bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potentiating apoptosis and modulation of p53, Bcl2, and Bax by a novel chrysin ruthenium complex for effective chemotherapeutic efficacy against breast cancer
Authors: Roy Souvik , Sil Anweshan , Chakraborty Tania 
Published: September 2018

AbstractBreast cancer is the most frequent cause of cancer in women. In the current study, transition metal ruthenium was complexed with flavonoid chrysin to evaluate the chemotherapeutic potential of this compound in Michigan Cancer Foundation‐7 (MCF‐7) human mammary cancer cell line and 7,12‐dimethylbenz(α)anthracene‐induced mammary cancer in female Sprague–Dawley rats. The characterizations of the complex were accomplished through UV–visible, NMR, IR, Mass spectra, and XRD techniques and antioxidant activity was assessed by DPPH, FRAP, and ABTS methods. In vitro studies included cell viability, cell cycle analysis, DNA fragmentation, and marker analysis by western blot analysis and found that complex treatment suppressed cell growth‐induced cell cycle arrest and enhanced the induction of apoptosis in cancer cells. Moreover, complex treatment modulated signaling pathways including mTOR, VEGF, and p53 in the MCF‐7 cells. Acute and subacute toxicity was performed in rats to determine the therapeutic doses. Breast cancer in rats was initiated by the administration of 7,12‐dimethylbenz(α)anthracene (0.5 mg/100 g body weight) via single tail vein injection. The histopathological analysis after 24 weeks of carcinogenesis study depicted substantial repair of hyperplastic lesions. Immunohistochemical analysis revealed upregulation of Bax and p53 and downregulation of Bcl2 proteins and TUNEL assay showed an increase in apoptotic index in ruthenium–chrysin‐treated groups as compared to the carcinogen control. Our findings from the in vitro and in vivo study support the continued investigation of ruthenium–chrysin complex possesses a potential chemotherapeutic activity against breast cancer and was efficient in reducing hyperplastic lesions in the mammary tissues of rats by inducing apoptosis.
The miR‐15a/16 gene cluster in human cancer: A systematic review
Authors: Liu Ting , Xu Zhenru , Ou Daming , Liu Jing , Zhang Ji 
Published: September 2018

AbstractMicroRNAs (miRNAs) are an important class of endogenous small noncoding single‐stranded RNAs that suppress the expression of their target genes through messenger RNA (mRNA) degradation to inhibit transcription and translation. MiRNAs play a crucial regulatory role in many biological processes including proliferation, metabolism, and cellular malignancy. miR‐15a/16 is an important tumor suppressor gene cluster with a variety of factors that regulate its transcriptional activity. It has been discovered that a relative reduction of miR‐15a/16 expression in various cancers is closely related to the occurrence and progression of tumors. miR‐15a/16 takes part in a wide array of biological processes including tumor cell proliferation, apoptosis, invasion, and chemoresistance by binding to the 3′‐untranslated region of its target gene's mRNA. In this review, we will examine the complex regulatory network of miR‐15a/16 gene expression and its biological functions in human cancers to further elucidate the molecular mechanisms of its antitumor effects.
USP49 inhibits ischemia–reperfusion‐induced cell viability suppression and apoptosis in human AC16 cardiomyocytes through DUSP1–JNK1/2 signaling
Authors: Zhang Wei , Zhang Yangyang , Zhang Hengbing , Zhao Qian , Liu Zheng , Xu Yawei 
Published: September 2018

AbstractDual‐specificity protein phosphatases (DUSP) also known as mitogen‐activated protein kinase (MAPK) phosphatases (MKPs) can dephosphorylate MAPKs, including extracellular signal‐regulated kinase, c‐Jun N‐terminal kinase (JNK), and p38. DUSP1‐mediated JNK dephosphorylation has been found to play an antiapoptotic role against cardiac ischemia–reperfusion (I/R) injury. However, the regulation of DUSP1–JNK pathway remains unclear. In the current study, ubiquitin‐specific peptidase 49 (USP49) expression in human AC16 cardiomyocytes following I/R injury was measured by real‐time polymerase chain reaction and western blot analysis. Cell viability, apoptosis, the Bax, Bcl‐2, and DUSP1 expression, and the activity of MAPKs in AC16 cardiomyocytes following indicated treatment was measured by CCK‐8, flow cytometry, and western blot analysis. The direct interaction between USP49 and DUSP1 was measured by coimmunoprecipitation and ubiquitination analysis. The effect of USP49 on apoptosis and JNK activity in rat cardiomyocytes following I/R injury was also measured by TUNEL and western blot analysis. Here, we found that USP49 expression was time‐dependently increased in AC16 cardiomyocytes following I/R. I/R‐induced cell apoptosis and JNK1/2 activation both in in vivo and in vitro reversed by USP49 overexpression in AC16 cardiomyocytes. Inhibiting JNK1/2 activation significantly inhibited USP49 knockdown‐induced the cell viability inhibition, apoptosis and the JNK1/2 activation in AC16 cardiomyocytes. Moreover, USP49 positively regulated DUSP1 expression through deubiquitinating DUSP1. Overall, our findings establish USP49 as a novel regulator of DUSP1–JNK1/2 signaling pathway with a protective role in cardiac I/R injury.
Long noncoding RNA SNHG12 promotes the progression of cervical cancer via modulating miR‐125b/STAT3 axis
Authors: Jin Xue‐J. , Chen Xiang‐J. , Zhang Zhi‐F. , Hu Wen‐S. , Ou Rong‐Y. , Li Shi , Xue Ji‐S. , Chen Lu‐L. , Hu Yan , Zhu Hua 
Published: September 2018

AbstractIncreasing evidence showed that long noncoding RNAs (lncRNAs) played an important role in the occurrence and development of tumors. To date, lncRNA small nucleolar RNA host gene 12 (SNHG12) has revealed an oncogenic role in various tumors. However, the role of SNHG12 in cervical cancer is still unclear. Therefore, we focused on the biological function and molecular mechanism of SNHG12 in the tumorigenesis of cervical cancer. In this study, the expression of miR‐125b was observably downregulated in cervical cancer cells. Meanwhile, the expression of SNHG12 was obviously upregulated in cervical cancer cell lines (HeLa, SiHa, Caski, C4‐1, and C33A) compared with the immortalized cervical epithelial cells. The further assay showed that miR‐125b was a target of SNHG12 in cervical cancer. Moreover, a negative relationship between miR‐125b and SNHG12 was found in cervical cancer. In addition, SNHG12 inhibition restrained the proliferation, migration, and invasion of cervical cancer cells. Meanwhile, miR‐125b mimics repressed the expression of signal transducer and activator of transcription 3 (STAT3). The further assay showed that STAT3 was a target of miR‐125b in cervical cancer. In addition, sh‐STAT3 repressed the migration and invasion of cervical cancer cells. Furthermore, it showed that miR‐125b inhibitors reversed STAT3 expression restrained by the reduction of SNHG12 expression. In general, SNHG12 modulated STAT3 by sponging miR‐125b in cervical cancer and played an important role in the development of cervical cancer.
Pediatric Obesity: Influence on Drug Dosing and Therapeutics
Authors: Ameer Barbara , Weintraub Michael A. 
Published: September 2018

AbstractObesity is an ongoing global health concern and has only recently been recognized as a chronic disease of energy homeostasis and fuel partitioning. Obesity afflicts 17% of U.S. children and adolescents. Severe obesity (≥120% of the 95th percentile of body mass index (BMI) for age, or a BMI ≥ 35 kg/m2) is the fastest‐growing subgroup and now approaches 6% of all U.S. youth. Health consequences (eg, type 2 diabetes, coronary heart disease) are related in a dose‐dependent manner to severity of obesity. Because therapeutic interventions are less effective in severe obesity, prevention is a high priority. Treatment plans involving combinations of behavioral therapy, nutrition, and exercise achieve limited success. Only one drug, orlistat, is U.S. Food and Drug Administration approved for long‐term obesity management in adolescents 12 years and older. As part of comprehensive medication management, clinicians should consider the propensity for a given drug to aggravate weight gain and to consider alternatives that minimize weight impact. Medication management must take into account developmental changes as well as the pathophysiology of obesity and comorbidities. Despite expanding insight into obesity pathophysiology, there are gaps in its translation to therapeutic application. The historical construct of obesity as simply a fat‐storage disorder is fundamentally inaccurate. The approach to adjusting doses based solely on body size and extrapolating from therapeutic knowledge of adult obesity may be based on assumptions that are not fully substantiated. Classes of drugs commonly prescribed for comorbidities associated with obesity should be prioritized for clinical research evaluations aimed at optimizing dosing regimens in pediatric obesity.
Analgesics and Sedatives in Critically Ill Newborns and Infants: The Impact on Long‐Term Neurodevelopment
Authors: Schiller R.M. , Allegaert K. , Hunfeld Maayke , van den Bosch G.E. , van den Anker John , Tibboel D. 
Published: September 2018

AbstractInadequate pain and/or stress management in preterm‐ and term‐born infants has been associated with increased morbidity and even mortality. However, exposure to analgosedatives during early infancy may also be one of the risk factors for subsequent neurodevelopmental impairment, at least in animal studies. Because infants admitted to neonatal or pediatric intensive care units may receive high amounts of these drugs for prolonged periods of time and the majority of these infants nowadays survive to discharge, this is of major concern. A balanced approach that incorporates the assessment and quantification of both wanted effects as well as unwanted side effects is therefore needed. In this article, the optimal dose determination of commonly used analgosedative drugs as well as their potential long‐term effects on the developing human brain and neuropsychological functioning are reviewed.
Pharmacometric Modeling and Simulation Is Essential to Pediatric Clinical Pharmacology
Authors: Neely Michael , Bayard David , Desai Amit , Kovanda Laura , Edginton Andrea 
Published: September 2018

AbstractPediatric clinical pharmacology now encompasses a wide range of activities, including drug pharmacokinetic and pharmacodynamic modeling and simulation, also known as pharmacometrics. Pediatric clinical pharmacologists may be physicians but are more likely to be pharmacists or PhD scientists, and pediatric clinical pharmacology today is largely a research specialty rather than a subspecialty for direct patient care. Pharmacometrics, including “top‐down” population modeling and “bottom‐up” physiologically based pharmacokinetic modeling, has become an indispensable tool for pharmaceutical industry scientists, government regulators, academic researchers, and even a handful of patient‐oriented practitioners. This review summarizes the application of pharmacometrics within each of these domains and predicts future trends of further applications across the spectrum of pediatric clinical pharmacology from drug development to patient care.
Elucidating the binding efficacy of β‐galactosidase on polyaniline–chitosan nanocomposite and polyaniline–chitosan–silver nanocomposite: activity and molecular docking insights
Authors: Khan Maryam , Husain Qayyum , Ahmad Nafees 
Published: September 2018

AbstractBACKGROUNDAspergillus oryzae β‐galactosidase (β‐gal; EC 3.2.1.23) was physically adsorbed on polyaniline–chitosan nanocomposite (PANI‐CS‐NC) and polyaniline–chitosan–silver nanocomposite (PANI‐CS‐Ag‐NC). Stability and kinetic studies were assessed, along with reusability and molecular docking interactions.RESULTSAccording to transmission electron microscopy images, the sizes of the respective NCs were found to be in the range of 23–39 and 6–18 nm. The η (effectiveness factor) values for PANI‐CS‐NC‐ and PANI‐CS‐Ag‐NC‐bound β‐gal were calculated to be 0.89 and 1.23, respectively, suggesting an enhancement in the activity of the enzyme in the presence of silver ions. Significant broadening was observed in pH and temperature profiles. Kinetic properties of PANI‐CS‐NC‐ and PANI‐CS‐Ag‐NC‐bound β‐gal showed lower Km, and two‐ and fourfold higher Vmax, respectively, compared to free enzyme. PANI‐CS‐Ag‐NC‐bound β‐gal was able to retain 94% of its initial activity after 10 repeated uses. Circular dichroism analysis revealed conformational changes in the secondary structure of protein upon immobilization. The genotoxic assessment revealed non‐toxic behaviour of both free and enzyme‐bound NC. The rate of lactose hydrolysis at 50 °C exhibited by PANI‐CS‐‐Ag‐NC bound β‐gal was 7% higher than that for the native enzyme. In‐silico analysis showed efficient binding of β‐gal on PANI‐CS‐ NCs due to interaction with residues that were exclusive of the active site of the enzyme.CONCLUSIONPANI‐CS‐Ag‐NC‐bound β‐gal preparation proved to be a robust nano‐biocatalyst due to remarkable enhancement in catalytic activity along with excellent stability and reusability characteristics, which could be further utilized for efficient construction of nano‐biosensors for producing lactose‐free dairy products to feed lactose‐intolerant patients. © 2018 Society of Chemical Industry
19F MRI of the Lungs Using Inert Fluorinated Gases: Challenges and New Developments
Authors: Couch Marcus J. , Ball Iain K. , Li Tao , Fox Matthew S. , Biman Birubi , Albert Mitchell S. 
Published: September 2018

Fluorine‐19 (19F) MRI using inhaled inert fluorinated gases is an emerging technique that can provide functional images of the lungs. Inert fluorinated gases are nontoxic, abundant, relatively inexpensive, and the technique can be performed on any MRI scanner with broadband multinuclear imaging capabilities. Pulmonary 19F MRI has been performed in animals, healthy human volunteers, and in patients with lung disease. In this review, the technical requirements of 19F MRI are discussed, along with various imaging approaches used to optimize the image quality. Lung imaging is typically performed in humans using a gas mixture containing 79% perfluoropropane (PFP) or sulphur hexafluoride (SF6) and 21% oxygen. In lung diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF), ventilation defects are apparent in regions that the inhaled gas cannot access. 19F lung images are typically acquired in a single breath‐hold, or in a time‐resolved, multiple breath fashion. The former provides measurements of the ventilation defect percent (VDP), while the latter provides measurements of gas replacement (ie, fractional ventilation). Finally, preliminary comparisons with other functional lung imaging techniques are discussed, such as Fourier decomposition MRI and hyperpolarized gas MRI. Overall, functional 19F lung MRI is expected to complement existing proton‐based structural imaging techniques, and the combination of structural and functional lung MRI will provide useful outcome measures in the future management of pulmonary diseases in the clinic.Level of Evidence: 3Technical Efficacy: Stage 1J. Magn. Reson. Imaging 2019;49:343–354.
The association between frailty and medicines use over time: an analysis using the Australian Longitudinal Study on Ageing population
Authors: Widagdo Imaina S. , Pratt Nicole L. , Roughead Elizabeth E. 
Published: September 2018

AbstractBackgroundFrailty and medicine‐related problems are common among the elderly and have been associated with an increased risk of adverse outcomes. However, there has been limited research on the association between frailty and medicines use.AimTo determine the distribution of frailty among older people who used medicines and to examine the difference in frailty scores over time with continuation or discontinuation of specific medicines.MethodsThe study population was from the Australian Longitudinal Study of Ageing (ALSA). The data used in the analysis were collected in 1992 (wave 1) and in 1995 (wave 3). Frailty scores were assessed at both waves using a modified version of the Frailty Index. Non‐parametric tests were used to examine the difference in the distribution of frailty scores in relation to medicines used at baseline. Medicine use was categorised into continued or stopped by comparing use at wave 3 to use at baseline. A t‐test was used to compare the mean changes in frailty scores between the two groups, with a p‐value of <0.05 considered to be significant.ResultsData from 2087 participants were included. At baseline, a higher number of medicines used was associated with higher frailty scores (p < 0.0001). Stopping any preventive medicines, as well as beta‐blockers, or potassium‐sparing diuretics, was associated with a higher increase in mean frailty score changes than continuing these medicines, p = 0.01, p = 0.03 and p = 0.004, respectively.ConclusionsThere was an association between frailty and medicines use. Further study is needed to assess whether the progression of frailty was due to medicine cessation or vice versa.
Joint sparse representation and denoising method for Raman spectrum
Authors: Fang Zheng , Tao Yu , Wang Wen , Zhang Wenxin , Duan Lingfeng , Liu Ying , Yan Changchun , Qu Lulu , Han Caiqin 
Published: September 2018

AbstractA new method based on joint sparse representation is developed to recover the peak information from high‐noise Raman signal. This method used the sparsity of Raman spectrum to recover the signals and preserve its useful peak information. The peak information is then reconstructed by using an orthogonal matching pursuit algorithm. The joint sparse representation method is found to be an effective approach to analyze the Raman spectrum, especially Raman spectrum that have high noise, thus improving the detection limit of Raman spectroscopy. Experimental results demonstrate that this approach is better than other approaches in case of low signal‐to‐noise ratios.
Immediate Negative Pressure Wound Therapy After Free Flap Transfer for Head and Neck Cancer Surgery
Authors: Lin Pao‐Yuan , Liou Tz‐Luen , Lin Ko‐Chien , Hsieh Mu‐Han , Chien Chih‐Yen , Hsieh Ching‐Hua 
Published: September 2018

ObjectiveThis study aimed to assess the outcomes of administering negative‐pressure wound therapy (NPWT) in patients immediately following free flap reconstruction after head and neck cancer surgery and radical neck lymph node dissection. The outcomes were compared with those of patients who received conventional wound care (CWC).MethodsA retrospective analysis was performed for 58 patients with head and neck cancer who underwent free flap reconstruction after tumor ablation and radical neck dissection between February 1, 2016, and October 31, 2016. All reconstructions were performed by the same plastic surgeon. Charts were reviewed for patient demographics, comorbidities, cancer type, operation time, flap type, postoperative drainage volume, complication rates, length of hospital stay, and wound outcomes.ResultsNo significant difference was observed between patients receiving NPWT and CWC regarding operation time and drainage volume from the vacuum ball. After the application of NPWT, no patients experienced flap failure or developed a wound infection. Significantly fewer patients receiving NPWT developed complications (9.7% vs. 37.0%; P = 0.025) and developed infections (0.0% vs. 14.8%; P = 0.041) compared with those receiving CWC.ConclusionOn the basis of fewer associated complications and infections, this study supports the immediate use of NPWT after free flap reconstruction in patients who have undergone head and neck cancer ablation and radical neck lymph node dissection.Level of Evidence4. Laryngoscope, 2478–2482, 2018
Anterior cervical incision‐sparing thyroidectomy: Comparing retroauricular and transoral approaches
Authors: Russell Jonathon O. , Razavi Christopher R. , Al Khadem Mai G. , Lopez Michael , Saraf Sejal , Prescott Jason D. , Starmer Heather M. , Richmon Jeremy D. , Tufano Ralph P. 
Published: September 2018

ObjectivesThe robotic retroauricular approach and transoral endoscopic thyroidectomy vestibular approach (TOETVA) have been employed to avoid anterior neck scarring in thyroidectomy with good success. However, outcomes have yet to be compared between techniques. We compare our initial clinical experience with these approaches for thyroid lobectomy at our institution.MethodsA review of initial consecutive patients who underwent robotic facelift thyroidectomy (RFT) (August 2011–August 2016) at our institution was conducted. This was compared with the same number of initial consecutive patients who underwent TOETVA (September 2016–September 2017) at our institution. Demographics, operative time, pathology, complications, and learning curve were compared between cohorts. Learning curve was defined based on the slope of linear regression models of operative time versus case number.ResultsThere were 20 patients in each cohort. There was no statistically significant difference in demographic data between cohorts. One hundred percent of RFT cases versus 95% TOETVA cases (P = .999) were completed without conversion to standard open technique with median operative times of 201 (124–293) minutes versus 188 (89–343) minutes with RFT and TOETVA, respectively (P = .36). There was no incidence of permanent recurrent laryngeal nerve injury in either cohort. The slopes of the regression models were 0.29 versus −8.32 (P = .005) for RFT and TOETVA, respectively.ConclusionRFT and TOETVA are safe and feasible options for patients motivated to avoid an anterior neck scar. However, the quicker learning curve without the need for a costly robotic system may make TOETVA the preferred technique for institutions wishing to perform anterior cervical incision‐sparing thyroidectomy.Level of Evidence4
Impacts of long‐term environmental variability on diapause phenology of coastal copepods in Tokyo Bay, Japan
Authors: Tachibana Aiko , Nomura Hideaki , Ishimaru Takashi 
Published: September 2018

AbstractMany common and abundant copepods in coastal areas adapt to complex environments through diapause (physiological dormancy) by laying resting eggs. However, the response mechanisms of these species’ phenology to environmental changes is poorly understood, especially the influence of both climatic and anthropogenic changes. Using monthly time series data for zooplankton in Tokyo Bay, Japan, from 1981 to 2010, we investigated phenological and quantitative changes in the dominant species Acartia omorii, Centropages abdominalis, and Labidocera rotunda in response to climatic and hydrographic variation in this semienclosed eutrophic coastal area. The first two species produce resting eggs in the warm season and the latter in the cold season. Decreasing abundance and increasing resting egg periods were observed for A. omorii and C. abdominalis, and the reverse for L. rotunda. Time series analysis revealed a possible mechanism driving these phenologic shifts. Wintertime warming of the water column associated with climate variability driven by the Pacific Decadal Oscillation index, followed by rapid development of summertime stratification and the formation of hypoxic bottom water layers, were responsible for the early initiation and delayed termination of the resting egg period for cold‐water species. The warming trend in Tokyo Bay, possibly induced by inflow of warm oceanic water due to anthropogenic factors, caused these phenologic changes in the resting period and subsequently affected zooplankton abundance. These results suggest that the multiple stressors caused by climate change and other anthropogenic impacts can affect regional zooplankton communities in coastal areas.