Nanomedicine-Nanotechnology Biology and Medicine
·
2015
·
IF 6.155
Zhangjian Chen,Yun Wang,Lin Zhuo,Shi Chen,Lin Zhao,Tian Chen,Yang Li,Wenxiao Zhang,Xin Gao,Ping Li,Haifang Wang,Guang Jia
Titanium dioxide nanoparticles (TiO 2 NPs) have a broad application prospect in replace with TiO 2 used as a food additive, especially used in sweets. Understanding the interaction of TiO 2 NPs with sugar is meaningful for health promotion. We used a young animal model to study the toxicological effect of orally administrated TiO 2 NPs at doses of 0, 2, 10 and 50 mg/kg per day with or without daily consumption of 1.8 g/kg glucose for 30 days and 90 days. The results showed that oral exposure to TiO 2 NPs and TiO 2 NPs + glucose both induced liver, kidney, and heart injuries as well as changes in the count of white and red blood cells in a dose, time and gender-dependent manner. The toxicological interactions between orally-administrated TiO 2 NPs and glucose were evident, but differed among target organs. These results suggest that it is necessary to limit dietary co-exposure to TiO 2 NPs and sugar. From the Clinical Editor Nanotechnology has gained entrance in the food industry, with the presence of nanoparticles now in many food items. Despite this increasing trend, the potential toxic effects of these nanoparticles to human remain unknown. In this article, the authors studied titanium dioxide nanoparticles (TiO2 NPs), which are commonly used as food additive, together with glucose. The findings of possible adverse effects on liver, kidney, and heart might point to a rethink of using glucose and TiO2 NPs combination.
研究领域:
毒理学
·
食品科学
·
生物医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOFACTORS
·
2024
·
IF 5
Yining Lei,Manqin Li,Xinran Liu,Lu Zhang,Ruyi Zhang,Fei Cai
Despite the observation of diabetes-induced brain tissue damage and impaired learning and memory, the underlying mechanism of damage remains elusive, and effective, targeted therapeutics are lacking. Notably, the NLRP3 inflammasome is highly expressed in the hippocampus of diabetic individuals. Nerolidol, a naturally occurring compound with anti-inflammatory and antioxidant properties, has been identified as a potential therapeutic option for metabolic disorders. However, the ameliorative capacity of nerolidol on diabetic hippocampal injury and its underlying mechanism remain unclear. Network pharmacology and molecular docking was used to predict the signaling pathways and therapeutic targets of nerolidol for the treatment of diabetes. Then established a diabetic rat model using streptozotocin (STZ) combined with a high-fat diet and nerolidol was administered. Morris water maze to assess spatial learning memory capacity. Hematoxylin and eosin and Nissl staining was used to detect neuronal damage in the diabetic hippocampus. Transmission electron microscopy was used to detect the extent of damage to mitochondria, endoplasmic reticulum (ER) and synapses. Immunofluorescence was used to detect GFAP, IBA1, and NLRP3 expression in the hippocampus. Western blot was used to detect apoptosis (Bcl-2, BAX, and Cleaved-Caspase-3); synapses (postsynaptic densifying protein 95, SYN1, and Synaptophysin); mitochondria (DRP1, OPA1, MFN1, and MFN2); ER (GRP78, ATF6, CHOP, and caspase-12); NLRP3 inflammasome (NLRP3, ASC, and caspase-1); inflammatory cytokines (IL-18, IL-1β, and TNF-α); AKT (P-AKT); and mitogen-activated protein kinase (MAPK) pathway (P-ERK, P-p38, and P-JNK) related protein expression. Network pharmacology showed that nerolidol's possible mechanisms for treating diabetes are the MAPK/AKT pathway and anti-inflammatory effects. Animal experiments demonstrated that nerolidol could improve blood glucose, blood lipids, and hippocampal neuronal damage in diabetic rats. Furthermore, nerolidol could improve synaptic, mitochondrial, and ER damage in the hippocampal ultrastructure of diabetic rats by potentially affecting synaptic, mitochondrial, and ER-related proteins. Further studies revealed that nerolidol decreased neuroinflammation, NLRP3 and inflammatory factor expression in hippocampal tissue while also decreasing MAPK pathway expression and enhancing AKT pathway expression. However, nerolidol improves hippocampal damage in diabetic rats cannot be shown to improve cognitive function. In conclusion, our study reveals for the first time that nerolidol can ameliorate hippocampal damage, neuroinflammation, synaptic, ER, and mitochondrial damage in diabetic rats. Furthermore, we suggest that nerolidol may inhibit NLRP3 inflammasome and affected the expression of MAPK and AKT. These findings provide a new experimental basis for the use of nerolidol to ameliorate diabetes-induced brain tissue damage and the associated disease.
研究领域:
药理学
·
神经科学
·
糖尿病研究
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
·
2025
·
IF 4.3
Fan Yanan,An Caizhelin,Wang Zhihui,Luo Jia,Wang Wenbin,Luo Qing,Song Guanbin
Hepatocytes are the primary functional cells in the liver, and the malignant transformation of hepatocytes significantly contributes to hepatocellular carcinoma (HCC) progression. Liver fibrosis and cirrhosis caused by extracellular matrix (ECM) remodeling during liver lesions is a pivotal driver of HCC. However, the impact of matrix stiffness on hepatocytes and the underlying molecular mechanisms are not fully understood. Herein, using gelatin/sodium alginate hydrogels with different stiffnesses to simulate the change of matrix stiffness during liver lesions, we found that matrix stiffening leads to a notable decrease in the expression of hepatocyte nuclear factor 4α (HNF4α) and functional hepatocyte genes and a significant increase in the expression of interleukin 6 (IL‒6) in human hepatocyte line L‒02 cells, indicating obvious damage of hepatocyte function. In addition, matrix stiffening causes extensive DNA damage to L‒02 cells. Mechanistically, matrix stiffening upregulates piezo‒type mechanosensitive ion channel component 1 (Piezo1) expression and activates extracellular signal‒regulated kinase 1/2 (ERK1/2) signaling. Piezo1 knockdown suppresses matrix stiffening‒induced functional impairment and DNA damage in L‒02 cells. Moreover, Piezo1 knockdown blocks matrix stiffening‒activated ERK1/2 signaling in L‒02 cells. U0126 (a selective inhibitor of ERK1/2 activation) treatment could rescue matrix stiffening‒induced functional impairment and DNA damage. Taken together, these findings demonstrate that matrix stiffening induces functional impairment and DNA damage in L‒02 cells via the Piezo1‒ERK1/2 signaling pathway, which provides evidence for a better understanding of the hepatocyte function damage caused by tissue mechanical microenvironment change in liver diseases and the mechanotransduction in this process. Graphical abstract An increase in matrix stiffness inhibits HNF4α expression and promotes IL‒6 expression in L‒02 cells. Meanwhile, matrix stiffening induces L‒02 cell DNA damage and upregulates the expression of γ‒H2AX and 53BP1. These findings prove that matrix stiffness is a crucial mechanical regulator of cellular functional impairment and DNA damage and plays an important role in liver disease.
研究领域:
医学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JCI Insight
·
2025
·
IF 6.1
Ping Gao,Xinwei Cheng,Maochang Liu,Hui Peng,Guodong Li,Tianze Shang,Jianqiao Wang,Qianyan Gao,Chenglong Zhu,Zhenpeng Qiu,Chengliang Zhang
Tacrolimus-induced chronic nephrotoxicity (TICN) hinders its long-term use, but its mechanism remains unclear. Tacrolimus exerts its pharmacological effect by inhibiting calcineurin and its substrate NFAT. Whether the inhibition of other calcineurin substrates is related to TICN remains to be explored. Transcription factor EB (TFEB), a substrate of calcineurin, plays a crucial role in various homeostasis. Herein, we found that tacrolimus inhibited TFEB nuclear translocation and activity in mouse kidneys and HK-2 cells. Then, TFEB gain- and loss-of-function rescued the effect of tacrolimus in HK-2 cells. Furthermore, TFEB activation both by phosphorylation sites mutation and agonist rescued TICN in mice. To elucidate the mechanism of TFEB, we analyzed ChIP-seq data. Growth arrest and DNA damage-inducible 45α (GADD45α) was identified as a transcriptional target of TFEB via chromatin immunoprecipitation and dual luciferase reporter assays. And then we revealed that GADD45α overexpression rescued DNA damage and kidney injury caused by tacrolimus or TFEB knockdown in vitro, and vise versa. The protective effect of GADD45α against TICN and DNA damage was further demonstrated by overexpressing it in mice. In conclusion, the persistent inhibition of TFEB-GADD45α pathway by tacrolimus contributes to TICN. This study identifies a specific target for intervention of TICN.
研究领域:
药理学
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肾病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acupuncture and Herbal Medicine
·
2024
·Vol. 4
·期 4
·487
·
IF 0
Wang Zhiyun,Shang Haihua,Gou Wenfeng,Xu Feifei,Hou Yue,Liu Gaiting,Ren Zhonghao,Li Yiliang,Tian Yuhua,Li Wei,Wang Yuefei,Hou Wenbin
Objective: Camellia nitidissima Chi, a Chinese medicine commonly used by ethnic minorities in Guangxi, China, is beneficial for clearing heat, detoxifying, inducing diuresis, and suppressing swelling. It has various pharmacological properties, including antitumor, anti-inflammatory, and antioxidant. However, its potential application in radioprotection remains unclear. In this study, we aimed to determine whether Camellia nitidissima Chi has radioprotective effects against radiation-induced gastrointestinal and hematopoietic damage. Methods: The 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) techniques were used to assess the ability of Camellia nitidissima Chi to scavenge free radicals. We conducted a 30-day survival rate experiment to evaluate the radioprotective capabilities of Camellia nitidissima Chi. Additionally, we developed models of radiation-induced intestinal and hematopoietic damage. Alterations in the white blood cell (WBC) count, total superoxide dismutase (T-SOD), glutathione (GSH), and protein expression linked to apoptosis were observed. Results: Camellia nitidissima Chi scavenged 84.72% and 93.47% of DPPH and ABTS, had a certain radiation protection potential, and increased the survival rate of mice to over 90%. Moreover, following exposure, Camellia nitidissima Chi enhanced WBC, T-SOD, and GSH levels. Camellia nitidissima Chi increased B-cell lymphoma-extra large (BCL-XL) expression and suppressed Bcl-2 associated X protein (BAX) expression, providing radioprotection to cells. Conclusions: Camellia nitidissima Chi has a strong antioxidant ability; it can improve the survival rate of mice after lethal dose irradiation and protect against radiation-induced hematopoietic and gastrointestinal damage. These findings can serve as a guide for using Chinese medicines for radioprotection.
研究领域:
药理学
·
放射医学
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民族医药
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生物学
✓ 已验证
DOI
Radiation Effects and Defects in Solids
·
2024
·
IF 1.1
X.L. Ren,G. Yao,L.M. Luo,Y. Xu,A. Yabuuchi,Q. Xu
In the present study, we developed Mo- and Zr-added W-Y2O3 composites, and investigated their surface damage, including commercially available W induced by He and D as well as He and D mixture plasmas. Blistering was not observed in the D-plasma-irradiated W and W composites. The thickness of the damaged surface layer due to He plasma exposure of the W-Mo-Y2O3 composite was similar to that of W. However, the thickness of the damaged surface layer of the W-Y2O3 composite was half that of W. In addition, the thickness of the damaged surface layer of the W-Zr-Y2O3 composite was further improved by 5 times. Y2O3 nanoparticles, especially refined Zr-Y-O nanoparticles, act as He trap sites to suppress the formation and growth of He bubbles. Furthermore, the W-O-Y and W-O-Zr-Y nanoparticles increased the solubility of He and delayed He diffusion, hindering the formation of He bubbles.
研究领域:
材料科学
·
核能工程
✓ 已验证
产品关联
DOI
高影响因子
PLoS One
·
2025
·Vol. 20
·期 4
·e0319605
·
IF 2.6
Hong-Fei He,Shuang Hou,Xiao-Ya Ma,Song-song Huang,Bo Yang,Jun-Kang Wang,Yuan Xu,Lei Tan,Hai-Yang Li
As one of the major causes of acute kidney injury, renal ischemia-reperfusion is a common health problem in a series of clinical situations, including renal transplantation. Although the mechanisms of renal IRI have been widely investigated, effective strategies are still in lacking for its prevention and treatment. In previous study, we found that the down-regulation of taurine upregulated gene 1, a long non-coding RNA (lncRNA TUG1), markedly alleviated renal IRI through mitigating the cell inflammation and apoptosis. At meanwhile, YTHDF2, an RNA methylation reading protein, was identified as a vital player in IRI of distinct organs, however, not reported in kidney. We then conducted the current study on the function of YTHDF2 in renal IRI and its regulatory role to TUG1. Based on renal IRI models in vitro and in vivo, dramatical down-regulation of YTHDF2 was presented. Subsequently, exogenous perturbation of YTHDF2 was conducted and its protective effects on cell apoptosis were demonstrated in acute IRI exogenous. Furthermore, with the same model, it was indicated that YTHDF2 protein negative regulated TUG1 RNA via direction interaction. Since then, YTHDF2 was proved as a potential protector of renal IRI through restraining of TUG1. In further speculation, induction of YTHDF2 in IRI will possibly become a possible strategy to combat the pathological process post renal transplantation or other clinical conditions.
研究领域:
分子生物学
·
肾脏病学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2025
·
IF 11.3
Huanxin Zhang,Yu Zhang,Shixuan Cui,Lihua Cui,Jiaxin Li,Jizhuang Chu,Yumiao Zhou,Youru Zhang,Qiang Kong
Pentachlorophenol (PCP) is widely distributed in marine environments and poses a threat to the health of marine organisms. Recent studies have demonstrated that PCP induces energy deficiency in marine organisms. However, the underlying toxification mechanism and the resulting adverse outcomes remain unclear. This study analyzed the energy metabolism of marine medaka ( Oryzias melastigma ) exposed to PCP at environmentally relevant concentrations via proteomic analysis and multiple physiological assessments. The results showed that PCP disrupted mitochondrial morphology, reduced mitochondrial membrane potential (MMP), and decreased adenosine triphosphate (ATP) levels in marine medaka. Proteomic analysis revealed that PCP induced oxidative stress, cytoskeletal disruption, and inhibition of the cytochrome bc1 complex and ATP synthase. These effects culminated in structural and functional impairments to mitochondria, which in turn inhibited ATP synthesis. Chronic PCP exposure led to enhanced glycolytic activity, the accumulation of liver lipids, and reduced liver function. The present study has deepened our understanding of the mechanism of PCP-induced energy production deficiency in marine fish and provides new insights into ecological risk assessment for PCP.
研究领域:
环境科学
·
毒理学
·
海洋生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2025
·
IF 5.4
Wenqian Chen,Zi Ye,Lixiong Gao,Yuhang Jiang,Yue Wei,Xuejun Chen,Liqin Li,Tengfei Mao,Zhaohui Li
The corneal epithelium, the outermost barrier of the eye, is particularly susceptible to UV-induced photodamage. Owing to the limited protection provided by physical defense strategies, there is a critical need for effective UV-protective ocular medications. In this study, novel fluorescent copolymers were synthesized and evaluated for their anti-UV properties in human corneal epithelial (HCE-T) cells. These copolymers provided substantial protection to HCE-T cells against damage from various types of UV radiation. The protective effects were attributed to their ability to attenuate oxidative damage caused by UVA radiation and mitigate direct DNA damage induced by UVB and UVC radiation. Mechanistic investigations revealed that their antioxidant and DNA repair activities are mediated through the regulation of the PERK and NER signaling pathways. These findings underscore the potential of these functional polymers as promising ophthalmic agents against broad-spectrum UV-damage.
研究领域:
生物医学
·
材料科学
·
眼科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
WATER RESEARCH
·
2024
·
IF 11.4
Zi-Bo Jing,Wen-Long Wang,Yu-Jia Nong,Lu Peng,Zi-Chen Yang,Bei Ye,Min-Yong Lee,Qian-Yuan Wu
Low-pressure mercury lamps emitting at 254 nm (UV254) are used widely for disinfection. However, subsequent exposure to visible light results in photoreactivation of treated bacteria. This study employed a krypton chloride excimer lamp emitting at 222 nm (UV222) to inactivate E. coli . UV222 and UV254 treatment had similar E. coli -inactivation kinetics. Upon subsequent irradiation with visible light, E. coli inactivated by UV254 was reactivated from 2.71-log to 4.75-log, whereas E. coli inactivated by UV222 showed negligible photoreactivation. UV222 treatment irreversibly broke DNA strands in the bacterium, whereas UV254 treatment primarily formed nucleobase dimers. Additionally, UV222 treatment caused cell membrane damage, resulting in wizened, pitted cells and permeability changes. The damage to the cell membrane was mainly due to the photolysis of proteins and lipids by UV222. Furthermore, the photolysis of proteins by UV222 destroyed enzymes, which blocked photoreactivation and dark repair. The multiple damages can be further evidenced by 4.0–61.1 times higher quantum yield in the photolysis of nucleobases and amino acids for UV222 than UV254. This study demonstrates that UV222 treatment damages multiple sites in bacteria, leading to their inactivation. Employing UV222 treatment as an alternative to UV254 could be viable for inhibiting microorganism photoreactivation in water and wastewater.
研究领域:
微生物学
·
环境科学
·
光生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Qiaohui Chen,Yongqi Yang,Xiaohong Ying,Changkun Huang,Jianlin Chen,Jue Wang,Ziyu Wu,Wan Zeng,Chenxi Miao,Xiaojing Shi,Yayun Nan,Qiong Huang,Kelong Ai
Acute kidney injury (AKI) manifests a hallmark pathological feature of extensive and severe DNA damage in renal tubules, primarily induced by the excessive of toxic reactive oxygen species (ROS) from the mitochondrial electron transport chain. The kidney's complex intricate physiological architecture and the heterogeneous intracellular environment pose significant challenges for effective sequential and high-resolution drug delivery—an urgent issue that remains unresolved. To address this, a hierarchical-targeting antioxidant nanodrug has been developed with a folic acid moiety (HAND) designed for high-resolution drug delivery in AKI treatment. For the first time, HAND enables sequential targeting from the kidney to the most severely damaged proximal tubular epithelial cells (PTECs), ultimately concentrating in the DNA-rich mitochondria and nucleus. As a result, HAND effectively scavenges ROS in situ, protecting both mitochondria and nuclei along with their vital genetic material. This action restores mitochondrial function, mitigates DNA oxidation and fragmentation, reduces apoptosis, and inhibits cGAS/STING-mediated sterile inflammation. Consequently, HAND demonstrates remarkable efficacy in safeguarding injured kidneys during AKI. Overall, this work pioneers a hierarchical, high-resolution antioxidant strategy, providing innovative guidance for the development of AKI therapies.
研究领域:
药理学
·
分子生物学
·
肾脏病学
✓ 已验证
DOI
高影响因子
TOXICOLOGY MECHANISMS AND METHODS
·
2025
·
IF 2.7
Dan Wang,Hui Sun,Kerong Hai,Ningkang Li,Yang Gu,Zengrui Ma
Traumatic brain injury (TBI), a prevalent neurological disorder in clinical practice, is primarily induced by external trauma. Propofol has been reported to alleviate the symptoms associated with TBI. In this study, a TBI model was established in mice using the controlled cortical impact (CCI) method. After treatment with propofol and BML-275, neuronal damage in the TBI model was assessed through the modified Neurological Severity Score (mNSS), Hematoxylin and Eosin (HE) staining, and Nissl staining. To investigate the role of the AMPK/SIRT1 pathway in propofol-regulated TBI, AMPKα-silenced vectors and overexpressed SIRT1 vectors were transfected. Western blot was performed to evaluate the expression of proteins involved in the AMPK/SIRT1 pathway and pyroptosis markers. The regulatory impact of Th17/Treg balance was examined by detecting the key transcription factors RORγt and FOXP3 through immunofluorescent staining and RT-qPCR. Enzyme-linked immunosorbent assay (ELISA) was used to measure IL-17 and IL-10 concentrations. Results showed that propofol significantly reduced neuronal injury in the TBI model, an effect that was reversed by BML-275. Moreover, propofol mitigated pyroptosis by downregulating Caspase-1 and GSDMD-N expression post-TBI. Propofol inhibited Th17 differentiation while promoting Treg differentiation by modulating RORγt/FOXP3 and IL-17/IL-10 levels. Silencing AMPKα markedly diminished propofol’s effects on Th17 and Treg differentiation, with these effects being reversed upon SIRT1 overexpression. Propofol suppressed neuronal pyroptosis through the regulation of Th17/Treg balance via activation of the AMPK/SIRT1 pathway. These findings suggest propofol exerts a protective effect against neuronal damage following TBI, potentially through the modulation of the Th17/Treg balance and AMPK/SIRT1 signaling pathway.
研究领域:
神经科学
·
免疫学
·
药理学
✓ 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）