Publications by authors named "Shichao Han"

46 Publications

Downregulation of LncRNA DARS-AS1 Inhibits the Tumorigenesis of Cervical Cancer via Inhibition of IGF2BP3.

Onco Targets Ther 2021 25;14:1331-1340. Epub 2021 Feb 25.

Department of Gynecology, The 2nd Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116021, People's Republic of China.

Background: Evidence has been shown that long noncoding RNAs (lncRNAs) play an important role in the development of cervical cancer. Recently, lncRNA DARS-AS1 was reported to be dysregulated in several cancer types; however, the role of DARS-AS1 in cervical cancer remains unclear.

Methods: Flow cytometry and transwell invasion assays were performed to determine the apoptosis and invasion in cervical cancer cells. In addition, RNA pull-down and fluorescence in situ hybridization (FISH) assays were conducted to assess the interaction between DARS-AS1 and IGF2BP3 in cervical cancer cells.

Results: Downregulation of DARS-AS1 significantly induced apoptosis and cell cycle arrest in cervical cancer cells. Meanwhile, the invasion ability of cervical cancer cells was inhibited by DARS-AS1 knockdown as well. RNA pull-down and FISH results showed that DARS-AS1 interacted with IGF2BP3. Mechanistically, DARS-AS1 positively regulated IGF2BP3 expression via stabilization of IGF2BP3 mRNA. Rescue assays confirmed that DARS-AS1 regulated the progression of cervical cancer through interacting with IGF2BP3 in vitro. In addition, in vivo experiments revealed that downregulation of DARS-AS1 inhibited tumor growth in SiHa xenograft model.

Conclusion: In this study, we found that downregulation of DARS-AS1 could inhibit the growth of cervical cancer cells via inhibition of IGF2BP3, suggesting DARS-AS1 might serve as a potential target for the treatment of cervical cancer.
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http://dx.doi.org/10.2147/OTT.S274623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920590PMC
February 2021

In-vitro and in-vivo monitoring of gold(III) ions from intermediate metabolite of sodium aurothiomalate through water-soluble ruthenium (II) complex-based luminescent probe.

Bioorg Chem 2021 Feb 19;110:104749. Epub 2021 Feb 19.

Key Laboratory of Xinjiang Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832002, China. Electronic address:

Real-time monitoring of drug metabolism in vivo is of great significance to drug development and toxicology research. The purpose of this study is to establish a rapid and visual in vivo detection method for the detection of an intermediate metabolite of the gold (I) drug. Gold (I) drugs such as sodium aurothiomalate (AuTM) have anti-inflammatory effects in the treatment of rheumatoid arthritis. Gold(III) ions (Au) are the intermediate metabolite of gold medicine, and they are also the leading factor of side effects in the treatment of patients. However, the rapid reduction of Au to Au by thiol proteins in organisms limits the in-depth study of metabolism of gold drugs in vivo. Here we describe a luminescence Au probe (RA) based on ruthenium (II) complex for detecting Au in vitro and in vivo. RA with large Stokes shift, good water solubility and biocompatibility was successfully applied to detect Au in living cells and vivo by luminescence imaging, and to trap the fluctuation of Au level produced by gold (I) medicine. More importantly, the luminescent probe was used to the detection of the intermediate metabolites of gold (I) drugs for the first time. Overall, this work offers a new detection tool/method for a deeper study of gold (I) drugs metabolite.
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http://dx.doi.org/10.1016/j.bioorg.2021.104749DOI Listing
February 2021

Histone deacetylase 10 exerts anti-tumor effects on cervical cancer via a novel microRNA-223/TXNIP/Wnt/β-catenin pathway.

IUBMB Life 2021 Jan 22. Epub 2021 Jan 22.

Department of Gynecology, The 2nd Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, P.R. China.

Dysfunction of histone deacetylase 10 (HDAC10) has been suggested in the carcinogenesis of cervical cancer (CC). However, its association with microRNAs (miRNAs) in CC remains exclusive. Hence, this study aims to probe the role of HDAC10 in regulating CC cell proliferation, migration, and invasion and its correlation with the screened-out miRNA target. Microarray analysis and RT-qPCR revealed that HDAC10 expressed poorly in CC cells relative to human immortalized endocervical cells (End1/E6E7). Moreover, HDAC10 downregulation predicted poor survival for patients with CC. Overexpression of HDAC10 reduced CC cell biological activities in vitro and tumor growth and lung metastases in vivo. miR-233, upregulated in CC, was regulated by HDAC10 through histone acetylation, while miR-233 inhibited the effects of HDAC10 overexpression in CC. miR-223 targeted the 3'-UTR of thioredoxin interacting protein (TXNIP) and suppressed its expression, leading to increased CC development in vitro and in vivo. TXNIP overexpression impaired Wnt/β-catenin pathway activity in CC cells. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/iub.2448DOI Listing
January 2021

Histone deacetylase 10 exerts antitumor effects on cervical cancer via a novel microRNA-223/TXNIP/Wnt/β-catenin pathway.

IUBMB Life 2021 Apr 23;73(4):690-704. Epub 2021 Feb 23.

Department of Gynecology, The 2nd Affiliated Hospital of Dalian Medical University, Dalian, P.R. China.

Dysfunction of histone deacetylase 10 (HDAC10) has been suggested in the carcinogenesis of cervical cancer (CC). However, its association with microRNAs (miRNAs) in CC remains exclusive. Hence, this study aims to probe the role of HDAC10 in regulating CC cell proliferation, migration, and invasion and its correlation with the screened-out miRNA target. Microarray analysis and RT-qPCR revealed that HDAC10 expressed poorly in CC cells relative to human immortalized endocervical cells (End1/E6E7). Moreover, HDAC10 downregulation predicted poor survival for patients with CC. Overexpression of HDAC10 reduced CC cell biological activities in vitro and tumor growth and lung metastases in vivo. miR-223, upregulated in CC, was regulated by HDAC10 through histone acetylation, while miR-223 inhibited the effects of HDAC10 overexpression in CC. miR-223 targeted the 3'-UTR of thioredoxin interacting protein (TXNIP) and suppressed its expression, leading to increased CC development in vitro and in vivo. TXNIP overexpression impaired Wnt/β-catenin pathway activity in CC cells.
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http://dx.doi.org/10.1002/iub.2450DOI Listing
April 2021

Attenuates Inflammation in Septic Mice Mediated by Gut Microbiota.

Front Microbiol 2020 15;11:598010. Epub 2020 Dec 15.

Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Sepsis is a life-threatening organ dysfunction condition caused by a dysregulated host response to infection and lack of effective treatment method. Supplementation of probiotics has emerged as a potential biotherapy for inflammatory diseases in recent years, but its role in protecting viscera against the damage caused by sepsis and the underlying mechanism is poorly understood. 19 is one of the most well-studied probiotics, which is selected in this study among seven strains isolated from homemade yogurt due to its optimal ability of suppressing the inflammation response . It showed significant decrease in the expression of TNF-α, IL-1β, and IL-6 in the co-culture of 19 and LPS-treated mouse macrophage. The effect of 19 in mice and the response of mice gut microbiota were subsequently investigated. In LPS-induced septic mouse model, 19 was highly resistant to LPS and exhibited significantly decreased expressions of inflammatory factors compared to LPS-treated mice. A MiSeq-based 16S rDNA sequence analysis revealed that the decrease of gut microbial diversity in mice intraperitoneally injected with 1 mg/ml LPS were mitigated by the administration of 19. significantly decreased during the development of sepsis and rose again after supplement strain 19, while showed the opposite trend, which demonstrated these two genera were the key bacteria that may function in the mice gut microbiota for alleviation of LPS-induced inflammation reaction. To conclude, 19 may be a potential candidate for novel biotherapeutic interventions against inflammation caused by sepsis.
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http://dx.doi.org/10.3389/fmicb.2020.598010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769777PMC
December 2020

SIRT1 suppresses burn injury-induced inflammatory response through activating autophagy in RAW264.7 macrophages.

J Investig Med 2021 Mar 23;69(3):761-767. Epub 2020 Dec 23.

Department of Burns and Cutaneous Surgery, Fourth Military Medical University, Xi'an, Shaanxi, China

The present study sought to investigate the association between silent information regulator 1 (SIRT1) and autophagy during systemic inflammatory response syndrome following burn injury. The experimental burn model in mice and macrophages were established. SIRT1 mRNA expression was quantified by quantitative real-time PCR. The protein levels of SIRT1 and the conversion of light chain 3 (LC3)-I to LC3-II were determined by western blot analysis. The formation of autophagosomes was assessed by green fluorescence protein-tagged LC3 fluorescence. The contents of inflammatory cytokines interleukin (IL)-1, IL-6, IL-10 and IL-18 were measured by ELISA. SIRT1 was highly expressed in burned tissues and RAW264.7 cells treated with serum obtained from mice with burn injuries. Moreover, SIRT1 overexpression augmented, whereas sirtinol, an inhibitor of SIRT1, attenuated burn injury-induced increasing number of autophagosomes and expression levels of LC3-II/LC3-I in RAW264.7 cells. Besides, sirtinol effectively prevented SIRT1-induced pro-inflammation during burn injury. Furthermore, autophagy inhibition by 3-methyladenine significantly attenuated SIRT1 overexpression-mediated pro-inflammatory cytokine production. SIRT1 abolished burn injury-induced inflammatory response by inducing autophagy.
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http://dx.doi.org/10.1136/jim-2019-001258DOI Listing
March 2021

DARS-AS1 Knockdown Inhibits the Growth of Cervical Cancer Cells via Downregulating HMGB1 via Sponging miR-188-5p.

Technol Cancer Res Treat 2020 Jan-Dec;19:1533033820971669

Department of Gynecology, The 2nd Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China.

Background: Evidence has been shown that long noncoding RNAs (lncRNAs) play an important role in the development of cervical cancer. Recently, lncRNA DARS-AS1 was shown to be dysregulated in several cancer types, but the role of DARS-AS1 in cervical cancer remains unclear.

Methods: Immunofluorescence staining, flow cytometry and transwell invasion assays were used to determine proliferation, apoptosis and invasion in cervical cancer cells, respectively. The dual luciferase reporter system assay was performed to assess the interaction between DARS-AS1, miR-188-5p, and high mobility group box 1 (HMGB1) in cervical cancer cells.

Results: Downregulation of DARS-AS1 markedly inhibited the proliferation and invasion of cervical cancer cells. Moreover, DARS-AS1 knockdown obviously induced the apoptosis of SiHa and HeLa cells. Meanwhile, luciferase reporter assay identified that miR-188-5p was the potential miRNA binding of DARS-AS1, and HMGB1 was the potential binding target of miR-188-5p. Mechanistic analysis indicated that downregulation of DARS-AS1 decreased the expression of HMGB1 by acting as a competitive "sponge" of miR-188-5p.

Conclusion: In this study, we found that DARS-AS1 knockdown suppressed the growth of cervical cancer cells via downregulating HMGB1 via sponging miR-188-5p. Therefore, DARS-AS1 might serve as a potential target for the treatment of cervical cancer.
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http://dx.doi.org/10.1177/1533033820971669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672739PMC
November 2020

Hypoxia-inducible factor prolyl-hydroxylase inhibitor roxadustat (FG-4592) alleviates sepsis-induced acute lung injury.

Respir Physiol Neurobiol 2020 10 26;281:103506. Epub 2020 Jul 26.

Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, China. Electronic address:

Acute lung injury (ALI) is one of the most severe outcomes of sepsis which still waiting for effective treatment method. Roxadustat (FG-4592) which is often used for treatment of anemia in patients with chronic kidney disease (CKD), its affection on LPS-induced ALI haven't been evaluated. MH-S and MLE-12 cell injury and ALI mouse model was induced LPS. Several assays were used to explore the role of FG-4592 in reducing the damage caused by LPS. FG-4592 treatment significantly upregulated HIF-1α and HO-1 and strikingly attenuated inflammation in vivo and in vitro. Furthermore, septic mice overexpressing HIF-1α had high level of survival rate and lower expression of inflammatory factors while down-regulation can enhance the damage of LPS. HIF-1α has a protective effect on acute lung injury in LPS induced septic mice. FG-4592 treatment remarkably ameliorated the LPS-induced lung injury through the stabilization of HIF-1α. Besides the role in treating CKD anemia, the clinical use of FG-4592 also might be extended to ALI.
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http://dx.doi.org/10.1016/j.resp.2020.103506DOI Listing
October 2020

Investigation of endogenous malondialdehyde through fluorescent probe MDA-6 during oxidative stress.

Anal Chim Acta 2020 Jun 13;1116:9-15. Epub 2020 Apr 13.

Key Laboratory of Xinjiang Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University, Shihezi, 832002, China. Electronic address:

The malondialdehyde (MDA)-specific detection probe (MDA-6) was successfully synthesised through the photoinduced electron transfer (PET) mechanism which possesses many biological applications. In vivo biological applicability of this probe was proved in different cell lines, zebrafish and mice. In these models, the MDA was produced by oxygen stress injury and the relationship between MDA and probe were evaluated in vitro as well as in vivo under different stress conditions. After comparing evaluated results with commercial MDA kit, MDA-6 was concluded with high specificity, low limit of detection (0.03 μM), and can achieve micro-detection of MDA with low cytotoxicity, demonstrating MDA-6 enables safe and effective detection.
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http://dx.doi.org/10.1016/j.aca.2020.04.030DOI Listing
June 2020

Early-onset type 2 diabetes: A high-risk factor for proliferative diabetic retinopathy (PDR) in patients with microalbuminuria.

Medicine (Baltimore) 2020 May;99(19):e20189

Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing.

We aim to explore the relationship between early-onset diabetes and proliferative diabetic retinopathy (PDR) in type 2 diabetes mellitus (T2DM) patients with microalbuminuria.A total of 461 T2DM patients with microalbuminuria were enrolled. Subjects were defined as early-onset or late-onset based on the age at which they were diagnosed with diabetes (<40 and ≥40 years, respectively). Medical history, anthropometry, and laboratory indicators were documented. PDR was defined as the presence of any of the following changes on fundus photography: neovascularization, vitreous hemorrhage, or preretinal hemorrhage.The prevalence of PDR was 6-fold higher in patients with early-onset than late-onset T2DM [(6.1% vs 1.0%), P = .004]. Univariate correlation analysis showed that early-onset diabetes, use of oral hypoglycemic drugs, and insulin therapy were risk factors for PDR. In multivariate logistic analysis, patients with early-onset diabetes exhibited a 7.00-fold [(95% confidence interval 1.40-38.26), P = .019] higher risk of PDR than subjects with late-onset diabetes after adjusting for sex; T2DM duration; systolic blood pressure; total triglyceride; glycated hemoglobin; insulin therapy; and the use of oral hypoglycemic drugs, antihypertensive drugs, and lipid-lowering drugs.In T2DM patients with microalbuminuria, early-onset diabetes is an independent risk factor for the development of PDR.
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http://dx.doi.org/10.1097/MD.0000000000020189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220424PMC
May 2020

Upregulation of Beta4 subunit of BK channels in the anterior cingulate cortex contributes to mechanical allodynia associated anxiety-like behaviors.

Mol Brain 2020 02 18;13(1):22. Epub 2020 Feb 18.

Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.

The anterior cingulate cortex (ACC) serves as a critical hub for the anxiety and pain perception. The large-conductance Ca-activated potassium channels, or BK channels, are ubiquitously expressed throughout the central nervous system including the cingulate cortex. However, what changes of cortical BK channels undergo in the ACC remains unknown in pain-related anxiety. In the present study, a significant upregulation of synaptic and non-synaptic BK channel accessory β4 subunits in the ACC was accompanied with pain-associated anxiety-like behaviors in the chronic compression of multiple dorsal root ganglia (mCCD) of the rat. NS1619, an opener of BK channels, significantly rescued the alteration of fAHP and AP duration of ACC pyramidal neurons in mCCD rats. The mRNA expression of BK β4 subunits was extremely upregulated in the ACC after mCCD with the increased amount of both synaptic and non-synaptic BK β4 subunit protein. Meanwhile, NS1619 reversed the enhanced AMPA receptor-mediated spontaneous excitatory postsynaptic current (sEPSC) frequency and the attenuated PPR of ACC neurons in mCCD rats. Local activation of BK channels in the ACC reversed mechanical allodynia and anxiety-like behaviors. These results suggest that the upregulation of postsynaptic and presynaptic BK β4 subunit may contribute to neuronal hyperexcitability and the enhanced synaptic transmission in the ACC in neuropathic pain state, and then may result in anxiety-like behavior induced by neuropathic pain.
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http://dx.doi.org/10.1186/s13041-020-0555-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029562PMC
February 2020

ING4 alleviated lipopolysaccharide-induced inflammation by regulating the NF-κB pathway via a direct interaction with SIRT1.

Immunol Cell Biol 2020 02 14;98(2):127-137. Epub 2020 Jan 14.

Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.

Sepsis is a complex inflammatory disorder in which high mortality is associated with an excessive inflammatory response. Inhibitor of growth 4 (ING4), which is a cofactor of histone acetyltransferase and histone deacetylase complexes, could negatively regulate this inflammation. However, the exact molecular signaling pathway regulated by ING4 remains uncertain. As a pivotal histone deacetylase, Sirtuin1 (SIRT1), which is widely accepted to be an anti-inflammatory molecule, has not been found to be linked to ING4. This study investigated how ING4 is involved in the regulation of inflammation by constructing lipopolysaccharide (LPS)-induced macrophage and mouse sepsis models. Our results revealed that ING4 expression decreased, whereas the levels of proinflammatory cytokines increased in LPS-stimulated cultured primary macrophages and RAW 264.7 cells. ING4 transfection was confirmed to alleviate the LPS-induced upregulation of proinflammatory cytokine expression both in vitro and in vivo. In addition, ING4-overexpressing mice were hyposensitive to an LPS challenge and displayed reduced organ injury. Furthermore, immunoprecipitation indicated a direct interaction between ING4 and the SIRT1 protein. Moreover, ING4 could block nuclear factor-kappa B (NF-κB) P65 nuclear translocation and restrict P65 acetylation at lysine 310 induced by LPS treatment. These results are the first to clarify that the anti-inflammatory role of ING4 is associated with SIRT1, through which ING4 inhibits NF-κB signaling activation. Our studies provide a novel signaling axis involving ING4/SIRT1/NF-κB in LPS-induced sepsis.
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http://dx.doi.org/10.1111/imcb.12308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384142PMC
February 2020

Patterns of protein expression in human head and neck cancer cell lines differ after proton vs photon radiotherapy.

Head Neck 2020 02 11;42(2):289-301. Epub 2019 Nov 11.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Proton radiotherapy (PRT) may be a less toxic alternative to photon radiotherapy (XRT) for patients with head and neck squamous cell carcinoma (HNSCC). However, the molecular responses of HNSCC cells to PRT vs XRT are unclear.

Methods: Proteomics analyses of protein expression profiles by reverse-phase protein arrays were done for two human papillomavirus [HPV]-negative and two HPV+ cell lines. Expression patterns of 175 proteins involved in several signaling pathways were tested.

Results: Compared with PRT, XRT tended to induce lower expression of DNA damage repair-and cell cycle arrest-related proteins and higher expression of cell survival- and proliferation-related proteins.

Conclusions: Under these experimental conditions, PRT and XRT induced different protein expression and activation profiles. Further preclinical verification is needed, as are studies of tumor pathway mutations as biomarkers for choice of treatment or as radiosensitization targets to improve the response of HNSCC to PRT or XRT.
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http://dx.doi.org/10.1002/hed.26005DOI Listing
February 2020

Direct Synthesis of Aluminosilicate IWR Zeolite from a Strong Interaction between Zeolite Framework and Organic Template.

J Am Chem Soc 2019 Nov 1;141(45):18318-18324. Epub 2019 Nov 1.

Department of Chemistry , Zhejiang University , Hangzhou 310028 , People's Republic of China.

A large amount of zeolite structures are still not synthetically available or not available in the form of aluminosilicate currently. Despite significant progress in the development of predictive concepts for zeolite synthesis, accessing some of these new materials is still challenging. One example is the IWR structure as well. Despite successful synthesis of Ge-based IWR zeolites, direct synthesis of aluminosilicate IWR zeolite is still not successful. In this report we show how a suitable organic structure directing agent (OSDA), through modeling of an OSDA/zeolite cage interaction, could access directly the aluminum-containing IWR structure (denoted as COE-6), which might allow access to new classes of materials and thus open opportunities in valuable chemical applications. The experimental results reveal that the COE-6 zeolites with a SiO/AlO ratio as low as 30 could be obtained. Very interestingly, the COE-6 zeolite has much higher hydrothermal and thermal stabilities than those of the conventional Ge-Al-IWR zeolite. In methanol-to-propylene (MTP) reaction, the COE-6 zeolite exhibits excellent selectivity for propylene, offering a potential catalyst for MTP reaction in the future.
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http://dx.doi.org/10.1021/jacs.9b09903DOI Listing
November 2019

Lidocaine inhibits cervical cancer cell proliferation and induces cell apoptosis by modulating the lncRNA-MEG3/miR-421/BTG1 pathway.

Am J Transl Res 2019 15;11(9):5404-5416. Epub 2019 Sep 15.

Department of Gynecology, The 2nd Affiliated Hospital of Dalian Medical University Dalian 116021, China.

This study aimed to explore the effect of lidocaine on the growth of cervical cancer cells (HeLa) and the underlying molecular mechanisms. Cell counting kit-8 (CCK-8) and flow cytometry (FCM) were used to detect the cell viability and apoptosis of cervical cancer cells after lidocaine treatment. Lidocaine inhibited cell viability and promoted apoptosis in HeLa cells. Long noncoding RNA maternally expressed gene 3 (lncRNA-MEG3) was significantly downregulated in cervical cancer cells, and lidocaine increased the expression of lncRNA-MEG3 in HeLa cells. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), CCK-8, and FCM assays were used to test indicators. MEG3-shRNA promoted the cell viability and inhibited apoptosis, while the effect of lidocaine was the opposite. The effects of lidocaine on HeLa cells were reversed by MEG3-shRNA. The level of miR-421 in cervical cancer and normal cervical cells was detected using qRT-PCR. The MEG3-plasmid could inhibit cell viability and induce cell apoptosis, but these effects were reversed by miR-421 upregulation. Hence, lidocaine suppressed tumor growth by regulating cell viability and inducing apoptosis. The results indicated that BTG anti-proliferation factor 1 (BTG1) was a direct target of miR-421. HeLa cells were transfected with inhibitor control, miR-421 inhibitor, control-shRNA, or BTG1-shRNA. The negative effects of the miR-421 inhibitor or knockdown BTG1 on cell viability and apoptosis were identified using CCK-8 assay and FCM. The miR-421 inhibitor improved cervical cancer progression by regulating BTG1 expression. The results suggested that lidocaine inhibited the growth of cervical cancer cells by modulating the lncRNA-MEG3/miR-421/BTG1 signaling pathway, providing opportunities for treating cervical cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789266PMC
September 2019

The Akt/FoxO/p27 axis contributes to the anti-proliferation of pentoxifylline in hypertrophic scars.

J Cell Mol Med 2019 09 3;23(9):6164-6172. Epub 2019 Jul 3.

Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.

Hypertrophic scars (HS) are characterized by the excessive production and deposition of extracellular matrix (ECM) proteins. Pentoxifylline (PTX), a xanthine derived antioxidant, inhibits the proliferation, inflammation and ECM accumulation of HS. In this study, we aimed to explore the effect of PTX on HS and further clarify the mechanism of PTX-induced anti-proliferation. We found that PTX could significantly attenuate proliferation of HS fibroblasts and fibrosis in an animal HS model. PTX inhibited the proliferation of HSFs in a dose- and time-dependent manner, and this growth inhibition was mainly mediated by cell cycle arrest. Transcriptome sequencing showed that PTX affects HS formation through the PI3K/Akt/FoxO1 signalling pathway to activate p27 . PTX down-regulated p-Akt and up-regulated p-FoxO1 in TGF-β1 stimulated fibroblasts at the protein level, and simultaneously, the expression of p27 was activated. In a mouse model of HS, PTX treatment resulted in the ordering of collagen fibres. The results revealed that PTX regulates TGFβ1-induced fibroblast activation and inhibits excessive scar formation. Therefore, PTX is a promising agent for the treatment of HS formation.
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http://dx.doi.org/10.1111/jcmm.14498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714140PMC
September 2019

Direct Synthesis of Aluminosilicate SSZ-39 Zeolite Using Colloidal Silica as a Starting Source.

ACS Appl Mater Interfaces 2019 Jul 18;11(26):23112-23117. Epub 2019 Jun 18.

Key Laboratory of Applied Chemistry of Zhejiang Province , Zhejiang University , Hangzhou 310028 , China.

For the first time, SSZ-39 zeolite has been directly prepared using conventional colloidal silica and sodium aluminate instead of using FAU zeolite as the raw material in the alkaline media. The adjustment of the Si/Al ratios in the starting materials to the suitable values is a key factor to prepare the aluminosilicate SSZ-39 zeolite. Various characterizations (for instance, X-ray diffraction, scanning electron microscopy, nitrogen sorption, solid Al NMR, and NH-temperature-programmed desorption) display that the aluminosilicate SSZ-39 zeolite owns high crystallinity, uniform cuboid morphology, large surface area, four-coordinated aluminum species, and strong acidic sites. Inductively coupled plasma analysis shows that the SiO/AlO ratios of the SSZ-39 products are ranged from 12.8 to 16.8. Considering the special framework of the SSZ-39 zeolite, the yield of this synthesis is not higher than 21.3%. Moreover, the catalytic performance of Cu-SSZ-39 catalyst synthesized from this route is excellent in the selective catalytic reduction of NO with NH (NH-SCR).
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http://dx.doi.org/10.1021/acsami.9b03048DOI Listing
July 2019

MCPIP1 alleviated lipopolysaccharide-induced liver injury by regulating SIRT1 via modulation of microRNA-9.

J Cell Physiol 2019 12 16;234(12):22450-22462. Epub 2019 May 16.

Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, China.

The severity of sepsis is associated with excessive inflammatory responses. MCP-1 induced protein (MCPIP1) could negatively regulate inflammatory responses by deubiquitinating K48 or K63 polyubiquitins of TNF receptor-associated factors. The function of MCPIP1 in negative regulation of inflammation is known, however, only the exact molecular pathway remains unknown. The aim of this study was to investigate whether and how MCPIP1 is involved in the regulation of lipopolysaccharides (LPS)-induced liver injury. Macrophages and a mouse model were induced by LPS treatment. Several in vitro assays, such as quantitative real-time PCR, immunoblotting, cell transfection, dual luciferase reporter assay, Enzyme-linked immunosorbent assay, and Hematoxylin-Eosin staining assay were used to explore the role of MCPIP1 and the interaction between MCPIP1, Sirtuin 1 (SIRT1), and microRNA-9 (miR-9). We found that the level of MCPIP1 increased and the level of SIRT1 decreased in LPS induced Kupffer cells or RAW 264.7 macrophages. Overexpression of MCPIP1 alleviated cytokine secretion and p65 nuclear translocation. Further study showed that MCPIP1 regulated p65 nuclear translocation by controlling p65 acetylation via promoting SIRT1 expression. Meanwhile, we found that miR-9 could directly regulate SIRT1 transcription by binding to the 3'-Untranslated Region of SIRT1 messenger RNA and that miR-9 was negatively regulated by MCPIP1. Importantly, overexpression of MCPIP1 in vivo could alleviate LPS-induced inflammation responses and liver injury in septic mice. These results demonstrated that MCPIP1 could alleviate inflammation responses and sepsis associated liver injury by promoting the expression of SIRT1, and miR-9 was involved in the MCPIP1-mediated regulation of SIRT1. Collectively, our results provide a possible novel signaling axis involving MCPIP1/miR-9/SIRT1 in LPS-induced septic mice.
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http://dx.doi.org/10.1002/jcp.28809DOI Listing
December 2019

ROR alpha protects against LPS-induced inflammation by down-regulating SIRT1/NF-kappa B pathway.

Arch Biochem Biophys 2019 06 6;668:1-8. Epub 2019 May 6.

Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, No.169 Changle West Road, Xi'an, 710032, Shaanxi, China. Electronic address:

Systemic inflammatory response syndrome (SIRS) is associated with excessive inflammatory response, however, the pathophysiology of inflammation is poorly understood. The retinoid-related orphan receptor α (RORα) is a key inflammatory regulator, but the mechanisms underlying its role remain unclear. The aim of this study was to investigate how RORα was involved in the regulation of inflammatory response. Here we put forward a hypothesis that RORα might negatively regulate inflammatory response by controlling silent information regulator Sirtuin 1 (SIRT1) expression. Stimulation of macrophages in vitro with LPS and LPS administration in vivo were used to explore the function of RORα and the relationship between RORα and SIRT1. We found that the level of RORα was suppressed in macrophages stimulated with LPS and overexpression or knockdown of RORα by transfection with lentivirus or siRNAs significantly decreased or increased, respectively, the pro-inflammatory cytokines IL-1β, TNF, IL-6 and MCP-1. Importantly, overexpression of RORα suppressed inflammation and alleviated LPS-induced organ injury in vivo. Further study showed that RORα could regulate SIRT1 expression and, consequently, affect deacetyation and nuclear translocation of nuclear factor-kappa B (NF-κB) subunit p65. Moreover, the activation of SIRT1 by its specific agonist, SR1720, could reduce the expression of proinflammatory cytokines in RORα knockdown macrophages stimulated with LPS. In conclusion, we demonstrated that RORα could alleviate LPS-induced inflammation and organ injury both in vivo and in vitro by blocking NF-κB p65 nuclear translocation and restricting acetylation of NF-κB p65 at lysine 310 via the regulation of SIRT1 expression. Targeting RORα might be a promising therapeutic strategy to regulate inflammatory disorders.
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http://dx.doi.org/10.1016/j.abb.2019.05.003DOI Listing
June 2019

MCPIP1 regulates RORα expression to protect against liver injury induced by lipopolysaccharide via modulation of miR-155.

J Cell Physiol 2019 Feb 27. Epub 2019 Feb 27.

Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, China.

Liver injury plays vital roles in the development of inflammation and organ dysfunction during sepsis. MCP-1-induced protein 1 (MCPIP1), as an endoribonuclease, is a critical regulator for the maintenance of immune homeostasis. However, whether MCPIP1 participates in the septic liver injury remains unknown. The aim of this study was to investigate the role of MCPIP1 in lipopolysaccharides-induced liver injury and the underlying modulatory mechanisms. Quantitative real-time polymerase chain reaction and immunoblotting were used to determine proinflammatory cytokines, MCPIP1, retinoid-related orphan receptor α (RORα), miR-155, and related protein from nuclear factor-κB (NF-κB) pathway expression. Dual luciferase reporter assay was used to analyze whether miR-155 regulates RORα transcription. Secretion of inflammatory cytokines into sera in mice were measured by enzyme-linked immunosorbent assay. Hematoxylin and eosin staining, alanine aminotransferase, and aspartate transaminase, assay were used to evaluate liver function. We found that MCPIP1 expression was notably upregulated and significantly downregulated inflammatory cytokine secretion and NF-κB signaling activation in macrophages following exposure to lipopolysaccharide. Moreover, miR-155, lowered by MCPIP1, directly targeted on 3'-untranslated region of RORα to activate an inflammatory response. Importantly, MCPIP1 overexpression in mice alleviated septic liver injury symptoms following lipopolysaccharides stimulation. Collectively, these data highlight MCPIP1/miR-155/RORα axis as a novel modulation of inflammation in liver injury and potential therapeutic target for future research.
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http://dx.doi.org/10.1002/jcp.28327DOI Listing
February 2019

miR-150-5p promotes the proliferation and epithelial-mesenchymal transition of cervical carcinoma cells via targeting SRCIN1.

Pathol Res Pract 2019 Apr 7;215(4):738-747. Epub 2019 Jan 7.

Department of Gynecology, The Second Affiliated Hospital, Dalian Medical University, Dalian, China. Electronic address:

Cervical carcinoma is one of the most universal cancers among women. Recent researches have reported that microRNA-150-5p (miR-150-5p) is up-regulated in diverse carcinomas containing cervical carcinoma. The purpose of this study was to further investigate the potential role of miR-150-5p in the progress of cervical carcinoma cells including proliferation and epithelial-mesenchymal transition (EMT).The ability of miR-150-5p to promote carcinogenesis was analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot assays, respectively. Bioinformatics analyses predicted and identified whether SRC kinase signaling inhibitor 1 (SRCIN1) was served as a potential target of miR-150-5p. C-33A and HeLa cells were utilized to determine the function of miR-150-5p through targeting SRCIN1. Among the aberrantly expressed miRNAs, miR-150-5p was significantly revealed differential expression in cervical carcinoma cell lines and was closely relevant to cell growth regulation. Furthermore, we found that SRCIN1 overexpression could obviously inhibit the proliferation and EMT of cervical cancer cells triggered by miR-150-5p mimics as well as accelerated the apoptosis of cervical carcinoma cells. In conclusion, our data demonstrated that miR-150-5p could promote the proliferation and EMT of cervical carcinoma cells via targeting SRCIN1. Thus, miR-150-5p may hold a promise as a prognostic biomarker and potential therapeutic target for cervical carcinoma.
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http://dx.doi.org/10.1016/j.prp.2019.01.004DOI Listing
April 2019

Retracted: miR-144 Potentially Suppresses Proliferation and Migration of Ovarian Cancer Cells by Targeting RUNX1.

Med Sci Monit Basic Res 2018 12 20;24:232. Epub 2018 Dec 20.

Department of Experimental Radiation Oncology, MD Anderson, Houston, TX, USA.

This article is being retracted by request of the author, who mistakenly submitted and processed the publication in the wrong journal.
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http://dx.doi.org/10.12659/MSMBR.914478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319437PMC
December 2018

Proton versus photon radiation-induced cell death in head and neck cancer cells.

Head Neck 2019 01 18;41(1):46-55. Epub 2018 Dec 18.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Photon (X-ray) radiotherapy (XRT) kills cells via DNA damage, however, how proton radiotherapy (PRT) causes cell death in head and neck squamous cell carcinoma (HNSCC) is unclear. We investigated mechanisms of HNSCC cell death after XRT versus PRT.

Methods: We assessed type of death in 2 human papillomavirus (HPV)-positive and two HPV-negative cell lines: necrosis and apoptosis (Annexin-V fluorescein isothiocyanate [FITC]); senescence (β-galactosidase); and mitotic catastrophe (γ-tubulin and diamidino-phenylindole [DAPI]).

Results: The XRT-induced or PRT-induced cellular senescence and mitotic catastrophe in all cell lines studied suggested that PRT caused cell death to a greater extent than XRT. After PRT, mitotic catastrophe peaked in HPV-negative and HPV-positive cells at 48 and 72 hours, respectively. No obvious differences were noted in the extent of cell necrosis or apoptosis after XRT versus PRT.

Conclusion: Under the conditions and in the cell lines reported here, mitotic catastrophe and senescence were the major types of cell death induced by XRT and PRT, and PRT may be more effective.
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http://dx.doi.org/10.1002/hed.25357DOI Listing
January 2019

Design Synthesis of ITE Zeolite Using Nickel-Amine Complex as an Efficient Structure-Directing Agent.

ACS Appl Mater Interfaces 2018 Oct 20;10(39):33214-33220. Epub 2018 Sep 20.

Key Laboratory of Applied Chemistry of Zhejiang Province , Zhejiang University , Hangzhou 310028 , China.

Modern methodologies for synthesizing zeolites typically involve the employment of costly organic structure-directing agents. Herein, we report the design synthesis of aluminosilicate zeolite with ITE structure using an inexpensive nickel-amine complex (nickel-pentaethylenexamine) as a novel structure-directing agent. Characterizations including X-ray diffraction, scanning electron microscopy, N sorption isotherms, and Al magic-angle spinning NMR techniques show that the ITE zeolite has high crystallinity, perfect crystals, large surface area, and abundant aluminum species in the framework. More importantly, catalytic tests on the hydrogenation of CO into methane show that the Ni-ITE zeolite exhibits better catalytic performance than aluminosilicate-supported and silica-supported nickel catalysts. Obviously, the use of nickel-amine complex offers an alternative and facile way to synthesize aluminosilicate zeolites.
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http://dx.doi.org/10.1021/acsami.8b10620DOI Listing
October 2018

MicroRNA-146a protects against LPS-induced organ damage by inhibiting Notch1 in macrophage.

Int Immunopharmacol 2018 Oct;63:220-226

Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi 710032, China. Electronic address:

MicroRNA-146a is a well-studied microRNA participating in immune and inflammatory diseases, but its role in sepsis has not been investigated. Here in our study, we found increased level of microRNA-146a in macrophage stimulated by lipopolysaccharide. In addition, the mRNA level of Notch1 was also increased. Up-regulation of microRNA-146a by miR-146a-mimic alleviated inflammatory responses of macrophage, for the levels of IL-1β, IL-6 and CCL-2 were decreased, and the activation of NF-κB signaling was inhibited. The histological examination showed that microRNA-146a protected against organ damage in mice with lipopolysaccharide injection, and the level of inflammatory factors, Cr, BUN, AST and ALT in serum were all decreased, reflecting the alleviated inflammation and recovered organ function. Then predicting databases were used and Notch1 was predicted as one of the potential targets of microRNA-146a. Knockout of Notch1 in macrophage showed reduced secretion of inflammatory factors and attenuated activation of NF-κB signaling in response to lipopolysaccharide. Specifically knockout of Notch1 in macrophage protected mice from LPS induced organ damage and dysfunction. Therefore, we prove that miR-146a acts as an inhibitor of inflammation by targeting Notch1 in macrophage, therefore protects mice from organ damage in sepsis.
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http://dx.doi.org/10.1016/j.intimp.2018.07.040DOI Listing
October 2018

Klf4 Alleviates Lipopolysaccharide-Induced Inflammation by Inducing Expression of MCP-1 Induced Protein 1 to Deubiquitinate TRAF6.

Cell Physiol Biochem 2018 5;47(6):2278-2290. Epub 2018 Jul 5.

Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Background/aims: Inflammation is an essential component of innate immunity against pathogens, but is tightly regulated, such as by Krüppel-like factor 4 (Klf4), to prevent injury. Klf4 also regulates macrophage polarization, although the mechanisms underlying both functions are poorly understood. The aim of this study was to investigate whether and how Klf4 prevents unregulated inflammation.

Methods: The bone marrow-derived macrophages and RAW264.7 cell line were used. Quantitative real-time PCR was used to determine inflammatory cytokines (IL-1β, TNF-α, IL-6 and MCP-1), Klf4 and MCPIP1 transcript levels. Extraction of nuclear and cytoplasmic proteins and Immunoblotting were used to determine Klf4, MCPIP1, relative kinases from NF-κB pathway and K63-linked polyubiquitins expression in nucleus and cytoplasm separately. Dual luciferase reporter assay was used to analyze whether Klf4 mediate MCPIP1 transcription. Immunoprecipitation was used to determine the protein interaction among Klf4, MCPIP1, TRAF6 and K63-linked polyubiquitins. Secretion of IL-1β and TNF-α into sera in mice was measured by Enzyme-linked immunosorbent assay.

Results: We found that exposure to lipopolysaccharides suppresses Klf4 expression, even as it induces release of pro-inflammatory cytokines. Strikingly, Klf4 overexpression significantly lowered cytokine secretion and NF-κB signaling in the cytoplasm following exposure to lipopolysaccharide, even though Klf4 was exclusively nuclear. The cytoplasmic effects are likely mediated by MCP-1 induced protein 1 (MCPIP1), a deubiquitinase and a key modulator of inflammation that accumulates both in the nucleus and cytoplasm in response to Klf4. Indeed, binding between MCPIP1 and K63 polyubiquitins is attenuated in macrophages overexpressing Klf4, suggesting that MCPIP1 is an intermediator induced by Klf4 in the nucleus to remove K63 polyubiquitins from TRAF6 in the cytoplasm, and thereby impede NF-κB and inflammatory signaling. Importantly, Klf4 overexpression in mice alleviated sepsis symptoms following exposure to lipopolysaccharides.

Conclusion: The data highlight Klf4 as an essential MCPIP1-dependent modulator of innate immunity that protects against excessive and self-destructive inflammation.
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http://dx.doi.org/10.1159/000491538DOI Listing
August 2018

Cell-free therapy based on adipose tissue stem cell-derived exosomes promotes wound healing via the PI3K/Akt signaling pathway.

Exp Cell Res 2018 09 28;370(2):333-342. Epub 2018 Jun 28.

Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, No. 127 West Changle Road, Xi'an 710032, Shaanxi, China. Electronic address:

Introduction: Adipose tissue-derived stem cells (ADSCs) have been shown to enhance wound healing via their paracrine function. Exosomes, as one of the most important paracrine factors, play an essential role in this process. However, the concrete mechanisms that underlie this effect are poorly understood. In this study, we aim to explore the potential roles and molecular mechanisms of exosomes derived from ADSCs in cutaneous wound healing.

Methods: Normal human skin fibroblasts and ADSCs were isolated from patient skin and adipose tissues. ADSCs were characterized by using flow cytometric analysis and adipogenic and osteogenic differentiation assays. Exosomes were purified from human ADSCs by differential ultracentrifugation and identified by electron microscopy, nanoparticle tracking, fluorescence confocal microscopy and western blotting. Fibroblasts were treated with different concentrations of exosomes, and the synthesis of collagen was analyzed by western blotting; the levels of growth factors were analyzed by real-time quantitative PCR (RT-PCR) and ELISA; and the proliferation and migration abilities of fibroblasts were analyzed by real-time cell analysis, CCK-8 assays and scratch assays. A mouse model with a full-thickness incision wound was used to evaluate the effect of ADSC-derived exosomes on wound healing. The level of p-Akt/Akt was analyzed by western blotting. Ly294002, a phosphatidylinositol 3-kinases (PI3K) inhibitor, was used to identify the underlying mechanisms by which ADSC-derived exosomes promote wound healing.

Results: ADSC-derived exosomes were taken up by the fibroblasts, which showed significant, dose-dependent increases in cell proliferation and migration compared to the behavior of cells without exosome treatment. More importantly, both the mRNA and protein levels of type I collagen (Col 1), type III collagen (Col 3), MMP1, bFGF, and TGF-β1 were increased in fibroblasts after stimulation with exosomes. Furthermore, exosomes significantly accelerated wound healing in vivo and increased the level of p-Akt/Akt in vitro. However, Ly294002 alleviated these exosome-induced changes, suggesting that exosomes from ADSCs could promote and optimize collagen deposition in vitro and in vivo and further promote wound healing via the PI3K/Akt signaling pathway.

Conclusions: This study demonstrates that ADSC-derived exosomes can promote fibroblast proliferation and migration and optimize collagen deposition via the PI3K/Akt signaling pathway to further accelerate wound healing. Our results suggest that ADSCs likely facilitate wound healing via the release of exosomes, and the PI3K/Akt pathway may play a role in this process. Our data also suggest that the clinical application of ADSC-derived exosomes may shed new light on the use of cell-free therapy to accelerate full-thickness skin wound healing and attenuate scar formation.
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http://dx.doi.org/10.1016/j.yexcr.2018.06.035DOI Listing
September 2018

miR-155 inhibits the formation of hypertrophic scar fibroblasts by targeting HIF-1α via PI3K/AKT pathway.

J Mol Histol 2018 Aug 21;49(4):377-387. Epub 2018 May 21.

Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.

Hypertrophic scar (HS) is a serious skin fibrotic disease characterized by the excessive proliferation of fibroblasts and often considered as a kind of benign skin tumor. microRNA-155 (miR-155) is usually served as a promising marker in antitumor therapy. In view of the similarities of hypertrophic scar and tumor, it is predicted that miR-155 may be a novel therapeutic target in clinical trials. Here we found the expression levels of miR-155 was gradually down regulated and HIF-1α was upregulated in HS tissue and HS derived fibroblasts (HFs). And cell proliferation was inhibited when miR-155 was overexpressed or HIF-1α was silenced. Moreover, overexpression of miR-155 in HFs could reduce the expression of collagens in vitro and inhibit the collagen fibers arrangement in vivo, whereas miR-155 knockdown gave opposite results. Furthermore, we found that miR-155 directly targeted the HIF-1α, which could also independently inhibit the expression of collagens in vitro and obviously improved the appearance and architecture of the rabbit ear scar in vivo when it was silencing. Finally, we found that PI3K/AKT pathway was enrolled in these processes. Together, our results indicated that miR-155 was a critical regulator in the formation and development of hypertrophic scar and might be a potential molecular target for hypertrophic scar therapy.
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http://dx.doi.org/10.1007/s10735-018-9778-zDOI Listing
August 2018

IL-17 Promotes Scar Formation by Inducing Macrophage Infiltration.

Am J Pathol 2018 07;188(7):1693-1702

Department of Burns and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an, People's Republic of China. Electronic address:

Trauma or burn injuries that affect the deep dermis often produce a hypertrophic scar, which limits patients' joint movement and generates an aesthetic problem. Inflammation is believed to be one of the main pathogenic mechanisms. We found that IL-17 was increased in scar tissues from patients with hypertrophic scar compared with normal skin. Recombinant mouse IL-17 was subcutaneously injected into mice that underwent full-thickness excision surgery to investigate the role of IL-17 in scar formation. Mice stimulated with IL-17 showed aggravated fibrogenesis, delayed wound healing, and increased inflammation. In addition, macrophage infiltration was also increased. According to the results of the Transwell assay, IL-17 promoted macrophage infiltration through an indirect mechanism. After depleting macrophages with clodronate liposomes, the effect of IL-17 disappeared. Levels of monocyte chemotactic protein (MCP) 1, MCP2, and MCP3 (together referred to as MCPs) were increased by IL-17 stimulation. Bindarit (an inhibitor of MCPs) was used to verify the role of MCPs. In addition, the Ly6C-low macrophages were responsible for wound fibrogenesis in mice. In this study, we detected the increased levels of IL-17 for the first time and revealed that IL-17 induced the infiltration of a specific subtype of macrophages to aggravate fibrosis through an MCP-dependent mechanism. Thus, our results provide a better understanding of scar formation and new strategies for scar prevention.
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http://dx.doi.org/10.1016/j.ajpath.2018.04.005DOI Listing
July 2018

miR-144 Potentially Suppresses Proliferation and Migration of Ovarian Cancer Cells by Targeting RUNX1.

Med Sci Monit Basic Res 2018 Feb 15;24:40-46. Epub 2018 Feb 15.

Department of Experimental Radiation Oncology, MD Anderson, Houston, TX, USA.

BACKGROUND Ovarian cancer (OC) is one of the most common malignant diseases of the female reproductive system worldwide. Evidence has shown that microRNAs are involved in the development of ovarian cancer. miR-144, one of these microRNAs, has been found have upregulated expression in various human malignancies. The present study aimed to investigate the role miR-144 in ovarian cancer cell lines and to elucidate the mechanism involved. MATERIAL AND METHODS Human ovarian cancer cell lines (SKOV3/OVCAR3) and a normal ovarian cell line (IOSE80) were used to identify the miR-144 expression though qRT-PCR method. SKOV3/OVCAR3 cells were transfected with miR-144 mimics by Lipofectamine, and the proliferation, migration, and invasion ability of these cells were detected by MTT assay, wound healing assay, and Transwell assays, respectively. MMP2 and MMP9 expression were detected at mRNA and protein levels. The results of dual luciferase reporter assay confirmed that miR-144 could down-regulate RUNX1 expression level. Finally, the expression of runt-related transcription factor 1 (RUNX1) was examined using qRT-PCR and Western blot analysis. RESULTS Our results demonstrate that the expression level of miR-144 was downregulated in SKOV3/OVCAR3 compared to IOSE80, and we found that miR-144 suppresses the proliferation and migration of ovarian cancer cells. Moreover, RUNX1 was predicted and confirmed to be a target of miRNA-144. Additionally, after 48-h transfection with miR-144 mimics, the expression of RUNX1 was downregulated in OC cells. CONCLUSIONS miR-144 mimics can inhibit the proliferation and migration of ovarian cancer cells though regulating the expression of RUNX1.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822934PMC
http://dx.doi.org/10.12659/msmbr.907333DOI Listing
February 2018