bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagic Schwann Cells Promote Perineural Invasion Mediated by the NGF/ATG7 Paracrine Pathway in Pancreatic Cancer
Authors: Zhang Wunai , He Rui , Yang Wenbin , Zhang Yan , Yuan Qinggong , Wang Jixin , Liu Yang , Chen Shuo , Zhang Simei , Zhang Weifan , Zhu Zeen , Zhang Jing , Wang Zheng , Li Junhui 
Published: September 2021

Abstract
BackgroundPerineural invasion (PNI) and autophagy are two common features in the tumor microenvironment of pancreatic cancer (PanCa) and have a negative effect on prognosis. Potential mediator cells and the molecular mechanism underlying their relationships need to be fully elucidated. MethodsTo investigate the autophagy of Schwann cells (SCs) in PNI, we reproduced the microenvironment of PNI by collecting clinical PNI tissue, performing sciatic nerve injection of nude mice with cancer cells and establishing a Dorsal root ganglion（DRG） coculture system with cancer cell lines. Autophagy was detected by IHC, IF, transmission electron microscopy (TEM) and western blotting assays. Apoptosis was detected by IF, TEM and western blotting. NGF targeting molecular RO 08-2750（RO） and the autophagy inhibitor Chloroquine（CQ）were utilized to evaluate the effect on autophagy and apoptosis in SCs and PanCa cells in PNI samples.ResultsSC autophagy is activated in PNI by paracrine NGF from PanCa cells. Autophagy-activated Schwann cells promote PNI through a) enhanced migration and axon guidance toward PanCa cells and b) increased chemoattraction to PanCa cells. The NGF-targeting reagent RO and autophagy inhibitor CQ inhibited Schwann cell autophagic flux and induced Schwann cell apoptosis. Moreover, RO and CQ could induce PanCa cell apoptosis and showed good therapeutic effects in the PNI model.ConclusionsPanCa cells can induce autophagy in SCs through paracrine pathways such as the NGF/ATG7 pathway. Autophagic SCs exert a "nerve-repair like effect", induce a high level of autophagy of cancer cells, provide a "beacon" for the invasion of cancer cells to nerve fibers, and induce directional growth of cancer cells. Targeting NGF and autophagy for PNI treatment can block nerve infiltration and is expected to provide new directions and an experimental basis for the research and treatment of nerve infiltration in pancreatic cancer.
Investigating the Multi-Target Pharmacological Mechanism of Rhodiola Wallichiana Var. Cholaensis Acting on Angina Pectoris by Combined Network Pharmacology and Molecular Docking
Authors: Zhang Haitao , Zhuang Xudong , Li Zhixiong , Wang Xinrui 
Published: September 2021

Abstract
Background: Angina pectoris is a kind of cardiovascular disease, which is caused by epicardial stenosis, microvascular dysfunction, dynamic stenosis area contraction or more comprehensive factors, eventually leading to Coronary artery disease. Rhodiola wallichiana var. cholaensis, which is one of the most well-known Traditional Chinese Medicine, is widely used to treat angina pectoris. However, the possible underlying mechanisms remain to be elucidated.Methods: In this study, systematic and comprehensive network pharmacology and molecular docking were utilized for the first time to reveal the potential pharmacological mechanisms of RW on AP. Firstly, the relative compounds were obtained by mining literature and potential targets of these compounds by target predicting were collected. Then, We built the AP target database using the DigSee and GeneCards Database. Based on the data, GO and KEGG pathway enrichment analysis, protein-protein interaction (PPI) analysis were performed and screen the hub targets by topology. Furthermore, evaluation of the binding potential of key targets and compounds through molecular docking.Results: The results indicate that 218 known RW therapeutic targets were selected. By systematic analysis, identified 9 hub targets (VEGFA, GAPDH, TP53, AKT1, CASP3, STAT3, TNF, MAPK1 and JUN) mainly involved in the complex treating effects associated with the protection of vascular endothelium, as well as the regulation of glucose metabolism, cellular processes, inflammatory responses, and cellular signal transduction.Conclusion: The results of this study preliminarily explain the potential targets and signaling pathways of RW in AP therapy and lay a good foundation for further experimental studies and clinical trials.
MFG-E8, A Novel Target of Promoting Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells
Authors: Bai Jinwu , Zhang Weijun , Hang Kai , Zhao Guangfeng , Zhong Huiming , Zhou Chenwei , Xu Jianxiang , Zhang Wei , Chen Erman , Wu Jiaqi , Liu Ling , Xue Deting 
Published: September 2021

Abstract
BackgroundFracture nonunion and bone defects are challenging for orthopedic surgeons. Milk fat globule-epidermal growth factor 8 (MFG-E8), a glycoprotein possibly secreted by macrophages in a fracture hematoma, participates in bone development. However, the role of MFG-E8 in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is unclear. MethodsWe investigated the osteogenic effect of MFG-E8 in vitro and in vivo. The CCK-8 assay was used to assess the effect of recombinant human MFG-E8 (rhMFG-E8) on the viability of human BMSCs (hBMSCs). Osteogenesis was investigated using real-time quantitative PCR, Western blotting, and immunofluorescence. Alkaline phosphatase (ALP) and Alizarin red staining were used to evaluate ALP activity and mineralization, respectively. An enzyme-linked immunosorbent assay was conducted to evaluate the secretory MFG-E8 concentration. Knockdown and overexpression of MFG-E8 in hBMSCs were established via siRNA and lentivirus vector transfection, respectively. Exogenous rhMFG-E8 was used to verify the in vivo therapeutic effect in a tibia bone-defect model based on radiographic analysis and histological evaluation. ResultsEndogenous and secretory MFG-E8 levels increased significantly during the early osteogenic differentiation of hBMSCs. Knockdown of MFG-E8 inhibited the osteogenic differentiation of hBMSCs. Overexpression of MFG-E8 and recombinant MFG-E8 protein increased the expression of osteogenesis-related genes and proteins and enhanced calcium deposition. The active β-catenin to total β-catenin ratio and the p-GSK3β protein level were increased by MFG-E8. The MFG-E8-induced enhanced osteogenic differentiation of hBMSCs was partially attenuated by a GSK3β/β-catenin signaling inhibitor. Recombinant MFG-E8 accelerated bone healing in a rat tibial-defect model.ConclusionsIn conclusion, MFG-E8 promotes the osteogenic differentiation of hBMSCs by regulating the GSK3β/β-catenin signaling pathway and so, is a potential therapeutic target.
Improving CoQ10 Productivity by Strengthening Glucose Transmembrane of Rhodobacter Sphaeroides
Authors: Yang Yuying , Li Lu , Sun Haoyu , Li Zhen , Zhengliang Qi , Liu Xinli 
Published: September 2021

Abstract
Background: Many Rhodobacter sphaeroides have been widely applied in commercial CoQ10 production, but they have poor glucose use. Strategies for enhancing glucose use have been widely exploited in R. sphaeroides. Nevertheless, little research has focused on the role of glucose transmembrane in the improvement of production.Results: There are two potential glucose transmembrane pathways in R. sphaeroides ATCC 17023: the fructose specific-phosphotransferase system (PTSFru, fruAB) and non-PTS that relied on glucokinase (glk). fruAB mutation revealed two effects on bacterial growth: inhibition at the early cultivation phase (12-24 h) and promotion since 36 h. Glucose metabolism showed a corresponding change in characteristic vs. the growth. For △fruA△fruB, maximum biomass (Biomax) was increased by 44.39 % and the CoQ10 content was 27.08 % more than that of the WT. glk mutation caused a significant decrease in growth and glucose metabolism. Overexpressing a galactose:H+ symporter (galP) in the △fruA△fruB relieved the inhibition and enhanced the growth further. Finally, a mutant with rapid growth and high CoQ10 yield was constructed (△fruA△fruB/tac::galPOP) using several glucose metabolism modifications and was verified by fermentation in a 10-L fermenter.Conclusions: The PTSFru mutation revealed two effects on bacterial growth: inhibition at the early cultivation phase and promotion later. Additionally, biomass yield to glucose (Ybio/glc) and CoQ10 synthesis can be promoted using fruAB mutation, and glk plays a key role in glucose metabolism. Strengthening glucose transmembrane via non-PTS improves the productivity of CoQ10 fermentation.
Separation of Flavonoids and the Evaluation of the Anti-inflammatory Potential of Flavonoid-enriched Extracts from the Thlaspi arvense Linn by Inhibiting the Activation of TLR-4/NF-κ B
Authors: Wang Xiang , Zeng Panke , Li Xuejiao , Cheng Liyuan , Rashidb Haroon , Liu Hong , Liu Xu , Wang Lisheng 
Published: September 2021

Abstract
Background: Thlaspi arvense Linn, belonging to the dicotyledonous cruciferous family, is distributed Europe and Asia. In this study, we evaluated for the first time the anti-inflammatory effects of Thlaspi arvense Linn on LPS-stimulated RAW264.7 macrophages, and explored the related mechanism.Methods: The extract was identified and quantified using the HPLC, NMR. The anti-inflammatory activities of crude extracts C11, C12, C13 were screened by xylene-induced ear swelling and carrageenan-induced foot swelling in mice. The inflammatory mediators, pro-inflammatory cytokines and TLR-4-mediated signals in LPS-stimulated RAW264.7 macrophages were determined using NO activity assay, MTS, ELISA and Western blot.Results:The extract of Thlaspi arvense Linn was found to enrich flavonoid（mainly Orientin,Isoorientin,Vitexin;,Isovitexin,Luteolin-7-O-β-D-glucoside,Apigenin-7-O-β-D-glucoside,Luteolin,Apigeni）.5,7-dihydroxy-flavone-4′-(6′′-β-O-glucopyranoside)-β-O-D-glucopyranoside was novel, whereas isosapogenin and 8-methoxyvitexin were isolated for the first time from Thlaspi arvense Linn. The extract (flavonoid-enriched) inhibited xylene-induced ear swelling and carrageenan-induced foot swelling in mice. And suppressed LPS-induced overrelease of iNOS,TNF-α,COX-2 and IL-6 in RAW264.7 macrophages. The extract inhibited the inflammatory response through the signaling pathway mediated by TLR-4/NF- kappa B pathway and its downstream signals, IκB-α, NF-κB-P65 and IL-1β in LPS-stimulated macrophages.Conclusions: The present results demonstrate that the extract of Thlaspi arvense Linn inhibit inflammatory responses via the TLR-4/NF-KB-mediated signaling pathway.
Impact of Myocardial Scars on Left Ventricular Deformation in Type 2 Diabetes Mellitus After Myocardial Infarction by Contrast-Enhanced Cardiac Magnetic Resonance
Authors: Gao Yue , Xu Hua-yan , Guo Ying-kun , Wen Xiao-ling , Shi Rui , Li Yuan , Yang Zhi-Gang 
Published: September 2021

Abstract
Background Type 2 diabetes mellitus (T2DM) is a major risk factor for coronary artery disease and myocardial infarction (MI). The interaction of diabetic cardiomyopathy and MI scars on myocardial deformation in T2DM patients is unclear. Therefore, we aimed to evaluated myocardial deformation using cardiac magnetic resonance (CMR) in T2DM patients with previous MI and investigated the influence of MI on left ventricular (LV) deformationMethods Two hundred and two T2DM patients, including 46 with MI (T2DM(MI+)) and 156 without MI (T2DM(MI−)), and 59 normal controls who underwent CMR scans were included. Myocardial scars were assessed by late gadolinium enhancement. LV function and deformation, including LV global function index, LV global peak strain (PS), peak systolic strain rate (PSSR), and peak diastolic strain rate (PSDR), were compared among these groups. Correlation analysis and multivariate linear regression analyses were used to investigate the relationship between myocardial scars and LV deformation.Results There was a decrease in LV function and LV global PS, PSSR, and PDSR in the T2DM(MI+) group compared with those of the other groups. Furthermore, reduced LV deformation (p < 0.017) was observed in the T2DM(MI+) group with anterior wall infarction. The increased total LV infarct extent and infarct mass of LV were related to decreased LV global PS (radial, circumferential, and longitudinal directions; p < 0.01) and LV global PSSR (radial and circumferential directions, p < 0.02). Multivariate analysis demonstrated that NYHA functional class and total LV infarct extent were independently associated with LV global radial PS (β = −0.400 and β = −0.446, respectively, all p < 0.01; model R2 = 0.37) and circumferential PS (β = −0.339 and β = −0.530, respectively, all p < 0.01; model R2 = 0.41), while LV anterior wall infarction was independently associated with LV global longitudinal PS (β = −0.398, p = 0.006).Conclusions The myocardial scarring size in T2DM patients after MI is negatively correlated with LV global PS and PSSR, especially in the circumferential direction. Additionally, different MI regions have different effects on the reduction of LV deformation, and relevant clinical evaluations should be strengthened.
Effect of MYH10 Variant on Acute Leukemia with Low Platelet Count Prognosis
Authors: Xiao Qirong , Lin Bicun , Lin Kaiting , Lin Xiaobin , chen ping 
Published: September 2021

Abstract
Background: Acute myeloid leukemia (AML) is a blood disorder characterized by abnormal white blood cell count, anemia, or abnormal platelet count. It is associated with molecular genetic changes. While platelet counts vary at first diagnosis，platelets recover after chemotherapy. Objectives:This study aimed to; (1) Investigate whether the platelet count and genotype at first diagnosis are related to chemotherapy and their significance on chemotherapy prognosis; (2) Determine whether newly diagnosed patients with low platelet count have a poor prognosis and if it can be used as a separate prognostic predictor; (3) Determine whether the mutation genotype affects platelet count and its prognosis at first diagnosis. Methods: A retrospective chart review of 301 AML patients was conducted. Univariate, multivariate unconditional Logistic regression and Cox regression analyses were also conducted. Bioinformatics technology was used to extract the GSE12662 data set from the GEO database to analyze differentially expressed genes in AML patients. Besides, biological functions, pathways, proteins, and prognosis were assessed. Conclusion: Increased platelet count in AML patients after chemotherapy was an independent risk factor affecting complete remission. The platelet count also had some guiding significance for evaluating the sensitivity of patients to chemotherapy. MYH10 causes thrombocytopenia in acute myeloid leukemia via RUNX1 gene alteration and influence of prognostic factors. MYH10 variant detection improves the identification of AML molecular characteristics and its prognostic impact on AML, helping in the response analysis to chemotherapeutic agents and further treatment decisions.
Safety and Effectiveness of Omnitrope® (Somatropin) in PATRO Children: A Multi-Center, Post-Marketing Surveillance Study Comparison of United States and Rest of World Data
Authors: Backeljauw Philippe , Kanumakala Shankar , Loche Sandro , Schwab Karl Otfried , Miller Bradley S , Levy Richard , McCormick Kenneth , Zouater Hichem , Zabransky Markus , Campbell Kim 
Published: September 2021

Abstract
PAtients TReated with Omnitrope® (PATRO) Children is an international, non-interventional study with Omnitrope® (somatropin, Sandoz Inc.), conducted across 14 different countries. Here we present a comparison of safety and effectiveness data from patients in the United States (US) and in other countries. All visits and assessments are carried out according to routine clinical practice, and doses of Omnitrope® are given according to country-specific prescribing information. By September 2018, 294 patients had been enrolled in the US (53.1% recombinant human growth hormone [rhGH]-naïve) and 6206 patients had been enrolled across 13 other countries (international group; 86.2% rhGH-naïve). The most common indication in both groups was growth hormone deficiency (GHD). Overall, 194 US patients (66.0%) and 2977 international patients (48.0%) experienced adverse events (AEs; 886 and 11,716 events, respectively), most of which were of mild or moderate intensity. The AEs were suspected to be treatment-related in five US patients (1.7%) and 452 international patients (7.3%). All reported neoplasms were benign, non-serious, and considered unrelated to rhGH therapy. No cases of diabetes mellitus or hyperglycemia were reported. In rhGH-naïve GHD patients, after 3 years of rhGH therapy, the improvement in mean height SD score from baseline was +1.25 and +1.35 in US and international patients, respectively. Conclusion Omnitrope® treatment appears to be well tolerated and effective in US patients and those from other countries. Across the pediatric indications included, there was no evidence of an increased risk of developing uncommon or unexpected AEs with rhGH.Trial registration: NA
A Novel Optimized Finite Element Model of Lenke 1 Adolescent Idiopathic Scoliosis Based on Dynamic Flexibility in Vivo
Authors: Niu Shengbo , Bai Jinyi , Yang Huan , Zhang Dongsheng , Wu Jianghong , Liu Siyong , Yang Changwei , Li Ming 
Published: September 2021

Abstract
Bacground: It is of great significance to optimize the finite element model by spinal flexibility of adolescent idiopathic scoliosis (AIS) patients. The elastic modulus of the intervertebral disc is of critical importance in determining the overall flexibility of the spine. The aim of the present study was to optimize the finite element model of Lenke 1 AIS based on the dynamic flexibility in vivo by matching the optimal elastic modulus of the intervertebral disc.Methods: The Cobb angles under different longitudinal traction loads of one patient with Lenke 1 AIS were dynamically measured by using a spine morphometer with a posture sensor to plot the Cobb angle-longitudinal traction load characteristic curve. A 3D finite element model of the patient was established. The patient’s Cobb angle-longitudinal traction load characteristic curve was used as the dynamic flexibility in vivo to determine the optimal intervertebral disc elastic modulus of the model. Results: The dynamic flexibility curve in vivo of one Lenke 1 AIS patient was successfully obtained, and the patient’s optimal elastic modulus of the intervertebral disc for the finite element model was 5 MPa according to the dynamic flexibility curve in vivo.Conclusions: The use of dynamic flexibility in vivo to optimize the finite element model can provide a new perspective and approach for model optimization, which can reproduce the biomechanical characteristics in vivo of AIS patients.
Association between health literacy and risk of depressive symptoms among Chinese college students
Authors: Ren Zhongyu , Cao Jianhua , Cao Bing , E Shuang , Kuang Jujiao 
Published: September 2021

Abstract
Background

The association between health literacy and depressive symptoms has been examined among Chinese middle school students, however there is no evidence are available from college students.
Aims

This study aimed to examined the association between health literacy and depressive symptoms among Chinese college students.
Methods

This cross-sectional study recruited 2771 college students in Southwest University. Depressive symptoms was assessed using Zung self-rating depression scale and a score of ≥ 50 represented having depressive symptoms. We used Chinese adolescent interactive health literacy questionnaire to assess health literacy. Multivariate logistic regressions analysis was applied to assess the association between health literacy and depressive symptoms.
Results

The prevalence of depressive symptoms was 34.9% (967/2771). Multivariate logistic regressions analysis showed an inverse association between health literacy and depressive symptoms after adjusting for potential confounders. The multivariate adjusted ORs (95%CIs) for depressive symptoms across quartiles of health literacy level were 1.000 (reference), 0.48 (0.39, 0.60), 0.25 (0.19, 0.32), and 0.16 (0.12, 0.21) (P for trend: <0.001). Similar associations were also found when all 6 health literacy dimensions were analyzed separately.
Conclusion

The results of this cross-sectional study indicated that higher health literacy level was associated with lower risks of depressive symptoms. Further prospective studies or randomized controlled trials should be conducted to prove the causal association between health literacy and risk of depressive symptoms.
XJP Inhibits Apoptosis, Invasion, EMT, and Wnt/Β-Catenin Pathway in Triple-Negative Breast Cancer
Authors: Feng Dandan , Chen Hongzhi , Shi Guangxi , Zhang Mengdi , Liang Hongyi , Liu Zhiyong , Li Jingwei 
Published: September 2021

Abstract
Background: Triple-negative breast cancer (TNBC) progresses at a rapid pace. Chemotherapy is a major clinical application. However, resistance and metastases are key barriers to chemotherapy. Xiaojin pills (XJP) have been used clinically for treating TNBC for decades. However, the potential molecular mechanisms of the effect of XJP on breast cancer is still not understood.Methods: The cell viability was analyzed using Cell Counting Kit-8 (CCK-8). Flow cytometry was used to detect apoptosis, and the migration and invasion abilities of TNBC were assessed using Transwell assay. For molecular mechanisms, the protein expression levels were determined by Western blot analysis. The expression of β-catenin in the Wnt/β-serial protein (β-catenin) pathway was detected with immunofluorescence (IF).Results: XJP inhibited the viability and proliferation of the TNBC cell line in vitro. Flow cytometry analysis showed that apoptosis increased in both MDA-MB-231 and MDA-MB-468 cells induced by XJP. The expression of the proteins associated with invasion, for example, matrix metalloproteinase (MMP) and MMP9, was reduced. Among epithelial–mesenchymal transition markers, E-cadherin was upregulated and N-cadherin was downregulated. The apoptosis-related proteins caspase-8, caspase-3, caspase-9, and Parp were all upregulated. Additionally, XJP effectively suppressed the expression of β-catenin, which belonged to the Wnt/β-catenin pathway.Conclusions: These results suggested that XJP suppressed the progression of TNBC cells by suppressing apoptosis, invasion, EMT, and Wnt/β-catenin pathway.