bluuebunny/crossref_metadata_2025_split huggingface dataset:
The sodium channel NaX: Possible player in excitation–contraction coupling
Authors: Bogdanovic Elena , Potet Franck , Marszalec William , Iyer Hari , Galiano Robert , Hong Seok J. , Leung Kai P. , Wasserstrom John Andrew , George Alfred L. , Mustoe Thomas A. 
Published: February 2020

AbstractThe sodium channel NaX (encoded by the SCN7A gene) was originally identified in the heart and skeletal muscle and is structurally similar to the other voltage‐gated sodium channels but does not appear to be voltage gated. Although NaX is expressed at high levels in cardiac and skeletal muscle, little information exists on the function of NaX in these tissues. Transcriptional profiling of ion channels in the heart in a subset of patients with Brugada syndrome revealed an inverse relationship between the expression of NaX and NaV1.5 suggesting that, in cardiac myocytes, the expression of these channels may be linked. We propose that NaX plays a role in excitation–contraction coupling based on our experimental observations. Here we show that in cardiac myocytes, NaX is expressed in a striated pattern on the sarcolemma in regions corresponding to the sarcomeric M‐line. Knocking down NaX expression decreased NaV1.5 mRNA and protein and reduced the inward sodium current (INa+) following cell depolarization. When the expression of NaV1.5 was knocked down, ~85% of the INa+ was reduced consistent with the observations that NaV1.5 is the main voltage‐gated sodium channel in cardiac muscle and that NaX likely does not directly participate in mediating the INa+ following depolarization. Silencing NaV1.5 expression led to significant upregulation of NaX mRNA. Similar to NaV1.5, NaX protein levels were rapidly downregulated when the intracellular [Ca2+] was increased either by CaCl2 or caffeine. These data suggest that a relationship exists between NaX and NaV1.5 and that NaX may play a role in excitation–contraction coupling.
The miR-143/145 Cluster, a Novel Diagnostic Biomarker in Chondrosarcoma, Acts as a Tumor Suppressor and Directly Inhibits Fascin-1
Authors: Urdinez Joaquin , Boro Aleksandar , Mazumdar Alekhya , Arlt Matthias JE , Muff Roman , Botter Sander M , Bode-Lesniewska Beata , Fuchs Bruno , Snedeker Jess G , Gvozdenovic Ana 
Published: February 2020

ABSTRACT
Chondrosarcoma is the second most frequent bone sarcoma. Due to the inherent chemotherapy and radiotherapy resistance and absence of known therapeutic targets, clinical management is limited to surgical resection. Consequently, patients with advanced disease face a poor prognosis. Hence, elucidating regulatory networks governing chondrosarcoma pathogenesis is vital for development of effective therapeutic strategies. Here, miRNA and mRNA next generation sequencing of different subtypes of human chondrogenic tumors in combination with in silico bioinformatics tools were performed with the aim to identify key molecular factors. We identified miR-143/145 cluster levels to inversely correlate with tumor grade. This deregulation was echoed in the miRNA plasma levels of patients and we provided the first evidence that circulating miR-145 is a potential noninvasive diagnostic biomarker and can be valuable as an indicator to improve the currently challenging diagnosis of cartilaginous bone tumors. Additionally, artificial upregulation of both miRNAs impelled a potent tumor suppressor effect in vitro and in vivo in an orthotopic xenograft mouse model. A combined in silico/sequencing approach revealed FSCN1 as a direct target of miR-143/145, and its depletion phenotypically resembled miR-143/145 upregulation in vitro. Last, FSCN1 is a malignancy-promoting factor associated with aggressive chondrosarcoma progression. Our findings underscore miR-143/145/FSCN1 as important players in chondrosarcoma and may potentially open new avenues for specific therapeutic intervention options. © 2020 American Society for Bone and Mineral Research.
circ‐CEP85L suppresses the proliferation and invasion of gastric cancer by regulating NFKBIA expression via miR‐942‐5p
Authors: Lu Jun , Wang Yao‐hui , Huang Xiao‐yan , Xie Jian‐wei , Wang Jia‐bin , Lin Jian‐xian , Chen Qi‐yue , Cao Long‐long , Huang Chang‐ming , Zheng Chao‐hui , Li Ping 
Published: February 2020

AbstractThe expression pattern and role of circular RNAs (circRNAs) in the pathogenesis of gastric cancer (GC) and their underlying mechanisms remain unresolved. In this study, we identified differentially expressed circRNAs by a circRNA microarray and verified the results by quantitative reverse transcription‐polymerase chain reaction using 117 clinical samples. Cell Counting Kit‐8, wound healing, Transwell, and tumorsphere formation assays were conducted to assess the effects of circ‐CEP85L on cell proliferation and invasion in vitro. Mouse intraperitoneal injection models were used to assess the functions of circ‐CEP85L in vivo. Luciferase reporter assays, fluorescence in situ hybridization, and rescue experiments were performed to elucidate the underlying mechanism of circ‐CEP85L. We found that circ‐CEP85L, which has not been studied in GC, was significantly downregulated in GC tissues and that decreased circ‐CEP85L expression correlated significantly with a worse prognosis. The knockdown of circ‐CEP85L promoted the proliferation and invasion of GC cells, which was reversed by overexpression of circ‐CEP85L. Furthermore, inhibition of circ‐CEP85L promoted tumor growth in vivo. Mechanistically, circ‐CEP85L was confirmed to be a direct target of miR‐942‐5p. In addition, rescue experiments indicated that circ‐CEP85L is able to inhibit the proliferation and invasion of GC cells by sponging miR‐942‐5p. Finally, western blot assays verified that the downregulation of miR‐942‐5p efficiently reversed the inhibition of NFKBIA induced by circ‐CEP85L overexpression. Therefore, we conclude that circ‐CEP85L promotes NFKBIA expression by acting as a sponge of miR‐942‐5p; thus, inhibiting GC proliferation and invasion. circ‐CEP85L is a potential target in the treatment of GC.
Exosome‐mediated transfer of miR‐1260b promotes cell invasion through Wnt/β–catenin signaling pathway in lung adenocarcinoma
Authors: Xia Yang , Wei Ke , Hu Liu‐Qing , Zhou Cun‐Rong , Lu Zhi‐Bin , Zhan Gen‐Sheng , Pan Xiang‐Long , Pan Chun‐Feng , Wang Jun , Wen Wei , Xu Jing , He Zhi‐Cheng , Huang Chen‐Jun , Chen Liang 
Published: February 2020

AbstractIncreasing evidence confirms that exosome‐mediated transfer of microRNAs can influence cancer progression including tumor cell invasion, cell proliferation, and drug resistance via cell–cell communication. However, the potential role of exosomal‐miR‐1260b in lung adenocarcinoma (LAC) remains poorly understood. Thus, this study focused on investigating the function of exosomal‐miR‐1260b on cell invasion. Exosomal‐miR‐1260b was found to be higher in plasma of patients with LAC than that of healthy persons via quantitative real‐time polymerase chain reaction assay. The sensitivity and specificity of exosomal‐miR‐1260b (cutoff point: 2.027) were 72% and 86%, and area under the curve of 0.845 (95% CI = 0.772–0.922). Elevated expression of miR‐1260b in LAC tissues was positively correlated with exosomal‐miR‐1260b in plasma (r = .642, p < .05). Furthermore, ceramide biosynthesis regulated exosomal‐miR‐1260b secretion. Exosome‐mediated transfer of miR‐1260b promoted A549 cell invasion and was still functional inside A549 cells. Moreover, exosomal‐miR‐1260b regulated Wnt/β–catenin signaling pathway by inhibiting sFRP1 and Smad4. This study identified a new regulation mechanism involving in cell invasion by exosome‐mediated tumor‐cell‐to‐tumor‐cell communication. Targeting exosome‐microRNAs may provide new insights into the diagnosis and treatment of LAC.
Resveratrol suppresses interleukin‐6 expression through activation of sirtuin 1 in hypertrophied H9c2 cardiomyoblasts
Authors: Akhondzadeh Fariba , Astani Akram , Najjari Razieh , Samadi Morteza , Rezvani Mohammad Ebrahim , Zare Fatemeh , Ranjbar Ali Mohammad , Safari Fatemeh 
Published: February 2020

AbstractInflammatory cytokine, interleukin‐6 (IL‐6), plays an important role in the pathogenesis of cardiac hypertrophy. Recent studies have documented that resveratrol exhibits cardioprotective effects. The present study attempts to explore whether resveratrol suppreses IL‐6 in hypertrophied H9c2 cardiomyoblasts through histone deacetylase, sirtuin 1 (SIRT1). To induce hypertrophy, the cells were incubated with angiotensin II (Ang II). Treatment groups were treated with different doses (1, 10, 25, 50, 75, and 100 μM) of resveratrol (R). Cell viability was measured using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Cell size was determined using crystal violet staining. Gene expression was assessed by real‐time polymerase chain reaction technique. Enzyme‐linked immunosorbent assay was used to measure IL‐6 concentration. The results showed that cell area and ANP messenger RNA (mRNA) levels decreased significantly in R25+Ang, R50+Ang, and R100+Ang groups, as compared with Ang group. Therefore, 10, 20, 30, 40, and 50 μM of resveratrol were used to to evaluate its anti‐inflammatory effects. The results revealed that Ang II upregulated IL‐6 at both mRNA and protein levels (p < .001 vs. normal) and resveratrol (50 μM) decreased IL‐6 mRNA (p < .01) and protein (p < .05) significantly in comparison to Ang group. However, in groups in which the cells were pretreated with SIRT1 inhibitor, EX‐527, the response of resveratrol was partially reversed. Transcription levels of IL‐6 receptor components (gp130 and gp80) did not change significantly among the experimental groups. The current data suggests that resveratrol protects H9c2 cells against Ang II‐induced hypertrophy by suppression of IL‐6 through SIRT1 activation.
A Drug‐Drug Interaction Study to Evaluate the Effect of TAS‐303 on CYP3A Activity in the Small Intestine and Liver
Authors: Kumagai Yuji , Fujita Tomoe , Maeda Mika , Sasaki Yoshinobu , Nagaoka Makoto , Huang Jinhong , Takenaka Toru , Kawai Masaki 
Published: February 2020

AbstractTAS‐303 (4‐piperidinyl 2,2‐diphenyl‐2‐[propoxy‐1,1,2,2,3,3,3‐d7] acetate hydrochloride) is a novel selective noradrenaline reuptake inhibitor being developed for the treatment of stress urinary incontinence. An in vitro study and a physiologically based pharmacokinetic model simulation showed that TAS‐303 had inhibitory potential against cytochrome P450 (CYP) 3A. This open‐label, single‐group study investigated the effect of TAS‐303 on CYP3A activity by evaluating the pharmacokinetics (PK) of single‐dose oral simvastatin 5 mg or intravenous midazolam 1 mg after repeated oral administration of TAS‐303 3 mg in 12 healthy participants. TAS‐303 plus simvastatin resulted in a 1.326‐fold and a 1.420‐fold increase of simvastatin in peak plasma concentration and area under the plasma concentration‐time curve from time zero to time t, where t is the final time of detection (AUC0‐t), respectively. The addition of midazolam resulted in a 1.090‐fold increase in the midazolam AUC0‐t. TAS‐303 had a weak PK interaction with simvastatin but no apparent interaction with midazolam. TAS‐303 at 3 mg/day is a weak inhibitor of intestinal but not hepatic CYP3A activity. No clinically important safety concerns related to TAS‐303 were raised.
Contrast‐enhanced ultrasonography of intraluminal inferior vena cava leiomyosarcoma: A case report
Authors: Wu Xiaobei , Zhou Pingping , Li Kaiyan 
Published: February 2020

AbstractPrimary leiomyosarcoma of the inferior vena cava (IVC) is a rare and fatal disease. Imaging is the main diagnostic method. CT and MRI images of IVC leiomyosarcoma have been published, but ultrasonographic features have been scarcely described, especially with contrast‐enhancement. We report the case of a patient in whom ultrasonography incidentally revealed a mass in the IVC. Contrast‐enhanced ultrasonography showed heterogeneous enhancement in the arterial phase with some irregular non‐enhanced areas, and mild clearance in the venous phase. The location and nature of the lesion as shown by ultrasonography were confirmed by CT and MRI.
Water quality performance of wetlands receiving nonpoint‐source nitrogen loads: Nitrate and total nitrogen removal efficiency and controlling factors
Authors: Crumpton William G. , Stenback Greg A. , Fisher Stephen W. , Stenback Jana Z. , Green David I. S. 
Published: February 2020

AbstractNonpoint‐source nitrogen (N) loads in the U.S. Corn Belt are a major concern both for local impacts on receiving waters and for contributing to hypoxia in the Gulf of Mexico. Nonpoint‐source nutrient loads can be ameliorated by a combination of in‐field and offsite practices, and wetland restoration is a particularly promising approach for reducing N loads from agricultural drainage. However, there is considerable variability among wetlands, and adequate performance data are available for relatively few systems receiving unregulated nonpoint‐source loads. We measured N mass balances of 26 restored wetlands receiving a wide range of unregulated, naturally varying hydraulic and nutrient loads to evaluate the N removal performance of these systems and the effects of major factors controlling their performance. Nitrogen loads were primarily in the form of nitrate, and all of the wetlands were effective in reducing both nitrate and total N loads. Nitrate N and total N removal rates averaged 1,500 and 1,440 kg N ha−1 yr−1, respectively, with the slightly lower total N removal rates reflecting a small net export of reduced N (averaging 66 kg N ha−1 yr−1). Average nitrate and total N removal rates were substantially higher than typically reported for Corn Belt wetlands but comparable with highly loaded systems elsewhere. Nitrate removal efficiency ranged from 9 to 92% and was strongly related to hydraulic loading rate and temperature. Results demonstrate the substantial capacity of wetlands to reduce unregulated and highly variable nonpoint‐source N loads over a broad range of weather and loading conditions and provide a reasonable basis for predicting average wetland performance based on hydraulic loading rate, temperature, and nitrate concentration.
Outcomes in patients with acute upper gastrointestinal bleeding following changes to management protocols at an Australian hospital
Authors: Papadinas Adrianna , Butt Joshua 
Published: February 2020

Background and AimUpper gastrointestinal bleeding (UGIB) has a high mortality rate and requires efficient and directed acute management. This project aimed to assess patient outcomes following changes to UGIB management protocols at Northern Hospital, Victoria, Australia. Changes involved streamlining management under a single inpatient unit, earlier endoscopy, blood transfusion thresholds, and risk stratification.MethodsThis was a cohort study of 400 patients aged ≥18 years admitted to Northern Hospital who underwent endoscopy for acute UGIB. Data of preprotocol changes (Group 1) and prospectively postprotocol changes (Group 2) were collected retrospectively. Primary outcomes were inpatient mortality, rebleeding, radiologic or surgical intervention, and endoscopic reintervention. Secondary outcomes included length of stay (LOS) ≥4 days and blood units transfused. Univariate analyses were conducted comparing groups and associations between variables and outcomes, followed by multivariate analyses for each outcome.ResultsThere was no difference in mortality on multivariate analysis (P = 0.95). Rebleeding reduced by 4% (adjusted odds ratio [AOR] 0.48; P = 0.03), LOS ≥4 days reduced by 15.1% (AOR 0.46; P < 0.00) and median blood units transfused decreased with adjusted incidence rate ratio of 0.81 (P = 0.00). Early endoscopy (i.e. ≤12 h) for all patients increased by 15% (P < 0.00) and there were 12% more high‐risk patients (i.e. Glasgow–Blatchford score ≥ 12) in Group 2 (P = 0.01).ConclusionFollowing changes to UGIB protocols at this Australian hospital, endoscopic times decreased with reductions in rebleeding, LOS ≥4 days, and blood transfusion rates. These findings demonstrate improved outcomes after the implementation of new treatment targets focusing on streamlined care of patients presenting with UGIB.
Repertoire analysis of memory T‐cell receptors in Japanese patients with inflammatory bowel disease
Authors: Kakuta Yoichi , Nakano Takeru , Naito Takeo , Watanabe Kazuhiro , Izumiyama Yasuhiro , Okamoto Daisuke , Ichikawa Ryo , Moroi Rintaro , Kuroha Masatake , Kanazawa Yoshitake , Kimura Tomoya , Shiga Hisashi , Naitoh Takeshi , Kinouchi Yoshitaka , Unno Michiaki , Masamune Atsushi 
Published: February 2020

Background and AimThe T‐cell receptor (TCR) repertoire was assessed in response to various antigens and was considered to be associated with the pathogenesis of inflammatory bowel disease (IBD). Thus, we performed TCR repertoire analysis to examine the pathology of IBD from changes in the TCR repertoire of memory T cells in the intestinal lamina propria mononuclear cells (LPMCs) and peripheral blood mononuclear cells (PBMCs) of patients with IBD.MethodsLPMCs in the surgical specimens and PBMCs were isolated from 12 patients with IBD (5 patients with ulcerative colitis [UC] and 7 patients with Crohn's disease [CD]). PBMCs were collected from 10 healthy individuals as controls. Comprehensive TCR sequence analyses of adaptor‐ligation polymerase chain reaction (PCR) products were performed using MiSeq.ResultsThe diversity of TCR‐α and TCR‐β in PBMCs was significantly lower in patients with IBD than that in controls (P = 0.00084 and 0.0013, respectively). Comparisons of TCR diversity in LPMCs and PBMCs between CD and UC showed that the diversity in LPMC was not affected by diseases, whereas that in PBMCs was significantly lower in CD than in UC (P = 0.045 and 0.049, respectively). Some TCR clones may have shown a specific increase or decrease in CD and UC, and many clones were common to both LPMCs and PBMCs in the same patients.ConclusionThe diversity of TCR clones in LPMCs and PBMCs in patients with IBD was significantly lower than that of PBMCs in controls. TCR diversity in PBMCs was particularly low in patients with CD.
Synthesis of novel quinoline‐thiosemicarbazide hybrids and evaluation of their biological activities, molecular docking, molecular dynamics, pharmacophore model studies, and ADME‐Tox properties
Authors: Patel Dhaval B. , Darji Drashti G. , Patel Krupa R. , Rajani Dhanji P. , Rajani Smita D. , Patel Hitesh D. 
Published: February 2020

AbstractIn the present study, a novel series of N‐((substituted)carbamothioyl)‐2,4‐dimethylquinoline‐3‐carboxamide (7a‐7s) was synthesized by microwave‐assisted method. Structure of these derivatives was examined by spectroscopic techniques such as 1H NMR, 13C NMR, FT‐IR, and ESI‐MS. Further, the novel synthesized compounds were evaluated for their in‐vitro biological activities against antibacterial, antifungal, antimalarial, and antituberculosis activity as well as for in‐silico study. The antimalarial results demonstrated that compounds 7c and 7q (0.02 μg/mL) have notable potency against Plasmodium falciparum compared with chloroquine (0.02 μg/mL); compounds 7l (0.10 μg/mL), 7e, 7s (0.19 μg/mL), 7b, 7p (0.15 μg/mL), 7a, 7f, and 7f (0.25 μg/mL) also exhibited good activity against P. falciparum compared with quinine (0.26 μg/mL) as standard drug. Docking was performed on PFDHFR‐TS, given the effect of compounds against the P. falciparum strain was excellent in comparison with standard drug. Molecular docking suggested that compounds 7b, 7i and 7c, 7e, and 7l closely bind with the active site of protein 3JSU and 4DP3, respectively, and compared with biological activity. We have also carried out molecular dynamics simulation on the best dock compound 7e complex with PDB: 3JSU to check the stability of docked complex and their molecular interaction. The calculated ADME‐Tox descriptors for the synthesized compounds validated good pharmacokinetics properties, suggesting that these compounds could be used as hit for the development of the new active agents.
Cavitating and tigroid‐like leukoencephalopathy in a case of NDUFA2‐related disorder
Authors: Alagia Marianna , Cappuccio Gerarda , Torella Annalaura , D'Amico Alessandra , Mazio Federica , Romano Alfonso , Fecarotta Simona , Casari Giorgio , Nigro Vincenzo ,   TUDP, Brunetti‐Pierri Nicola 
Published: February 2020

AbstractBiallelic variants in nuclear gene NDUFA2 have been reported so far in only three children with variable presentations including Leigh syndrome or leukoencephalopathy. Herein, we report a further female child affected by NDUFA2‐related disorder presenting with cavitating and tigroid‐like pattern of leukodystrophy and without systemic biochemical abnormalities of mitochondrial disorders.
Genomic variance of the 2019‐nCoV coronavirus
Authors: Ceraolo Carmine , Giorgi Federico M. 
Published: February 2020

AbstractThere is a rising global concern for the recently emerged novel coronavirus (2019‐nCoV). Full genomic sequences have been released by the worldwide scientific community in the last few weeks to understand the evolutionary origin and molecular characteristics of this virus. Taking advantage of all the genomic information currently available, we constructed a phylogenetic tree including also representatives of other coronaviridae, such as Bat coronavirus (BCoV) and severe acute respiratory syndrome. We confirm high sequence similarity (>99%) between all sequenced 2019‐nCoVs genomes available, with the closest BCoV sequence sharing 96.2% sequence identity, confirming the notion of a zoonotic origin of 2019‐nCoV. Despite the low heterogeneity of the 2019‐nCoV genomes, we could identify at least two hypervariable genomic hotspots, one of which is responsible for a Serine/Leucine variation in the viral ORF8‐encoded protein. Finally, we perform a full proteomic comparison with other coronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti‐coronavirus approaches.
Early Human‐Milk Metabolome in Cases of Intrauterine Growth–Restricted and Macrosomic Infants
Authors: Briana Despina D. , Fotakis Charalambos , Kontogeorgou Anna , Gavrili Stavroula , Georgatzi Sophia , Zoumpoulakis Panagiotis , Malamitsi‐Puchner Ariadne 
Published: February 2020

AbstractBackgroundAbnormal fetal growth is associated with short‐term and long‐term metabolic dysregulation and susceptibility to obesity‐related disorders. Maternal milk, the ideal source of infantile nutrition, protects from metabolic diseases in adulthood. By applying nuclear magnetic resonance (NMR) metabolomics, this study investigated the metabolic profile of early human milk/colostrum (EHM/C) at the extremes of fetal‐growth conditions, which could affect its nutritional value.MethodsFrom 98 mothers delivering 60 appropriate‐for‐gestational‐age (AGA), 19 large‐for‐gestational‐age (LGA), and 19 intrauterine growth–restricted (IUGR) full‐term neonates, milk samples collected on the third to fourth day post partum were examined by NMR spectroscopy. Multivariate data analysis elicited information from NMR spectra and probed to metabolic signatures of EHM/C.ResultsLGA and IUGR EHM/C samples depicted increased content in lactose, citric acid, choline, phosphocholine, and N‐acetylglutamine. AGA samples exhibited increased isoleucine and valine. Metabolic pathways involved were valine, leucine/isoleucine biosynthesis and degradation, glycerophospholipid metabolism, aminoacyl–transfer RNA biosynthesis, and citrate cycle. Orthogonal projections to latent structures discriminant analysis models were validated.ConclusionThis holistic metabolomics study framed an increased content of certain essential nutrients in EHM/C samples following the birth of LGA and IUGR infants prone to short‐ and long‐term metabolic disorders, thus stressing additional benefits of early breastfeeding. Assessing the metabolic profile of EHΜ/C enables evaluation of its nutrition value, adjusted to fetal growth, and introduction of appropriate dietary interventions.