bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secreted phosphoprotein 24 kD (Spp24) inhibits growth of human osteosarcoma through the BMP-2/Smad signaling pathway
Authors: Chen Hongfang , Li Chenshuang , Zhou Tangjun , Li Xunlin , Wu Aimin , Duarte Maria Eugenia L. , Tian Haijun , Zhao Jie , Daubs Michael D , Buser Zorica , Brochmann Elsa J. , Wang Jeffrey C. , Murray Samuel S. 
Published: May 2020

Abstract
Background

Autocrine stimulation of tumors cells is an important mechanism for the growth of skeletal tumors. In tumors that are sensitive, growth factor inhibitors can dramatically reduce tumor growth. In this study, we aimed to investigate the effects of Secreted phosphoprotein 24 kD (Spp24) on the growth of osteosarcoma cells induced by BMP-2 both in vitro and in vivo.
Methods

Two osteosarcoma cell lines, 143B and MG63, were used in this study. MTT assay, flow cytometry, wound-healing assay, Matrigel invasion assay and immunohistochemical staining were used to evaluate the effects of Spp24 inhibition on the osteosarcoma cells induced by BMP-2 in vitro. Subcutaneous and intratibial tumor models in nude mice were used to evaluate the effects of Spp24 in vivo. Quantitative real-time PCR, western blotting and co-immunoprecipitation were used to investigate the underlying mechanisms.
Results

Our study demonstrated that Spp24 can inhibit proliferation and promote apoptosis of osteosarcoma cells as confirmed by MTT assays and immunohistochemical staining. We found that BMP-2 increased the mobility and invasiveness of tumor cells in vitro whereas Spp24 inhibited both effects either in the presence or absence of exogenous BMP-2. Intracellular binding of Spp24 and BMP-2 was confirmed by co-immunoprecipitation. Mechanically, phosphorylation of Smad1/5/8 was enhanced by treatment with BMP-2 but was significantly inhibited by treatment with Spp24. Subcutaneous and intratibial tumor models in nude mice demonstrated that BMP-2 promoted osteosarcoma growth in vivo, while Spp24 significantly inhibited tumor growth and reduced osteolytic lesions in the tibia induced by BMP-2.
Conclusions

From this study, we concluded that the BMP-2/Smad signaling pathway is involved in the pathogenesis of osteosarcoma growth, and that Spp24 inhibits the growth of human osteosarcoma induced by BMP-2 both in vitro and in vivo. These results validate the potential of Spp24 as a therapeutic agent for the treatment of osteosarcoma.
TSHZ3 is A Prognostic Biomarker with Immune Infiltration in Stomach Adenocarcinoma and Bladder Urothelial Carcinoma
Authors: Zhang Xi , Wang Ming , Lu Han-qi , He Qiu-xing , You Yan-ting , Zhou Xing-hong , Fu Xiu-qiong , Liang Dong-hui , Kwan Hiu Yee , Zhao Xiao-shan , Zhou Lin 
Published: May 2020

Abstract
Background: This study aimed to investigate the expressions of Teashirt zinc finger homeobox 3 (TSHZ3) in different cancer types and identify the cancers of which prognosis can be predicted by TSHZ3 expression. Furthermore, we aimed to explore the correlations between tumor-infiltrating immune cells (TIICs) and TSHZ3 expression in these cancers.Methods: TSHZ3 expression was analyzed by the Oncomine database and Gene Expression Profiling Interactive Analysis (GEPIA). We examined the influence of TSHZ3 on the clinical prognosis with Kaplan-Meier plotter and TIMER (Tumor Immune Estimation Resource). The correlations between tumor immune infiltrates and TSHZ3 expressions were investigated with TIMER and validated by GEPIA.Results: TSHZ3 expressions were significantly higher in stomach adenocarcinoma (STAD) and bladder urothelial carcinoma (BLCA) when compared to normal tissues. Survival analysis results showed that high TSHZ3 expression was correlated with poor overall survival (OS) in STAD and BLCA. The infiltrations of pro-tumorigenic TIICs (M2 macrophages, monocytes, B cells and pDCs) were positively correlated with TSHZ3 expression in STAD and BLCA. Besides, the infiltration of other pro-tumorigenic TIICs (tumor-associated macrophages (TAMs), Th2 cells and Tregs) and expression of T cell exhaustion markers (PD-1 and TIM-3) were positively correlated with TSHZ3 expression in STAD.Conclusions: TSHZ3 expression was up-regulated in STAD and BLCA. High TSHZ3 expression predicted poor prognosis of patients with STAD or BLCA. In addition, TSHZ3 expression potentially contributes to the increased infiltrations of pro-tumorigenic TIICs. TSHZ3 can be used as a prognostic biomarker for predicting prognosis and immune infiltration in STAD and BLCA.
The spectral scalings of magnetic fluctuations upstream and downstream of the Venusian bow shock
Authors: XIAO S. D. , Wu M. Y. , Wang G. Q. , Chen Y. Q. , Zhang T. L. 
Published: May 2020

Abstract
We statistically investigate the spectral scalings of magnetic fluctuations at the upstream and downstream regions near the Venusian bow shock and perform a differentiation by shock geometry. Based on the Venus Express data, 115 quasi-parallel (

{Q}_{\parallel }
) bow shock crossings and 303 quasi-perpendicular (

{Q}_{\perp }
) bow shock crossings are selected. The statistical results suggest that the bow shock tends to modify the upstream spectra flatter to 1/f noise in the magnetohydrodynamics (MHD) regime and steeper to turbulence in the kinetic regime after the magnetic fluctuations crossing the bow shock, and this modification for the

{Q}_{\parallel }
and

{Q}_{\perp }
bow shock is basically consistent. While the upstream spectral scalings are associated with the shock geometry. The changes of the spectral scalings of magnetic fluctuations near the

{Q}_{\parallel }
bow shocks are not as significant as near the

{Q}_{\perp }
bow shock crossings. That might result from the fluctuations generated by the backstreaming ions which can escape across the

{Q}_{\parallel }
bow shock into the foreshock. Our results suggest that the energy cascade and dissipation near Venus can be modified by the Venusian bow shock, and the

{Q}_{\parallel }
bow shock plays an important role on the energy injection and dissipation in the solar wind interaction with Venus.
Mesenchymal Stem Cells Suppress Tgf-β Release to Decrease Α- Sma Expression in Ameliorating Ccl4-Induced Liver Fibrosis
Authors: Putra Agung , Wirastuti Ken , Sadyah Nur Anna Chalimah , Trisnadi Setyo , Muhar Adi Muradi , Pasongka Zenitalia 
Published: May 2020

Abstract
Background: Liver fibrosis (LF) is the excessive deposition of extracellular matrix (ECM),produced by overactivated hepatic stellate cells, following prolonged transforming growth factor-β (TGF-b) stimulation.The ability of mesenchymal stem cells (MSCs) to improveLF has been reported. However, the mechanismsof MSCs to ameliorate LF through suppressing TGF-β and α-smooth muscle actin (a-SMA) remain unclear.In this study, we investigated the ability of MSCs to ameliorate LF by suppressing TGF-band a-SMA expression.Methods: Twenty-four,male, Wistar rats were injected intraperitoneal (IP) by with carbon tetrachloride (CCL4),twice weekly, for eight weeks, to induce LF. Rats were randomly assigned to four groups: Sham, Control, and MSC-treated groups, at doses of 1´106 (T1) and 2´106 (T2) cells. TGF-blevels were analyzed by enzyme-linked immunosorbent assay (ELISA),whereas a-SMA expression was determined by immunohistochemistry staining.Results: This study showed that TGF-bconcentrations significantly decreased in all treatment groupsat day 3 and 14. The T2 group showed lower TGF-blevels than that in the T1 group. This finding was in line with the observed decreasesina-SMA expression andnumber of colagen.Conclusions: MSCs treatmentamelioratedLF by suppressing TGF-b production,leading to decreaseda-SMA expressionin a CCL4-induced LF animal model.
Reversibility of Hat-mscs Phenotypic and Metabolic Changes After Exposure to and Withdrawal Form Hcc-conditioned Medium Through Regulation of the Ros/mapk/hif-1α Signalling Pathway
Authors: Wang Chenyang , Hu Jie , Chen Zheng , Wang Yifan , Lu Sinan , Zhang Yuan , Li Yufeng , Xiang Yucheng , Ji Yutian , Zeng Cheng , Ding Yuan , Wang Weilin 
Published: May 2020

Abstract
Background: Mesenchymal stem cells (MSCs) play an important role in tumour progression; concomitantly, MSCs also undergo profound changes in thetumour microenvironment (TME). These changes can directly impact the application and efficacy of MSC-based anti-tumour therapy. However, few studies have focused on the regulation of MSC fate in TME, which will limit the progress of MSC-based anti-tumour therapy. Herein, we investigated the effects of conditioned medium from human hepatocellular carcinoma cells (HCC-CM) on the phenotype and glucose metabolism of human adipose tissue-derived MSCs (hAT-MSCs).Methods: hAT-MSCs were exposed to conditioned medium from Hep3B, Huh7 and HCCLM3cells for 4-8 weeks in vitro. Then, CCK-8 assay, EdU assay, Transwell assay, and flow cytometry were used to assess the alterations in cell phenotype in terms of cell proliferation, migration, invasion, cell cycle, and apoptosis. In addition, glucose metabolism was evaluated by related kits. Next,cells were subjected to withdrawal from HCC-CM for 2-4 weeks, andalterations in phenotype and glucose metabolism were reevaluatedin hAT-MSCs.Finally, the molecular mechanism was clarified by Western blotting.Results: The results revealed that after exposure to HCC-CM, hAT-MSCs developed a stellate-shaped morphology. In association with cytoskeleton remodelling, hAT-MSCs showed enhanced capacities for migration and invasion, while cell proliferation was inhibited by regulating the cell cycle by downregulatingcyclins and cyclin-dependent kinases and activating the mitochondrial apoptosis pathway. In terms of glucose metabolism, our results showed mitochondrial dysfunction and elevated glycolysis of hAT-MSCs. However, interestingly, when hAT-MSCs were subjected towithdrawal from HCC-CM, the alterations in phenotype and glucose metabolism could be reversed. Further studies showed that these changes in hAT-MSCs may be regulated bythe ROS/MAPK/HIF-1α signalling pathway.Conclusion:Taken together, the effects of long-term HCC-CM treatment on phenotype and glucose metabolism in hAT-MSCs are modest and largely reversible after withdrawal. This is the first report on the reversal of phenotype and glucose metabolism in tumour-associated MSCs (TA-MSCs), and it is anticipated that new insights into TA-MSCs will lead to the development of novel strategies for MSC-based anti-tumour therapy.
Time-Varying Discrimination Accuracy of Longitudinal Biomarkers for the Prediction of Mortality Compared to Assessment at Fixed Time Point in Severe Burns Patients
Authors: Yoon Jaechul , Kym Dohern , Hur Jun , Won Jae Hee , Yim Haejun , Cho Yong Suk , Chun Wook 
Published: May 2020

Abstract
Background: The distribution of biomarkers over time is considered an indicator of disease formation and helps in early detection of disease, thus reducing the disease-related mortality. The ability of biomarkers to predict outcomes has been evaluated using conventional cross-sectional methods; therefore, we investigated the prognostic potential of longitudinal biomarkers over time.Methods: The patients aged > 18 y who were admitted within 24 h of the burn incident in the burn intensive care unit were enrolled. Longitudinal biomarkers, such as WBC, platelet count, lactate, creatinine, TB, and PT were retrieved from a clinical database warehouse. Time-dependent ROC curves using a cumulative/dynamic and incident/dynamic approach were employed to evaluate time-varying prognostic performance.Results: Total 2259 patients were included in this retrospective study and divided into the survival group and non-survival group. With AUC using the ID approach, platelets showed the highest c-index with 0.930 (0.919 ~ 0.941) as well as the highest during all time points. PT and creatinine show over 8 c-index with 0.862 (0.843 ~ 0.881) and 0.828 (0.809 ~ 0.848), respectively.Conclusions: The platelet count was the best prognostic marker. PT and creatinine also showed good overall diagnostic ability. Lactate is known as a strong predictor; however, it showed relatively poorer prognostic performance in burns.
Efficient Production of 2,3-Butanediol from whey Powder by Metabolic Engineered Klebsiella Oxytoca
Authors: Meng Wensi , Zhang Yongjia , Cao Menghao , Zhang Wen , Lü Chuanjuan , Yang Chunyu , Gao Chao , Xu Ping , Ma Cuiqing 
Published: May 2020

Abstract
Backgrounds: Whey is the major pollution source from the dairy industry. Exploring new outlets for whey utilization is urgently needed to decline its environmental pollution. In this study, we explored the possibility of using whey powder to produce 2,3-butanediol (2,3-BD), an important platform chemical.Results: A Klebsiella oxytoca strain PDL-0 was selected from five 2,3-BD producing strains based on its ability to efficiently produce 2,3-BD from lactose, the major fermentable sugar in whey. Five genes including pox, pta, frdA, ldhD, and pflB were knocked out in K. oxytoca PDL-0 to decrease the production of byproducts like acetate, succinate, lactate, and formate. Using fed-batch fermentation of K. oxytoca PDL-0 ΔpoxΔptaΔfrdAΔldhDΔpflB, 74.9 g/L 2,3-BD was produced with a productivity of 2.27 g/L/h and a yield of 0.43 g/g from lactose. In addition, when whey powder was used as the substrate, 65.5 g/L 2,3-BD was produced within 24 h with a productivity of 2.73 g/L/h and a yield of 0.44 g/g.Conclusion: This study proved the efficiency of K. oxytoca PDL-0 to metabolize whey for 2,3-BD production. Due to its characteristics of non-pathogenicity and efficient lactose utilization, K. oxytoca PDL-0 might also be used in the production of other important chemicals using whey as the substrate.
Rh-relaxin-2 Attenuates Degranulation of mast cells by Inhibiting NF-κB through PI3K-AKT/TNFAIP3 Pathway in an Experimental Germinal Matrix Hemorrhage Rat Model
Authors: Li Peng , Zhao Gang , Chen Fanfan , Ding Yan , Wang Tianyi , Liu Shengpeng , Lu Weitian , Xu Weilin , Flores Jerry , Ocak Umut , Zhang Tongyu , Zhang John H. , Tang Jiping 
Published: May 2020

Abstract
Background:
Mast cells play an important role in early immune reactions in the brain by inducing degranulation and releasing inflammatory mediators. Our aim of the study is to investigate the effects of rh-relaxin-2 on mast cells and the underlying mechanisms in a GMH rat model.
Methods:
One hundred and sixty-four P7 rat pups were subjected to germinal matrix hemorrhage (GMH) by an intraparenchymal injection of bacterial collagenase. Clodronate liposome was administered through intracerebroventricular (i.c.v.) injections 24 hours prior to GMH to inhibit microglia. Rh-relaxin-2 was administered intraperitoneally at 1 hour and 12 hours after GMH. Small interfering RNA of RXFP1 and PI3K inhibitor LY294002 were given by i.c.v. injections. Post-GMH evaluation included neurobehavioral function, Western blot analysis, immunofluorescence, Nissl staining, and Toluidine staining.
Results:
Our results demonstrated that endogenous relaxin-2 was downregulated and that RXFP1 level peaked on the first day after GMH. Administration of rh-relaxin-2 improved neurological functions, attenuated degranulation of mast cells and neuroinflammation, and ameliorated post-hemorrhagic hydrocephalus after GMH. These effects were associated with RXFP1 activation, increased expression of PI3K, phosphorylated AKT and TNFAIP3, and decreased levels of phosphorylated NF-κB, tryptase, chymase, IL-6 and TNF-α. However, knockdown of RXFP1 and PI3K abolished the protective effects of rh-relaxin-2.
Conclusions:
Our findings showed that rh-relaxin-2 attenuated degranulation of mast cells and neuroinflammation, improved neurological outcomes and ameliorated hydrocephalus after GMH through RXFP1/PI3K-AKT/TNFAIP3/NF-κB signaling pathway.
Structure and regulation of the cervicovaginal microbiome in a cohort of Afro-Caribbean women
Authors: Roachford Orville St. E , Alleyne Angela T , Kuelbs Claire , Torralba Manolito G , Nelson Karen E 
Published: May 2020

Abstract
Background The cervicovaginal microbiome, with its well documented dynamic community state types (CSTs I-V) is known to interact with the host immune system in a complex regulatory ecosystem that guards against dysbiosis and invading pathogens. However, the regulatory mechanism of the cervicovaginal microbiome in vaginal eubiosis is not well understood. Therefore, we characterized the cervicovaginal microbiome in a cohort of Afro-Caribbean women to the species-strain taxonomic level using high-throughput targeted sequencing and shotgun metagenomics and conceptualized a hypothetical model that aids in understanding vaginal ecosystem regulation. Results Compared to targeted 16S rRNA V4 sequencing, whole genome shotgun (WGS) metagenomics offered greater species resolution of the cervicovaginal microbiome in the Afro-Caribbean women cohort. Community state type IV predominated in the microbiome of these women, with Prevotella (13.91%), Gardnerella (12.14%) and Lactobacillus (9.37%) being the three most abundant genera. For Prevotella and Lactobacillus the most abundant species-strains were P. timonensis DSM 22865 (5.0%) and L. iners DSM 13335 (7.0%), respectively. The less virulent strain of Gardnerella, G. vaginalis 409-05 (8.0%) was more abundant than G. vaginalis ATCC 14019 (4.0%). In the resistome, 2,753 antimicrobial resistance (AMR) genes consisting of 28 types (mostly tet and Emr; abundances 51% and 15%, respectively) which confer resistance to tetracyclines and the macrolide-lincosamide streptogramin B (MLSb phenotype) group were observed. Functional profiling showed a high abundance of biological processes (bacterial-type flagellum-dependent cell motility, cell adhesion, response to biotic stimulus and quorum sensing) associated with biofilm activity. Conclusions Characterized for the first time, the cervicovaginal microbiome in Afro-Caribbean women is predominantly CST IV with the three most abundant taxa consisting of bacterial strains P. timonensis DSM 22865, G. vaginalis 409-05 and L. iners DSM 13335. Its resistome had multiple AMR genes that confer resistance to antibiotics commonly used in the treatment of sexually transmitted infections (STIs) and bacterial vaginosis (BV). In this study, the occurrence of biofilm activity within the cervicovaginal microbiome suggested a possible regulatory role. We present a conceptual immuno-munibiome model that advances a mechanistic approach for the structure and regulation of the vaginal ecosystem in the Afro-Caribbean women cohort.
Efficacy of alendronate for the treatment of ankylosing spondylitis: a protocol for systematic review and meta-analysis
Authors: Tang Yu-hua , Li Yu-zhi , Tang Zhao-chen , Jiang Quan-wei , Zhao Yu 
Published: May 2020

Abstract
Background Ankylosing spondylitis (AS) is a very tricky orthopedic disorder. If such condition can not be managed fairly well, it may significantly affect quality of life and even leads to disability among such population. A variety of studies have reported that alendronate is utilized for the treatment of AS. However, their results are still contrary, and no systematic review has addressed on this topic. Thus, this study will systematically assess the efficacy and safety of alendronate for the treatment of patients with AS. Methods A comprehensive literature search will be performed from the below electronic databases from their commencement to the January 31, 2020 without language and publication status limitations: PUBMED, EMBASE, Cochrane Library, Web of Science, Allied and Complementary Medicine Database, WANGFANG, and China National Knowledge Infrastructure. Only randomized controlled trials (RCTs) focusing on the alendronate for the treatment of patients with AS will be considered for inclusion in this study. Two authors will independently select all identified records, extract essential data from all included studies, and appraise study quality for each eligible trial using Cochrane risk of bias. If any differences occur, another experienced author will be invited to solve them by discussion and a consensus decision will be made. We will implement RevMan 5.3 software to analyze the extracted data. Results This study will summarize high quality RCTs to assess the efficacy and safety of alendronate for the treatment of patients with AS through primary outcome of bone densitometry; and secondary outcomes of pain intensity, quality of life, disease activity, functional status, and adverse events. Conclusions This study will provide evidence to help determine whether alendronate is an effective and safe management for patient with AS or not.
Serum Zinc Deficiency in Squamous Cell Carcinomas of Oral and Maxillofacial Region: A Risk Factor to its Development and Metastasis
Authors: Xu Zhenq , Shang Jianw , Wang Guoq , Long Li , Zhang Ping 
Published: May 2020

Abstract
Objectives To explore whether serum Zinc deficiency (sZnd) is a promoter to the development and lymphonode metastasis of squamous cell carcinoma (SCC) of oral and maxillofacial region (OMF). Methods 610 patients with SCC were enrolled in the study group, the controls consisted of the same number of age-gender matched subjects without cancers, serum Zinc level was tested in both groups. Characteristics of SCCs were investigated. Different concentration of serum Zinc and prevalence of sZnd between the two groups were calculated using Chi-square test. The association between serum Zinc status and SCC with different T-stages and lymphonode metastasis was focused on research. Results The patients varied from 19 to 87 years with a mean age of 58.89±10.91 years. Oral cavity was the most commonly affected region. Males were involved predominantly with a ratio of 1.44:1 to females. The concentration of serum Zinc in malignancies was 12.57±2.53 μmol/L, 19.2% suffered from sZnd; in the control group were 14.65±2.25 μmol/L and 6.1%. Decreased serum Zinc and increased prevalence of sZnd in SCC were statistically significant to controls (p=0.000) . Increased incidence of sZnd and reduced level of serum Zinc correlated significantly to the the progression and lymphnode metastasis of SCC (p<0.01). Conclusions sZnd was a predisposing indicator to the tumorigenesis of SCC and also a promoter to its aggravation and lymphonode metastasis, which should be considered as a factor in devising the treatment plannings.
The postoperative outcomes of the dominant lung adenocarcinoma with multiple synchronous ground glass nodules.
Authors: Hotta Takamasa , Tsubata Yukari , Tanino Akari , Nakao Mika , Amano Yoshihiro , Hamaguchi Megumi , Hamaguchi Shunichi , Kishimoto Koji , Isobe Takeshi 
Published: May 2020

Abstract
Background
Multiple synchronous ground glass nodules (GGNs) are known to be malignant but progress slowly. Multiple synchronous lesions in the same patient show independent characteristics and must be treated individually.
Methods
This was a retrospective review of 34 lung adenocarcinoma patients with multiple synchronous GGNs in an Asian population. One hundred twenty-seven single lung adenocarcinoma patients were included for comparison. The follow-up period was 5 years for all patients.
Results
The 5-year overall survival (OS) patients with multiples did not differ from that of patients with single lesion to a statistically significant extent (Single: 81.8% vs. Multiple: 88.2%, P = 0.3602). Dominant tumors (DTs) with a ground glass component and consolidation were divided into three categories based on the consolidation-to-tumor ratio on radiological imaging. No significant differences were observed among the three DT categories. Twenty-four patients had unresected GGNs, progression of the unresected GGN occurred in 10 of these cases. The OS and disease-free survival (DFS) curves of patients with and without GGN progression did not differ to a statistically significant extent (OS: 80% vs. 92.9%, P = 0.3870; DFS: 80% vs. 100%, P = 0.0977).
Conclusions
The outcomes were best predicted by the stage of the DT. After surgery patients require careful follow-up because unresected GGNs may progress. At the same time, the increase in residual lesions and the appearance of new GGNs were not related to OS. The management should be determined by the DT with the worst prognosis.