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      • KCI등재

        Phosphodiesterase 4D contributes to angiotensin II-induced abdominal aortic aneurysm through smooth muscle cell apoptosis

        Gao Ran,Guo Wenjun,Fan Tianfei,Pang Junling,Hou Yangfeng,Feng Xiaohang,Li Bolun,Ge Weipeng,Fan Tianhui,Zhang Tiantian,Lu Jiakai,Jing He,Jin Mu,Yan Chen,Wang Jing 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

        Abdominal aortic aneurysm (AAA) is a permanent expansion of the abdominal aorta that has a high mortality but limited treatment options. Phosphodiesterase (PDE) 4 family members are cAMP-specific hydrolyzing enzymes and have four isoforms (PDE4A-PDE4D). Several pan-PDE4 inhibitors are used clinically. However, the regulation and function of PDE4 in AAA remain largely unknown. Herein, we showed that PDE4D expression is upregulated in human and angiotensin II-induced mouse AAA tissues using RT-PCR, western blotting, and immunohistochemical staining. Furthermore, smooth muscle cell (SMC)-specific Pde4d knockout mice showed significantly reduced vascular destabilization and AAA development in an experimental AAA model. The PDE4 inhibitor rolipram also suppressed vascular pathogenesis and AAA formation in mice. In addition, PDE4D deficiency inhibited caspase 3 cleavage and SMC apoptosis in vivo and in vitro, as shown by bulk RNA-seq, western blotting, flow cytometry and TUNEL staining. Mechanistic studies revealed that PDE4D promotes apoptosis by suppressing the activation of cAMP-activated protein kinase A (PKA) instead of the exchange protein directly activated by cAMP (Epac). Additionally, the phosphorylation of BCL2-antagonist of cell death (Bad) was reversed by PDE4D siRNA in vitro, which indicates that PDE4D regulates SMC apoptosis via the cAMP-PKA-pBad axis. Overall, these findings indicate that PDE4D upregulation in SMCs plays a causative role in AAA development and suggest that pharmacological inhibition of PDE4 may represent a potential therapeutic strategy.

      • SCIESCOPUS

        Withanone-Rich Combination of Ashwagandha Withanolides Restricts Metastasis and Angiogenesis through hnRNP-K

        Gao, Ran,Shah, Navjot,Lee, Jung-Sun,Katiyar, Shashank P.,Li, Ling,Oh, Eonju,Sundar, Durai,Yun, Chae-Ok,Wadhwa, Renu,Kaul, Sunil C. American Association for Cancer Research 2014 Molecular Cancer Therapeutics Vol.13 No.12

        <P>Ashwagandha is an important herb used in the Indian system of traditional home medicine, Ayurveda. Alcoholic extract (i-Extract) from its leaves and its component, withanone, were previously shown to possess anticancer activity. In the present study, we developed a combination of withanone and withaferin A, major withanolides in the i-Extract, that retained the selective cancer cell killing activity and found that it also has significant antimigratory, -invasive, and -angiogenic activities, in both <I>in vitro</I> and <I>in vivo</I> assays. Using bioinformatics and biochemical approaches, we demonstrate that these phytochemicals caused downregulation of migration-promoting proteins hnRNP-K, VEGF, and metalloproteases and hence are candidate natural drugs for metastatic cancer therapy. <I>Mol Cancer Ther; 13(12); 2930–40. ©2014 AACR</I>.</P>

      • Higher order plate theory for buckling analysis of plates based on exact solution

        Ran Bi,Jun Gao,Seyedmahmoodreza Allahyari 국제구조공학회 2021 Steel and Composite Structures, An International J Vol.40 No.3

        In this paper, buckling analyses of composite plate reinforced by Graphen platelate (GPL) is studied. The Halphin-Tsai model is used for obtaining the effective material properties of nano composite plate. The nano composite plate is modeled by Third order shear deformation theory (TSDT). The elastic medium is simulated by Winkler model. Employing nonlinear strains-displacements, stress-strain, the energy equations of plate are obtained and using Hamilton's principal, the governing equations are derived. The governing equations are solved based on Navier method. The effect of GPL volume percent, geometrical parameters of plate and elastic foundation on the buckling load are investigated. Results showed that with increasing GPLs volume percent, the buckling load increases.

      • Association Between the Pre-mir-218 Polymorphism and Cancer Risk in the Chinese Population: a Meta-Analysis

        Gao, Yue,Liu, Yan,Liu, Ge-Li,Ran, Long-Ke,Zeng, Fan,Wu, Jia-Yan,Song, Fang-Zhou Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6

        Background: Several recent studies have explored associations between pre-mir-218 polymorphism (rs11134527) and cancer risk. However, published data are still inconclusive. To obtain a more precise estimation of the relationship in the Chinese population, we carried out a meta-analysis for the first time. Materials and Methods: Through retrieval from the PubMed, Medline, Embase, Web of Science databases, China National Knowledge Infrastructure and the Chinese BioMedical Literature Database, a total of four studies were analyzed with 3,561 cases and 3,628 controls for SNP pre-mir-218 rs11134527. We calculated odds ratios (ORs) and 95% confidence intervals (95%CIs) to explore the strength of associations. Results: The results showed that the rs11134527 polymorphism was associated with decreased cancer risk in GG versus AA and GG versus AA+AG models tested ( GG vs AA: OR=0.82, 95%CI: 0.71-0.94; GG vs AA+AG: OR=0.84, 95%CI: 0.74-0.96), and significantly decreased cervical cancer risk was observed in GG versus AA and GG versus AA+AG models (GG vs AA: OR=0.79, 95%CI: 0.66-0.94; GG vs AA+AG: OR=0.80, 95%CI: 0.68-0.94). However, no significant association between the rs11134527polymorphism and hepatocellular carcinoma risk was observed in all comparison models tested (AG vs AA: OR=0.94, 95%CI: 0.79-1.11; GG vs AA: OR=0.88, 95%CI: 0.70-1.10; GG+AG vs AA: OR=0.92, 95%CI: 0.79-1.08; GG vs AA+AG: OR=0.91, 95%CI: 0.75-1.11). Conclusion: The findings suggest that pre-miR-218 rs11134527 polymorphism may have some relation to cancer development in Chinese. However, well-designed studies with larger sample size and more detailed data are needed to confirm these conclusions.

      • KCI등재

        Characteristics and significance of heterogeneity of sea−land transitional facies shale gas reservoir in North Guizhou, China

        Ran Wang,Shuxun Sang,Jun Jin,Lingyun Zhao,Wei Gao,Wei Fu,Fulun Shi,Ende Deng 한국지질과학협의회 2019 Geosciences Journal Vol.23 No.1

        In order to identify the characteristics of the longitudinal heterogeneity of the sea–land transitional facies shale gas reservoir in the upper Yangtze region of North Guizhou, studies on the lithological combination, rock and mineral composition, geochemical parameters and reservoir microanisotropy characteristics of Longtan Formation in the study area are conducted on the basis of core observation, testing of geochemistry and reservoir physical property and well logging interpretation. The studies show that the lithological assemblages of the Longtan Formation are diverse and form an amina interbedding of “sand-mud-coal” with obvious cyclicity characteristics. There is a large longitudinal difference in rock and mineral composition and the average mass fraction of the clay mineral is 39.83%, which is obviously higher than that of the marine shale in North America and South China; the longitudinal heterogeneity of the organic matter abundance is high, with an average of 2.17% in the upper part, and 4.51% in the lower part; in accordance with the results observed with the scanning electron microscope and results calculated through pore fractal, the microscopic pore heterogeneity of the reservoir is high. The comparison and analysis of connecting wells with different scales in the study area show that the control effect of the depositional environment on longitudinal macroscopic heterogeneity of Longtan Formation is obvious, and the longitudinal microscopic heterogeneity is controlled through diagenesis. Meanwhile, studies with main coal mining seam as the seam section division method conclude that the heterogeneity of Coal Seam Sections 4 to 5 and Coal Seam Sections 13 to 15 is significantly smaller than that in other seam sections, and the Coal Seam Sections 4 to 5 and Coal Seam Sections 13 to 15 can be considered as a priority key seam section during development of shale gas.

      • KCI등재

        Subcutaneous Streptococcus dysgalactiae GAPDH vaccine in mice induces a proficient innate immune response

        Ran An,Yongli Guo,Mingchun Gao,Junwei Wang 대한수의학회 2023 Journal of Veterinary Science Vol.24 No.5

        Background: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) on the surface of Streptococcus dysgalactiae, coded with gapC, is a glycolytic enzyme that was reported to be a moonlighting protein and virulence factor. Objective: This study assessed GAPDH as a potential immunization candidate protein to prevent streptococcus infections. Methods: Mice were vaccinated subcutaneously with recombinant GAPDH and challenged with S. dysgalactiae in vivo. They were then evaluated using histological methods. rGAPDH of mouse bone marrow-derived dendritic cells (BMDCs) was evaluated using immunoblotting, reverse transcription quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay methods. Results: Vaccination with rGAPDH improved the survival rates and decreased the bacterial burdens in the mammary glands compared to the control group. The mechanism by which rGAPDH vaccination protects against S. dysgalactiae was investigated. In vitro experiments showed that rGAPDH boosted the generation of interleukin-10 and tumor necrosis factor-α. Treatment of BMDCs with TAK-242, a toll-like receptor 4 inhibitor, or C29, a toll-like receptor 2 inhibitor, reduced cytokines substantially, suggesting that rGAPDH may be a potential ligand for both TLR2 and TLR4. Subsequent investigations showed that rGAPDH may activate the phosphorylation of MAPKs and nuclear factor-κB. Conclusions: GAPDH is a promising immunization candidate protein for targeting virulence and enhancing immune-mediated protection. Further investigations are warranted to understand the mechanisms underlying the activation of BMDCs by rGAPDH in a TLR2- and TLR4-dependent manner and the regulation of inflammatory cytokines contributing to mastitis pathogenesis.

      • SCIESCOPUSKCI등재

        Construction of Mammalian Cell Expression Vector for pAcGFP-bFLIP(L) Fusion Protein and Its Expression in Follicular Granulosa Cells

        Yang, Run Jun,Li, Wu Feng,Li, Jun Ya,Zhang, Lu Pei,Gao, Xue,Chen, Jin Bao,Xu, Shang Zhong Asian Australasian Association of Animal Productio 2010 Animal Bioscience Vol.23 No.3

        FLICE inhibitory protein (FLIP) is one of the important anti-apoptotic proteins in the Fas/FasL apoptotic path which has death effect domains, mimicking the pro-domain of procaspase-8. To reveal the intracellular signal transduction molecules involved in the process of follicular development in the bovine ovary, we cloned the c-FLIP(L) gene in bovine ovary tissue with the reverse transcription polymerase chain reaction (RT-PCR), deleted the termination codon in its cDNA, and directionally cloned the amplified c-FLIP(L) gene into eukaryotic expression vector pAcGFP-Nl, including AcGFP, and successfully constructed the fusion protein recombinant plasmid. After identifying by restrictive enzyme BglII/EcoRI and sequencing, pAcGFP-bFLIP(L) was then transfected into follicular granulosa cells, mediated by Lipofectamine 2000, the expression of AcGFP observed and the transcription and expression of c-FLIP(L) detected by RT-PCR and Western blot. The results showed that the cattle c-FLIP(L) was successfully cloned; the pAcGFPbFLIP(L) fusion protein recombinant plasmid was successfuly constructed by introducing a BglII/EcoRI cloning site at the two ends of the c-FLIP(L) open reading frame and inserting a Kozak sequence before the start codon. AcGFP expression was detected as early as 24 h after transfection. The percentage of AcGFP positive cells reached about 65% after 24 h. A 1,483 bp transcription was amplified by RT-PCR, and a 83 kD target protein was detected by Western blot. Construction of the pAcGFP-bFLIP(L) recombinant plasmid should be helpful for further understanding the mechanism of regulation of c-FLIP(L) on bovine oocyte formation and development.

      • Community Life Sport Evaluation Based on C4.5and Improved DRNN

        Fei Gao,RanLi 보안공학연구지원센터 2014 International Journal of Database Theory and Appli Vol.7 No.6

        With the development of our national sport consciousness, sports are a more and more important role in people's daily life. Community sports have been adopted by more and more people. But due to historical and economic reasons, community sport level in China is quite low. How to conduct an evaluation of the community life sport, not only is the community residents request, but also an important means to make corresponding improvement for a city builder. However, due to the mathematical algorithm has high complexity for the general case, applicants to environmental assessment is difficult, In this paper, introduce the C4.5 and improved DRNN as machine learning methods, and data mining the existing community life sport, to construct the evaluate model of community life sport , Not only can make up for the algorithm less shortcoming of current community sport research, but also can get the objective conclusion, to evaluate the mechanism of factors, and to give counsel for the development of community sport.

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