Glia maturation factor beta deficiency protects against diabetic osteoporosis by suppressing osteoclast hyperactivity

Shi Si,Gu Huijie,Xu Jinyuan,Sun Wan,Liu Caiyin,Zhu Tong,Wang Juan,Gao Furong,Zhang Jieping,Ou Qingjian,Jin Caixia,Xu Jingying,Chen Hao,Li Jiao,Xu Guotong,Tian Haibin,Lu Lixia 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Excessive osteoclast activation, which depends on dramatic changes in actin dynamics, causes osteoporosis (OP). The molecular mechanism of osteoclast activation in OP related to type 1 diabetes (T1D) remains unclear. Glia maturation factor beta (GMFB) is considered a growth and differentiation factor for both glia and neurons. Here, we demonstrated that Gmfb deficiency effectively ameliorated the phenotype of T1D-OP in rats by inhibiting osteoclast hyperactivity. In vitro assays showed that GMFB participated in osteoclast activation rather than proliferation. Gmfb deficiency did not affect osteoclast sealing zone (SZ) formation but effectively decreased the SZ area by decreasing actin depolymerization. When GMFB was overexpressed in Gmfb-deficient osteoclasts, the size of the SZ area was enlarged in a dose-dependent manner. Moreover, decreased actin depolymerization led to a decrease in nuclear G-actin, which activated MKL1/SRF-dependent gene transcription. We found that pro-osteoclastogenic factors (Mmp9 and Mmp14) were downregulated, while anti-osteoclastogenic factors (Cftr and Fhl2) were upregulated in Gmfb KO osteoclasts. A GMFB inhibitor, DS-30, targeting the binding site of GMFB and Arp2/3, was obtained. Biocore analysis revealed a high affinity between DS-30 and GMFB in a dose-dependent manner. As expected, DS-30 strongly suppressed osteoclast hyperactivity in vivo and in vitro. In conclusion, our work identified a new therapeutic strategy for T1D-OP treatment. The discovery of GMFB inhibitors will contribute to translational research on T1D-OP.

MicroRNA-27a Inhibits Cell Migration and Invasion of Fibroblast-Like Synoviocytes by Targeting Follistatin-Like Protein 1 in Rheumatoid Arthritis

Shi, Dong-liang,Shi, Gui-rong,Xie, Jing,Du, Xu-zhao,Yang, Hao Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.8

Fibroblast-like synoviocytes (FLS) with aberrant expression of microRNA (miRNA) are critical pathogenic regulators in rheumatoid arthritis (RA). Previous studies have found that overexpression or silencing of miRNA can contribute to the development of miRNA-based therapeutics in arthritis models. In this study, we explored the effects of miR-27a on cell migration and invasion in cultured FLS from RA patients. We found that miR-27a was markedly downregulated in the serum, synovial tissue, and FLS of RA patients. Meanwhile, the expression of follistatin-like protein 1 (FSTL1) was upregulated, which suggests that FSTL1 plays a key role in RA development. The results of a Transwell assay showed that miR-27a inhibited FLS migration and invasion. However, miR-27a inhibition promoted the migration and invasion of FLS. In addition, the down-regulated expression of matrix metalloproteinases (MMP2, MMP9, and MMP13) and Rho family proteins (Rac1, Cdc42, and RhoA) was detected after treatment with miR-27a in RA-FLS by quantitative reverse transcription-PCR and western blot analysis. Then, a luciferase reporter assay validated that miR-27a targeted the 3-untranslated region (3'-UTR) of FSTL1. Moreover, miR-27a caused a significant decrease of FSTL1. In addition, the expression of TLR4 and $NF{\kappa}B$ was inhibited by miR-27a but increased by FSTL1 overexpression. In conclusion, we found that miR-27a inhibited cell migration and invasion of RA-FLS by targeting FSTL1 and restraining the $TLR4/NF{\kappa}B$ pathway.

A Fast Voxel-based Method for Outlier Removal in Laser Measurement

Hao Chen,Yu Chen,Xu Zhang,Baiyuan Li,Xiaoqiang Liu,Xuefei Shi,Jie Shen 한국정밀공학회 2019 International Journal of Precision Engineering and Vol.20 No.6

Discrete data points are noncontinuous without structural information. In this paper, we propose a new fast outlier removal method via voxel-based surface propagation. The main technical components of our approach include (a) an efficient and simple spatial partitioning scheme and (b) a specially-designed surface propagation method. Numerical analyses indicate that our method is about 10 times faster than an existing method and significantly better than other two methods in terms of denoising accuracy. This provides an efficient solution to handling noisy laser-scanning data.

Clinicopathologic Characteristics and Prognoses for Multicentric Occurrence and Intrahepatic Metastasis in Synchronous Multinodular Hepatocellular Carcinoma Patients

Li, Shi-Lai,Su, Ming,Peng, Tao,Xiao, Kai-Yin,Shang, Li-Ming,Xu, Bang-Hao,Su, Zhi-Xiong,Ye, Xin-Ping,Peng, Ning,Qin, Quan-Lin,Chen, De-Feng,Chen, Jie,Li, Le-Qun Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the outcomes for patients are still poor. It is important to determine the original type of synchronous multinodular HCC for preoperative assessment and the choice of treatment therapy as well as for the prediction of prognosis after treatment. Aims: To analyze clinicopathologic characteristics and prognoses in patients with multicentric occurrence (MO) and intrahepatic metastasis (IM) of synchronous multinodular hepatocellular carcinoma (HCC). Methods: The study group comprised 42 multinodular HCC patients with a total of 112 nodules. The control group comprised 20 HCC patients with 16 single nodular HCC cases and 4 HCC cases with a portal vein tumor emboli. The mitochondrial DNA (mtDNA) D-loop region was sequenced, and the patients of the study group were categorized as MO or IM based on the sequence variations. Univariate and multivariate analyses were used to determine the important clinicopathologic characteristics in the two groups. Results: In the study group, 20 cases were categorized as MO, and 22 as IM, whereas all 20 cases in the control group were characterized as IM. Several factors significantly differed between the IM and MO patients, including hepatitis B e antigen (HBeAg), cumulative tumor size, tumor nodule location, cirrhosis, portal vein and/or microvascular tumor embolus and the histological grade of the primary nodule. Multivariate analysis further demonstrated that cirrhosis and portal vein and/or microvascular tumor thrombus were independent factors differentiating between IM and MO patients. The tumor-free survival time of the MO subjects was significantly longer than that of the IM subjects ($25.7{\pm}4.8$ months vs. $8.9{\pm}3.1$ months, p=0.017). Similarly, the overall survival time of the MO subjects was longer ($31.6{\pm}5.3$ months vs. $15.4{\pm}3.4$ months, p=0.024). The multivariate analysis further demonstrated that the original type (p=0.035) and Child-Pugh grade (p<0.001) were independent predictors of tumor-free survival time. Cirrhosis (p=0.011), original type (p=0.034) and Child-Pugh grade (p<0.001) were independent predictors of overall survival time. Conclusions: HBeAg, cumulative tumor size, tumor nodule location, cirrhosis, portal vein and/or microvascular tumor embolus and histological grade of the primary nodule are important factors for differentiating IM and MO. MO HCC patients might have a favorable outcome compared with IM patients.

Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing

Li Shi-Dan,Xing Wei,Wang Shao-Chuan,Li You-Bin,Jiang Hao,Zheng Han-Xuan,Li Xiao-Ming,Yang Jing,Guo De-Bin,Xie Xiao-Yu,Jiang Ren-Qing,Fan Chao,Li Lei,Xu Xiang,Fei Jun 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Bone fracture remains a common occurrence, with a population-weighted incidence of approximately 3.21 per 1000. In addition, approximately 2% to 50% of patients with skeletal fractures will develop an infection, one of the causes of disordered bone healing. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) plays a key role in disordered bone repair. However, the specific mechanisms underlying BMSC dysfunction caused by bone infection are largely unknown. In this study, we discovered that Fibulin2 expression was upregulated in infected bone tissues and that BMSCs were the source of infection-induced Fibulin2. Importantly, Fibulin2 knockout accelerated mineralized bone formation during skeletal development and inhibited inflammatory bone resorption. We demonstrated that Fibulin2 suppressed BMSC osteogenic differentiation by binding to Notch2 and inactivating the Notch2 signaling pathway. Moreover, Fibulin2 knockdown restored Notch2 pathway activation and promoted BMSC osteogenesis; these outcomes were abolished by DAPT, a Notch inhibitor. Furthermore, transplanted Fibulin2 knockdown BMSCs displayed better bone repair potential in vivo. Altogether, Fibulin2 is a negative regulator of BMSC osteogenic differentiation that inhibits osteogenesis by inactivating the Notch2 signaling pathway in infected bone.

Aqueous two-phase extraction to separate alpha-ketoglutaric acid from fermentation broth by combining crystallization

Xueqi Shi,Weiyi Su,Hongyu Zhang,Jing Fang,Ning Xu,Yanjun Jiang,Hao Li 한국공업화학회 2022 Journal of Industrial and Engineering Chemistry Vol.115 No.-

Alpha-ketoglutaric acid (a-KG) is a crucial intermediate with broad application prospects. However, thedownstream separation of a-KG from fermentation broth with low concentration and complex componentshas become the bottleneck of large-scale production. In this study, a-KG was separated from theactual fermentation broth by aqueous two-phase system (ATPS) and crystallization. The optimal ATPScomposed of acetone/(NH4)2SO4 was selected by studying the phase diagram and a-KG distributionbehavior in different organic solvents and salts/sugars. Under the optimized conditions, the purity ofa-KG products from crude fermentation broth reached 98.08%, and the one-pass extraction efficiencywas 90.52%. The removal of cell debris and soluble proteins increased with the increase of acetone and(NH4)2SO4 concentrations, with the removal ratios reaching up to 99.44% and 86.54%. In addition,92.56% of the glucose was distributed in the aqueous phase. Although the a-KG fermentation broth ismore complex than the whole-cell biotransformation, impurities in the crude fermentation broth couldbe efficiently removed and a higher a-KG distribution coefficient was obtained. Meanwhile, the recovered(NH4)2SO4 could be reused for fermentation medium. This strategy provides an economical and effectivemethod combined with upstream biosynthesis to recover a-KG and other bioproducts from crude fermentationbroth.

End-to-End Performance Analysis of AF Relaying M2M Cooperative System

Lingwei Xu,Hao Zhang,Jingjing Wang,Wei Shi,T. Aaron Gulliver 보안공학연구지원센터 2015 International Journal of Multimedia and Ubiquitous Vol.10 No.9

In this paper, the end-to-end performance of the mobile-relay-based mobile-to-mobile (M2M) system with amplify-and-forward (AF) relaying over N-Nakagami fading channels is investigated. The exact closed-form expressions for the lower bound on average symbol error probability (ASEP) and upper bound on channel capacity are derived. Then the ASEP and channel capacity performance under different conditions is evaluated to confirm the accuracy of the analysis. Results are presented which show that the fading coefficient, the number of cascaded components, the relative geometrical gain, and the power-allocation parameter have an important influence on the ASEP and channel capacity performance.

Diffusion Weighted Imaging for Differentiating Benign from Malignant Orbital Tumors: Diagnostic Performance of the Apparent Diffusion Coefficient Based on Region of Interest Selection Method

Xiao-Quan Xu,Hao Hu,Guo-Yi Su,Hu Liu,Hai-Bin Shi,Fei-Yun Wu 대한영상의학회 2016 Korean Journal of Radiology Vol.17 No.5

Objective: To evaluate the differences in the apparent diffusion coefficient (ADC) measurements based on three different region of interest (ROI) selection methods, and compare their diagnostic performance in differentiating benign from malignant orbital tumors. Materials and Methods: Diffusion-weighted imaging data of sixty-four patients with orbital tumors (33 benign and 31 malignant) were retrospectively analyzed. Two readers independently measured the ADC values using three different ROIs selection methods including whole-tumor (WT), single-slice (SS), and reader-defined small sample (RDSS). The differences of ADC values (ADC-ROIWT, ADC-ROISS, and ADC-ROIRDSS) between benign and malignant group were compared using unpaired t test. Receiver operating characteristic curve was used to determine and compare their diagnostic ability. The ADC measurement time was compared using ANOVA analysis and the measurement reproducibility was assessed using Bland-Altman method and intra-class correlation coefficient (ICC). Results: Malignant group showed significantly lower ADC-ROIWT, ADC-ROISS, and ADC-ROIRDSS than benign group (all p < 0.05). The areas under the curve showed no significant difference when using ADC-ROIWT, ADC-ROISS, and ADC-ROIRDSS as differentiating index, respectively (all p > 0.05). The ROISS and ROIRDSS required comparable measurement time (p > 0.05), while significantly shorter than ROIWT (p < 0.05). The ROISS showed the best reproducibility (mean difference ± limits of agreement between two readers were 0.022 [-0.080–0.123] x 10-3 mm2/s; ICC, 0.997) among three ROI methods. Conclusion: Apparent diffusion coefficient values based on the three different ROI selection methods can help to differentiate benign from malignant orbital tumors. The results of measurement time, reproducibility and diagnostic ability suggest that the ROISS method are potentially useful for clinical practice.

A Novel In Situ Gel Formulation of Ranitidine for Oral Sustained Delivery

( Tao Ma ),( Hao Ping Xu ),( Min Shi ),( Jin Ling Jiang ) 한국응용약물학회 2014 Biomolecules & Therapeutics(구 응용약물학회지) Vol.22 No.2

The main purpose of this study was to develop a novel, in situ gel system for sustained delivery of ranitidine hydrochloride. Ranitidinein situ gels at 0.2%, 0.5%, and 1.0% gellan gum concentration (w/v) were prepared, respectively, and characterized in termsof preparation, viscosity and in vitro release. The viscosity of the gellan gum formulations in solution increased with increasingconcentrations of gellan gum. In vitro study showed that the release of ranitidine from these gels was characterized by an initialphase of high release (burst effect) and translated to the second phase of moderate release. Single photon emission computingtomography technique was used to evaluate the stomach residence time of gel containing 99mTc tracer. The animal experimentsuggested in situ gel had feasibility of forming gels in stomach and sustained the ranitidine release from the gels over the periodof at least 8 h. In conclusion, the in situ gel system is a promising approach for the oral delivery of ranitidine for the therapeuticeffects improvement.

MicroRNA-27a Inhibits Cell Migration and Invasion of Fibroblast-Like Synoviocytes by Targeting Follistatin-Like Protein 1 in Rheumatoid Arthritis

Dong-liang Shi,Gui-rong Shi,Jing Xie,Xu-zhao Du,Hao Yang 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.8

Fibroblast-like synoviocytes (FLS) with aberrant expres-sion of microRNA (miRNA) are critical pathogenic regula-tors in rheumatoid arthritis (RA). Previous studies have found that overexpression or silencing of miRNA can contribute to the development of miRNA-based therapeutics in arthritis models. In this study, we explored the effects of miR-27a on cell migration and invasion in cultured FLS from RA patients. We found that miR-27a was markedly downregulated in the serum, synovial tissue, and FLS of RA patients. Meanwhile, the expression of follistatin-like protein 1 (FSTL1) was upregulated, which suggests that FSTL1 plays a key role in RA development. The results of a Transwell assay showed that miR-27a inhibited FLS migration and invasion. However, miR-27a inhibition promoted the migration and invasion of FLS. In addition, the down-regulated expression of matrix metalloproteinases (MMP2, MMP9, and MMP13) and Rho family proteins (Rac1, Cdc42, and RhoA) was detected after treatment with miR-27a in RA-FLS by quantitative reverse transcription-PCR and western blot analysis. Then, a luciferase reporter assay validated that miR-27a targeted the 3-untranslated region (3-UTR) of FSTL1. Moreover, miR-27a caused a significant decrease of FSTL1. In addition, the expression of TLR4 and NFκB was inhibited by miR-27a but increased by FSTL1 overexpression. In conclusion, we found that miR-27a inhibited cell migration and invasion of RA-FLS by targeting FSTL1 and restraining the TLR4/NFκB pathway.