bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chondrocyte mTORC1 activation stimulates miR‐483‐5p via HDAC4 in osteoarthritis progression
Authors: Wang Hua , Zhang Haiyan , Sun Qiuyi , Yang Jian , Zeng Chun , Ding Changhai , Cai Daozhang , Liu Anling , Bai Xiaochun 
Published: August 2018

The hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) in chondrocytes has been shown to accelerate the severity of destabilization of the medial meniscus‐induced and age‐related osteoarthritis (OA) phenotypes with aberrant chondrocyte hypertrophy and angiogenesis. Meanwhile, we previously reported that miR‐483‐5p is essential for the initiation and development of OA by stimulating chondrocyte hypertrophy and angiogenesis. The connection between mTORC1 and miR‐483‐5p activation in OA progression, however, remains unclear. In this study, we elucidated their relationship and identified the underlying mechanisms. The expression of miR‐483‐5p in the articular cartilage of cartilage‐specific TSC1 knockout mice was assessed compared with control mice using the Agilent Mouse miRNA (8*60K) V19.0 array and real‐time polymerase chain reaction (RT‐PCR). The functional effects of the stimulation of miR‐483‐5p via histone deacetylase 4 (HDAC4) by mTORC1 in OA development, subsequently modulating its downstream targets matrilin 3 and tissue inhibitor of metalloproteinase 2, were examined by immunostaining, western blotting, and real‐time PCR. This study revealed that miR‐483‐5p was responsible for mTORC1 activation‐stimulated OA. Mechanistically, mTORC1 controls the HDAC4‐dependent expression of miR‐483‐5p to stimulate chondrocyte hypertrophy, extracellular matrix degradation, and subchondral bone angiogenesis, and it consequently initiates and accelerates the development of OA. Our findings revealed a novel mTORC1‐HDAC4‐miR‐483‐5p pathway that is critical for OA development.
Antrodia salmonea‐induced oxidative stress abrogates HER‐2 signaling cascade and enhanced apoptosis in ovarian carcinoma cells
Authors: Yang Hsin‐Ling , Lin Ruei‐Wan , Rajendran Peramaiyan , Mathew Dony Chacko , Thigarajan Varadharajan , Lee Chuan‐Chen , Hsu Chih‐Jung , Hseu You‐Cheng 
Published: August 2018

AbstractAntrodia salmonea is well known in Taiwan as a traditional Chinese medicinal fungus and has demonstrated antioxidant, anti‐inflammatory, and anticancer effects. However, the anticancer activity of A. salmonea against human ovarian cancer is still elusive. Therefore, we investigated the antiovarian tumor activity of a fermented culture broth of A. salmonea and exhibits its underlying molecular mechanism. A. salmonea shows a significant effect on cell viability in human ovarian carcinoma (SKOV‐3 or A2780) cell lines with an 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Increased terminal deoxynucleotidyl transferase dUTP nick‐end labeling‐positive cells and annexin V–propidium iodide stained cells indicate that A. salmonea induces late apoptosis in SKOV‐3 cells. Notably, treatment with A. salmonea induced the following events: Apoptosis; caspase‐3, ‐8, ‐9 and poly(ADP‐ribose) polymerase activation; first apoptosis signal (Fas) and Fas ligand activation; Bid cleavage; and Bax2–B‐cell lymphoma 2 dysregulation. The results show that A. salmonea‐induced apoptosis was mediated by both mitochondrial and death receptor pathways. An increase in intracellular reactive oxygen species (ROS) was also observed in A. salmonea‐treated cells, whereas the antioxidant N‐acetylcysteine (NAC) prevented A. salmonea‐induced cell death and DNA fragmentation, indicating that A. salmonea‐induced apoptosis was mediated by ROS generation. Interestingly, A. salmonea‐induced apoptosis is associated with the suppression of human epidermal growth factor receptor‐2 (HER‐2/neu) and phosphoinositide 3‐kinase (PI3K)–protein kinase B (AKT) expression in HER‐2/neu overexpressing SKOV‐3 cells. NAC significantly prevented A. salmonea‐induced HER‐2/neu depletion and PI3K/AKT inactivation, indicating that A. salmonea‐triggered apoptosis is mediated by ROS‐inhibited HER‐2/neu signaling cascades. To our knowledge, this is the first report describing the anticancer activity of this potentially beneficial mushroom against human ovarian carcinoma.
Emerging role of circulating microRNA in the diagnosis of human infectious diseases
Authors: Ojha Rupal , Nandani Raj , Pandey Rajan Kumar , Mishra Amit , Prajapati Vijay Kumar 
Published: August 2018

AbstractThe endogenic microRNAs (miRNA) are evolutionary, conserved, and belong to a group of small noncoding RNAs with a stretch of 19–24 nucleotides. The miRNAs play an indispensable role in gene modulation at the posttranscriptional level, inclusive of stem‐cell differentiation, embryogenesis, hematopoiesis, metabolism, immune responses, or infections. The miRNAs secreted from the cells and their presence in the biological fluids signifies the regulatory role of circulating miRNAs in the pathogenesis. The phenomenal expression levels of circulating miRNAs in serum or plasma during infection makes them the potential therapeutic biomarkers for the diagnosis of assorted human infectious diseases. In this article, we have accentuated the methods for the profiling of circulating miRNA as well as the importance of miRNA as biomarkers for the diagnosis of human infectious diseases. To date, numerous biomarkers have been identified for the diagnostic or prognostic purpose; for instance, miR‐182, miR‐486, and miR15a in sepsis; miR‐320 and miR505 in inflammatory bowel disease; miR‐155 and miR‐1260 in influenza; miR‐12, miRVP‐3p, and miR‐184 in arboviruses; and miR‐29b and miR‐125 in hepatitis infection. Nevertheless, the noninvasive diagnostic approach, with the aid of biomarkers, currently plays a decisive role in the untimely diagnosis of human infections. So, in the near future, the exploitation of circulating miRNAs as therapeutic biomarkers for the diagnosis of human infections will help us to cure the associated diseases promptly and effectively.
hiPSC‐derived hepatocytes closely mimic the lipid profile of primary hepatocytes: A future personalised cell model for studying the lipid metabolism of the liver
Authors: Kiamehr Mostafa , Alexanova Anna , Viiri Leena E. , Heiskanen Laura , Vihervaara Terhi , Kauhanen Dimple , Ekroos Kim , Laaksonen Reijo , Käkelä Reijo , Aalto‐Setälä Katriina 
Published: August 2018

AbstractHepatocyte‐like cells (HLCs) differentiated from human‐induced pluripotent stem cells offer an alternative platform to primary human hepatocytes (PHHs) for studying the lipid metabolism of the liver. However, despite their great potential, the lipid profile of HLCs has not yet been characterized. Here, we comprehensively studied the lipid profile and fatty acid (FA) metabolism of HLCs and compared them with the current standard hepatocyte models: HepG2 cells and PHHs. We differentiated HLCs by five commonly used methods from three cell lines and thoroughly characterized them by gene and protein expression. HLCs generated by each method were assessed for their functionality and the ability to synthesize, elongate, and desaturate FAs. In addition, lipid and FA profiles of HLCs were investigated by both mass spectrometry and gas chromatography and then compared with the profiles of PHHs and HepG2 cells. HLCs resembled PHHs by expressing hepatic markers: secreting albumin, lipoprotein particles, and urea, and demonstrating similarities in their lipid and FA profile. Unlike HepG2 cells, HLCs contained low levels of lysophospholipids similar to the content of PHHs. Furthermore, HLCs were able to efficiently use the exogenous FAs available in their medium and simultaneously modify simple lipids into more complex ones to fulfill their needs. In addition, we propose that increasing the polyunsaturated FA supply of the culture medium may positively affect the lipid profile and functionality of HLCs. In conclusion, our data showed that HLCs provide a functional and relevant model to investigate human lipid homeostasis at both molecular and cellular levels.
Modulation of the immune response by Middle East respiratory syndrome coronavirus
Authors: Shokri Somayeh , Mahmoudvand Shahab , Taherkhani Reza , Farshadpour Fatemeh 
Published: August 2018

AbstractCoronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. In 2012, a new human disease called Middle East respiratory syndrome (MERS) emerged in the Middle East. MERS was caused by a virus that was originally called human coronavirus‐Erasmus Medical Center/2012 but was later renamed as Middle East respiratory syndrome coronavirus (MERS‐CoV). MERS‐CoV causes high fever, cough, acute respiratory tract infection, and multiorgan dysfunction that may eventually lead to the death of the infected individuals. The exact origin of MERS‐CoV remains unknown, but the transmission pattern and evidence from virological studies suggest that dromedary camels are the major reservoir host, from which human infections may sporadically occur through the zoonotic transmission. Human to human transmission also occurs in healthcare facilities and communities. Recent studies on Middle Eastern respiratory continue to highlight the need for further understanding the virus‐host interactions that govern disease severity and infection outcome. In this review, we have highlighted the major mechanisms of immune evasion strategies of MERS‐CoV. We have demonstrated that M, 4a, 4b proteins and Plppro of MERS‐CoV inhibit the type I interferon (IFN) and nuclear factor‐κB signaling pathways and therefore facilitate innate immune evasion. In addition, nonstructural protein 4a (NSP4a), NSP4b, and NSP15 inhibit double‐stranded RNA sensors. Therefore, the mentioned proteins limit early induction of IFN and cause rapid apoptosis of macrophages. MERS‐CoV strongly inhibits the activation of T cells with downregulation of antigen presentation. In addition, uncontrolled secretion of interferon ɣ‐induced protein 10 and monocyte chemoattractant protein‐1 can suppress proliferation of human myeloid progenitor cells.
Therapeutic potential of A2 adenosine receptor pharmacological regulators in the treatment of cardiovascular diseases, recent progress, and prospective
Authors: Bahreyni Amirhossein , Avan Amir , Shabani Mohammad , Ryzhikov Mikhail , Fiuji Hamid , Soleimanpour Saman , Khazaei Majid , Hassanian Seyed Mahdi 
Published: August 2018

AbstractAdenosine and its analogs are of particular interest as potential therapeutic agents for treatment of cardiovascular diseases (CVDs). A2 adenosine receptor subtypes (A2a and A2b) are extensively expressed in cardiovascular system, and modulation of these receptors using A2 adenosine receptor agonists or antagonists regulates heart rate, blood pressure, heart rate variability, and cardiovascular toxicity during both normoxia and hypoxia conditions. Regulation of A2 adenosine receptor signaling via specific and novel pharmacological regulators is a potentially novel therapeutic approach for a better understanding and hence a better management of CVDs. This review summarizes the role of pharmacological A2 adenosine receptor regulators in the pathogenesis of CVDs.
Stem cell‐based therapy for Parkinson’s disease with a focus on human endometrium‐derived mesenchymal stem cells
Authors: Bagheri‐Mohammadi Saeid , Karimian Mohammad , Alani Behrang , Verdi Javad , Tehrani Rana Moradian , Noureddini Mahdi 
Published: August 2018

AbstractParkinson’s disease (PD) as an increasing clinical syndrome is a multifunctional impairment with systemic involvement. At present, therapeutic approaches such as l‐3,4‐dihydroxy‐phenylalanine replacement therapy, dopaminergic agonist administration, and neurosurgical treatment intend to relieve PD symptoms which are palliative and incompetent in counteracting PD progression. These mentioned therapies have not been able to replace the lost cells and they could not effectively slow down the relentless neurodegenerative process. Till now, there is a lack of eligible treatment for PD, and stem cells therapy recently has been considered for PD treatment. In this review, we demonstrate how human stem cell technology especially human endometrium‐derived stem cells have made advancement as a therapeutic source for PD compared with other treatments.
5′‐Adenosine monophosphate‐activated protein kinase: A potential target for disease prevention by curcumin
Authors: Soltani Arash , Salmaninejad Arash , Jalili‐Nik Mohammad , Soleimani Anvar , Javid Hossein , Hashemy Seyed Isaac , Sahebkar Amirhossein 
Published: August 2018

AbstractCurcumin (diferuloylmethane), a yellowish agent extracted from turmeric, is a bioactive compound known for its anti‐inflammatory, antiproliferative, antidiabetic, and anticancer activities. Multiple lines of evidence have indicated that curcumin regulates several regulatory proteins in the cellular signal transduction pathway. AMP‐activated protein kinase (AMPK) is one of the central regulators of cellular metabolism and energy homeostasis, which is activated in response to increasing cellular adenosine monophosphate/adenosine triphosphate ratio. AMPK plays a critical role in regulating growth and reprogramming metabolism and is linked to several cellular processes including apoptosis and inflammation. Recently, it has been demonstrated that AMPK is a new molecular target affected by curcumin and its derivatives. In this review, we discuss recent findings on the targeting of AMPK signaling by curcumin and the resulting impact on the pathogenesis of proinflammatory diseases. We also highlight the therapeutic value of targeting AMPK by curcumin in the prevention and treatment of proinflammatory diseases, including cancers, atherosclerosis, and diabetes.
Subacute treatment of carprofen facilitate splenocardiac resolution deficit in cardiac injury
Authors: Halade Ganesh V , Kain Vasundhara , Wright Griffin M , Jadapalli Jeevan Kumar 
Published: August 2018

Abstract
Inflammation-limiting nonsteroidal pain relievers magnify myocardial infarction (MI) incidences and increase re-admission events in heart failure (HF) patients. However, the molecular and cellular mechanism of this provocative adverse effect is unclear. Our goal was to determine whether carprofen (CAP) impedes splenic leukocyte-directed acute inflammation-resolving response in cardiac injury. After subacute CAP treatment, mice were subjected to permanent coronary ligation maintaining MI- and naïve-controls. Spleen and left ventricle (LV) leukocytes were quantitated using flow cytometry pre- and 24 h post-MI. The inflammation resolution mediators were quantified using mass spectrometry while splenocardiac apoptosis and leukocyte phagocytosis were measured by immunofluorescence and ImageStream, respectively. Subacute CAP treatment promoted strain and cardiac dysfunction before MI and coronary occlusion showed signs of acute HF in CAP and MI-controls. Subacute CAP-injected mice had pre-activated splenic neutrophils, an over activated “don't eat me” signal (CD47) with reduced total Mϕs (F4/80+) and reparative Mϕs (F4/80/Ly6Clo/CD206) compared with control in LV and spleen. Post-MI, CAP pre-activated neutrophils (Ly6G+) were intensified and reduced reparative neutrophils (Ly6G+/CD206+) and Mϕs (F4/80/Ly6Clo) in LV was indicative of non-resolving inflammation compared with MI-control. Subacute CAP treatment deferred neutrophil phagocytosis functions in the spleen and LV and was more evident post-MI compared with MI-control. CAP pre-activated splenic neutrophils that tailored the Mϕ phagocytosis thereby increased splenocardiac leukocyte death. CAP over amplified COX-1 and COX-2 compared with MI-control and failed to limit prostaglandins and thromboxane in post-MI setting. Further, CAP reduced cardiac-protective epoxyeicosatrienoic acids and over amplified pyrogenic inflammatory cytokines and reduced reparative cytokines, thereby non-resolving inflammation.
Inflammation-limiting pain relievers magnify myocardial infarction incidences, and therefore redefined the mechanism that subacute carprofen treatment in mice pre-activates splenic neutrophils with signs of nonresolving inflammation.
Integrated population model to improve knowledge and management of Idaho wolves
Authors: Horne Jon S. , Ausband David E. , Hurley Mark A. , Struthers Jennifer , Berg Jodi E. , Groth Kayte 
Published: August 2018

ABSTRACTRecently, several states in the western United States have assumed management authority of gray wolves (Canis lupus). Wolves pose a challenge for management agencies who must reconcile interests related to conservation of an ecologically important carnivore with management of a dominant predator of ungulates that are highly valued by the hunting public. Thus, managers seek reliable information on the status of wolf populations, the implications of management actions, and the effects of wolf predation on ungulates. We developed an integrated population model (IPM) for wolves in Idaho to assess their status and evaluate the effects of harvest on wolf demographics. We combined pack counts with known‐fate data from global positioning system (GPS)‐collared wolves to obtain estimates of pack size, harvest, non‐harvest mortality, dispersal, and recruitment. Our application emphasizes some of the key benefits of an IPM approach including estimation of parameters for which no direct data are available, the ability to reconstruct pack sizes during periods when count data were missing, and an evaluation of harvest effects on wolf population dynamics. Mean size of wolf packs averaged 5.5 from 2005–2016. There was a general decline in pack size from 2006–2012 with the smallest occurring in 2012, just after the 2011–2012 harvest season. Since 2012, mean pack size has increased, coinciding with a declining trend in the probability of harvest. We found no difference in mid‐year recruitment of wolves into packs during periods with versus without harvest and concluded that harvest mortality is additive to non‐harvest mortality. Thus, harvest may be an effective tool for agencies to manage wolf populations. Although our IPM was informative for wolf management, future monitoring will likely benefit from seeking less costly data sources within an IPM framework. © 2018 The Wildlife Society.
Effects of distribution, behavior, and climate on mule deer survival
Authors: Schuyler Elizabeth M. , Dugger Katie M. , Jackson Dewaine H. 
Published: August 2018

ABSTRACTMule deer (Odocoileus hemionus hemionus) populations in North America are a valuable economic wildlife resource, with the managed harvest of this species reflecting societal values and recreational opportunities in many parts of the western United States. Managing mule deer populations while allowing for harvest requires an understanding of the species’ population dynamics, including the specific factors associated with population change. We conducted a 7‐year (2005–2012) study designed to investigate habitat use and survival of mule deer in eastern Oregon, USA. We used known‐fate data for 408 adult female radio‐collared mule deer to estimate monthly survival rates and to investigate factors that might affect these rates, including seasonal distribution, temporal effects (seasonal, annual, and trends across season and year), movement behavior, and local weather and regional climatic covariates. Variation in survival rates of female mule deer was best explained by an additive effect of migration behavior, differences in survival during the fall migration period compared to the rest of the annual cycle, and precipitation levels on winter ranges of individual deer. Estimates of annual survival were higher for migrants (0.81–0.82), compared to residents (0.76–0.77). Survival was lower for migrants and residents during fall migration (Oct–Nov) and higher amounts of winter precipitation increased survival of both groups. The results of our study suggest that migrating to potentially higher quality summer foraging areas outweighed the cost of traveling through unfamiliar habitats and energy expenditure associated with migration. © 2018 The Wildlife Society.
Mobile app technology is associated with improved otolaryngology resident in‐service performance
Authors: Kuperstock Jacob E. , Horný Michal , Platt Michael P. 
Published: August 2018

ObjectiveOtolaryngology residents face time‐management challenges between clinical duties and self‐directed learning. Mobile devices provide a new medium for education that could aid with educational efficiency. The objective of this study was to investigate whether spaced repetition mobile app use of an otolaryngology question bank was associated with improving factual knowledge as measured by in‐service exam performance.MethodsFor approximately 6 months prior to the 2016 in‐service examination, 12 otolaryngology residents at a single institution were provided access to a spaced‐repetition app with a preloaded licensed otolaryngology review question bank. The number of questions answered, as well as the time spent on the app, were electronically tracked. The associations of app usage on in‐service results were analyzed using an autoregressive model adjusted for prior historical Otolaryngology Trainee Examination performance and postgraduate year.ResultsEleven residents used the mobile app and were included in the analysis for an average of 304 minutes (range: 3 to 1,020) and reviewed on average 679 questions (range: 6 to 1,934). Controlling for residency year and prior performance, app usage was associated with an improvement by 2.92 percentage points (pp) (95% confidence interval [CI]: 0.14, 5.70) on overall in‐service score. Allergy and pediatric subsection scores improved by 11.3 pp (95% CI: 3.8, 18.8) and 15.2 pp. (95% CI: 8.9, 21.5), respectively. Increased app use was associated with a score improvement by 0.008 pp per minute of use (95% CI: 0.004, 0.012).ConclusionUse of mobile spaced‐repetition technology can aid resident factual knowledge retention measured by improved in‐service exam performance.Level of Evidence4 Laryngoscope, 129:E15–E20, 2019
Compensation of Otolaryngologists in the Veterans Health Administration: Is There a Gender Gap?
Authors: Dermody Sarah M. , Litvack Jamie R. , Randall James A. , Malekzadeh Sonya , Maxwell Jessica H. 
Published: August 2018

Objectives/HypothesisTo determine if gender pay disparity exists amongst otolaryngologists employed by the Veterans Health Administration (VHA).Study Designcross‐sectional analysis.MethodsBoard‐certified otolaryngologists employed at all complex Veterans Affairs Medical Centers (VAMCs) in 2016 were identified. Salaries were collated using the Enterprise Human Resources Integration–Statistical Data Mart dataset. Additional variables, including gender, years since medical school graduation, professorship status, h‐index, and geographic location were collected. A multivariate linear regression analysis was performed where salary was the primary outcome of interest and gender was accounted for as an independent predictor while controlling for professional characteristics, geographic location, and seniority.ResultsSixty‐nine VHA surgical programs with an operative designation of “complex” were identified. Two hundred sixty board‐certified otolaryngologists, including 197 (75.8%) men and 63 (24.2%) women, were identified. Salary data were available on 210 of these otolaryngologists. In 2016, the mean salary for male and female otolaryngologists was not significantly different ($266,707 ± $31,624 vs. $264,674 ± $27,027, P = .918) nor were salaries in early career ($243,979 ± $31,749 vs. $254,625 ± $24,558, respectively; P = .416). On multivariate linear regression analysis, number of years since graduation (P = .009) and h‐index (P = .049) were independent predictors of salary, but gender, geographic location, and faculty rank were not.ConclusionsAlthough the gender pay gap persists in many areas of medicine and surgery, otolaryngologists employed at complex VAMCs do not experience gender pay disparity. The use of specific and objective criteria to establish and adjust salaries can reduce and potentially eliminate gender pay disparity. These findings may help to guide institutional policies in other practice environments.Level of Evidence2b. Laryngoscope, 129:113–118, 2019