bluuebunny/crossref_metadata_2025_split huggingface dataset:
ABCA1 inhibits PDGF‐induced proliferation and migration of rat airway smooth muscle cell through blocking TLR2/NF‐κB/NFATc1 signaling
Authors: Cheng Wei , Yan Kun , Chen Yanni , Zhang Wen , Ji Zongzheng , Dang Chengxue 
Published: May 2018

AbstractAirway remodeling is a key feature of asthma, characterized by abnormal proliferation and migration of airway smooth muscle cells (ASMCs). ABCA1, a member of the ATP‐binding cassette family of active transporters, plays an essential role in the progression of lung diseases. However, the contributions of ABCA1 in ASMCs remain to be explored. The purpose of the present study was to investigate the functional role and potential molecular mechanism of ABCA1 in platelet derived growth factor (PDGF)‐induced primary rat ASMC proliferation and migration. We observed that PDGF‐ led to a significant decrease in the expression of ABCA1. Overexpression of ABCA1 strikingly suppressed PDGF‐induced ASMC proliferation accompanied by a decrease in the expression of PCAN stimulated by PDGF. Additionally, augmentation of ABCA1 dramatically restrained PDGF‐induced migration concomitant with attenuate the accumulation of MMP‐2 and MMP‐9 in response to PDGF. Furthermore, forced expression of ABCA1 enhanced contractile phenotype markers proteins including α‐SMA along with sm‐MHC, sm‐α‐actin, and calponin reduced by PDGF. Meanwhile, introduction of ABCA1 depressed ECM over‐deposition induced by PDGF as reflected by a decrease in the expression of ECM protein collagen I and fibronectin. More importantly, addition of ABCA1 effectively suppressed the activity of TLR2/NF‐κB signaling as well as diminished the expression of NFATc1 in rat ASMCs after PDGF stimulation. Interestingly, blockage of TLR2/NF‐κB signaling effectively inhibited PDGF‐induced proliferation and migration, these effects were similar to ABCA1. Taken together, these data implicated that ABCA1 suppressed PDGF‐induced proliferation, migration, and contraction in rat ASMCs at least partly through TLR2/NF‐κB/NFATc1 signaling, which might offer hope for the future treatment of airway remodeling in asthma.
Uroprotective mechanism of quercetin against cyclophosphamide‐induced urotoxicity: Effect on oxidative stress and inflammatory markers
Authors: Sherif Iman O. 
Published: May 2018

AbstractThe urotoxicity is a common complication associated with patients receiving cyclophosphamide (CYP). This study was designed to investigate the uroprotective mechanism of quercetin (Quer) flavonoid against CYP induced urotoxicity via determination of oxidative stress markers as well as inflammatory mediators in bladder tissue. Forty male Wistar rats were divided into four groups; Normal group: received saline for 10 days. Quer control group: received quercetin 50 mg/kg/day for 10 days. CYP group: received saline for 10 days and injected with a single dose of 150 mg/kg CYP intraperitoneal (i.p) at day 8. The Quer + CYP group: received Quer 50 mg/kg/day for 10 days plus CYP 150 mg/kg i.p. injection at day 8. The CYP injection produced a significant elevation in bladder contents of malondialdehyde (MDA), and nitric oxide (NO), and bladder protein levels and expressions of tumor necrosis factor‐alpha (TNF‐α), and interleukin‐6 (IL‐6) in addition to the upregulation of cyclooxygenase‐2 (COX‐2) bladder gene expression. Also, CYP injection showed a marked reduction in bladder levels of catalase, superoxide dismutase (SOD), and IL‐10 when compared with normal group. Moreover, histopathological examination of the bladder showed degenerative alterations, severe edema, and inflammation following CYP injection. Quer attenuated the biochemical markers and histopathological changes induced by CYP. The uroprotective effect of Quer was exerted by restoring the balance between oxidative/antioxidative status and pro‐/anti‐inflammatory cytokines via its antioxidant and anti‐inflammatory activities.
Protective and therapeutic effects of dexpanthenol on isoproterenol‐induced cardiac damage in rats
Authors: Kalkan Ferhat , Parlakpinar Hakan , Disli Olcay M. , Tanriverdi Lokman H. , Ozhan Onural , Polat Alaaddin , Cetin Aslı , Vardi Nigar , Otlu Yılmaz O. , Acet Ahmet 
Published: May 2018

AbstractThe purpose of the study was to explore the protective and therapeutic effects of dexpanthenol (DEX) on isoproterenol (ISO)‐induced cardiac damage. Forty rats were distributed into four groups: group I (Control); group II (ISO); ISO (150 mg/kg/day) was given to rats once a day for 2 consecutive days with an interval of 24 h; group III (DEX+ISO): DEX (250 mg/kg) was applied 30 min before the first ISO administration and continued in the next two days after second ISO administration; group IV (ISO+DEX): After the ISO treatment at 1st and 2nd days, DEX was given at 3rd and 4th days. Rats were monitored for mean arterial blood pressure (BP), heart rate, oxygen saturation (%SO2), and electrocardiography (ECG). Heart tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), reduced glutathione (GSH), total oxidant status (TOS); total antioxidant capacity (TAC), oxidative stress index (OSI), and caspase‐3 were determined. BP and SO2 values indicated a significant decrease in the ISO group. Also, T wave negativity was observed in 6 of 10 rats, SOD, CAT, and GPX levels were significantly lower in ISO group than control group. ISO administration increased TOS and OSI levels, whereas DEX treatment significantly reduced these parameters. Also, ISO‐induced morphological alterations such as disorganization of cardiomyocytes, loss of myofibrils and cytoplasmic vacuolization whereas these histological damages were significantly decreased in ISO+DEX and DEX+ISO groups when compared to the ISO group. This study implies the cardioprotective effects of DEX on ISO‐induced cardiotoxicity.
Cystatin C Is a More Reliable Biomarker for Determining eGFR to Support Drug Development Studies
Authors: Kar Sumit , Paglialunga Sabina , Islam Rafiqul 
Published: May 2018

AbstractGlomerular filtration rate (GFR) is routinely used as a surrogate endpoint for the development of investigational drugs in clinical trials. GFR and staging of chronic kidney disease are typically assessed by measuring the concentration of endogenous serum biomarkers such as albumin and creatinine. However, creatinine is subject to high biological variability, and levels of creatinine do not rise until nearly 50% of kidney function is damaged, leading to inaccurate chronic kidney disease staging and false negatives. A newer biomarker for GFR, cystatin C, has been shown to be subject to less biological interference and more sensitive to early declines in kidney function. Cystatin C has also been shown to outperform creatinine as an indicator of true GFR and to add information about the occurrence of acute kidney injury. Comparison studies of cystatin C and creatinine continue to demonstrate its increased accuracy and sensitivity for changes in true GFR. While challenges remain for use of cystatin C, international agencies and working groups continue to validate cystatin C as a biomarker and accompanying GFR estimating equations for diagnostic and drug development use. In this review, we summarize these comparison studies, regulatory and industry guidelines, and clinical trial case studies for use of cystatin C in drug development.
Individual‐Specific QT Interval Correction for Drugs With Substantial Heart Rate Effect Using Holter ECGs Extracted Over a Wide Range of Heart Rates
Authors: Panicker Gopi Krishna , Kadam Pramod , Chakraborty Saikat , Kothari Snehal , Turner J. Rick , Karnad Dilip R. 
Published: May 2018

AbstractAlthough fixed QT correction methods are typically used to adjust for the effect of heart rate on the QT interval in thorough QT/QTc studies, individual‐specific QT correction (QTcI = QT/RRI) is advisable for drugs that increase the heart rate by >5 to 10 beats/minute (bpm). QTcI is traditionally derived using resting drug‐free electrocardiograms (ECGs) collected at prespecified times. However, the resting heart rate range in healthy individuals is narrow, and extrapolation of inferences from these data to higher heart rates could be inappropriate. Accordingly, the QTcI derived from triplicate ECGs extracted at prespecified times (the traditional [T] method, yielding QTcIT) was compared with QTcIs obtained using ECGs with a wider heart rate range (alternative Holter [H] method, yielding QTcIH) from 24‐hour Holter recordings from 40 healthy individuals selected from a central ECG laboratory database. For QTcIH, 10‐second ECGs were extracted at stable heart rates in the ranges of 51‐60, 61‐70, 71‐80, and 81‐90 bpm (9 ECGs in each bin = 36 ECGs). An independent set of 40 ECGs with heart rates from 51 to 90 bpm was extracted from each individual to validate the accuracy of QTcI by the 2 methods. For the validation set, the QTcIH was a better QT correction method (slope of QTc vs heart rate closer to zero) than QTcIT. The mean difference between QTcIT and QTcIH increased from 3.1 milliseconds at 65 bpm to 10.0 milliseconds at 90 bpm (P < 0.01). The QTcIT exceeded QTcIH at heart rates > 60 bpm. Employment of the QTcIH may be more appropriate for studies involving drugs that increase heart rate.
Searching for a mitochondrial root to the decline in muscle function with ageing
Authors: Gonzalez‐Freire Marta , Adelnia Fatemeh , Moaddel Ruin , Ferrucci Luigi 
Published: May 2018

AbstractSarcopenia, the age‐related loss of muscle mass and strength, is linked to a range of adverse outcomes, such as impaired physical performance, cognitive function, and mortality. Preventing sarcopenia may reduce the burden of functional decline with aging and its impact on physiological and economic well‐being in older adults. Mitochondria in muscle cells lose their intrinsic efficiency and capacity to produce energy during aging, and it has been hypothesized that such a decline is the main driver of sarcopenia. Oxidative phosphorylation becomes impaired with aging, affecting muscle performance, and contributing to an age‐associated decline in mobility. However, it is unclear whether this deterioration is due to a reduced mitochondria population, decreased mitochondrial energetic efficiency, or a reduced capacity to dynamically transport oxygen and nutrients into the mitochondria, and addressing these questions is an active area of research. Further research in humans will require use of new “omics” technologies, progress in neuroimaging techniques that permit energy production assessment, and visualization of molecules critical for energetic metabolism, as well as proxy biomarkers of muscle perfusion.
Study of hyperpigmentation in human skin disorder using different electron microscopy techniques
Authors: Noh Seulgi , Choi Hyosun , Kim Ji Soo , Kim Il‐Hwan , Mun Ji Young 
Published: May 2018

AbstractThere is a global trend of increase in the demand for three‐dimensional electron microscopy with high resolution. The ultrastructural change and related functional studies are necessary to investigate biological phenomena. In this study, currently available 3D reconstruction techniques of electron microscopes (serial block‐face scanning electron microscopy and focused ion beam—scanning electron microscopy) were used to investigate hyperpigmentary disorders in human skin. In the basal layer of the epidermis in the human skin, there are melanocytes that produce melanin and keratinocytes that act as a barrier against environmental damage. The 3D structure from serial images through scanning electron microscopy showed locations of melanosomes between melanocyte and keratinocyte in the hyperpigmentary disorder, in addition, the electron tomography showed pigment transfer through melanin instead melanosome. These results support the exocytosis‐endocytosis theory of pigment in human skin.
Alcohol enhances symptoms and propensity for infection in inflammatory bowel disease patients and a murine model of DSS-induced colitis
Authors: Cannon Abigail R , Kuprys Paulius V , Cobb Adrienne N , Ding Xianzhong , Kothari Anai N , Kuo Paul C , Eberhardt Joshua M , Hammer Adam M , Morris Niya L , Li Xiaoling , Choudhry Mashkoor A 
Published: May 2018

Abstract
Over 1.4 million Americans have been diagnosed with inflammatory bowel disease (IBD), and ulcerative colitis (UC) makes up approximately half of those diagnoses. As a disease, UC cycles between periods of remission and flare, which is characterized by intense abdominal pain, increased weight loss, intestinal inflammation, rectal bleeding, and dehydration. Interestingly, a widespread recommendation to IBD patients for avoidance of a flare period is “Don’t Drink Alcohol” as recent work correlated alcohol consumption with increased GI symptoms in patients with IBD. Alcohol alone not only induces a systemic pro-inflammatory response, but can also be directly harmful to gut barrier integrity. However, how alcohol could result in the exacerbation of UC in both patients and murine models of colitis has yet to be elucidated. Therefore, we conducted a retrospective analysis of patients admitted for IBD with a documented history of alcohol use in conjunction with a newly developed mouse model of binge alcohol consumption following dextran sulfate sodium (DSS)-induced colitis. We found that alcohol negatively impacts clinical outcomes of patients with IBD, specifically increased intestinal infections, antibiotic injections, abdomen CT scans, and large intestine biopsies. Furthermore, in our mouse model of binge alcohol consumption following an induced colitis flare, we found alcohol exacerbates weight loss, clinical scores, colonic shortening and inflammation, and propensity to infection. These findings highlight alcohol’s ability to potentiate symptoms and susceptibility to infection in UC and suggest alcohol as an underlying factor in perpetuating symptoms of IBD.
This study builds on previous findings that alcohol has adverse effects in IBD and establishes these effects in a mouse model of colitis.
Neuroinflammation and microglia in glaucoma: time for a paradigm shift
Authors: Wei Xin , Cho Kin‐Sang , Thee Eric F. , Jager Martine J. , Chen Dong Feng 
Published: May 2018

AbstractGlaucoma is a complex neurodegenerative disease with many clinical subtypes. Some of its rare forms include pigmentary glaucoma, uveitic glaucoma and congenital glaucoma. While they all share common features of progressive retinal ganglion cell (RGC) loss, optic nerve damage and corresponding visual field loss, the exact mechanisms underlying glaucomatous neuron loss are not clear. This has largely hindered the development of a real cure for this disease. Elevated intraocular pressure (IOP) is a known major risk factor of glaucoma; however, progressive degeneration of RGCs and axons can also be found in patients with a normal IOP, i.e., normal tension glaucoma (NTG). Interestingly, patients who carry the gain‐of‐function mutation of the pro‐inflammatory gene TBK1 – tumor necrosis factor (TNF) receptor associated factor NF‐κB activator (TANK) binding kinase 1 – are at increased risk to develop NTG. This finding suggests a causal link between neuroinflammatory processes and glaucoma. Various studies have reported the presence of neuroinflammatory responses by microglia, astrocytes and other blood‐born immune cells in the optic nerve head (ONH) at early stages of experimental glaucoma. Inhibition of certain pro‐inflammatory pathways, particularly those associated with microglial activation, appears to be neuroprotective. In this review, we will focus on the inflammatory responses, in particular the proposed roles of microglia, in the pathogenesis of glaucoma.
Cement interface and bone stress in total hip arthroplasty: Relationship to head size
Authors: Alonso‐Rasgado Teresa , Del‐Valle‐Mojica Jose F. , Jimenez‐Cruz David , Bailey Colin G. , Board Tim N. 
Published: May 2018

ABSTRACTThe use of larger prosthetic femoral heads in total hip arthroplasty (THA) has increased considerably in recent years in response to the need to improve joint stability and reduce risk of dislocation. However, data suggests larger femoral heads are associated with higher joint failure rates. For cemented implants, ensuring the continued integrity of the cement mantle is key to long term fixation. This paper describes an investigation into the effect of variation in femoral head size on stresses in the acetabular cement mantle and pelvic bone. Three commonly used femoral head sizes: 28, 32, and 36 mm diameter were investigated. The study was undertaken using a finite element model validated using surface strains obtained from Digital Image Correlation (DIC) during experimentation on a composite hemipelvis implanted with a cemented all‐polyethylene acetabular cup. Following validation, the models were used to investigate stresses in the pelvic bone and acetabular cement mantle resulting from two loading scenarios; an average weight subject (700 N) and an overweight subject (1,000 N) undertaking a single leg stand. We found that the highest peak stresses occurred in the anterosuperior and posterosuperior regions of the bone‐cement interface, in the line of action of the load, where debonding usually initiates. Stress on the cortical bone‐cement interface increased with femoral head diameter by up to 9% whilst stresses in the trabecular bone remained relatively invariant. Our findings may help to explain higher joint failure rates associated with larger femoral heads. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2966–2977, 2018.
Promoting the use of isotopic techniques to combat soil erosion: An overview of the key role played by the SWMCN Subprogramme of the Joint FAO/IAEA Division over the last 20 years
Authors: Mabit Lionel , Bernard Claude , Lee Zhi Yi Amelia , Fulajtar Emil , Dercon Gerd , Zaman Mohammad , Toloza Arsenio , Heng Lee 
Published: May 2018

AbstractThe International Atomic Energy Agency (IAEA), through the Joint Division with the Food and Agriculture Organization (FAO) of the United Nations, assists its Member States in applying nuclear techniques to alleviate challenges in food safety, food security and sustainable agricultural development. The Soil and Water Management & Crop Nutrition (SWMCN) Subprogramme, within the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture, has made significant contributions to the development of isotopic techniques for the assessment of soil degradation and the development of efficient soil and land conservation approaches. These techniques include fallout radionuclides such as 137Cs, 210Pbex, 7Be, and 239+240Pu as well as 13C stable isotope and compound‐specific stable isotope analyses. These methodologies were developed and/or refined through the work of researchers from developed and developing countries who were selected to work within the frame of IAEA's Coordinated Research Projects (CRPs). Internal research activities implemented in the Joint FAO/IAEA's SWMCN Laboratory in Seibersdorf supported the work accomplished in the CRPs.The methodologies thus developed have been subsequently disseminated to developing countries by IAEA's Technical Cooperation Programme to assist Member States to adopt climate‐smart agriculture and reduce soil degradation that poses a threat to food security and the environment. This review paper provides an overview of the activities conducted in the frame of CRPs for combating soil erosion over the last 20 years and highlights the major achievements. Examples of the success and the impact obtained in Morocco, Madagascar, and Vietnam in using these isotopic techniques are presented.
Vegetation dynamic trends and the main drivers detected using the ensemble empirical mode decomposition method in East Africa
Authors: Wei Fangli , Wang Shuai , Fu Bojie , Pan Naiqing , Feng Xiaoming , Zhao Wenwu , Wang Cong 
Published: May 2018

AbstractUnderstanding vegetation changes and the underlying causes are critical to predict the future ecosystem dynamics. Water‐limited ecosystems in East Africa have been identified as particularly vulnerable to the impacts of increased environmental change, but relatively little is known about the vegetation dynamic trends and the main drivers. Taking the satellite‐derived normalized difference vegetation index (NDVI) as a proxy of vegetation growth, we detected the spatiotemporal evolution of NDVI trends and explored the main drivers based on the ensemble empirical mode decomposition method. Results showed that greening (restoration) and browning (degradation) coexisted in East Africa during 1982–2013. However, the early greening stalled or even reversed as the browning continuously intensified over time. Greening‐to‐browning prevailed in East Africa after 2000. Generally, more than half of the study area (54.77%, 13.77% with a significant decrease) experienced a browning trend during 1982–2013, with an average change rate of (−0.12 ± 1.10) × 10−3. We also found that the percentage of greening area in each land cover type overall decreased. Furthermore, the remarkable spatiotemporal correlations between NDVI and soil water suggested that water was a dominant factor governing the vegetation changes in East Africa. The effectiveness of different types of protected areas (PAs) on vegetation change varied, depending to some extent on management policy (legal laws and on‐site patrols). Therefore, a big challenge for sustainable management of protected areas is how to balance conservation and development objectives in East Africa.
Influence of Nanoclay Localization on Structure–Property Relationships of Polylactide‐Based Biodegradable Blend Nanocomposites
Authors: Salehiyan Reza , Ray Suprakas Sinha 
Published: May 2018

AbstractThis article highlights the recent research achievements regarding the development of nanoclay‐containing biodegradable composites of polylactide (PLA)‐based immiscible blends. The structure–property relationships of particular blends, namely, PLA/poly(ε‐caprolactone), PLA/poly(butylene succinate), and PLA/poly[(butylene succinate)‐adipate], are studied with respect to the nanoclay incorporations. For different nanoclay types and concentrations, the morphologies of these nanocomposites are probed and correlated to their viscoelastic, mechanical, and thermal properties, along with their crystallization behavior and kinetics and gas permeability. The nanoclay dispersion and distribution characteristics are found to be key parameters influencing the final properties. In particular, nanocomposites with a higher degree of nanoclay dispersion exhibit significant enhancement in their mechanical, thermal, and barrier properties, and some agglomerations are effective as regards favorable crystallization behavior. In terms of the clay localization, the positioning of nanoclays at the interface reduces the minor phase size remarkably, because of the droplet encapsulation that counteracts coalescence. However, for improved understanding of the influence of nanoclay localization on the structure–property relationships of these blends, further systematic study is required. That is, nanocomposites with different localizations but the same nanoclay loads should be compared. This can be achieved by tuning the processing protocols and the nanoclay inclusion orders in the blends.