bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eribulin activity in soft tissue sarcoma monolayer and three-dimensional cell line models: Could the combination with other drugs improve its antitumoral effect?
Authors: Escudero Javier , Heredia-Soto Victoria , Wang Yiyin , Ruiz Patricia , Gallego Alejandro , Pozo-Kreilinger Jose Juan , Martinez-Marin Virginia , Berjon Alberto , Ortiz-Cruz Eduardo , Bernabeu Daniel , Feliu Jaime , Tang Jing , Redondo Andres , Mendiola Marta 
Published: August 2021

Abstract
Background
Eribulin has shown antitumour activity in some soft tissue sarcomas (STSs), but it has only been approved for advanced liposarcoma (LPS).
Methods
In this study, we evaluated the effect of eribulin on proliferation, migration and invasion capabilities in LPS, leiomyosarcoma (LMS) and fibrosarcoma (FS) models, using both monolayer (2D) and three-dimensional (3D spheroid) cell cultures. Additionally, we explored combinations of eribulin with other drugs commonly used in the treatment of STS with the aim of increasing its antitumour activity.
Results
Eribulin showed activity inhibiting proliferation, 2D and 3D migration and invasion in most of the cell line models. Furthermore, we provide data that suggest for the first time a synergistic effect with ifosfamide in all models and with pazopanib in LMS as well as in myxoid and pleomorphic LPS.
Conclusions
Our results support the effect of eribulin on LPS, LMS and FS cell line models. The combination of eribulin with ifosfamide or pazopanib has shown in vitro synergy, which warrants further clinical research.
Development of a Human Umbilical Cord-derived Mesenchymal Stromal Cells-based Advanced Therapy Medicinal Product to treat immune and/or inflammatory diseases
Authors: MEBARKI Miryam , Iglicki Nathan , Marigny Céline , Abadie Camille , Nicolet Claire , Churlaud Guillaume , Maheux Camille , Boucher Hélène , Monsel Antoine , Menasché Philipe , Larghero Jérôme , Faivre Lionel , Cras Audrey 
Published: August 2021

Abstract
Background
Umbilical Cord-derived Mesenchymal Stromal Cells (UC-MSCs) revealed their key role in immune regulation, offering promising therapeutic perspectives for immune and inflammatory diseases. We aimed to develop a production process of an UC-MSCs-based product, then to characterize UC-MSCs properties and immunomodulatory activities in vitro, related to their clinical use and finally, to transfer this technology to a good manufacturing practice (GMP) compliant facility, to manufacture an Advanced Therapy Medicinal Product (ATMP).
Methods
Fifteen human umbilical cords (UCs) were collected to develop the production process. Three batches of UC-MSCs from a single donor were characterized at basal state and after in vitro pro-inflammatory stimulation by interferon-γ (IFNγ) and Tumor Necrosis Factor-α (TNFα). Proliferation, immunophenotype, activation markers expression and the inhibition of T-cells proliferation were assessed. Finally, this technology was transferred to a GMP-compliant facility to manufacture an UC-MSCs-based ATMP, from a single donor, using the explant method followed by the establishment of master and work cell stocks.
Results
Twelve UCs were processed successfully allowing to isolate UC-MSCs with doubling time and population doubling remaining stable until passage 4. CD90, CD105, CD73, CD44, CD29, CD166 expression was positive; CD14, CD45, CD31, HLA-DR, CD40, CD80 and CD86 negative, while CD146 and HLA-ABC expression was heterogeneous. Cell morphology, proliferation and immunophenotype were not modified by inflammatory treatment. Indoleamine 2,3-dioxygenase (IDO) expression was significantly induced by IFNγ and IFNγ + TNFα versus non-treated cells. Inter Cellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule 1 (VCAM-1) expression was induced significantly after priming. T-cells proliferation was significantly decreased in the presence of UC-MSCs in a dose-dependent manner. This inhibitory effect was improved by IFNγ or IFNγ + TNFα, at UC-MSCs:PBMC ratio 1:10 and 1:30, whereas only IFNγ allowed to decrease significantly T-cells proliferation at ratio 1:100. The manufacturing process of the UC-MSCs-based ATMP was qualified and authorized by the French regulatory agency for clinical use (NCT04333368).
Conclusion
This work allowed to develop an investigational UC-MSCs-based ATMP authorized for clinical use. Our results showed that an inflammatory environment preserves the biological properties of UC-MSCs with an improvement of their immunomodulatory functions.
Archaeometric studies on a Pompeian blue glass fragment from Regio I, Insula 14 for the characterization of glassmaking technology
Authors: Gelzo Monica , Corso Gaetano , Vergara Alessandro , Rossi Manuela , Miedico Oto , Arcari Ottavia , Chiaravalle Antonio Eugenio , Piccioli Ciro , Arcari Paolo 
Published: August 2021

Abstract
A Pompeian glass sample found in Reg. I, Insula 14, during the 1950’s Pompeii excavation was examined by Raman and Fourier transformed infrared spectroscopy, scanning electron microscopy, and inductively coupled plasma mass spectrometry. The analyzed specimen was selected based on its intense blue color and its well-preserved aspect. The purpose of the work was the chemical characterization of Pompeii’s glass in correlation to the actual knowledge of Roman glassmaking technology from the Mediterranean area. The results suggested that the Pompeii’s glass was a soda-lime-silica glass, but with a higher calcium content that, given the low content of lead, was used to stabilize the glass. The sample was in origin produced most likely as non-decolorized primary raw materials from eastern Mediterranean sites. Moreover, the intense blue color was related to the use mainly of cobalt, present in a weighty amount, and likely used as important coloring agents in the ancient secondary glass-making workshop.
Revisiting Szent-Györgyi's Cancer Hypothesis
Authors: Johnson Morris Alfred , Smits Michael 
Published: August 2021

Abstract
Rationale for this communication • -The promine/retine hypothesis on the control of cancer never reached a definite conclusion.• -The chemical natures of promine and retine remain unsettled though usually assumed to be glyoxalases and methylglyoxal.• -Many years ago we published some data that indicated the hypothesis may be operating in plants in which glyoxalase I may exist in normal cells in an inhibited state rather than compartmentalized as in early versions of the hypothesis.• -Manju Ray in India has published many papers claiming that methylglyoxal can be used to successfully treat cancer in humans.• -We present here previously unpublished data that shows depriving glyoxalase I of GSH allows methylglyoxal to kill mouse lymphoma cells. During treatment of two human cancer cell lines, killing of one line was enhanced by blocking thioredoxin as well as GSH.It is hoped that what is conveyed here may reignite interest in the near term. Nuclear methodology and statistics can be found in Figure 1. The data show a strong interaction between the hypothesis and thiols. It is concluded that the hypothesis has yet to be thoroughly investigated.
Association Between Schizoid and Aggressive Behaviors in Chinese Adolescents and the Mediating Influences of Childhood Trauma and Adverse Life Events
Authors: Yang Tingyu , He Yuqiong , Wu Shuxian , Luo Xuerong , Liu Jianbo 
Published: August 2021

Abstract
Background: This study investigated an association between schizoid and aggressive behaviors in Chinese adolescents, and the influences of childhood trauma and adverse life events on this association.Methods: The cross-sectional data of 3094 adolescents aged 12 to 16 years was collected from an epidemiological survey of child and adolescent mental disorders in Hunan Province, China. All these subjects completed the Achenbach’s Child Behavior Checklist, the Childhood Trauma Questionnaire-Short Form, and the Adolescent Self-rating Life Event Checklist. Use independent-sample t-test, Pearson’s correlation analysis, linear regression, mediation analysis and moderation analysis for data analysis.Results: The regression analysis showed that schizoid (βmale = 0.618, βfemale = 0.637, both P < 0.001) and adverse life events (βmale = 0.113, βfemale = 0.057, all P < 0.01) predicted aggressive behaviors. In addition, childhood trauma predicted aggressive behaviors (female: emotional abuse and sexual abuse (β = 0.118 and –0.062, both P < 0.01). Adverse Life events mediated the association between schizoid and aggressive behaviors in male and female adolescents. Emotional neglect in boys, and emotional abuse and sexual abuse in girls mediated the association. Only in female adolescents, the interaction between childhood trauma and life events affected the association between schizoid and aggressive behaviors (P = 0.023).Conclusions: Schizoid are associated with aggressive behaviors in Chinese adolescents. Life events and childhood trauma mediated the association between schizoid and aggressive behaviors, and the interaction between childhood trauma and life events affected girls’ aggressive behaviors. Hence, reducing childhood trauma and adverse life events can reduce the risk of aggressive behaviors in adolescents.
Study Of The Association Of Tumor Deposits With Tumour-infiltrating Lymphocytes And Prognosis In Gastric Cancer Patients
Authors: Li Xinyue , Yang Jing 
Published: August 2021

Abstract
Background: To investigate the relationship between tumour deposits(TDs) with the clinicopathological characteristics,prognosis of gastric cancer and tumour-infiltrating lymphocytes( TILs）.Methods: The pathological findings of 369 patients with gastric cancer were retrospectively analysed to observe the expression of TDs, and the levels of stromal TILs . The relationships between TDs status, clinicopathological characteristics, and TILs infiltration level were compared using the chi-square test, and rank data were tested using the rank sum test. Kaplan-Meier was used for survival analysis, and the log-rank test was used to determine the differences in survival curves between groups. The prognostic value of TDs was assessed using multivariate Cox proportional hazards regression analysis.Results: TDs were significantly associated with sex, Lymphovascular invasion, Perineural invasion, pathological TNM stage, and clinical stage (all P<0.05). TILs levels were lower in TDs(+) group and higher in TDs(-) group. TDs(+) group had poor Disease-free survival, cancer-specific survival , and overall survival as compared with TDs(-) groups.Conclusions: TDs is negatively correlated with TILs , and TDs+ was an Independent predictors of the prognosis of gastric cancer.
Cardiac-Specific Gene TNNI3 as a Potential Oncogene for Kidney Cancer and Its Involvement in Wnt Signaling Pathway
Authors: Zhao Weian , Yang Lu , Chen Xiaoxiang , Huang Wenqi 
Published: August 2021

Abstract
BackgroundCardiac troponin I (cTnI), encoded by TNNI3, is an inhibitory subunit of troponin complex expressed in cardiac muscle and is well known for its central role in the regulation of cardiac contraction. Although its aberrant expression has been reported in non-small cell lung cancer tissues and human carcinoma cells, its roles in cancers are still largely unknown. MethodsIn this work, the mRNA expression profiles of 289 Kidney renal papillary cell carcinoma (KIRP) samples were obtained from The Cancer Genome Atlas (TCGA) database. The tumor samples were classified into TNNI3-low and TNNI3-high groups. A total of 361 differentially expressed genes (DEgenes) were found correlated with TNNI3 expression. Univariate Cox analysis, log-rank test and the least absolute shrinkage and selection operator analysis were used to identify the candidate prognostic genes. The regulatory role of TNNI3 on Wnt signaling pathway was detected by western blot, wound healing assay and cell counting kit-8 assay.ResultsMultivariable Cox regression analysis was performed to establish a prognostic risk formula including genes PTPRH, LGR5 and DMRT3. The low-risk group had a better overall survival than the high-risk group (p < 0.0001), and the areas under the receiver operating characteristic curve for 3- and 5-year overall survival were 0.75 and 0.74, respectively. We thereafter constructed an target gene network to explore the potential functions of the three genes. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis identified their involvement with canonical Wnt signaling and several cancer-related pathways. In wound healing assay, the wound was closed obviously faster in the TNNI3 over-expression group as compared to control and blank groups. Significant increase in cell proliferation was seen at 72 h after transfection with TNNI3 as compared to the control and blank groups.The expressions of LGR5 and β-catenin increased in the TNNI3 over-expression group as compared to control and blank groups.ConclusionCollectively, our data provide evidence that TNNI3 could enhance cell migration and proliferation in 786-O cells and the three-gene signature related to TNNI3 could serve as an independent prognostic biomarker for KIRP. Insights are indeed provided into the potential oncogenic functions of TNNI3 in cancer research.
Citric Acid-Based Bicarbonate Dialysate Attenuates Aortic Arch Calcification in Maintenance Haemodialysis Patients: An Observational Study
Authors: Akiyama Ken-ichi , Hanafusa Norio , Miura Yutaka , Seki Momoko , Miyabe Yoei , Iwabuchi Yuko , Karasawa Kazunori , Sugiura Hidekazu , Uchida Keiko , Kawaguchi Hiroshi , Tsuchiya Ken , Kuro-o Makoto , Nitta Kosaku , Moriyama Takahito 
Published: August 2021

Abstract
Introduction: The progression of aortic calcification is associated with mortality in haemodialysis patients. Blood calciprotein particle (CPP) levels are associated with coronary artery calcification, and was reported to be inhibited when using citric acid-based bicarbonate dialysate (CD). Therefore, we examined the effect of CD on the progression of the aortic arch calcification score (AoACS) and blood CPP levels in haemodialysis patients.Methods: A 12-month retrospective observational study of 262 haemodialysis patients who met the eligibility criteria was conducted at Joban Hospital. Patients taking warfarin or bisphosphonates and those with baseline AoACS of 100% were excluded. Progression, defined as ΔAoACS (12 months – baseline) > 0%, was compared between the CD and acetic acid-based bicarbonate dialysate (AD) groups.Results: The CD group had significantly lower AoACS progression than the AD group (P = 0.037). ΔCPP and ΔAoACS were not correlated in the AD group (R2 = 0.030, P = 0.098), but were negatively correlated in the CD group (R2 = 0.065, P = 0.022). Multivariate logistic analysis showed that the CD (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.27‒0.97, P = 0.042) was significantly associated with the AoACS progression.Conclusion: CD may suppress the progression of vascular calcification in haemodialysis patients.
A Novel Rhizospheric Bacterium, Bacillus Velezensis NKMV-3 as a Biocontrol Agent against Alternaria Leaf Blight in Tomato
Authors: Murthy Vignesh , BodethalaNarayanan VedhaHari , Davoodbasha MubarakAli , ShankarRamakrishanan MadhanShankar 
Published: August 2021

Abstract
A novel strain of Bacillus isolated from rhizosphere has shown to be excellent biocontrol agents against various plant pathogens. In this study, a first report of a Bacillus strain NKMV-3 which effectively controlling Alternaria solani, which cause the Early Blight disease in tomato. Based on the cultural and molecular sequencing of 16S rRNA gene sequence, the identity of the strain was confirmed as Bacillus velezensis NKMV-3. The presence of the lipopeptide which are antibiotic synthesis genes namely Iturin C, Surfactin A, Fengycin B and D were confirmed through gene amplification. In addition, lipopetides was also confirmed through liquid chromatography. The extract showed inhibitory effect against A.solani in-vitro and detached tomato leaf assays. Bacillus velezensis strain NKMV-3 based formulations may provide an effective solution in controlling early blight disease in tomato and other crops.
Analysis of Prognostic and Therapeutic Values of Drug Resistance-Related Genes in the Lung Cancer Microenvironment
Authors: Zhu Liang , Chen Peixin , Wang Hao , Zhao Lishu , Guo Haoyue , Jiang Minlin , Zhao Sha , Li Wei , Zhu Jun , Yu Jia , Dai Jiawei , He Yayi 
Published: August 2021

Abstract
Background: The interaction between cancer cells and stromal cells has a significant contribution in tumorigenesis and tumor development, and plays an anti-tumor immune effect under the regulation of drug resistance related genes, which affects the outcome of patients. CCDC73, DLGAP1, DSEL, ESR1, and SEC14L5 were identified as drug resistance-related genes in lung cancer. However, these genes have no clear value in lung cancer in terms of expression and prognosis.Results: The transcriptional expression level of DLGAP1 was remarkably increased in lung cancer tissues, while the transcriptional level of SEC14L5 was significantly decreased. The pathological stage of lung adenocarcinoma (LUAD) was tightly correlated with the expression of SEC14L5. The lung cancer patients with high transcription level of CCDC73 gene tended to have a good prognosis. The function of drug resistance-related genes is mainly related to RNA polymerization. Our results showed that infiltration of six types of immune cells (dendritic cells, macrophages, neutrophils, B cells, CD4+T cells, and CD8+ T cells) significantly correlated with the expression of these drug resistance-related genes.Conclusions: Novel screening for immunotherapy targets and prognostic biomarkers in lung cancer may draw inspiration from our results.
Mean Corpuscular Hemoglobin Predicts Length of Hospital Stay Independent of Severity Classification in Acute Pancreatitis Patients: a Retrospective Study
Authors: Lin Hao , Yu Ting , Xu Rong , Li Xing 
Published: August 2021

Abstract
Background/Objectives: The aim of this study is to explore the relationship between length of hospital stay and mean corpuscular hemoglobin (MCH) in acute pancreatitis (AP) patients.Methods: The study included 273 AP patients without coronary heart disease, diabetes, hypertension, tumor, psychosis and anemia. The clinical data was collected from electronic medical records.Results: We separated all data into three groups according to length of hospital stay. We observed that gender (P=0.017) and severity classification (P=0.000) were significantly correlated with length of hospital stay among three groups. Notably, MCH level was significant increased among three groups (30.02±1.91, 30.21±1.81, 30.92±2.47 pg, P=0.009). Thus, we separated all data into two groups according to MCH level, and observed significant increases of length of hospital stay between two groups (11.95±7.03, 13.96±8.18 days, P=0.030). A positive correlation between length of hospital stay and MCH was observed in these individuals (r=0.172, P=0.004). Multiple linear regression analysis showed that MCH was independent correlated with length of hospital stay, no matter whether severity classification of AP was included (beta=0.248, P=0.000; beta=0.212, P=0.000).Conclusions: We concluded that length of hospital stay is correlated with MCH level in AP patients, and the MCH level may predict length of hospital stay independent of severity classification in this disease. Our results may provide a potential evaluation basis for the management of patients with AP.
Loss of RPS27a expression regulates cell cycle, apoptosis, and proliferation via the RPS27a-RPL11-MDM2-p53 pathway in lung adenocarcinoma cells
Authors: Li Hongyan , Zhang Hong , Huang Guomin , Bing Zhitong , Luo Hongtao , Xu Duling , Liu Jiadi , An Xiaoli 
Published: August 2021

Abstract
Background
Some ribosomal proteins (RPs) might regulate the MDM2–p53 loop by binding to RPL5 or RPL11. This study aimed to explore whether ribosomal protein S27a (RPS27a) interacted with the ribosomal protein L11 (RPL11) to regulate p53 in lung adenocarcinoma (LUAD) cells.
Methods
RPL11-interacting proteins were identified using a proteomics approach. Co-immunoprecipitation (co-IP), docking analysis, GST-fusion and in vitro ubiquitination assay were used to analyze the interaction of RPS27a and RPL11. Cell cycle, apoptosis, cell invasion, cell viability and colony-formation assay were analyzed by knocking down RPS27a. The RPS27a mRNA expression in LUAD was analyzed based on the TCGA dataset and the RPS27a expression was detected by immunohistochemistry in LUAD samples. At last, the RPS27a and p53 expression were analyzed by immunohistochemistry in xenograft tumors by blocking RPS27a.
Results
The ablation of RPS27a inhibits murine double minute 2 (MDM2)-mediated p53 ubiquitination, induced G1/S cell cycle arrest and apoptosis, and inhibited the proliferation of LUAD cells. Also, it induced p53-dependent cell cycle arrest and RPL11-dependent p53 activation. The protein–protein docking results revealed that RPS27a and RPL11 formed a stable complex structure. The GST-fusion protein–protein association assay demonstrated that RPS27a bound to RPL11. The overexpressed RPS27a in LUAD was found to be correlated with a poorer prognosis based on the TCGA dataset. RPS27a expression was high in patients with LUAD. Blocking RPS27a increased p53, thus, suppressing cell proliferation and A549 xenograft growth in nude mice.
Conclusions
This study was novel in reporting that RPs bound to RPL11 to regulate the MDM2-p53 feedback loop, revealing that RPS27a plays an important function in LUAD growth. Hence, RPS27a might provide a diagnostic marker or therapeutic target for patients with LUAD.