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1.
Environ Res ; 184: 109368, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32192990

RESUMO

Large areas of mainland China have been suffering frequently from heavy haze pollution during the past years, which feature high concentrations of fine particulate matter (PM2.5, particulate matters with aerodynamic diameters less than 2.5 µm) and low visibility. Moreover, these areas manifested strong regional complex pollution characteristics, particularly in North China including Beijing and the five surrounding provinces (BSFP). In this study, by using the localized comprehensive emission inventory of BSFP region in 2012 as an input, the Comprehensive Air Quality Model with Extensions-Particulate Matter Source Apportionment Technology (CAMx/PSAT) was used to assess the seasonal variations and source apportionment of PM2.5 in the highly polluted BSFP region, with a specific focus on the sectoral and sub-regional contributions to PM2.5 in Beijing during winter and summer. Results showed that the PM2.5 concentrations of BSFP region was higher in winter than that in summer. And the heavily polluted area in BSFP region shrinked noticeably in summer, compared with winter. As for source apportionment of PM2.5, residential and remaining industrial sectors constituted the top two sources of PM2.5 mass concentrations in Beijing. In addition, agricultural source represented a major contributor to ammonium, whereas transportation and power sectors constituted major sources to nitrates. In terms of contributions from sub-regions, the local sources ranked as the dominant contributors to PM2.5 in Beijing, while the main external contributions originated from the surrounding areas, such as Hebei and Shandong. Results of daily source apportionment to PM2.5 in Beijing showed that sub-regional long-distance transport became stronger when haze pollution was severe, in which contribution from remaining industrial sector would be higher than that of other periods. The results will allow for an improved understanding of the causes and origins of heavy regional PM2.5 pollution, and thus will benefit the development of effective joint control policies and identification of key polluting emission categories in North China and ultimately serve as references for other highly polluted megacities in the world.

2.
Nat Cell Biol ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32203416

RESUMO

Piwi proteins are normally restricted in germ cells to suppress transposons through associations with Piwi-interacting RNAs (piRNAs), but they are also frequently activated in many types of human cancers. A great puzzle is the lack of significant induction of corresponding piRNAs in cancer cells, as we document here in human pancreatic ductal adenocarcinomas (PDACs), which implies that such germline-specific proteins are somehow hijacked to promote tumorigenesis through a different mode of action. Here, we show that in the absence of piRNAs, human PIWIL1 in PDAC functions as an oncoprotein by activating the anaphase promoting complex/cyclosome (APC/C) E3 complex, which then targets a critical cell adhesion-related protein, Pinin, to enhance PDAC metastasis. This is in contrast to piRNA-dependent PIWIL1 ubiquitination and removal by APC/C during late spermiogenesis. These findings unveil a piRNA-dependent mechanism to switch PIWIL1 from a substrate in spermatids to a co-activator of APC/C in human cancer cells.

3.
Bioorg Med Chem ; : 115436, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32209297

RESUMO

A polymer based dynamic combinatorial library (DCL) was generated through condensation between aldehyde functionalized linear poly(glycidol) (APG) and galactose containing acylhydrazide derivatives. Pentameric E. coli heat labile enterotoxin B subunit (LTB) was subsequently applied to the DCL as external stimulus, resulting in amplification of a specific acylhydrazone side chain that was further used for the synthesis of a multivalent LTB inhibitor. In the in vitro biological evaluation, this inhibitor exhibited strong inhibition properties as well as low cytotoxicity.

4.
J Am Coll Radiol ; 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32208140

RESUMO

OBJECTIVE: To describe the strategy and the emergency management and infection control procedures of our radiology department during the COVID-19 outbreak. METHODS: We set up emergency management and sensing control teams. The team formulated various measures, such as reconfiguration of the radiology department, personal protection and staff training, standardized imaging examination procedures for fever patients and common patients, and so on. RESULTS: From January 21 to March 9, 3,083 people underwent fever-CT examinations. Including the initial examination and reexamination, the total number of fever CT examination is 3,340. As a result of our precautions, none of the staff of the radiology department was infected with COVID-19. CONCLUSION: Strategic planning and adequate protections can help protect patients and staff against a highly infectious disease while allow normal functioning at a high-volume capacity.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32193575

RESUMO

Ribosome-inactivating proteins (RIPs) consist of three varieties. Type 1 RIPs are single-chained and approximately 30-kDa in molecular weight. Type 2 RIPs are double-chained and composed of a type 1 RIP chain and a lectin chain. Type III RIPs, such as maize b-32 barley and JIP60 which are produced as single-domain proenzymes, possess an N-terminal domain corresponding to the A domain of RIPs and fused to a C-terminal domain. In addition to the aforementioned three types of RIPs originating from flowering plants, there are recently discovered proteins and peptides with ribosome-inactivating and protein synthesis inhibitory activities but which are endowed with characteristics such as molecular weights distinctive from those of the regular RIPs. These new/unusual RIPs discussed in the present review encompass metazoan RIPs from Anopheles and Culex mosquitos, antimicrobial peptides derived from RIP of the pokeweed Phytolacca dioica, maize RIP (a type III RIP derived from a precursor form), RIPs from the garden pea and the kelp. In addition, RIPs with a molecular weight smaller than those of regular type 1 RIPs are produced by plants in the Cucurbitaceae family including the bitter gourd, bottle gourd, sponge gourd, ridge gourd, wax gourd, hairy gourd, pumpkin, and Chinese cucumber. A small type II RIP from camphor tree (Cinnamomum camphora) seeds and a snake gourd type II RIP with its catalytic chain cleaved into two have been reported. RIPs produced from mushrooms including the golden needle mushroom, king tuber mushroom, straw mushroom, and puffball mushroom are also discussed in addition to a type II RIP from the mushroom Polyporus umbellatus. Bacterial (Spiroplasma) RIPs associated with the fruitfly, Shiga toxin, and Streptomyces coelicolor RIP are also dealt with. The aforementioned proteins display a diversity of molecular weights, amino acid sequences, and mechanisms of action. Some of them are endowed with exploitable antipathogenic activities.

6.
Cancer Cell ; 37(3): 324-339.e8, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32183950

RESUMO

Here, we show that tumor ADORA1 deletion suppresses cell growth in human melanoma cell lines in vitro and tumor development in vivo in immune-deficient xenografts. However, this deletion induces the upregulation of PD-L1 levels, which inactivates cocultured T cells in vitro, compromises anti-tumor immunity in vivo, and reduces anti-tumor efficacy in an immune-competent mouse model. Functionally, PD-1 mAb treatment enhances the efficacy of ADORA1-deficient or ADORA1 antagonist-treated melanoma and NSCLC immune-competent mouse models. Mechanistically, we identify ATF3 as the factor transcriptionally upregulating PD-L1 expression. Tumor ATF3 deletion improves the effect of ADORA1 antagonist treatment of melanoma and NSCLC xenografts. We observe higher ADORA1, lower ATF3, and lower PD-L1 expression levels in tumor tissues from nonresponders among PD-1 mAb-treated NSCLC patients.

7.
Chin J Nat Med ; 18(2): 81-89, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32172951

RESUMO

Nervosine VII is one of the known saturated pyrrolizidine alkaloids isolated from the plant of Liparis nervosa. This is first study to investigate the antitumor activity of nervosine VII in vitro, and the results indicated that nervosine VII induced autophagy and apoptosis in HCT116 human colorectal cancer cells. Mechanistic studies showed that nervosine VII-induced apoptosis was associated with the intrinsic pathway by the activation of caspase-9, -3 and -7. Autophagy induced by nervosine VII was characteristic with the regulation of autophagic markers including the increase of LC3-II and beclin 1 proteins, and the decrease of p62 protein. Nervosine VII simultaneously induced autophagy and apoptosis by activated MAPKs signaling pathway including JNK, ERK1/2 and p38, suppressing the p53 signaling pathway.

8.
Drug Dev Res ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32173888

RESUMO

This study aimed to assess the protective effect of nitroglycerin, a commonly used drug in cardiovascular diseases, on mice with acute liver injury induced by carbon tetrachloride (CCl4 ). The mice were randomly divided into three groups: control, CCl4 , and CCl4 + nitroglycerin. They were killed at 0, 6, 12, 24, and 48 h after treatment. Blood and liver tissue samples were collected for analysis. Analysis of the amounts of serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST), hepatic glutathione (GSH), and malondialdehyde (MDA) showed that nitroglycerin protected against CCl4 -induced acute liver injury. Liver histological analysis provided further evidence of the protective effect of nitroglycerin. Furthermore, we found that nitroglycerin suppressed the increase of T helper 17 (Th17) cells in CCl4 -induced acute liver injury mice. The results indicate that nitroglycerin is a potential candidate for hepatic disease.

9.
J Cell Mol Med ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32129945

RESUMO

Malignant melanoma is one of the most invasive tumours. However, effective therapeutic strategies are limited, and overall survival rates remain low. By utilizing transcriptomic profiling, tissue array and molecular biology, we revealed that two key ubiquitin-specific proteases (USPs), ubiquitin-specific peptidase10 (USP10) and ubiquitin-specific peptidase10 (USP13), were significantly elevated in melanoma at the mRNA and protein levels. Spautin-1 has been reported as a USP10 and USP13 antagonist, and we demonstrated that spautin-1 has potent anti-tumour effects as reflected by MTS and the colony formation assays in various melanoma cell lines without cytotoxic effects in HaCaT and JB6 cell lines. Mechanistically, we identified apoptosis and ROS-mediated DNA damage as critical mechanisms underlying the spautin-1-mediated anti-tumour effect by utilizing transcriptomics, qRT-PCR validation, flow cytometry, Western blotting and immunofluorescence staining. Importantly, by screening spautin-1 with targeted or chemotherapeutic drugs, we showed that spautin-1 exhibited synergy with cisplatin in the treatment of melanoma. Pre-clinically, we demonstrated that spautin-1 significantly attenuated tumour growth in a cell line-derived xenograft mouse model, and its anti-tumour effect was further enhanced by cotreatment with cisplatin. Taken together, our study revealed a novel molecular mechanism of spautin-1 effecting in melanoma and identified a potential therapeutic strategy in treatment of melanoma patients.

10.
Fungal Biol ; 124(2): 135-143, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32008754

RESUMO

Lentinula edodes is a widely-produced mushroom in China that forms a brown film via pigment accumulation on mature mycelial surfaces to ensure high-quantity and high-quality fruiting body formation. Here, ultraviolet-visible, infrared spectra, and elemental analyses predicted that the pigment in the brown film was melanin. Electron microscopy revealed the size, morphological characteristics, accumulation, and morphogenesis of electron-dense material, which were similar to those of melanin, as well as subcellular structural changes during brown film formation. The electron-dense material appeared as granules, vesicles, and polymers. The accumulation of electron-dense materials on the cell wall was followed plasmolysis, plasma membrane disruption, electron-dense material accumulation in the interstitial space, and gradual accumulation on the outer cell wall. Dolipore septa degradation and morphogenetic cell death occurred during browning. In the final stage of browning, the dolipore septum disappeared and the cell was nearly empty. This study provides a cytological foundation for evaluating the regulation of brown film formation in L. edodes.

11.
Environ Pollut ; 259: 113918, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32023794

RESUMO

Natural sources, such as soil and wind-erosion dust (SWD), biomass open burning (BOB), sea salt spray (SSAS) and biogenic source (BIO), are major contributors to atmospheric emissions of trace elements (TEs) globally. In this study, we used a comprehensive approach to account for area-, production- and biofuel consumption-based emission factor calculation methods, and thus developed an integrated high-resolution emission inventory for 15 types of TEs (As, B, Cd, Co, Cr, Cu, Hg, Mn, Mo, Ni, Pb, Sb, Se, V and Zn) originated from natural sources in China for the year 2015. The results show that national emissions of TEs in 2015 range from 7.45 tons (Hg) to 1, 400 tons (Zn) except for the extremely high emissions of Mn (10, 677 tons). SWD and BIO are identified as the top two source contributors, accounting for approximately 67.7% and 26.1% of the total emissions, respectively. Absolute emissions of TEs from natural sources are high in the Xinjiang, Inner Mongolia and Tibet autonomous regions with large areas of bare soil and desert. However, emission intensity of TEs per unit area in the Southern provinces of China is higher than those in Northern China and Southwestern China, with the Yunnan and Sichuan provinces displaying the highest emission intensity. Our results suggest that controlling SWD can play a significant role in reducing fugitive particulate matter and the associated emissions of TEs from natural sources in China; and desertification control is particularly critical in the Northwest provinces where the majority of deserts are located.

12.
Int J Biol Macromol ; 152: 576-583, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32105684

RESUMO

Polyacrylamide (PAM) has been used as a coagulant aid in water treatment process for past decades, but it has caused great damages to human nervous system. Developing new coagulant aid with high biological safety is urgently demanded. This study provides a natural biomacromolecule coagulant aid with good biosecurity-Enteromorpha prolifera polysaccharide (Ep). Its coagulant aid efficiency and mechanism were investigated in terms of organics removal, floc properties and membrane fouling degree. In addition, contrast experiments were conducted with PAM to evaluate its potential of industrial applications. Results showed that organics removal could be increased by 23% when 0.3 mg/L Ep was used, which exhibited comparable aid effects to PAM. Due to the bridging-sweep aid role of Ep, flocs sizes, growth rate and recovery factor reached 470 µm, 62.6 µm/min and 0.492, respectively, while only 170 µm, 14.0 µm/min and 0.326 were obtained by PAM. Additionally, flocs exhibited more porous and multi-branched structures when Ep was applied, which caused less ultrafiltration membrane fouling (eventual J/J0 value = 0.52). As a result, Ep could be considered as a potential substitute of PAM, since better biosecurity, higher organics removal and lower membrane fouling could be obtained simultaneously by Ep addition.

13.
Mol Cell Endocrinol ; 506: 110761, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32088313

RESUMO

Inborn defects in thyroid hormone biosynthesis contribute to nearly half of congenital hypothyroidism (CH) cases in China. The thyroid peroxidase (TPO) mutation is one of the most frequent mutations that results in thyroid dyshormonogenesis. In this study, 35 non-synonymous mutations in 15 TPO sites, including 6 novel mutations, were identified in 230 Chinese patients with CH. The enzyme activity of the mutations in TPO was investigated in vitro, and patients with less than 15% residual enzyme activity showed severe CH, such as markedly increased thyroid-stimulating hormone (TSH) at diagnosis (>100 µIU/mL) and pronounced goiter, and required a higher dose of L-thyroxine to maintain the euthyroid. However, CH patients with greater than 16% TPO activity showed mild CH, a typical childhood socially without L-thyroxine treatment before 3 years of age, and the appearance of a macroscopic goiter at childhood. The findings indicated that the residual enzymatic activity of TPO was correlated with clinical phenotypes of CH patients with TPO biallelic mutations.

14.
Mikrochim Acta ; 187(3): 172, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-32062754

RESUMO

Emerging evidence suggests that exosomal microRNAs are potential biomarkers for the early diagnosis and prognostic assessment of tumor. Here, we design a strand displacement-initiated G-quadruplex/rolling circle amplification (RCA) strategy for highly specific and sensitive electrochemical sensing of exosomal microRNAs. In the presence of exosomal miRNA-21, a locked nucleic acid (LNA)-labeled toehold mediated strand displacement reaction (TMSDR) is initiated, releasing output P2 to trigger the subsequent RCA reaction by hybridizing with the C-rich circular template. Then the obtained G-rich RCA products can bind to the probe anchored on the surface of gold electrode and generate G-quadruplex conformations. Based on the TMSDR-triggered G-quadruplex/RCA strategy, the detection limit of this electrochemical biosensor is down to 2.75 fM. Moreover, our biosensor exhibits excellent repeatability, stability, and high consistency compared to RT-PCR for clinical detection. In conclusion, this assay is expected to provide a hopeful strategy for the early non-invasive diagnosis and prognostic estimation of cancer. Graphical abstract Schematic illustration of electrochemical sensing of exosomal microRNAs based on strand displacement-initiated G-quadruplex/rolling circle amplification (RCA) strategy.

16.
Mol Pharm ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32073273

RESUMO

The composition of amphiphilic nanocarriers can affect the antitumor efficacy of drug-loaded nanoparticles and should be researched systematically. In this paper, to study the influence of hydrophobic chains, an amphiphilic copolymer (PEG45PCL17) and hydrophilic PEG (PEG45) were utilized as nanocarriers to prepare docetaxel-loaded nanoparticles (DTX/PEG45PCL17 nanoparticles and DTX/PEG45 nanoparticles) through an antisolvent precipitation method. The two DTX nanoparticles presented a similar drug loading content of approximately 60% and a sheet-like morphology. During the preparation procedure, the drug loading content affected the morphology of DTX nanoparticles, and the nanocarrier composition influenced the particle size. Compared with DTX/PEG45 nanoparticles, DTX/PEG45PCL17 nanoparticles showed a smaller mean diameter and better in vitro and in vivo antitumor activity. The cytotoxicity of DTX/PEG45PCL17 nanoparticles against 4T1 cells was 1.31 µg mL-1, 3.4-fold lower than that of DTX/PEG45 nanoparticles. More importantly, DTX/PEG45PCL17 nanoparticles showed significantly higher antitumor activity in vivo, with an inhibition rate over 80%, 1.5-fold higher than that of DTX/PEG45 nanoparticles. Based on these results, antitumor activity appears to be significantly affected by the particle size, which was determined by the composition of the nanocarrier. In summary, to improve antitumor efficacy, the amphiphilic structure should be considered and optimized in the design of nanocarriers.

17.
Cancer Med ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32074407

RESUMO

BACKGROUND: China has an increasing burden of breast cancer. However, with a large population of dense breast patients, the diagnostic efficiency of conventional digital mammography is attenuated. METHODS: From July 2017 to October 2018, we retrospectively reviewed 397 dense breast patients who underwent contrast-enhanced spectral mammography (CESM) in West China Hospital. Among them, 53 patients who had both CESM and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) results and 114 patients who had pathological diagnoses were finally enrolled. All images were reviewed by two independent radiologists according to the 2013 Breast Imaging Reporting and Data System (BI-RADS) with all disagreements handed to an associate professor for final decisions. Correlation analyses between CESM and DCE-MRI were conducted. The diagnostic performance of CESM were investigated. RESULTS: The kappa value of the BI-RADS scores between CESM and DCE-MRI was 0.607 (P < .001), indicating high correspondence between CESM and DCE-MRI. As for lesion size measurement, moderate correlation (Kendall's tau coefficient: 0.556, P < .001) was detected between CESM and DCE-MRI. Using pathological diagnoses as the reference standard, the sensitivity, specificity, and area under the curve (AUC) of CESM were 82.4%, 96.4%, and 0.894, respectively. CONCLUSION: CESM demonstrated excellent overall diagnostic accuracy and a moderate correlation in lesion size estimation against DCE-MRI in dense breast patients, supporting it to be an alternative to DCE-MRI in breast cancer detection and diagnosis, especially for exclusion diagnosis.

18.
Life Sci ; : 117424, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32057900

RESUMO

AIMS: Dysfunction of the Hippo-Yes-Associated Protein (YAP) signaling pathway is known to be associated with hepatocellular carcinoma (HCC). Evodiamine (Evo), a plant-derived bioactive alkaloid, exerts inhibitory effects on cancer. However, the precise influence of Evo on HCC and its potential effects on Hippo-YAP signaling have yet to be ascertained. Here, the effects of Evo on cell proliferation and apoptosis were evaluated using HCC cell lines (HepG2 and Bel-7402) and nude mice with xenograft tumors. We further investigated whether Evo exerts anti-HCC activity through effects on Hippo-YAP signaling in vitro with the aid of XMU-MP-1, an inhibitor of the key component of this pathway, mammalian sterile 20-like kinase 1/2. MAIN METHODS: Cell proliferation and apoptosis were assessed using 5-ethynyl-2'-deoxyuridine staining, colony formation, flow cytometry, hematoxylin-eosin and dUTP nick-end labeling experiments. Bioinformatics and real-time quantitative polymerase chain reaction (RT-qPCR) arrays were performed to determine the associations among Evo, HCC progression and the Hippo-YAP pathway. The expression patterns of components of Hippo-YAP signaling and apoptotic genes were further examined via RT-qPCR and immunoblotting. KEY FINDINGS: Evo inhibited proliferation and promoted apoptosis of HCC cell lines in vitro, and attenuated xenograft tumor formation in nude mice in vivo. Mechanistically, Evo treatment stimulated the Hippo-YAP signaling pathway. In vitro, the effects of Evo on HCC cell proliferation and apoptosis were alleviated by XMU-MP-1. SIGNIFICANCE: Our collective results revealed that the anti-HCC effects of Evo were correlated with the Hippo-YAP signaling pathway.

19.
Lasers Surg Med ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31922272

RESUMO

BACKGROUND AND OBJECTIVES: Plantar warts are a viral infectious lesion on the foot. The regression of plantar warts can be challenging despite the presence of a variety of available treatment modalities. Photodynamic therapy (PDT) has been recommended for the treatment of plantar warts. However, the effect of PDT in the treatment of plantar warts is not clear. Thus, we compared the efficacy of combining superficial shaving with PDT (SS-PDT) with that of cryotherapy in the treatment of recalcitrant plantar warts. STUDY DESIGN/MATERIALS AND METHODS: Forty-six patients with 271 warts received SS-PDT, and 26 patients with 147 warts received cryotherapy. For the SS-PDT group, the lesions were shaved in situ, and PDT was performed immediately. For the cryotherapy group, appropriate pressure was applied by freezing rod to fully freeze the lesion tissue. The overall clinical response effects, recurrence rates, adverse events, patient satisfaction and the quality of life were assessed. RESULTS: The SS-PDT group achieved a 91.3% success rate (defined as >50% on clearance) after treatment for 6 months, whereas only 23.1% of treatment in the cryotherapy group was successful. After 6 months of follow-up, the recurrence rate in the SS-PDT group was significantly lower than that in the cryotherapy group (8.7% vs. 76.9%, P < 0.001). The patients with SS-PDT were more satisfied with the treatment than the patients with cryotherapy (8.8 ± 1.4 vs. 4.9 ± 1.4, P < 0.001). Moderate pain was the main adverse event in SS-PDT, and cryotherapy may cause severe pain and blistering. CONCLUSIONS: Our results suggest that superficial shaving combined with PDT is promising as a safe and effective therapy for patients with plantar warts, especially for patients with multiple recalcitrant warts. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

20.
Acta Pharmacol Sin ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932644

RESUMO

Chronic tissue injury with fibrosis results in the disruption of tissue architecture, organ dysfunction, and eventual organ failure. Therefore, the development of effective antifibrotic drugs is urgently required. IMB-S7 is novel biphenyl compound derived from bifendate (biphenyldicarboxylate) that is used for the treatment of chronic hepatitis in China. In the current study we investigated the potential of IMB-S7 as an antihepatic fibrosis agent. In bile duct ligation (BDL) rat model, oral administration of IMB-S7 (400 mg· kg-1· d-1, for 14 days) significantly ameliorated BDL-induced liver necrosis, bile duct proliferation, and collagen accumulation. We then showed that IMB-S7 treatment markedly suppressed the TGF-ß/Smad pathway in human hepatic stellate cell line LX2 and mouse primary HSCs, as well as in liver samples of BDL rats, thus inhibiting the transcription of most fibrogenesis-associated genes, including TGF-ß1, COL1A1, and ACTA2. Furthermore, IMB-S7 treatment significantly suppressed the expression of integrin αv at the mRNA and protein levels in TGF-ß-treated LX2 cells and liver samples of BDL rats. Using integrin αv overexpression and silencing, we demonstrated that integrin αv activity correlated positively with the activation of TGF-ß/Smad pathway. Based on dual luciferase assay and DNA affinity precipitation assay, we revealed that IMB-S7 inactivated integrin αv through competitively inhibiting the binding of Sp1, a transcription factor, to the integrin αv (ITGAV) promoter (-173/-163 bp). These results suggest that IMB-S7 inhibits HSCs activation and liver fibrosis through Sp1-integrin αv signaling, and IMB-S7 may be a promising candidate to combat hepatic fibrosis in the future.

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