bluuebunny/crossref_metadata_2025_split huggingface dataset:
Micelles Self-Assembled by 3-O-β-D-Glucopyranosyl Latycodigenin Enhance Cell Membrane Permeability, Promote Antibiotic Pulmonary Targeting and Improve Anti-infective Efficacy
Authors: Zhang Man , Ye Lili , Huang Hao , Cheng Dandan , Liu Kaixin , Wu Wenbo , Shen Fukui , Jiang Zhihong , Hou Yuanyuan , Bai Gang 
Published: July 2020

Abstract
Background: Nanoparticle-based pulmonary drug delivery systems are commonly developed and applied for drug-targeted delivery. It exhibits significant advantages compared to traditional pulmonary drug delivery systems. However, developing a formulation for each drug is a time-consuming and laborious task. Results: This study designed and constructed a universal lung-targeting nanoparticle. The self-assembled micelles were composed of a platycodon secondary saponin, 3-O-β-D-glucopyranosyl platycodigenin 682 (GP-682), via its specific amphiphilic structure. GP-682 micelles obtained a relatively stable zeta potential with a particle size between 60 to 90 nm, and the critical micelle concentration (CMC) value was approximately 42.3 μg/mL. Pre-incubation of GP-682 micelles markedly enhanced the cell membrane permeability, and improved drug uptake in vitro. The results were visualized using fluorescent dye tracing, transmission electron microscopy (TEM) observation and lactate dehydrogenase (LDH) releasing assay. The benefits enhanced the distribution of levofloxacin (Lev) in mouse lung tissue and reduced the overdosing of antibiotics. The acute lung injury mice model induced by Pseudomonas aeruginosa PA 14 strain demonstrated that pre-injection of GP-682 micelles before antibiotic administration produced a higher survival rate and anti-infective efficacy in vivo. It included a reduction in pulmonary injury, bacterial invasion and cytokines expression compared to treatment with Lev alone. Conclusions: GP-682 micelles are another nanoparticle-based pulmonary drug delivery system and provides a new option for lung-targeting therapy.
The Circular RNA circZFR Phosphorylates Rb Promoting Cervical Cancer Progression by Regulating the SSBP1/CDK2/cyclin E1 Complex
Authors: Zhou Mingyi , Yang Zhuo , Wang Danbo , Chen Peng , Zhang Yong 
Published: July 2020

Abstract
Background: As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown. Methods: We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change >2, and P <0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR.Results: Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation. Conclusion: Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.
Integrating the lncRNA and mRNA expression profiles of TLR4-primed mesenchymal stem cells in ankylosing spondylitis
Authors: Li Yuxi , Li Ming , Huang Jiajun , Liang Yuwei , Huang Junshen , Liu Xiangge , Cheng Ziying , Lu Shixin , Liu Ting , Huang Lin 
Published: July 2020

Abstract
Background

Our previous study found that the toll-like receptor 4 (TLR4) expression of ankylosing spondylitis (AS) patients was significantly different from that of healthy donors. The goals of this study were to explore the expression profiles and functional networks of lncRNAs and mRNAs in TLR4-primed mesenchymal stromal cells from AS patients (AS-MSCs) and to clarify the mechanisms by which TLR4-primed MSCs exert immunoregulatory effects in AS.
Methods

Firstly, the immunoregulatory effects of MSCs were determined after TLR4 activation. Then, the differentially expressed (DE) lncRNAs and mRNAs between the control group (AS-MSCs without stimulation) and experimental group (AS-MSCs stimulated with lipopolysaccharide) were identified through high-throughput sequencing followed by qRT-PCR confirmation. Finally, bioinformatic analyses were performed to identify the critical biological functions, signalling pathways and associated functional networks involved in the TLR4-primed immunoregulatory function of AS-MSCs.
Results

TLR4-primed AS-MSCs showed a strong ability to inhibit the proliferation of peripheral blood mononuclear cells (PBMCs) with 1 µg/ml LPS stimulation for 4 hours. A total of 147 DE lncRNAs and 698 DE mRNAs were identified between TLR4-primed AS-MSCs and unstimulated AS-MSCs. Significant fold changes in lncRNA and mRNA levels were confirmed by qRT-PCR. GO and KEGG analysis demonstrated that the DE mRNAs and lncRNAs were highly associated with the inflammatory response. Cis-regulation prediction revealed 9 novel lncRNAs while trans-regulation prediction revealed 15 lncRNAs, respectively.
Conclusions

Our research describes the lncRNA and mRNA expression profiles and functional networks in TLR4-primed AS-MSCs, which is supposed to enhance the understanding of the pathogenesis of AS-MSC immunoregulatory dysfunction.
Melphalan induces cardiotoxicity through oxidative stress in cardiomyocytes derived from human induced pluripotent stem cells
Authors: Liu Rui , Li Dong , Sun Fangxu , Rampoldi Antonio , Maxwell Joshua , Wu Ronghu , Fischbach Peter , Castellino Sharon , Du Yuhong , Fu Haian , Mandawat Anant , Xu Chunhui 
Published: July 2020

Abstract
Background: Treatment-induced cardiotoxicity is a leading noncancer-related cause of acute and late onset morbidity and mortality in cancer patients on antineoplastic drugs such as melphalan—increasing clinic case reports have documented that it could induce cardiotoxicity including severe arrhythmias and heart failure. As the mechanism by which melphalan impairs cardiac cells remains poorly understood, here we aimed to use cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) to investigate the cellular and molecular mechanisms of melphalan-induced cardiotoxicity and to explore potential targeted therapeutics.Methods: hiPSC-CMs were generated and treated with clinically relevant doses of melphalan. For the characterization of melphalan-induced cardiotoxicity, cell viability and apoptosis were quantified. Ca 2+ transient and contractility analyses were used to examine the alterations of hiPSC-CM function. Proteomic analysis, reactive oxygen species detection, and RNA-Sequencing were conducted to investigate underlying mechanisms. Results: Melphalan treatment of hiPSC-CMs induced oxidative stress, caused Ca 2+ -handling defects and dysfunctional contractility, altered global transcriptomic and proteomic profiles, and resulted in apoptosis and cell death. The antioxidant N-acetyl-L-cysteine attenuated these genomic, cellular and functional alterations. In addition, several other signaling pathways including the p53 and transforming growth factor-β signaling pathways were also implicated in melphalan-induced cardiotoxicity according to the proteomic and transcriptomic analyses. Conclusions: Melphalan induces cardiotoxicity through the oxidative stress pathway. This study provides a unique resource of the global transcriptomic and proteomic datasets for melphalan-induced cardiotoxicity and can potentially open up new clinical mechanism-based targets to prevent and treat melphalan-induced cardiotoxicity.
Impact of bilateral-coordinated movement on manipulative skill competency in school-aged children
Authors: Chen Jun , Wang Xiaozan , Chen Weiyun 
Published: July 2020

Abstract
Background Researchers found that manipulative skill competency in childhood not only help improve physical activity participation, but also help adolescent learn specialized sport skills. This study aimed at examining the effects of an 8-week bilateral-coordinated movement (BCM) intervention on manipulative skill competency in school-aged children.Methods Participants were 314 fourth-grade students in two elementary schools. This study used 2-arm quasi-experimental research design. For one elementary school, two fourth-grade classes were assigned to the BCM group, the other two fourth-grade classes were assigned to the control group. For another elementary school, one fourth-grade class was assigned to the BCM group and another fourth-grade class to the control group. The students in the BCM group received an 8-week, two 40-minute BCM lessons in soccer and another 8-week, two 40-minute BCM lessons in basketball, while the control group received an 8-week, two 40-minute regular PE lessons in soccer and basketball, respectively. Students’ manipulative skill competency in soccer and basketball skills were pre- and post-tested using the two PE Metric assessment rubrics. Data were analyzed by means of descriptive statistics, independent sample t test, ANCOVA and ANOVA repeated measures.Results The results showed a significant main effect of time (pre-test vs. post-test) in soccer skills (F = 273.095, p = .000, 𝜂2 = .468) and in basketball skills (F = 74.619, p = .000, 𝜂2 = .193). Also, the results revealed a significant main effect of group (BCM group vs. control group) in soccer skills (F = 37.532, p = .000, 𝜂2 = .108), marginal significant main effect of group in basketball skills (F = 3.619, p = .058, 𝜂2 = .011). Further, there was significant interaction effect between the time and group in soccer skills (F = 37.532, p = .000, 𝜂2 = .108) and in basketball skills (F = 18.380, p = .000, 𝜂2 = .056).Conclusions It was concluded that after participated in the 8-week, 16 40-min lessons of BCM, the fourth-grade students had greater improvement in soccer and basketball dribbling, passing and receiving skills, compared to the control group.
Medical Waste Management: An Assessment at District-Level Public Health Facilities in Bangladesh
Authors: Sujon Hasnat , Biswas Taposh Kumar , Chowdhury Aklima , Chowdhury Mahbub Elahi 
Published: July 2020

Abstract
Background Due to the heavy patient-load and various types of services, the public health facilities produce a bulk of medical wastes (MW) in Bangladesh. Improper disposal of MW increases the risk of infection among the healthcare service personnel, patients, and attendants. The current study aimed to assess the practices of MW management and quantify those to find out the gaps in the specific steps of waste management.Methods As part of a larger intervention study, a facility assessment was conducted during November 2015 to March 2016 at a District Hospital (DH) and a Mother and Child Welfare Centre (MCWC) both being located in the same district, Non-participatory observation of MW management was done using a checklist developed following the Guideline for Medical Waste Management of Bangladesh. Scoring was applied for various activities of MW management performed in the study facilities.Results The overall scores in bin management, segregation, and collection of wastes were 64.5%, 58.1%, and 62.0% in the DH and 53.1%, 41.5%, and 48.0% in the MCWC respectively. The performance of operation theatre in MCWC was the lowest among different corners (16.7–36.0%). Re-usable waste was segregated poorly (32% in DH and 0% in MCWC), and almost none was shredded (4% in DH and 0% in MCWC). The wastes were transported from in-house to out-house temporary storage area in open-bin without any trolley or specific route. Storage area was accessible to unauthorized persons, e.g. waste-picker in DH. While DH segregated 84% of its infectious wastes at source, they eventually got mixed-up with other wastes in the storage area and delivered to municipality for dumping. MCWC could segregate only 40% of its infectious wastes at source and disposed those, using pit method. Both the facilities disposed sharp medical wastes by open-air burning and liquid wastes through sewerage without any treatment.Conclusions The performance of MW management was poor in both the study facilities. Advocacy to the healthcare personnel and refresher training, along with supportive supervision and monitoring, may improve the situation. Moreover, larger study is needed to find out the reasons behind such poor MW management.
How does area-level deprivation depress an individual’s self-rated health and life satisfaction? Evidence from a nationwide population-based survey in Japan
Authors: Oshio Takashi , Kimura Hiromi , Nishizaki Toshimi , Omori Takashi 
Published: July 2020

Abstract
Background: Area-level deprivation is well known to have an adverse impact on mortality, morbidity, or other specific health outcomes. This study examined how area-level deprivation may affect self-rated health (SRH) and life satisfaction (LS), an issue that is largely understudied.Methods: We used individual-level data obtained from a nationwide population-based internet survey conducted between 2019–2020, as well as municipality-level data obtained from a database provided by the Japanese government (N=12 461 living in 366 municipalities). We developed multilevel regression models to explain an individual’s SRH and LS scores using four alternative measures of municipality-level deprivation, controlling for individual-level deprivation and covariates. We also examined how health behavior and interactions with others mediated the impact of area-level deprivation on SRH and LS.Results: Participants in highly deprived municipalities tended to report poorer SRH and lower LS. For example, when living in municipalities falling in the highest tertile of municipality-level deprivation as measured by the z-scoring method, SRH and LS scores worsened by a standard deviation of 0.05 (p<0.05) when compared with those living in municipalities falling in the lowest tertile of deprivation. In addition, health behavior mediated between 17.6 % and 33.1 % of the impact of municipality-level deprivation on SRH and LS, depending on model specifications.Conclusion: This study showed that area-level deprivation modestly depressed an individual’s general health conditions and subjective well-being. The results underscore the need for public health policies to improve area-level socioeconomic conditions and to promote healthy lifestyles to alleviate the negative impact of area-level deprivation.
Significance of Coagulation and Fibrinolysis Markers for Benign and Malignant Soft Tissue Tumors
Authors: Asanuma Kunihiro , Nakamura Tomoki , Hagi Tomohito , Okamoto Takayuki , Kita Kouji , Nakamura Koichi , Matsuyama Yumi , Yoshida Keisuke , Asanuma Yumiko , Sudo Akihiro 
Published: July 2020

Abstract
Background: The intimate relationship between coagulation and fibrinolysis in malignant tumors is a well-known phenomena, with the malignant phenotype enhancing coagulation and fibrinolysis. We hypothesized that soft tissue sarcoma (STS) affects the expression of coagulation and fibrinolysis markers, which could be used to distinguish STS from benign soft tissue tumors. We analyzed the correlations between plasma levels of D-dimer (DD), plasmin-α2 plasmin inhibitor complex (PIC), soluble fibrin (SF), and thrombin-antithrombin III complex (TAT) in benign soft tissue tumors and STS to elucidate whether these markers can be used to predict STS.Methods: Plasma DD, PIC, SF and TAT levels in primary soft tissue tumors (benign, 67, STS 68) were measured before biopsy or treatment. The marker levels were analyzed and compared to various clinicopathological parameters.Results: In malignancy (STS), the average DD, PIC and SF levels were significantly higher than in benign tumors. Multivariate logistic analysis of continuous variables indicated that only PIC exhibited a significant difference (OR: 24.5, 95%CI: 3.55-170, p=0.0012). Receiver operating characteristic curve analysis produced area under the curve values for DD: 0.691, PIC: 0.784, SF: 0.734 and TAT: 0.588. Youden’s index was used to establish thresholds of 0.37 (DD), 0.80 (PIC), 0.90 (SF) and 0.82 (TAT). Threshold values for PIC and SF indicated high specificity (0.881, 0.791) and high positive predictive value (0.818, 0.745), respectively The highest accuracy value among the markers was observed for PIC (0.704). Significant differences in multivariate analysis of binary variables were demonstrated by categorizing low and high groups based on their threshold, PIC (≥0.80) (OR: 3.36, 95%CI: 1.19-9.43, p=0.0212) and SF (≥0.90) (OR: 2.63, 95%CI: 1.04-6.66, p=0.0404) . Conclusions: Of the coagulation and fibrinolysis markers studied, increased PIC levels were related to STS and over 0.80 PIC was the most suitable for the prediction of STS, which, along with other diagnostic tools, represents a helpful subsidiary tool for the prediction of STS.
Determination of Localized Skin Temperature of the Transtibial Residual Limb
Authors: Ghoseiri Kamiar , Allami Mostafa , Murphy Justin R. , Page Phil , Button Duane C. 
Published: July 2020

Abstract
Background: Interventions to resolve thermal discomfort as a common complaint in amputees, are usually chosen based on the residual limb skin temperature while wearing prosthesis; whereas, less attention was paid to residual limb skin temperature while outside of the prosthesis. The objective of this study was to explore the localized and regional skin temperature over the transtibial residual limb (TRL) while outside of the prosthesis.Methods: Eight unilateral transtibial amputees were enrolled in this cross sectional study. Participants sat on a chair and rested for 30 minutes while their prosthesis was removed. Twelve sites were marked in four columns (anterolateral, anteromedial, posteromedial, and posterolateral) and three rows (proximal, middle, and distal) over the residual limb and used for attachment of analog thermistors. Skin temperature was recorded and compared during 11 minutes. Furthermore, the relationship of skin temperature with participants’ demographic and clinical characteristics were explored.Results: The middle and distal zones of the anteromedial column had the highest and lowest skin temperatures (29.8 and 26.3°C, p<0.05), respectively. The average temperature of the TRL was 27.73±0.83°C and had no significant relationships (p>0.05) with participants’ demographic and clinical characteristics.Conclusions: An unequal distribution of temperature over the TRL was found with significantly higher and lower temperatures at its anterior column and distal row, respectively. This temperature pattern should be considered for thermoregulation strategies. Further investigation of the residual limb temperature while considering muscles thickness and blood perfusion rate are warranted with and without prosthesis.
hPMSCs protects against aging-induced oxidative damage of CD4+ T cells through activating Akt-mediated Nrf2 antioxidant signaling
Authors: Xiong Yanlian , Wang Yueming , Zhang Jiashen , Zhao Nannan , Zhang Aiping , Zhao Dongmei , Yu Zhenhai , Yin Yancun , Song Lele , Xiong Yanlei , Luan Xiying 
Published: July 2020

Abstract
Background: Mesenchymal stem cells (MSCs) was considered as regenerative therapeutic approach in both acute and chronic diseases. However, whether MSCs regulate the antioxidant metabolism of CD4+ T cells and weaken immunosenescence remains unclear. Here, we reported the protective effects of hPMSCs in aging-related CD4+ T cell senescence and identified the underlying mechanisms using a D-gal induced mouse aging model.Methods: In vivo study, 40 male C57BL/6 mice (8 weeks) were randomly divided into four groups: control group, D-gal group, hPMSC group and PBS group. In in vitro experiment, human naive CD4+ T (CD4CD45RA) cells were prepared using a naive CD4+ T cell isolation kit II and pretreated with the Akt inhibitor LY294002 and Nrf2 inhibitor ML385. Then, isolated naive CD4+ T cell were cocultured with hPMSCs for 72 h in the absence or presence of anti-CD3/CD28 Dynabeads and IL-2 as a mitogenic stimulus. Intracellular ROS changes were detected by flow cytometry. The activities of the antioxidant enzymes superoxide dismutase, glutathione peroxidase and catalase were measured by colorimetric analysis. The senescent T cells were detected SA-β-gal stain. The expression of aging related proteins were detected by Western blotting, RT-PCR and confocal microscopy.Results: We found that hPMSC treatment markedly decreased the ROS level, SA-β-gal positive cells number, senescence-associated secretory phenotype (IL-6 and OPN) expression and aging-related protein (P16 and P21) expression in senescent CD4+ T cells. Furthermore, hPMSC treatment effectively upregulated Nrf2 nuclear translocation and the expression of downstream target genes (HO-1, CAT, GCLC and NQO1) in senescent CD4+ T cells. Moreover, in vitro studies revealed that hPMSCs attenuated CD4+ T cell senescence by upregulating the Akt/GSK-3β/Fyn pathway to activate Nrf2 functions. Conversely, the antioxidant effects of hPMSCs were blocked by the Akt inhibitor LY294002 and Nrf2 inhibitor ML385 in senescent CD4+ T cells.Conclusions: Our results indicate that hPMSCs attenuate D-gal induced CD4+ T cell senescence by activating Nrf2-mediated antioxidant defenses and that upregulation of Nrf2 by hPMSCs is regulated via the Akt/GSK-3β/Fyn pathway.
Comparative evaluation of methods testing in vitro sensitivity to azithromycin in multi-drug resistant Pseudomonas aeruginosa isolated from cystic fibrosis patients
Authors: Soerensen Michael , Nurjadi Dennis , Khakimov Bakhodur , Boutin Sébastien , Dalpke Alexander H. , Eigenbrod Tatjana 
Published: July 2020

Abstract
Long-term treatment with azithromycin is a therapeutic option in Cystic Fibrosis (CF) patients chronically infected with P. aeruginosa . It was recently shown that azithromycin has direct antimicrobial activity when P. aeruginosa isolates are tested in Roswell Park Memorial Institute medium supplemented with fetal calf serum (RPMI 1640/FCS) by broth microdilution. We now investigated whether (i) azithromycin might also be active against multidrug resistant (MDR) P. aeruginosa isolated from CF patients and (ii) how in vitro sensitivity assays perform in synthetic cystic fibrosis sputum medium (SCFM), a medium that mimics the particular CF airway environment. In 17 (59%) out of 29 MDR P. aeruginosa CF isolates MICs for azithromycin ranged between 0.25 and 8 µg/ml and 12 isolates (41%) showed a MIC ≥512 µg/ml when measured in RPMI/FCS. In contrast, MICs were ≥256 µg/ml for all P. aeruginosa MDR isolates when tested in either SCFM or in conventional cation-adjusted Mueller Hinton Broth. High MIC values observed in CF adapted medium SCFM for both PAO1 and MDR P. aeruginosa CF isolates, as opposed to findings in RPMI, argue against routine azithromycin MIC testing of CF isolates.