CHEMISTRY & BIODIVERSITY
·
2012
·Vol. 9
·期 9
·1916-1922
·
IF 1.804
Zhihan Xu,Chengyue Zhang,Yue Zhang,Xiaoda Yang
Measurement of paracellular permeation is an important assay for tight-junction investigations of drug toxicity, especially for metal-based drugs, and routine validation of the integrity of cell monolayers for models of drug absorption. Great efforts have been made in discovery and validation of novel paracellular diffusion indicators. In the present work, we prepared three Eu complexes, i.e. , [Eu(dtpa)] (dtpa=diethylenetriaminepentaacetic acid), [Eu(dtpa)(BSA)], and [Eu(dtpa)(PLL)] (PLL=poly( L -lysine)), and tested their permeation properties on Madin Darby canine kidney (MDCK) cells. The experimental results showed that all three probes were nontoxic to MDCK cells, permeated across MDCK monolayer exclusively via the paracellular pathways, and responded well to the changes on tight junction with high correlation of P app values to the decrease of trans-epithelial electric resistance (TEER). In addition, time-resolved fluorescence assays were conducted in a high-sensitivity and background-free mode. All these results confirmed the Eu complexes as novel and practical paracellular indicators.
研究领域:
药理学
·
细胞生物学
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2020
·
IF 7.1
Ying Zhang,Xie-an Yu,Yiting Hu,Xuefei Bai,Ran Zhang,Mi Lu,Jianhui Sun,Jiangwei Tian,Bo-Yang Yu
Cell surface charge serves a significant role in maintaining cell membrane stability and integrity, affecting cell structure/functions and the expression of signaling molecules. With the aggravation of the cell injury, cell surface charge would have a difference, which could be treated as a vital indicator for the discernment of cell pathological states. Herein, we developed a novel and instantaneous response method for the determination of cell viability based on cell surface charge. This study introduced a fluorescence resonance energy transfer-based polydopamine-polyethyleneimine/quantum dot (PDA-PEI/QD) sensor constructed by PDA-PEI with positive charge and QD with negative charge via electrostatic interaction, which can be used to instantaneously read out the cell injured states through fluorescent signal change induced by the comprehensive charged materials on the cell surface. The resulting fluorescence signals induced by different hepatotoxic drugs showed the difference. Furthermore, it was worth noting that the fluorescence change induced by 12 hepatotoxic drugs had a close relationship with cellular states, presenting the consistent tendency with cell viability. Accordingly, this method may have applications in the fields of cell viability detection, drug toxicity evaluation, and even elucidating the mechanism of drug-induced liver injury in the future.
研究领域:
生物传感器
·
细胞生物学
·
药学
·
毒理学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
·
2020
·Vol. 108
·期 8
·3331-3344
·
IF 2.831
Jiaojun Wei,Dongmei Lei,Maohua Chen,Pan Ran,Xiaohong Li
In vitro cell and tissue models are playing essential roles in the identification of active pharmaceutical ingredients. Though HepG2 cells have attractive profiles over primary hepatocytes in the availability and viability retention, the expression of metabolizing enzymes is quite low. In the current study, three-dimensional (3D) HepG2 spheroids with smaller sizes of 150 μm (3Ds) and bigger sizes of 300 μm (3Db) are engineered using injectable fiber fragments as the substrate. In contrast to two-dimensional (2D) culture, the enzyme activities for drug metabolisms are restored in 3Ds and the pathophysiological profiles of tumor tissues are rebuilt in 3Db spheroids. Compared with spheroid culture without fiber fragments, 3Ds spheroids show higher activities of metabolizing enzymes (CYP3A4, CYP2A9, and phase II) and higher sensitivities to enzyme inducers (rifampicin and glutathione) and inhibitors (ketoconazole and probenecid). The drug clearance and toxicity to 3Ds spheroids predict better the clinical observations and drug–drug interactions. In addition, compared to scaffold-free spheroid culture, stronger expressions of E-cadherin and hypoxia-inducible factor-1α (HIF-1α) and higher fibronectin secretions are determined in 3Db spheroids, displaying apparent hypoxic and apoptotic regions similar to those found in solid tumors. In contrast to the overestimated drug toxicity in other systems, the infiltrations of free drug and drug-loaded micelles are apparently restricted in 3Db spheroids, exhibiting drug resistance just like in tumor tissues. Thus, this study demonstrates HepG2 spheroids with different sizes as predictable and physiologically relevant models for high-throughput screening of drug metabolism and tumor infiltration.
研究领域:
药学
·
生物医学工程
·
细胞生物学
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Shuneng Zhou,Chao Chen,Junfeng Yang,Lirui Liao,Zekun Wang,Dong Wu,Jiaru Chu,Li Wen,Weiping Ding
At present, microscale high-throughput screening (HTS) for drug toxicity has drawn increased attention. Reported methods are often constrained by the inability to execute rapid fusion over diverse droplets or the inflexibility of relying on rigid customized templates. Herein, a light-responsive candle-soot-hybridized lubricant-infused slippery surface (CS-LISS) was reported by one-step femtosecond laser cross-scanning to realize highly effective and flexible drug HTS. Due to its low-hysteresis merits, the CS-LISS can readily steer diverse droplets toward arbitrary directions at a velocity over 1.0 mm/s with the help of tracing lateral near-infrared irradiation; additionally, it has the capability of self-cleaning and self-deicing. Significantly, by integrating the CS-LISS with a GFP HeLa cell chip, high-efficiency drug toxicity screening can be successfully achieved with the aid of fluorescence imaging. This work provides insights into the design of microscale high-throughput drug screening.
研究领域:
生物医学工程
·
药理学
·
材料科学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Chang Liu,Zhengjiang Cao,Li Li,Qingyin Li,Chunle Zhang,Yunbing Wang,Linhua Li,Ping Fu
Sepsis is a severe and complex systemic infection that can result in multiple organ dysfunction. Sepsis-associated acute kidney injury (SAKI), caused by inflammatory response, oxidative stress, and cellular apoptosis, is a common complication that seriously impacts patient survival rates. Herein, a potent and novel metal-polyphenol nanomicelle can be efficiently self-assembled with Pt4+ and honokiol (HK) by the chelation, π–π conjugation, hydrophobic action, and the surfactant properties of Tween-80. These nanomicelles not only enhance drug bioavailability (encapsulation rates: Pt─49%, HK─70%) and reduce drug toxicity (safety dose: <20 μg/g) but also improve targeting toward damaged renal tissues. Furthermore, Pt4+ and HK in the nanomicelles exert a synergistic physiological effect by scavenging free radicals to alleviate oxidative damage, inhibiting macrophage activation and the release of inflammatory factors to regulate inflammation, and displaying broad-spectrum antimicrobial activity to control infection. These actions collectively protect renal tissue and restore its functionality. Here, we constructed metal-polyphenol nanomicelles (Pt/HK-NMs) via ingenious and efficient self-assembly, providing a new strategy to compensate for deficiencies in the hemodialysis and antibiotic treatment of SAKI.
研究领域:
药学
·
纳米技术
·
感染病学
·
肾脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2022
·Vol. 59
·期 11
·6934-6955
·
IF 5.682
Wu Yueshan,Chang Jing,Ge Juanjuan,Xu Kangyan,Zhou Quan,Zhang Xiaowen,Zhu Ni,Hu Meichun
Glioblastoma multiforme (GBM) is the most malignant intracranial tumor with high mortality rates and invariably poor prognosis due to its limited clinical treatments. There is an urgent need to develop new therapeutic drugs for GBM treatment. As a natural prenylated chalcone compound, Isobavachalcone (IBC)’s favorable pharmacological activities have been widely revealed. However, potential inhibitory effects of IBC on GBM have not been explored. In the present study, we aimed to detect the effects of IBC on GBM and clarify its anti-GBM mechanisms for the first time. It was observed that IBC could inhibit GBM cell proliferation, migration, and invasion in vitro and prevent tumor growth without any significant drug toxicity in both subcutaneous and orthotopic GBM xenograft tumor models in vivo. Mechanistically, IBC may target NOD-like receptor family pyrin domain-containing 3 (NLRP3) transcription factor estrogen receptor α ( ESR1 gene) by network pharmacology and molecular docking analysis. Experimentally, IBC alleviated NLRP3 inflammasome-related pyroptosis and inflammation, arrested cell cycle at G1 phase, and induced mitochondria-dependent apoptosis in GBM cells. IBC’s inhibition on NLRP3 could be rescued by the NLRP3 antagonist CY-09 both in vitro and in vivo. These results indicate that IBC is a potential therapeutic drug against GBM and provide a new insight into GBM treatment.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Jiahui Zhang,Wei Xin,Yechi Qin,Yuhao Hong,Zijie Xiahou,Kunxi Zhang,Peiliang Fu,Jingbo Yin
Based on “bottom-up” strategy, cell-laden 3D bioprinting is an important process of fabricating sophisticated biomimetic structures. Stem cell spheroids possess better biological properties and are advanced as printing units. However, efficient and convenient preparation, collection and printing of cell spheroids remains a challenge. The present study developed a composite granular hydrogel acted as “all-in-one” multi-functional bioink to realize Adipose-derived stem cell (ASC) spheroids Production and reorganization. Poly(sulfobetaine methacrylate) (PSBMA) based microspheres were fabricated and self-assembled to a granular hydrogel. Then, N -isopropylacrylamide (NIPAM) and SBMA were co-polymerized in-situ inside of assembled PSBMA microspheres to further crosslink the assembled microspheres, forming a composite granular hydrogel, which possesses bulk feature and shear-thinning, self-healing properties. Caves were created by compressing composite granular hydrogels into sugar particles that removed via dissolution in water. Due to the non-fouling feature and the porous structure, numerous ASC spheroids were formed spontaneously inside the porous composite granular hydrogel, which were transferred conveniently to 3D printer. The spheroids-laden composite granular hydrogels showed well-performed extrudability and fidelity, realizing reorganization of the produced spheroids to the stable 3D constructs for further in vitro culture . ASC spheroids in granular hydrogel after 3D printing showed high level of viability and stemness, as well as efficient chondrogenic/osteogenic/adipogenic differentiation. The composite granular hydrogel thus shows potential toward stem cell researches such as organoids construction. The results of both in vitro drug toxicity and in vivo cartilage regeneration experiments showed spheroids-laden granular hydrogel is promising in drug screening and tissue regeneration.
研究领域:
组织工程
·
干细胞生物学
·
生物打印
·
材料科学
·
再生医学
✓ 已验证
产品关联
DOI
高影响因子
REDOX REPORT
·
2025
·
IF 7.4
Fang Cheng,Minzhu Zhao,Qi Wang,Hongli Xiong,Kai Yu,Chong Chen,Ying Zhu,Yemiao Chen,Jianbo Li
Objectives Doxorubicin (DOX) induces dose-dependent cardiotoxicity, primarily through oxidative stress and metabolic dysregulation. Although NAD+ deficiency has been implicated in cardiovascular pathology, its role in DOX-induced cardiotoxicity (DIC) remains poorly understood. This study investigated NAD+ metabolism dysregulation as a redox-sensitive mechanism in DIC pathogenesis.Methods Human cardiomyocytes (AC16), mouse atrial myocytes (HL-1), and C57BL/6 mice were used to establish the DIC model. The role and mechanism of NAD+ in DIC were investigated using a range of methods.Results Using integrated in vitro and in vivo models, we demonstrated that DOX induces myocardial oxidative damage accompanied by NAD+ depletion. Exogenous NAD+ supplementation mitigated the DOX-induced cardiomyocyte death and redox imbalance. Mechanistically, pharmacological CD38 inhibition with 78C or genetic silencing failed to restore the NAD+ pool, whereas nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3) overexpression, combined with nicotinamide mononucleotide (NMN) administration, effectively rescued NAD+ levels and attenuated oxidative stress. Computational and functional analyses identified FOXO1 as a transcriptional repressor of NMNAT3 following DOX exposure.Conclusion This study establishes the dysregulation of the FOXO1-NMNAT3 axis as a key mechanism underlying NAD+ depletion in DIC. Targeting this axis through NAD+ replenishment, particularly by activating NMNAT3, offers a novel redox-based therapeutic strategy against DIC.
研究领域:
心血管病理学
·
分子生物学
·
药理学
·
氧化应激
·
代谢调控
·
转化医学
·
药物毒性
✓ 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）