NANOTECHNOLOGY
·
2021
·Vol. 32
·期 20
·205103
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IF 3.874
Ran Sun,Yuyang Zhao,Yanan Wang,Qian Zhang,Ping Zhao
Dual-modal molecular imaging that combines photoacoustic imaging with near-infrared fluorescence imaging integrates the benefits of both imaging modalities and may achieve more precise detection of disease. In this study, silver sulfide quantum dots (Ag2S QDs) with superior photoacoustic properties and a strong fluorescent emission in the NIR region were successfully synthesized. They were further modified with the insulin-like growth factor 1 receptor (IGF-1R) targeted small scaffold protein, Affibody (ZIGF-1) to achieved targeted photoacoustic/fluorescent dual-modal imaging of cancer. Our results showed that the prepared nanoprobe had good tumor targeting properties in vivo, and the probe also showed good biocompatibility without any significant toxicity.
研究领域:
生物医学工程
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癌症研究
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分子成像
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纳米技术
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生物相容性
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PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2023
·Vol. 25
·期 4
·1-11
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IF 2.7
Chun-Lian Liang,Xiu-Li Li,Xiao-Juan Quan,Lin Zhang
Idiopathic pulmonary fibrosis (IPF) is a heterogeneous lung disease associated with high mortality. Disabled‑2 (DAB2), an adapter protein, regulates cell‑fibrinogen adhesion and fibrinogen uptake. DAB2 is differentially expressed in mouse fibrotic lungs induced by bleomycin according to a genome microarray analysis based on Gene Expression Omnibus database. However, the role of DAB2 in IPF has not been revealed. A bleomycin‑induced mouse model of pulmonary fibrosis was constructed in the present study. It found that the expression of DAB2 was upregulated in bleomycin‑induced fibrotic lung tissue with collagen fiber deposition and pulmonary interstitium thickening. Colocalization of DAB2 with α‑smooth muscle actin (SMA) was observed in lung tissue sections. In vitro, human lung fibroblast MRC‑5 cells were treated with TGF‑β1 and the expression of DAB2 was increased. Knockdown of DAB2 suppressed cell proliferation and the expression of α‑SMA, collagen I, collagen IV and fibronectin in TGF‑β1‑treated MRC‑5 cells. The phosphorylation levels of PI3K and AKT were suppressed in DAB2‑knockdown cells. IGF‑1/IGF‑1R has been reported to promote pulmonary fibrosis and activate the PI3K/Akt signaling. In the present study, the activation of IGF‑1/IGF‑1R signaling pathways in bleomycin‑induced fibrotic lung tissues were positively associated with DAB2 expression. The phosphorylation level of IGF‑1R was increased in MRC‑5 cells with TGF‑β1 treatment, and DAB2 expression was decreased by silencing of IGF‑1R. This suggested that DAB2 might be a downstream target of the IGF‑1R pathway and thus induced PI3K/AKT signaling activation and fibrogenesis. The current study demonstrated the importance of DAB2 in pulmonary fibrosis and suggested the potential of IGF‑1R/DAB2/PI3K in the pathogenesis of IPF.
研究领域:
肺科学
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细胞生物学
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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
BIOCHEMICAL PHARMACOLOGY
·
2026
·
IF 5.6
Majid Manzoor,Danni Chen,Ting Jiang,Jiahui Lin,Jiayuan Zeng,Lan Xiang,Jianhua Qi
Current pharmacological treatments for alopecia mainly aim to prevent further hair loss. However, efforts to identify therapeutic agents capable of reactivating the hair cycle have limited success. Herein, we identify that TBG096, a novel natural product-derived molecule with anti-aging properties promotes hair growth. In particular, we investigated hair regeneration effects of topical and oral TBG096 treatments across various models, including female and male rats, naturally aged and dihydrotestosterone (DHT)-induced alopecia model mice. TBG096 facilitated the transition of hair follicles from the telogen to the anagen phase, enhancing hair growth rate in a dose-dependent manner. Mechanistically, TBG096 directly binds and activates insulin-like growth factor 1 receptor (IGF-1R) that in turn activates downstream phosphatidylinositol 3-kinase /protein Kinase B (PI3K/AKT) signaling pathway. IGF-1R/PI3K/AKT activation increased angiogenesis in the dermal papilla to promote hair follicle proliferation and differentiation. Conversely, inhibition of IGF-1R impaired TBG096 mediated angiogenesis and hair regrowth. In addition, TBG096 also reduced DHT levels, increased keratin 15 (k15) expression and regulated growth factors like IGF-1 and epidermal growth factor (EGF), suggesting a restoration of normal follicular function. This is the first study to comprehensively demonstrate that TBG096 effectively promotes hair regeneration independent of age, gender, or application method, making it a promising candidate for treating androgenic alopecia and age-related hair loss.
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高影响因子
Clinical and Experimental Nephrology
·
2022
·Vol. 26
·期 7
·630-639
·
IF 2.617
Xia Yangyang,Wan Cheng,Zhang Qingyan,Wang Hengjin,Feng Yuan,Jiang Chunming
Background Peritoneal fibrosis (PF) is caused by epithelial-mesenchymal transdifferentiation (EMT) in the peritoneum under high glucose (HG) conditions. The study aimed to explored the role of Insulin-like growth factor 1 receptor (IGF-1R) in the regulation of EMT in human peritoneal mesothelial cells (HPMCs). Methods We used HG peritoneal dialysis fluid (PDF) to induce in vivo PF in mice, and treated HPMCs with HG in vitro to stimulate EMT. Results In the mice, the higher the glucose concentration in the dialysate, the more obvious the peritoneal tissue thickening and the more that collagen was deposited. The in vitro study indicated that the expression of IGF-1R, α-SMA, vimentin was upregulated, while the expression of occludin, ZO-1, and E-cadherin was downregulated in HPMCs under HG and IGF-1R overexpression conditions. Conversely, the expression of IGF-1R, α-SMA, and vimentin was downregulated, while the expression of occludin, ZO-1, and E-cadherin was upregulated in IGF-1R-underexpressed HPMCs under HG conditions. The cell migration abilities were increased, while the cell adhesion abilities were reduced in HPMCs under HG and IGF-1R overexpression conditions. In contrast, cell migration abilities were reduced, while cell adhesion abilities were increased in IGF-1Runderexpressed HPMCs under HG conditions. Conclusions Targeting at IGF-1R may provide novel insights into the prevention and treatment of PF.
研究领域:
肾病学
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细胞生物学
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分子生物学
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高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Majid Manzoor,Danni Chen,Jiahui Lin,Ying Wang,Lan Xiang,Jianhua Qi
Background Hair follicles play a crucial role in hair growth, wound healing, thermoregulation, and sebum production. Hair loss affects millions of people worldwide, yet therapeutic options for managing hair loss and pattern baldness are limited. Isoquercitrin (IQ), a natural small molecule from drinkable Chinese tea, is famous for anti-aging properties. Purpose This study aimed to explore the potential of IQ in treating and preventing hair loss, along with its underlying mechanisms. Methods The adult male and female, as well as middle-aged female sprague dawley (SD) rats were used to conduct hair growth experiments in vivo . Signaling pathways and target protein identification were analyzed through western blotting, drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR) analyses. Further, the targets were confirmed through in vivo inhibition experiments. Results IQ is reported here to stimulate anagen phase initiation and hair regrowth by directly interacting with adenosine 5′-monophosphate-activated protein kinase (AMPK) and insulin-like growth factor 1 receptor (IGF-1R). This process involves the AMPK/mammalian target of rapamycin (mTOR)/ unc-51-like autophagy-activating kinase 1 (ULK1) signalling pathway to trigger autophagy and the IGF-1R/phosphatidylinositol 3-kinase (PI3 K)/protein Kinase B (AKT), vascular endothelial growth factor (VEGF)/ vascular endothelial growth factor receptor (VEGFR)/ angiotensin (ANG) pathways to promote angiogenesis in female rats. Furthermore, the hair regrowth efficacy of IQ in adult male rats and middle-aged female rats was verified and shown. Similarly, our findings indicate that IQ promotes hair regrowth in middle-aged rats through autophagy and angiogenesis, akin to its effects in adult rats. Conclusion AMPK and IGF-1R proteins are identified as the target proteins of IQ and the AMPK/mTOR/ULK1, IGF-1R/PI3K/AKT and VEGF/VEGFR/ANG signalling pathways take important roles in hair growth effect of IQ. Thus, these signaling pathways are crucial for developing future treatments and clinical strategies for hair regeneration.
研究领域:
药理学
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皮肤病学
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分子生物学
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Xiaojun Yan,Yulin Zhang,Wen Zeng,Yang Li,Chenhui Zhu
Tendon repair remains a major clinical challenge, largely because current strategies often fail to simultaneously achieve early inflammatory control and subsequent matrix remodeling. To address this problem, we developed a dynamically responsive nano-hydrogel, CAPP@IGF-1, composed of 3-carboxyphenylboronic acid-modified chitosan, polyvinyl alcohol, and IGF-1-loaded PLGA microspheres, which were integrated through phenylborate ester crosslinking. The hydrogel exhibited favorable self-healing behavior together with enhanced mechanical properties, with an elastic modulus of 4.5 MPa and a toughness of 15.3 MJ/m³, enabling it to maintain local structural stability under the complex dynamic conditions of tendon repair. Under the acidic inflammatory microenvironment, CAPP@IGF-1 enabled controlled local release of IGF-1 and activated the IGF-1R/AKT signaling pathway, thereby markedly promoting macrophage reprogramming from the pro-inflammatory M1 state to the pro-reparative M2 state. This was accompanied by suppression of IL-6, IL-2, and TNF-α and upregulation of IL-10, leading to the establishment of a local immune microenvironment favorable for repair. On this basis, the hydrogel further promoted tendon stem/progenitor cell migration, proliferation, extracellular matrix remodeling, and more ordered collagen deposition. In a rabbit tendon injury model, CAPP@IGF-1 notably reduced peritendinous adhesion, and enhanced the mechanical recovery of repaired tendons. Collectively, CAPP@IGF-1 achieves stage-specific intervention during tendon healing through the combined effects of a dynamically crosslinked network, enhanced mechanical properties, and intelligent IGF-1 release. This study demonstrates the feasibility of using materials design to connect inflammatory microenvironment regulation with tissue regeneration and provides a new strategic basis for the precise repair of complex tendon injuries.
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高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
·
IF 6.51
Yu Zou,Quan Zhou,Yinan Zhao,Defu Zhi,Huiying Chen,Rui Wang,Benzhi Ju,Shubiao Zhang
Ionizable lipids are the leading vectors for gene therapy. Understanding the effects of molecular structure on efficient gene delivery is one of the most important challenges for maximizing the utility of such lipid vectors. We synthesized an array of pH-responsive and ionizable lipids to investigate the relationship between lipid structure and activity. The optimized lipid (EDM) has double tertiary amines in the headgroup and an ester linker. EDM exhibited efficient DNA and siRNA delivery to, and gene silencing of, A549 cells. EDM has a p K a value of 6.67, which enabled it to quickly escape from the endosome after entering the cell; the ester linkages rapidly degraded and enabled gene release into the cytoplasm. EDM also delivered IGF-1R siRNA to inhibit tumor growth and induce cancer cell apoptosis by efficient inhibition of IGF-1R expression in mice. Our study on the structure–activity relationships of ionizable lipids will facilitate clinical applications.
研究领域:
药学
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基因治疗
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分子生物学
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癌症研究
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 20
·15403
·
IF 5.6
Li Chen,Meng Tian,Jing Yang,Zhenxu Wu
Polymer microspheres have recently shown outstanding potential for bone tissue engineering due to their large specific surface area, good porosity, injectable property, good biocompatibility, and biodegradability. Their good load-release function and surface modifiability make them useful as a carrier of drugs or growth factors for the repair of bone defects in irregularly injured or complex microenvironments, such as skull defects. In this study, berberine (BBR)-encapsulated poly(lactic-co-glycolic acid) (PLGA)/hydroxyapatite (HA) microspheres were fabricated using electrified liquid jets and a phase-separation technique, followed by modification with the 3,4-hydroxyphenalyalanine-containing recombinant insulin-like growth–factor-1 (DOPA-IGF-1). Both the BBR and the IGF-1 exhibited sustained release from the IGF-1@PLGA/HA-BBR microspheres, and the composite microspheres exhibited good biocompatibility. The results of the alkaline phosphatase (ALP) activity assays showed that the BBR and IGF-1 in the composite microspheres synergistically promoted the osteogenic differentiation of MC3T3-E1 cells. Furthermore, it was confirmed that immobilized IGF-1 enhances the mRNA expression of an osteogenic-related extracellular matrix and that BBR accelerates the mRNA expression of IGF-1-mediated osteogenic differentiation and cell mineralization. Further cellular studies demonstrate that IGF-1 could further synergistically activate the IGF-1R/PI3K/AKT/mTOR pathway using BBR, thereby enhancing IGF-1-mediated osteogenesis. Rat calvarial defect repair experiments show that IGF-1@PLGA/HA-BBR microspheres can effectively promote the complete bony connection required to cover the defect site and enhance bone defect repair. These findings suggest that IGF-1@PLGA/HA-BBR composite microspheres show a great potential for bone regeneration.Keywords:polymer microspheres;berberine (BBR);IGF-1;bone regeneration;osteogenic differentiation
研究领域:
生物医学工程
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组织工程
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骨再生
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药学
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PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2024
·Vol. 30
·期 10
·e70076
·
IF 4.8
Jing An,Lulu Wen,Haiyang Yu,Zhongqi Bu,Juan Feng
Aims Insulin-like growth factor binding protein 2 (IGFBP2) is implicated in various neurodegenerative diseases. However, its role in Parkinson's disease (PD) is unclear. Methods PD rat model was established by 6-OHDA injection. After 3 weeks, mRNA-seq was conducted. Rats received rIGFBP2 via intra-MFB injection 6 h prior to 6-OHDA infusion, and the effect of IGFBP2 in PD rats was investigated by western blotting, IHC, specific kits, JC-1 staining, and TUNEL analysis. In vitro, PC12 cells were treated with 6-OHDA, and CCK-8, specific kits, Hoechst 33258 staining, Western blotting, and JC-1 staining were performed to assess the IGFBP2's role. Results mRNA-seq revealed DEGs in PD, with attention to downregulated IGFBP2. rIGFBP2 treatment aggravated neurobehavioral deficits, decreased TH expression, Ψm, ATP level and SOD, GSH-Px activities but increased α-synuclein, ROS, MDA, mitochondrial cytochrome c contents, cell apoptosis in 6-OHDA-lesioned rats, which might be mediated through inactivating IGF-1R/AKT pathway. In 6-OHDA-treated PC12 cells, rIGFBP2 aggravated cell injury, demonstrated by decreased cell viability and increased apoptosis, oxidative stress, and mitochondrial dysfunction. Co-treatment with rIGFBP2 and rIGF-1 partially reversed the effect of rIGFBP2 on cell damage. Conclusion IGFBP2 exacerbates neurodegeneration in PD through increasing oxidative stress, mitochondrial dysfunction, and apoptosis via inhibiting IGF-1R/AKT pathway.
研究领域:
神经科学
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分子生物学
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药理学
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病理学
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PubMed
高影响因子
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