CHEMICO-BIOLOGICAL INTERACTIONS
·
2022
·
IF 5.168
Liangping Li,Wenqing Du,Hui Wang,Yufei Zhao,Zetian Huang,Yan Peng,Shulan Zeng,Guohai Zhang
p53 inactivation is a common feature in non-small cell lung cancer (NSCLC) resulting in NSCLC malignant transformation . Targeting serine 392 phosphorylation to restore p53 anticancer activity has proven to be an effective therapeutic strategy against NSCLC. A synthetic p53 activator, NA-17, has been developed that shows promise in preclinical models of NSCLC. However, NA-17 exhibits limited therapeutic efficacy in oncogene-driven tumors as well as relatively high toxicity to normal cells. It is possible that high efficiency and low toxicity p53 activators can be obtained by optimizing the leading molecule. Here, we performed high-throughput screening of compounds optimized based on NA-17 to identify new p53 activators. Two promising candidates named MX-C2 and MX-C3 were identified, both exhibited considerable therapeutic efficacy in oncogene-driven tumor models. Similar to NA-17, MX-C2/3 induced p53 activation via phosphorylating serine-392 without DNA damage. Both compounds showed broad antitumor activity in NSCLC cells and limited toxicity in normal cell lines. Moreover, MX-C2/3 suppressed tumor progression by arresting the cell cycle at G2/M phase, exhibiting a different mechanism of cell cycle arrest than NA-17. In addition, MX-C2/3 promoted the enrichment of p-p53 (s392) in mitochondria, leading to the conformational activation of Bak for cell apoptosis, which is consistent with NA-17. Finally, we demonstrated that MX-C2 significantly inhibited tumor growth without obvious systemic toxicity in oncogene-driven HCC-827 xenograft models. Collectively, we report two p53 activators with high-efficiency and low-toxicity that target p53 serine 392 phosphorylation for anticancer translational investigation.
研究领域:
肿瘤学
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分子生物学
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药理学
·
癌症研究
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Nan Zhao,Hao Wang,Jiarui Li,Xi Lin,Liming Guo,Xinhua Guo
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) is emerging as the most powerful tool for the identification of bacteria. Herein, we demonstrated that the capability of MALDI-TOF-MS towards the discrimination of clinical bacteria can be further dramatically improved. A cooperative matrix consisting of (E)-propyl α-cyano-4-hydroxylcinnamylate (CHCA-C3) and α-cyano-4-hydroxycinnamic acid (CHCA) was used to replace the commonly used matrix CHCA. As a result, 1.4–3.8 times more fingerprint peaks have been identified by the cooperative matrix in comparison with CHCA when six different bacteria were studied. The peaks distribute in the wider m / z range, and the spectral quality has also been significantly improved. As an example of practical applications, the direct and more reliable discrimination between Escherichia coli (E. coli) and Shigella sonnei ( S. sonnei) was achieved based on their protein fingerprints, which was previously claimed to be impossible by CHCA. Thus, a promoted MALDI-TOF-MS platform towards bacterial identification has been established by utilizing the new cooperative matrix, which will exhibit great potential for many applications.
研究领域:
分析化学
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微生物学
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质谱学
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产品关联
DOI
高影响因子
Nanoscale
·
2013
·Vol. 5
·期 24
·12633-12644
·
IF 6.233
Yun Zeng,Shaojuan Zhang,Menghui Jia,Yang Liu,Jin Shang,Youmin Guo,Jianhua Xu,Daocheng Wu
A new hypoxia-sensitive coordination compound, bis(2-(2′-benzothienyl)pyridinato-N,C3′)iridium[poly(n-butyl cyanoacrylate)], hereafter denoted as (btp)2Ir(PBCA), is synthesized and characterized by 13C nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR). (btp)2Ir(PBCA)/chitosan [(btp)2Ir(PBCA)/CS] nanoparticles (NPs) with a core–shell structure are prepared by a two-step fabrication process. The size distributions of these NPs are measured with a Malvern size analyzer, and their morphology is observed by transmission electron microscopy (TEM). The functional groups on the surface are confirmed by FTIR. Phosphorescence spectra are obtained and lifetimes are determined with a spectrophotofluorometer and a time-correlated single photon counting (TCSPC) apparatus, respectively. HeLa and CT26 cell lines are used to examine the cytotoxicity by the MTT assay, as well as to determine the imaging capability of the samples in air and nitrogen atmospheres, respectively. Tumor-bearing mouse models of colon adenocarcinoma are used for tumor imaging in vivo, and the imaging effect is evaluated with a Maestro 2 fluorescence imaging system. Compared with the hypoxia-associated probe bis(2-(2′-benzothienyl)pyridinato-N,C3′)iridium(acetylacetonate) (BTP), the phosphorescence lifetime of (btp)2Ir(PBCA)/CS NPs significantly decreases, but the hypoxia-sensitivity increases after preparation of NPs. Apart from the significantly lower cytotoxicity, (btp)2Ir(PBCA)/CS NPs also enhance the tumor imaging effect by more than 10 times, maintaining the phosphorescence signal in tumor tissue for over 24 h and significantly decreasing the phosphorescence signal in normal tissue in vivo compared with the BTP probe.
研究领域:
生物医学工程
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肿瘤学
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材料科学
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DOI
PubMed
高影响因子
ENERGY & FUELS
·
2023
·
IF 5.3
Xiaojun Dai,Yan Cheng,Tingting Liu,Lingjuan Mao,Qiang Wei,Yasong Zhou
SAPO-11 molecular sieves with different crystal sizes and particle sizes, especially nanosized small-crystal SAPO-11 molecular sieves, were successfully synthesized, and the corresponding NiWS-supported catalysts were prepared for the hydroisomerization of n-hexadecane. XRD, SEM, N2 adsorption–desorption, Py-IR, and HRTEM were used to analyze the effects of crystal size and particle size of the supports on their physicochemical properties, active phase properties, and catalytic performance of the catalysts. Through reaction evaluation and analysis of isomeric products, the effects of the size change of the support on the hydroisomerization performance of the catalyst and the hydroisomerization depth of n-hexadecane were determined. Through comprehensive analysis of the cracking products, it was determined that secondary cracking occurred when the conversion of n-hexadecane on the NiW/SAPO-11-S catalyst reached about 42.7%, and the secondary isomerization occurred when the conversion of n-hexadecane reached about 80%. The hydroisomerization reaction network of n-hexadecane over the NiWS/SAPO-11 catalyst was studied emphatically, and it was found for the first time that the secondary cracking of n-hexadecane during hydroisomerization followed the C3-β-scission mechanism.
研究领域:
化学工程
·
催化
·
材料科学
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DOI
高影响因子
Journal of Xenobiotics
·
2024
·Vol. 14
·期 3
·923-938
·
IF 6.8
Junhua Huang,Zhengyi Fu,Wei Yu,Zemin Bai,Zhenhua Ma
This study examines the physiological and immunological effects of 0.5 ppm carbaryl exposure on juvenile Asian seabass (Lates calcarifer) over 12 h to 72 h. Notable results include decreased activities of liver enzymes catalase (CAT), lactate dehydrogenase (LDH), and glutathione peroxidase (GSH-PX), while superoxide dismutase (SOD) levels remained stable, with the lowest activities of CAT and GSH-PX observed at 72 h. Serum biochemistry revealed increased alkaline phosphatase (AKP) and acid phosphatase (ACP) at 24 h, with declining aspartate aminotransferase (AST) and a peak in creatinine at 48 h. Histopathological analysis showed carbaryl-induced necrosis in liver and spleen cells, and increased melanomacrophage centers in both organs. Additionally, immune gene expression analysis indicated an upregulation of heat shock proteins and consistent elevation of complement component C3 and interleukin-8 (IL-8). These findings suggest that carbaryl exposure significantly impairs organ function and modulates immune responses inL. calcarifer, underlining the need for further research on protective strategies against pesticide impacts in aquaculture.
研究领域:
水产毒理学
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环境科学
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免疫学
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生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF POWER SOURCES
·
2026
·
IF 8.4
Guanghui Zhou,Yumeng Jia,Kai Chen,Haiguang Gao,Jian Zang,Yucheng Huang,Juan Xu,Jianyu Cao
Organic cathode materials present a highly viable alternative, offering abundant resources, environmental compatibility, and highly designable molecular structures. However, conventional organic materials suffer from high solubility and low electronic conductivity. To overcome these inherent drawbacks, we propose a structural design strategy based on constructing extended π-conjugated molecular frameworks with high-density electrochemically reversible groups. Inspired by this strategy, we synthesized a novel sulfur-linked C3-symmetric conjugated organic compound, tris-benzothioxanthenedione 2,3-b (denoted as 6S6O), via a facile condensation reaction. The unique structure of 6S6O provides multiple high-density C=O/C=N moieties for reversible lithium storage, excellent solvent tolerance, and high intrinsic conductivity due to electron delocalization. Electrochemical testing demonstrates outstanding performance in a Li//6S6O half-cell, delivering a high reversible capacity of 352 mAh g −1 at 0.1 A g −1 , corresponding to a high energy density of ∼748.6 Wh kg −1 . Importantly, the electrode demonstrates excellent rate capability (retaining 65.3% capacity with a 20-fold current increase) and superior long-term cycling stability, maintaining 77.5% capacity retention over 2409 cycles at 2 A g −1 . Ex situ characterization and DFT calculations confirm a highly reversible, capacitive-controlled Li + storage mechanism involving the C=O and C=N bonds of the quinone/pyrazine units. The results validate the effectiveness of the extended π-conjugated design for developing high-performance organic cathode materials.
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产品关联
DOI
高影响因子
Nano Today
·
2024
·
IF 13.2
Keying Chen,Chunxiong Zheng,Yunjuan Lv,Pengkai Zhao,Tong Lin,Yanteng Xu,Huimin Kong,Ke Yi,Qingguo Zhong,Mingqiang Li,Yu Tao,Haixia Wang
In acute inflammation, the heightened activation and recruitment of immune cells present an opportunity to leverage them as natural carriers for efficient transport of diagnostic probes and nanotherapeutics. Although complement opsonization facilitates the internalization of nanomedicines by activated neutrophils, the development of strategies to specifically augment complement deposition remains a challenge. Herein, we engineer silymarin-loaded liposomes (Lips) coated with immunoglobulin G (IgG) to enhance complement 3 (C3) deposition in the protein corona, thereby enabling neutrophil-mediated, precise targeting to the site of inflammation. Through the examination of various serum proteins, we discover that IgG adsorption, particularly with its Fc portion exposed, prominently promotes C3 enrichment in the protein corona, resulting in C3 cleavage into iC3b. This facilitates the uptake of C3-enriched Lips by activated neutrophils with elevated C3 receptor expression, thus improving the efficiency and specificity of nanomedicine delivery to inflammatory site. Following the formation of neutrophil extracellular traps, the released nanomedicine effectively mitigates hepatocyte damage by eliminating accumulated reactive oxygen species and inducing a shift in macrophage polarization towards the anti-inflammatory M2 phenotype. Our IgG-modified nanomedicine demonstrates significant therapeutic efficacy against acute liver failure by regulating the protein corona and hitchhiking neutrophils, offering a promising strategy for efficient and precise treatment of inflammation.
研究领域:
药理学
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免疫学
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纳米技术
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肝病学
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DOI
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2018
·Vol. 106
·期 5
·1223-1235
·
IF 3.231
Mengxia Guo,Yifan Dong,Jiangwei Xiao,Ruicai Gu,Maochao Ding,Tao Huang,Junhua Li,Naru Zhao,Hua Liao
Inorganic/organic hybrid silica-chitosan (CS) scaffolds have promising potential for bone defect repair, due to the controllable mechanical properties, degradation behavior, and scaffold morphology. However, the precise in vivo immuno-reactivity of silica-CS hybrids with various compositions is still poorly defined. In this study, we fabricated the three-dimensional (3D) interconnected porous chitosan-silica (CS/SiO 2 ) and chitosan-silica-hydroxyapatite (CS/SiO 2 /HA) hybrids, through sol–gel process and 3D plotting skill, followed by the naturally or freeze drying separately. Scanning electron microscopy demonstrated the hybrids possessed the uniform geometric structure, while, transmission electron microscopy displayed nanoscale silica, or HA nanoparticles dispersed homogeneously in the CS matrix, or CS/silica hybrids. After intramuscular implantation, CS/SiO 2 and CS/SiO 2 /HA hybrids triggered a local and limited monocyte/macrophage infiltration and myofiber degeneration. Naturally dried CS/SiO 2 hybrid provoked a more severe inflammation than the freeze-dried ones. Dendritic cells were attracted to invade into the implants embedded-muscle, but not be activated to prime the adaptive immunity, because the absence of cytotoxic T cells and B cells in muscle received the implants. Fluorescence-activated cell sorting (FACS) analysis indicated the implanted hybrids were incapable to initiate splenocytes activation. Plasma complement C3 enzyme linked immunosorbent assay (ELISA) assay showed the hybrids induced C3 levels increase in early implanting phase, and the subsequent striking decrease. Thus, the present results suggest that, in vivo , 3D plotted porous CS/SiO 2 and CS/SiO 2 /HA hybrids are relatively biocompatible in vivo, which initiate a localized inflammatory procedure, instead of a systematic immune response. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1223–1235, 2018.
研究领域:
生物材料
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组织工程
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免疫学
·
生物医学材料
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产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2024
·Vol. 38
·期 13
·e23781
·
IF 4.4
Wenfang Lai,Siying Huang,Junjie Liu,Binbin Zhou,Zhengshuang Yu,John Brown,Guizhu Hong
Reactive astrocytes are important pathophysiologically and synthesize neurosteroids. We observed that LPS increased immunoreactive TLR4 and key steroidogenic enzymes in cortical astrocytes of rats and investigated whether corticosteroids are produced and mediate astrocytic TLR4-dependent innate immune responses. We found that LPS increased steroidogenic acute regulatory protein (StAR) and StAR-dependent aldosterone production in purified astrocytes. Both increases were blocked by the TLR4 antagonist TAK242. LPS also increased 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and corticosterone production, and both were prevented by TAK242 and by siRNAs against 11β-HSD1, StAR, or aldosterone synthase (CYP11B2). Knockdown of 11β-HSD1, StAR, or CYP11B2 or blocking either mineralocorticoid receptors (MR) or glucocorticoid receptors (GR) prevented dephosphorylation of p-Ser 9 GSK-3β, activation of NF-κB, and the GSK-3β-dependent increases of C3, IL-1β, and TNF-α caused by LPS. Exogenous aldosterone mimicked the MR- and GSK-3β-dependent pro-inflammatory effects of LPS in astrocytes, but corticosterone did not. Supernatants from astrocytes treated with LPS reduced MAP2 and viability of cultured neurons except when astrocytic StAR or MR was inhibited. In adrenalectomized rats, intracerebroventricular injection of LPS increased astrocytic TLR4, StAR, CYP11B2, and 11β-HSD1, NF-κB, C3 and IL-1β, decreased astrocytic p-Ser 9 GSK-3β in the cortex and was neurotoxic, except when spironolactone was co-injected, consistent with the in vitro results. LPS also activated NF-κB in some NeuN + and CD11b + cells in the cortex, and these effects were prevented by spironolactone. We conclude that intracrine aldosterone may be involved in the TLR4-dependent innate immune responses of astrocytes and can trigger paracrine effects by activating astrocytic MR/GSK-3β/NF-κB signaling.
研究领域:
神经科学
·
免疫学
·
药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Peng Zhang,Guanghua Lu,Yu Sun,Zhenhua Yan,Leibo Zhang,Jianchao Liu
Microplastics and antibiotics are prevalent and emerging pollutants in aquatic ecosystems, but their interactions in aquatic food chains remain largely unexplored. This study investigated the impact of polypropylene microplastics (PP-MPs) on oxytetracycline (OTC) trophic transfer from the shrimp ( Neocaridina denticulate ) to crucian carp ( Carassius auratus ) by metagenomic sequencing. The carrier effects of PP-MPs promoted OTC bioaccumulation and trophic transfer, which exacerbated enterocyte vacuolation and hepatocyte eosinophilic necrosis. PP-MPs enhanced the inhibitory effect of OTC on intestinal lysozyme activities and complement C3 levels in shrimp and fish, and hepatic immunoglobulin M levels in fish (p < 0.05). Co-exposure of MPs and OTC markedly increased the abundance of Actinobacteria in shrimp and Firmicutes in fish, which caused disturbances in carbohydrate, amino acid, and energy metabolism. Moreover, OTC exacerbated the enrichment of antibiotic resistance genes (ARGs) in aquatic animals, and PP-MPs significantly increased the diversity and abundance of ARGs and facilitated the trophic transfer of teta and tetm . Our findings disclosed the impacts of PP-MPs on the mechanism of antibiotic toxicity in aquatic food chains and emphasized the importance of gut microbiota for ARGs trophic transfer, which contributed to a deeper understanding of potential risks posed by complex pollutants on aquatic ecosystems.
研究领域:
环境科学
·
生态毒理学
·
微生物学
·
水生生态学
·
污染研究
·
基因组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Hao Wu,Xiping Yuan,Yong He,Jinwei Gao,Min Xie,Zhonggui Xie,Rui Song,Dongsheng Ou
Niclosamide (NIC) is a commonly used insecticide and molluscicide in the prevention and treatment of parasitic diseases in fish. The utilization of NIC has the potential to disrupt the microbial community present on the mucosal tissue of fish, leading to localized inflammatory responses. The objective of this study was to evaluate the impact of NIC on the immune system and bacterial populations within the gill and gut of Mylopharyngodon piceus . Fish were subjected to varying concentrations of NIC, including a control group (0 μg/L), a low NIC group (15% 96 h LC50, LNG, 9.8 μg/L), and a high NIC group (80% 96 h LC50, HNG, 52.5 μg/L). Gill and gut samples were collected 28 days post-exposure for analysis. The findings revealed that the 96-h LC 50 for NIC was determined to be 65.7 μg/L, and histopathological examination demonstrated that exposure to NIC resulted in gill filament subepithelial edema, exfoliation, degeneration, and a decrease in gill filament length. Furthermore, the gut exhibited apical enterocyte degeneration and leucocyte infiltration following NIC exposure. Additionally, NIC exposure led to a significant elevation in the levels of immunoglobulin M (IgM), complement component 3 (C3), and complement component 4 (C4) in both gill and gut tissues. Moreover, the activity of lysozyme (LYZ) was enhanced in the gill, while the activities of peroxidase (POD) and immunoglobulin T (IgT) were increased in gut tissue. The exposure to NIC resulted in enhanced mRNA expression of c3 , c9 , tnfα , il6 , il8 , and il11 in the gill tissue, while decreasing c3 and il8 expression in the gut tissue. Furthermore, the natural resistance-associated macrophage protein ( nramp ) mRNA increased, and liver-expressed antimicrobial peptide 2 ( leap2 ) mRNA decreased in gill and gut tissues. And hepcidin ( hepc ) mRNA levels rose in gill but fell in gut tissue. NIC exposure also led to a decrease in gill bacterial richness and diversity, which significantly differed from the control group, although this separation was not significant in the gut tissue. In conclusion, the administration of NIC resulted in alterations in both the immune response and mucosal microbiota of fish. Furthermore, it was noted that gills displayed a heightened vulnerability to sublethal effects of NIC in comparison to gut tissues.
研究领域:
水生毒理学
·
免疫学
·
微生物学
·
鱼类生物学
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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）