bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Study Between Promoter Polymorphisms of ADAM17 and Progression of Sepsis
Authors: Shao Yiming , He Junbing , Chen Feng , Cai Yujie , Zhao Jianghao , Lin Yao , Yin Zihan , Tao Hua , Shao Xin , Huang Pengru , Yin Mingkang , Zhang Wenying , Liu Zhou , Cui Lili
Published: September 2016

Background: A disintegrin and metalloproteinase 17 (ADAM17) has been confirmed to play a significant role in the pathogenesis of sepsis. However, little is known about the clinical relevance of ADAM17 polymorphisms to sepsis onset and development. Methods: This study analyzed the associations of five ADAM17 promoter polymorphisms (rs55790676, rs12692386, rs11684747, rs1524668 and rs11689958) with sepsis (370 sepsis cases and 400 controls). Genotyping was performed using pyrosequencing and polymerase chain reaction-length polymorphism method. The ADAM17 expression was measured using the real-time PCR method and the concentrations of related cytokines were detected using enzyme-linked immunosorbent assay. Results: No associations were observed between these polymorphisms and sepsis susceptibility, while the rs12692386GA/GG genotypes were overrepresented among the patients with severe sepsis (P=0.002) or septic shock (P=0.0147) compared to those with sepsis subtype, suggesting a susceptible role of rs12692386A>G in the progression of sepsis. Moreover, ADAM17 expression was increased in the sepsis patients with the rs12692386GA/GG genotypes, accompanied by up-regulation of expression of the ADAM17 substrates (TNF-α, IL-6R and CX3CL1) and pro-inflammatory cytokines (IL-1β and IL-6). Conclusion: The present study has provided potentially valuable clinical evidence that the ADAM17 rs12692386 polymorphism is a functional variant that might be used as a relevant risk estimate for the progression of sepsis.
Ischemia/Reperfusion Injury Alters Sphingolipid Metabolism in the Gut
Authors: Hoehn Richard S. , Seitz Aaron P. , Jernigan Peter L. , Gulbins Erich , Edwards Michael J.
Published: September 2016

Background: Intestinal ischemia/reperfusion injury (I/R) is a significant cause of morbidity and mortality in surgical patients. Ceramide is a mediator of apoptosis and has been implicated as increasing bacterial infection susceptibility. The metabolite of ceramide, sphingosine, was recently shown to play an important role in the cell-autonomous, innate immune response of the upper respiratory tract by killing bacterial pathogens. The role of ceramide and/or sphingosine after mesenteric I/R is unknown. We investigated the specific effects of intestinal I/R on tissue ceramide and sphingosine concentration and resulting susceptibility to bacterial invasion. Methods: To simulate intestinal I/R, C57BL/6 mice underwent 30 minutes of vascular clamp-induced occlusion of the superior mesenteric artery followed by variable reperfusion times. Jejunum segments and intraluminal contents were analyzed for ceramide, sphingosine and bacteria using immunohistochemistry. Jejunum samples were also homogenized and cultured to quantify bacterial presence in the proximal intestine. Results: We hypothesized that I/R induces an increase of ceramide in the intestine resulting in increased permeability, while a concomitant decrease of sphingosine may permit bacterial overgrowth. Control mice had no measurable bacteria in their proximal jejunum as measured by tissue culture and immunohistochemistry. After I/R, bacterial counts in the jejunum increased in a time-dependent manner, reaching a peak at 12 hours after reperfusion. Immunohistochemical analysis revealed a marked increase in ceramide in the vasculature of jejunal villi. In contrast, while ceramide concentrations in the epithelial cells decreased after I/R, sphingosine levels appeared to remain unchanged. Surprisingly, bacteria present in the jejunal lumen following I/R contained a ceramide coat. Conclusion: These data indicate that intestinal I/R leads to small intestine bacterial overgrowth as well as ceramide formation in the jejunal vasculature, which may contribute to the gut permeability associated with this injury. Moreover, our novel finding of ceramide in bacterial membranes represents a new opportunity to investigate the dynamic pathogenicity of the gut microbiome. The hypothesis that a decrease of sphingosine after I/R permits bacterial overgrowth in the intestine was not confirmed.
Short-Term Pretreatment of Sub-Inhibitory Concentrations of Gentamycin Inhibits the Swarming Motility of Escherichia Coli by Down-Regulating the Succinate Dehydrogenase Gene
Authors: Zhuang Yijing , Chen Weidong , Yao Fen , Huang Yuanchun , Zhou Shuqin , Li Haiyan , Zhang Zijie , Cai Congyi , Gao Yi , Peng Qing
Published: September 2016

Background/Aims: Motility is a feature of many pathogens that contributes to the migration and dispersion of the infectious agent. Whether gentamycin has a post-antibiotic effect (PAE) on the swarming and swimming motility of Escherichia coli (E. coli) remains unknown. In this study, we aimed to examine whether short-term pretreatment of sub-inhibitory concentrations of gentamycin alter motility of E. coli and the mechanisms involved therein. Methods: After exposure to sub-inhibitory concentrations (0.8 μg/ml) of gentamicin, the swarming and swimming motility of E. coli was tested in semi-solid media. Real-time PCR was used to detect the gene expression of succinate dehydrogenase (SDH). The production of SDH and fumarate by E. coli pretreated with or without gentamycin was measured. Fumarate was added to swarming agar to determine whether fumarate could restore the swarming motility of E. coli. Results: After pretreatment of E. coli with sub-inhibitory concentrations of gentamycin, swarming motility was repressed in the absence of growth inhibition. The expression of all four subunits of SDH was down-regulated, and the intracellular concentration of SDH and fumarate, produced by E. coli, were both decreased. Supplementary fumarate could restore the swarming motility inhibited by gentamycin. A selective inhibitor of SDH (propanedioic acid) could strongly repress the swarming motility. Conclusion: Sub-inhibitory concentrations of gentamycin inhibits the swarming motility of E. coli. This effect is mediated by a reduction in cellular fumarate caused by down-regulation of SDH. Gentamycin may be advantageous for treatment of E. coli infections.
Inhibition of MicroRNA-383 Ameliorates Injury After Focal Cerebral Ischemia via Targeting PPARγ
Authors: Pei Lichun , Meng Songyan , Yu Weigang , Wang Qiujun , Song Fangfang , Ma Lan
Published: September 2016

Background: Peroxisome proliferator-activated receptor gamma (PPARγ) plays a critical role in protecting against distinct brain damages, including ischemia. Our previous data have shown that the protein level of PPARγ is increased in the cortex after middle cerebral artery occlusion (MCAO); PPARγ up-regulation contributes to PPARγ activation and is effective in reducing ischemic damage to brain. However, the regulatory mechanism of PPARγ after focal cerebral ischemia in rats is still unclear. In this study, we evaluated the effect of microRNA on PPARγ in rats subjected to MCAO. Methods: Focal cerebral ischemia was established by surgical middle cerebral artery occlusion; the protein level of PPARγ was detected by Western blotting; the level of microRNA-383 (miR-383) was quantified by real-time PCR; the neurological outcomes were defined by infarct volume and neurological deficits. Luciferase assay was used to identify the luciferase activities of PPARγ and miR-383. Results: We showed here that miR-383 level was down-regulated in the ischemic hemisphere of rats 24h after MCAO. Overexpression of miR-383 by miR-383 agomir increased infarct volume and aggravated neurological damage. Administration of miR-383 antagomir had the opposite effects. Furthermore, we found that PPARγ protein was down-regulated by miR-383 overexpression, and up-regulated by miR-383 inhibition both in rat model of MCAO and in primary culture cells. Finally, we found that miR-383 suppressed the luciferase activity of the vector carrying the 3'UTR of PPARγ, whereas mutation of the binding sites relived the repressive effect of miR-383. Conclusion: Our study demonstrated that miR-383 may play a key role in focal cerebral ischemia by regulating PPARγ expression at the post-transcriptional level, and miR-383 may be a potential therapeutic target for stroke.
Astragalus Polysaccharide Attenuated Iron Overload-Induced Dysfunction of Mesenchymal Stem Cells via Suppressing Mitochondrial ROS
Authors: Yang Fan , Yan Gege , Li Yuan , Han Zhenbo , Zhang Lai , Chen Simon , Feng Chao , Huang Qi , Ding Fengzhi , Yu Ying , Bi Chongwei , Cai Benzhi , Yang Lei
Published: September 2016

Background/Aims: Bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to differentiate into multilineage cells such as osteoblasts, chondrocytes, and cardiomyocytes. Dysfunction of BMSCs in response to pathological stimuli participates in the development of diseases such as osteoporosis. Astragalus polysaccharide (APS) is a major active ingredient of Astragalus membranaceus, a commonly used anti-aging herb in traditional Chinese medicine. The aim of this study was to investigate whether APS protects against iron overload-induced dysfunction of BMSCs and its underlying mechanisms. Methods: BMSCs were exposed to ferric ammonium citrate (FAC) with or without different concentrations of APS. The viability and proliferation of BMSCs were assessed by CCK-8 assay and EdU staining. Cell apoptosis, senescence and pluripotency were examined utilizing TUNEL staining, β-galactosidase staining and qRT-PCR respectively. The reactive oxygen species (ROS) level was assessed in BMSCs with a DCFH-DA probe and MitoSOX Red staining. Results: Firstly, we found that iron overload induced by FAC markedly reduced the viability and proliferation of BMSCs, but treatment with APS at 10, 30 and 100 μg/mL was able to counter the reduction of cell proliferation. Furthermore, exposure to FAC led to apoptosis and senescence in BMSCs, which were partially attenuated by APS. The pluripotent genes Nanog, Sox2 and Oct4 were shown to be downregulated in BMSCs after FAC treatment, however APS inhibited the reduction of Nanog, Sox2 and Oct4 expression. Further study uncovered that APS treatment abrogated the increase of intracellular and mitochondrial ROS level in FAC-treated BMSCs. Conclusion: Treatment of BMSCs with APS to impede mitochondrial ROS accumulation can remarkably inhibit apoptosis, senescence, and the reduction of proliferation and pluripotency of BMSCs caused by FAC-induced iron overload.
Resveratrol Specifically Kills Cancer Cells by a Devastating Increase in the Ca2+ Coupling Between the Greatly Tethered Endoplasmic Reticulum and Mitochondria
Authors: Madreiter-Sokolowski Corina T. , Gottschalk Benjamin , Parichatikanond Warisara , Eroglu Emrah , Klec Christiane , Waldeck-Weiermair Markus , Malli Roland , Graier Wolfgang F.
Published: September 2016

Background/Aims: Resveratrol and its derivate piceatannol are known to induce cancer cell-specific cell death. While multiple mechanisms of actions have been described including the inhibition of ATP synthase, changes in mitochondrial membrane potential and ROS levels, the exact mechanisms of cancer specificity of these polyphenols remain unclear. This paper is designed to reveal the molecular basis of the cancer-specific initiation of cell death by resveratrol and piceatannol. Methods: The two cancer cell lines EA.hy926 and HeLa, and somatic short-term cultured HUVEC were used. Cell viability and caspase 3/7 activity were tested. Mitochondrial, cytosolic and endoplasmic reticulum Ca2+ as well as cytosolic and mitochondrial ATP levels were measured using single cell fluorescence microscopy and respective genetically-encoded sensors. Mitochondria-ER junctions were analyzed applying super-resolution SIM and ImageJ-based image analysis. Results: Resveratrol and piceatannol selectively trigger death in cancer but not somatic cells. Hence, these polyphenols strongly enhanced mitochondrial Ca2+ uptake in cancer exclusively. Resveratrol and piceatannol predominantly affect mitochondrial but not cytosolic ATP content that yields in a reduced SERCA activity. Decreased SERCA activity and the strongly enriched tethering of the ER and mitochondria in cancer cells result in an enhanced MCU/Letm1-dependent mitochondrial Ca2+ uptake upon intracellular Ca2+ release exclusively in cancer cells. Accordingly, resveratrol/piceatannol-induced cancer cell death could be prevented by siRNA-mediated knock-down of MCU and Letm1. Conclusions: Because their greatly enriched ER-mitochondria tethering, cancer cells are highly susceptible for resveratrol/piceatannol-induced reduction of SERCA activity to yield mitochondrial Ca2+ overload and subsequent cancer cell death.
Isolation, Culture and Identification of Choriocarcinoma Stem-Like Cells from the Human Choriocarcinoma Cell-Line JEG-3
Authors: Cai Jingting , Peng Tianfang , Wang Jing , Zhang Jingli , Hu Hui , Tang Dihong , Chu Chaonan , Yang Ting , Liu Huining
Published: September 2016

Background/Aims: Cancer stem cells (CSCs) exhibit enhanced proliferative capacity and resistance to chemotherapy; however, choriocarcinoma CSCs have not yet been reported. In this study the human choriocarcinoma cell line JEG-3 was cultured in serum free media, and the characteristics of suspension and parental adherent JEG-3 cells were compared. Methods: Cell proliferation, colony-formation, soft agar clonogenicity, and transwell invasion assays were performed in vitro, and tumor xenografts in BALB/c nude mice were used to evaluate stem cell properties. Results: In serum-supplemented medium (SSM), JEG-3 cells were 4.51 ± 1.71% CD44+, 7.67 ± 2.67% CD133+, and 13.85 ± 2.95% ABCG2+. In serum-free medium (SFM), the expression of these markers increased to 53.08 ± 3.15%, 47.40 ± 2.67%, and 78.70 ± 7.16%, respectively. Moreover, suspension JEG-3 cells exhibited enhanced colony-formation capability as well as invasive and proliferative ability in vitro, alongside enhanced tumorigenic properties in vivo. Suspension JEG-3 cells also exhibited resistance to the chemotherapeutic drugs methotrexate, fluorouracil and etoposide. When seeded in serum supplemented medium, suspension JEG-3 cells readopted an adherent phenotype and continued to differentiate with no significant difference in the morphology between suspension and parent cells. Conclusion: In this study, choriocarcinoma stem-like cells (CSLCs) were isolated from the human choriocarcinoma JEG-3 cell line by SFM culture and characterized.
Vitamin C Inhibits Aggravated Eryptosis by Hydrogen Peroxide in Glucose-6-Phosphated Dehydrogenase Deficiency
Authors: Shan Feng , Yang Rui , Ji Tiemei , Jiao Fengjun
Published: September 2016

Background/Aims: The study was aimed to investigate if vitamin C could exert protective effects on development of eryptosis caused by glucose-6-phosphate dehydrogenase (G6PD) deficiency and hydrogen peroxide. Methods: Isolated erythrocytes with different G6PD activity (normal or deficient) were divided into various groups treated by either Vitamin C or H2O2. Phosphatidylserine (PS) extroversion rate was detected by Annexin V binding. The intracellular Ca2+ concentration was detected by Fluo3-fluorescence, and western blot was used to detect the expression of apoptosis factor caspase 3. Results: Compared with the blank group, the PS extroversion rate (P < 0.001), intracellular Ca2+ concentration (P < 0.001) and active caspase 3 expression level (P < 0.05) of erythrocytes significantly increased after treatment of 0.05% H2O2. Then the index of eryptosis significantly decreased after erythrocytes were treated with Vitamin C (1 mg/ml) for 30 min (all P < 0.05). The decline in erythrocytes with G6PD normal activity was more significant than those with G6PD deficiency. Conclusion: Vitamin C could effectively inhibit the eryptosis contributed by H2O2 oxidative stress, and the suppression on eryptosis with G6PD normal activity was more effective than that with G6PD deficiency.
HIV Protease Inhibitors Apoptotic Effect in SH-SY5Y Neuronal Cell Line
Authors: Tricarico Paola Maura , de Oliveira Franca Rafael Freitas , Pacor Sabrina , Ceglia Valentina , Crovella Sergio , Celsi Fulvio
Published: September 2016

Background: Prophylactic treatment regimens to prevent mother-to-child HIV transmission include protease inhibitors Lopinavir and Ritonavir. Lopinavir and Ritonavir have been reported to be able to induce intracellular oxidative stress in diverse cellular models, however scarce informations are available about protease inhibitor effects of in the central nervous system (CNS). In our study we evaluated the impact of protease inhibitors on a cell neuronal model. Methods: We treated a neuroblastoma cell line (SH-SY5Y) with increasing doses of Lopinavir and Ritonavir (0.1-1-10-25-50 µM), used alone or in combination, evaluating the impact of these drugs in terms of mitochondrial activity, with MTT cell proliferation assay; mRNA expression of heme oxygenase (HemeOH) and reactive oxygen species (ROS) levels with 2',7'-dichlorofluorescin diacetate (H2DCFDA) in order to assess oxidative stress; apoptotic cell death with flow cytometry. Results: We observed that Lopinavir and Ritonavir treatment, at 25 and/or 50 µM concentrations, induced mitochondrial damage, increase of heme oxygenase RNA expression levels and ROS generation, followed by apoptosis in SH-SY5Y. Conclusions: Our in vitro model demonstrates a damaging effect of HIV protease inhibitors on the neuroblastoma cell line, thus partially mimicking the impact of these drugs on the CNS of children born to HIV positive mothers undergone to antiretroviral treatment.
The rs9932581 and rs1049255 Polymorphisms in CYBA is not Associated with Preeclampsia in Chinese Han Women
Authors: Liu Shiguo , Li Xueying , Wang Jingli , Ji Jing , Liu Jingjing , Lin Yan , Jia Xuewen , Song Weiqing , Wu Cuijiao , Li Lan
Published: September 2016

Background/Aims: Several lines of evidence have been reported that oxidative stress plays an important role in the pathogenesis of Preeclampsia (PE). Therefore, this research is aimed to investigate whether polymorphisms of CYBA are related to susceptibility to PE in Chinese Han women. Methods: We studied the genetic frequency of the rs9932581 and 1049255 polymorphisms in CYBA in 1029 PE patients and 1400 controls of later pregnant women by the TaqMan allelic discrimination real-time PCR and a case-control model. Results: Our research indicated that no significant differences were found for the genotypic or allelic frequencies at the two polymorphic sites in CYBA between PE patients and controls. To further study the relationship between the polymorphic sites and PE, we also found that there is no significant difference in the genetic distributions identified between the mild or severe PE and early or the late-onset PE and controls. Conclusion: The study demonstrated that the genetic variants of rs9932581 and rs1049255 in CYBA might not be associated with PE. However, investigations of genetic variability that influence on the disease outcome are needed in other large prospective populations or regions, so the complicated interconnection of genetic and environmental elements can be emulated for better understanding.
Breastfeeding Duration and Childhood Caries: A Cohort Study
Authors: Nirunsittirat Areerat , Pitiphat Waranuch , McKinney Christy M. , DeRouen Timothy A. , Chansamak Nusara , Angwaravong Onauma , Patcharanuchat Piyachat , Pimpak Taksin
Published: September 2016

This cohort study was conducted in Khon Kaen, Thailand, to test the hypothesis that a longer breastfeeding duration increases the risk for dental caries in primary teeth. We collected information on infant feeding practices and potential confounders using a structured questionnaire to interview mothers or caregivers during the second trimester of pregnancy and after birth at 21 days and at 3, 12, 18, 24, and 36 months. Regardless of other liquids and foods, full breastfeeding was defined as feeding breast milk but not formula, while any breastfeeding was feeding breast milk with or without formula. Two calibrated dentists measured dental caries when the children were 3-4 years of age using the decayed, missing, and filled surfaces (dmfs) index following the World Health Organization criteria. Negative binomial regression with a generalized linear model was used to estimate relative risks (RRs) and 95% confidence intervals (CIs) using dmfs as an outcome. Log-binomial regression was performed to model the caries prevalence. Of 556 children, 88.1% had dental caries with a mean dmfs of 14.2. Full breastfeeding for 6-11 months was significantly associated with a lower dmfs (adjusted RR 0.77, 95% CI 0.63, 0.93) and a lower caries prevalence (adjusted RR 0.45, 95% CI 0.22, 0.90). The frequency of sleeping while breast- or bottle-feeding increased the caries risk in a dose-response manner. There was no association between duration of any breastfeeding and dental caries. In conclusion, full breastfeeding for 6-11 months may protect against dental caries in primary teeth. Prolonged breastfeeding was not associated with dental caries in this population.
Idiopathic Granulomatous Mastitis: Cytologic and Histologic Study of 65 Egyptian Patients
Authors: Helal Thanaa El A. , Shash Lobna S. , Saad El-Din Somaia A. , Saber Sally M.
Published: September 2016

Background: The etiology of idiopathic granulomatous mastitis (IGM) is unknown, and it is commonly misdiagnosed clinically and/or radiologically as breast cancer. The role of fine-needle aspiration cytology (FNAC) in its diagnosis is still a matter of debate. The aim of the current study is to assess the value of FNAC in the diagnosis of IGM, and to search for the presence of bacteria in IGM with cystic vacuoles, which was described recently by a few authors. Materials and Methods: Retrospective study of cytologic smears and histologic tissue sections of 65 Egyptian IGM cases was done along with microbiologic testing. A comparison of the frequency of IGM in Egypt to that of other populations was also made. Results: IGM has typical FNA features which can easily exclude malignancy. Histologically, cystic vacuoles were encountered in 35 out of 65 cases (53.9%), with only 6 (17.14%) of these cases showing Gram-positive bacilli (GPB). The frequency of IGM in Egypt is comparable to those in other Middle Eastern countries but much higher than in Western countries. Conclusion: IGM is a common breast disease in Egypt. FNAC in IGM has a high diagnostic accuracy. This study supports the few recent studies that have detected GPB in IGM with cystic vacuoles. Thus, bacteriologic examination in such cases may affect the treatment strategy.
Systems Perspective of Morbillivirus Replication
Authors: Kumar Naveen , Barua Sanjay , Thachamvally Riyesh , Tripathi Bhupendra Nath
Published: September 2016

Systems biology refers to system-wide changes in biological components such as RNA/DNA (genomics), protein (proteomics) and lipids (lipidomics). In this review, we provide comprehensive information about morbillivirus replication. Besides discussing the role of individual viral/host proteins in virus replication, we also discuss how systems-level analyses could improve our understanding of morbillivirus replication, host-pathogen interaction, immune response and disease resistance. Finally, we discuss how viroinformatics is likely to provide important insights for understanding genome-genome, genome-protein and protein-protein interactions.
Successful Treatment of Fibrosing Organising Pneumonia Causing Respiratory Failure with Mycophenolic Acid
Authors: Paul Christina , Lin-Shaw Ammy , Joseph Mariamma , Kwan Keith , Sergiacomi Gianluigi , Mura Marco
Published: September 2016

Organising pneumonia (OP) is usually promptly responsive to corticosteroid treatment. We describe a series of 3 cases of severe, progressive, biopsy-proven fibrosing OP causing respiratory failure. All cases presented with peribronchial and subpleural consolidations, had a fibro-inflammatory infiltrative component in the alveolar septa, and only had a partial and unsatisfactory response to corticosteroids. However, they responded to mycophenolic acid (MPA) treatment with resolution of respiratory failure as well as clinical and functional improvement. MPA as an additional treatment option for aggressive forms of fibrosing OP and interstitial lung disease needs to be further explored.
Hypoxia-Inducible Factor-1α Activates the Transforming Growth Factor-β/SMAD3 Pathway in Kidney Tubular Epithelial Cells
Authors: Kushida Natsuki , Nomura Seitaro , Mimura Imari , Fujita Takanori , Yamamoto Shogo , Nangaku Masaomi , Aburatani Hiroyuki
Published: September 2016

Background: Kidney injury, including chronic kidney disease and acute kidney injury, is a worldwide health problem. Hypoxia and transforming growth factor-β (TGF-β) are well-known factors that promote kidney injury. Hypoxia-inducible factor (HIF) and SMAD3 are their main downstream transcriptional factors. Hypoxia-HIF pathway and TGF-β/SMAD3 pathway play a crucial role in the progression of kidney injury. However, reports on their interactions are limited, and the global transcriptional regulation under their control is almost unknown. Methods: Kidney tubular epithelial cells were cultured and stimulated by hypoxia and TGF-β. We detected global binding sites of HIF-1α and SMAD3 in cells using chromatin immunoprecipitation-sequencing (ChIP-Seq), and measured the gene expression using RNA-sequencing (RNA-Seq). ChIP-quantitative PCR (qPCR) was used to quantitatively evaluate bindings of SMAD3. Results: ChIP-Seq revealed that 2,065 and 5,003 sites were bound by HIF-1α and SMAD3, respectively, with 614 sites co-occupied by both factors. RNA-Seq showed that hypoxia and TGF-β stimulation causes synergistic upregulation of 249 genes, including collagen type I alpha 1 (COL1A1) and serpin peptidase inhibitor, clade E, member 1, which are well-known to be involved in fibrosis. Ontology of the 249 genes implied that the interaction of HIF-1α and SMAD3 is related to biological processes such as fibrosis. ChIP-qPCR of SMAD3 at HIF-1α binding sites near COL1A1 and SERPINE1 indicated that HIF-1α promotes the bindings of SMAD3, which is induced by TGF-β. Conclusions: These findings suggest that HIF-1α induced by hypoxia activates the TGF-β/SMAD3 pathway. This mechanism may promote kidney injury, especially by upregulating genes related to fibrosis.
Potentially Serious Drug-Drug Interactions in Older Patients Hospitalized for Acute Ischemic and Hemorrhagic Stroke
Authors: Caratozzolo Salvatore , Gipponi Stefano , Marengoni Alessandra , Pari Elisa , Scalvini Andrea , Pasina Luca , Magoni Mauro , Padovani Alessandro
Published: September 2016

Background: Polypharmacy is very common in older persons and it is associated with inappropriate prescribing and potential drug-drug interactions (DDIs). Aims of this study were to identify prevalence of DDIs in older persons with acute stroke and to evaluate the association between stroke and DDIs. Methods: One hundred forty-six patients admitted with diagnosis of acute stroke were enrolled. The therapeutic regimen of patients was analyzed at admission to identify the number of DDIs, prevalence and sorts of serious DDIs according to subtype of acute stroke (ischemic or hemorrhagic) and to its recurrence. Results: Five hundred eighty-two DDIs were identified: 18 mild, 415 moderate and 149 serious. Sixty-one percent of patients were exposed to at least one serious DDI. A higher percentage of patients were exposed to at least one serious DDI among those with a recurring ischemic event compared to those with a first event (74 vs. 50%; p < 0.01, respectively). Serious DDIs potentially associated with an increased risk of a cerebral event were identified in 19 (17%) patients with ischemic stroke, and in 7 (19%) patients with hemorrhagic stroke. Conclusions: The prevalence of serious DDIs was high in aging patients with acute stroke but different according to subtype and recurrence of the cerebrovascular event.
Studies of the interaction of ticagrelor with the P2Y13 receptor and with P2Y13-dependent pro-platelet formation by human megakaryocytes
Authors: Björquist Anna , Di Buduo Christian A. , Femia Eti A. , Storey Robert F. , Becker Richard C. , Balduini Alessandra , Nylander Sven , Cattaneo Marco
Published: September 2016

Ticagrelor is an antagonist of the platelet P2Y12 receptor for ADP, approved for the prevention of thromboembolic events in patients with acute coronary syndrome. Previous studies showed that ticagrelor has no significant activity versus P1 receptors for adenosine and other known P2Y receptors, with the exception of P2Y13, which was not tested. The P2Y12 antagonist cangrelor has been shown to also inhibit P2Y13 and to decrease the P2Y13-regulated capacity of megakaryocytes to produce pro-platelets. We tested whether or not ticagrelor inhibits P2Y13 signalling and function. The in vitro effects of ticagrelor, its active (TAM) and inactive (TIM) metabolites, cangrelor and the P2Y13 antagonist MRS2211 were tested in two experimental models: 1) a label-free cellular response assay in P2Y13-transfected HEK293 T-REx cells; and 2) pro-platelet formation by human megakaryocytes in culture. Ticagrelor, TAM, cangrelor and MRS2211, but not TIM, inhibited the cellular responses in P2Y13-transfected cells. In contrast, only MRS2211 and cangrelor, confirming previous results, inhibited pro-platelet formation by megakaryocytes in vitro. The platelet count of patients randomised to treatment with ticagrelor in the PLATO trial did not change during treatment and was comparable to those of patients randomised to clopidogrel. In conclusion, ticagrelor and TAM act as P2Y13 antagonists in a transfected cell system in vitro but this does not translate into any impact on pro-platelet formation in vitro or altered platelet count in patients.
ADAMTS13 deficiency promotes microthrombosis in a murine model of diet-induced liver steatosis
Authors: Geys Lotte , Bauters Dries , Roose Elien , Tersteeg Claudia , Vanhoorelbeke Karen , Hoylaerts Marc F. , Scroyen Ilse , Lijnen Roger H.
Published: September 2016

ADAMTS13 cleaves ultralarge multimeric von Willebrand Factor (VWF), thereby preventing formation of platelet-rich microthrombi. ADAMTS13 is mainly produced by hepatic stellate cells, and numerous studies have suggested a functional role of ADAMTS13 in the pathogenesis of liver diseases. The aim of our study was to investigate a potential role of ADAMTS13 in formation of hepatic microthrombi and development of non-alcoholic steatohepatitis (NASH), and furthermore to evaluate whether plasmin can compensate for the absence of ADAMTS13 in removal of thrombi. Therefore, we used a model of high-fat diet-induced steatosis in Adamts13 deficient (Adamts13−/−) and wild-type (WT) control mice. Microthrombi were more abundant in the liver of obese Adamts13−/− as compared to obese WT or to lean Adamts13−/− mice. Obese Adamts13−/− mice displayed lower platelet counts and higher prevalence of ultra-large VWF multimers. Hepatic plasmin-α2-antiplasmin complex levels were comparable for obese WT and Adamts13−/− mice and were lower for lean Adamts13−/− than WT mice, not supporting marked activation of the fibrinolytic system. High fat diet feeding, as compared to normal chow, resulted in enhanced liver triglyceride levels for both genotypes (p < 0.0001) and steatosis (p < 0.0001 for WT mice, p = 0.002 for Adamts13−/− mice) without differences between the genotypes. Expression of markers of inflammation, oxidative stress, steatosis and fibrosis was affected by diet, but not by genotype. Thus, our data confirm that obesity promotes NASH, but do not support a detrimental role of ADAMTS13 in its development. However, Adamts13 deficiency in obese mice promotes hepatic microthrombosis, whereas a compensatory role of plasmin in removal of microthrombi in the absence of ADAMTS13 could not be demonstrated.
Associação entre níveis de atividade física e polifarmácia em pacientes hipertensos
Authors: Bueno Denise R. , Monteiro Henrique L. , Rosa Clara S. C. , Codogno Jamile S. , Fernandes Rômulo A. , Marucci Maria F. N.
Published: September 2016

Introdução: o exercício reduz o uso de medicamentos em indivíduos hipertensos. Contudo, diferentes domínios de atividade física (AF) não têm sido estudados no intuito de analisar suas relações com o uso de múltiplos medicamentos, conhecido como polifarmácia. Objetivo: analisar a associação entre AF em diferentes domínios (tempo livre, locomoção e ocupação) e polifarmácia em indivíduos hipertensos. Métodos: trata-se de um estudo transversal realizado com 190 hipertensos. Polifarmácia foi definida como o uso simultâneo de três ou mais drogas. As variáveis independentes foram os domínios de AF: Locomoção (AFL); Tempo Livre (AFTL) e Ocupacional (AFO). A regressão logística múltipla foi empregada para analisar as associações. O teste de Mann Whitney foi empregado para comparar se a média de medicamentos usados diferia entre domínios de AF. Resultados: o número total de drogas usadas variou de 0 a 7, com média de 2.35 (±1.6) por pessoa. Escores de AFTL (OR: 3.25; IC95%: 1.61-6.54) e AFL (OR: 2.15; IC95%: 1.09-4.25) foram inversamente associadas à polifarmácia em hipertensos (controlado por IMC, número de doenças crônicas, fumo, consumo de álcool e cor da pele). Conclusão: menor AF no tempo livre e de locomoção foi associada à polifarmácia em indivíduos hipertensos
The tuberculosis recurrence in city of Jundiaí since 2006 to 2011: a clinical and epidemiological profile
Authors: Bardou Maine L. D. , Ervolino Sandra , Martins Filho Iran S. P. , Yang Hyun M. , Passos Saulo D.
Published: September 2016

The TB recurrence occurs when a patient presents current diagnosis of tuberculosis with positive bacteriology ( microscopy or culture) , with history of cured TB with anti -TB drugs. Evaluation of the clinical and epidemiological aspects of TB recurrence is extremely important, because this data is able to guide and clarify the effectiveness of DOTS ( Directly Observed Treatment Short), the pharmacological treatment regimen used and the predisposing factors for recurrence. Objective: Describe some characteristics of clinical and epidemiological profile of tuberculosis recurrence in Jundiaí in the period 2006-2011. Methods: This is a descriptive study, type of survey data from the Officer of the Ministry of health of Brazil named Tbweb. Results: In the period from 2006 to 2011 were reported 34 cases of recurrence, all pacients being residents in the city of Jundiaí. The median age was 51 ± 17.5 years. The serology for human immunodeficiency virus (HIV ) was performed in 34 (100 %) patients and was positive in 10 ( 29.4%) of them. For other comorbidities 6 (17.6%) cases were alcoholics, and 1 (2.9%) , drug user. The quadruple regimen ( rifampicin , isoniazid , pyrazinamide , ethambutol ) drugs was adopted since 2006. The Strategy Directly Observed Treatment ( DOTS) was held in 21 cases ( 61.7 % ) . The pulmonary type was the most common, presenting 82.3 % of cases. Tb laboratory tests were positive in 17 ( 50.0 %) cases of pulmonary involvement , and 6 ( 17.6 %) cases of extrapulmonary involvement. The duration of treatment was on average 6.5 mounths. The pharmacological treatment ended with 29 cases (85.2 %) cured , 2 ( 5.9%) with treatment neglect and 1 (2.9%) death due to tuberculosis. Conclusion: The relapse of TB was more common in HIV-positive patients. The job of the quadruple (rifampicin , isoniazid , pyrazinamide , ethambutol ) schema in the treatment showed no reduction in the number of cases of TB recurrence of this sample. The use of DOTS had no impact on the cases of relapse in the municipality of Jundiaí. However, new studies with longer historical series must be carried out to check their epidemiological significance appropriate
Saúde ocular dos povos indígenas do Brasil
Authors: Biberg-Salum Tânia Gisela , Rodrigues Maria de Lourdes Veronese
Published: September 2016

Quanto à saúde ocular indígena, há escassez de relatos de avaliações em índios brasileiros e, por isso, o objetivo deste estudo é apresentar uma contextualização desta situação no Brasil, baseada em revisão da bibliografia. São apresentados os mais variados resultados de pesquisas, que datam desde 1897 até os dias atuais, sendo que, o maior número desses artigos publicados está relacionado com problemas apresentados pelas etnias residentes na região Amazônica. Muitas averiguações são feitas de maneira pontual, tanto em relação aos aspectos temporais quanto espaciais, o que dificulta que se tenham conclusões comparativas. Portanto, é importante que sejam realizadas avaliações sistematizadas e continuadas que possam orientar políticas públicas no que tange à saúde ocular desses povos
Economic Impact of Moderate‐Vigorous Physical Activity Among Those With and Without Established Cardiovascular Disease: 2012 Medical Expenditure Panel Survey
Authors: Valero‐Elizondo Javier , Salami Joseph A. , Osondu Chukwuemeka U. , Ogunmoroti Oluseye , Arrieta Alejandro , Spatz Erica S. , Younus Adnan , Rana Jamal S. , Virani Salim S. , Blankstein Ron , Blaha Michael J. , Veledar Emir , Nasir Khurram
Published: September 2016

Background

Physical activity (
PA
) has an established favorable impact on cardiovascular disease (
CVD
) outcomes and quality of life. In this study, we aimed to estimate the economic effect of moderate‐vigorous
PA
on medical expenditures and utilization from a nationally representative cohort with and without
CVD
.

Methods and Results

The 2012 Medical Expenditure Panel Survey data were analyzed. Our study population was limited to noninstitutionalized
US
adults ≥18 years of age. Variables of interest included
CVD
(coronary artery disease, stroke, heart failure, dysrhythmias, or peripheral artery disease) and cardiovascular modifiable risk factors (
CRF
s; hypertension, diabetes mellitus, hypercholesterolemia, smoking, and/or obesity). Two‐part econometric models were utilized to study cost data; a generalized linear model with gamma distribution and link log was used to assess expenditures per capita. The final study sample included 26 239 surveyed individuals. Overall, 47% engaged in moderate‐vigorous
PA
≥30 minutes, ≥5 days/week, translating to 111.5 million adults in the United States stratifying by
CVD
status; 32% reported moderate‐vigorous
PA
among those with
CVD
versus 49% without
CVD
. Generally, participants reporting moderate‐vigorous
PA
incurred significantly lower health care expenditures and resource utilization, displaying a step‐wise lower total annual health care expenditure as moving from
CVD
to non‐
CVD
(and each
CRF
category).

Conclusions

Moderate‐vigorous
PA
≥30 minutes, ≥5 days/week is associated with significantly lower health care spending and resource utilization among individuals with and without established
CVD
.
Mortality Risk Among Heart Failure Patients With Depression: A Nationwide Population‐Based Cohort Study
Authors: Adelborg Kasper , Schmidt Morten , Sundbøll Jens , Pedersen Lars , Videbech Poul , Bøtker Hans Erik , Egstrup Kenneth , Sørensen Henrik Toft
Published: September 2016

Background

The prevalence of depression is 4‐ to 5‐fold higher in heart failure patients than in the general population. We examined the influence of depression on all‐cause mortality in patients with heart failure.

Methods and Results

Using Danish medical registries, this nationwide population‐based cohort study included all patients with a first‐time hospitalization for heart failure (1995–2014). All‐cause mortality risks and 19‐year mortality rate ratios were estimated based on Cox regression analysis, adjusting for age, sex, time period, comorbidity, and socioeconomic status. The analysis included 9636 patients with and 194 887 patients without a diagnosis of depression. Compared with patients without a history of depression, those with depression had higher 1‐year (36% versus 33%) and 5‐year (68% versus 63%) mortality risks. Overall, the adjusted mortality rate ratio was 1.03 (95% CI 1.01–1.06). Compared with no depression, the adjusted mortality rate ratios for mild, moderate, and severe depression, as defined by diagnostic codes, were 1.06 (95%
CI
1.00–1.13), 1.03 (95%
CI
0.99–1.08), and 1.02 (95%
CI
0.96–1.09), respectively. In a subcohort of patients, the mortality rate ratios were modified by left ventricular ejection fraction, with adjusted mortality rate ratios of 1.17 (95%
CI
, 1.05–1.31) for ≤35%, 0.98 (95%
CI
0.81–1.18) for 36% to 49%, and 0.96 (95%
CI
0.74–1.25) for ≥50%. Results were consistent after adjustment for alcohol abuse and smoking.

Conclusions

A history of depression was an adverse prognostic factor for all‐cause mortality in heart failure patients with left ventricular ejection fraction ≤35% but not for other heart failure patients.
Incarnation without the Fall
Authors: Crisp Oliver D.
Published: September 2016

An important Christological question is whether the incarnation depends on human sin. This paper sets out one version of an “incarrnation anyway” doctrine, i.e. the view according to which Christ would have been incarnate without a fall (an issue that has begun to receive more attention in the recent theological literature). This version of incarnation anyway I call the christological union account. It is argued that far from being theologically speculative in a pejorative sense, the christological union account sheds important light upon several related issues such as the image of God, and God’s ultimate end in creating the world. After setting out the doctrine in an extended narrative, some of the principal reasons in favor of the view and against it are weighed up.
Can We Still Sing the Lyrics “Come Holy Spirit”?
Authors: Riches Tanya
Published: September 2016

Australian Pentecostals, both Indigenous and non-Indigenous, are speaking new tongues in their worship practices, forming new poetic languages of singing and conversation relevant for spatially dislocated twenty-first-century life. Using Nimi Wariboko’s three-city model offered in Charismatic City and the Public Resurgence of Religion, this article assesses Australian pentecostal worship practice in light of his “Charismatic City.” The article suggests that this emergent, poetic language of Spirit empowerment situates the worshipper in a rhizomatic network that flows with pentecostal energies, forming a new commons or space that is the basis of its global civil society. It presents two local case studies from Hillsong Church’s pneumatological song repertoire (1996–2006), and yarning conversation rituals at Ganggalah Church led by Aboriginal Australian pastors. These new languages identify and attune participants to the Spirit’s work in the world, particularly useful for urban cities and cyberspace.
Three new species of anthracine bee flies (Diptera: Bombyliidae) from Egypt
Authors: EL-HAWAGRY MAGDI S.
Published: September 2016

Three new anthracine species of Bombyliidae are described. Two of these species (Anthrax galali El-Hawagry, sp. nov. and Anthrax zohrayensis El-Hawagry, sp. nov.) were proposed by Efflatoun Bey in his unpublished manuscript in the genus Anthrax Scopoli (sensu lato). These species names are maintained but the descriptions are shortened and revised. A third species, not included in Efflatoun unpublished manuscript, Spogostylum hamadnallahi El-Hawagry, sp. nov., is herein described and illustrated.
Checklist of the marine fishes of Turkey
Authors: BILECENOGLU MURAT , TASKAVAK ERTAN , MATER SAVAS , KAYA MURAT
Published: September 2016

A checklist of the marine fish fauna of Turkey is presented for the first time. Examination of the previous studies revealed the presence of 448 species in 133 families. A total of 45 species, that has a doubtful presence at Turkish seas, was briefly discussed. The ichthyofaunal similarities of seas surrounding Turkey were compared, and the Black Sea and the Sea of Marmara were found to be 55.6% similar, whereas, the proportion computed for the Aegean and the Mediterranean Sea was 83.2%.
Paranarthrura Hansen, 1913 (Crustacea: Tanaidacea) from the Angola Basin, description of Paranarthrura angolensis n. sp.
Authors: GUERRERO-KOMMRITZ JÜRGEN , SCHMIDT ANJA , BRANDT ANGELIKA
Published: September 2016

Tanaidacea were collected from board of RV Meteor (M48) and RV Atlantis II (42) in the deep Angola Basin. Within the samples containing Tanaidacea, one species of Paranarthrura could be identified, Paranarthrura angolensis n.sp, which is described on the basis of 42 individuals from depths between 631 to 5464 m off the deep Angola Basin, South Atlantic Ocean. Until now, 10 species of Paranarthrura are reported from the Atlantic Ocean. Data on the distribution of these species are presented.
Scottia birigida sp. nov. (Cypridoidea: Ostracoda) from western Honshu, Japan and a key to the subfamily Scottiinae Bronstein, 1947
Authors: SMITH ROBIN J. , MATZKE-KARASZ RENATE , KAMIYA TAKAHIRO , IKEDA YOSHINORI
Published: September 2016

A new species of the ostracod genus Scottia Brady and Norman, 1889 from Kanazawa, western Honshu, Japan is described. This species is only the third living representative of this genus. It is most similar to the populations of S. pseudobrowniana Kempf, 1971 from western Europe, but it is smaller, and has unique features of the hemipenes, Zenker organs, antennae and mandibles. A prominent projection on the dorsal lobe of the hemipenes gives this species its name, Scottia birigida sp. nov.. It lives in wet leaf litter around the discharge of a spring, leading a semi-terrestrial lifestyle. This is the first record of Scottia and the subfamily Scottiinae Bronstein, 1947 from Japan and North East Asia, and significantly increases the known distribution of these taxa. This record of Scottia from Japan, together with numerous reports from Europe and two areas in the USA, indicates that in the northern hemisphere this genus is probably widespread. A key to the subfamily Scottiinae is also provided.
Two new water mite species from Iran of the water mite families Torrenticolidae and Hygrobatidae (Acari: Hydrachnidia)
Authors: PESIC VLADIMIR M. , ASADI MAHDIEH
Published: September 2016

Two water mite species (Acari: Hydrachnidia) are reported from the Kerman area (Southeastern Iran). Atractides iranicus and Torrenticola saboorii are described as new species.
Quill mites (Acari: Prostigmata: Syringophilidae) from African passeriform birds
Authors: SKORACKI MACIEJ , SIKORA BOZENA
Published: September 2016

Two new species of quill mites (Acari: Prostigmata: Syringophilidae) collected from passeriform birds from Africa are described and illustrated: Aulobia cisticolae sp. n. from the Red-faced Cisticola Cisticola erythrops (Hartlaub, 1857), the Singing Cisticola C. cantans (Heuglin, 1869) and the Whistling Cisticola C. lateralis (Fraser, 1843) (Sylviidae) and Syringophilopsis corvinae sp. n. from the Yellow-billed Shrike Corvinella corvina (Shaw, 1809) (Laniidae). Two new host species of the family Syrinophilidae are given.
Panurgus platymerus Pérez, 1895 (Hymenoptera: Andrenidae) synonymy, status of the Warncke lectotype
Authors: PATINY SEBASTIEN
Published: September 2016

The usual definition of Panurgus platymerus Pérez, 1895 does not fit the lectotype designated by Warncke in the Pérez collection. We propose here to place the specimens previously determined as Panurgus platymerus under the name Panurgus pyropygus Friese, 1901. Panurgus platymerus will be reserved for specimens of a large North-African species close to Panurgus cephalotes Latreille, 1811.
Odontamblyopus rebecca, a new species of amblyopine goby from Vietnam with a key to known species of the genus (Gobiidae: Amblyopinae)
Authors: MURDY EDWARD O. , SHIBUKAWA KOICHI
Published: September 2016

A new species of amblyopine goby, Odontamblyopus rebecca, is described on the basis of 37 specimens from Vietnam. It differs from other species of Odontamblyopus by the following combination of characters: caudal vertebrae typically 20; dorsal fin with 44-48 total elements; anal fin with 37-42 total elements; and pectoral-fin ray count 40-51. This species is figured and compared with other known species of Odontamblyopus.