OPTICAL MATERIALS
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2019
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IF 2.687
Huazhen Liao,Song Ye,Yanling Shi,Deping Wang
Small size optical-magnetic bifunctional upconversion nanoparticles (UCNPs) that can be effectively triggered by 808 nm exhibit distinct advantages of improved tissue penetrating depth, minimized overheating effect, possible for multimodal imaging and high clearance rate, which therefore are considered as desirable candidates for bioapplications. In this research, the 808 nm triggered sub-20 nm β-NaYF 4 :Yb 3+ /Er 3+ @NaGdF 4 :Yb 3+ /Nd 3+ @NaGdF 4 active-core@active-shell@inert-shell structured UCNPs with optical and magnetic bifunctional properties were developed by seed-mediated growth method with NaOA as sodium source instead of the generally used NaOH. Through optimizing Nd 3+ doping concentration and outermost NaGdF 4 inert-shell thickness, the optical-magnetic bifunctional core-shell-shell structured UCNPs exhibited strong UC emission intensity and improved magnetic property . Furthermore, the core-shell-shell NPs were validated to be no cytotoxicity by cell viability assessment. Therefore, this research may open a general avenue for the synthesis of small size multifunctional UCNPs for practical bioapplications without overheating.
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Translational Oncology
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2022
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IF 4.803
Yongxiu Du,Yanlan Yang,Wenbo Zhang,Chenxi Yang,Pu Xu
Oral squamous cell carcinoma (OSCC) is a usual oral cancer. Therefore, it's essential to identify targets for its early diagnosis and therapy. This research aimed to explore the roles of human β-defensin-3 (hBD-3) and nuclear factor-kappa B (NF-κB) p65 in the pathogenesis and progression of OSCC. The connection between NF-κB p65 and the carcinogenesis of oral cancer was analyzed by immunohistochemical staining. The relative expressions of hBD-3 and NF-κB p65 in OSCC cells were evaluated by qRT-PCR and Western blot. Afterward, hBD-3 was knocked down, and NF-κB p65 was overexpressed. The cell viability and invasion were tested via CCK-8 and Transwell experiment, and the expression of hBD-3, NF-κB p65, and its downstream molecules was evaluated by Western blot. The expression of NF-κB p65 was increased with the aggravation of the oral submucosal fibrosis. HBD-3 and NF-κB p65 were high-expressed in OSCC cells. The viability and invasion abilities of OSCC cells that knocked down hBD-3 were markedly decreased, while they were restored by the overexpression of NF-κB p65. The expressions of NF-κB p65 and c-myc were diminished while IκB and p21 were raised with the knockdown of hBD-3. After overexpression of NF-κB p65, the expression of hBD-3 and IκB did not change markedly, while c-myc was increased and p21 was decreased dramatically. HBD-3 and NF-κB p65 facilitate the proliferation and invasion of OSCC cells, and hBD-3 may promote this process by governing the expression of NF-κB p65 and its downstream c-myc and p21.
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COMPOSITES PART B-ENGINEERING
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2022
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IF 11.322
Yonghong Fan,Juan Pei,Xinxin Li,Yinhua Qin,Youqian Xu,Ming Ke,Jie Zhang,Yong Liu,Ju Tan,Mingcan Yang,Gang Li,Tianqing Li,Chuhong Zhu
Tissue-engineered vascular grafts (TEVGs) show great potential in clinics for treating vascular diseases. However, the complications including thrombosis, delayed endothelialization , and endothelial-to-mesenchymal transition (EndMT) induced pathological remodeling have been demonstrated to be the main cause of graft failure. Here, we have developed a multifunctional surface by immobilizing ALK5 inhibitor loaded covalent organic framework (COF) nanoparticles , recombinant CD47 protein, and vascular endothelial growth factor (VEGF). Such a surface can prevent thrombosis and stenosis in TEVGs. Immobilization of VEGF facilitated the recruitment of endothelial-forming cells to accelerate endothelialization. Grafting of CD47 endowed the TEVGs with stealth function to inhibit the adhesion and activation of platelets and macrophages, thereby suppressing thrombus formation and reducing the secretion of EndMT triggers (i.e. TNF-α and IL-1β). In addition, long-term in situ delivery of ALK5 inhibitor could block the TGF-β signaling pathway that mediated EndMT to prevent intima hyperplasia and endothelial dysfunction during graft remolding. This synergistic strategy is competent to support the formation of functional endothelium on the neo-intima, and has shown promising preliminary results in keeping the patency of TEVGs.
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JOURNAL OF MEDICINAL CHEMISTRY
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2019
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IF 6.054
Yao-Ling Wang,Sha Liu,Zhu-Jun Yu,Yuan Lei,Meng-Yi Huang,Yu-Hang Yan,Qiang Ma,Yang Zheng,Hui Deng,Ying Sun,Chengyong Wu,Yamei Yu,Qiang Chen,Zhenling Wang,Yong Wu,Guo-Bo Li
The emergence and spread of bacterial pathogens acquired metallo-β-lactamase (MBL) and serine-β-lactamase (SBL) medicated β-lactam resistance gives rise to an urgent need for the development of new dual-action MBL/SBL inhibitors. Application of a pharmacophore fusion strategy led to the identification of (2′S)-(1-(3′-mercapto-2′-methylpropanamido)methyl)boronic acid (MS01) as a new dual-action inhibitor, which manifests broad-spectrum inhibition to representative MBL/SBL enzymes, including the widespread VIM-2 and KPC-2. Guided by the VIM-2:MS01 and KPC-2:MS01 complex structures, further structural optimization yielded new, more potent dual-action inhibitors. Selectivity studies indicated that the inhibitors had no apparent inhibition to human angiotensin-converting enzyme-2 and showed selectivity across serine hydrolyases in E. coli and human HEK293T cells labeled by the activity-based probe TAMRA-FP. Moreover, the inhibitors displayed potentiation of meropenem efficacy against MBL- or SBL-positive clinical isolates without apparent cytotoxicity. This work will aid efforts to develop new types of clinically useful dual-action inhibitors targeting MBL/SBL enzymes.
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2021
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IF 6.514
Fangfang Chen,Mengmeng Bai,Wentian Liu,Hongtao Kong,Tingting Zhang,Hong Yao,En Zhang,Juan Du,Shangshang Qin
The emergence and dissemination of metallo-β-lactamases (MBLs) producing Enterobacterales is a great concern for public health due to the limited therapeutic options. No MBL inhibitors are currently available in clinical practice. Herein, we synthesized a series of H 2 dpa derivatives containing pentadentate-chelating ligands and evaluated their inhibitory activity against MBLs. Related compounds inhibited clinically relevant MBLs (Imipenemase, New Delhi metallo-β-lactamase (NDM) and Verona integron-encoded metallo-β-lactamase) with IC 50 values of 1–4.9 μM. In vitro , the most promising compounds, 5b and 5c , which had a chiral methyl at the acid adjacent to 5a , demonstrated potent synergistic activity against engineered strains, with fractional inhibitory concentration index values as low as 0.07–0.18. The addition of 5b and 5c restored meropenem efficacy against 42 MBL-producing Enterobacterales and Pseudomonas aeruginosa to satisfactory clinical levels. In addition, safety tests revealed that 5b/5c showed no toxicity in red blood cells, cell lines or mouse model. Further studies demonstrated that compounds 5b and 5c were non-competitive MBL inhibitors. In vivo compounds 5b and 5c potentiated meropenem efficacy and increased the survival rate from 0 to at least 83% in mice with sepsis caused by an NDM-1-positive clinical strain. The activity of the compounds exhibited consistency at the molecular, cellular, and in vivo levels. These data indicated that H 2 dpa derivatives 5b and 5c containing pentadentate-chelating ligands may be worthy of further study.
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Diabetology & Metabolic Syndrome
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2023
·Vol. 15
·期 1
·1-13
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IF 4.8
Li Tianrong,Yang Jingjing,Tan Anjun,Chen Hewen
Background Irisin plays a key role in metabolic diseases, including type 2 diabetes mellitus (T2DM). However, the mechanism underlying the link between irisin and the development of T2DM, particularly in pancreatic islet β-cells, remains unknown.Methods In vitro, Min6 cells were treated with high glucose (HG) to generate T2DM cell models. GSDMD-N staining, Western blotting assays, and ELISA were performed to measure the expression levels of GSDMD, caspase 1, IL-1β, and IL-18. Next, the NLRP3 stimulator, ATP, was used to assess the effect of irisin on NLRP3 inflammasome. To evaluate the function of the Nrf2-TrX/TXNIP signaling axis, the Nrf2 inhibitor ML385 was used. For in vivo assessment, we first established T2DM model mice. Then, hematoxylin and eosin (H&E) staining was performed to observe the islet morphology, and the immunofluorescence technique was used to examine the mass of α and β cells. To confirm the role of the Nrf2-TrX/TXNIP signaling axis, ML385 was injected into the mice. Immunofluorescence of Nrf2, caspase 1, and GSDMD was detected in the islet cells of the model mice to verify the results.Results We found that irisin treatment significantly decreased the expression of GSDMD-N (P31) and cleaved caspase-1 (p20), decreased caspase1 activity, and inhibited the secretion of IL-1β and IL-18 in HG-treated Min6 cells. We also found that irisin inhibited oxidative stress and NLRP3 expression by activating the Nrf2-TrX/TXNIP signaling axis. Additionally, in the T2DM model mice, irisin enhanced the function of islet cells, decreased insulin resistance, and preserved the morphology of pancreatic islets.Conclusion We showed in this study that irisin can be used for treating pyroptosis in HG-induced islet β-cells and T2DM model mice. We also found that irisin inhibits pyroptosis and oxidative stress by inhibiting the NLRP3-GSDMD pathway and activating the Nrf2-TrX/TXNIP signaling axis.
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Journal of Oleo Science
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2023
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IF 1.5
Ting Wu,Yueqing Xie,Zhikai Wu,Yifei Li,Mingzhen Jiang,Hongsen Yu,Xuhai Li,Jingjing Wang,Ershun Zhou,Zhengtao Yang
Acute liver injury (ALI), posing a serious threaten to our life, has emerged as a public health issue around the world. β-carotene has plenty of pharmacologic effects, such as anti-inflammatory, antioxidant, and antitumor activities. In this study, we focused on studying the protective role and potential molecular mechanisms of β-carotene against D-galactosamine (D-GalN) and lipopolysaccharide (LPS) induced ALI. Our results indicated that β-carotene pretreatment effectively hindered abnormal changes induced by LPS/D-GalN in liver histopathology. Meanwhile, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were downgraded with β-carotene pretreatment. β-carotene pretreatment also decreased malondialdehyde content and myeloperoxidase activity, increased glutathione peroxidase and superoxide dismutase levels, and reduced the levels of tumor necrosis factor-a (TNF-α) and interleukin 6 (IL-6) in liver tissues. Further investigations found that β-carotene mediated multiple signaling pathways in LPS/D-GalN-induced ALI, inhibiting NF-κB and MAPK signaling and upregulating the expression of Nrf2 and HO-1 proteins. All findings indicate that β-carotene appears to protect mice against LPS/D-GalN induced ALI by reducing oxidative stress and inflammation, possibly via regulating NF-κB, MAPK, and Nrf2 signaling.
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FOOD RESEARCH INTERNATIONAL
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2023
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IF 8.1
Wanmei Lin,Yifan Zhang,Jihong Huang,Zhonghong Li
A pH-responsive double-layer film comprising chitosan (CS), zein (Z), curcumin-β-cyclodextrin complex (Cur- β-CD), alizarin (AL) and cinnamaldehyde (CIN) was developed to detect spoilage and prolong the shelf life of pork. The outer Z/AL is the colorimetric responsive and highly protective outer layer, while the CS/Cur- β-CD/CIN is the fluorescence responsive and functional layer. The CS/Cur- β-CD/CIN-Z/AL film demonstrated excellent barrier properties against oxygen (8.48 × 10 -13 g (m s Pa) -1 ) and water (2.42 × 10 -11 g (m s Pa) -1 ) primarily due to the polar interactions in the Z structure and its hydrophobic nature. The addition of AL and Cur provided the CS/Cur- β-CD/CIN-Z/AL film with pH colorimetric and fluorescence response capabilities, respectively. Furthermore, the inclusion of Cur- β-CD, CIN and AL significantly enhanced the film’s antioxidant and antibacterial properties, with radical scavenging rates of 79.29 % (DPPH) and 89.84 % (ABTS), as well as antibacterial efficiencies of 96.2 % ( S. aureus ) and 85.78 % ( E. coli ). To test the effectiveness of the double-layer film, a freshness monitoring and maintenance experiment was conducted on pork stored at 4 °C for 8 days. Various parameters of pork, including surface color, pH value, total volatile bases nitrogen (TVB-N), total viable counts (TVC), thiobarbituric acid reactive substance (TBARS), hardness and springiness, were measured, along with the color and fluorescence intensity (FL) of the film. The shelf life of the pork was extended by at least 2 days compared to the control group, and the pork was considered inedible if ΔE ≥ 12 or FL intensity ≤ 2160. Overall, this food packaging film shows promise in simultaneously monitoring and maintaining the freshness of pork.
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JOURNAL OF CHROMATOGRAPHY A
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2023
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IF 4.1
Chun-Ying Xu,Yuan-Yuan Cui,Cheng-Xiong Yang
Endocrine disrupting chemicals (EDCs) are a typical class of natural or man-made endogenous hormone agonists or antagonists that can directly or potentially interfere with human endocrine system. However, it is still difficult to analyze trace EDCs directly from complex environment and food matrices. Therefore, the proper sample pretreatment is highly desired and the preparation of efficient adsorbents is of great challenge and importance. Herein, we report the facile one-pot solvothermal synthesis of Fe 3 O 4 nanoparticle doped magnetic β-cyclodextrin microporous organic network composites (MCD-MONs) for the magnetic solid phase extraction (MSPE) of four phenolic EDCs in water and food takeaway boxes prior to the high-performance liquid chromatography analysis. The sheet-like Fe 3 O 4 doped MCD-MONs offered good magnetic property (16.5 emu g −1 ) and stability, and provided numerous hydrogen bonding, hydrophobic, π-π, and host-guest interaction sites for EDCs. Under the optimal experimental conditions, the established method was successfully verified with wide linear range (2.0–1000 µg L −1 ), low limits of detection (0.6–1.0 µg L −1 ), good precisions (intra-day and inter-day RSDs < 5.2 %, n = 3), large enrichment factors (88–98) and adsorption capacity (90.3–255.8 mg g −1 ), short extraction time (6 min), less adsorbent consumption (3 mg), and good reusability (at least 8 times) for EDCs. The proposed method was successfully applied to detect the trace EDCs in real samples with the recovery of 84.0–99.7 %. This work demonstrated the great potential of MCD-MONs for the efficient MSPE of trace EDCs from complex food takeaway boxes and water samples and uncovered the prospect of CD-based MONs in sample pretreatment.
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JOURNAL OF THE EUROPEAN CERAMIC SOCIETY
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2023
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IF 5.7
Binwei Huang,Pingzhan Si,Quanxing Ren,Zhuang Qian,Ziqiang Yin,Zhengren Huang,Qing Huang,Yinsheng Li
SiC ceramic was fabricated by spark plasma sintering of β-SiC powder and Y 2 O 3 -MgO additives in argon. The effects of β→α phase transformation of SiC on microstructure and thermal conductivity of densified bulks were systematically investigated, in comparison to the counterparts using α-SiC as starting powder. The β→α phase transformation led to a “unimodal to bimodal” transition in grain size distribution. After sintering at 1850 o C, the incomplete β→α phase transformation induced the appearance of β/α heterophase boundary with strong effect of phonon-scattering. After sintering at 2050 o C, the completion of β→α phase transformation resulted in enlarged grains and disappearance of β/α heterophase boundary in SiC ceramic. The lattice oxygen content was decreased primarily by enhanced grain growth and oxygen picking-up of sintering additives, and possibly some contribution from β→α phase transformation. The optimized microstructure enabled SiC ceramic to obtain a remarkable increase in thermal conductivity from 126 to 204 W/mK after the replacement of α-SiC by β-SiC as starting powder and the accomplishment of β→α phase transformation.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Yanli Wang,Siwei Zhong,Ke Yang,Ruifeng Luo,Linxin Dai,Wenzhen Zhong,Yan Ye,Chaomei Fu,Dasheng Lin,Nan Li,Jianping Chen,Chuan Zheng,Shu Fu,Fei Gao
Herein, a β-1,3- D -glucan based yeast cell wall loaded with co-loaded nanoparticles of Rhein (RH) and Emodin (EMO), was developed for the combined treatment of ulcerative colitis (UC) by modulating gut microbiota and the Th17/Treg cell balance. This was achieved through an oral “nano-in-micro” advanced drug delivery system. Specifically, RH was grafted onto the HA chain via disulfide bonds to synthesize a reduction-sensitive carrier material and then used to encapsulate EMO to form nanoparticles with a specific drug ratio (denoted as HA-RH/EMO NPs). As anticipated, HA-RH/EMO NPs were encased within the “nests”-yeast cell wall microparticles (YPs), efficiently reach the colon and then released gradually, this occurs mainly due to the degradation of β-1,3- D -glucan by β-glucanase. Additionally, HA-RH/EMO NPs demonstrated a significant reduction-sensitive effect in GSH stimulation evaluations and a remarkable ability to target macrophages in in vitro cell uptake studies. Notably, HA-RH/EMO NYPs reduced inflammatory responses by inhibiting the PI3K/Akt signaling pathway. Even more crucially, the oral delivery and drug combination methods significantly enhanced the regulatory effects of HA-RH/EMO NYPs on gut microbiota and the Th17/Treg balance. Overall, this research marks the first use of YPs to encapsulate two components, RH and EMO, presenting a promising therapeutic strategy for UC.
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Molecular Medicine Reports
·
2023
·Vol. 28
·期 3
·1-14
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IF 3.4
Gui-Bo Liu,Yong-Xia Cheng,Hua-Min Li,Yong Liu,Li-Xin Sun,Qi Wu,Shang-Fu Guo,Ting-Ting Li,Chuan-Ling Dong,Ge Sun
Adipose tissue‑derived mesenchymal stem cells (ADMSCs) differentiate into cardiomyocytes and may be an ideal cell source for myocardial regenerative medicine. Ghrelin is a gastric‑secreted peptide hormone involved in the multilineage differentiation of MSCs. To the best of our knowledge, however, the role and potential downstream regulatory mechanism of ghrelin in cardiomyocyte differentiation of ADMSCs is still unknown. The mRNA and protein levels were measured by reverse transcription‑quantitative PCR and western blotting. Immunofluorescence staining was used to show the expression and cellular localization of cardiomyocyte markers and β‑catenin. RNA sequencing was used to explore the differentially expressed genes (DEGs) that regulated by ghrelin. The present study found that ghrelin promoted cardiomyocyte differentiation of ADMSCs in a concentration‑dependent manner, as shown by increased levels of cardiomyocyte markers GATA binding protein 4, α‑myosin heavy chain (α‑MHC), ISL LIM homeobox 1, NK2 homeobox 5 and troponin T2, cardiac type. Ghrelin increased β‑catenin accumulation in nucleus and decreased the protein expression of secreted frizzled‑related protein 4 (SFRP4), an inhibitor of Wnt signaling. RNA sequencing was used to determine the DEGs regulated by ghrelin. Functional enrichment showed that DEGs were more enriched in cardiomyocyte differentiation‑associated terms and Wnt pathways. Dead‑box helicase 17 (DDX17), an upregulated DEG, showed enhanced mRNA and protein expression levels following ghrelin addition. Overexpression of DDX17 promoted protein expression of cardiac‑specific markers and β‑catenin and enhanced the fluorescence intensity of α‑MHC and β‑catenin. DDX17 upregulation inhibited protein expression of SFRP4. Rescue assay confirmed that the addition of SFRP4 partially reversed ghrelin‑enhanced protein levels of cardiac‑specific markers and the fluorescence intensity of α‑MHC. In conclusion, ghrelin promoted cardiomyocyte differentiation of ADMSCs by DDX17‑mediated regulation of the SFRP4/Wnt/β‑catenin axis.
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