Hypoxia Mediates Runt-Related Transcription Factor 2 Expression via Induction of Vascular Endothelial Growth Factor in Periodontal Ligament Stem Cells

Manjing Deng,Qian Xu,Zhihua Liu1,Ling Guo,Rui Liu,Rulei Li,Xiang Chu,Jiajia Yang,Jia Luo,Faming Chen 한국분자세포생물학회 2019 Molecules and cells Vol.42 No.11

Periodontitis is characterized by the loss of periodontal tissues, especially alveolar bone. Common therapies cannot satisfactorily recover lost alveolar bone. Periodontal ligament stem cells (PDLSCs) possess the capacity of self-renewal and multilineage differentiation and are likely to recover lost alveolar bone. In addition, periodontitis is accompanied by hypoxia, and hypoxia-inducible factor-1α (HIF-1α) is a master transcription factor in the response to hypoxia. Thus, we aimed to ascertain how hypoxia affects runt-related transcription factor 2 (RUNX2), a key osteogenic marker, in the osteogenesis of PDLSCs. In this study, we found that hypoxia enhanced the protein expression of HIF-1α, vascular endothelial growth factor (VEGF), and RUNX2 ex vivo and in situ. VEGF is a target gene of HIF-1α, and the increased expression of VEGF and RUNX2 proteins was enhanced by cobalt chloride (CoCl2, 100 μmol/L), an agonist of HIF-1α, and suppressed by 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1, 10 μmol/L), an antagonist of HIF-1α. In addition, VEGF could regulate the expression of RUNX2, as RUNX2 expression was enhanced by human VEGF (hVEGF165) and suppressed by VEGF siRNA. In addition, knocking down VEGF could decrease the expression of osteogenesis-related genes, i.e., RUNX2, alkaline phosphatase (ALP), and type I collagen (COL1), and hypoxia could enhance the expression of ALP, COL1, and osteocalcin (OCN) in the early stage of osteogenesis of PDLSCs. Taken together, our results showed that hypoxia could mediate the expression of RUNX2 in PDLSCs via HIF-1α-induced VEGF and play a positive role in the early stage of osteogenesis of PDLSCs

ATP6V0d2 Suppresses Alveoli Macrophage Alternative Polarization and Allergic Asthma via Degradation of PU.1

Liu Na,Feng Yuchen,Liu Huicheng,Wu Wenliang,Liang Yuxia,Li Pingfei,Wei Zhengping,Wu Min,Tang Zhao-Hui,Han Junyan,Cheng Xiang,Liu Zheng,Laurence Arian,Li Huabin,Zhen Guohua,Yang Xiang-Ping 대한천식알레르기학회 2021 Allergy, Asthma & Immunology Research Vol.13 No.3

Purpose Macrophages are important regulators of environmental allergen-induced airway inflammation and asthma. ATP6V0d2 is a subunit of vacuolar ATPase highly expressed in macrophages. However, the functions of ATP6V0d2 in the regulation of pathogenesis of allergic asthma remain unclear. The aim of this study is to determine the function and related molecular mechanisms of macrophage protein ATP6V0d2 in allergic asthma. Methods We compared the disease severity between female C57BL/6 wild-type and ATP6V0d2−/− mice in an ovalbumin (OVA)-induced asthma model. We also investigated the association of expression of ATP6V0d2, PU.1 and CCL17 with disease severity among asthmatic patients. Results The expression of ATP6V0d2 in sputum cells of asthmatic patients and in the lungs of OVA-challenged mice was enhanced compared to healthy subjects and their counterparts, respectively. However, ATP6V0d2-deficient mice exaggerated inflammatory cell infiltration as well as enhanced alternative activated macrophage (AAM) polarization and mucus production in an OVA-induced asthma model. Furthermore, we found that Atp6v0d2 promoted lysosomal degradation of Pu.1, which induced AAM polarization and Ccl17 production. Among asthma patients, ATP6V0d2 expression was inversely associated with disease severity, whereas PU.1 and CCL17 expression was positively associated with disease severity. Conclusions Our results identify macrophage Atp6v0d2, as an induced feedback inhibitor of asthma disease severity by promoting Pu.1 lysosomal degradation, which may in turn leads to reduced AAM polarization and Ccl17 production.

Targeting treatment of bladder cancer using PTK7 aptamer-gemcitabine conjugate

Xiang Wei,Peng Yongbo,Zeng Hongliang,Yu Chunping,Zhang Qun,Liu Biao,Liu Jiahao,Hu Xing,Wei Wensu,Deng Minhua,Wang Ning,Liu Xuewen,Xie Jianfei,Hou Weibin,Tang Jin,Long Zhi,Wang Long,Liu Jianye 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Gemcitabine (GEM) is one of the first-line chemotherapies for bladder cancer (BC), but the GEMs cannot recognize cancer cells and have a low long-term response rate and high recurrence rate with side effects during the treatment of BC. Targeted transport of GEMs to mediate cytotoxicity to tumor and avoid the systemic side effects remains a challenge in the treatment of BC.Based on a firstly confirmed biomarker in BC-protein tyrosine kinase 7 (PTK7), which is overexpressed on the cell membrane surface in BC cells, a novel targeting system protein tyrosine kinase 7 aptamer-Gemcitabine conjugate (PTK7-GEMs) was designed and synthesized using a specific PTK7 aptamer and GEM through auto-synthesis method to deliver GEM against BC. In addition, the antitumor effects and safety evaluation of PTK7-GEMs was assessed with a series of in vitro and in vivo assays.PTK7-GEMs can specifically bind and enter to BC cells dependent on the expression levels of PTK7 and via the macropinocytosis pathway, which induced cytotoxicity after GEM cleavage from PTK7-GEMs respond to the intracellular phosphatase. Moreover, PTK7-GEMs showed stronger anti-tumor efficacy and excellent biosafety in three types of tumor xenograft mice models.These results demonstrated that PTK7-GEMs is a successful targeted aptamer-drug conjugates strategy (APDCs) to treat BC, which will provide new directions for the precision treatment of BC in the field of biomarker-oriented tumor targeted therapy.

Expression and Prognostic Implications of FOXO3a and Ki67 in Lung Adenocarcinomas

Liu, Hong-Bin,Gao, Xiang-Xiang,Zhang, Qing,Liu, Jian,Cui, Yuan,Zhu, Yan,Liu, Yi-Fei Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.4

To investigate the significance of FOXO3a and Ki67 in human lung adenocarcinomas. Envision immunohistochemical staining and Western blotting were used to examine the protein expression of FOXO3a in 127 cases of human lung adenocarcinoma specimens. The positive rate in lung adenocarcinoma (55.9%) was lower than that in normal tissues (80%). We found that the expression of FOXO3a was closely related with the degree of differentiation, TNM staging, lymph node metastasis and survival. In addition, significant differences in the different pathological types of lung adenocarcinoma cases (P<0.01). The FOXO3a positive rate of the acini as the main type (APA) (86.7%) and the lepidic as the main type (LPA) (82.4%) was higher than the solid as the main type (SPA) (50.0%), the papilla as the main type (PPA) (42.9%) and the micropapilla as the main type (MPA) (9.4%). Moreover, the expression of FOXO3a was negatively related with Ki67 expression. Our results suggested that the expression of FOXO3a is closely correlated with the aggressiveness of lung adenocarcinoma. It was indicated that disregulation of FOXO3a might play key roles in the occurrence and development of lung a denocarcinoma and joint detection of the two markers might play an important role in diagnosing tumors.

A stochastic finite element method for dynamic analysis of bridge structures under moving loads

Xiang Liu,Lizhong Jiang,Ping Xiang,Zhipeng Lai,Yuntai Zhang,Lili Liu 국제구조공학회 2022 Structural Engineering and Mechanics, An Int'l Jou Vol.82 No.1

In structural engineering, the material properties of the structures such as elastic modulus, shear modulus, density, and size may not be deterministic and may vary at different locations. The dynamic response analysis of such structures may need to consider these properties as stochastic. This paper introduces a stochastic finite element method (SFEM) approach to analyze moving loads problems. Firstly, Karhunen-Loéve expansion (KLE) is applied for expressing the stochastic field of material properties. Then the mathematical expression of the random field is substituted into the finite element model to formulate the corresponding random matrix. Finally, the statistical moment of the dynamic response is calculated by the point estimation method (PEM). The accuracy and efficiency of the dynamic response obtained from the KLE-PEM are demonstrated by the example of a moving load passing through a simply supported Euler-Bernoulli beam, in which the material properties (including elastic modulus and density) are considered as random fields. The results from the KLE-PEM are compared with those from the Monte Carlo simulation. The results demonstrate that the proposed method of KLE-PEM has high accuracy and efficiency. By using the proposed SFEM, the random vertical deflection of a high-speed railway (HSR) bridge is analyzed by considering the random fields of material properties under the moving load of a train.

Electrospun porous lithium manganese phosphate-carbon nanofibers as a cathode material for lithium ion batteries

Liu, L.,Song, T.,Han, H.,Park, H.,Xiang, J.,Liu, Z.,Feng, Y.,Paik, U. Royal Society of Chemistry 2015 Journal of Materials Chemistry A Vol.3 No.34

Silencing of Rac3 Inhibits Proliferation and Induces Apoptosis of Human Lung Cancer Cells

Liu, Tie-Qin,Wang, Ge-Bang,Li, Zheng-Jun,Tong, Xiang-Dong,Liu, Hong-Xu Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.7

Background: Rac3, a member of the Rac family of small guanosine triphosphatases (GTPases), regulates a variety of cell functions, including the organization of the cytoskeleton, cell migration, and invasion. Overexpression of Rac3 has been reported in several human cancers. However, the role of Rac3 in lung cancer (LC) has not been determined in detail. The purpose of this study was to investigate the effect of silencing of Rac3 expression in human LC cells and the consequences for cell survival. Materials and Methods: Lentivirus small hairpin RNA (shRNA) interference techniques were utilized to knock down the Rac3 gene. Gene and protein expression was quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. LC cell apoptosis was examined by annexin V-APC /propidium iodide staining. Results: Efficient silencing of Rac3 strongly inhibited A549 cell proliferation and colony formation ability, and significantly decreased tumor growth. Moreover, flow cytometry analysis showed that knockdown of Rac3 led to G2/M phase cell cycle arrest as well as an excess accumulation of cells in the G1 and S phase. Conclusions: Thus, functional analysis using shRNAs revealed a critical role for Rac3 in the tumor growth of LC cells. shRNA silencing of Rac3 could provide an effective strategy to treat LC.

MTHFR C677T Polymorphism and Pancreatic Cancer Risk: a Meta-analysis

Liu, Xiang-Ming,Liu, Feng-Hua,Tang, Yong,Li, Qiang Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.8

Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, and the role of the MTHFR C677T polymorphism in pancreatic carcinogenesis is still controversial. Methods: A literature search was performed using Pubmed and CNKI databases for published studies through May 2012. We performed a meta-analysis of all relevant case-control studies that examined the association between MTHFR C677T polymorphism and pancreatic cancer risk. Results: Finally, 9 individual case-control studies with a total of 1,299 pancreatic cancer cases and 2,473 controls were included into this meta-analysis. Results: This metaanalysis showed there was an obvious association between MTHFR C677T polymorphism and pancreatic cancer risk in East Asians (for allele model, OR = 1.67, 95%CI 1.11-2.51; For homozygote model, OR = 2.77, 95%CI 1.40-5.48; for recessive model, OR = 1.96, 95%CI 1.54-2.50; for dominant model, OR = 2.11, 95%CI 1.01-4.41). However, no significant association was found in Caucasians. Conclusions: The MTHFR C677T polymorphism is associated with pancreatic cancer risk, and a race-specific effect may exist in this association. More studies with a larger sample size are needed to further clarify this association.

MicroRNA Expression Profile Analysis Reveals Diagnostic Biomarker for Human Prostate Cancer

Liu, Dong-Fu,Wu, Ji-Tao,Wang, Jian-Ming,Liu, Qing-Zuo,Gao, Zhen-Li,Liu, Yun-Xiang Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

Prostate cancer is a highly prevalent disease in older men of the western world. MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression via posttranscriptional inhibition of protein synthesis. To identify the diagnostic potential of miRNAs in prostate cancer, we downloaded the miRNA expression profile of prostate cancer from the GEO database and analysed the differentially expressed miRNAs (DE-miRNAs) in prostate cancerous tissue compared to non-cancerous tissue. Then, the targets of these DE-miRNAs were extracted from the database and mapped to the STRING and KEGG databases for network construction and pathway enrichment analysis. We identified a total of 16 miRNAs that showed a significant differential expression in cancer samples. A total of 9 target genes corresponding to 3 DE-miRNAs were obtained. After network and pathway enrichment analysis, we finally demonstrated that miR-20 appears to play an important role in the regulation of prostate cancer onset. MiR-20 as single biomarker or in combination could be useful in the diagnosis of prostate cancer. We anticipate our study could provide the groundwork for further experiments.

Chemotherapy and Late Course Three Dimensional Conformal Radiotherapy for Treatment of Patients with Stage III Non-small Cell Lung Cancer

Liu, Yang-Chen,Zhou, Shao-Bing,Gao, Fei,Ye, Hong-Xun,Zhao, Ying,Yi, Xiao-Xiang,Huang, Xin-En,Xiang, Jin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

Objective: To compare the efficacy and complications of chemotherapy and late course three-dimensional conformal radiotherapy (3DCRT) in treating patients with stage III non-small cell lung cancer (NSCLC). Patients and Methods: All patients were divided into two groups: to receive chemotherapy and late course 3DCRT (3DCRT group), or chemotherapy and conventional fraction radiation (control group). In the 3DCRT-group, patients were given 6~15 MV X-rays with a total dose of 40 Gy, followed by 3DCRT, 2.5 Gy~3.0 Gy per fraction, 1 fraction/every day, total 68 Gy~70 Gy; in the control group, with conventional fraction radiation the total dose was 64~66 Gy. The chemotherapy regimen in both cases was EP (VP-16 and DDP). Results: Sixty four patients with stage III NSCLC were divided into two groups: 32 patients into 3DCRT, 32 into the control group. One and 2-year survival rates in 3DCRT and control group were 87.5%, 56.3%mad 65.6%, 34.4%, respectively (P<0.05); local control rates were 90.6%, 81.3% and 65.6%, 53.1%, respectively (P<0.05). Conclusion: Chemotherapy and late course 3DCRT is associated with improved survival rate in patients with stage III NSCLC with good tolerability.