Small Molecule-Based Strategy Promotes Nucleus Pulposus Specific Differentiation of Adipose-Derived Mesenchymal Stem Cells

Hua, Jianming,Shen, Ning,Wang, Jingkai,Tao, Yiqing,Li, Fangcai,Chen, Qixin,Zhou, Xiaopeng Korean Society for Molecular and Cellular Biology 2019 Molecules and cells Vol.42 No.9

Adipose tissue-derived mesenchymal stem cells (ADSCs) are promising for regenerating degenerated intervertebral discs (IVDs), but the low efficiency of nucleus pulposus (NP)-specific differentiation limits their clinical applications. The Sonic hedgehog (Shh) signaling pathway is important in NP-specific differentiation of ADSCs, and Smoothened Agonist (SAG) is a highly specific and effective agonist of Shh signaling. In this study, we proposed a new differentiation strategy with the use of the small molecule SAG. The NP-specific differentiation and extracellular matrix (ECM) synthesis of ADSCs were measured in vitro, and the regenerative effects of SAG pretreated ADSCs in degenerated IVDs were verified in vivo. The results showed that the combination of SAG and transforming growth factor-${\beta}3$ ($TGF-{\beta}3$) is able to increase the ECM synthesis of ADSCs. In addition, the gene and protein expression levels of NP-specific markers were increased by treatment with SAG and $TGF-{\beta}3$. Furthermore, SAG pretreated ADSCs can also improve the disc height, water content, ECM content, and structure of degenerated IVDs in vivo. Our new differentiation scheme has high efficiency in inducing NP-specific differentiation of ADSCs and is promising for stem cell-based treatment of degenerated IVDs.

Associations of Plasma Glucagon Levels with Estimated Glomerular Filtration Rate, Albuminuria and Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus

Hua-Xing Huang,Liang-Lan Shen,Hai-Yan Huang,Li-Hua Zhao,Feng Xu,Dong-Mei Zhang,Xiu-Lin Zhang,Tong Chen,Xue-Qin Wang,Yan Xie,Jian-Bin Su 대한당뇨병학회 2021 Diabetes and Metabolism Journal Vol.45 No.6

Background: Type 2 diabetes mellitus (T2DM) is characterized by elevated fasting glucagon and impaired suppression of postprandial glucagon secretion, which may participate in diabetic complications. Therefore, we investigated the associations of plasma glucagon with estimated glomerular filtration rate (eGFR), albuminuria and diabetic kidney disease (DKD) in T2DM patients.Methods: Fasting glucagon and postchallenge glucagon (assessed by area under the glucagon curve [AUCgla]) levels were determined during oral glucose tolerance tests. Patients with an eGFR <60 mL/min/1.73 m2 and/or a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g who presented with diabetic retinopathy were identified as having DKD.Results: Of the 2,436 recruited patients, fasting glucagon was correlated with eGFR and UACR (r=–0.112 and r=0.157, respectively; P<0.001), and AUCgla was also correlated with eGFR and UACR (r=–0.267 and r=0.234, respectively; P<0.001). Moreover, 31.7% (n=771) presented with DKD; the prevalence of DKD was 27.3%, 27.6%, 32.5%, and 39.2% in the first (Q1), second (Q2), third (Q3), and fourth quartile (Q4) of fasting glucagon, respectively; and the corresponding prevalence for AUCgla was 25.9%, 22.7%, 33.7%, and 44.4%, respectively. Furthermore, after adjusting for other clinical covariates, the adjusted odds ratios (ORs; 95% confidence intervals) for DKD in Q2, Q3, and Q4 versus Q1 of fasting glucagon were 0.946 (0.697 to 1.284), 1.209 (0.895 to 1.634), and 1.521 (1.129 to 2.049), respectively; the corresponding ORs of AUCgla were 0.825 (0.611 to 1.114), 1.323 (0.989 to 1.769), and 2.066 (1.546 to 2.760), respectively. Additionally, when we restricted our analysis in patients with glycosylated hemoglobin <7.0% (n=471), we found fasting glucagon and AUCgla were still independently associated with DKD.Conclusion: Both increased fasting and postchallenge glucagon levels were independently associated with DKD in T2DM patients.

SET8 suppression mediates high glucose-induced vascular endothelial inflammation via the upregulation of PTEN

Shen Xuefang,Chen Xiangyuan,Wang Jing,Liu Jing,Wang Zhiyao,Hua Qing,Wu Qichao,Su Yanguang,He Huanzhong,Hu Yuqin,Meng Zhipeng,Xiong Wanxia,Zhu Minmin 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

Hyperglycemia-mediated endothelial inflammation participates in the pathogenesis of cardiovascular complications in subjects with diabetes. Previous studies reported that phosphatase and tensin homolog deleted on chromosome ten (PTEN) and SET8 participate in high glucose-mediated endothelial inflammation. In this study, we hypothesize that SET8 regulates PTEN expression, thus contributing to high glucose-mediated vascular endothelial inflammation. Our data indicated that plasma soluble intercellular adhesion molecule-1 (sICAM-1) and endothelial selectin (e-selectin) were increased in patients with diabetes and diabetic rats. PTEN expression was augmented in the peripheral blood mononuclear cells of patients with diabetes and in the aortic tissues of diabetic rats. Our in vitro study indicated that high glucose increased monocyte/endothelial adhesion, endothelial adhesion molecule expression and p65 phosphorylation in human umbilical vein endothelial cells (HUVECs). Moreover, high glucose led to endothelial inflammation via upregulation of PTEN. Furthermore, high glucose inhibited SET8 expression and histone H4 lysine 20 methylation (H4K20me1), a downstream target of SET8. SET8 overexpression reversed the effects of high-glucose treatment. shSET8-mediated endothelial inflammation was counteracted by siPTEN. Furthermore, SET8 was found to interact with FOXO1. siFOXO1 attenuated high glucose-mediated endothelial inflammation. FOXO1 overexpression-mediated endothelial inflammation was counteracted by siPTEN. H4K20me1 and FOXO1 were enriched in the PTEN promoter region. shSET8 increased PTEN promoter activity and augmented the positive effect of FOXO1 overexpression on PTEN promoter activity. Our in vivo study indicated that SET8 was downregulated and FOXO1 was upregulated in the peripheral blood mononuclear cells of patients with diabetes and the aortic tissues of diabetic rats. In conclusion, SET8 interacted with FOXO1 to modulate PTEN expression in vascular endothelial cells, thus contributing to hyperglycemia-mediated endothelial inflammation.

Effects of pores and temperature on mechanics of gold nanowires using molecular dynamics

Shen-Yung Lin,Tong Hong Wangs,Te-Hua Fang,Wen-Li Chen 한국물리학회 2010 Current Applied Physics Vol.10 No.1

The deformation mechanisms of gold nanowires with different nanopores under tension were simulated by molecular dynamics (MD). The stress–strain curves varied from different porous defects, and the tension caused dislocations to take place and slip along plane (1 1 1). Moreover, the tensile strength of the nanoporous monocrystalline gold was decreased when the simulated temperature increased. The stress concentrations factors of porous nanowires were calculated, and it was found that there was a great influence of size and model effects on the stress concentration factors.

Cervical Cancer Screening and Analysis of Potential Risk Factors in 43,567 Women in Zhongshan, China

Wang, Ying,Yu, Yan-Hong,Shen, Keng,Xiao, Lin,Luan, Feng,Mi, Xian-Jun,Zhang, Xiao-Min,Fu, Li-Hua,Chen, Ang,Huang, Xiang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2

Objective: The objective of this study was to establish a program model for use in wide-spread cervical cancer screening. :Methods: Cervical cancer screening was conducted in Zhongshan city in Guangdong province, China through a coordinated network of multiple institutes and hospitals. A total of 43,567 women, 35 to 59 years of age, were screened during regular gynecological examinations using the liquid-based ThinPrep cytology test (TCT). Patients who tested positive were recalled for further treatment. Results: The TCT-positive rate was 3.17%, and 63.4% of these patients returned for follow-up. Pathology results were positive for 30.5% of the recalled women. Women who were younger than 50 years of age, urban dwelling, low-income, had a history of cervical disease, began having sex before 20 years of age, or had sex during menstruation, were at elevated risk for a positive TCT test. The recall rate was lower in women older than 50 years of age, urban dwelling, poorly educated, and who began having sex early. Ahigher recall rate was found in women 35 years of age and younger, urban dwelling, women who first had sex after 24 years of age, and women who had sex during menstruation. The positive pathology rate was higher in urban women 50 years of age and younger and women who tested positive for human papillomavirus. Conclusion: An effective model for large-scale cervical cancer screening was successfully established. These results suggest that improvements are needed in basic education regarding cervical cancer screening for young and poorly educated women. Improved outreach for follow-up is also necessary to effectively control cervical cancer.

Aldol condensation of acetic acid with formaldehyde to acrylic acid over SiO2-, SBA-15-, and HZSM-5-supported V-P-O catalysts

Jing Hua,Zhipeng Lu,Hengbo Yin,Wuping Xue,Aili Wang,Lingqin Shen,Shuxin Liu 한국공업화학회 2016 Journal of Industrial and Engineering Chemistry Vol.40 No.-

Aldol condensation of acetic acid with formaldehyde to acrylic acid was catalyzed by the SiO2-, SBA-15-,and HZSM-5-supported vanadium phosphorous oxide (V-P-O) catalysts prepared by the incipientwetness impregnation. The supports obviously increased the surface areas and changed the acid–baseproperties of the as-prepared catalysts. V-P-O/SBA-15 catalysts with high acid and alkali quantitiesexhibited high catalytic activities for the aldol condensation of acetic acid with formaldehyde to acrylicacid. When the V-P-O/SBA-15 catalyst with the P/V mole ratio of 2.0:1 catalyzed the reaction at 330–370 8C, the acrylic acid selectivities were 90.8–70.2% at the formaldehyde conversions of 14.3–68.7%.

Low Carbon Concrete Prepared with Scattering-Filling Coarse Aggregate Process

Weiguo Shen,Chuan Zhang,Xinling Li,Hua Shi,Guiming Wang,Xiaowu Tian 한국콘크리트학회 2014 International Journal of Concrete Structures and M Vol.8 No.4

The volume fraction of the coarse aggregate in the conventional plastic concrete is controlled relatively low to ensure a required workability. In this paper, a new type of coarse aggregate interlocking concrete with strength ranging from C30 to C80 was prepared with scattering-filling aggregate process. The strength of concrete prepared with this method increases obviously whereas the shrinkage decreases significantly, the cement dosage in the concrete decreased 20 % at the same time. The microhardness of the ITZ between the cement paste and scattering-filling aggregate is higher than that of the original aggregate, the ITZ become narrower and tighter also. The interlocking and more even distribution of the coarse aggregate and the water absorption of the addition of extra amount of coarse aggregates contribute to the strength and performance improvement of the concrete prepared with scattering-filling aggregate process.

Small Molecule-Based Strategy Promotes Nucleus Pulposus Specific Differentiation of Adipose-Derived Mesenchymal Stem Cells

Jianming Hua,Ning Shen,Jingkai Wang,Yiqing Tao,Fangcai Li,Qixin Chen,Xiaopeng Zhou 한국분자세포생물학회 2019 Molecules and cells Vol.42 No.9

Adipose tissue-derived mesenchymal stem cells (ADSCs) are promising for regenerating degenerated intervertebral discs (IVDs), but the low efficiency of nucleus pulposus (NP)-specific differentiation limits their clinical applications. The Sonic hedgehog (Shh) signaling pathway is important in NP-specific differentiation of ADSCs, and Smoothened Agonist (SAG) is a highly specific and effective agonist of Shh signaling. In this study, we proposed a new differentiation strategy with the use of the small molecule SAG. The NP-specific differentiation and extracellular matrix (ECM) synthesis of ADSCs were measured in vitro, and the regenerative effects of SAG pretreated ADSCs in degenerated IVDs were verified in vivo. The results showed that the combination of SAG and transforming growth factor-β3 (TGF-β3) is able to increase the ECM synthesis of ADSCs. In addition, the gene and protein expression levels of NP-specific markers were increased by treatment with SAG and TGF-β3. Furthermore, SAG pretreated ADSCs can also improve the disc height, water content, ECM content, and structure of degenerated IVDs in vivo. Our new differentiation scheme has high efficiency in inducing NP-specific differentiation of ADSCs and is promising for stem cell-based treatment of degenerated IVDs.

Test and Analysis on the Interference to the CBTC Systems by Wi-Fi Signals

Li Ming,Wang Hua-shen,Zhao Hong-li,Zhu Li 보안공학연구지원센터 2015 International Journal of u- and e- Service, Scienc Vol.8 No.3

Communication-Based Train Control (CBTC) system is an automated train control system using bidirectional train-ground communications to ensure the safe operation of rail vehicles. The interference from Wi-Fi signals to the CBTC signals has significant impacts on the train control performance. Most of previous works use data from simulation platform. This paper proposes a method to test the Wi-Fi interference to the Communication Based Train Control(CBTC) systems. The test is made mainly based on real subway, and supplemented by laboratory simulation platform. The collected data is to be compared and analyzed. The test result shows that the signal transmission mode of waveguide is the most reliable, followed by the leaky cable. The transmission mode of free wave has the worst anti-interference capability to Wi-Fi signals. This is because that both the waveguide and leaky cable transmission have a better encapsulation compared with the free space transmission. Also applying for specific bands can effectively reduce the interference transferred from Wi-Fi signals to the CBTC.

Prognostic Significance of Tumor Mutation Burden among Patients with Non-small Cell Lung Cancer Who Received Platinum-based Adjuvant Chemotherapy: An Exploratory Study

Wei-Xi Shen,Guang-Hua Li,Yu-Jia Li,Peng-Fei Zhang,Jia-Xing Yu,Di Shang,Qiu-Shi Wang 대한암예방학회 2023 Journal of cancer prevention Vol.28 No.4

This study aimed to investigate the prognostic significance of tumor mutation burden (TMB) among patients with non-small cell lung cancer (NSCLC) who received platinum-based adjuvant chemotherapy. Tumor tissue specimens after surgical resection were collected for DNA extraction. Somatic mutation detection and TMB analysis were conducted using next-generation sequencing (NGS). Recurrence status of the patients was assessed in the hospital during the adjuvant chemotherapy period, and long-term survival data of patients were obtained by telephone follow-up. Univariate analysis between TMB status and prognosis was carried out by survival analysis. A retrospective review of 78 patients with non-squamous NSCLC who received platinum-based adjuvant chemotherapy showed a median disease-free survival of 3.6 years and median overall survival (OS) of 5.3 years. NGS analysis exhibited that the most common mutated somatic genes among the 78 patients were tumor suppressor protein p53 (TP53), epidermal growth factor receptor, low-density lipoprotein receptor related protein 1B, DNA methyltransferase 3 alpha and FAT atypical cadherin 3, and their prevalence was 56.4%, 48.7%, 37.2%, 30.7%, and 25.6%, respectively. TMB status was divided into TMB-L (≤ 4.5/Mb) and TMB-H (> 4.5/Mb) based on the median TMB threshold. Relevance of TMB to prognosis suggested that the median OS of patients with TMB-L was significantly longer than that of patients with TMB-H (NR vs. 4.6, P = 0.014). Higher TMB status conferred a worse implication on OS among patients with non-squamous NSCLC who received platinum-based adjuvant chemotherapy.