migration, invasion, and epithelial mesenchymal transition (EMT). However, the specific impact of IGSF8 on trophoblast cells in PE has not been definitively demonstrated. To address this, placental tissues from PE patients and normal subjects was collected. A PE-like rat model was established by administering L-NAME (60 mg/kg) intragastrically to pregnant rats from the 10th to the 19th day of gestation. Knockdown and overexpression plasmids of IGSF8 were transfected into JEG-3 cells for further experiments. Clinical samples indicated impaired spiral artery remodeling, and high IGSF8 expression in the placental tissues of PE patients. PE rats exhibited increased mean arterial pressure, elevated 24-h urine protein levels, higher abortion rates, and decreased placental and fetal weight compared to rats of sham group. Failure of physiological transformation of spiral arteries was observed in PE rats, along with increased IGSF8 expression. IGSF8 overexpression inhibited JEG-3 cell migration, invasion and EMT, as well as reduced release of VEGF in JEG-3 cells, impairing HUVEC tube formation. mRNA-sequencing analysis of JEG-3 cells transfected with shIGSF8 showed differentially expressed genes related to angiogenesis, and mesenchymal cell differentiation, with IGSF8 knockdown being associated with the activation of pathways involved in blood vessel development and cell migration. Overall, this study suggests that IGSF8 plays a role in the development of PE and provides new insights for potential treatments.
研究领域:
妇产科学
·
分子生物学
·
细胞生物学
·
病理生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Lin Yang,Ying Zhang,Jing Liu,Xiaofen Wang,Li Zhang,Hao Wan
Combination therapy with high efficacy and precision shows great potential in breast cancer treatment. Herein, we developed a multifunctional nanocarrier (NBP@mSiO 2 -PEG-cRGD) for tumor-targeting chemo-photothermal therapy of breast cancer in a controlled manner. The nanocarrier was constructed by enveloping nano-sized black phosphorus (NBP) within a mesoporous silica shell (mSiO 2 ) modified with the tumor-targeting peptide c(Arg-Gly-Asp-dPhe-Cys) (cRGD). Due to the existence of pore channels within mSiO 2 , NBP@mSiO 2 -PEG-cRGD achieved high loading efficiency of indole-3-carbinol (I3C) molecules (NBP@mSiO 2 -PEG-cRGD/I3C), an anti-tumor agent derived from food. Mediated by cRGD/integrin αvβ3 interaction, NBP@mSiO 2 -PEG-cRGD/I3C reached breast tumors in a targeted manner. Once irradiated by the near-infrared laser, our nanocarrier exhibited superior photothermal conversion, which not only induced photothermal therapy but also facilitated the release of I3C from NBP@mSiO 2 -PEG-cRGD/I3C within tumor cells to inhibit the activation of proto-oncogenic phosphoinositide 3-kinase (PI3K)-AKT signaling pathway and drive chemotherapy. All these attributes contributed to a satisfactory therapeutic effect toward breast tumors, manifesting in significant inhibition of cell proliferation, promotion of cell apoptosis, and reduction of tumor micro-vessel formation, which led to the efficient inhibition of tumor growth. Collectively, the nanocarrier developed here provided useful insights into the development of multifunctional platforms to effectively combat cancer.
研究领域:
癌症研究
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Yawen Chen,Wenjing Dai,Wanli Xiong,Yi Zhou,Ziying Chen,Chengxin Ge,Yan Zhou
As a meat substitute, cell cultured meat aims to simulate the composition of real meat to provide nutrient substance. The myotube formation efficiency of myoblasts in vitro is the key for simulating the structure and composition of muscle tissue. Therefore, this study is aimed to explore the most effective groove widths for myoblasts fusion and related molecular mechanism. The results of immunofluorescence showed that the grooves with a width range of 50 μm–1000 μm were beneficial to cell arrangement compared to flat structure. At the same time, the expression of myogenin ( Myog ) and myosin heavy chain 2 ( Myh2 ) up-regulated. However, the cell fusion index of myoblasts was higher in grooves with a width of 100 μm, 200 μm and 300 μm. Furthermore, Cytochalasin D disrupted intracellular stress fibers and myotube formation. However, there were still many myotubes formed in the 200 μm groove with the addition of Cytochalasin D. The expression of fusion related genes was higher than the flat group. Moreover, incorporating groove structure into scaffolds of soybean protein isolate and pea protein isolate could enhance cell adhesion, activity and myogenic differentiation of myoblasts. This could provide ideas for scaffolds design of cultured meat products using groove structure.
研究领域:
组织工程
·
细胞生物学
·
生物技术
·
食品科学
✓ 已验证
DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Lina Guo,Ziqing Zhu,Chuanzhou Gao,Kaiwen Chen,Shenzhou Lu,Hexin Yan,Wenming Liu,Mingqi Wang,Yanfang Ding,Lin Huang,Xiuli Wang
Constructing an engineered hepatic lobule-mimetic model is challenging owing to complicated lobular architecture and crucial hepatic functionality. Our previous study has demonstrated the feasibility of using silk fibroin (SF) scaffolds as functional templates for engineering hepatic lobule-like constructs. But the unsatisfactory chemical and physical performances of the SF-only scaffold and the inherent defect in the functional activity of the carcinoma-derived seeding cells remain to be addressed to satisfy the downstream application demand. In this study, SF-collagen I (SFC) composite scaffolds with improved physical and chemical properties were fabricated, and their utilization for bioengineering a more hepatic lobule-like construct was explored using the immortalized human hepatocyte-derived liver progenitor-like cells (iHepLPCs) and endothelial cells incorporated in the dynamic culture system. The SFC scaffolds prepared through the directional lyophilization process showed radially aligned porous structures with increased swelling ratio and porosity, ameliorative mechanical stiffness that resembled the normal liver matrix more closely, and improved biocompatibility. The iHepLPCs displayed a hepatic plate-like distribution and differentiated into matured hepatocytes with improved hepatic function in vitro and in vivo . Moreover, hepatocyte–endothelial cell interphase arrangement was generated in the co-culture compartment with improved polarity, bile capillary formation, and enhanced liver functions compared with the monocultures. Thus, a more biomimetic hepatic lobule-like model was established and could provide a valuable and robust platform for various applications, including bioartificial liver and drug screening.
研究领域:
组织工程
·
生物医学工程
·
细胞生物学
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
Science Advances
·
2025
·Vol. 11
·期 28
·
IF 12.5
Desheng Cao,Junliang Zhu,Yang Guo,Yang Zhou,Jia Zeng,Yuanyuan Tu,Ziyin Zhao,Laiqing Xie,E Song,Manhui Zhu,Lichen Yin
As an important modality for choroidal neovascularization (CNV) treatment, intravitreal injection of vascular endothelial growth factor A (VEGFA) inhibitors suffers from undesired response rate, low patient compliance, and ocular damage. Here, dynamically covalent lipid nanoparticles (LNPs) were engineered to mediate VEGFA gene editing and CNV treatment by codelivering Cas9 mRNA (mCas9) and single guide RNA (sgRNA) targeting VEGFA (sgVEGFA). A library of lipidoids bearing iminoboronate ester linkage was developed via facile “one-pot” synthesis, and the top-performing lipidoid-A 4 B 3 C 7 was formulated into LNP-A 4 B 3 C 7 with the highest mRNA transfection efficiency. Inside the diseased retinal pigment epithelial cells, LNPs were dissociated upon H 2 O 2 -triggered lipidoid degradation, facilitating mRNA/sgRNA release to potentiate the gene editing efficiency. In laser-induced CNV mice, mCas9/sgVEGFA@LNP-A 4 B 3 C 7 after single intravitreal injection led to pronounced VEGFA disruption and CNV area reduction, outperforming the clinical anti-VEGF drug in eliciting sustained therapeutic effect. This study establishes a robust nonviral platform for mRNA delivery and genome editing and renders a promising strategy for CNV treatment.
研究领域:
生物医学工程
·
基因治疗
·
眼科
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2019
·Vol. 33
·期 5
·1579-1591
·
IF 3.766
Li Wan,Qun Zhang,Sheng Wang,Yong Gao,Xiaofei Chen,Yang Zhao,Xiaoping Qian
Angiogenesis is central to a wide range of physiological and pathological processes including wound healing, macular degeneration, and cancer. Excessive or inappropriate vascular supply of tumors is one of the main targets for cancer therapy. Recently, critical and selective transcriptional factors such as yes-associated protein (YAP) that control the expression of angiogenesis factors have gained increasing attention in antiangiogenic therapy. In this study, we have identified and characterized a novel inhibitor of YAP, gambogic acid (GA), which exerted striking antiangiogenic effects both in vitro and in vivo. We demonstrated that GA remarkably inhibited a variety of vascular endothelial growth factor-induced angiogenesis processes including proliferation, migration, sprouting, and tube formation of endothelial cells in vitro. In addition, GA resulted in decreased neo-vessel formation in Matrigel plugs of mice and chick chorioallantoic membrane. More importantly, we showed that GA limited tumor growth via preventing tumor angiogenesis and vascular maturation. Further mechanistic studies illustrated that GA directly targeted YAP/STAT3 signaling axis, which is critical for the transcriptional regulation of a series of angiogenic factors. Taken together, these preclinical findings suggest that GA significantly repressed tumor angiogenesis and may serve as a promising drug candidate against cancer.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2024
·
IF 4.9
Hairui Zhang,Jiali Yao,Qianyang Jiang,Yurou Shi,Weihong Ge,Xiaoling Xu
Androgenetic alopecia (AGA) is a highly prevalent condition in contemporary society. The conventional treatment of minoxidil tincture is hindered by issues such as skin irritation caused by ethanol, non-specific accumulation in hair follicles, and short retention due to its liquid form. Herein, we have developed a novel minoxidil-incorporated engineered exosomes biopotentiated hydrogel (Gel@MNs) that has the capability to modulate the perifollicular microenvironment for the treatment of AGA. Leveraging the exceptional skin penetration abilities of flexible liposomes and the targeting properties of exosomes, the encapsulated minoxidil can be effectively delivered to the hair follicles. In comparison to free minoxidil, Gel@MNs demonstrated accelerated hair regeneration in an AGA mouse model without causing significant skin irritation. This was evidenced by an increase in both the number and size of hair follicles within the dermal layer, enhanced capillary formation surrounding the follicles, and the regulation of the transition of hair follicle cells from the telogen phase to the anagen growth phase. Therefore, this safe and microenvironment-modifying hybrid exosome-embedded hydrogel shows promising potential for clinical treatment of AGA.
研究领域:
皮肤病学
·
药学
·
生物技术
·
组织工程
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）