bluuebunny/crossref_metadata_2025 huggingface dataset:
Eribulin Treatment in Patients with Liver Metastatic Breast Cancer: Eight Italian Case Reports
Authors: Giordano Guido , Febbraro Antonio , Quaquarini Erica , Turletti Anna , Pedersini Rebecca , Raffaele Mimma , Villa Federica , Rossello Rosalba ,   The Italian Eribulin Working Group
Published: July 2018

Liver metastases are very common in metastatic breast cancer (MBC); current treatments for these lesions are based on systemic chemotherapy, endocrine- or human epidermal growth factor receptor 2 (HER2)-targeted therapy, and palliative therapy. However, no standard approach has been clearly identified for second and further chemotherapy lines in MBC patients. In the phase III clinical trial EMBRACE, eribulin was particularly effective in reducing liver lesions and improving both overall survival and progression-free survival in liver MBC patients. In this series, we collected 8 case reports of Italian clinical practice in which eribulin has shown significant efficacy in reducing liver metastases in MBC patients: complete response was reported in 2 patients, and 4 patients achieved partial response. The treatment was well tolerated, thus confirming that eribulin is a suitable therapeutic option for elderly patients and for those who have metastatic HER2-negative disease. In the setting of MBC, the sequencing of therapeutic agents should consider expected response, side effects, tumor characteristics, and patient’s preferences, in order to successfully tailor the most appropriate therapy beyond earlier lines.
Management of Spontaneous Pneumothorax and Post-Interventional Pneumothorax: German S3 Guideline
Authors: Schnell Jost , Beer Meinrad , Eggeling Stephan , Gesierich Wolfgang , Gottlieb Jens , Herth Felix J.F. , Hofmann Hans-Stefan , Jany Berthold , Kreuter Michael , Ley-Zaporozhan Julia , Scheubel Robert , Walles Thorsten , Wiesemann Sebastian , Worth Heinrich , Stoelben Erich
Published: July 2018

In Germany, 10,000 cases of spontaneous pneumothorax are treated inpatient every year. The German Society for Thoracic Surgery, in co-operation with the German Society for Pulmonology, the German Radiological Society, and the German Society of Internal Medicine has developed an S3 guideline on spontaneous pneumothorax and post-interventional pneumothorax moderated by the German Association of Scientific Medical Societies. Method: Based on the source guideline of the British Thoracic Society (2010) for spontaneous pneumothorax, a literature search on spontaneous pneumothorax was carried out from 2008 onwards, for post-interventional pneumothorax from 1960 onwards. Evidence levels according to the Oxford Center for Evidence-Based Medicine (2011) were assigned to the relevant studies found. Recommendations according to grade (A: “we recommend”/“we do not recommend,” B: “we suggest”/“we do not suggest”) were determined in 3 consensus conferences by the nominal group process. Results: The algorithms for primary and secondary pneumothorax differ in the indication for CT scan as well as in the indication for chest drainage application and video-assisted thoracic surgery. Indication for surgery is recommended individually taking into account the risk of recurrence, life circumstances, patient preferences, and procedure risks. For some forms of secondary pneumothorax, a reserved indication for surgery is recommended. Therapy of post-interventional spontaneous pneumothorax is similar to that of primary spontaneous pneumothorax. Discussion: The recommendations of the S3 Guideline provide assistance in managing spontaneous pneumothorax and post-interventional pneumothorax. Whether this will affect existing deviant diagnostic and therapeutic measures will be demonstrated by future epidemiological studies.
Extracellular Vesicles Secreted by Human Urine-Derived Stem Cells Promote Ischemia Repair in a Mouse Model of Hind-Limb Ischemia
Authors: Zhu Qingwei , Li Qing , Niu Xin , Zhang Guowei , Ling Xiaozheng , Zhang Jieyuan , Wang Yang  , Deng Zhifeng
Published: July 2018

Background/Aims: Our previous studies have shown that human urine-derived stem cells (USCs) have great potential as a cell source for cytotherapy and tissue engineering and that extracellular vesicles (EVs) secreted by USCs (USCs-EVs) can prevent diabetes-induced kidney injury in an animal model. The present study was designed to evaluate the effects of USCs-EVs on ischemia repair. Methods: USCs-EVs were isolated and purified by a battery of centrifugation and filtration steps. The USCs-EVs were then characterized by transmission electron microscopy, western blot and tunable resistive pulse sensing techniques. After intramuscularly transplanting USCs-EVs into an ischemic mouse hind-limb, we observed the therapeutic effects of USCs-EVs on perfusion by laser doppler perfusion imaging, angiogenesis and muscle regeneration by histology and immunohistochemistry techniques over 21 days. We subsequently tested whether USCs-EVs can induce the proliferation of a human microvascular endothelial cell line HMEC-1 and a mouse myoblast cell line C2C12 by cell counting kit 8 assay in vitro. Meanwhile, the potential growth factors in the USCs-EVs and supernatants of the USCs cultures were detected by enzyme-linked immunosorbent assay. Results: The USCs-EVs were spherical vesicles with a diameter of 30–150 nm and expressed exosomal markers, such as CD9, CD63 and Tsg101. Ischemic limb perfusion and function were markedly increased in the hind-limb ischemia (HLI) model after USCs-EVs administration. Moreover, angiogenesis and muscle regeneration levels were significantly higher in the USCs-EVs treatment group than in the PBS group. The in vitro experiments showed that USCs-EVs facilitated HMEC-1 and C2C12 cell proliferation in a dose-dependent manner. Conclusions: These results revealed for the first time that USCs-EVs efficiently attenuate severe hind-limb ischemic injury and represent a novel therapy for HLI.
Gastrointestinal Vascular Malformations in Patients with Turner’s Syndrome: A Systematic Review of Case Reports
Authors: Kucharska Anna , Józefczuk Paweł , Ksiązyk Maciej , Labochka Dominika , Banaszkiewicz Aleksandra
Published: July 2018

Background/Aim: There is a paucity of data on gastrointestinal (GI) vascular abnormalities in patients with Turner’s syndrome (TS). Therefore, this literature review aimed to characterize the nature of GI vascular malformations in patients with TS, their localization in the GI tract, and their clinical and laboratory manifestations. Methods: A systematic search for articles was conducted using Medline and Embase (until August 2017). A manual search of the references of the included papers was performed to identify any potential additional references. We also conducted a retrospective chart review of all patients with TS and GI bleeding who were hospitalized at our institution. Results: A total of 29 articles published between 1947 and 2015 that described 39 cases were reviewed. Additionally, we included 2 patients who were hospitalized at our institution. The median age of patients with TS was 15 years (range: 0.1–57 years). Iron deficiency anaemia (35/40), haematochezia (15/37), and melaena (14/36) were the most common symptoms. Abnormal GI vessels occurred throughout the entire bowel, with a predilection for the small intestine (72%, 29/40). The most common abnormal vessels (65%, 24/37) were telangiectasias and dilated veins. Conclusion: Telangiectasias and dilated veins of the small intestine were the most commonly seen abnormal GI vessels in patients with TS.
Effect of Human Coronavirus OC43 Structural and Accessory Proteins on the Transcriptional Activation of Antiviral Response Elements
Authors: Beidas Meshal , Chehadeh Wassim
Published: July 2018

Objectives: The molecular mechanisms underlying the pathogenesis of human coronavirus OC43 (HCoV-OC43) infection are poorly understood. In this study, we investigated the ability of HCoV-OC43 to antagonize the transcriptional activation of antiviral response elements. Methods: HCoV-OC43 structural (membrane M and nucleocapsid N) and accessory proteins (ns2a and ns5a) were expressed individually in human embryonic kidney 293 (HEK-293) cells. The transcriptional activation of antiviral response elements was assessed by measuring the levels of firefly luciferase expressed under the control of interferon (IFN)-stimulated response element (ISRE), IFN-β promoter, or nuclear factor kappa B response element (NF-κB-RE). The antiviral gene expression profile in HEK-293 cells was determined by PCR array. Results: The transcriptional activity of ISRE, IFN-β promoter, and NF-κB-RE was significantly reduced in the presence of HCoV-OC43 ns2a, ns5a, M, or N protein, following the challenge of cells with Sendai virus, IFN-α or tumor necrosis factor-α. The expression of antiviral genes involved in the type I IFN and NF-κB signaling pathways was also downregulated in the presence of HCoV-OC43 structural or accessory proteins. Conclusion: Both structural and accessory HCoV-OC43 proteins are able to inhibit antiviral response elements in HEK-293 cells, and to block the activation of different antiviral signaling pathways.
Accelerated Episodic Luteinizing Hormone Release Accompanies Blunted Progesterone Regulation in PCOS-like Female Rhesus Monkeys (Macaca Mulatta) Exposed to Testosterone during Early-to-Mid Gestation
Authors: Abbott David H. , Vepraskas Sarah H. , Horton Teresa H. , Terasawa Ei , Levine Jon E.
Published: July 2018

Background/Aims: Ovarian theca cell hyperandrogenism in women with polycystic ovary syndrome (PCOS) is compounded by androgen receptor-mediated impairment of estradiol and progesterone negative feedback regulation of episodic luteinizing hormone (LH) release. The resultant LH hypersecretion, likely the product of accelerated episodic release of gonadotropin-releasing hormone (GnRH) from the median eminence of the hypothalamus, hyperstimulates ovarian theca cell steroidogenesis, enabling testosterone (T) and androstenedione excess. Prenatally androgenized (PA) female monkeys exposed to fetal male levels of T during early-to-mid gestation, when adult, demonstrate PCOS-like traits, including high T and LH levels. This study tests the hypothesis that progesterone resistance-associated acceleration in episodic LH release contributes to PA monkey LH excess. Methods: A total of 4 PA and 3 regularly cycling, healthy control adult female rhesus monkeys of comparable age and body mass index underwent (1) a 10 h, frequent intravenous sampling assessment for LH episodic release, immediately followed by (2) IV infusion of exogenous GnRH to quantify continuing pituitary LH responsiveness, and subsequently (3) an SC injection of a progesterone receptor antagonist, mifepristone, to examine LH responses to blockade of progesterone-mediated action. Results: Compared to controls, the relatively hyperandrogenic PA females exhibited ~100% increase (p = 0.037) in LH pulse frequency, positive correlation of LH pulse amplitude (p = 0.017) with androstenedione, ~100% greater increase (p = 0.034) in acute (0–10 min) LH responses to exogenous GnRH, and an absence (p = 0.008) of modest LH elevation following acute progesterone receptor blockade suggestive of diminished progesterone negative feedback. Conclusion: Such dysregulation of LH release in PCOS-like monkeys implicates impaired feedback control of episodic release of hypothalamic GnRH reminiscent of PCOS neuroendocrinopathy.
A Simple Noninvasive Score Predicts Disease Activity and Deep Remission in Ulcerative Colitis
Authors: Hanafy Amr Shaaban , Monir Mohamed Hesham , Abdel Malak Hany , Desoky Aiad Mohamed 
Published: July 2018

Background: There is a need to use noninvasive markers in refining the management of ulcerative colitis to reduce the number of unnecessary colonoscopies, which facilitates the follow-up of activity and the response to treatment. Aim: Postulation of a sensitive, specific, simple and noninvasive score to monitor disease activity in ulcerative colitis. Methods: A case-control study was conducted: 168 patients with ulcerative colitis, 40 healthy individuals, and 60 patients for validation. Patients were divided into new diagnosis (n = 50), clinical remission (n = 60), and relapse (n = 58). The main outcome measures if the score correlates with clinical, endoscopic and histopathological characteristics and if it correlates with deep remission. Results: A scoring system was established composed of lactoferrin at a cutoff of 148.5 μg/mL, neutrophil lymphocyte ratio at a cutoff of 2.35, erythrocyte sedimentation rate at the first hour at a cutoff of 29.5 mm/h, C-reactive protein at a cutoff of 3.85 mg/L, mean platelet volume at a cutoff of 8.8 fL, fecal white blood cells at a cutoff of 9 cells/HPF, and fecal red blood cells at a cutoff of 6 cells/HPF. A score ≥5 can detect 94% of cases of UC as determined by the receiver operating characteristic curve with a sensitivity of 94% and a specificity 100%, AUC 0.92, SE 0.05, p = 0.001, 95% CI 0.82–1.1. In the validation group, it identified severely affected patients with a sensitivity of 95% and a specificity of 85.7%. Conclusions: This easily applied and reproducible noninvasive activity score showed high performance in predicting disease activity and deep remission in ulcerative colitis.
Gut Microbiota Composition in Healthy Japanese Infants and Young Adults Born by C-Section
Authors: Nagpal Ravinder , Yamashiro Yuichiro
Published: July 2018

Our gut microbiome plays a fundamental role in our health and disease. The microbial colonization of human gut begins immediately at birth and is an indispensable natural process that modulates our physiology and immunity. Recent studies are elegantly revealing how and when these microbes colonize the gut and what elements could potentially influence this natural phenomenon. The vertical mother-to-baby transmission of microbes is a crucial factor for normal development and maturation of newborn’s immune, metabolic as well as neurological health. This important and delicate process of gut microbiota development may be impacted by various factors such as birth mode, type of feeding, gestational age at birth, antibiotics exposure in early life, surrounding environment and hygiene settings, and so on. Perturbations in early life gut microbial colonization have been associated with the development of several diseases such as diabetes, obesity, asthma, allergies, celiac disease, neurodevelopmental disorders, and so on. However, it remains unclear whether predisposition to these diseases is due to the lack of acquisition of the mother’s (vaginal and perianal) microbes during birth or because of abnormal exposure to unsolicited bacteria. Hence, studies are required to scrutinize the colonization pattern of infant gut microbiome in context to birth mode and also to elucidate how long these differences could persist. In these contexts, we review and discuss some of the findings obtained from recent investigation of the gut microbiota composition in healthy Japanese infants and young adults born vaginally or by C-section.
C-section and the Neonatal Gut Microbiome Acquisition: Consequences for Future Health
Authors: Arboleya Silvia , Suárez M. , Fernández N. , Mantecón L. , Solís G. , Gueimonde M. , de los Reyes-Gavilán C.G.
Published: July 2018

Background: The human gut microbiota is assembled during infancy with an increase in diversity and stability. The correct colonization and the establishment of this microbiome are linked to the early and future health status of the individual. It is known that caesarean delivery alters this optimal microbial foundation. C-section (CS) is a common obstetrician surgery; however, it is not without risk for the mother/infant dyad. The World Health Organization recommends not exceeding 10–15% of the total deliveries; nevertheless, this rate has been increasing rapidly worldwide in the last decades. Summary: This review discloses the clinical parameters for correct CS recommendation. Moreover, the major microbial changes in the infant gut microbiome acquisition as a consequence of delivery mode and medical practices surrounding it, as well as, the early and long-lasting effects for both mother and babies are discussed. In addition, some strategies for the gut microbiota restoration are analysed. The aim of this review is to show the need for the development of strategies for minimizing or limiting the impact of caesarean on the microbiome development, favouring future health.
Hoodwinking the Big-Eater to Prosper: The Salmonella-Macrophage Paradigm
Authors: Gogoi Mayuri , Shreenivas Meghanashree M. , Chakravortty Dipshikha
Published: July 2018

Salmonella is a major cause of morbidity and mortality in the developing and underdeveloped nations. Being a foodborne disease, Salmonella infection is primarily contracted through the ingestion of contaminated food or water, or due to close contact with infected/carrier individuals. It is an intracellular pathogen, which can survive and replicate in various cells including macrophages, dendritic cells, epithelial cells, and other white blood cells. Once Salmonella crosses the intestinal barrier, it disseminates to various systemic sites by circulation via immune cells. One of the major cell types which are involved in Salmonella infection are host macrophages. They are the niche for intracellular survival and proliferation of Salmonella and a mode of dissemination to distal systemic sites. These cells are very crucial as they mediate the mounting of an appropriate innate and adaptive anti-Salmonella immune response. In this review, we have tried to concise the current knowledge of complex interactions that occur between Salmonella and macrophages.
Temperament and Character Inventory in Bipolar Disorder versus Healthy Controls and Modulatory Effects of 3 Key Functional Gene Variants
Authors: Porcelli Stefano , Marsano Agnese , Caletti Elisabetta , Sala Michela , Abbiati Vera , Bellani Marcella , Perlini Cinzia , Rossetti Maria Gloria , Mandolini Gian Mario , Pigoni Alessandro , Paoli Riccardo Augusto , Piccin Sara , Lazzaretti Matteo , Fabbro Dora , Damante Giuseppe , Bonivento Carolina , Ferrari Clarissa , Rossi Roberta , Pedrini Laura , Serretti Alessandro , Brambilla Paolo ,   GECOBIP Group
Published: July 2018

Background: Bipolar disorder (BD) has been associated with temperamental and personality traits, although the relationship is still to be fully elucidated. Several studies investigated the genetic basis of temperament and character, identifying catechol-O-methyltransferase (COMT), brain derived neurotrophic factor (BDNF), and serotonin transporter (5-HTT) gene variants as strong candidates. Methods: In the GECO-BIP study, 125 BD patients and 173 HC were recruited. Subjects underwent to a detailed assessment and the temperament and character inventory 125 items (TCI) was administrated. Three functional genetic variants within key candidate genes (COMT rs4680, BDNF rs6265, and the serotonin-transporter-linked polymorphic region (5-HTTLPR)) were genotyped. Univariate and multivariate analyses were performed. Results: Compared to HC, BD patients showed higher scores in novelty seeking (NS; p = 0.001), harm avoidance (HA; p < 0.001), and self transcendence (St; p < 0.001), and lower scores in self directness (p < 0.001) and cooperativeness (p < 0.001) TCI dimensions. Concerning the genetic analyses, COMT rs4680 was associated with NS in the total sample (p = 0.007) and in the male subsample (p = 0.022). When performing the analysis in the HC and BD samples, the association was confirmed only in HC (p = 0.012), and in the HC male subgroup in particular (p = 0.004). BDNF rs6265 was associated with St in the BD group (p = 0.017). Conclusion: COMT rs4680 may modulate NS in males in the general population. This effect was not detected in BD patients, probably because BD alters the neurobiological basis of some TCI dimensions. BDNF rs6265 seems to modulate St TCI dimension only in BD patients, possibly modulating the previously reported association between rs6265 and BD treatment response. Further studies are needed to confirm our findings.
High Mobility Group B-1 (HMGB-1) Promotes Apoptosis of Macrophage-Derived Foam Cells by Inducing Endoplasmic Reticulum Stress
Authors: Wu Han , Chen Zheng , Chen Jian-Zhou , Pei Li-Gang , Xie Jun , Wei Zhong-Hai , Kang Li-Na , Wang Lian , Xu Biao 
Published: July 2018

Background/Aims: High mobility group B-1 (HMGB-1)-induced endoplasmic reticulum stress (ERS) has been implicated in inflammation and dendritic cell maturation. C/EBP-homologous protein (CHOP) is a vital component of ERS and apoptosis and plays a critical role in atherosclerosis. However, only a little information is available about the role of HMGB-1 in foam cell formation. Thus, the role of HMGB-1-induced ERS/CHOP pathway in apoptosis and formation of macrophage-derived foam cells is investigated. Methods: RAW264.7 cells were treated with oxidized low-density lipoprotein (oxLDL) in the absence and/or presence of HMGB-1, N-acetylcysteine (NAC, an antioxidant), glycyrrhizin (Gly, an HMGB-1 inhibitor), tunicamycin (TM, an ERS inducer), and 4-phenylbutyrate (4-PBA, an ERS inhibitor). Reactive oxygen species (ROS) production was examined by dihydroethidium (DHE) staining. Oil Red O staining, intracellular total cholesterol assay, and Dil-oxLDL uptake assay evaluated the accumulation of lipids in macrophages. Cell apoptosis was measured by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Western blot detected the expression of HMGB-1/ERS/CHOP pathway. Results: oxLDL induced HMGB-1 translocation and secretion in a dose- and time-dependent manner, which was inhibited by NAC. oxLDL-induced lipid accumulation in macrophages was promoted synergistically by HMGB-1 that was attenuated by Gly. Moreover, TM synergized with oxLDL induced lipid accumulation and apoptosis of macrophages; however, 4-PBA alleviated the oxLDL-induced apoptotic foam cells. Additionally, the inhibition of ERS with 4-PBA suppressed the expression of HMGB-1-induced CHOP. Conclusions: OxLDL triggered HMGB-1 secretion in macrophages via oxidative stress. Furthermore, HMGB-1 promoted the formation and apoptosis of macrophage-derived foam cells via activation of ERS/CHOP pathway.
Coreopsis Tinctoria Modulates Lipid Metabolism by Decreasing Low-Density Lipoprotein and Improving Gut Microbiota
Authors: Ren Zhigang , Li Yali , Liu Jiangyun , Li Haitao , Li Ang , Hong Liangjie , Cui Guangying , Sun Ranran , Wulasihan Muhuyati , Sun Junhui , Song Yujun , Yu Zujiang , Chen Xinhua
Published: July 2018

Background/Aims: The prevalence of hyperlipidemia is increasing rapidly. The role of Coreopsis tinctoria (CT) in amending lipid metabolism in hyperlipidemia patients has not been reported. This study aims to evaluate the role of CT in altering lipid metabolism in hyperlipidemia patients and to explore the possible mechanisms mediated by gut microbiota in hyperlipidemia mice models. Methods: A retrospective analysis in 40 hyperlipidemia patients was conducted, in which 20 patients took fenofibrate and another 20 patients normatively drank water with CT. Hyperlipidemia mice models were also established. Blood biochemical tests were performed using an automatic biochemical analyzer. Liver histopathology was observed by hematoxylin and eosin staining. Ileocecal samples were collected from mice, and bacterial DNA was extracted and sequenced by MiSeq sequencing. Bacterial composition and differences were analyzed. Results: In hyperlipidemia patients, CT was associated with decreased triglyceride and low-density lipoprotein (LDL) levels without liver injury. The experimental hyperlipidemia model also verified a similar result. Gut microbial richness and diversity were significantly decreased in hyperlipidemic mice, but increased after CT treatment. Bacterial communities were significantly differentiated between normal controls and hyperlipidemic mice. CT administration improved gut microbiota composition to an approximately normal status. Meanwhile, CT administration attenuated bacterial alterations at the class, order, family, and genus levels in hyperlipidemic mice. Importantly, the genera Barnesiella, Lactobacillus, and Helicobacter achieved high discriminatory power in hyperlipidemic mice relative to normal controls. Conclusions: CT can modulate blood lipid metabolism with improvement of liver function by decreasing LDL and improving gut microbiota compositions. These findings may provide novel therapeutic strategies for patients with hyperlipidemia.
Mechanisms Underlying H2O2-Evoked Carbonyl Modification of Cytoskeletal Protein and Axon Injury in PC-12 Cells
Authors: Zhang Xiejun , Li Zongyang , Zhang Qiusheng , Chen Lei , Huang Xianjian , Zhang Yuan , Liu Xiaojia , Liu Wenlan , Li Weiping
Published: July 2018

Background/Aims: To investigate the mechanism that enables oxidative stress and cytoskeleton protein carbonylation to contribute to axonal dysfunction in traumatic brain injury (TBI). Methods: We created an in vitro model of neuronal oxidative damage by exposing a neuron-like cell line (PC-12) to different concentrations (100 μM, 200 μM, and 300 μM) of H2O2 for 24 h or 48 h. Carbonyl modification of cytoskeletal proteins (β-actin and β-tubulin) and its impact on β-actin/β-tubulin filament dynamics were determined by enzyme-linked immunosorbent assay, immunostaining, and western blotting. Depolymerization of β-actin/β-tubulin filaments was evaluated using the monomer/polymer ratio of each protein via western blotting. Phosphorylation of the neurofilament heavy chain (P-NFH) was used as an axonal injury marker and detected by immunostaining. Results: Our results showed that H2O2 treatment led to increased oxidative stress in PC-12 cells, as indicated by the increased generation of malondialdehyde and 8-hydroxydeoxyguanosine and decreased intracellular glutathione levels. H2O2 treatment also increased carbonyl modification of total proteins and cytoskeleton proteins β-actin/β-tubulin, which occurred concurrently with the suppression of proteasome activity. Moreover, H2O2 treatment increased the generation of the axonal injury marker P-NFH, and depolymerization of the β-actin/β-tubulin filaments was indicated by increased monomer/polymer ratios of each protein. Lastly, overexpression of the proteasome β5 subunit in PC-12 cells significantly reduced the H2O2-induced accumulation of carbonylated β-actin/ β-tubulin, P-NFH, and β-actin/β-tubulin depolymerization. Conclusions: We concluded that carbonylation of cytoskeleton proteins could lead to depolymerization of their filaments and axonal injury, and proteasome suppression contributes to the accumulation of carbonylated proteins under oxidative conditions.
ONZIN Upregulation by Mutant p53 Contributes to Osteosarcoma Metastasis Through the CXCL5-MAPK Signaling Pathway
Authors: Zhang Yanqin , Hu Qianghua , Li Guixin , Li Lili , Liang Shoulei , Zhang Yun , Liu Jiayong , Fan Zhengfu , Li Lin , Zhou Bingzheng , Ruan Yongxin , Yang Xueli , Chen She’an , Mu Tianyang  , Wang Guowen , Xiong Shunbin
Published: July 2018

Background/Aims: Gain-of-function of mutant p53 is associated with a high rate of lung metastasis in osteosarcoma. To investigate the mechanism of mutant p53-induced osteosarcoma metastasis, expression array analysis was performed, comparing non-metastatic osteosarcomas from p53+/- mice with metastatic osteosarcomas from p53R172H/+ mice. Onzin (Plac8) was identified as one of the genes upregulated in p53R172H/+ mouse metastatic osteosarcomas. Accordingly, we investigated the role of ONZIN in human osteosarcoma metastasis. Methods: ONZIN function and its downstream targets were examined in osteosarcoma cell lines. Assays related to tumorigenesis and metastasis, including cell migration, invasion, clonogenic survival, and soft agar colony formation, were performed in osteosarcoma cells. Additionally, mouse xenograft models were used to examine the role of ONZIN overpression in tumorigenesis in vivo. Lastly, 87 osteosarcoma patients were recruited to investigate the clinical relevance of ONZIN overexpression in metastasis and prognosis. Results: ONZIN overexpression enhanced osteosarcoma cell proliferation, clonogenic survival, migration, and invasion independent of p53 status. Furthermore, ONZIN overexpression induced CXCL5 upregulation and resulted in increased ERK phosphorylation, which contributed to more aggressive osteosarcoma metastatic phenotypes. More importantly, overexpression of ONZIN in human osteosarcoma patients was closely associated with lung metastasis, poor prognoses, and survival. Conclusions: Overexpression of ONZIN promotes osteosarcoma progression and metastasis, and can serve as a clinical biomarker for osteosarcoma metastasis and prognosis.
Pharmacological Effects of EGLP-1, a Novel Analog of Glucagon-Like Peptide-1, on Carbohydrate and Lipid Metabolism
Authors: Gao Huashan , Song Ziwei , Zhao Qian , Wu You , Tang Shanshan , Alahdal Murad , Shen Yumeng , Xing Yun , Pan Yi , Li Jing , Zhang Yanfeng , Jin Liang
Published: July 2018

Background/Aims: Abnormal glucose metabolism and lipid metabolism are two key issues in Type 1 diabetes mellitus (T1DM). Insulin can control carbohydrate metabolism adequately, but cannot regulate lipid metabolism well in patients with T1DM. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have cured type 2 diabetes mellitus in clinical trials and have improved T1DM glycemic control in preclinical studies. However, previous studies have not reported whether GLP-1 can lower the serum concentration of non-esterified fatty acids (NEFAs). In this study, we examine whether GLP-1 can affect serum NEFA levels. Methods: The bioactivity of EGLP-1 (a novel GLP-1 analog) in vitro was analyzed in CG-HEK293 cells and with high-performance liquid chromatography. An intraperitoneal glucose tolerance test (IPGTT) was used to analyze the acute and sustained hypoglycemic effects of EGLP-1 in normal C57BL/6J mice. Streptozotocin-induced hyperglycemic mice were used to study the effects of EGLP-1 on blood glucose and NEFAs as well as its mechanism. Results: EGLP-1 activated GLP-1R and resisted dipeptidyl peptidase-IV digestion in vitro. Additionally, EGLP-1 had an insulinotropic action in vivo that lasted for approximately 6 h. In Streptozotocin-induced hyperglycemic mice, EGLP-1 improved hyperglycemia, inhibited food intake, and increased β-cell area. Serum physiological indexes showed that insulin and C-peptide levels were increased, while NEFA and triacylglycerol concentrations were decreased. Western blot analysis revealed that EGLP-1 significantly reduced phosphorylated-hormone sensitive lipase (pHSL) levels in white adipose tissue. Conclusions: EGLP-1 can improve hyperglycemia by increasing islet β-cell area and improving β-cell function, possibly due to reduced NEFA content in serum by lowering pHSL levels.
Dysbiosis in Children Born by Caesarean Section
Authors: Salas Garcia Mariana C. , Yee Alyson L. , Gilbert Jack A. , Dsouza Melissa
Published: July 2018

The rate of Caesarean-section delivery in the United States has increased by 60% from 1996 through to 2013 and now accounts for > 30% of births [CDC, 2017]. The purpose of this review is to present the current understanding of both the microbial risk factors that increase the likelihood of a Caesarean-section delivery and the microbial dysbiosis that is thought to result from the Caesarean section. We provide examples of research into the impact of early-life microbial dysbiosis on infant development and long-term health outcomes, as well as consider the efficacy and the long-term implications of microbiome-based therapies to mitigate this dysbiosis. The steep rise in the Caesarean-section delivery rate makes it imperative to understand the potential of microbiota modulation for the treatment of dysbiosis.
Increased Energy Expenditure, Lipolysis and Hyperinsulinemia Confer Resistance to Central Obesity and Type 2 Diabetes in Mice Lacking Alpha2α-Adrenoceptors
Authors: Ruohonen Suvi T. , Valve Laura , Tuomainen Katja , Ailanen Liisa , Röyttä Matias , Manz Georg , Baur Nadja , Joos Thomas O. , Savontaus Eriika , Scheinin Mika
Published: July 2018

The alpha2A-adrenoceptors (α2A-ARs) are Gi-coupled receptors, which prejunctionally inhibit the release of norepinephrine (NE) and epinephrine (Epi), and postjunctionally inhibit insulin secretion and lipolysis. We have earlier shown that α2A–/– mice display sympathetic hyperactivity, hyperinsulinemia and improved glucose tolerance. Here we employed α2A–/– mice and placed the mice on a high-fat diet (HFD) to test the hypothesis that lack of α2A-ARs protects from diet-induced obesity and type 2 diabetes (T2D). In addition, a high-caloric diet was combined with running wheel exercise to test the interaction of diet and exercise. HFD was obesogenic in both genotypes, but α2A–/– mice accumulated less visceral fat than the wild-type controls, were protected from T2D, and their insulin secretion was unaltered by the diet. Lack of α2A-ARs is associated with an increased sympatho-adrenal tone, which resulted in increased energy expenditure and fat oxidation rate potentiated by HFD. Fittingly, α2A–/– mice displayed enhanced lipolytic responses to Epi, and increased faecal lipids suggesting altered fat mobilization and absorption. Subcutaneous white fat appeared to be thermogenically more active (measured as Ucp1 mRNA expression) in α2A–/– mice, and brown fat showed an increased response to NE. Exercise was effective in reducing total body adiposity and increasing lean mass in both genotypes, but there was a significant diet-genotype interaction, as even modestly increased physical activity combined with lack of α2A-AR signalling promoted weight loss more efficiently than exercise with normal α2A-AR function. These results suggest that blockade of α2A-ARs may be exploited to reduce visceral fat and to improve insulin secretion.
Cosmocinepolítica tikm’n-maxakali: ensaio sobre a invenção de uma cultura e de um cinema indígena (Dossiê Olhares Cruzados)
Authors: Queiroz Ruben Caixeta de , Diniz Renata Otto
Published: July 2018

Neste trabalho refletimos acerca dos Tikm'n (também chamado de Maxakali) e suas maneiras de fazer cinema e ritual. Defendemos a ideia de que não se pode compreender a maneira de filmar e fazer cinema maxakali se não compreendemos a lógica e a estratégia em ação para fazer os rituais que, em geral, guiam a produção dos filmes. Por outro lado, ao fazer registros sobre esses rituais, estes multiplicam-se ao mesmo tempo que recuperam-se, em conjunto com a cultura de um povo. Mais do que isso, sugerimos que para melhor compreender esse cinema é necessário colocá-lo lado a lado aos conceitos que informam a cosmologia maxakali, sem esquecer que a história é narrada (para os filmes e além deles) do ponto de vista dos Maxakali sobre a pacificação ou a boa convivência que buscam com os “espíritos” e com o mundo dos brancos. Trata-se de uma cinecosmopolítica, ou, dito de outra forma, de um tipo de filme-ritual.
Cilende: o baile das máscaras no Festival da Cultura Luvale (Angola)
Authors: Penoni Isabel
Published: July 2018

Este artigo apresenta um material etnográfico e visual inédito sobre a performance dos makixi, ancestrais manifestados na forma de bailarinos mascarados, originais dos rituais de circuncisão (mukanda) praticados por povos bantu da grande área de confluência entre Angola, Zâmbia e República Democrática do Congo, entre eles, os Luvale. Proclamados Patrimônio Oral e Imaterial da Humanidade pela UNESCO em 2005, o lócus principal de sua performance é hoje o grande festival da “cultura” luvale, realizado desde os anos 1950 na Zâmbia e, mais recentemente, em Angola. Com base numa etnografia da versão angolana do festival, realizada entre 2012 e 2013, a autora focaliza os bailes de makixi que constituem a atração principal do festival, mostrando a estreita relação entre a morfologia das máscaras e seus estilos de dança, e contribuindo para reduzir a enorme lacuna aberta pelos quase quarenta anos sem nenhuma pesquisa realizada na área em decorrência da guerra.
Da rua para os palcos, relações insuspeitas entre dança popular e dança teatral (Resenha de Marianna Monteiro)
Authors: Rocha Ewelter
Published: July 2018

A relação conflituosa entre uma suposta “natureza dançante” do povo brasileiro e a participação apenas remota que a dança de palco ocupa no cenário cultural do Brasil constitui a provocação inicial que motivou Marianna Monteiro a realizar sua pesquisa, oportunamente nominada Dança popular: espetáculo e devoção. Como preconizado no subtítulo, a investigação lida com vetores aparentemente opostos – advindos da velha dialética do sagrado e do profano – contudo, marcados por relações insuspeitas, em que política, economia, estética e religião se interceptam nos processos formativos das danças populares brasileiras, considerados pela autora como parte integrante da expansão do Estado Moderno português, entre os séculos XVI e XVIII. A pesquisa é fruto da tese de doutorado apresentada ao Departamento de Filosofia da Faculdade de Filosofia, Letras e Ciências Humanas da Universidade de São Paulo (FFLCH-USP), sob orientação da professora Olgária Feres Matos.
As imagens e a potência dos encontros
Authors: Santos Carolina Junqueira dos
Published: July 2018

O livro A experiência da imagem na etnografia, resultado de pesquisas realizadas pelo GRAVI – Grupo de Antropologia Visual /USP, aborda, a partir de artigos e filmes, os mais diversos usos da imagem dentro de uma perspectiva antropológica, procurando novas linguagens e possibilidades visuais para a etnografia.
Rafucko entrevista Eduardo Viveiros de Castro
Authors: Rafucko Rafael Puetter
Published: July 2018

Rafucko Álvares Cabral tenta redescobrir o Brasil em entrevista com o antropólogo Eduardo Viveiros de Castro.
“A câmera é minha arma de caça” A poética dos filmes de Réal J. Leblanc, cineasta innu (Dossiê Olhares Cruzados)
Authors: Sztutman Renato
Published: July 2018

Este ensaio explora o conjunto de filmes do jovem cineasta Innu, Real Junior Leblanc, ligados ao Projeto Wapikoni Mobile, que atua em comunidades indígenas do Quebec (Canadá), formando realizadores. Seu argumento é o de que estes filmes, tanto os mais experimentais como os mais documentais, privilegiam uma dimensão poética, que acenam a uma estética cosmopolítica, esta que insiste em não separar mundos humanos e além do humano e que se oferece como instrumento de luta e resistência política.
BORÇ HEDEFLEMESİ REJİMİ VE MAKROEKONOMİK PERFORMANS
Authors: ÇETİN İrem
Published: July 2018

Çalışmada, borç hedeflemesi rejimin, makroekonomik
performans üzerindeki etkilerinin, politik makroekonomi modelleri kullanılarak,
merkez bankasının bağımsız olduğu kurumsal yapıda araştırılması amaçlanmıştır.
Bu çerçevede, çalışmada, ilk olarak borç hedeflemesinin, politik
istikrarsızlığın arttığı durumda makroekonomik sonuçları incelenmektedir. Daha
sonra, daha sıkı borç hedeflemesinin ekonomik performans üzerindeki etkileri
değerlendirilmektedir. Çalışmada, son olarak, seçim sonuçlarına ilişkin belirsizlik
durumunda, borç hedeflemesi politikasının makroekonomik etkileri analiz
edilmektedir.  Çalışmadan elde edilen sonuçlara
göre, politik istikrarsızlık sonucu mali sürdürülebilirlik problemleri ile
karşı karşıya kalan ekonomilerde kamu borcunun makul bir seviyede seyretmesini
sağlayacak bir borç hedeflemesi rejimi, politik istikrarsızlığın zamanlar arası
maliyetinin azaltılmasına yardımcı olmaktadır.
The Heart of Heresy: Inquisition, Medicine, and False Sanctity
Authors: Bouley Bradford
Published: July 2018

This paper examines the engagement of various officials and tribunals of the Roman Inquisition with the new anatomical studies of the early modern period. It argues that although inquisition officers were frequently very aware of the latest medical theories, they actively chose not to employ anatomical or medical evidence when evaluating the unusual physical symptoms that might be associated with false or affected sanctity. This attitude stands in contrast to the employment of anatomical knowledge by other ecclesiastical institutions – e.g. the Congregation of Rites – and suggests that the Inquisition held a different, and perhaps more modern, view about the relationship between natural knowledge and religion.
Contra medicos: Physicians Facing the Inquisition in Sixteenth-Century Venice
Authors: Celati Alessandra
Published: July 2018

Since the Middle Ages, ecclesiastical authorities considered medical activity worthy of their attention and control. During the Counter-Reformation, they toughened their disciplinary action, aware of the peculiarity of an ars that mixed together the cure of the body with the cure of the soul. Moreover, the authorities became increasingly suspicious of practitioners who were highly involved in the Reformation movement, and who distanced themselves from Catholicism in the epistemological premises of their work. By examining original sources from the Venetian Inquisition archive, this paper discusses the factors that put the Roman Church and the medical profession in op­­position to each other in the sixteenth century, and describes the professional solidarity put forward by physicians. It also examines the problematic relationship between doctors and the Inquisition, dealing with the former as effective agents of heretical propaganda.
Between Galen and St Paul: How Juan Huarte de San Juan Responded to Inquisitorial Censorship
Authors: Giglioni Guido
Published: July 2018

The Examen de ingenios para las sciencias, published in 1575 for the Spanish physician Juan Huarte de San Juan (1529/1530-1588), was a bold attempt to apply the principles of Galenic naturalism to a better understanding of human capabilities. Inevitably, the work also touched upon a number of theological issues, especially the delicate question of the interplay between natural abilities and supernatural gifts. When the treatise was included in the Portuguese Index of 1581, and then in the Spanish Indexes of 1583 and 1584, Huarte was allowed to amend some of his positions, as is evident in the second edition published posthumously in 1594. The aim of this article is to shed light on the identity of an ‘expurgated’ book by concentrating on some of the most significant changes in the Examen triggered by the intervention of the Spanish Inquisition. It will become apparent that Huarte’s response to censorship was not acquiescence or dissembling, but active engagement with the inquisitorial challenge.
Chara kirghisorum (Charales): lectotypification, first reliable record in Europe and update of species distribution in Russia
Authors: ROMANOV ROMAN E. , ABDULLIN SHAMIL R.
Published: July 2018

Charophytes are commonly easily recognizable plants irrespective of their size due to the recurrent combination of very similar parts within their thalli. A few species are outstanding due to their unusual whip-like appearance with regularly distributed small nodules on the stems formed with whorls of short and nearly rudimentary branchlets. The central and north-European Chara filiformis A. Braun in Hertzsch (1855: 81) and mainly Middle-Asian C. kirghisorum Lessing (1834: 212) are examples of this distinctive habit. The species differ essentially in gametangia arrangement as well as in their distribution range. Monoecious C. filiformis does not have reliable records east of Pskov Oblast of Russia (29° E), while dioecious C. kirghisorum is unknown west of Orenburg Oblast of Russia (58° E) (Hollerbach 1941; Hollerbach & Krassavina 1983; LE!, PSK!). Therefore, they may be recognized as vicariate species.
Seychellister mornicus, a new genus and species of Clavigeritae (Coleoptera, Staphylinidae, Pselaphinae) from Seychelles
Authors: HLAVÁČ PETER , NAKLÁDAL OTO
Published: July 2018

Seychellister mornicus, gen. and sp. nov. is described based on three specimens collected by sifting of leaf-litter in Mahé, Seychelles. The genus is tentatively placed in the subtribe Clavigerodina (Pselaphinae: Clavigeritae: Clavigerini).
Can the Impact of Aerosols on Deep Convection be Isolated from Meteorological Effects in Atmospheric Observations?
Authors: Grabowski Wojciech W.
Published: July 2018

Influence of pollution on dynamics of deep convection continues to be a controversial topic. Arguably, only carefully designed numerical simulations can clearly separate the impact of aerosols from the effects of meteorological factors that affect moist convection. This paper argues that such a separation is virtually impossible using observations because of the insufficient accuracy of atmospheric measurements and the fundamental nature of the interaction between deep convection and its environment. To support this conjecture, results from numerical simulations are presented that apply modeling methodology previously developed by the author. The simulations consider small modifications, difficult to detect in observations, of the initial sounding, surface fluxes, and large-scale forcing tendencies. All these represent variations of meteorological conditions that affect deep convective dynamics independently of aerosols. The setup follows the case of daytime convective development over land based on observations during the Large-Scale Biosphere–Atmosphere (LBA) field project in Amazonia. The simulated observable macroscopic changes of convection, such as the surface precipitation and upper-tropospheric cloudiness, are similar to or larger than those resulting from changes of cloud condensation nuclei from pristine to polluted conditions studied previously using the same modeling case. Observations from Phase III of the Global Atmospheric Research Program Atlantic Tropical Experiment (GATE) are also used to support the argument concerning the impact of the large-scale forcing. The simulations suggest that the aerosol impacts on dynamics of deep convection cannot be isolated from meteorological effects, at least for the daytime development of unorganized deep convection considered in this study.
On the Dynamical Mechanisms Governing El Niño–Southern Oscillation Irregularity
Authors: Berner Judith , Sardeshmukh Prashant D. , Christensen Hannah M.
Published: July 2018

This study investigates the mechanisms by which short time-scale perturbations to atmospheric processes can affect El Niño–Southern Oscillation (ENSO) in climate models. To this end a control simulation of NCAR’s Community Climate System Model is compared to a simulation in which the model’s atmospheric diabatic tendencies are perturbed every time step using a Stochastically Perturbed Parameterized Tendencies (SPPT) scheme. The SPPT simulation compares better with ECMWF’s twentieth-century reanalysis in having lower interannual sea surface temperature (SST) variability and more irregular transitions between El Niño and La Niña states, as expressed by a broader, less peaked spectrum. Reduced-order linear inverse models (LIMs) derived from the 1-month lag covariances of selected tropical variables yield good representations of tropical interannual variability in the two simulations. In particular, the basic features of ENSO are captured by the LIM’s least damped oscillatory eigenmode. SPPT reduces the damping time scale of this eigenmode from 17 to 11 months, which is in better agreement with the 8 months obtained from reanalyses. This noise-induced stabilization is consistent with perturbations to the frequency of the ENSO eigenmode and explains the broadening of the SST spectrum (i.e., the greater ENSO irregularity). Although the improvement in ENSO shown here was achieved through stochastic physics parameterizations, it is possible that similar improvements could be realized through changes in deterministic parameterizations or higher numerical resolution. It is suggested that LIMs could provide useful insight into model sensitivities, uncertainties, and biases also in those cases.