JOURNAL OF HAZARDOUS MATERIALS
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2022
·
IF 14.224
Guoliang Chen,Mingxing Wang,Panpan Zhu,Guixue Wang,Tingzhang Hu
As a newly-invented and highly-efficiency strobilurin fungicide , pyraoxystrobin (SYP-3343) has been recognized as a highly poisonous toxin for a variety of aquatic organisms. Nevertheless, the developmental toxicity and potential mechanism of SYP-3343 have not been well-documented. The results showed that SYP-3343 was relatively stable and maintained within the range of 20 % in 24 h, and the LC 50 value to embryos at 72 hpf was 17.13 μg/L. The zebrafish embryotoxicity induced by 1, 2, 4, and 8 μg/L SYP-3343 is demonstrated by repressive embryo incubation, enhancive mortality rate, abnormal heart rate, malformed morphological characteristic, and impaired spontaneous coiling, indicating SYP-3343 mostly exerted its toxicity in a dose- and time-dependent manner. Besides SYP-3343 was critically involved in regulating cell cycle, mitochondrial membrane potential, and reactive oxygen species production as well as zebrafish primary cells apoptosis, which can be mitigated using antioxidant N-acetyl- L -cysteine. A significant change occurred in total protein content, the biochemical indices, and antioxidant capacities owing to SYP-3343 exposure. Additionally, SYP-3343 altered the mRNA levels of heart development-, mitochondrial function-, and apoptosis-related genes in zebrafish embryos. These results indicated that SYP-3343 induced apoptosis accompanying reactive oxygen species-initiated mitochondrial dysfunction in zebrafish embryos.
研究领域:
毒理学
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水生毒理学
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发育生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2022
·
IF 7.088
Xing-Rong Wang,Shuai Wang,Hong-Xia Mu,Kai-Yan Xu,Xue-Ting Wang,Jian-Tao Shi,Qi-Hang Cui,Li-Wen Zhang,Shi-Wu Chen
VEGFR-2 is an attractive therapeutic target for antitumor drug research by blocking tumor angiogenesis and PROTAC provides a new technology for targeted protein knockout. Herein, a library of novel VEGFR-2-PROTAC degraders were rationally designed and synthesized based on the Lys residue region on the surface of VEGFR-2 protein using protein structure-based drug design strategy. Among them, P7 exhibited preferable antitumor activity against HGC-27 cells and less toxic to human normal HUVEC, HEK293T and GES-1 cells in vitro , as well as the potent degradation activity of VEGFR-2 protein in HGC-27 cells (DC 50 : 0.084 ± 0.04 μM, D max : 73.7%) and HUVEC cells (DC 50 : 0.51 ± 0.10 μM, Dmax: 76.6%). Additionally, P7 degraded VEGFR-2 protein by the formation of ternary complex and the ubiquitin proteasome pathway in HGC-27 cells. Furthermore, P7 shortened the half-life of VEGFR-2 protein synthesis and had no inhibitory effect on the expression of VEGFR-2 mRNA in HGC-27 cells. Moreover, P7 inhibited the colony formation, migration and invasion of HGC-27 cells in a time- and dose-dependent manner, and meanwhile induced G 2 /M phase cycle arrest and apoptosis . All the results demonstrated that P7 could be as a promising VEGFR-2-PROTAC degrader for gastric cancer therapy.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Sijia Wu,Ping Jiang,Xiaoliang Zhang,Chen Mao,Yaxi Dai,Hong Zhuang,Yong Pang
Understanding the transport mechanism of the peptide Asn-Cys-Trp (NCW) is crucial to improving its intestinal absorption and bioavailability. This study investigated the absorption of NCW through Caco-2 cell monolayers and its interaction with the DPPC bilayers. Results revealed that after a 3 h incubation, the Papp (AP-BL) and Papp (BL-AP) values of NCW at a concentration of 5 mmol/L were (22.24 ± 4.52) × 10–7 and (6.63 ± 2.31) × 10–7 cm/s, respectively, with the transport rates of 1.59 ± 0.32 and 0.62 ± 0.20%, indicating its moderate absorption. NCW was found to be transported via PepT1 and paracellular transport pathways, as evidenced by the significant impact of Gly-Pro and cytochalasin D on the Papp values. Moreover, NCW upregulated ZO-1 mRNA expression. Further investigation of the ZO-1-mediated interaction between NCW and tight junction proteins will contribute to a better understanding of the paracellular transport mechanism of NCW. The interaction between NCW and the DPPC bilayers was predominantly driven by entropy. NCW permeated the bilayers through electrostatic, hydrogen bonding, and hydrophobic interactions, resulting in increased fluidity, flexibility, and disorder as well as phase transition and phase separation of the bilayers.
研究领域:
药理学
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生物物理学
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细胞生物学
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膜科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xueting Wang,Jing Yang,Qimeng Zhao,Xianchang Xie,Fuling Deng,Ziyi Wang,Kunpeng Jiang,Xiaoming Li,Hu Liu,Zhenhao Shi,Xu Zhu,Lei Chen,Dalun Lv
Macromolecule hydrogels made from natural extracts have received much attention because of their favorable biocompatibility and wound healing properties. However, their clinical applications are limited by their insufficient mechanical strength and low adhesion properties. To overcome these limitations, we developed a novel injectable Aloe vera hydrogel (PDMA-GelMA@AV). By integrating gelatin methacrylate (GelMA) and polydopamine methacrylamide (PDMA), we significantly improved the mechanical and adhesion properties of the hydrogel. The PDMA-GelMA@AV hydrogel degraded in a simulated wound environment, which was synchronized with the sustained release of the bioactive components of A. vera . In vitro and in vivo analyses revealed that this hydrogel has good biocompatibility. In vitro studies also revealed that the sustained release of the active ingredients of A. vera promoted fibroblast proliferation and migration and increased the expression of key proteins and mRNAs required for wound healing. In addition, it modulated LPS-stimulated macrophages and decreased the expression of TNF-α, IL-1β and iNOS while increasing the expression of TGF-β and ARG. In vivo experiments further confirmed the efficacy of hydrogels in wound healing applications. These findings offer a novel perspective on the application of natural macromolecules as hydrogel-based delivery vehicles in wound care.
研究领域:
生物医学工程
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材料科学
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伤口愈合
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药剂学
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生物材料
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2020
·
IF 3.292
Zuntao Wu,Lin Bai,Runqi Tu,Lijie Zhang,Yue Ba,Huizhen Zhang,Xing Li,Xuemin Cheng,Wenjie Li,Hui Huang
Lead (Pb) is recognized as a potent inducer of synaptic toxicity generally associated with reduced synaptic transmission and increased neuronal fiber excitability, becoming an environmental risk for neurodegenerative processes. Despite numerous toxicological studies on Pb have been directed to the developing brain, attention concerning long-term consequences of pubertal chronic Pb exposure on neuronal activity is still lacking. Thus, we exposed 4-week-old male mice to 0.2 % lead acetate solution for one month, then, conducted behavioral tests or extracted brain homogenate from mice prefrontal cortex (PFC) and hippocampus at the age of 4, 13 and 16-month-old respectively. Our results showed that treated mice exhibited an evident increase in latency to reach platform following pubertal Pb exposure and aging. The increase of 8-OHdG revealed evident neural DNA oxidative damage across time upon pubertal Pb exposure. In the hippocampus of lead exposed mice at three age nodes, the expression of brain-derived neurotrophic factor precursor (proBDNF) increased, while that of mature BDNF (mBDNF), cAMP-response element binding protein (CREB) and phosphorylated CREB (pCREB) decreased compared with the control group. Furthermore, the expression of BACE1 protein and tau phosphorylation level in PFC and hippocampus increased, APP mRNAs in PFC and prolonged induction of BACE1 in hippocampus. Our results show that chronic Pb exposure from pubertal stage onward can either initiate divergent synaptic-related gene expression patterns in adulthood or trigger time-course of neurodegenerative profile within the PFC or hippocampus, which can contribute consistent deficits of cognition across subsequent age-nodes.
研究领域:
神经毒理学
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神经科学
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分子生物学
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行为科学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENT INTERNATIONAL
·
2016
·
IF 5.929
Ping Xiang,Rui-Wen He,Yong-He Han,Hong-Jie Sun,Xin-Yi Cui,Lena Q. Ma
Human cornea is highly susceptible to damage by dust. Continued daily exposure to housedust has been associated with increasing risks of corneal injury, however, the underlying mechanism has not been elucidated. In this study, a composite housedust sample was tested for its cytotoxicity on primary human corneal epithelial (PHCE) cells, which were exposed to dust at 5–320 μg/100 μL for 24 h. PHCE cell viability showed a concentration-dependent toxic effect, attributing to elevated intracellular ROS. Moreover, when exposed at > 20–80 μg/100 μL, dust-induced oxidative damage was evidenced by increased malondialdehyde and 8-hydroxy-2-deoxyguanosine (1.3–2.3-fold) and decreased antioxidative capacity (1.6–3.5-fold). Alteration of mRNA expression of antioxidant enzymes ( SOD1 , CAT , HO-1 , TRXR1 , GSTM1 , GSTP1 , and GPX1 ) and pro-inflammatory mediators ( IL-1β , IL-6 , IL-8 , TNF-α , and MCP-1 ) were also observed. Furthermore, the mitochondrial transmembrane potential was dissipated from 9.2 to 82%. Our results suggested that dust-induced oxidative stress probably played a vital role in the cytotoxicity in PHCE cells, which may have contributed to dust-induced impairment of human cornea.
研究领域:
眼科学
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毒理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2022
·
IF 6.832
Kun Xiao,Pengfei Liu,Peng Yan,Yanxin Liu,Licheng Song,Yuhong Liu,Lixin Xie
Lung ischemia/reperfusion (I/R) injury (LIRI) is a common complication after lung transplantation, embolism, and trauma. N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of I/R injury. However, there are no or few reports of m6A-related regulators in LIRI till now. In this text, dysregulated genes in lung tissues of LIRI rats versus the sham group were identified by RNA sequencing (RNA-seq). RNA-seq outcomes revealed that only YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) were differentially expressed in the LIRI versus sham group among 20 m6A-related regulators. Next, the functions and molecular mechanisms of YTHDF3 and IGF2BP2 in LIRI were investigated in a hypoxia/reoxygenation-induced BEAS-2B cell injury model in vitro. Results showed that YTHDF3 or IGF2BP2 knockdown attenuated hypoxia/reoxygenation-mediated inhibitory effects on cell survival and cell cycle progression and inhibited hypoxia/reoxygenation-induced cell apoptosis and pro-inflammatory cytokine secretion in BEAS-2B cells. Genes that could be directly regulated by YTHDF3 or IGF2BP2 were identified based on prior experimental data and bioinformatics analysis. Moreover, multiple potential downstream pathways of YTHDF3 and IGF2BP2 were identified by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis of the above-mentioned genes. Among these potential pathways, we demonstrated that YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, ERK1/2, AKT, and NF-κB pathways in BEAS-2B cells. In conclusion, YTHDF3 or IGF2BP2 knockdown weakened hypoxia/reoxygenation-induced human lung bronchial epithelial cell injury by inactivating p38, AKT, ERK1/2, and NF-κB pathways.
研究领域:
分子生物学
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细胞生物学
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免疫学
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移植医学
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DOI
PubMed
高影响因子
Food & Function
·
2024
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IF 5.1
Sijia Zhu,Jiyu Yang,Pengkui Xia,Sha Li,Qi Wang,Kaikai Li,Bin Li,Jing Li
Konjac glucomannan (KGM) is a dietary fiber supplement that exhibits multiple biological activities, including weight control and regulation of glucose and lipid metabolism. Currently, KGM intake patterns in practical applications include KGM sol, thermal irreversible gel, and frozen thermal irreversible gel. In this study, four intake patterns of KGM, namely KGM sol (KS), deacetylated KGM (DK), KGM gel (KG) and frozen KGM gel (FKG), were used as materials to explore the effects of KGM intake patterns on glucose and lipid metabolism and intestinal flora of obese mice induced by high fat diet under the same dose. Results showed that any type of KGM intake could reduce body weight, fat mass, lipid levels, and insulin resistance in obese mice, as well as partially alleviating liver damage and inflammation caused by obesity. However, KS has the most significant effect on controlling blood glucose and blood lipid in obese mice. Additionally, it was found that KS, DK, KG and FKG can increase the α-diversity of intestinal microflora in high-fat mice, and improve the microflora disorder in high-fat mice. Finally, KS may increase the levels of fasting appetite hormones GLP-1 and PYY in mice, up-regulate the expression of LDLR, GCK and G-6-pase mRNA, and increase the production of short-chain fatty acids (SCFAs) in the intestinal flora of mice, thus regulating glucose and lipid metabolism . This study systematically investigated the effects of different intake forms of KGM on metabolism and intestinal flora in obese mice, which is of great significance for further understanding the role of KGM in the prevention and treatment of obesity metabolic diseases, and for developing targeted dietary interventions.
研究领域:
营养学
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代谢研究
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肥胖研究
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肠道微生物
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产品关联
DOI
PubMed
高影响因子
Toxicology Research
·
2021
·Vol. 10
·期 5
·1013-1021
·
IF 3.524
Liu Yan-ping,Cai Ying,Lei Yuan-di,Yuan Xiao-yan,Wang Ye,Yi Shan,Li Xun-ya,Huang Lian,Long Ding-xin,Zhang Zhao-hui
Circular RNAs (circRNAs), is a novel type of endogenous non-coding RNAs (ncRNAs) participated in the pathogenesis of many diseases. Beryllium is one of the carcinogenesis elements. However, the mechanism and function of circRNAs in human bronchial epithelial cells (16HBE) induced by beryllium sulfate (BeSO4) was rarely reported. Therefore, the high-throughput RNA sequencing analysis was performed to detect the circRNA profiles between control groups and BeSO4-induced groups. Furthermore, circRNA-miRNA-mRNA network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and PPI network analysis were used for bioinformatics analysis. CircRNA sequencing analysis revealed that 36 circRNAs were up-regulated and 35 circRNAs were down-regulated in the BeSO4-exposed groups. The selected circRNAs were verified by real-time fluorescent quantitative PCR (qRT-PCR). Hsa_circ_0004214 and hsa_circ_0003586 were validated to be up-regulated, hsa_circ_0047958, hsa_circ_0001944, and hsa_circ_0008982 were down-regulated. The circRNA-miRNA-mRNA network annotated the key signaling pathway including cellular senescence, TNF signaling pathway, NF-kappa B signaling pathway, HIF-1 signaling pathway, and Hippo signaling pathway. The PPI network indicated the most circRNAs might participate in the BeSO4 toxicity by acting as a sponge for the miR-663b through JAK–STAT signaling pathway. In summary, our study suggests that circRNAs may play roles in the mechanism of beryllium toxicity.
研究领域:
分子生物学
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毒理学
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生物信息学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Jia Liu,Liuting Zheng,Xinyue Li,Wei Tang,Manyu Guo,Yuxing Wang,Xiaoqi Tan,Jiajia Chang,Huiyue Zhao,Dongsheng Zhu,Yu-qiang Ma,Da Huo
Understanding the interaction between nanomaterials and cellular structures is crucial for nanoparticle applications in biomedicine. We have identified a subtype of stress granules, called nanomaterial-provoked stress granules (NSGs), induced by gold nanorods (AuNRs). These NSGs differ from traditional SGs in their physical properties and biological functions. Uptake of AuNRs causes reactive oxygen species accumulation and protein misfolding in the cell, leading to NSG formation. Physically, NSGs have a gel-like core and a liquid-like shell, influenced positively by HSP70 and negatively by HSP90 and the ubiquitin-proteasome system. AuNRs promote NSG assembly by interacting with G3BP1, reducing the energy needed for liquid–liquid phase separation (LLPS). NSGs impact cellular functions by affecting mRNA surveillance and activating Adenosine 5′-monophosphate (AMP)-activated protein kinase signaling, crucial for a cellular stress response. Our study highlights the role of LLPS in nanomaterial metabolism and suggests NSGs as potential targets for drug delivery strategies, advancing the field of nanomedicine.
研究领域:
纳米生物技术
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细胞生物学
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分子生物学
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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
Frontiers in Immunology
·
2022
·
IF 8.786
Lifang Ye,Yu Zuo,Fang Chen,Yuetong Xu,Puli Zhang,Hongxia Yang,Qinglin Peng,Guochun Wang,Xiaoming Shu
Objective To evaluate adrenomedullin mRNA levels in the peripheral blood mononuclear cells (PBMCs) of patients with dermatomyositis (DM) as well as their correlation with the severity of interstitial lung disease (ILD). Methods A total of 41 DM patients and seven immune-mediated necrotizing myopathy (IMNM) patients were recruited, in addition to 21 healthy controls (HCs). The adrenomedullin mRNA levels in PBMCs were measured via quantitative reverse-transcription real-time polymerase chain reaction (qRT-PCR). The associations between adrenomedullin expression levels and major clinical, laboratory, pulmonary function parameters and the prognosis of patients with DM-related ILD (DM-ILD) were analyzed. Immunohistochemical analysis was performed on lung tissues of DM-ILD patients to determine adrenomedullin expression. Results Adrenomedullin mRNA levels in PBMCs were significantly higher in DM patients than in IMNM patients and HCs (p = 0.022 and p<0.001, respectively). Among DM patients, the levels were significantly higher in those with rapidly progressive ILD (RP-ILD) than in those with chronic ILD (p = 0.002) or without ILD (p < 0.001). The adrenomedullin mRNA levels in DM-ILD were positively correlated with serum ferritin (r =0.507, p =0.002), lactate dehydrogenase (LDH) (r =0.350, p =0.045), and lung visual analog scale (VAS) (r=0.392, p=0.021) and were negatively correlated with pulmonary function test parameters, including predicted forced vital capacity (FVC)% (r = −0.523, p = 0.025), forced expiratory volume in 1 s (FEV1)% (r = -0.539, p = 0.020), and diffusing capacity of carbon monoxide (DLco)% (r = -0.495, p = 0.036). Immunohistochemical analysis of adrenomedullin confirmed higher expression in the alveolar epithelial cells and macrophages of DM patients with RP-ILD. Among the DM patients with ILD, the six decedents exhibited higher adrenomedullin levels than the 28 survivors (p = 0.042). The cumulative survival rate was significantly lower (62.5% vs . 100%, P = 0.005) in patients with an adrenomedullin level > 0.053 than in those with a level <0.053. Conclusions Adrenomedullin levels are upregulated in DM patients with RP-ILD and are associated with ILD severity and poor prognosis. Adrenomedullin may be a potential prognostic biomarker in DM patients with ILD, although need further investigation.
研究领域:
风湿病学
·
肺科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PeerJ
·
2024
·
IF 2.3
Mengxiang Du,Shengwei Huang,Zihan Huang,Lijuan Qian,Yang Gui,Jing Hu,Yujun Sun
Although Morchella esculenta (L.) Pers. is an edible and nutritious mushroom with significant selenium (Se)-enriched potential, its biological response to selenium stimuli remains unclear. This study explored the effect of selenium on mushroom growth and the global gene expression profiles of M. esculenta . While 5 µg mL −1 selenite treatment slightly promoted mycelia growth and mushroom yield, 10 µg mL −1 significantly inhibited growth. Based on comparative transcriptome analysis, samples treated with 5 µg mL −1 and 10 µg mL −1 of Se contained 16,061 (452 upregulated and 15,609 downregulated) and 14,155 differentially expressed genes (DEGs; 800 upregulated and 13,355 downregulated), respectively. Moreover, DEGs were mainly enriched in the cell cycle, meiosis, aminoacyl-tRNA biosynthesis, spliceosome, protein processing in endoplasmic reticulum pathway, and mRNA surveillance pathway in both selenium-treated groups. Among these, MFS substrate transporter and aspartate aminotransferase genes potentially involved in Se metabolism and those linked to redox homeostasis were significantly upregulated, while genes involved in isoflavone biosynthesis and flavonoid metabolism were significantly downregulated. Gene expression levels increased alongside selenite treatment concentration, suggesting that high Se concentrations promoted M. esculenta detoxification. These results can be used to thoroughly explain the potential detoxification and Se enrichment processes in M. esculenta and edible fungi.
研究领域:
真菌学
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转录组学
·
分子生物学
·
营养学
✓ 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）