bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of SN38-Resistant T47D Breast Cancer Cell Sublines Overexpressing BCRP, MRP1, MRP2, MRP3, and MRP4
Authors: Lee Hee-Jeong , Choi Cheol-Hee 
Published: January 2021

Abstract
BackgroundAlthough several novel resistant breast cancer cell lines have been established, only a few resistant breast cancer cell lines overexpress breast cancer resistance proteins (BCRP). The aim of this study was to establish new resistant breast cancer cell lines overexpressing BCRP using SN38 (7-ethyl-10-hydroxycamptothecin), an active metabolite of irinotecan and was to discover genes and mechanisms associated with multidrug resistance.MethodsSN38-resistant T47D breast cancer cell sublines were selected from the wild-type T47D cells by gradually increasing SN38 concentration. The sensitivity of the cells to anti-cancer drugs was assessed by 3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Expression profiles of the resistance-related transporters were examined using the resistance diagnostic kit (Drugsporter®), real time RT-PCR, and western blot analysis. Intracellular drug accumulation in the resistant cells was determined using flow cytometry.ResultsThe SN38-resistant T47D breast cancer cell sublines T47D/SN120 and T47D/SN150 were established after long-term exposure (more than 16 months) of wild-type T47D cells to 120 nM and 150 nM SN38, respectively. T47D/SN120 and T47D/SN150 cells were more resistant to SN38 (14.5 and 59.1 times, respectively), irinotecan (1.5 and 3.7 times, respectively), and topotecan (4.9 and 12 times, respectively), than the wild-type parental cells. Both T47D/SN120 and T47D/SN150 sublines were cross-resistant to various anti-cancer drugs. These resistant sublines overexpressed mRNAs of MRP1, MRP2, MRP3, MRP4, and BCRP. The DNA methylase inhibitor 5-aza-2'-deoxycytidine and the histone deacetylase inhibitor trichostatin A increased the expression levels of BCRP, MRP1, MRP2, MRP3, and MRP4 transcripts in T47D/WT cells. Drug accumulation was found to be lower in T47D/SN120 and T47D/SN150 cells, compared to that in T47D/WT cells. However, treatment with known chemosensitizers increased the intracellular drug accumulation and sensitivity of anti-tumor agents.ConclusionT47D/SN120 and T47D/SN150 cells overexpressed MRP1, MRP2, MRP3, MRP4, and BCRP due to the suppression of epigenetic gene silencing via DNA hypermethylation and histone deacetylation. Although these resistant cells present a higher resistance to various anti-cancer drugs than their parental wild-type cells, multidrug resistance was overcome by treatment with chemosensitizers. These SN38 resistant T47D breast cancer cell sublines expressing resistance proteins can be useful for the development of new chemosensitizers.
The Association of the BRAF V600E Mutation with Clinicopathologic Characteristics in Chinese Population with Conventional Papillary Thyroid Carcinoma
Authors: Zhou Sheng Li , Guo Yan Ping , Zhang Lei , Deng Tao , Xu Zi Guang , Ding Chao , Sun Wen Cong , Zhao Yue Wu , Kong Ling Fei 
Published: January 2021

Abstract
Objective:The aim of the study is to evaluate the association of the BRAFV600E mutation with the clinicopathologic characteristics in Chinese population with papillary thyroid carcinoma (PTC).MethodsA total of 943 PTC patients who underwent thyroidectomy from 2014 to 2016 at Henan Provincial People’s Hospital were included in the present study. The BRAFV600E mutation was examined in each resected specimen by quantitative Real-time PCR (qRT-PCR) technique. Results The PTC patients were subclassified into the overall, PTC>10mm and papillary thyroid microcarcinoma(PTMC) groups. The positive rate of BRAFV600E mutation was 85.4% in Chinese patients with PTC. In both overall PTC and PTC> 10mm groups, the BRAFV600E mutation was much more frequently detected in elderly patients and patients at T1 stage (P< 0.05). In addition, the positive rate of BRAFV600E mutation was significantly higher in PTC patients without concomitant Hashimoto’s thyroiditis in overall PTC and PTMC groups (P< 0.05). Furthermore, logistic regression analysis suggested that the risk of having a larger tumor diameter was increased by 6-fold when BRAFV600E mutation in the PTMC group. No association between the BRAFV600E mutation and other clinicopathologic factors was observed. ConclusionThe BRAFV600E mutation was significantly associated with patients age and T stage. Furthermore, the risk of having a larger tumor size was significantly increased when BRAFV600E mutation in the PTMC group. which suggests that BRAFV600E mutation might play an important role in the activation of early thyroid carcinogenesis, the effect might weaken in the progression of PTC.
Ultrasound-targeted Simvastatin-loaded Microbubble Destruction Promotes OA Cartilage Repair by Modulating Cholesterol Efflux Pathway Mediated by PPARγ in Rabbits.
Authors: Wang Xinwei , Wang Danbi , Cheng Kai , Wang Qi , Wang Xiaoju , Lin Qiang , Song Jiulong , Xia Peng , Li Xueping 
Published: January 2021

Abstract
Objective: To evaluate ultrasound-targeted simvastatin-loaded microbubble destruction (UTMDSV) attenuation of osteoarthritis (OA) progression in rabbits through modulation of the peroxisome proliferator-activated receptor (PPARγ)-mediated cholesterol efflux pathway.Methods: In vitro, chondrocytes were treated with ultrasound (US), US-targeted microbubble destruction (UTMD), simvastatin (SV) and UTMDsv on alternate days for 4 weeks. Chondrocytes were also treated with PPARγ inhibitor, PPARγ inhibitor+UTMDsv and UTMDsv. The cholesterol efflux rate and triglyceride were measured respectively by assay kit and oil red O staining. In vivo, the OA rabbits were treated with a single intra-articular injection of UTMD, SV and UTMDSV every 7 days for 4 weeks. Cartilage histopathology was assessed by safranin-O staining and the Mankin score. Total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) in rabbit knee synovial fluid were detected by enzyme-marker assay. Aggrecan, collagen II and PPARγ expression levels were analyzed western blotting (WB).Results: OA models exhibited primarily by a loss of aggrecan and collagen II, changes to subchondral bone architecture and cartilage degradation. In vitro, UTMDSV significantly increased the cholesterol efflux rate and aggrecan, collagen II and PPARγ levels in OA chondrocytes; these effects were blocked by the PPARγ inhibitor. In vivo, UTMDSV significantly increased aggrecan, collagen II, PPARγ and HDL-C levels, while TC levels and Mankin scores were decreased compared with the UTMD, SV, OA and control groups (95% CI: 0.069 to 6.671).Conclusion: UTMDSV promotes the expression of aggrecan and collagen II and relieve cartilage degradation by modulating the PPARγ-mediated cholesterol efflux pathway in rabbits.
Frequent, Quantitative Bone Planar Scintigraphy for Determination of Bone Anabolism in Growing Mice
Authors: Zaloszyc Ariane , Schmitt Claus Peter , Sayeh Amira , Higel Laetitia , Gros Catherine Isabelle , Bornert Fabien , Aubertin-Kirch Gaelle , Dillenseger Jean-Philippe , Goetz Christian , Constantinesco André , Fischbach Michel , Bahram Siamak , Choquet Philippe 
Published: January 2021

Abstract
BackgroundTo provide insight into bone turnover, quantitative measurements of bone remodeling are required. Radionuclide studies are widely used in clinical care, but have been rarely used in the exploration of the bone in preclinical studies. We describe a bone planar scintigraphy method for frequent assessment of bone activity in mice across the growing period. Since repeated venous radiotracer injections are hardly feasible in mice, we investigated the subcutaneous route.MethodsRepeated phosphonate tracer bone planar scintigraphy studies of the knee region and μCT to measure femur growth rate were performed in eight mice between week 6 and week 27 of life, i.e. during their growth period. Three independent investigators assessed the regions of interest (ROI). An index was calculated based on the counts in knees ROI (normalized by pixels and seconds), corrected for the activity administered, the decay between administration and imaging, and individual weights.ResultsA total of 97 scintigraphy studies and 90 μCT were performed. Repeated subcutaneous tracer injections were well tolerated and allowed for adequate radionuclide studies. Mean scintigraphic indexes in the knees ROI decreased from 87.4 ± 13.0x10-6 counts.s-1.pixel-1.MBq-1.g-1 at week 6 to 13.1 ± 3.9x10-6 counts.s-1.pixel-1.MBq-1.g-1 at week 27. The time constant of the fitted exponential decay was equal to 23.6 days. Mean femur length assessed by μCT increased from 12.2 ± 0.8 mm at week 6 to 15.8 ± 0.2 mm at week 24. The time constant of the fitted Gompertz law was equal to 26.7 days.ConclusionThis study demonstrates the potential of repeated bone planar scintigraphy in growing mice, with subcutaneous route for tracer administration, for quantitative assessment of bone remodeling.
Design and Experimental Investigation of a Novel Spiral Microfluidic Chip to Separate Wide Size Range of Micro-Particles Aimed at Cell Separation
Authors: Tabatabaei Seyed Ali , targhi Mohammad Zabetian 
Published: January 2021

Abstract
BackgroundIsolation of microparticles and biological cells on microfluidic chips has received considerable attention due to their applications in numerous areas such as medical and engineering fields. Microparticles separation are of great importance in bioassays owing to the need for a smaller sample and device size, and lower manufacturing costs. In this study, we first explain the concepts of separation and microfluidic science along with their applications in the medical sciences, and then, a conceptual design of a novel inertial microfluidic system is proposed and analyzed. The PDMS spiral microfluidic device was fabricated, and its effects on the separation of particles with sizes similar to biological particles were experimentally analyzed. This separation technique can be used in the process of separating cancer cells from the normal ones in the blood samples.ResultsThese components required for testing were selected, assembled, and finally, a very affordable microfluidic kit was provided. Different experiments were designed, and the results were analyzed using appropriate software and methods. Separator system tests with polydisperse hollow glass particles (diameter 2-20 µm), and monodisperse Polystyrene particles (diameter 5,15 µm), and the results exhibit an acceptable chip performance with 86 percent of efficiency for both monodisperse particles and polydisperse particles. The microchannel collects particles with an average diameter of 15.8 μm, 9.4 μm, and 5.9 μm at the Proposed reservoirs. ConclusionThis chip can be integrated into a more extensive point-of-care diagnostic system to test blood samples, and it could be said Based on the results of the experiments, this low-cost and user-friendly setting can be used for a variety of microparticle separation programs such as cell separation in biological assays.
Favorable Outcomes with Reduced Steroid Use in Juvenile Dermatomyositis
Authors: Orandi Amir B. , Fotis Lampros , Lai Jamie , Morris Hallie , White Andrew , French Anthony R. , Baszis Kevin 
Published: January 2021

Abstract
Background
High-intensity glucocorticoid regimens are commonly used to induce and maintain remission in Juvenile Dermatomyositis (JDM) but are associated with several adverse side-effects. Eminence-based treatment guidelines from CARRA and SHARE both advocate induction of intravenous pulse steroids followed by high dose oral steroids (2 mg/kg) tapered over 12 months. This study compares the time to disease control with reduced glucocorticoid dosing.
Methods
We retrospectively reviewed the records at a single tertiary-care children’s hospital of patients with JDM between 2000 and 2014 who had a minimum of 2 years of follow-up. The primary outcome measure was time to control of muscle and skin disease. Additional outcome measures included glucocorticoid dosing, effect of treatment on height, frequency of calcinosis and complications from treatment.
Results
Of the 69 patients followed during the study period, 31 fulfilled inclusion criteria. Median length of follow-up was 4.58 years, (3–7.5). Myositis control was achieved in a median of 7.1 months (range 0.9–63.4). Cutaneous disease control was achieved in a median of 16.7 months (range 4.3–89.5). The median starting dose of glucocorticoids was 0.85 mg/kg/day, (range 0.5–1.74). The median duration of steroid treatment was 9.1 months, (range 4.7–17.4), while the median duration of any pharmacotherapy was 29.2 months (range 10.4 to 121.3). Sustained disease control off medications was achieved in 21/31 (68%) patients by the end of review. Persistent calcinosis was identified in only one patient (3%).
Conclusion
Current accepted treatment paradigms for JDM include oral glucocorticoids beginning at 2 mg/kg/d reduced over 12 months; however, our results suggest that treatment using reduced doses and durations with early use of steroid-sparing agents are comparably effective in achieving favorable outcomes in JDM.
A pentagonal hydrogen-bond network facilitates an exceptional preference for asparagine in the S2 subsite of Stenotrophomonas maltophilia dipeptidyl peptidase 7
Authors: Nakamura Akihiro , Suzuki Yoshiyuki , Sakamoto Yasumitsu , Roppongi Saori , Kushibiki Chisato , Yonezawa Natsuri , Takahashi Masato , Shida Yosuke , Gouda Hiroaki , Nonaka Takamasa , Tanaka Nobutada , Ogasawara Wataru 
Published: January 2021

Abstract
The emergence of drug-resistant bacteria has become a major problem worldwide. Bacterial dipeptidyl peptidases 7 and 11 (DPP7s and DPP11s), belonging to the family-S46 peptidases, are important enzymes for bacterial growth and are not present in mammals. Therefore, specific inhibitors for these peptidases are promising as potential antibiotics. While the molecular mechanisms underlining strict substrate specificity at the S1 subsite of S46 peptidases have been well studied, those of relatively broad substrate preference at the S2 subsite of these peptidases are unknown. In this study, we performed structural and biochemical analyses on DPP7 from Stenotrophomonas maltophilia (SmDPP7). SmDPP7 showed substrate preference for hydrophobic amino acids at the S2 subsite in general, but as an exception, also for asparagine, a hydrophilic amino acid. Structural analyses of SmDPP7 revealed that this exceptional preference to asparagine is caused by a hydrogen bonding network at the bottom of the S2 subsite. The residues in the S2 subsite are well conserved among S46 peptidases as compared with those in the S1 subsite. We expect that our findings will contribute toward the development of a universal inhibitor of S46 peptidases. (184 words / 200 words)
Network Pharmacology-Based Investigation of Potential Targets of Astragalus-Angelica Compound Acting on Diabetic Nephropathy
Authors: Dong Youzi , Zhao Quanlin 
Published: January 2021

Abstract
Through network pharmacology and molecular docking to explore the mechanism of astragalus-angelica compound in the treatment of diabetic nephropathy (DN). Screen the components and targets of astragalus and angelica compound on the TCMSP and the BATMAN-TCM, and use Cytoscape 3.7.2 to establish a component-target interaction network. Relevant targets of DN were searched through related databases, and the common targets of astragalus-angelica compound prescription and DN were obtained after comparison. The target protein interaction analysis and visualization processing were performed, and gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis were performed through David database, and molecular docking was performed using PyMoL and AutoDock Vina software. Through network pharmacology screening, 142 main targets of astragalus-angelica compound in the treatment of DN have been identified. KEGG pathway enrichment analysis shows that the above key targets are related to apoptosis, oxidative stress, inflammation, insulin resistance and other related pathways. Molecular docking shows that the target protein has a good combination with the main active ingredients of astragalus-angelica compound. Astragalus-angelica compound may act on VEGFA, TP53, IL-6, TNF, mark1 and other targets to treat DN by regulating apoptosis, oxidative stress, inflammation, glucose and lipid metabolism and other pathways. Research methods based on network pharmacology and molecular docking provide new ideas for the pathogenesis and treatment of DN.
Effect of Pelvic Floor Muscle Electrical Stimulation on Lumbopelvic Control in Women With Stress Urinary Incontinence: Randomized Controlled Trial
Authors: Hwang Ui-jae , Lee Min-seok , Jung Sung-hoon , Kwon Oh-yun 
Published: January 2021

Abstract
Background: This study was performed to determine the effectiveness of 8 weeks of pelvic floor muscle (PFM) training by electrical stimulation (ES) on PFM function, lumbopelvic control, abdominal muscle thickness, and the contraction ratio in women with stress urinary incontinence (SUI). Methods: Women with SUI were randomized into an ES group (n = 18) or control group (n = 18). The ES group underwent a PFM ES training during 8-week, and the control group underwent only a general exercise without PFM training. PFM functions was measured using a perineometer. Lumbopelvic control was measured by one- and double-leg lowering tests. Abdominal muscle thickness and the contraction ratio during the active straight leg raise maneuver were measured by sonography. Results: The ES group showed significantly higher PFM strength and power than controls (p < 0.05) at after 8 weeks of training. PFM strength and power were significantly increased after 8 weeks of training in the ES group (p < 0.05). The ES group showed significantly higher values than the controls in both the one- and double-leg lowering tests (p < 0.05) at after 8 weeks of training. There were no significant between- or within-group differences, at rest or during contraction, in transverse abdominis (TrA), internal oblique abdominis (IO), or external oblique abdominis (EO) muscle thickness. Conclusion: Improvements in PFM functions by PFM ES could enhance lumbopelvic control in women with SUI.Trial registration: Clinical Research information Service, KCT0003357. Registered 11th November 2018 - Retrospectively registered, https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=12678&ltype=&rtype=
Soil Nitrogen Treatment Alters Microbiome Networks Across Farm Niches
Authors: Wang XinYue , Reilly Kerri , Biswas Ambarish , Johnson Linda , Teasdale Suliana , Grelet Gwen , Podolyan Ana , Gregorini Pablo , Morales Sergio , Attwood Graeme 
Published: January 2021

Abstract
BackgroundAgriculture is fundamental for food production, and microbiomes support agricultural through multiple essential ecosystem services. Despite the importance of individual (i.e. niche specific) agricultural microbiomes, microbiome interactions across niches are not well-understood. To observe the linkages between nearby agricultural microbiomes, multiple approaches (16S, 18S, and ITS) were used to inspect a broad coverage of niche microbiomes. Here we examined agricultural microbiome responses to 3 different nitrogen treatments (0 kg/ha/yr, 150kg/ha/yr and 300kg/ha/yr) in soil and tracked linked responses in other neighbouring farm niches (rumen, faecal, white clover leaf, white clover root, rye grass leaf, rye grass root)ResultsNitrogen treatment had little impact on microbiome structure or composition across niches, but drastically reduced the microbiome network connectivity in soil. Networks of 16S microbiomes were the most sensitive to nitrogen treatment across amplicons, where ITS microbiome networks were the least responsive.ConclusionsNitrogen enrichment in soil altered soil and the neighbouring microbiome networks, supporting our hypotheses that nitrogen treatment in soil altered microbiomes in soil and in nearby niches. This suggested that agricultural microbiomes across farm niches are ecologically interactive. Therefore, knock-on effects on neighbouring niches should to be considered when management is applied to a single agricultural niche.
Decreased neutrophil phagocytosis and killing of bacteria in COVID-19 patients
Authors: Nomani Masoumeh , Varahram Mohammad , Tabarsi Payam , Hashemian Seyed MohamadReza , Jamaati Hamidreza , Malekmohammad Majid , Ghazi Mona , Adcock Ian M. , Mortaz Esmaeil 
Published: January 2021

Abstract
A new coronavirus disease was described in December 2019 (COVID-19) in Wuhan City, Hubei Province, China and has reached pandemic status. According to the World Health Organization, the incubation time from being infected to symptom emergence averages 5-6 days for COVID-19 but can be up to 14 days. The mortality rate varies in different countries but is greater in elderly people and in patients with cardiovascular disease, diabetes and chronic respiratory diseases. Patients with chronic respiratory diseases often have reduced neutrophil function. We sought to measure neutrophil phagocytosis and bacterial killing in COVID-19 patients. 30 COVID-19 patients and 9 healthy individuals were recruited from the Masih Daneshvari Hospital (Tehran, Iran) from March-May 2020. Polymorphonuclear (PMN) cells were isolated from whole fresh blood and incubated with green fluorescent protein (GFP) labelled methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Phagocytosis was determined by measuring the florescence of co-cultures of bacteria and neutrophils and reported as the lag time before exponential growth. The number of viable bacteria was determined after 70 h by the Colony-Forming Unit (CFU). Bacterial phagocytosis of SA (22±0.9 versus 9.2±0.5h, p<0.01) and PA (12.4±0.6 versus 4.5±0.22, p<0.01) was significantly reduced in COVID-19 patients compared with healthy control subjects. After 70h there was a significant increase in CFU in COVID-19 subjects compared with healthy control subjects for both SA (2.6±0.09 x 108 versus 0.8±0.04 x 108 CFU/ml, p<0.001) and PA (2.2±0.09 x 109 versus 1.0±0.06 x 109 CFU/ml, p<0.001).These results suggests a defect in bacterial clearance by neutrophils in COVID-19 patients.
EEG Patterns in Patients with Prader-Willi Syndrome
Authors: Elia Maurizio , Rutigliano Irene , Sacco Michele , Madeo Simona , Wasniewska Malgorzata , Pomi Alessandra Li , Trifirò Giuliana , Bella Paolo Di , De Lucia Silvana , Vetri Luigi , Iughetti Lorenzo , Delvecchio Maurizio 
Published: January 2021

Abstract

Prader-Willi syndrome (PWS) is a rare disease determined by the loss of the paternal copy of the 15q11-q13 region, characterized by hypotonia, hyperphagia and obesity, short stature, hypogonadism, craniofacial dysmorphisms, cognitive and behavioral disturbances. The aims of this retrospective study were to analyze interictal EEG findings in a group of PWS patients and to correlate them with genetic, clinical and neuroimaging data. Demographic, clinical, genetic, EEG, and neuroimaging data about seventy-four patients were collected. Associations between the presence of EEG paroxysmal abnormalities, genotype, clinical and neuroimaging features were investigated. Four patients (5.4%) presented a drug-sensitive epilepsy. Interictal EEG paroxysmal abnormalities, focal or multifocal, were present in 25.7% of the cases, and normalization of EEG occurred in about 25% of the cases. In 63.2% of the cases paroxysmal abnormalities were localized over the middle-posterior regions bilaterally. Brain magnetic resonance imaging (MRI) was performed in 39 patients (abnormal in 59%). No relevant associations were found between EEG paroxysmal abnormalities and all the other variables considered. Interictal EEG paroxysmal abnormalities, in particular with a bilateral middle-posterior localization, could represent an important neurological feature of PWS not associated with genotype, cognitive or behavior endophenotypes, MRI anomalies, or prognosis.