JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2023
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IF 6.1
Bing-hao Lin,Run-xun Ma,Jing-tao Wu,Shi-qi Du,Yi-yun Lv,Hao-nan Yu,Wei Zhang,Shu-ming Mao,Guang-yao Liu,Yi-tian Bu,Zi-hao Chen,Chen Jin,Zong-yi Wu,Lei Yang
Osteoporosis (OP) is typically brought on by disruption of bone homeostasis. Excessive oxidative stress and mitochondrial dysfunction are believed to be the primary mechanisms underlying this disorder. Therefore, in order to restore bone homeostasis effectively, targeted treatment of oxidative stress and mitochondrial dysfunction is necessary. Cinnamaldehyde (CIN), a small molecule that acts as an agonist for the nuclear factor erythroid 2-related factor (Nrf2), has been found to possess antiapoptotic, anti-inflammatory, and antioxidant properties. We found that CIN, while rescuing apoptosis, can also reduce the accumulation of reactive oxygen species (ROS) to improve mitochondrial dysfunction and thus restore the osteogenic differentiation potential of BMSCs disrupted by hydrogen peroxide (H2O2) exposure. The role of CIN was preliminarily considered to be a consequence of Nrf2/HO-1 axis activation. The ovariectomized mice model further demonstrated that CIN treatment ameliorated oxidative stress in vivo, partially reversing OVX-induced bone loss. This improvement was seen in the trabecular microarchitecture and bone biochemical indices. However, when ML385 was concurrently injected with CIN, the positive effects of CIN were largely blocked. In conclusion, this study sheds light on the intrinsic mechanisms by which CIN regulates BMSCs and highlights the potential therapeutic applications of these findings in the treatment of osteoporosis.
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FOOD AND CHEMICAL TOXICOLOGY
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2023
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IF 4.3
Sailing Chen,Shaowei Wang,Jingyi Zheng,Han Lu,Huiqian Chen,Yunbing Tang,Nan Wang,Yang Zhu,Yiyan Wang,Ping Duan,Ren-shan Ge
Bisphenols , estrogenic endocrine-disrupting chemicals, disrupt at least one of three endocrine pathways (estrogen, androgen, and thyroid). 17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) is a steroidogenic enzyme that catalyzes the activation of estradiol from estrone in human placenta and rat ovary. However, whether bisphenols inhibit 17β-HSD1 and the mode of action remains unclear. This study we screened 17 bisphenols for inhibiting human 17β-HSD1 in placental microsomes and rat 17β-HSD1 in ovarian microsomes and determined 3D-quantitative structure-activity relationship (3D-QSAR) and mode of action. We observed some bisphenols with substituents were found to significantly inhibit both human and rat 17β-HSD1 with the most potent inhibition on human enzyme by bisphenol H (IC 50 = 0.90 μM) when compared to bisphenol A (IC 50 = 113.38 μM). Rat enzyme was less sensitive to the inhibition of bisphenols than human enzyme with bisphenol H (IC 50 = 32.94 μM) for rat enzyme. We observed an inverse correlation between IC 50 and hydrophobicity (expressed as Log P). Docking analysis showed that they bound steroid-binding site of 17β-HSD1. The 3D-QSAR models demonstrated that hydrophobic region, hydrophobic aromatic, ring aromatic, and hydrogen bond acceptor are key factors for the inhibition of steroid synthesis activity of 17β-HSD1.
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ENVIRONMENTAL RESEARCH
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2023
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IF 8.3
Yuqing Liu,Huiqing Ma,Ang Li,Haixia Pan,Xianliang Yi,Yang Liu,Jingjing Zhan,Hao Zhou
Tellurium (Te) is a rare element within the chalcogen group, and its biogeochemical cycle has been studied extensively. Tellurite (Te(IV)) is the most soluble Te species and is highly toxic to organisms. Chemical or biological Te(IV) reduction to elemental tellurium (Te 0 ) is generally considered an effective detoxification route for Te(IV)-containing wastewater. This study unveils a previously unnoticed Te 0 oxidation process mediated by the manganese-oxidizing bacterium Bacillus sp. FF-1. This bacterium, which exhibits both Mn(II)-oxidizing and Te(IV)-reducing abilities, can produce manganese oxides (BioMnO x ) and Te 0 (BioTe 0 ) when exposed to Mn(II) and Te(IV), respectively. When 5 mM Mn(II) was added after incubating 0.1 mM or 1 mM Te(IV) with strain FF-1 for 16 h, BioTe 0 was certainly re-oxidized to Te(IV) by BioMnOx. Chemogenic and exogenous biogenic Te 0 can also be oxidized by BioMnOx, although at different rates. This study highlights a new transformation process of tellurium species mediated by manganese-oxidizing bacteria, revealing that the environmental fate and ecological risks of Te 0 need to be re-evaluated.
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JOURNAL OF DRUG TARGETING
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2023
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IF 4.5
Chen Guo,Mingyi Yu,Jinghua Liu,Zhe Jia,Hui Liu,Shaozhen Zhao
Dry eye disease (DED) is often secondary to diabetes mellitus (DM). We explored the action of Wilms tumor 1-associated protein (WTAP) in DM-DED via lncRNA NEAT1 m6A methylation. DM-DED mouse models were treated with sh-WTAP/sh-NEAT1 plasmid, followed by assessment of corneal epithelial damage/histopathological changes. HCE-2 cells were exposed to hyperosmotic conditions to establish in vitro DED models and treated with oe-NEAT1/sh-NEAT1/sh-WTAP/nigericin (an NLRP3 inflammasome inducer). Cell viability/apoptosis were evaluated by CCK-8/TUNEL. The levels of WTAP/NEAT1/inflammatory factors/NLRP3 inflammasome- and apoptosis-related markers were determined. m6A modification was examined by MeRIP-qPCR and NEAT1 stability was also detected. DM-DED mice exhibited up-regulated WTAP/NEAT1 expression and severe corneal damage, whereas WTAP/NEAT1 knockdown alleviated inflammation/corneal damage. In hyperosmolarity-induced HCE-2 cells, NEAT1 aggravated inflammation and apoptosis, while NEAT1 knockdown suppressed NLRP3 inflammasome activation and ameliorated cell injury. Hyperosmolarity-induced WTAP expression increased m6A modification and NEAT1 mRNA stability. WTAP mediated m6A methylation of NEAT1 and NLRP3 inflammasome activation in DM-DED mice. Collectively, WTAP upregulates NEAT1 expression and facilitates NLRP3 inflammasome activation by increasing m6A methylation, thereby accelerating DM-DED development. WTAP or lncRNA NEAT1 may become a therapeutic target for DM-DED, which offers a theoretical foundation for the investigation and advancement of nanocarrier-based targeted therapeutic medications for DM-DED.
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PHYTOMEDICINE
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2023
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IF 7.9
Baohong Li,Zichao Chen,Zhenyong Zhang,Hui Liu,Dongli Han,Haolin Yang,Zhen Zhang
Background: Breast cancer bone metastasis is closely associated with the bone microenvironment. Zuogui Pill (ZGP), a clinically approved formulation in China, effectively regulates the bone microenvironment for the prevention and treatment of osteoporosis. Purpose: Few reports have utilized the ZGP for bone metastasis models. This study investigated the intervention and bone-protective properties of ZGP against breast cancer bone metastasis, explored the potential mechanism, and screened for its active compositions by molecules fishing. Methods: To investigate the intervention efficacy of ZGP and its protein-level mechanism of action, the mouse bone metastasis model and in vitro cell co-culture model were constructed. Affinity ultrafiltration, molecular docking, cellular thermal shift assay and physical scale detection were used to investigate the affinity components of the RANKL protein in ZGP. Results: The administration of ZGP combined with zoledronic acid inhibited the development of tumors and secondary lung metastasis in mice. This translated to a prolonged survival period and enhanced quality of life. ZGP could disrupt the malignant cycle by modulating the Piezo1-Notch-1-GPX4 signaling pathway in the "bone-cancer" communication in the cell co-culture model. Furthermore, 25 chemical components of ZGP were identified, with 10 active compounds exhibiting significant affinity for the RANKL protein. Conclusion: The findings of this work highlighted ZGP's potential for intervening in the progression of breast cancer bone metastasis. Thus, this investigation served as an experimental foundation for expanding the application scope of ZGP and for advancing drug development efforts in bone metastasis treatment.
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BIOSENSORS & BIOELECTRONICS
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2023
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IF 12.6
Zhijun Lin,Mengyao Liu,Wei Xing,Feng-Hua Wang,Hongxia Zhang,Xiao-Li Wei,Hans Schmitthenner,Xi Xie,Xiaojun Xia,Jiang Yang
Sensitive and accurate biomarker-driven assay guidance has been widely adopted to identify responsive patients for immune checkpoint blockade (ICB) therapy to impede disease progression and extend survival. However, most current assays are invasive, requiring surgical pathology specimens and only informing monochronic information. Here, we report a multiplexed enhanced fluorescence microarray immunoassay (eFMIA) based on a nanostructured gold nanoisland substrate (AuNIS), which macroscopically amplifies near-infrared fluorescence (NIRF) of a structurally symmetric IRDye78 fluorophore by over two orders of magnitude of 202.6-fold. Aided by non-contact piezo-driven micro-dispensing (PDMD), eFMIA simultaneously and semi-quantitatively detected intracellular and secreted programmed death-ligand 1 (PD-L1) and intercellular adhesion molecule-1 (ICAM-1) in human nasopharyngeal carcinoma (NPC) cells. The assay performance was superior to fluorescence immunoassays (FIA) and enzyme-linked immunosorbent assays (ELISA), with lower detection limits. Using eFMIA, we found significantly differential levels of soluble PD-L1 (sPD-L1) and sICAM-1 in the sera of 28 cancer patients, with different clinical outcomes following anti-PD-1 ICB therapy. With a well-characterized mechanism, the high-performance plasmonic multiplexed assay with the composite biomarkers may be a valuable tool to assist clinicians with decision-making and patient stratification to afford predictive ICB therapy responses.
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MOLECULES
·
2023
·Vol. 28
·期 17
·6344
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IF 4.6
Shuanghui Wang,Chuhong Chen,Yan Lu
Cadmium (Cd), a harmful heavy metal that has no biological purpose, can harm healthy fetal and child development. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in tea, has been shown to increase cell viability under Cd exposure and ameliorate Cd-induced kidney injury in adult male rats. Using theCaenorhabditis elegans(C. elegans) model, we demonstrated that EGCG mitigated Cd-induced body size developmental toxicity through a mechanism that did not involve chelation with EGCG and was not associated with Cd accumulation and efflux. Our research indicated that the beneficial effects of EGCG on Cd-induced body size developmental toxicity were associated with the mitigation of endoplasmic reticulum stress. Furthermore, our observations indicate that EGCG reduced Cd-induced developmental toxicity inC. elegansvia the PEK-1/eIF-2α/ATF-4 pathway. Our results provide important evidence for the potential benefits of consuming tea as a detoxification agent.Keywords:tea;EGCG;cadmium;Caenorhabditis elegans;developmental toxicity;endoplasmic reticulum stress
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AGING CELL
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2023
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IF 7.8
Chaweewan Sirakawin,Dongfa Lin,Ziyue Zhou,Xiaoxin Wang,Rhianne Kelleher,Shangyuan Huang,Weimiao Long,Andre Pires-daSilva,Yu Liu,Jingjing Wang,Ilya A. Vinnikov
Vitamin A (VA) is a micronutrient essential for the physiology of many organisms, but its role in longevity and age-related diseases remains unclear. In this work, we used Caenorhabditis elegans to study the impact of various bioactive compounds on lifespan. We demonstrate that VA extends lifespan and reduces lipofuscin and fat accumulation while increasing resistance to heat and oxidative stress. This resistance can be attributed to high levels of detoxifying enzymes called glutathione S-transferases, induced by the transcription factor skinhead-1 (SKN-1). Notably, VA upregulated the transcript levels of skn-1 or its mammalian ortholog NRF2 in both C. elegans , human cells, and liver tissues of mice. Moreover, the loss-of-function genetic models demonstrated a critical involvement of the SKN-1 pathway in longevity extension by VA. Our study thus provides novel insights into the molecular mechanism of anti-aging and anti-oxidative effects of VA, suggesting that this micronutrient could be used for the prevention and/or treatment of age-related disorders.
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Advanced Healthcare Materials
·
2023
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IF 10
Hanru Zhang,Zhiyu Wu,Jingjing Zhou,Zhaopeng Wang,Changyan Yang,Panpan Wang,Muhammad Subaan Fareed,Yuhang He,Jie Su,Ruitao Cha,Kairong Wang
Peptide hydrogels were believed to be potential biomaterials with wide application in the biomedical field because of their good biocompatibility, injectability, and three-dimensional (3D) printability. Most of the previously reported polypeptide hydrogels are composed of L-peptides, while the hydrogels formed by self-assembly of D-peptides are rarely reported. Herein, we reported a peptide hydrogel constructed by D-J-1, which was the all-D-enantiomer of antimicrobial peptide Jelleine-1. Field emission scanning electron microscope (FE-SEM) and rheologic study were performed to characterize the hydrogel. Antimicrobial, hemostatic, and anti-adhesion studies were carried out to evaluate its biofunction. Our results showed that D-J-1 hydrogel was formed by self-assembly and cross-linking driven by hydrogen bonding, hydrophobic interaction, and π-π stacking force of aromatic ring in the structure of D-J-1. It exhibited promising antimicrobial activity, hemostatic activity, and anti-adhesion efficiency in a rat sidewall defect-cecum abrasion model. In addition, it also exhibited good biocompatibility. Notably, D-J-1 hydrogel showed improved in vitro and in vivo stability when compared with its L-enantiomer J-1 hydrogel. Therefore, the present study would provide new insight into the application of D-peptide hydrogel, and provide a new peptide hydrogel with antibacterial, hemostatic, and anti-adhesion efficacy for clinical use. This article is protected by copyright. All rights reserved
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MOLECULES
·
2023
·Vol. 28
·期 9
·3935
·
IF 4.6
Peng Lu,Xiangjian Cao,Jinghui Zheng,Ying Sun,Ziyu Tang,Meiping Zhao
As a major apurinic/apyrimidinic endonuclease and a redox signaling protein in human cells, APE1 plays a crucial role in cellular function and survival. The relationship between alterations of APE1 expression and subcellular localization and the initiation, development and treatment of various cancers has received extensive attention. However, comparing the in-vivo activity of APE1 in normal and cancerous breast live cells remains challenging due to the low efficiency of commonly used liposome transfection methods in delivering DNA substrate probes into human normal breast epithelial cells (MCF-10A). In this work, we develop a DNA/RNA hybrid-based small magnetic fluorescent nanoprobe (25 ± 3 nm) that can be taken up by various live cells under magnetic transfection. The D0/R-nanoprobe demonstrates an outstanding specificity toward APE1 and strong resistance to the cellular background interference. Using this nanoprobe, we are not only able to visualize the intracellular activity of APE1 in breast ductal carcinoma (MCF-7) live cells, but also demonstrate the APE1 activity in MCF-10A live cells for the first time. The method is then extended to observe the changes in APE1 levels in highly metabolically active neuroendocrine cells under normal conditions and severe attacks by reactive oxygen species in real-time. The fluorescent nanoprobe provides a useful tool for studying the dynamic changes of intracellular APE1 in normal or cancerous live cells. It also displays the potential for visible and controllable release of miRNA drugs within live cells for therapeutic purposes.Keywords:apurinic/apyrimidinic endonuclease 1 (APE1);fluorescent nanoprobe;live cell fluorescence imaging;human normal breast epithelial cells (MCF-10A);human breast adenocarcinoma cells (MCF-7)
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Nano Energy
·
2023
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IF 17.6
Shule Huang,Gui Wang,Xinmiao Xuan,Moran Qin,Jieming Huang,Lirong Wang,Xiaoming Zhang,Nan Wang,Junwei Zhang,Zhipeng Hou,Xingsen Gao,Zhang Zhang,Junming Liu
Piezoelectricity in 2D transition metal dichalcogenides (TMDs) has gathered significant interest due to their massive exposure of unsaturated edge sites and high piezoelectric modulus. Nevertheless, the piezoelectricity in 1 T′ phase TMDs is inhibited by its center symmetry of space group. Herein, to break the shackles of piezoelectric polarization, we synthesize a piezoelectric material composed of an atomic molybdenum array bound to distorted 1 T′ ReS 2 (MDR). The phase transition from 1 T′ to distorted 1 T′ (D-1 T′) removes the special Peierl's distortion of ReS 2 , breaking its center symmetry and allowing for piezoelectric generation. Remarkably, MDR exhibits a large piezoelectric coefficient ( d 33 ) value of 15.45 pm/V, which is an order of magnitude higher than those reported in other TMDs. Combining with excellent piezocatalytic activity, a 0D/3D di-piezoelectric porous electret featuring an enhanced quantum confinement piezoelectric effect based on the MDR quantum dots (QDs) and inverse opal g-C 3 N 4 (IOCN) is demonstrated for high-efficiency piezoelectric catalysis.
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International Journal of Nanomedicine
·
2023
·
IF 8
Qi Lou,Lu Pan,Shengjin Xiang,Yueting Li,Jiahui Jin,Jingyang Tan,Baoshan Huang,Kaihui Nan,Sen Lin
Introduction Benzalkonium chloride (BAC) is widely employed as a preservative in eye drops, which will cause the death of corneal epithelial cells due to ROS production, DNA strand breakage, and mitochondrial dysfunction, resulting in dry eye disease (DED)-like changes in ocular surface tissues. In this study, Melatonin (MT) liposomes (TAT-MT-LIPs) designed by loading MT into TAT-modified liposomes have been developed, characterized, and used for inhibiting BAC-induced DED (BAC-DED).Methods The TAT was chemically grafted onto the Mal-PEG2000-DSPE by Michael’s addition between the sulfhydryl group in TAT and the maleimide group in Mal-PEG2000-DSPE. TAT-MT-LIPs were prepared using film dispersion followed by the extrusion method and topically treated in rats once a day. BAC-DED was induced in rats by topical administration with 0.2% BAC twice daily. Defects, edema, and inflammation of the corneas, as well as IOP, were examined. Histologic analyses of corneas were performed to assess the change of mitochondrial DNA oxidation and NLRP3/Caspase-1/GSDMD signaling transduction.Results After topical administration, TAT-MT-LIPs significantly alleviated DED-clinical symptoms of experimental animals by inhibiting tissue inflammation and preventing the loss of the corneal epithelium and conjunctival goblet cells. Our data suggested continuous ocular surface exposure of BAC-induced NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis, which was not reported before. BAC caused substantial mt-DNA oxidation, which promoted the transduction of NLRP3/Caspase-1/GSDMD and consequent corneal epithelium pyroptosis. TAT-MT-LIPs could efficiently suppress the BAC-induced corneal epithelium pyroptosis and inflammation by inhibiting mt-DNA oxidation and the subsequent signal transmission.Conclusion NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis is involved in the development of BAC-DED. The present study provided new insights into the adverse effects of BAC, which can serve as a new target for protecting corneal epithelium when applying BAC as a preservative in eye drops. The developed TAT-MT-LIPs can efficiently inhibit BAC-DED and give great potential to be developed as a new DED treatment.
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