MATERIALS & DESIGN
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2023
·
IF 8.4
Chao-ping He,Wen-juan Quan,Ya-ling Zeng,Hong-yan Zhou,Pei-dong You,Zhen-xian Li,Ya-mei Li,Li-mei Lin,Bin Liu,Duan-fang Liao,Qin-hui Tuo
Reducing lipid uptake of macrophages and stimulating cholesterol efflux are two necessary steps for atherosclerotic plaque regression. In this study, a compound of curcumin nicotinate (CN) was synthesized from nicotinic acid which can raise raising high-density lipoprotein (HDL) and curcumin which can lower lipid. However, the shortcomings of CN, such as poor water solubility and low bioavailability, limit its clinical application. In this article, a CN loaded biomimetic nanosystem was constructed by using Prussian blue nanoparticles (PB NPs) to improve its solubility, thereby changing its administration route. In addition, hyaluronic acid (HA) modification on the biomimetic PB NPs was adopted to prolong circulation time and improve the accumulation of drugs in the plaque region. Mechanism studies have shown that the constructed nanosystem could exert anti-AS effects through the pathway of Proprotein Convertase Subtilisin/Kexin Type 9(PCSK9) /Low-density lipoprotein receptor (LDL-R), ATP Binding Cassette Transporter A1(ABCA1) /Caveolin-1 /Liver X Receptor (LXR). These findings indicated that the designed nano-platform is expected to be used for prevention and targeted therapy of atherosclerosis.
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高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Bo Li,Tong Yang,Jin Liu,Xixi Yu,Xinying Li,Fei Qin,Jiefei Zheng,Jinxia Liang,Youyan Zeng,Zhenhua Zhou,Lu Liu,Bin Zhang,Weiwei Yao,Zhuo Feng,Guandi Zeng,Qian Zhou,Liang Chen
Non-small cell lung cancer (NSCLC) remains the most frequently diagnosed lung cancer and the leading cause of cancer-related mortality worldwide. PD-1/PD-L1 axis inhibitors have changed the treatment paradigm for various cancer types, including NSCLC. However, success of these inhibitors in lung cancer clinic is severely limited by their inability to inhibit the PD-1/PD-L1 signaling axis due to heavy glycosylation and heterogeneity expression of PD-L1 in NSCLC tumor tissue. Taking advantage of the facts that tumor cell derived nanovesicles could efficiently accumulate in the homotypic tumor sites due to their innate targeting abilities and that specific and high affinity existed between PD-1 and PD-L1, we developed NSCLC targeting biomimetic nanovesicles (NV) cargos from genetically engineered NSCLC cell lines that overexpressed PD-1 (P-NV). We showed that P-NVs efficiently bound NSCLC cells in vitro and targeted tumor nodules in vivo . We further loaded P-NVs with 2-deoxy-D-glucose (2-DG) and doxorubicin (DOX), and found that these drugs co-loaded P-NVs efficiently shrank lung cancers in mouse models for both allograft and autochthonous tumor. Mechanistically, drug-loaded P-NVs efficiently caused cytotoxicity to tumor cells and simultaneously activated anti-tumor immunity function of tumor-infiltrating T cells. Our data therefore strongly argue that 2-DG and DOX co-loaded, PD-1-displaying nanovesicles is a highly promising therapy for treatment of NSCLC in clinic. Statement of significance Lung cancer cells overexpressing PD-1 are developed for preparing nanoparticles (P-NV). PD-1s displayed on NVs enhance their homologous targeting abilities to tumor cells expressing PD-L1s. Chemotherapeutics such as DOX and 2-DG, are packaged in such nanovesicles (PDG-NV). These nanovesicles efficiently delivered chemotherapeutics to tumor nodules specifically. The synergy between DOX and 2-DG is observed in inhibiting lung cancer cells in vitro and in vivo . Importantly, 2-DG causes deglycosylation and downregulation of PD-L1 on tumor cells while PD-1 displayed on nanovesicles’ membrane blocks PD-L1 on tumor cells. 2-DG loaded nanoparticles thus activate anti-tumor activities of T cells in the tumor microenvironment. Our work thus highlights the promising antitumor activity of PDG-NVs, which warrants further clinical evaluation.
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高影响因子
DIGESTIVE DISEASES AND SCIENCES
·
2023
·
IF 3.1
Zhao Lianrong,Wu Di,Qu Qiao,Li Zhilong,Yin Hongzhuan
Background/Aims Aberrant nuclear factor-κB p65 (NF-κB p65) nuclear import commonly occurs in multiple cancers, including colon cancer. According to BioGRID, we noted that Karyopherin subunit alpha 1 (KPNA1), an important molecular transporter between the nucleus and the cytoplasm, may interact with NF-κB p65. KPNA1 itself is highly expressed in colon adenocarcinoma samples ( N = 286) based on The Cancer Genome Atlas (TCGA) database. We aimed to explore the role of KPNA1 in colonic carcinogenesis and to determine whether NF-κB p65 nuclear translocation was involved. Methods KPNA1 expressions at mRNA and protein levels were analyzed in colon cancer tissues. The regulatory effect of KPNA1 on malignant biological properties was detected in SW480 and HCT116 colon cancer cells. Coimmunoprecipitation and immunofluorescence were performed to verify the relationship between KPNA1 and NF-κB p65. KPNA1 ubiquitination was also preliminarily investigated. Results KPNA1 was firstly confirmed as a significantly upregulated gene in our collected clinical colon cancer samples ( N = 35). KPNA1 depletion inhibited cell proliferation, induced cell cycle arrest, and diminished migratory and invasive capacity of SW480 and HCT116 cells. Colon cancer cells overexpressing KPNA1 acquired more aggressive behaviors. KPNA1 acted as a transporter to induce the nuclear accumulation of NF-κB p65, thereby activating NF-κB signaling pathway in colon cancer cells. Furthermore, HECT, C2, and WW Domain-Containing E3 Ubiquitin (HECW2) interacted with KPNA1 to induce its ubiquitination. KPNA1 labeled with polyubiquitins was degraded through ubiquitin–proteasome system. Conclusion The present study uncovers a role of KPNA1-NF-κB p65 axis in promoting colonic carcinogenesis. Graphical Abstract
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Experimental and Therapeutic Medicine
·
2023
·Vol. 26
·期 1
·1-10
·
IF 2.7
Shixiong Lei,Xilin Du,Kai Tan,Xiaojun He,Yejing Zhu,Shoujie Zhao,Zhenyu Yang,Gang Dou
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. It has been reported that cysteine rich protein 1 (CRP‑1) is dysregulated in several types of human cancer; however, its role in HCC is poorly understood. Therefore, the current study aimed to investigate the role of CRP‑1 in HCC. Western blotting and reverse transcription‑quantitative PCR results showed that CRP‑1 was upregulated in HCC cell lines. Furthermore, for in vitro experiments, CRP‑1 was knocked down and overexpressed in the HCC cell lines Hep 3B2.1‑7 and BEL‑7405, respectively. c‑Myc and proliferating cell nuclear antigen upregulation, and cleaved caspase 3 and poly(ADP‑ribose) polymerase downregulation suggested that CRP‑1 silencing could inhibit the proliferation and colony‑forming ability of HCC cells, and induce apoptosis. In addition, CRP‑1 overexpression promoted the malignant behavior of HCC cells and induced epithelial‑mesenchymal transition (EMT), as verified by E‑cadherin downregulation, and N‑cadherin and vimentin upregulation. Additionally, CRP‑1 overexpression promoted the nuclear translocation of β‑catenin, and activated the expression of cyclin D1 and matrix metalloproteinase‑7. Furthermore, inhibition of Wnt/β‑catenin signaling, following cell treatment with XAV‑939, an inhibitor of the Wnt/β‑catenin signaling pathway, abrogated the effects of CRP‑1 on enhancing the proliferation and migration of HCC cells. These findings indicated that the regulatory effect of CRP‑1 on HCC cells could be mediated by the Wnt/β‑catenin signaling pathway. Overall, CRP‑1 could promote the proliferation and migration of HCC cell lines, partially via promoting EMT and activating the Wnt/β‑catenin signaling pathway.
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Drug Design Development and Therapy
·
2023
·
IF 4.8
Huan Xue,Hao-Jie Xing,Bin Wang,Chao Fu,Yu-Shan Zhang,Xi Qiao,Chao Guo,Xiao-Li Zhang,Bin Hu,Xin Zhao,Li-Jiao Deng,Xiao-Chan Zhu,Yi Zhang,Yun-Feng Liu
Purpose The glucagon-like peptide-1 receptor (GLP-1R) is an effective therapeutic target for type 2 diabetes mellitus (T2DM) and non-alcoholic steatohepatitis (NASH). Research has focused on small-molecule GLP-1R agonists because of their ease of use in oral formulations and improved patient compliance. However, no small-molecule GLP-1R agonists are currently available in the market. We aimed to screen for a potential oral small-molecule GLP-1R agonist and evaluated its effect on blood glucose and NASH.Methods The Connectivity map database was used to screen for candidate small-molecule compounds. Molecular docking was performed using SYBYL software. Rat pancreatic islets were incubated in different concentrations glucose solutions, with cinchonine or Exendin (9–39) added to determine insulin secretion levels. C57BL/6 mice, GLP-1R−/− mice and hGLP-1R mice were used to conduct oral glucose tolerance test. In addition, we fed ob/ob mice with the GAN diet to induce the NASH model. Cinchonine (50 mg/kg or 100 mg/kg) was administered orally twice daily to the mice. Serum liver enzymes were measured using biochemical analysis. Liver tissues were examined using Hematoxylin-eosin staining, Oil Red O staining and Sirius Red staining.Results Based on the small intestinal transcriptome of geniposide, a recognized small-molecule GLP-1R agonist, we identified that cinchonine exerted GLP-1R agonist-like effects. Cinchonine had a good binding affinity for GLP-1R. Cinchonine promoted glucose-dependent insulin secretion, which could be attenuated significantly by Exendin (9–39), a specific GLP-1R antagonist. Moreover, cinchonine could reduce blood glucose in C57BL/6 and hGLP-1R mice, an effect that could be inhibited with GLP-1R knockout. In addition, cinchonine reduced body weight gain and food intake in ob/ob-GAN NASH mice dose-dependently. 100 mg/kg cinchonine significantly improved liver function by reducing the ALT, ALP and LDH levels. Importantly, 100 mg/kg cinchonine ameliorated hepatic steatosis and fibrosis in NASH mice.Conclusion Cinchonine, a potential oral small-molecule GLP-1R agonist, could reduce blood glucose and ameliorate NASH, providing a strategy for developing small-molecule GLP-1R agonists.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2023
·
IF 5.2
Jinyu Pi,Mengjin Chen,Tianqi Chen,Qi Wang,Shijian Cheng,Chaoyang Fu
A combined experimental and theoretical study was performed on corrosion inhibition effect of 1-Phenyl-5-mercaptotetrazole (PMT) on nickel-aluminum bronze (NAB) in seawater . Gravimetric measurement and electrochemical method, such as the open circuit potential (OCP), electrochemical impedance spectroscopy (EIS), Tafel polarization curve were used to verify the corrosion inhibition effect of PMT. It was found that the corrosion inhibition efficiency (IE) of PMT achieved 94.4 %, 99.5 %, 98.7 % at a concentration of 1.12 mM, respectively. The slump of the degree of corrosion on NAB surface was also revealed based on SEM and AFM images analysis with the addition of PMT. According to the Langmuir isotherm model based on EIS, PMT was confirmed as a mixed-type corrosion inhibitor between −20 kJ mol –1 and −40 kJ mol –1 . Besides, the successful adsorption of PMT on NAB has been revealed by the results of XPS and the change of water contact angle on NAB surface. In combination XPS with quantum chemistry calculations, PMT molecules are adsorbed on the surface of NAB by the active S atom and the tetrazole ring as the major adsorption groups, thus, the protective barrier formed by PMT on the surface of NAB can effectively insulate NAB from contact with seawater. The research results in this paper have showed that PMT as a drug intermediate has an excellent corrosion inhibition effect on the NAB at extremely low concentration in seawater.
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HYPERTENSION RESEARCH
·
2022
·Vol. 46
·期 4
·972-983
·
IF 5.528
Shen Yuchen,Wang Zhenfeng,Su Lixin,Zheng Lianzhou,Han Yifeng,Jiao Xiaohui,Fan Xindong,Wang Deming
This study aimed to examine whether the administration of losartan can prevent acute elevation of pulmonary arterial pressure (AEPAP) induced by endovascular ethanol injection and to assess its related mechanisms. Male swine were selected and performed with absolute ethanol endovascular injection. Saline was used as the negative control. Losartan was administered preoperatively. Pulmonary arterial pressure (PAP), femoral arterial pressure (FAP) and heart rate (HR) were monitored during operations. Venous plasma and pulmonary artery (PA) tissue were harvested for analyses. Protein level was detected by Western blotting and ELISA, whereas qRT-PCR was used in mRNA detection. H & E staining and immunohistochemistry were conducted to evaluate histopathology. Ethanol injection elevated PAP in swine. The concentration of RAS ligands was elevated in plasma (all P < 0.0001) but not in PA. The level of oxidative stress increased in both plasma and PA. MRNA level of AT1R ( P < 0.01, 95% CI: 0.251–1.006), not AT2R increased in PA. Losartan failed to inhibit AEPAP after all sessions of ethanol injection, and partially reversed the ethanol-induced PA remodeling. The P38 MAPK was activated after ethanol injection and could be inhibited by losartan ( P < 0.01, 95% CI: −0.391 to −0.164). Ethanol also promoted the translocation of the P40-PHOX/P47-PHOX/P67-PHOX complex and the activation of NOX, which was independent from RAS. Endovascular ethanol injection can induce AEPAP mainly by activating RAS and P38 MAPK signaling. Losartan can partially prevent AEPAP and vascular remodeling owing to the promotion of NOX activity by ethanol.
Mechanism diagram of endovascular ethanol injection-induced acute elevation of pulmonary arterial pressure (AEPAP) partially prevented by losartan. RAS: Renin–angiotensin system; AGT: angiotensinogen; Ang I: angiotensin I; ACE: angiotensin I converting enzyme; Ang II: angiotensin II. AT1R: angiotensin II type 1 receptor. NOX2: NADPH oxidase 2. PA: pulmonary artery.
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Food Bioscience
·
2023
·
IF 5.2
Yuxin Guo,Zheng Jia,Liting Wan,Jun Cao,Yajing Fang,Weimin Zhang
This study aimed to explore the changes in phytochemical composition and inflammatory response of Camellia vietnamensis oil (CO) during refining. Four refined CO samples [degummed (DGO), deacidified (DAO), decolorized (DCO), and deodorized (DOO)] were prepared from crude CO (CCO). Five CO samples were measured for their composition of fatty acids , sterols, tocopherols , polyphenols, and oxidation products as well as anti-inflammatory activity in lipopolysaccharide (LPS)-induced THP-1 macrophages. The content of phytochemicals was significantly decreased with the deepening of the refining degree, especially after deacidification. CCO and DGO showed anti-inflammatory activity by inhibiting the production of pro-inflammatory cytokines and activation of NF-κB induced by LPS. Deacidification and decolorization of CO decreased its anti-inflammatory activity. The accumulation of oxidation products after deodorization in CO aggravated the inflammatory response. Trans -cinnamic, kaempferol , and protocatechuic acid in CO were crucial for their anti-inflammatory effects. These findings underlined that moderate refinement is suggested to retain its bioactive ingredients and anti-inflammatory ability.
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MOLECULES
·
2023
·Vol. 28
·期 3
·922
·
IF 4.6
Pengcheng Li,Jingjing Zhu,Hongyu Zhang,Lan Wang,Shulin Wang,Mengting Zhang,Jianping Wu,Lirong Yang,Gang Xu
Chiral amines are essential components for many pharmaceuticals and agrochemicals. However, the difficulty in obtaining enantiomerically pure amines limits their application. In this study, hollow amorphous ZIF-90 (HamZIF-90) materials were prepared by template engraving, and chemical–enzyme coupling catalysts (HamZIF-90@Pd@CALB) were constructed for the chiral resolution of 1-phenylethylamine. Different from conventional materials, HamZIF-90 had tunable hollow structures by altering its central node zinc ion concentrations, and the embedded hydrogel template gave it more pore structures, which facilitated the loading of enzyme molecules and Pd nanoparticles (NPs). The establishment of the coupling catalysts shortened the mass transfer distance of the reactant molecules between the metal nanoparticles and the enzyme catalyst in the dynamic kinetic resolution (DKR) reaction, resulting in 98% conversion of 1-phenylethylamine and 93% selectivity of Sel.R-amide. The proposal of this idea provided a good idea for future tailor-made MOFs loaded with chemical and enzyme coupled catalyst.Keywords:hollow amorphous;HamZIF-90@Pd@CALB;DKR;1-phenylethylamine
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CHEMOSPHERE
·
2023
·
IF 8.8
Sini Lv,Fengzhen Zheng,Zeyu Wang,Luyao Dai,Huan Liu,Dzmitry Hrynshpan,Tatsiana Savitskaya,Jun Chen
The high hydrophobicity of n -hexane is the main reason why it is difficult to be removed biologically. In this study, the effects of bamboo-charcoal modified by bimetallic Fe/Pd (BBC) on n -hexane biodegradation by Pseudomonas mendocina NX-1 (PM) was investigated. The n- hexane removal efficiency was increased in the presence of BC. The highest n- hexane removal efficiency at 90.0% was achieved at 0.05 g L −1 BCE and 3 g L −1 NH 4 + under pH 7.7 and 35 °C. Additionally, protein content (45.9 μg mL −1 ) and negative cell surface zeta potential (−26.4 mV) were increased during biodegradation process, with PM-BBC being 43.1 μg mL −1 and 19.1 mV. Bacterial growth was improved and maximum cell surface hydrophobicity was obtained after 20 h, which was 59.4% higher than the control with PM-BBC (37.7%) or PM (16.1%), showing biodegradation products of 1-butanol and acetic acid. The results indicate that BBC improved n- hexane biodegradation efficiency by promoting bacterial growth, reducing cell zeta potential, exposing hydrophobic proteins, and increasing cell surface hydrophobicity of bacterial strain NX-1. This investigation suggests that BBC-enhanced biodegradation can be promising to treat n- hexane-containing gas.
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LABORATORY INVESTIGATION
·
2023
·
IF 5
Rui Yu,Yan Wu,Ping He,Yu Bai,Yongzhe Zhang,Xiaohui Bian,Guangping Sun,Beiru Zhang
Renal fibrosis is the major pathologic manifestation of chronic kidney disease (CKD). LIM and cysteine-rich domains 1 (LMCD1) is upregulated in the kidney tissue from patients with CKD and the transforming growth factor β1 (TGF-β1)–treated human renal tubular epithelial cell line human kidney 2 (HK-2) (Gene Expression Omnibus: GSE66494 and GSE23338). Previously, we have demonstrated that the knockdown of LMCD1 ameliorated renal fibrosis in mice by blocking the activation of the extracellular signal-regulated kinase pathway. In this study, we sought to further investigate whether LMCD1 affects TGF-β1–induced epithelial–mesenchymal transition (EMT) of kidney tubular epithelial cells and its potential role in the TGF-β1/Smad signaling pathway. First, we confirmed that LMCD1 expression was increased in the fibrotic kidneys of patients with CKD compared with that in normal kidneys and that LMCD1 was predominantly localized in the renal tubules. LMCD1 and mesenchymal markers were upregulated in obstructed kidney tissues of mice at 21 days after unilateral ureteral obstruction surgery compared with the tissues in sham mice. Next, we demonstrated that TGF-β1 significantly increased LMCD1 expression through Smad-mediated transcription in HK-2 cells in vitro. In turn, LMCD1 acted as a transcriptional coactivator of E2F transcription factor 1 to promote the transcription of TGF-β1 . Moreover, TGF-β1 increased the interaction between LMCD1 and Smad ubiquitination regulatory factor 2 (Smurf2) and accelerated Smurf2-mediated LMCD1 degradation via the ubiquitination system. The knockdown of LMCD1 inhibited TGF-β1–induced EMT in both HK-2 cells and unilateral ureteral obstruction mice. Our results indicate a positive feedback loop between TGF-β1 and LMCD1 for EMT induction in HK-2 cells and that Smurf2 acts as a negative regulator in this process by accelerating LMCD1 degradation.
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Pharmaceuticals
·
2022
·Vol. 15
·期 12
·1548
·
IF 5.215
Fei Yang,Cuizhen Shen
On the basis of the mice pressure ulcers (PU) model, the protective effect and potential mechanism of sodium Danshensu (SDSS) cream against PU were investigated. The mice were randomly divided into three groups: the negative control group (cream without 0.5 g SDSS), the SDSS group (cream containing 0.5 g SDSS), and the positive group (0.5 g Hirudoid®). After 7 and 14 days of ointment application, the wound-healing rate of the SDSS and positive groups was significantly higher than that of the control group (p< 0.05). The results of hematoxylin–eosin staining also indicated that SDSS has the potential to promote the healing of PU. In addition, the serum IL-6, IL-1β, TNF-α, and MDA levels decreased significantly (p< 0.01) after 14 days of SDSS treatment, while the SOD, CAT, and GSH-Px activities increased significantly (p< 0.01). In addition, SDSS cream was able to significantly increase the expression of Nrf2, HO-1, GCLM, NQO1, NF-κB p65, NF-κB p50, IKKα, and IKKβ while decreasing the expression of Keap1 and IκBαin the Nrf2/HO-1 and NF-κB pathways. Our research will provide a foundation for the future clinical prevention and treatment of PU with SDSS cream.Keywords:pressure ulcers;sodium Danshensu cream;ischemia/reperfusion injury;Nrf2/HO-1 pathway;NF-κB pathway
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