Publications by authors named "Guoxin Liu"

11 Publications

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METTL3 induces bone marrow mesenchymal stem cells osteogenic differentiation and migration through facilitating M1 macrophage differentiation.

Am J Transl Res 2021 15;13(5):4376-4388. Epub 2021 May 15.

Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University Harbin 150081, China.

Despite the crucial role of mA methyltransferase METTL3 in multiple diseases onset and progression, there are still lacking hard evidence proving that METTL3 could affect macrophage polarization in the stage of bone repair. Here, we aimed to explore the potential involvement of METTL3 in bone repair through modulating macrophage polarization and decipher the underlying cellular/molecular mechanisms. Here we treated RAW 264.7 cells and BM-derived primary macrophages (BMDM) with lipopolysaccharide (LPS) to induce M1 differentiation. METTL3 expression was upregulated in pro-inflammatory macrophages (M1) as compared with macrophages (M0). And overexpression of METTL3 promoted the expression of IL-6 and iNOS secretion by M1 macrophage. In the coculture condition, M1 macrophages with forced expression of METTL3 significantly enhanced migration ability of BMSCs, and also remarkably facilitated osteogenesis ability of BMSCs; the opposite was true when expression of METTL3 was knockdown. In addition, the mA-RIP microarray suggested that METTL3 silencing significantly reduce the mA modification of DUSP14, HDAC5 and Nfam1. Furthermore, the findings showed that expression of HADC5 was downregulated in M1 macrophages with METTL3 knockdown, while the DUSP14 expression had slight change and Nfam1 expression was very low. In contrast, METTL3 overexpression promoted HDAC5 expression, indicating that HDAC5 is the critical target gene of METTL3. Under such a theme, we proposed that METTL3 overexpression might be a new approach of replacement therapy for the treatment of bone repair.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205672PMC
May 2021

Peroxiredomin-4 ameliorates lipotoxicity-induced oxidative stress and apoptosis in diabetic cardiomyopathy.

Biomed Pharmacother 2021 Jun 12;141:111780. Epub 2021 Jun 12.

Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China. Electronic address:

Diabetic cardiomyopathy (DCM), one severe complication in the diabetes, leads to high mortality in the diabetic patients. However, the understanding of molecular mechanisms underlying DCM is far from completion. Herein, we investigated the disease-related differences in the proteomes of DCM based on db/db mice and verified the protective roles of peroxiredoxin-4 (Prdx4) in H9c2 cardiomyocytes treated by palmitic acid (PA). Fasting blood glucose (FBG) and cardiac function was detected in the 6-month-old control and diabetic mice. The hearts were then collected and analyzed by a coupled label-free and mass spectrometry approach. In vivo investigation indicated that body weight and FBG of db/db mice markedly increased, and diabetic heart exhibited obvious cardiac hypertrophy and lipid droplet accumulation, and cardiac dysfunction as is indicated by the increases of left ventricle posterior wall thickness in systole (LVPWd) and diastole (LVPWs), and reduction of fractional shortening (FS). We used proteomic analysis and then detected a grand total of 2636 proteins. 175 differentially expressed proteins (DEPs) were markedly detected in the diabetic heart. Thereinto, Prdx4 was markedly down-regulated in the diabetic heart. In vitro experiments revealed that 250 μM PA significantly inhibited viability of H9c2 cell. PA induced much accumulation of lipid droplet in cardiomyocytes and resulted in an increase of mRNA expressions of lipogenic genes (FASN and SCD1) and cardiac hypertrophic genes. Additionally, protein level of Prdx4 evidently reduced in the PA-treated H9c2 cell. It was further found that shRNA-mediated Prdx4 knockdown exacerbated PA-induced oxidative stress and cardiomyocyte apoptosis, whereas overexpressing Prdx4 in the H9c2 cells noteworthily limited PA-induced ROS generation and cardiomyocytes apoptosis. These data collectively reveal the essential role of abnormal Prdx4 in pathological alteration of DCM, and provide potentially therapeutic target for the prevention of DCM.
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http://dx.doi.org/10.1016/j.biopha.2021.111780DOI Listing
June 2021

AB4 inhibits Notch signaling and promotes cancer cell apoptosis in liver cancer.

Oncol Rep 2021 06 28;45(6). Epub 2021 Apr 28.

Department of Pharmacy, Hospital 971 of The Navy of Chinese PLA, Qingdao, Shandong 266071, P.R. China.

The etiology for liver cancer has been clearly defined. Unfortunately, therapeutic approaches for liver cancer are rather limited, and liver cancer is insensitive to chemotherapy and radiotherapy. Traditional Chinese medicine (TCM) has become a promising strategy for cancer treatment as TCM elicits broad spectrum anticancer activity. In the present study, we evaluated the anticancer efficacy of AB4, an extract from the medical herb (Bunge) Regel, in liver cancer and . We found that AB4 readily dose‑ and time‑dependently inhibited liver cancer HepG2 and Huh‑7 cell proliferation and colony formation. Western blot and flow cytometry analyses suggested that AB4 treatment induced liver cancer cell apoptosis. Moreover, these findings could be readily recaptured , in which the AB4 regimen resulted in tumor suppression and cancer cell apoptosis in xenograft tumor‑bearing nude mice. Importantly, we noted that treatment with a Notch signaling inhibitor DAPT produced very similar anticancer efficacy in both HepG2 and Huh‑7 cell lines, and administration of DAPT also efficiently suppressed HepG2 xenograft outgrowth. To this end, we anticipated that AB4 and DAPT may act on the same signaling pathway, probably through inhibition of the Notch pathway. Indeed, we found decreased expression of Notch1 protein, as well as downstream targets Hes1 and Hey1, after AB4 treatment. Immunohistochemistry analysis further confirmed the suppression of Notch signaling in HepG2 xenograft‑bearing mice. Taken together, our study highlighted the anticancer efficacy of AB4 in liver cancer. We also provided preliminary data showing Notch as a therapeutic target of AB4. It would be interesting to investigate the anticancer efficacy of AB4 in other types of cancer with elevated Notch activity.
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http://dx.doi.org/10.3892/or.2021.8063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107656PMC
June 2021

Assembly of multifunction dyes and heat shock protein 90 inhibitor coupled to bovine serum albumin in nanoparticles for multimodal photodynamic/photothermal/chemo-therapy.

J Colloid Interface Sci 2021 May 27;590:290-300. Epub 2021 Jan 27.

Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi 712100, PR China. Electronic address:

The proangiogenic protein, survivin, is a client protein for heat shock protein 90 (Hsp-90), whose overexpression is induced by photodynamic therapy (PDT), leading to the inhibition of capase-9 and the blockage of apoptosis. The overexpression of Hsp-90 in cancer cells can rapidly acquire thermoresistance during photothermal therapy (PTT), leading to insufficient apoptosis, increased cell viability, and tumor recurrence. A potential approach to block the PTT-induced overexpression of Hsp-90 and the overexpression of survivin is developed by using an Hsp-90 inhibitor and anticancer agent, namely, geldanamycin (GM). These inhibitors also develop a mild-temperature PTT strategy to reach synergistic PDT and PTT efficiency. Thus, Cy7-SQ is designed by a covalent disulfide linkage between a photothermal agent (i.e., canine dye 7 [Cy7]) and a photosensitizer (i.e., squaraine dye [SQ]) for the improved photostability and thermal stability of Cy7 and SQ. The cleavage of the Cy7-SQ linkage by glutathione in a tumor microenvironment increases the efficiency of synergistic PDT and PTT. In the current study, bovine serum albumin (BSA)/Cy7-SQ/GM nanoparticles are developed through the self-assembly of BSA, Cy7-SQ, and GM to accelerate the apoptosis of cancer cells via near-infrared (NIR) laser irradiation, thus realizing Hsp-90-regulated synergistic PDT/PTT combined with chemotherapy.
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http://dx.doi.org/10.1016/j.jcis.2021.01.052DOI Listing
May 2021

The effects of deletion of cellobiohydrolase genes on carbon source-dependent growth and enzymatic lignocellulose hydrolysis in Trichoderma reesei.

J Microbiol 2020 Aug 10;58(8):687-695. Epub 2020 Jun 10.

State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao, 266237, P. R. China.

The saprophytic fungus Trichoderma reesei has long been used as a model to study microbial degradation of lignocellulosic biomass. The major cellulolytic enzymes of T. reesei are the cellobiohydrolases CBH1 and CBH2, which constitute more than 70% of total proteins secreted by the fungus. However, their physiological functions and effects on enzymatic hydrolysis of cellulose substrates are not sufficiently elucidated. Here, the cellobiohydrolase-encoding genes cbh1 and cbh2 were deleted, individually or combinatively, by using an auxotrophic marker-recycling technique in T. reesei. When cultured on media with different soluble carbon sources, all three deletion strains (Δcbh1, Δcbh2, and Δcbh1Δcbh2) exhibited no dramatic variation in morphological phenotypes, but their growth rates increased apparently when cultured on soluble cellulase-inducing carbon sources. In addition, Δcbh1 showed dramatically reduced growth and Δcbh1Δcbh2 could hardly grew on microcrystalline cellulose (MCC), whereas all strains grew equally on sodium carboxymethyl cellulose (CMC-Na), suggesting that the influence of the CBHs on growth was carbon source-dependent. Moreover, five representative cellulose substrates were used to analyse the influence of the absence of CBHs on saccharification efficiency. CBH1 deficiency significantly affected the enzymatic hydrolysis rates of various cellulose substrates, where acid pre-treated corn stover (PCS) was influenced the least. CBH2 deficiency reduced the hydrolysis of MCC, PCS, and acid pre-treated and delignified corncob but improved the hydrolysis ability of filter paper. These results demonstrate the specific contributions of CBHs to the hydrolysis of different types of biomass, which could facilitate the development of tailor-made strains with highly efficient hydrolysis enzymes for certain biomass types in the biofuel industry.
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http://dx.doi.org/10.1007/s12275-020-9630-5DOI Listing
August 2020

Establishment of a rapid and effective plate chromogenic assay for screening of Aspergillus species with high β-fructofuranosidase activity for fructooligosaccharides production.

J Microbiol Methods 2019 11 12;166:105740. Epub 2019 Oct 12.

State Key Laboratory of Microbial Technology, Department of Science and Technology Management, Shandong University, Qingdao, Shandong Province, PR China. Electronic address:

Fructooligosaccharides (FOS) are commonly regarded as prebiotics and used as components of functional foods. Currently, the industrial sucrose-to-FOS biotransformation is mainly carried out using the microbial-derived β-fructofuranosidases with transglycosylation activity as catalysts. Evaluation of the ability of a microorganism to produce β-fructofuranosidase is commonly conducted by measuring enzyme activity. However, the traditional method requires several steps to identify strains with high β-fructofuranosidase activity, which is not suitable for high-throughput screening. To facilitate screening of a large number of microbial cultures, this study developed a plate chromogenic assay method based on the glucose oxidase (GOD) - peroxidase (POD) bienzymatic system for screening of β-fructofuranosidase-producing fungal strains and predicting their potential to produce FOS. This method used the amount of glucose released from sucrose as indicator to form clear pink halos around the microbial colonies with β-fructofuranosidase activity. Cultivation conditions for the plate assay were optimized as cultivation time 5 h and spore inoculum concentration 10/ml. Moreover, the method was applied to screening of an Aspergillus niger ATCC 20611 mutant library. The mutant A11 displaying the largest pink halo was screened out and its β-fructofuranosidase activity was determined to be 1.65 fold than that of the parental strain. Thin layer chromatography (TLC) assay further indicated that A11 with the largest halo possessed the highest FOS synthesis ability. These results demonstrated the potential of this plate chromogyenic assay method in the rapid and effective identification of excellent FOS producers from a large number of strain samples.
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http://dx.doi.org/10.1016/j.mimet.2019.105740DOI Listing
November 2019

Mean almost periodicity and moment exponential stability of semi-discrete random cellular neural networks with fuzzy operations.

PLoS One 2019 7;14(8):e0220861. Epub 2019 Aug 7.

City College, Kunming University of Science and Technology, Kunming, China.

By using the semi-discretization technique of differential equations, the discrete analogue of a kind of cellular neural networks with stochastic perturbations and fuzzy operations is formulated, which gives a more accurate characterization for continuous-time models than that by Euler scheme. Firstly, the existence of at least one p-th mean almost periodic sequence solution of the semi-discrete stochastic models with almost periodic coefficients is investigated by using Minkowski inequality, Hölder inequality and Krasnoselskii's fixed point theorem. Secondly, the p-th moment global exponential stability of the semi-discrete stochastic models is also studied by using some analytical skills and the proof of contradiction. Finally, a problem of stochastic stabilization for discrete cellular neural networks is studied.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220861PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685627PMC
March 2020

Anemoside B4 exerts anti-cancer effect by inducing apoptosis and autophagy through inhibiton of PI3K/Akt/mTOR pathway in hepatocellular carcinoma.

Am J Transl Res 2019 15;11(4):2580-2589. Epub 2019 Apr 15.

Department of Pharmacy, Hospital 971 of The Navy of Chinese PLA Qingdao 266071, Shandong, China.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and novel therapeutic approaches are urgently required. Anemoside B4 (AB4) is a compound extracted from (). Previous studies have indicated that extract saponins has anti-cancer activity. However, the pharmacological effect of AB4 in cancer is largely unknown. In this study, we investigated the anti-cancer efficacy of AB4 in HCC. We used CCK-8 assay and colony formation assay to evaluate the cytotoxicity of AB4 and found that this agent markedly inhibited SMMC7721 cell proliferation. By using a panel of morphological and molecular experiments, we reported that AB4 induced HCC SMMC7721 cell apoptosis and autophagy. Notably, AB4 treatment acts on the Bcl-2-caspase-3 pathway and Beclin-1-LC3-p62 pathway, thereby regulates both apoptosis and autophagy. Finally, we showed that AB4-induced apoptosis and autophagy converges at the PI3K/Akt/mTOR signaling. AB4 treatment inhibits this signaling transduction pathway and leads to HCC cell death. Collectively, our study highlighted the anti-cancer efficacy of AB4 and suggested that AB4 might be a novel way to treat HCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511782PMC
April 2019

Long non-coding RNA HOTTIP promotes hypoxia-induced epithelial-mesenchymal transition of malignant glioma by regulating the miR-101/ZEB1 axis.

Biomed Pharmacother 2017 Nov 5;95:711-720. Epub 2017 Sep 5.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. Electronic address:

Hypoxia is a universal characteristic of solid tumor and involving cancer metastasis via epithelial-mesenchymal transition (EMT). Long non-coding RNAs (lncRNAs) are known to regulate carcinogenesis and metastasis of various cancers. The aim of this study was to identify the function role of lncRNAs in the hypoxia-induced EMT of malignant glioma. We used U87 and U251 cell lines were treated under hypoxia to induce EMT, then lncRNA microarray analyse was performed between U87-hypoxia and parental cell line. The relative expression of lncRNA and HIF-1α were detected by qRT-PCR between glioma tissues without metastasis and that with metastasis. Hypoxia could induce EMT and increase HOTTIP expression in glioma cells. Among the different expressions of lncRNAs, HOTTIP was the most upregulated lncRNA in glioma cells treated by hypoxia. High levels of HOTTIP and HIF-1α were correlated with glioma metastasis and poor patient prognosis. Knockdown of HIF-1α and HOTTIP blocked hypoxia-induced EMT, and suppressed invasion and migration of glioma cells. Finally, HOTTIP sponged endogenous miR-101 and inhibited its activity, which resulted in increased ZEB1 expression and promoted process of EMT. HIF-1α/HOTTIP/miR-101/ZEB1 axis plays essential role in hypoxia-induced EMT and metastasis of glioma, and HOTTIP may serve as a therapeutic target to reverse EMT and prevent glioma progression.
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http://dx.doi.org/10.1016/j.biopha.2017.08.133DOI Listing
November 2017

Simultaneous determination of ethyl carbamate and urea in alcoholic beverages by high-performance liquid chromatography coupled with fluorescence detection.

J Agric Food Chem 2014 Apr 19;62(13):2797-802. Epub 2014 Mar 19.

Key Laboratory of Industrial Fermentation Microbiology ( Tianjin University of Science and Technology ), Ministry of Education, Tianjin 300457, P. R. China.

On the basis of the similar fluorescence of ethyl carbamate (EC) and urea derivatives, a high-performance liquid chromatography method coupled with fluorescence detection was developed for the simultaneous determination of EC and urea in alcoholic beverages. The chromatographic separation and derivatization conditions of EC and urea were optimized. Under the established conditions, the detection limit, relative standard deviation, linear range, and recovery were 4.8 μg/L, 1.0-4.2%, 10-500 μg/L, and 93.8-104.6%, respectively, for EC; the corresponding values were 0.003 mg/L, 1.2-4.8%, 0.01-100 mg/L, and 90.7-104.8%, respectively, for urea. The method showed satisfactory values for precision, recovery, and sensitivity for both analytes and is well-suited for routine analysis and kinetic studies of the formation of EC from urea alcoholysis in alcoholic beverages.
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http://dx.doi.org/10.1021/jf405400yDOI Listing
April 2014

Local suppression of IL-21 in submandibular glands retards the development of Sjögren's syndrome in non-obese diabetic mice.

J Oral Pathol Med 2012 Nov 29;41(10):728-35. Epub 2012 May 29.

Shandong Provincial Key Laboratory of Oral Biomedicine, School of Stomatology, Shandong University, Jinan, China.

Background: The aim of this study was to verify the validity of IL-21 local suppression in submandibular glands of preventing the development of Sjögren's syndrome in non-obese diabetic (NOD) mice and figure out the mechanism.

Methods: IL-21 levels in submandibular glands were suppressed by ductal cannulation of IL-21 shRNA lentivirus. Then, saliva flow rates (SFR) and histopathologic changes of submandibular glands were measured to assess the severity of disease development. Real-time PCR, flow cytometry, and immunohistochemistry were used to detect the changes of T helper cells and related cytokines.

Results: The reduction in SFRs in NOD mice was significantly alleviated from 9 to 17 weeks of age along with the suppression of IL-21 in submandibular glands. Lymphocytic infiltration was also milder than control NOD mice. Moreover, the lower level of IL-21 led to the down-regulation of follicular helper T (Tfh) cells.

Conclusions: Local suppression of IL-21 in submandibular glands could retard the development of Sjögren's syndrome in NOD mice. IL-21 might contribute to the development of B-cell disorder in Sjögren's syndrome via Tfh cells pathway.
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http://dx.doi.org/10.1111/j.1600-0714.2012.01175.xDOI Listing
November 2012