Journal of Nanostructure in Chemistry
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2021
·Vol. 11
·期 4
·707-719
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IF 6.391
Enwereuzo Onyekachi Oluchi,Akakuru Obinna Chigoziem,Uwaoma Romanus Chinonso,Elemike Elias Emeka,Akakuru Ozioma Udochukwu
Controlled release technology has continuously attracted attention as a strategy to deliver active agents to specific internal body regions with attendant cost-effectiveness among other intriguing merits. Here, drug-loaded nanoparticles (NPs) are synthesized for ultimate application in the treatment of gastroesophageal reflux disease (GERD), leveraging the benefits of controlled release strategy. To achieve this, eggshell membranes (ESMs) were extracted and combined with chitosan (CHS) to rationally obtain self-assembled CHS–ESM NPs that served as a novel nanocarrier to effectively compartmentalize a GERD-therapeutic drug famotidine (FTD) and form self-assembled FTD@CHS–ESM NPs. Advantageously, the proof-of-concept FTD@CHS–ESM NPs offer superlative tissue tolerance. The cumulative FTD release is 89% after 12 h at pH 1.2, suggesting the capability of FTD@CHS–ESM NPs for effectual controlled drug release; a testimonial of the effective compartmentalization of FTD in the nanocarrier. Furthermore, the release of FTD from the FTD@CHS–ESM NPs is best described by Higuchi square root model, in a non-Fickian diffusional release mechanism ( n = 0.584 and 0.582 in pH 1.2 and pH 6.8, respectively). The drug release system demonstrated in this work, therefore, holds strong promise for the oral nanomedical treatment of GERD in vivo, and promotes the rational synthesis of organic-based biocompatible nanomaterials for biomedical application. Graphic abstract
研究领域:
药剂学
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生物医学工程
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材料科学
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DOI
高影响因子
ACS Nano
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2024
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IF 15.8
Weike Shaoyong,Lu Sun,Yujie Gan,Hongli Jin,Wusu Wang,Lin Yin,Yizhen Wang,Mingliang Jin
Contaminant-bearing polystyrene microplastics (PSMPs) may exert significantly different toxicity profiles from their contaminant-free counterparts, with the role of PSMPs in promoting contaminant uptake being recognized. However, studies investigating the environmentally relevant exposure and toxic mechanisms of aged PSMPs binding to Cr are limited. Here, we show that loading of chromium (Cr) markedly alters the physicochemical properties and toxicological profiles of aged PSMPs. Specifically, Cr-bearing aged PSMPs induced severe body weight loss, oxidative stress (OS), autophagy, intestinal barrier injury, inflammation–pyroptosis response, and enteropathogen invasion in mice. Mechanistic investigations revealed that PSMPs@Cr exacerbated the OS, resulting in intestinal barrier damage and inflammation–pyroptosis response via overactivated Notch signaling and autophagy/cathepsin B/IL-1β pathway, respectively, which ultimately elevated mortality related to bacterial pathogen infection. In vitro experiments confirmed that autophagy-mediated reactive oxygen species (ROS) overproduction resulted in severe pyroptosis and impaired intestinal stem cells differentiation alongside the overactivation of Notch signaling in PSMPs@Cr-exposed organoids. Overall, our findings provide an insight into autophagy-modulated ROS overproduction within the acidic environment of autophagosomes, accelerating the release of free Cr from PSMPs@Cr and inducing secondary OS, revealing that PSMPs@Cr is a stable hazard material that induces intestinal injury. These findings provided a potential therapeutic target for environmental MPs pollution caused intestinal disease in patients.
研究领域:
环境科学
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毒理学
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胃肠病学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2022
·
IF 14.224
Tianyu Gao,Bingbing Sun,Zhenbiao Xu,Qiaoyun Chen,Meng Yang,Qinli Wan,Linxia Song,Guo Chen,Chunxia Jing,Eddy Y. Zeng,Guang Yang
The potential adverse effects of microplastics (MPs) on ecosystems and human health have received much attention in recent years. However, only limited data are available on the mechanisms for the uptake, distribution, and effects of MPs in freshwater organisms , especially with respect to tissue repair, regeneration and impairment of stem cell functions. To address this knowledge gap, we conducted exposure experiments in which planarians ( Dugesia japonica ) were exposed to polystyrene (PS)-MPs mixed in liver homogenate and examined the tissue growth and regeneration, stem cell functions, and oxidative stress . The body and blastema areas decreased upon exposure to PS-MPs, indicating that the growth and regeneration of planarians were delayed. The proliferation and differentiation processes of stem cells were inhibited, and the proportion of mitotic stem cells decreased, which may be related to the activation of the TGFβ/SMAD4 and Notch signaling pathways. The enhancement of antioxidant enzyme activities and malondialdehyde on the first day of exposure to PS-MPs confirmed the oxidative stress response of planarians to PS-MPs. The present study demonstrated the likelihood of biotoxicity induced by PS-MPs. These results will provide clues for further investigations into the potential risks of PS-MPs to human stem cells.
研究领域:
生态学
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毒理学
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细胞生物学
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DOI
PubMed
高影响因子
ENGINEERING FRACTURE MECHANICS
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2012
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IF 1.353
Abdel-Hamid I. Mourad,Aly El-Domiaty,Yuh J. Chao
The effect of specimen notch root radius ρ and specimen size (thickness B and ligament b ) on the apparent fracture toughness K I,app is investigated. Series of fracture tests on nonstandard compact tension CT specimen of low alloy steel EN34NiCrMo6, which is equivalent to AISI 4340 low alloy steel with different values of ρ and crack length to width ratio a / W were conducted to measure the K I,app . The experimental results show that, K I,app depends on ρ and specimen size. There is a critical notch root radius ρ c under which K I,app becomes independent of ρ . Two empirical models have been proposed to predict K I,app and can be used to transfer the data among specimens of different ρ . One additional empirical model is developed to transfer the data among specimens of different ligament, b. Finally, a model is developed by modifying the ASTM E1921 standard equation (which predicts the thickness effect only) to include the combined effect of B and b . The model predictions are in good agreement with the experimental results.
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DOI
高影响因子
Oxidative Medicine and Cellular Longevity
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2020
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IF 5.076
Xing Li,Dan Luo,Yu Hou,Yonghui Hou,Shudong Chen,Jiheng Zhan,Jiyao Luan,Le Wang,Dingkun Lin
Spinal cord microcirculation involves functioning endothelial cells at the blood spinal cord barrier (BSCB) and maintains normal functioning of spinal cord neurons, axons, and glial cells. Protection of both the function and integrity of endothelial cells as well as the prevention of BSCB disruption may be a strong strategy for the treatment of spinal cord injury (SCI) cases. Sodium Tanshinone IIA silate (STS) is used for the treatment of coronary heart disease and improves microcirculation. Whether STS exhibits protective effects for SCI microcirculation is not yet clear. The purpose of this study is to investigate the protective effects of STS on oxygen-glucose deprivation- (OGD-) induced injury of spinal cord endothelial cells (SCMECs) in vitro and to explore effects on BSCB and neurovascular protection in vivo. SCMECs were treated with various concentrations of STS (1 μM, 3 μM, and 10 μM) for 24 h with or without OGD-induction. Cell viability, tube formation, migration, and expression of Notch signaling pathway components were evaluated. Histopathological evaluation (H&E), Nissl staining, BSCB permeability, and the expression levels of von Willebrand Factor (vWF), CD31, NeuN, and Notch signaling pathway components were analyzed. STS was found to improve SCMEC functions and reduce inflammatory mediators after OGD. STS also relieved histopathological damage, increased zonula occludens-1 (ZO-1), inhibited BSCB permeability, rescued microvessels, protected motor neuromas, and improved functional recovery in a SCI model. Moreover, we uncovered that the Notch signaling pathway plays an important role during these processes. These results indicated that STS protects microcirculation in SCI, which may be used as a therapeutic strategy for SCI in the future.
研究领域:
神经科学
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药理学
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细胞生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Molecular Neuroscience
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2026
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IF 4.4
Ping Yuan,Jin Chen,Li Jiang
Background Notch overactivation and aberrant neurogenesis following status epilepticus (SE) has been identified by our previous study. The current study further supplements this by exploring additional pathological changes during epileptogenesis post-SE, as well as the potential role of Notch in these processes. Methods Rats were administered N-[N-(3,5-difluorophenacetyl)-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT) immediately after SE induction. Spontaneous recurrent seizures were monitored via electroencephalogram (EEG). Hippocampal synaptic ultrastructure was analyzed using transmission electron microscopy. Nissl staining and Timm staining were performed at 28 days post-SE to evaluate neuronal loss and mossy fiber sprouting (MFS), respectively. Results EEG recordings demonstrated that DAPT treatment significantly reduced the severity of epileptiform discharges post-SE. Transmission electron microscopy revealed decreased presynaptic active zone length and postsynaptic density thickness in the hippocampal CA1 region of DAPT-treated rats. Nissl staining indicated attenuated hippocampal neuronal loss and partial structural restoration following DAPT administration. Notably, Timm staining showed no significant effect of DAPT on MFS compared to controls. Conclusion Inhibition of Notch signaling alleviates EEG epileptic activity, mitigates synaptic damage, and partially preserves hippocampal neuronal structure in adolescent rats post-SE, without altering MFS. These findings suggest Notch signaling as a potential therapeutic target for post-SE neuroprotection, though its role in MFS remains unclear.
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Jianwei Cui,Liting Zhou,Xuehan Ding,Hui Ye,Tianyou Wang,Wen Qi
Decabromodiphenyl ethane (DBDPE) is a kind of commonly used novel brominated flame retardants, and widely exists in environments. DBDPE could be enriched in the liver, but its effects on lipid metabolism in liver and underlying mechanisms remain largely unknown. In the present study, firstly, we investigated the impact of DBDPE on the liver in rats and L02 cells. We found that DBDPE exposure could induce lipid metabolism disorders, up-regulate the expressions of Notch pathway genes, and promote Arrestin domain containing protein 1-mediated microvesicles (ARMMs)-derivation. Subsequently, siRNAs were used to inhibit the Notch pathway and the ARMMs-derivation in L02 cells respectively. It demonstrated that inhibition of Notch or ARMMs-derivation could reverse the lipid accumulation induced by DBDPE, and the inhibition of ARMMs-derivation could suppress the activation of the Notch pathway. Extracellular vesicles from L02 cells exposed to DBDPE co-culture with L02 cells confirmed that ARMMs can directly activate the Notch signaling pathway and induce lipid accumulation. In conclusion, our study is the first to explore the role of ARMMs in lipid metabolism disorders caused by environmental pollutants. We found that exposure to DBDPE increases the levels of ARMMs, which directly activates the Notch signaling pathway and triggers disruptions of liver lipid metabolism.
研究领域:
毒理学
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环境健康
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分子生物学
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细胞生物学
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代谢
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2016
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IF 7.145
Ningxiao Yuan,Lu Xu,Hualiang Wang,Youpeng Fu,Zhe Zhang,Lan Liu,Cuiling Wang,Jianhao Zhao,Jianhua Rong
Double-network (DN) hydrogels with high strength and toughness have been developed as promising materials. Herein, we explored a dual physically cross-linked polyacrylamide/xanthan gum (PAM/XG) DN hydrogel. The nonchemically cross-linked PAM/XG DN hydrogels exhibited fracture stresses as high as 3.64 MPa (13 times higher than the pure PAM single network hydrogel) and compressive stresses at 99% strain of more than 50 MPa. The hydrogels could restore their original shapes after continuously loading–unloading tensile and compressive cyclic tests. In addition, the PAM/XG DN hydrogels demonstrated excellent fatigue resistance, notch-insensitivity, high stability in different harsh environments, and remarkable self-healing properties, which might result from their distinctive physical-cross-linking structures. The attenuated total reflectance infrared spectroscopy (ATR-IR) and dynamic thermogravimetric analysis (TGA) results indicated that there were no chemical bonds (only hydrogen bonds) between the XG and PAM networks. The PAM/XG DN hydrogel synthesis offers a new avenue for the design and construction of DN systems, broadening current research and applications of hydrogels with excellent mechanical properties.
研究领域:
材料科学
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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
EUROPEAN JOURNAL OF MEDICAL RESEARCH
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2024
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IF 2.8
Lu Yan,Yin-Sen Song,Jian Zhou,Lin Zhu,Tian-Wei Shi,Hui-Qian Yu,Zi-Qing Dong,Wei Wang,Ting Long,Hao-Ying Liu,Zhe-Ye Shi,Jian-Guo Li
Background Nicastrin, a subunit of the γ-secretase complex, is encoded by the NCSTN gene and regulates notch signaling, it is involved in the pathogenesis of hidradenitis suppurativa (HS), Alzheimer disease (AD), and liver cancer. However, the animal models for studying HS are relatively scarce. Methods CRISPR/Cas-mediated genetic engineering was used to generate targeted knockout offspring mice (C57BL/6J). Different doses (10 mg/kg, 20 mg/kg, and 30 mg/kg) and injection methods (subcutaneous/intraperitoneal/gavage injection) of tamoxifen were used to induce the construction of NCSTN knockout mice (mice model). The expressions of nicastrin, NICD1, hes1 in skin, brain, and liver tissue in mice model and wild-type (WT) mice were measured by qRT-PCR and IHC. Results The construction of mice model was successfully induced by tamoxifen, knockout efficiency was 93%, there was no difference in knockout efficiency among three doses, injection methods, genders ( P > 0.05). HS-like lesions appeared on the skin of NCSTN knockout mice after 1 month of treatment with tamoxifen, male mice had a higher number of skin lesions compared to female mice (male vs female = 76.5% vs 41.7%, P = 0.027). Compared with WT mice, the expressions of nicastrin (skin P = 0.0009, brain P = 0.0194, liver P = 0.0066), NICD1 (skin P = 0.0115, brain P = 0.0307, liver P = 0.008), hes1 (skin P = 0.0476, brain P = 0.0143, liver P = 0.0003) in mice model all decreased. Conclusions The NCSTN knockout mouse might be employed as HS animal model; Reducing nicastrin may affect the expression of notch1–hes1 pathway molecules in skin, brain, and liver tissues; low dose (10 mg/kg/d) tamoxifen could be used to induce the deletion of the target gene in mice.
研究领域:
分子生物学
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遗传学
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病理学
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肿瘤学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2020
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IF 4.545
Hui Wu,Qian-Yun Chen,Wen-Zhu Wang,Si Chu,Xing-Xing Liu,Yu-Jin Liu,Chen Tan,Feng Zhu,Shuang-Jiao Deng,Ya-Lan Dong,Ting Yu,Fei Gao,Hong-Xia He,Xue-Yuan Leng,Heng Fan
Background Compound sophorae decoction (CSD), a Chinese Herbal decoction, is frequently clinically prescribed for patients suffered from ulcerative colitis (UC) characterized by bloody diarrhea. Yet, the underlying mechanism about how this formulae works is remain elusive. Methods In the present study, the experimental colitis in C57BL/6 J mice was induced by oral administration of standard diets containing 3% dextran sodium sulfate (DSS), and CSD was given orally for treatment at the same time. The clinical symptoms including stool and body weight were recorded each day, and colon length and its histopathological changes were observed. Apoptosis of colonic epithelium was studied by detecting protein expression of cleaved caspase-3, and cell proliferation by Ki-67 immunohistochemistry. Tight junction complex like ZO-1 and occludin were also determined by transmission electron microscope and immunofluorescence. The concentration of FITC-dextran 4000 was measured to evaluate intestinal barrier permeability and possible signaling pathway was investigated. Mucin2 (MUC2) and notch pathway were tested through western blot. The M1/M2 ratio in spleen and mesenteric lymph nodes were detected by flow cytometry. And the mRNA levels of iNOS and Arg1 were examined by qRT-PCR. Results CSD could significantly alleviate the clinical manifestations and pathological damage. Body weight loss and DAI score of mice with colitis were improved and shortening of colon was inhibited. The administration of CSD was able to reduce apoptotic epithelial cells and facilitate epithelial cell regeneration. Increased intestinal permeability was reduced in DSS-induced colitis mice. In addition, CSD treatment obviously up-regulated the expression of ZO-1 and occludin and the secretion of MUC2, regulated notch signaling, and decreased the ratio of M1/M2. Conclusions These data together suggest that CSD can effectively mitigate intestinal inflammation, promote phenotypic change in macrophage phenotype and enhance colonic mucosal barrier function by, at least in part, regulating notch signaling in mice affected by DSS-induced colitis.
研究领域:
药理学
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免疫学
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胃肠病学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Autophagy
·
2026
·
IF 18.6
Zhengran Li,Huiqing Zhao,Danjie Zhang,Jing Wei,Xiyue Tao Liu,Ruiyan Kong,Xuejing Ren,Hang Zhao,Xiaomin Fang,Jingyan Fu,Zhouhua Li
The self-renewal and differentiation of stem cells are tightly controlled to maintain tissue homeostasis. Failure in stem cell maintenance results in stem cell depletion and precocious aging. However, how stem cells are maintained still remains not fully understood. Here, through a large-scale RNAi screen for maintenance and proliferation of adult Drosophila intestinal stem cells (ISCs), we identify several subunits of V-ATPase including Vha68-2/ATP6V1A, required for ISC proliferation, differentiation and tissue regeneration. Inactivation of Vha68-2 results in accumulation of plasma membrane (PM)-derived structures in autophagosomes and lysosomes through Atg16 and Rab5. Furthermore, Vha68-2-defective ISCs undergo direct differentiation due to ectopic Notch activation. Mechanistically, Vha68-2 facilitates Notch receptor internalization and subsequent degradation in autolysosomes to quench ectopic Notch activation, thereby maintaining ISC fate. Truncated Notch product devoid of its extracellular domain is accumulated in autolysosomes upon Vha68-2 deficiency. The Notch products accumulated in autolysosomes still require further cleavage to drive ISC differentiation. The functions of Vha68-2 in macroautophagy/autophagy and ISC maintenance are evolutionarily conserved. Our results provide new insights into the underlying mechanism of how autophagy is involved in stem cell maintenance under physiological conditions.Abbreviations: aph-1: anterior pharynx defective 1; ATP6V1A: ATPase H+ transporting V1 subunit A; CASM: conjugation of ATG8s to single membranes; EB: enteroblast; EC: absorptive enterocyte; ER: endoplasmic reticulum; ISC: intestinal stem cell; kuz: kuzbanian; LTDR: LysoTracker Deep Red; LTR: LysoTracker Red; MARCM: mosaic analysis with a repressible cell marker; NECD: Notch extracellular domain; NICD: Notch intracellular domain; PM: plasma membrane; PAS: phagophore assembly site; SNARE: soluble N-ethylmaleimide-sensitive factor-attachment protein receptor; TEM: transmission electron microscopy; TM: tunicamycin.
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产品关联
DOI
高影响因子
Materials Today Bio
·
2026
·
IF 11
Rui Zhang,Xiaoyu Zhang,Jiangbo Guo,Yilin Yang,Junjie Niu,Hao Shen,Yi Zheng,Jiaqi Wang,Suhao Wang,Li Ni,Huilin Yang,Qin Shi
Intervertebral disc degeneration (IVDD) is the major pathological cause of low back pain and global disability. Its chronic and persistent inflammatory microenvironment, resembling a flowing flood to erode the ecosystems relentlessly, disrupts the intervertebral disc homeostasis. In the present study, we first verified that Notch signaling is negatively correlated with inflammation in IVDD samples. Meanwhile, we identified a natural flavonoid hesperetin (Hes) as a potential agonist of Notch1 by molecular docking predicting. Herein, we developed an EV-inspired bioactive reservoir system, in which the natural extracts hes was encapsulated into liposomes (Hes@lipo) and embedded within a gelatin methacryloyl (GM) hydrogel (GM/Hes@lipo)to achieve sustained release. By mimicking the extracellular matrix (ECM)-like microenvironment of the intervertebral disc (IVD), GM/Hes@lipo provided physiological environment for nucleus pulposus cells (NPCs) adhesion and growth maintenance. Furthermore, by activating Notch signaling, GM/Hes@lipo effectively restored the dynamic balance between pro- and anti-inflammatory cytokines and maintained ECM metabolic homeostasis, attenuating NOD-like receptor signaling, thereby inhibiting NPC pyroptosis. Based on these aspects, GM/Hes@lipo relieved the IVDD process, maintained annulus fibrosus integrity, and effectively alleviated discogenic pain after the platform was administrated into the intervertebral disc of the rats. Collectively, as an anti-inflammatory “flood-control” system, the Notch signaling-targeted biomimetic hydrogel presents a biomimetic–natural compound combinatorial strategy offering promising therapy for mitigating IVDD progression.
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DOI
PubMed
高影响因子
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