bluuebunny/crossref_metadata_2025 huggingface dataset:
A Method for Noise Source Levels Inversion with Underwater Ambient Noise Generated by Typhoon in Deep Ocean
Authors: Yang Qiulong , Yang Kunde , Duan Shunli
Published: June 2018

Sea-surface wind agitation can be considered the dominant noise sources whose intensity relies on local wind speed during typhoon period. Noise source levels in previous researches may be unappreciated for all oceanic regions and should be corrected for modeling typhoon-generated ambient noise fields in deep ocean. This work describes the inversion of wind-driven noise source level based on a noise field model and experimental measurements, and the verification of the inverted noise source levels with experimental results during typhoon period. A method based on ray approach is presented for modeling underwater ambient noise fields generated by typhoons in deep ocean. Besides, acoustic field reciprocity is utilized to decrease the calculation amount in modeling ambient noise field. What is more, the depth dependence and the vertical directionality of noise field based on the modeling method and the Holland typhoon model are evaluated and analyzed in deep ocean. Furthermore, typhoons named “Soulik” in 2013 and “Nida” in 2016 passed by the receivers deployed in the western Pacific (WP) and the South China Sea (SCS). Variations in sound speed profile, bathymetry, and the related oceanic meteorological parameters are analyzed and taken into consideration for modeling noise field. Boundary constraint simulated annealing (SA) method is utilized to invert the three parameters of noise source levels and to minimize the objective function value. The prediction results with the inverted noise source levels exhibit good agreement with the measured experiment data and are compared with predicted results with other noise sources levels derived in previous researches.
A Numerical Evidence of Biosonar Beam Formation of a Neonate Yangtze Finless Porpoise (Neophocaena asiaeorientalis)
Authors: Wei Chong , Song Zhongchang , Au Whitlow W. L. , Zhang Yu , Wang Ding
Published: June 2018

Yangtze finless porpoises (Neophocaena asiaeorientalis) are known to use the narrowband signals for echolocation. In this study, a finite-element model was configured based on computed tomography imaging technique and tissue physical properties measurement to simulate biosonar signal emission and transmission processes through animal’s head. The roles of the main structures in the head such as the air sacs, melon, bony structures, connective tissue, blubber, mandibular fat on the biosonar beam formation were investigated, and the relative importance of these structures was compared. The biosonar beam properties of this neonate porpoise were compared with those of adult ones. The method in this paper suggested an effective way for investigating the acoustic processes in the heads of the neonate odontocetes.
A Pollution Effect in the Boundary Element Method for Acoustic Problems
Authors: Marburg Steffen
Published: June 2018

The pollution effect is a well-known and well-investigated phenomenon of the finite element method for wave problems in general and for acoustic problems in particular. It is understood as the problem that a local mesh refinement cannot compensate the numerical error which is generated and accumulated in other regions of the model. This is the case for the phase error of the finite element method which leads to dispersion resulting in very large numerical errors for domains with many waves in them and is of particular importance for low order elements. Former investigations have shown that a pollution effect resulting from dispersion is unlikely for the boundary element method. However, numerical damping in the boundary element method can account for a pollution effect. A further investigation of numerical damping reveals that it has similar consequences as the phase error of the finite element method. One of these consequences is that the number of waves within the domain may be controlling the discretization error in addition to the size and the order of the boundary elements. This will be demonstrated in computational examples discussing traveling waves in rectangular ducts. Different lengths, element types and mesh sizes are tested for the boundary element collocation method. In addition to the amplitude error which is due to numerical damping, a rather small phase error is observed. This may indicate numerical dispersion.
A novel bioluminescence-based method to investigate uptake of bile acids in living cells
Authors: Ticho Alexander L. , Lee Hyunjin , Gill Ravinder K. , Dudeja Pradeep K. , Saksena Seema , Lee Daesung , Alrefai Waddah A.
Published: June 2018

Bile acid transporters, including the ileal apical sodium-dependent bile acid transporter (ASBT) and the hepatic sodium-taurocholate cotransporting polypeptide (NTCP), are crucial for the enterohepatic circulation of bile acids. Our objective was to develop a method for measuring bile acid transporter activity in real time to precisely evaluate rapid changes in their function. We designed a reporter system relying on a novel probe: cholic acid attached to luciferin via a disulfide-containing, self-immolating linker (CA-SS-Luc). Incubation of human embryonic kidney-293 cells coexpressing luciferase and ASBT with different concentrations of CA-SS-Luc (0.01–1 μM) resulted in bioluminescence with an intensity that was concentration- and time-dependent. The bioluminescence measured during incubation with 1 μM CA-SS-Luc was dependent on the levels of ASBT or NTCP expressed in the cells. Coincubation of CA-SS-Luc with natural bile acids enhanced the bioluminescence in a concentration-dependent manner with kinetic parameters for ASBT similar to those previously reported using conventional methods. These findings suggest that this method faithfully assesses ASBT function. Further, incubation with tyrosine phosphatase inhibitor III (PTPIII) led to significantly increased bioluminescence in cells expressing ASBT, consistent with previous studies showing an increase in ASBT function by PTPIII. We then investigated CA-SS-Luc in isolated mouse intestinal epithelial cells. Ileal enterocytes displayed significantly higher luminescence compared with jejunal enterocytes, indicating a transport process mediated by ileal ASBT. In conclusion, we have developed a novel method to monitor the activity of bile acid transporters in real time that has potential applications both for in vitro and in vivo studies.

NEW & NOTEWORTHY This article reports the development of a real-time method for measuring the uptake of bile acids using a bioluminescent bile acid-based probe. This method has been validated for measuring uptake via the apical sodium-dependent bile acid transporter and the sodium-taurocholate cotransporting polypeptide in cell culture and ex vivo intestinal models.
Validation of noninvasive photoacoustic measurements of sagittal sinus oxyhemoglobin saturation in hypoxic neonatal piglets
Authors: Kang Jeeun , Boctor Emad M. , Adams Shawn , Kulikowicz Ewa , Zhang Haichong K. , Koehler Raymond C. , Graham Ernest M.
Published: June 2018

We hypothesize that noninvasive photoacoustic imaging can accurately measure cerebral venous oxyhemoglobin saturation (So2) in a neonatal model of hypoxia-ischemia. In neonatal piglets, which have a skull thickness comparable to that of human neonates, we compared the photoacoustic measurement of sagittal sinus So2against that measured directly by blood sampling over a wide range of conditions. Systemic hypoxia was produced by decreasing inspired oxygen stepwise (i.e., 100, 21, 19, 17, 15, 14, 13, 12, 11, and 10%) with and without unilateral or bilateral ligation of the common carotid arteries to enhance hypoxia-ischemia. Transcranial photoacoustic sensing enabled us to detect changes in sagittal sinus O2saturation throughout the tested range of 5–80% without physiologically relevant bias. Despite lower cortical perfusion and higher oxygen extraction in groups with carotid occlusion at equivalent inspired oxygen, photoacoustic measurements successfully provided a robust linear correlation that approached the line of identity with direct blood sample measurements. Receiver-operating characteristic analysis for discriminating So2<30% showed an area under the curve of 0.84 for the pooled group data, and 0.87, 0.91, and 0.92 for hypoxia alone, hypoxia plus unilateral occlusion, and hypoxia plus bilateral occlusion subgroups, respectively. The detection precision in this critical range was confirmed with sensitivity (87.0%), specificity (86.5%), accuracy (86.8%), positive predictive value (90.5%), and negative predictive value (81.8%) in the combined dataset. These results validate the capability of photoacoustic sensing technology to accurately monitor sagittal sinus So2noninvasively over a wide range and support its use for early detection of neonatal hypoxia-ischemia.

NEW & NOTEWORTHY We present data to validate the noninvasive photoacoustic measurement of sagittal sinus oxyhemoglobin saturation. In particular, this paper demonstrates the robustness of this methodology during a wide range of hemodynamic and physiological changes induced by the stepwise decrease of fractional inspired oxygen to produce hypoxia and by unilateral and bilateral ligation of the common carotid arteries preceding hypoxia to produce hypoxia-ischemia. This technique may be useful for diagnosing risk of neonatal hypoxic-ischemic encephalopathy.
Near-infrared spectroscopy using indocyanine green dye for minimally invasive measurement of respiratory and leg muscle blood flow in patients with COPD
Authors: Louvaris Zafeiris , Habazettl Helmut , Wagner Harrieth , Zakynthinos Spyros , Wagner Peter , Vogiatzis Ioannis
Published: June 2018

Reliability of near-infrared spectroscopy, measuring indocyanine green (ICG) for minimally invasive assessment of relative muscle blood flow during exercise has been examined in fit young individuals but not in chronic obstructive pulmonary disease (COPD). Here we ask whether it could be used to evaluate respiratory and locomotor muscle perfusion in COPD patients. Vastus lateralis muscle blood flow (MBF, the reference method calculated from arterial and muscle ICG concentration curves) and a blood flow index [BFI, calculated using only the (same) muscle ICG concentration curves] were compared in 10 patients (forced expiratory volume in 1 s: 51 ± 6% predicted) at rest and during cycling at 25, 50, 75, and 100% of peak work rate (WRpeak). Intercostal muscle MBF and BFI were also compared during isocapnic hyperpnea at rest, reproducing ventilation levels up to those at WRpeak. Intercostal and vastus lateralis BFI increased with increasing ventilation during hyperpnea (from 2.5 ± 0.3 to 4.5 ± 0.7 nM/s) and cycling load (from 1.0 ± 0.2 to 12.8 ± 1.9 nM/s), respectively. There were strong correlations between BFI and MBF for both intercostal ( r = 0.993 group mean data, r = 0.872 individual data) and vastus lateralis ( r = 0.994 group mean data, r = 0.895 individual data). Fold changes from rest in BFI and MBF did not differ for either the intercostal muscles or the vastus lateralis. Group mean BFI data showed strong interrelationships with respiratory and cycling workload, and whole body metabolic demand ( r ranged from 0.913 to 0.989) simultaneously recorded during exercise. We conclude that BFI is a reliable and minimally invasive tool for evaluating relative changes in respiratory and locomotor muscle perfusion from rest to peak exercise in COPD patient groups.

NEW & NOTEWORTHY We show that noninvasive near-infrared spectroscopic (NIRS) detection of indocyanine green dye (ICG) after peripheral venous injection adequately reflects intercostal and locomotor muscle perfusion during exercise and hyperpnea in patients with chronic obstructive pulmonary disease (COPD). Mean, individual, and fold change responses from rest to exercise or hyperpnea correlated closely with the reference method, which requires arterial sampling. NIRS-ICG is a reliable, robust, and essentially noninvasive tool for assessing relative changes in intercostal and locomotor muscle perfusion in COPD patient groups.
Intermittent hypoxia improves behavioral and adrenal gland dysfunction induced by posttraumatic stress disorder in rats
Authors: Manukhina Eugenia B. , Tseilikman Vadim E. , Tseilikman Olga B. , Komelkova Maria V. , Kondashevskaya Marina V. , Goryacheva Anna V. , Lapshin Maxim S. , Platkovskii Pavel O. , Alliluev Anatoly V. , Downey H. Fred
Published: June 2018

Nonpharmacological treatments of stress-induced disorders are promising, since they enhance endogenous stress defense systems, are free of side effects, and have few contraindications. The present study tested the hypothesis that intermittent hypoxia conditioning (IHC) ameliorates behavioral, biochemical, and morphological signs of experimental posttraumatic stress disorder (PTSD) induced in rats with a model of predator stress (10-day exposure to cat urine scent, 15 min daily followed by 14 days of stress-free rest). After the last day of stress exposure, rats were conditioned in an altitude chamber for 14 days at a 1,000-m simulated altitude for 30 min on day 1 with altitude and duration progressively increasing to 4,000 m for 4 h on day 5. PTSD was associated with decreased time spent in open arms and increased time spent in closed arms of the elevated X-maze, increased anxiety index, and increased rate of freezing responses. Functional and structural signs of adrenal cortex degeneration were also observed, including decreased plasma concentration of corticosterone, decreased weight of adrenal glands, reduced thickness of the fasciculate zone, and hydropic degeneration of adrenal gland cells. The thickness of the adrenal fasciculate zone negatively correlated with the anxiety index. IHC alleviated both behavioral signs of PTSD and morphological evidence of adrenal cortex dystrophy. Also, IHC alone exerted an antistress effect, which was evident from the increased time spent in open arms of the elevated X-maze and a lower number of rats displaying freezing responses. Therefore, IHC of rats with experimental PTSD reduced behavioral signs of the condition and damage to the adrenal glands.

NEW & NOTEWORTHY Intermittent hypoxia conditioning (IHC) has been shown to be cardio-, vaso-, and neuroprotective. For the first time, in a model of posttraumatic stress disorder (PTSD), this study showed that IHC alleviated both PTSD-induced behavioral disorders and functional and morphological damage to the adrenal glands. Also, IHC alone exerted an antistress effect. These results suggest that IHC may be a promising complementary treatment for PTSD-associated disorders.
A Case of Pyriform Sinus Fistula with Respiratory Distress in the Neonatal Period
Authors: Hamaguchi Noriko , Ishinaga Hajime , Chiyonobu Kazuki , Morishita Hiroyuki , Takeuchi Kazuhiko
Published: June 2018

Pyriform sinus fistula (PSF) is an anomaly that can arise due to failure of involution of the third or fourth branchial cleft during embryogenesis. It can manifest clinically as sinuses, cysts, or abscesses in the neck and is common in childhood. Herein, we describe a neonate who presented with neck swelling and respiratory distress, which was secondary to a fourth branchial pouch sinus. Physical examination revealed swollen areas in the posterolateral pharyngeal wall and on the external left side of the neck. Computed tomography imaging showed a left-sided mass that was filled with air and fluid. Eventually, the pyriform sinus cyst and the entire fistulous tract were excised. The postoperative course was uneventful. Follow-up after 18 months showed no recurrence.
A Type III Monteggia Injury with Ipsilateral Fracture of the Distal Radius and Ulna in a Child: Case Report Followed for 21 Years
Authors: Inoue Takeshi , Kubota Makoto , Marumo Keishi
Published: June 2018

Bado type III Monteggia injuries complicated by ipsilateral forearm fractures are extremely rare. We report a case of a 6-year-old boy who sustained such an injury after falling from the top of a 3 m climbing pole. He was diagnosed with a Bado type III Monteggia fracture and forearm fractures. Manual reduction was attempted on the day of injury. However, because it was difficult to maintain the reduction of the radial head, open and percutaneous procedures were performed to reduce and fixate the fractures with Kirschner wires. The postoperative course was favorable. Twenty-one years later, the patient, now 27 years old, had no decreased range of joint motion or problems with activities of daily living. The fracture morphology observed in this case is rare, and this is the only case for which long-term follow-up has been carried out to adulthood.
Very Small Embryonic-Like Stem Cells, Endothelial Progenitor Cells, and Different Monocyte Subsets Are Effectively Mobilized in Acute Lymphoblastic Leukemia Patients after G-CSF Treatment
Authors: Eljaszewicz Andrzej , Bolkun Lukasz , Grubczak Kamil , Rusak Malgorzata , Wasiluk Tomasz , Dabrowska Milena , Radziwon Piotr , Marlicz Wojciech , Kamiński Karol , Kloczko Janusz , Moniuszko Marcin
Published: June 2018

Background. Acute lymphoblastic leukemia (ALL) is a malignant disease of lymphoid progenitor cells. ALL chemotherapy is associated with numerous side effects including neutropenia that is routinely prevented by the administration of growth factors such as granulocyte colony-stimulating factor (G-CSF). To date, the effects of G-CSF treatment on the level of mobilization of different stem and progenitor cells in ALL patients subjected to clinically effective chemotherapy have not been fully elucidated. Therefore, in this study we aimed to assess the effect of administration of G-CSF to ALL patients on mobilization of other than hematopoietic stem cell (HSCs) subsets, namely, very small embryonic-like stem cells (VSELs), endothelial progenitor cells (EPCs), and different monocyte subsets. Methods. We used multicolor flow cytometry to quantitate numbers of CD34+ cells, hematopoietic stem cells (HSCs), VSELs, EPCs, and different monocyte subsets in the peripheral blood of ALL patients and normal age-matched blood donors. Results. We showed that ALL patients following chemotherapy, when compared to healthy donors, presented with significantly lower numbers of CD34+ cells, HSCs, VSELs, and CD14+ monocytes, but not EPCs. Moreover, we found that G-CSF administration induced effective mobilization of all the abovementioned progenitor and stem cell subsets with high regenerative and proangiogenic potential. Conclusion. These findings contribute to better understanding the beneficial clinical effect of G-CSF administration in ALL patients following successful chemotherapy.
Regulatory Role of CD4+T Cells in Myocarditis
Authors: Vdovenko Daria , Eriksson Urs
Published: June 2018

Myocarditis is an important cause of heart failure in young patients. Autoreactive, most often, infection-triggered CD4+T cells were confirmed to be critical for myocarditis induction. Due to a defect in clonal deletion of heart-reactive CD4+T cells in the thymus of mice and humans, significant numbers of heart-specific autoreactive CD4+T cells circulate in the blood. Normally, regulatory T cells maintain peripheral tolerance and prevent spontaneous myocarditis development. In the presence of tissue damage and innate immune activation, however, activated self-antigen-loaded dendritic cells promote CD4+effector T cell expansion and myocarditis. So far, a direct pathogenic role has been described for both activated Th17 and Th1 effector CD4+T cell subsets, though Th1 effector T cell-derived interferon-gamma was shown to limit myocarditis severity and prevent transition to inflammatory dilated cardiomyopathy. Interestingly, recent observations point out that various CD4+T cell subsets demonstrate high plasticity in maintaining immune homeostasis and modulating disease phenotypes in myocarditis. These subsets include Th1 and Th17 effector cells and regulatory T cells, despite the fact that there are still sparse and controversial data on the specific role of FOXP3-expressing Treg in myocarditis. Understanding the specific roles of these T cell populations at different stages of the disease progression might provide a key for the development of successful therapeutic strategies.
The Effects of the Honey‐Roasting Process on the Pharmacokinetics of the Six Active Compounds of Licorice
Authors: Zhang Yulong , Wang Mengyue , Yang Jingyu , Li Xiaobo
Published: June 2018

A convenient UPLC‐MS/MS method was established to determine the contents of six bioactive compounds, namely, liquiritin apioside, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, and glycyrrhetinic acid, in rat plasma and their pharmacokinetics. By comparing the pharmacokinetic parameters of these compounds in rats by orally administering raw and honey‐roasting licorice, the Cmax of isoliquiritin showed a significant decrease, while the AUC0-24h showed no significant differences. The Cmax and AUC0-24h of isoliquiritigenin were increased by 49.3% and 42.7% over those of the raw licorice group, respectively. These results indicate that the absorption of isoliquiritin in rats was reduced while the absorption of isoliquiritigenin was promoted in the honey‐roasting process. These results may provide one explanation as to why licorice is more able to relieve cough, while honey‐roasting licorice is better at invigorating qi and restoring pulse. Furthermore, the Cmax of glycyrrhetinic acid was increased, suggesting that it may enhance the tonic effect of licorice. Additionally, the amount of honey added in the honey‐roasting process influenced the pharmacokinetic parameters of the six compounds whose absorption decreased when the 50% honey‐roasting licorice water decoction was administered. These results provide an experimental basis for studying the influence of licorice processing on bioactive compound pharmacokinetics.
The Importance of Recognizing Wandering Spleen as a Cause of Recurrent Acute Pancreatitis
Authors: Lourdusamy Vennis , Patel Dhrumil , Docobo Ramon , Tantry Shyamanand , Lourdusamy Dennis , Farukh Saeed
Published: June 2018

Wandering spleen, as its name suggests, is a rare condition where the spleen wanders in the abdomen and is most commonly found in the inferior quadrant as a palpable mass. It can have varying presentations and commonly presents as splenic torsion and very rarely as acute pancreatitis. It is imperative not to miss this diagnosis as it can lead to life-threatening complications in the form of splenic torsion/infarction. Here we describe a rare manifestation of wandering spleen where a young female presented with recurrent episodes of acute pancreatitis.
Reduction in Ocular Hypotensive Eyedrops by Ab Interno Trabeculotomy Improves Not Only Ocular Surface Condition But Also Quality of Vision
Authors: Kashiwagi Kenji , Matsubara Mio
Published: June 2018

Purpose. To investigate the effect of ab interno trabeculotomy using the Trabectome surgical system on tear film stability and functional visual acuity (FVA). Patients and Methods. Adult glaucoma patients who underwent Trabectome surgery alone or Trabectome surgery combined with phacoemulsification with intraocular lens insertion were included in this study. Corneal epithelial defects, tear film breakup time (TBUT), tear meniscus height, tear film spreading grade, tear interferometry grade, and FVA were assessed before and after surgery in addition to routine ophthalmic examinations. Changes in ocular surface conditions and visual acuity as a result of the Trabectome surgery were investigated. Results. Thirty eyes of 22 patients with a mean age of 72.2 ± 7.9 years, including 8 males and 14 females, were enrolled. The Trabectome surgery significantly reduced the intraocular pressure (IOP) from 20.3 ± 5.2 to 15.0 ± 3.3 mmHg (P<0.001) and the number of different types of ocular hypotensive eyedrops used from 3.2 ± 0.7 to 1.1 ± 0.7 types (P<0.001). The surgery significantly improved corneal epithelial defects, the tear spreading grade, the tear interferometry grade, and FVA. The surgery also improved the visual maintenance ratio among all enrolled patients, including those who underwent Trabectome surgery only. Conclusion. Trabectome surgery may be beneficial not only for IOP reduction but also for improving ocular surface conditions and FVA.
Anti‐Inflammatory Effect of Gamisoyo‐San in an Animal Model of Amyotrophic Lateral Sclerosis
Authors: Park Sunjung , Yang Eun Jin
Published: June 2018

Inflammation is considered a critical factor in the pathogenesis of amyotrophic lateral sclerosis (ALS). We aimed to evaluate the effect of the herbal formula Gamisoyo‐San (GSS) on the muscles of hSOD1G93A transgenic mice, a mouse model of ALS, by examining the tissue expression of inflammation‐ and oxidative stress‐related proteins. The mice were randomly divided into three groups: nontransgenic mice (non‐Tg, n = 4), hSOD1G93A transgenic mice (Tg, n = 4), and GSS‐treated hSOD1G93A transgenic mice (Tg+GSS, n = 4). Eight‐week‐old female hSOD1G93A transgenic mice were fed GSS (1 mg/g body weight) for 6 weeks. Gastrocnemius (GA) tissues were analyzed for inflammatory proteins [CD11b and toll‐like receptor 4 (TLR4)] and oxidative stress‐related proteins [heme oxygenase 1 (HO1) and ferritin] by western blot analysis. Administration of GSS significantly reduced the level of inflammation‐ and oxidative stress‐related proteins in hSOD1G93A transgenic mice. GSS ameliorated inflammation by downregulating TLR4 and CD11b expression and regulated iron homeostasis in the GA muscle of hSOD1G93A mice. GSS could help reduce inflammation by regulating immune reactions in patients with ALS. To the best of our knowledge, this is the first study to demonstrate the effect of GSS on muscle inflammation in an ALS animal model.
Potential Antiproliferative Activity and Evaluation of Essential Oil Composition of the Aerial Parts of Tamarix aphylla (L.) H.Karst.: A Wild Grown Medicinal Plant in Jordan
Authors: Alhourani N. , Kasabri V. , Bustanji Y. , Abbassi R. , Hudaib M.
Published: June 2018

Essential (volatile) oil from aerial parts of Tamarix aphylla (L.) H.Karst. (Tamaricaceae) grown wild in Jordan was hydrodistilled by Clevenger apparatus and analyzed by means of GC and GC‐MS techniques. In vitro screening of potential cytotoxicity of the aqueous (AE) and ethanol (EE) extracts was also evaluated against human breast adenocarcinoma (MCF‐7), colorectal adenocarcinoma (Caco‐2), and pancreatic carcinoma (Panc‐1) cancer cell lines as well as normal human fibroblasts. GC‐MS analysis of T. aphylla EO revealed its richness in nonterpenoid nonaromatic hydrocarbons (52.39%), with predominance of 6,10,14‐trimethyl‐2‐pentadecanone as the principal component. Biologically, the plant extracts exhibited cytotoxicity effects in dose‐dependent manner against most of the tested cell lines, but potent effects were only predicted against MCF‐7 cells with IC50 values of 2.17 ± 0.10 and 26.65 ± 3.09 μg/mL for T. aphylla AE and EE, respectively. T. aphylla AE demonstrated a comparable cytotoxic effect with that offered by the control drug cisplatin (IC50 value of 1.17 ± 0.13 μg/mL), even with higher safety profile against normal fibroblast cells (IC50 values of T. aphylla AE versus cisplatin: 79.99 ± 4.90 versus 9.08 ± 0.29 μg/mL). T. aphylla extracts could be a valuable source for cytotoxic agents with high safety and selective cytotoxicity profiles. Unfortunately, no antiproliferative potential against Caco‐2 or Panc‐1 cancer cell lines was detected at a concentration less than 30 μg/mL.
Interplay between ShcA Signaling and PGC-1α Triggers Targetable Metabolic Vulnerabilities in Breast Cancer
Authors: Im Young Kyuen , Najyb Ouafa , Gravel Simon-Pierre , McGuirk Shawn , Ahn Ryuhjin , Avizonis Daina Z. , Chénard Valérie , Sabourin Valerie , Hudson Jesse , Pawson Tony , Topisirovic Ivan , Pollak Michael , St-Pierre Julie , Ursini-Siegel Josie
Published: June 2018

The ShcA adaptor protein transduces oncogenic signals downstream of receptor tyrosine kinases. We show here that breast tumors engage the ShcA pathway to increase their metabolism. ShcA signaling enhanced glucose catabolism through glycolysis and oxidative phosphorylation, rendering breast cancer cells critically dependent on glucose. ShcA signaling simultaneously increased the metabolic rate and flexibility of breast cancer cells by inducing the PGC-1α transcriptional coactivator, a central regulator of mitochondrial metabolism. Breast tumors that engaged ShcA signaling were critically dependent on PGC-1α to support their increased metabolic rate. PGC-1α deletion drastically delayed breast tumor onset in an orthotopic mouse model, highlighting a key role for PGC-1α in tumor initiation. Conversely, reduced ShcA signaling impaired both the metabolic rate and flexibility of breast cancer cells, rendering them reliant on mitochondrial oxidative phosphorylation. This metabolic reprogramming exposed a targetable metabolic vulnerability, leading to a sensitization of breast tumors to inhibitors of mitochondrial complex I (biguanides). Genetic inhibition of ShcA signaling in the Polyoma virus middle T (MT) breast cancer mouse model sensitized mammary tumors to biguanides during the earliest stages of breast cancer progression. Tumor initiation and growth were selectively and severely impaired in MT/ShcA-deficient animals. These data demonstrate that metabolic reprogramming is a key component of ShcA signaling and serves an unappreciated yet vital role during breast cancer initiation and progression. These data further unravel a novel interplay between ShcA and PGC-1α in the coordination of metabolic reprogramming and demonstrate the sensitivity of breast tumors to drugs targeting oxidative phosphorylation.

Significance: This study uncovers a previously unrecognized mechanism that links aberrant RTK signaling with metabolic perturbations in breast cancer and exposes metabolic vulnerabilities that can be targeted by inhibitors of oxidative phosphorylation. Cancer Res; 78(17); 4826–38. ©2018 AACR.
Differential Associations of Walking and Cycling with Body Weight, Body Fat and Fat Distribution - the ACTI-Cités Project
Authors: Menai Mehdi , Charreire Hélène , Galan Pilar , Simon Chantal , Nazare Julie-Anne , Perchoux Camille , Weber Christiane , Enaux Christophe , Hercberg Serge , Fezeu Léopold , Oppert Jean-Michel
Published: June 2018

Background: Research on the associations between walking and cycling with obesity-related phenotypes is growing but relies mostly on the use of BMI. The purpose of this study was to analyze associations of walking and cycling behaviors assessed separately with various obesity markers in French adults. Methods: In 12,776 adult participants (71.3% women) of the on-going NutriNet Santé web-cohort, we assessed by self-report past-month walking and cycling (for commuting, errands and leisure), and obesity measures were taken during a visit at a clinical center (weight, height, waist circumference, and percent body fat by bioimpedance). Results: In analyses not taking into account other types of physical activity (household, leisure), walking more than 2.5 h/week was associated in women with lower weight (-1.8 kg), waist circumference (-1.7 cm) and percent body fat (-1.1%) (all p < 0.001). Cycling more than 1.5 h/week was associated in men and women with lower weight (-4.3 and -1.4 kg, respectively), waist circumference (-4.4 and -2.1 cm, respectively), and percent body fat (-2.5 and -1.9 % respectively) (all p < 0.001). Results were unaltered when analyses were further adjusted on household and leisure physical activity. Conclusion: These results show important differences between walking and cycling in their association with obesity markers in men and women. These findings provide some evidence for the need to consider separately walking and cycling when designing public health measures for prevention of obesity in adults.
Qiliqiangxin Rescues Mouse Cardiac Function by Regulating AGTR1/TRPV1-Mediated Autophagy in STZ-Induced Diabetes Mellitus
Authors: Tong Jing , Lai Yan , Yao Yi-An , Wang Xue-Jun , Shi Yu-Shuang , Hou Han-Jin , Gu Jian-Yun , Chen Fei , Liu Xue-Bo
Published: June 2018

Background/Aims: To explore the potential role of qiliqiangxin (QLQX) A traditional Chinese medicine and the involvement of angiotensin II receptor type 1 (AGTR1) and transient receptor potential vanilloid 1 (TRPV1) in diabetic mouse cardiac function. Methods: Intragastric QLQX was administered for 5 weeks after streptozotocin (STZ) treatment. Additionally, Intraperitoneal injections of angiotensin II (Ang II) or intragastric losartan (Los) were administered to assess the activities of AGTR1 and TRPV1. Two-dimensional echocardiography and tissue histopathology were used to assess cardiac function Western blot was used to detect the autophagic biomarkers Such as light chain 3 P62 and lysosomal-associated membrane protein 2 And transmission electron microscopy was used to count the number of autophagosomes. Results: Decreased expression of TRPV1 and autophagic hallmarks and reduced numbers of autophagolysosomes as well as increased expression of angiotensin converting enzyme 1 and AGTR1 were observed in diabetic hearts. Blocking AGTR1 with Los mimicked the QLQX-mediated improvements in cardiac function Alleviated myocardial fibrosis and enabled autophagy Whereas Ang II abolished the beneficial effects of QLQX in wild type diabetic mice but not in TRPV1-/- diabetic mice. Conclusions: QLQX may improve diabetic cardiac function by regulating AGTR1/ TRPV1-mediated autophagy in STZ-induced diabetic mice.
Dexmedetomidine Protects Neural Stem Cells from Ketamine-Induced Injury
Authors: Lu Pan , Lei Shan , Li Weisong , Lu Yang , Zheng Juan , Wang Ning , Xia Yongjun , Lu Haixia , Chen Xinlin , Liu Yong , Zhang Peng-bo
Published: June 2018

Background/Aims: Ketamine inhibits the proliferation of neural stem cells (NSCs) and disturbs normal neurogenesis. Dexmedetomidine provides neuroprotection against volatile anesthetic-induced neuroapoptosis and cognitive impairment in the developing brain. Whether it may protect NSCs from ketamine-induced injury remains unknown. In this study, we investigated the protective effects of dexmedetomidine on ketamine-exposed NSCs and explored the mechanisms potentially involved. Methods: Primary NSC cultures were characterized using immunofluorescence. Cell viability was determined using a Cell Counting Kit 8 assay. Proliferation and apoptosis were assessed with BrdU incorporation and TUNEL assays, respectively. Protein levels of cleaved caspase-3, phosphorylated protein kinase B (p-Akt), and glycogen synthase kinase-3β (p-GSK-3β) were quantified using western blotting. Results: Ket-amine significantly decreased NSC viability and proliferation and increased their apoptosis. Dexmedetomidine increased NSC proliferation and decreased their apoptosis in a dose-dependent manner. Furthermore, dexmedetomidine pretreatment notably augmented the viability and proliferation of ketamine-exposed NSCs and reduced their apoptosis. Moreover, dexmedetomidine lessened caspase-3 activation and increased p-Akt and p-GSK-3β levels in NSCs exposed to ketamine. The protective effects of dexmedetomidine on ketamine-exposed NSCs could be partly reversed by the PI3K inhibitor LY294002. Conclusions: Collectively, these findings indicate that dexmedetomidine may protect NSCs from ketamine-induced injury via the PI3K/Akt/GSK-3β signaling pathway.
Cpg-ODN, a TLR9 Agonist, Aggravates Myocardial Ischemia/Reperfusion Injury by Activation of TLR9-P38 MAPK Signaling
Authors: Xie Liang , He Songqing , Kong Na , Zhu Ying , Tang Yi , Li Jianhua , Liu Zhengbing , Liu Jing , Gong Jianbin
Published: June 2018

Background/Aims: Toll-like receptors (TLRs) have been implicated in myocardial ischemia/ reperfusion (I/R) injury. We examined the effect of CpG-oligodeoxynucleotide (ODN) on myocardial I/R injury. Methods: Male Sprague-Dawley rats were treated with either CpG-ODN or control ODN 1 h prior to myocardial ischemia (30 min) followed by reperfusion. Rats treated with phosphate-buffered saline (PBS) served as I/R controls (n = 8/group). Infarct size was determined by 2,3,5-triphenyltetrazolium chloride and Evans blue straining. Cardiac function was examined by echocardiography before and up to 14 days after myocardial I/R. Results: CpG-ODN administration significantly increased infarct size and reduced cardiac function and survival rate after myocardial I/R, compared to the PBS-treated I/R group. Control-ODN did not alter I/R-induced myocardial infarct size, cardiac dysfunction, and survival rate. Additionally, CpG-ODN promoted I/R-induced myocardial apoptosis and cleaved caspase-3 levels in the myocardium. CpG-ODN increased TLR9 activation and p38 phosphorylation in the myocardium. In vitro data also suggested that CpG-ODN treatment induced TLR9 activation and p38 phosphorylation. Importantly, p38 mitogen-activated protein kinase (MAPK) inhibition abolished CpG-ODN-induced cardiac injury. Conclusion: CpG-ODN, the TLR9 ligand, accelerates myocardial I/R injury. The mechanisms involve activation of the TLR9-p38 MAPK signaling pathway.
Salt-Inducible Kinase 1 (SIK1) is Induced by Alcohol and Suppresses Microglia Inflammation via NF-κB Signaling
Authors: Zhang Yu , Gao Weida , Yang Kongbin , Tao Haiquan , Yang Haicheng
Published: June 2018

Background/Aims: Alcohol consumption has been shown to cause neuroinflammation and increase a variety of immune-related signaling processes. Microglia are a crucial part of alcohol-induced neuroinflammation and undergo apoptosis. Even though the importance of these inflammatory processes in the effects of alcohol-related neurodegeneration have been established, the mechanism of alcohol-induced microglia apoptosis is unknown. In prior research, we discovered that alcohol increases expression of salt-inducible kinase 1 (SIK1) in rodent brain tissue. In this study, we sought to determine what role SIK1 expression plays in alcohol-induced neuroinflammation as well as whether and by what mechanism it regulates microglia apoptosis. Methods: Adult C57BL/6 mice were divided into four groups and for 3 weeks treated with either 0%, 5%, 10%, or 15% alcohol during 3 hour periods. The mice were sacrificed and their brains excised for analysis. Additionally, primary microglia were isolated from neonatal mice. SIK1 expression in alcohol-treated brain tissue and microglia was analyzed via RT-PCR and western blotting. TUNEL staining, caspase-3, and caspase-9 activity assays were performed to evaluate microglial apoptosis. Cell fluorescence staining and NF-κB luciferase activity assays were used to evaluate the effects of SIK1 expression on the NF-κB signaling pathway. Results: SIK1 expression was increased in the brains of mice that consumed alcohol, and this effect was seen in mouse primary microglia. SIK1 knockdown in microglia increased alcohol-induced apoptosis in these cells. Furthermore, SIK1 reduced NF-κB signaling pathway factors, and SIK1 knockdown in microglia promoted alcohol-induced NF-κB activity. TUNEL staining, caspase-3, and caspase-9 activity assays consistently revealed that alcohol-induced microglial apoptosis was inhibited by depletion of p65. Finally, we determined that NF-κB signaling is required for alcohol-induced, SIK1-mediated apoptosis in microglia. Conclusion: This study establishes for the first time not only that SIK1 is crucial to regulating alcohol-induced microglial apoptosis, but also that the NF-κB signaling pathway is required for its activity. Overall, our results help elucidate mechanisms of alcohol-induced neuroinflammation.
ВАЛІДАЦІЯ МЕТОДИКИ КІЛЬКІСНОГО СПЕКТРОФОТОМЕТРИЧНОГО ВИЗНАЧЕННЯ ВЕРАПАМІЛУ ГІДРОХЛОРИДУ У СКЛАДІ ЛІКАРСЬКИХ ФОРМ
Authors: Sulyma M. I. , Ogurtsov V. V. , Zhuk Yu. M. , Vasyuk S. O.
Published: June 2018

Мета роботи. Валідація методики кількісного спектрофотометричного визначення верапамілу гідрохлориду у складі лікарських форм згідно з ДФУ за такими валідаційними характеристиками, як лінійність, діапазон застосування, специфічність, прецизійність, правильність та робасність.Матеріали і методи. У дослідженні використано робочий стандартний зразок верапамілу гідрохлориду, бромкрезоловий зелений (БКЗ), зразки готових лікарських форм вітчизняного та закордонного виробництва. Реагенти і розчинники: стандартний зразок дилтіазему, бромкрезоловий зелений, ацетон. Аналітичне обладнання: спектрофотометр Specord 200, ваги електронні АВТ-120-5DM, ультразвукова баня ELMASONICE60 H.Результати й обговорення. Експериментально встановлено, що верапамілу гідрохлорид взаємодіє з бромкрезоловим зеленим у середовищі ацетону з утворенням забарвленої сполуки з максимумом абсорбції при 409 нм. Проведено валідацію розробленої методики. Визначено основні валідаційні характеристики, а саме лінійність, прецизійність, правильність, робасність та діапазон застосування. Лінійність методики підтверджується у всьому діапазоні концентрацій 60–135 % (1,9648–4,4208 мг/100 мл).  Запропонована методика відповідає вимогам ДФУ, які висувають до методик кількісного аналізу лікарських речовин.Висновки. Проведено валідацію спектрофотометричної методики кількісного визначення верапамілу гідрохлориду у складі лікарських форм згідно зі стандартизованою процедурою валідації методом стандарту. Доведено, що за такими валідаційними характеристиками як лінійність, специфічність, прецизійність, правильність та робасність методика є валідною.
ДО ПИТАННЯ МАКРО-, МІКРОДІАГНОСТИКИ ГАРБУЗА НАСІННЯ ЯК ЛІКАРСЬКОЇ РОСЛИННОЇ СИРОВИНИ
Authors: Vovk O. , Sokolova O. , Кotov S. , Gontova T. , Kotov A.
Published: June 2018

Мета роботи. Вивчення діагностичних макроскопічних і мікроскопічних ознак сировини гарбуза насіння для розробки відповідних розділів національної монографії  «Гарбуза насіння».Матеріали і методи. Об’єкти дослідження – 7 серій ЛРС гарбуза насіння, зібрані  в різних районах Харківської області. Макроскопічні ознаки вивчали неозброєним оком і за допомогою лупи (збільшення х10), мікроскопічне дослідження проводили за допомогою бінокулярного мікроскопа БМ-51-2 і світлового мікроскопа «Биолам ЛОМО».Результати й обговорення. Проаналізовано зміст інформації щодо обраного об’єкта у фармакопеях (ДФ ХІ,  ДФ РБ, ВНР, DAB 10) та інших наукових джерелах. Виявлено, що розділ «Макроскопія» включає:  опис зовнішніх –  морфологічних, якісних і кількісних характеристик насіння;  характеристику насінної шкірки; монографія ВНР підкреслює, що зріла насінина гарбуза не має  ендосперму; надає опис будови зародку. Аналіз розділу «Мікроскопія» свідчить, що всі аналізовані фармакопеї майже однотипно описують характерні риси будови тканин досліджуваної ЛРС на поперечному зрізі насінини.Експериментально досліджено важливі для стандартизації діагностичні макроскопічні ознаки 7 серій сировини: забарвлення, форма, розміри насінин; поверхня насінин; будова насінної шкірки; зародок.Експериментально досліджено важливі для стандартизації діагностичні мікроскопічні ознаки 7 серій сировини. На поперечному зрізі зрілої насінини гарбуза діагностичними є: тканини насінної шкірки, алейронового шару і сім’ядолі. Визначено відповідність досліджуваної сировини вимогам зазначених фармакопей.Висновки. На основі виконаної роботи розроблено проект розділів «Ідентифікація А» та «Ідентифікація В» до національної монографії «Гарбуза насіння»N.
СИНТЕЗ ТА ПЕРВИННА ОЦІНКА ПРОТИЗАПАЛЬНОЇ АКТИВНОСТІ 1,4,5,6-ТЕТРАГІДРОПІРИМІДИН-2-КАРБОКСАМІДІВ
Authors: Horishny V. Ya. , Frolov D. A. , Nektegayev I. O. , Ostapiuk Yu. V. , Matiychuk V. S.
Published: June 2018

Мета роботи. Розробити методики отримання ряду нових морфолін-4-іл-2-тіоксоацетамідів та дослідити їх взаємодію з 1,3-диамінопропаном. Здійснити синтез нових 1,4,5,6-тетрагідропіримідин-2-карбоксамідів та провести первинний скринінг їх протизапальних властивостей.Матеріали і методи. Органічний синтез, спектроскопія ЯМР, елементний аналіз, фармакологічний скринінг.Результати й обговорення. Взаємодією хлороацетамідів, синтезованих на основі заміщених анілінів та 2-аміно-5-бензилтіазолів, з сіркою та морфоліном отримано ряд нових морфолін-4-іл-2-тіоксоацетамідів. Встановлено, що  їх взаємодія з 1,3-діамінопропаном приводить до утворення  1,4,5,6-тетрагідропіримідин-2-карбоксамідів. Досліджено протизапальну активність деяких синтезованих сполукВисновки. Розроблено методику синтезу 1,4,5,6-тетрагідропіримідин-2-карбоксамідів. За результатами дослідження протизапальної активності синтезованих похідних ідентифіковано високоактивні сполуки, які з показниками пригнічення запальної реакції в межах 37,5–46,7 % співмірні з дією еталонного нестероїдного протизапального засобу «Диклофенаку натрію».
A arte como procedimento de ressurreição da palavra: Viktor Chklóvski e a filosofia da causa comum
Authors: Kalinin Iliá
Published: June 2018

Tendo influenciado muitas figuras da vanguarda russa, como Vladimir Maiakóvski e Velimír Khlébnikov, Pável Filónov e Andrei Platónov, os ensinamentos de Nikolai Fiódorov deixaram de ser citados já nos anos 1930 e foram suprimidos junto com o utopismo da cultura revolucionária inicial. Por isso, é mais interessante ainda encontrar menções abertas ao seu nome e às suas ideias nos trabalhos de um autor como Viktor Chklóvski, tão reconhecido oficialmente a partir dos anos 1930 e sobretudo depois da época do degelo, quando suas origens ligadas à vanguarda da cultura soviética o revestiram de um peso simbólico adicional. E é ainda mais curioso notar que, na obra inicial de Chklóvski, que fincava suas raízes na arte de vanguarda, o nome de Fiódorov está completamente ausente. Entretanto, a partir da camada Fiodoroviana já revelada, pode-se encontrar ecos do cosmismo russo também nos primeiros trabalhos de Chklóvski.
Dominação abstrata ou concepção abstrata? Considerações sobre a teoria crítica do capitalismo de Moishe Postone
Authors: Pereira Leonardo Jorge da Hora
Published: June 2018

A relevância da tarefa de elaboração de uma teoria crítica do capitalismo adequada aos tempos atuais é central atualmente. Este artigo pretende apresentar, em suas linhas mestras, o trabalho de Moishe Postone e, sobretudo, avaliar até que ponto ele se apresenta como um ponto de partida adequado ao objetivo de compreender e criticar a dinâmica capitalista. Este artigo divide-se assim em duas partes: a primeira visa destacar os aspectos centrais do pensamento de Postone e a segunda procura suscitar alguns questionamentos e críticas acerca tanto da interpretação de Postone sobre Marx quanto, mais geralmente, da sua teorização do capitalismo.