bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dihydroartemisinin, an Anti-Malaria Drug, Suppresses Estrogen Deficiency-Induced Osteoporosis, Osteoclast Formation, and RANKL-Induced Signaling Pathways
Authors: Zhou Lin , Liu Qian , Yang Mingli , Wang Tao , Yao Jun , Cheng Jianwen , Yuan Jinbo , Lin Xixi , Zhao Jinmin , Tickner Jennifer , Xu Jiake 
Published: December 2015

ABSTRACT

Osteoporosis is an osteolytic disease that features enhanced osteoclast formation and bone resorption. Identification of agents that can inhibit osteoclast formation and function is important for the treatment of osteoporosis. Dihydroartemisinin is a natural compound used to treat malaria but its role in osteoporosis is not known. Here, we found that dihydroartemisinin can suppress RANKL-induced osteoclastogenesis and bone resorption in a dose-dependent manner. Dihydroartemisinin inhibited the expression of osteoclast marker genes such as cathepsin K, calcitonin receptor, and tartrate-resistant acid phosphatase (TRAcP). Furthermore, dihydroartemisinin inhibited RANKL-induced NF-κB and NFAT activity. In addition, using an in vivo ovariectomized mouse model, we show that dihydroartemisinin is able to reverse the bone loss caused by ovariectomy. Together, this study shows that dihydroartemisinin attenuates bone loss in ovariectomized mice through inhibiting RANKL-induced osteoclast formation and function. This indicates that dihydroartemisinin, the first physiology or medicine nobel prize discovery of China, is a potential treatment option against osteolytic bone disease. © 2015 American Society for Bone and Mineral Research.
Expression of cFLIPL Determines the Basal Interaction of Bcl‐2 With Beclin‐1 and Regulates p53 Dependent Ubiquitination of Beclin‐1 During Autophagic Stress
Authors: Ranjan Kishu , Pathak Chandramani 
Published: December 2015

ABSTRACTAutophagy and apoptosis are two different physiological processes, which is required for the maintenance of cellular homeostasis. The apoptosis associated proteins such as Bcl‐2 and p53 have a close association with autophagic proteins HMGB1 and Beclin‐1 to modulate autophagic signaling. We demonstrate here the involvement of anti‐apoptotic protein cFLIPL in the regulation of autophagy during cellular stress. We found that ectopic expression of cFLIPL decreases the sensitivity of HEK 293T cells against rapamycin and H2O2 induced autophagic stress. Notably, the selective knockdown of cFLIPL augments autophagic stress in the cells accompanied with JNK1 activation and p53 dependent ubiquitination of Beclin‐1. However, re‐expression of cFLIPL in cFLIP knockdown cells restores autophagic equilibrium collectively with reversible effects on JNK1 and Beclin‐1 integrity. The co‐immunoprecipitation analysis suggests that cFLIPL is essential to maintain the canonical interaction of Bcl‐2 with Beclin‐1 to regulate autophagic stress and cell death. Altogether, our findings suggest that expression of cFLIPL regulates the basal interaction of Bcl‐2 with Beclin‐1 and substantiates p53 dependent ubiquitination of Beclin‐1 during autophagic stress to determine the fate of cell death or survival. J. Cell. Biochem. 117: 1757–1768, 2016. © 2015 Wiley Periodicals, Inc.
microRNA‐16 Is Downregulated During Insulin Resistance and Controls Skeletal Muscle Protein Accretion
Authors: Lee David E. , Brown Jacob L. , Rosa Megan E. , Brown Lemuel A. , Perry Richard A. , Wiggs Michael P. , Nilsson Mats I. , Crouse Stephen F. , Fluckey James D. , Washington Tyrone A. , Greene Nicholas P. 
Published: December 2015

ABSTRACTInsulin resistant diabetes, currently at epidemic levels in developed countries, begins in the skeletal muscle and is linked to altered protein turnover. microRNAs downregulate targeted mRNA translation decreasing the amount of translated protein, thereby regulating many cellular processes. Regulation of miRNAs and their function in skeletal muscle insulin resistance is largely unexplored. The purpose of this study was to identify the effects of insulin resistance on contents of skeletal muscle miRNAs with potential functions in protein turnover. We examined miRs ‐1, ‐16, ‐23, ‐27, ‐133a, ‐133b, and ‐206 in muscles of Zucker rats. miR‐1 was 5‐ to 10‐fold greater in obesity, whereas miRs‐16 and ‐133b were repressed ∼50% in obese compared to lean rats, with no other alterations in miRNA contents. miR‐16 correlated to protein synthesis in lean, but not obese rats. miR‐16 reduction by lipid overload was verified in‐vivo by diet‐induced obesity and in‐vitro using a diacylglycerol analog. A role for miR‐16 in protein turnover of skeletal myocytes was established using transient overexpression and anti‐miR inhibition. miR‐16 overexpression resulted in lower protein synthesis (puromycin incorporation, ∼25–50%), mTOR (∼25%), and p70S6K1 (∼40%) in starved and insulin stimulated myoblasts. Conversely, anti‐miR‐16 increased basal protein synthesis (puromycin incorporation, ∼75%), mTOR (∼100%), and p70S6K1 (∼100%). Autophagy was enhanced by miR‐16 overexpression (∼50% less BCL‐2, ∼100% greater LC3II/I, ∼50% less p62) and impaired with miR‐16 inhibition (∼45% greater BCL‐2, ∼25% less total LC3, ∼50% greater p62). This study demonstrates reduced miR‐16 during insulin resistance and establishes miR‐16 control of protein accretion in skeletal muscle. J. Cell. Biochem. 117: 1775–1787, 2016. © 2015 Wiley Periodicals, Inc.
Clinical and biological significance of PIM1 kinase in osteosarcoma
Authors: Liao Yunfei , Feng Yong , Shen Jacson , Gao Yan , Cote Gregory , Choy Edwin , Harmon David , Mankin Henry , Hornicek Francis , Duan Zhenfeng 
Published: December 2015

ABSTRACTOsteosarcoma is the most prevalent histological form of primary malignant bone tumor. The majority of osteosarcoma patients have limited alternative therapeutic options and metastatic patients generally have a poor prognosis. Proto‐oncogene serine/threonine‐protein kinase PIM1 is associated with growth and survival of many kinds of tumor cells. However, the role of PIM1 in osteosarcoma remains largely unknown. In this study, we investigated the functional and therapeutic relevance of PIM1 as a putative target in osteosarcoma. We found PIM1 was highly expressed in various osteosarcoma cell lines and in tumor tissues from osteosarcoma patients. Tissue microarray and immunohistochemistry analysis showed that the overall and disease‐free survival rate of patients with high levels of PIM1 protein expression were significantly shorter than patients with low levels. High levels of PIM1 were also associated with present metastasis and can be considered as an independent prognostic factor in osteosarcoma patients. Knockdown of PIM1 expression by synthetic siRNA or shRNA greatly inhibited cell growth, migration, and invasion. Moreover, these changes accompanied with down‐regulation of anti‐apoptotic protein Bcl‐2. The similar results were obtained in osteosarcoma cells treated with PIM1 specific inhibitor (SMI‐4a). These results suggest that PIM1 kinase is critical for the growth and metastasis of osteosarcoma cells and can be a potential therapeutic target for osteosarcoma treatment. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1185–1194, 2016.
Substantia Nigra Echogenicity Predicts Response to Drug Withdrawal in Suspected Drug‐Induced Parkinsonism
Authors: López‐Sendón Moreno Jose L. , Alonso‐Cánovas Araceli , Buisán Catevilla Javier , García Barragán Nuria , Corral Corral Iñigo , de Felipe Mimbrera Alicia , Matute Lozano María Consuelo , Masjuan Vallejo Jaime , Martínez‐Castrillo Juan Carlos 
Published: December 2015

AbstractIntroductionResponse to drug withdrawal in patients with suspected drug‐induced parkinsonism (DIP) is of prognostic and therapeutic importance, but cannot be predicted solely on clinical information. The aim of this study was to validate SN hyperechogenicity (SN+) assessed by transcranial sonography as a predictor of response to drug withdrawal in this group of patients.MethodsPatients were diagnosed according to previously published criteria and prospectively included in the study. All patients were followed until complete recovery of parkinsonian symptoms or at least for 6 months after discontinuation of the offending drug and then diagnosed as DIP or parkinsonism following neuroleptic exposure (PFNE). Transcranial sonography (TCS) findings were compared with the clinical diagnosis.ResultsSixty patients comprised the group for the final analysis. Sixteen patients were classified as PFNE and 44 as DIP. The area of SN echogenicity was significantly increased in the PFNE group (0.23 cm2; standard deviation [SD]: 0.04), compared to the DIP group (0.14 cm2; SD, 0.05; one‐way analysis of variance; P < 0.001). Normal SN was significantly associated with complete recovery after withdrawal of the parkinsonism‐inducing drug (P < 0.0005). Accuracy of SN+ to distinguish PFNE from DIP was: sensitivity 81.2%; specificity 84.1%; positive predictive value 47.4%; and negative predictive value 96.2%.ConclusionsWe believe that SN+ assessed with TCS is a valid prognostic marker in the setting of suspected DIP. It is a nonexpensive, feasible technique that can be implemented for proper counseling and guidance of treatment decisions.
A New Approach to Health Services and Pharmacy in Cuba
Authors: Sánchez Alina M. 
Published: December 2015

In December 17, 2014, U.S. President Barack Obama surprised the world by announcing his intention to enter into negotiations aimed at reestablishing diplomatic relations with Cuba. Since then, expectations and interest regarding the health system of that country have increased. This report focuses on the Cuban health and pharmacy systems from a practical and educational standpoint. Pharmaceutical services, strengths, opportunities, and challenges are described. Cuba's new trends toward patient‐centered care are analyzed to provide insights for developing pharmaceutical care practice and implementing policies suitable for practice in all health care settings.
Comparison of the Safety of Adenosine and Regadenoson in Patients Undergoing Outpatient Cardiac Stress Testing
Authors: Brink Heidi L. , Dickerson Jennifer A. , Stephens Julie A. , Pickworth Kerry K. 
Published: December 2015

Study ObjectiveTo compare the adverse effect profiles of adenosine and regadenoson in patients undergoing outpatient cardiac stress testing.DesignSingle‐center retrospective cohort study.SettingTwo outpatient clinics, both of which are part of a single tertiary academic medical health system; one clinic exclusively used adenosine for cardiac stress testing, and the other clinic exclusively used regadenoson.PatientsA total of 489 patients who underwent an outpatient cardiac stress test between January 1, 2014, and December 31, 2014; of those patients, 254 received adenosine and 235 received regadenoson.Measurements and Main ResultsBaseline characteristics were similar between groups, except for chronic kidney disease (p<0.001), congestive heart failure (p=0.041), and mean age (p=0.004). The primary outcome was the occurrence of adverse effects—arrhythmia, chest pain or tightness, dizziness, dyspnea, flushing, or headache, and use of the rescue agent aminophylline—in the adenosine and regadenoson groups. A significantly higher proportion of patients who were given regadenoson during cardiac stress testing experienced at least one adverse effect compared with patients who underwent an adenosine stress test (79.6% vs 31.5%, p<0.001). The patients given regadenoson experienced a significantly higher occurrence of arrhythmia (30.6% vs 16.1%, p<0.001), dyspnea (66.0% vs 17.7%, p<0.001), and headache (25.1% vs 3.1%, p<0.001), and they had a significantly higher rate of aminophylline rescue use (19.2% vs 0.8%, p<0.001). A secondary objective evaluated the financial impact of each agent, and adenosine exhibited a medication price that was more than $100/patient lower than regadenoson based on the average wholesale price.ConclusionAmong patients undergoing an outpatient pharmacologic stress test, the use of adenosine was associated with a lower occurrence of adverse effects and lower rate of a rescue agent use and may provide a potential medication cost savings opportunity compared with regadenoson.
Antiretroviral Treatment Efficacy and Safety in Older HIV‐Infected Adults
Authors: Jourjy Jacqueline , Dahl Keelin , Huesgen Emily 
Published: December 2015

Highly active antiretroviral therapy (ART) and its widespread availability have revolutionized the landscape of HIV care and patient outcomes, transforming infection with HIV into a manageable chronic condition rather than a life‐limiting disease. This transformation has created an older patient demographic. The effect that older age has on the outcomes of ART is not completely understood. Limited data are available in older individuals due to underrepresentation in clinical trials. To better understand this relationship, we conducted a literature search to assess the impact of older age on the outcomes of ART in the older HIV‐infected population, including immunologic and virologic outcomes, mortality, disease progression, toxicity of ART, and pharmacokinetic considerations. In addition, package inserts of antiretroviral (ARV) medications were reviewed for efficacy, safety, and pharmacokinetic information pertaining to the older population. Most studies in older adults (50 yrs or older) demonstrated slower and blunted CD4 immune recovery but better virologic suppression in response to ART. Higher rates of mortality and faster disease progression have been observed in adults 50 years and older, particularly during the first year after ART initiation. HIV‐infected patients aged 50 years and older appear to be at greater risk for certain ART‐associated toxicities including nephrotoxicity, decline in bone mineral density and bone fracture, symptomatic peripheral neuropathy, and cardiovascular disease including myocardial infarction. The available literature suggests that clinicians should consider avoiding agents such as tenofovir disoproxil fumarate (TDF) in older patients with risk factors for renal impairment and/or osteoporosis. If TDF is used in patients aged 50 years or older, more frequent monitoring should be considered. Older age was a significant predictor for higher atazanavir exposure and higher lopinavir trough concentration at 24 weeks. The clinical implications of these findings are unknown. It is imperative that future development of novel ARV drug therapies includes a greater proportion of older subjects in clinical trials.
Rapid‐Onset Thrombocytopenia Following Piperacillin‐Tazobactam Reexposure
Authors: Nguyen Van Dong , Tourigny Jean‐François , Roy Renaud , Brouillette Denis 
Published: December 2015

Drug‐induced thrombocytopenia is a rare but serious adverse event that has been associated with multiple drugs including β‐lactams. Although it mostly occurs with prolonged medication use, some cases of rapid‐onset thrombocytopenia have been reported. We describe the case of a 69‐year‐old man who developed severe and immediate thrombocytopenia following reexposure to piperacillin‐tazobactam in the critical care setting. He received a 6‐day course of piperacillin‐tazobactam for a possible pneumonia immediately after cardiac surgery. During this course of therapy, his platelet count decreased (fluctuating between 69 × 103/mm3 and 104 × 103/mm3) and then progressively increased after completion of the antibiotic to 340 × 103/mm3 on postoperative day 15. Ten days after the antibiotic course was completed (postoperative day 16), the patient developed new signs of infection (fever and neutrophilia), and piperacillin‐tazobactam was restarted. Eight hours after reintroducing the antibiotic, his platelet count dropped from 317 × 103/mm3 to 7 × 103/mm3. After reviewing all the medications administered to the patient as well as other potential causes of thrombocytopenia, and given the chronology of events, piperacillin‐tazobactam was suspected as the most likely offending agent and was therefore replaced by meropenem on postoperative day 17. The patient's platelet count began to rise 2 days after discontinuation of piperacillin‐tazobactam and reached 245 × 103/mm3 by postoperative day 30. No spontaneous bleeding or thrombosis occurred while the patient was thrombocytopenic. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6) between the patient's development of thrombocytopenia and piperacillin‐tazobactam therapy. This case highlights the severity and swiftness in which drug‐induced thrombocytopenia may present in the context of cardiac surgery.
Synthesis and characterization of PDEAEMA‐based magneto‐nanogels: Preliminary results on the biocompatibility with cells of human peripheral blood
Authors: Pikabea Aintzane , Ramos Jose , Papachristos Nikos , Stamopoulos Dimosthenis , Forcada Jacqueline 
Published: December 2015

ABSTRACTNanogels based on biocompatible, dual pH‐ and temperature‐sensitive poly(2‐(diethylamino)ethyl) methacrylate (PDEAEMA) have been successfully used as nanocontainers for the encapsulation of magnetite, Fe3O4 magnetic nanoparticles (MNPs). For this purpose, citric acid‐coated MNPs were encapsulated into previously synthesized PDEAEMA‐based nanogels using a poly(ethyleneglycol)‐based stabilizer. After the encapsulation of the magnetite MNPs, the so‐called magneto‐nanogels (MNGs) were proved to be multiresponsive on temperature, pH, and magnetic field and colloidally stable. Moreover, preliminary studies on the biocompatibility of these MNGs with cells of human peripheral blood were performed and evidenced quite tolerable biocompatibility, thus suggesting potential use in biomedical applications. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 1479–1494
Strikingly improved toughness of nonpolar rubber by incorporating sacrificial network at small fraction
Authors: Zhang Xuhui , Tang Zhenghai , Huang Jing , Lin Tengfei , Guo Baochun 
Published: December 2015

ABSTRACTIt poses a huge challenge to create nonpolar rubber with high fracture toughness. In the present letter, inspired by the concept of sacrificial bonding associated with many biological materials, we propose that a small fraction of additional sacrificial network can strikingly improve the fracture toughness of nonpolar rubbers. As a proof of concept, we created the additional “fragile” epoxidized natural rubber (ENR) network in commercially available SBR rubber in a facile process. With addition of only 10 phr ENR, the SBR/ENR double network (DN) exhibits a fracture energy nearly fourfold higher than that for the neat SBR. The formation of DN formation and the correlation between the high toughness and presence of the second brittle network have been fully discussed. This is the first time sacrificial networks are created in diene‐based rubber towards high toughness elastomers in a facile and efficient way. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 781–786
On the Thermal Stability of Partially Decomposed Ammonium Perchlorate
Authors: Hedman Trevor D. , Gross Matthew L. 
Published: December 2015

AbstractThe response of propellants and explosives to thermal stimuli is an important aspect of their behavior, especially for their safe storage and handling. In the case of ammonium perchlorate (AP), the principal oxidizer used in solid composite propellants, exposure to elevated temperatures causes various levels of decomposition and morphological changes. These changes occur in both neat AP particles and AP based propellants. The hazards associated with thermally damaged, or partially decomposed AP are investigated. It is found that AP is more thermally stable after partial low temperature decomposition. Also, it is found that the extent of decomposition of the AP particles is strongly influenced by prior thermal damage. This dependency is attributed to the exhaustion of nucleation sites on certain crystal planes. Specific surface area measurements of the thermally damaged particles show that the particles recrystallize before they can decompose to a further extent in low temperature decomposition. The behavior of partially decomposed AP in the presence of a propellant binder is also examined.
Resolving the ambiguity: Making sense of intrinsic disorder when PDB structures disagree
Authors: DeForte Shelly , Uversky Vladimir N. 
Published: December 2015

AbstractMissing regions in X‐ray crystal structures in the Protein Data Bank (PDB) have played a foundational role in the study of intrinsically disordered protein regions (IDPRs), especially in the development of in silico predictors of intrinsic disorder. However, a missing region is only a weak indication of intrinsic disorder, and this uncertainty is compounded by the presence of ambiguous regions, where more than one structure of the same protein sequence “disagrees” in terms of the presence or absence of missing residues. The question is this: are these ambiguous regions intrinsically disordered, or are they the result of static disorder that arises from experimental conditions, ensembles of structures, or domain wobbling? A novel way of looking at ambiguous regions in terms of the pattern between multiple PDB structures has been demonstrated. It was found that the propensity for intrinsic disorder increases as the level of ambiguity decreases. However, it is also shown that ambiguity is more likely to occur as the protein region is placed within different environmental conditions, and even the most ambiguous regions as a set display compositional bias that suggests flexibility. The results suggested that ambiguity is a natural result for many IDPRs crystallized under different conditions and that static disorder and wobbling domains are relatively rare. Instead, it is more likely that ambiguity arises because many of these regions were conditionally or partially disordered.
Dimensions, energetics, and denaturant effects of the protein unstructured state
Authors: Li Maodong , Liu Zhirong 
Published: December 2015

AbstractDetermining the energetics of the unfolded state of a protein is essential for understanding the folding mechanics of ordered proteins and the structure–function relation of intrinsically disordered proteins. Here, we adopt a coil‐globule transition theory to develop a general scheme to extract interaction and free energy information from single‐molecule fluorescence resonance energy transfer spectroscopy. By combining protein stability data, we have determined the free energy difference between the native state and the maximally collapsed denatured state in a number of systems, providing insight on the specific/nonspecific interactions in protein folding. Both the transfer and binding models of the denaturant effects are demonstrated to account for the revealed linear dependence of inter‐residue interactions on the denaturant concentration, and are thus compatible under the coil‐globule transition theory to further determine the dimension and free energy of the conformational ensemble of the unfolded state. The scaling behaviors and the effective θ‐state are also discussed.