bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ascorbate induces apoptosis in melanoma cells by suppressing Clusterin expression
Authors: Mustafi Sushmita , Sant David W. , Liu Zhao-Jun , Wang Gaofeng 
Published: June 2017

AbstractPharmacological levels of ascorbate have long been suggested as a potential treatment of cancer. However, we observed that EC50 of ascorbate was at a similar level for cultured healthy melanocytes and melanoma cells, suggesting a limit of pharmacological ascorbate in treating cancer. Loss of 5-hydroxymethylcytosine (5 hmC) is an epigenetic hallmark of cancer and ascorbate promotes 5 hmC generation by serving as a cofactor for TET methylcytosine dioxygenases. Our previous work demonstrated that ascorbate treatment at physiological level (100 μM) increased 5 hmC content in melanoma cells toward the level of healthy melanocytes. Here we show that 100 µM of ascorbate induced apoptosis in A2058 melanoma cells. RNA-seq analysis revealed that expression of the Clusterin (CLU) gene, which is related to apoptosis, was downregulated by ascorbate. The suppression of CLU was verified at transcript level in different melanoma cell lines, and at protein level in A2058 cells. The anti-apoptotic cytoplasmic CLU was decreased, while the pro-apoptotic nuclear CLU was largely maintained, after ascorbate treatment. These changes in CLU subcellular localization were also associated with Bax and caspases activation, Bcl-xL sequestration, and cytochrome c release. Taken together, this study establishes an impending therapeutic role of physiological ascorbate to potentiate apoptosis in melanoma.
Prognostic value of olfactory nerve damage measured with thallium-based olfactory imaging in patients with idiopathic olfactory dysfunction
Authors: Shiga Hideaki , Taki Junichi , Okuda Koichi , Watanabe Naoto , Tonami Hisao , Nakagawa Hideaki , Kinuya Seigo , Miwa Takaki 
Published: June 2017

AbstractIdiopathic olfactory disorder is resistant to treatment, and the recovery time is long. This study investigated the prognostic value of the migration of nasally administered thallium-201 to the olfactory bulb (thallium migration to the OB), a measure of olfactory nerve damage, in patients with idiopathic olfactory disorders. Twenty-four patients with idiopathic olfactory disorders were enrolled in the study (7 women and 17 men; aged 23–73 years). We retrospectively analyzed potential prognostic markers in subjects who underwent thallium-based olfactory imaging with the nasal administration of thallium-201 before conventional treatment with the Japanese herbal medicine tokishakuyakusan and compared those data with the prognosis. Log-rank tests were performed to assess the relationship between thallium migration to the OB (<4.6% [low] vs. ≥4.6% [high]; data dichotomized at the optimal cutoff value) and the duration until recovery of the odor recognition threshold determined by a standard olfactory function test (T&T olfactometry) after the treatment. Upon statistical analysis, we found that high thallium migration to the OB was significantly correlated with better prognosis in patients. Our results suggest that patients with intact olfactory nerve fibers could be selected using thallium-based imaging for the long-term follow-up of olfactory dysfunction.
A non-ionotropic activity of NMDA receptors contributes to glycine-induced neuroprotection in cerebral ischemia-reperfusion injury
Authors: Chen Juan , Hu Rong , Liao Huabao , Zhang Ya , Lei Ruixue , Zhang Zhifeng , Zhuang Yang , Wan Yu , Jin Ping , Feng Hua , Wan Qi 
Published: June 2017

AbstractNMDA receptor (NMDAR) is known for its ionotropic function. But recent evidence suggests that NMDAR also has a non-ionotropic property. To determine the role of non-ionotropic activity of NMDARs in clinical relevant conditions, we tested the effect of glycine, a co-agonist of NMDARs, in rat middle cerebral artery occlusion (MCAO), an animal model of cerebral ischemia-reperfusion injury after the animals were injected with the NMDAR channel blocker MK-801 and the glycine receptor antagonist strychnine. We show that glycine reduces the infarct volume in the brain of ischemic stroke animals pre-injected with MK-801 and strychnine. The effect of glycine is sensitive to the antagonist of glycine-GluN1 binding site and blocked by Akt inhibition. In the neurobehavioral tests, glycine improves the functional recovery of stroke animals pre-injected with MK-801 and strychnine. This study suggests that glycine-induced neuroprotection is mediated in part by the non-ionotropic activity of NMDARs via Akt activation in cerebral ischemia-reperfusion injury.
Chinese Milk Vetch Improves Plant Growth, Development and 15N Recovery in the Rice-Based Rotation System of South China
Authors: Xie Zhijian , He Yaqin , Tu Shuxin , Xu Changxu , Liu Guangrong , Wang Huimin , Cao Weidong , Liu Hui 
Published: June 2017

AbstractChinese milk vetch (CMV) is vital for agriculture and environment in China. A pot experiment combined with 15N labeling (including three treatments: control, no fertilizer N and CMV; 15N-labeled urea alone, 15NU; substituting partial 15NU with CMV, 15NU-M) was conducted to evaluate the impact of CMV on plant growth, development and 15NU recovery in rice-based rotation system. The 15NU-M mitigated oxidative damage by increasing antioxidant enzymes activities and chlorophyll content while decreased malondialdehyde content in rice root and shoot, increased the biomass, total N and 15N uptake of plant shoots by 8%, 12% and 39% respectively, thus inducing a noticeable increase of annual 15N recovery by 77% versus 15NU alone. Remarkable increases in soil NH4+ and populations of bacteria, actinomycetes and azotobacter were obtained in legume-rice rotation system while an adverse result was observed in soil NO3− content versus fallow-rice. CMV as green manure significantly increased the fungal population which was decreased with cultivating CMV as cover crop. Therefore, including legume cover crop in rice-based rotation system improves plant growth and development, annual N conservation and recovery probably by altering soil nitrogen forms plus ameliorating soil microbial communities and antioxidant system which alleviates oxidative damages in plants.
Designing a molecular magnetic button based on 4d and 5d transition-metal phthalocyanines
Authors: Ferriani P. , Heinze S. , Bellini V. 
Published: June 2017

AbstractThe field of molecular spintronics exploits the properties of organic molecules possessing a magnetic moment, either native in the form of radicals or induced by the insertion of transition metal magnetic ions. To realize logic or storage molecular spin-tronics devices, molecules with stable different magnetic states should be deposited on a substrate, and switching between the states controllably achieved. By means of a first-principles calculations, we have devised a functional molecule exhibiting different magnetic states upon structural changes induced by current injection. We investigate the prototypical case of non-planar M-Phthalocyanine (MPc), where M is a transition-metal ion belonging to the 4d and 5d series. We find that for ZrPc and HfPc deposited on a graphene decorated Ni(111) substrate, two different structural conformations could be stabilized, for which the molecules attain different magnetic states depending on the position of the M ion – whether above the Pc or between the Pc and the substrate –, acting therefore as molecular magnetic button. Our work indicates an intuitive way to engineer a magnetic molecular switch with tailored properties, starting from the knowledge of the basic atomic properties of elements and surfaces.
Improved Growth Patterns in Cystic Fibrosis Mice after Loss of Histone Deacetylase 6
Authors: Rymut Sharon M. , Corey Deborah A. , Valerio Dana M. , Erokwu Bernadette O. , Flask Chris A. , Kelley Thomas J. , Hodges Craig A. 
Published: June 2017

AbstractGrowth failure in cystic fibrosis (CF) patients has been well-documented and shown to correlate with poorer disease outcomes. This observation is also true in CF animal models, including mouse, pig, rat, and ferret. The etiology underlying growth deficits is unknown, and our previous work demonstrated reduced tubulin acetylation in CF cell models and tissue that is correctable by inhibition of histone deacetylase-6 (HDAC6). Here, we hypothesize that loss of HDAC6 will improve growth phenotype in a CF mouse model. Hdac6 knockout mice were crossed with F508del (CF) mice to generate F508del/Hdac6 (CF/HDA) mice. Growth, fat deposits, survival, and bioelectric measurements were analyzed. CF/HDA mice displayed improvements in length and weight with no correction of CFTR function. Mechanistically, Igf1 levels likely account for increased length and improvements in fertility. Weight gain is attributed to increased fat deposits potentially mediated by increased adipocyte differentiation. CF-related growth deficits can be improved via inhibition of HDAC6, further implicating it as a potential therapeutic target for CF.
Dengue virus activates cGAS through the release of mitochondrial DNA
Authors: Sun Bo , Sundström Karin B. , Chew Jun Jie , Bist Pradeep , Gan Esther S. , Tan Hwee Cheng , Goh Kenneth C. , Chawla Tanu , Tang Choon Kit , Ooi Eng Eong 
Published: June 2017

AbstractCyclic GMP-AMP synthetase (cGAS) is a DNA-specific cytosolic sensor, which detects and initiates host defense responses against microbial DNA. It is thus curious that a recent study identified cGAS as playing important roles in inhibiting positive-sense single-stranded RNA (+ssRNA) viral infection, especially since RNA is not known to activate cGAS. Using a dengue virus serotype 2 (DENV-2) vaccine strain (PDK53), we show that infection creates an endogenous source of cytosolic DNA in infected cells through the release of mitochondrial DNA (mtDNA) to drive the production of cGAMP by cGAS. Innate immune responses triggered by cGAMP contribute to limiting the spread of DENV to adjacent uninfected cells through contact dependent gap junctions. Our result thus supports the notion that RNA virus indirectly activates a DNA-specific innate immune signaling pathway and highlights the breadth of the cGAS-induced antiviral response.
Salivary testosterone measurement in women with and without polycystic ovary syndrome
Authors: Sathyapalan Thozhukat , Al-Qaissi Ahmed , Kilpatrick Eric S. , Dargham Soha R. , Adaway Joanne , Keevil Brian , Atkin Stephen L. 
Published: June 2017

AbstractClinical and/or biochemical hyperandrogenism is one of the diagnostic criteria for PCOS. An evaluation of the role of salivary testosterone (salT) and androstenedione (salA) for the diagnosis of PCOS was undertaken in a cross sectional study involving 65 women without PCOS and 110 women with PCOS fulfilling all 3 diagnostic Rotterdam criteria. Serum and salivary androgen measurements were determined by LC-MS/MS. salT and salA were significantly elevated in PCOS compared to controls (P < 001). No androgen marker was more predictive than another using ROC curves, but multiple logistic regression suggested salT was more predictive than free androgen index (FAI) (p < 0.01). The combination of salT or FAI identified 100% of PCOS women. PCOS women with both biochemical and clinical hyperandrogenism as opposed to clinical hyperandrogenism alone showed a metabolic phenotype (p < 0.05) and insulin resistance (p < 0.001). PCOS patients with an isolated elevated FAI showed increased insulin resistance compared to those with an isolated salT (P < 0.05). salT appeared to be at least as predictive as FAI for the diagnosis of the classical PCOS phenotype, and the combination of salT or FAI identified 100% of PCOS patients. This suggests that salT measurement by LC-MS/MS holds the promise of complementing existing laboratory tests as a means of assessing hyperandrogenemia.
Regulation of Angiopoietin Signalling by Soluble Tie2 Ectodomain and Engineered Ligand Trap
Authors: Alawo Deborah O. A. , Tahir Tariq A. , Fischer Marlies , Bates Declan G. , Amirova Svetlana R. , Brindle Nicholas P. J. 
Published: June 2017

AbstractAngiopoietin-1 (Angpt1) is a glycoprotein ligand important for maintaining the vascular system. It signals via a receptor tyrosine kinase expressed on the surface on endothelial cells, Tie2. This receptor can undergo regulated ectodomain cleavage that releases the ligand-binding domain (sTie2) into the circulation. The concentration of sTie2 is increased in a range of conditions, including peripheral arterial disease and myocardial infarction, where it has been suggested to bind and block Angpt1 resulting in vascular dysfunction. Here we use a joint mathematical modelling and experimental approach to assess the potential impact of sTie2 on the ability of Angpt1 to signal. We find that the concentrations of sTie2 relative to Angpt1 required to suppress signalling by the ligand are more than ten–fold higher than those ever seen in normal or disease conditions. In contrast to the endogenous sTie2, an engineered form of sTie2, which presents dimeric ligand binding sites, inhibits Angpt1 signalling at seventy-fold lower concentrations. While loss of Tie2 ectodomain can suppress Angpt1 signalling locally in the cells in which the receptor is lost, our study shows that the resulting increase in circulating sTie2 is unlikely to affect Angpt1 activity elsewhere in the body.
Factors controlling the mechanical properties degradation and permeability of coal subjected to liquid nitrogen freeze-thaw
Authors: Qin Lei , Zhai Cheng , Liu Shimin , Xu Jizhao 
Published: June 2017

AbstractFreeze-thaw induced fracturing coal by liquid nitrogen (LN2) injection exerts a significant positive effect on the fracture permeability enhancement of the coal reservoir. To evaluate the different freeze-thaw variables which modify the mechanical properties of treated coals, the effects of freezing time, number of freeze-thaw cycles, and the moisture content of coal were studied using combined uniaxial compression and acoustic emission testing systems. Freezing the samples with LN2 for increasing amounts of time degraded the strength of coal within a certain limit. Comparison to freezing time, freeze-thaw cycling caused much more damage to the coal strength. The third variable studied, freeze-thaw damage resulting from high moisture content, was restricted by the coal’s moisture saturation limit. Based on the experimental results, equations describing the amount of damage caused by each of the different freeze-thaw variables were empirically regressed. Additionally, by using the ultrasonic wave detection method and fractal dimension analyses, how freeze-thaw induced fractures in the coal was quantitatively analyzed. The results also showed that the velocity of ultrasonic waves had a negative correlation with coal permeability, and the freeze-thaw cycles significantly augment the permeability of frozen-thawed coal masses.
UV-induced damage to DNA: effect of cytosine methylation on pyrimidine dimerization
Authors: Martinez-Fernandez Lara , Banyasz Akos , Esposito Luciana , Markovitsi Dimitra , Improta Roberto 
Published: June 2017

AbstractMethylation/demethylation of cytosine plays an important role in epigenetic signaling, the reversibility of epigenetic modifications offering important opportunities for targeted therapies. Actually, methylated sites have been correlated with mutational hotspots detected in skin cancers. The present brief review discusses the physicochemical parameters underlying the specific ultraviolet-induced reactivity of methylated cytosine. It focuses on dimerization reactions giving rise to cyclobutane pyrimidine dimers and pyrimidine (6–4) pyrimidone adducts. According to recent studies, four conformational and electronic factors that are affected by cytosine methylation may control these reactions: the red-shift of the absorption spectrum, the lengthening of the excited state lifetime, changes in the sugar puckering modifying the stacking between reactive pyrimidines and an increase in the rigidity of duplexes favoring excitation energy transfer toward methylated pyrimidines.
Clinical Scoring Systems in Thrombotic Microangiopathies
Authors: Upadhyay Vivek , Sun Lova , Marques Marisa , Makar Robert , Bendapudi Pavan 
Published: June 2017

AbstractThrombotic microangiopathies (TMAs) are a group of rare but potentially lethal hematologic disorders characterized by platelet-rich thrombi in the microvasculature. In evaluating patients with TMA, it is crucial to identify those who have thrombotic thrombocytopenic purpura (TTP), a subtype of TMA that occurs due to a severe deficiency in ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13). Individuals with TTP require urgent therapeutic plasma exchange, which is associated with a significant reduction in mortality; however, at most centers, the results of ADAMTS13 activity testing are usually not available for 3 to 5 days. Given the possible need for urgent intervention and the lack of timely test results to guide therapy, the assessment of patients with TMA represents an ideal situation for the deployment of diagnostic scoring systems to predict the presence of severe ADAMTS13 deficiency. Here, we review the literature surrounding clinical prediction tools in the diagnosis and prognostication of patients with TMA, describe the experience at our center with evaluating TMA patients, and discuss the utility of clinical scoring systems for TMA in the context of patient care.
Visceral Leishmaniasis in Children: Diagnosis, Treatment, and Prevention
Authors: Gupta Anil , Singh Amit , Srivastava Saumya , Shankar Prem , Singh Sarman 
Published: June 2017

AbstractLeishmaniasis is a neglected tropical parasitic disease caused by an obligate intracellular protozoan of the genus Leishmania. The disease is transmitted by the bite of infected sand flies (Phlebotomus species) and affects all ages and both genders. Nearly half of the visceral leishmaniasis (VL) cases occur in children. The clinical manifestations of pediatric leishmaniasis may be different from the adults associated with host-related factors. In this review, only the visceral form is covered. Confirmation of diagnosis is made by the parasitological, immunological, or by molecular methods. Sodium antimony gluconate (stibogluconate) has been the drug of choice for more than 60 years. However, in last three decades, its efficacy against leishmaniasis has gone significantly down especially in the Indian subcontinent where most cases of VL are seen. Therefore, other drugs, such as pentamidine-isothionate, paromomycin, amphotericin B, and miltefosine, are being used as alternative drugs for VL treatment. In the absence of an effective vaccine for VL, control measures are based on the prevention of disease transmission via vector control and community awareness. The present review focuses on the current state of the leishmaniasis, its diagnosis, treatment, and prevention with emphasis on pediatric leishmaniasis.
Choice of Intra-arterial Therapy for Hepatocellular Carcinoma: Evidence and Future Horizons
Authors: Ghani Mansur , Thakur Vinayak , Geschwind Jean-François 
Published: June 2017

AbstractHepatocellular carcinoma is the second most common cause of cancer-related deaths worldwide. Along with viral and alcoholic hepatitis, obesity is the leading cause for increasing incidence in the western world, specifically in the United States. As most patients initially present with intermediate to advanced stage disease, curative therapies such as ablation, surgical resection, or liver transplantation cannot usually be applied. Thus, intra-arterial therapies (IATs), such as transarterial chemoembolization (TACE), have become a mainstay of treatment. Several variations of transarterial embolotherapy, such as bland transarterial embolization or drug-eluting bead TACE, are currently available and used in clinical practice. Yttrium-90 radioembolization is a distinct IAT that relies on delivery of radiation to surrounding tissue for tumor death. However, no clear guidelines or evidence exist that would favor one of these options over the other, leaving the decision-making process open to influence by local expertise and experience. In addition, combining TACE with systemic antiangiogenic agents, such as the multityrosine kinase inhibitor sorafenib, has been investigated in several prospective clinical trials without clearly demonstrating substantial survival benefits of the combination over TACE alone. This review will summarize and discuss the available clinical evidence and indications for each treatment modality with the goal of facilitating clinical decision-making processes, and provide an overview of the ongoing efforts to compare different IAT modalities.
Erhöhte Leberwerte bei einem Rheumapatienten. Was nun?
Authors: Fiehn Christoph 
Published: June 2017

ZusammenfassungRegelmäßige Kontrollen der Leberwerte sind ein fester Bestandteil der rheumatologischen Routine. Erhöhte Transaminasen sind dabei ein häufiger Befund, für den viele verschiedene Gründe in Frage kommen. Als Erstes muss die Möglichkeit einer unerwünschten Wirkung eines der rheumatologischen Medikamente erwogen werden. Am häufigsten sind dies NSAR, vor allem Diclofenac, gefolgt von den DMARD Methotrexat oder Leflunomid. Die Kombination der letztere beiden verursacht besonders häufig Transaminasenanstiege. Der aktive Metabolit von Leflunomid muss dann unter Umständen mit Colestyramin aus dem enterohepatischen Kreislauf ausgewaschen werden. Leberwerterhöhungen durch Sulfasalazin sind selten, schwere nekrotisierende Hepatitiden als Teil einer systemischen Medikamentenreaktion können jedoch auftreten. Unter den biologischen DMARD sind es v. a. die TNF-alpha-Hemmer Infliximab und Adalimumab welche Hepatitiden verursachen können. Bei Patienten mit ankylosierender Spondylitis waren aber auch unter Etanercept Leberwertanstiege beobachtet worden. Als weitere Substanz kann der Interleukin-6-Rezeptor Antikörper Tocilizumab zu einem Anstieg der Transaminasen führen, selten auch zu schweren Leberreaktionen. Schließlich gibt es noch eine ganze Reihe von anderen Ursachen für Anstiege der Leberwerte bei Rheumapatienten, die von einer Reaktivierung oder Neuinfektion einer Virushepatitis, dem Auftreten einer Autoimmunhepatitis bis zu Begleiterkrankungen der Leber reichen. Dies alles macht ein systematisches differentialdiagnostisches Vorgehen notwendig.
Hypothyreose nach Hemithyreoidektomie − überraschend häufige Komplikation während der Nachsorge
Authors: Elmas Firat , Lauber Fabienne , Linder Thomas , Müller Werner 
Published: June 2017

Zusammenfassung
Hintergrund Hemithyreoidektomie ist eine häufige Behandlung einseitiger Schilddrüsenknoten. Postoperative Hypothyreose ist eine häufig
unterschätzte Komplikation. Wir untersuchten Inzidenz, Zeitpunkt, Symptomatik sowie mögliche Risikofaktoren der postoperativen
Hypothyreose.
Material und Methoden 127 Patienten nach Hemithyreoidektomie wurden mit retrospektiver Datenanalyse sowie strukturierter Befragung der
nachbetreuenden Hausärzte und Endokrinologen untersucht. Patienten wurden mit dem postoperativen TSH als hypothyreot (> 4.0 mU/L) oder
euthyreot (0.4–4.0 mU/L) klassifiziert. Schilddrüsenhormone wurden nach 4–6 Wochen, 6 Monaten und 1 Jahr gemessen.
Ergebnisse 55 Patienten (43 %) entwickelten eine postoperative Hypothyreose und 72 (57%) blieben euthyreot. Die Hypothyreose zeigte
sich innerhalb der ersten 2 Monaten bei 39 Patienten (71 %), zwischen 2–6 Monaten bei 13 Patienten (24 %) sowie nach 6–12 Monaten bei 3
Patienten (5 %). 33 Patienten (60 %) waren zum Zeitpunkt der Diagnose asymptomatisch. Nur 16 Patienten (29 %) hatten Symptome. Der
präoperative TSH Wert war signifikant höher in der Gruppe der hypothyreoten Patienten (1.64), verglichen mit der euthyreoten Gruppe (1.13, P
= 0.0017). Die anderen Variablen wie Alter, Geschlecht und präoperativen Werte von T3, T4, Calcium und PTH zeigten keinen signifikanten
Unterschied.
Schlussfolgerung Die postoperative Hypothyreose ist eine häufige Komplikation nach Hemithyreoidektomie, welche nicht verpasst werden
sollte. Präoperativ erhöhter TSH Wert ist ein Risikofaktor für die postoperative Hypothyreose. Alle Patienten nach Hemithyreoidektomie
sollten postoperative TSH Kontrollen nach 4–6 Wochen, 6 Monaten und 12 Monaten haben.