bluuebunny/crossref_metadata_2025_split huggingface dataset:
The PDK1 Inhibitor Dichloroacetate Controls Cholesterol Homeostasis Through the ERK5/MEF2 Pathway
Authors: Khan Abrar Ul Haq , Allende-Vega Nerea , Gitenay Delphine , Gerbal-Chaloin Sabine , Gondeau Claire , Vo Dang-Nghiem , Belkahla Sana , Orecchioni Stefania , Talarico Giovanna , Bertolini Francesco , Bozic Milica , Valdivielso Jose M. , Bejjani Fabienne , Jariel Isabelle , Lopez-Mejia Isabel C. , Fajas Lluis , Lecellier Charles-Henri , Hernandez Javier , Daujat Martine , Villalba Martin 
Published: August 2017

AbstractControlling cholesterol levels is a major challenge in human health, since hypercholesterolemia can lead to serious cardiovascular disease. Drugs that target carbohydrate metabolism can also modify lipid metabolism and hence cholesterol plasma levels. In this sense, dichloroacetate (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, augments usage of the glycolysis-produced pyruvate in the mitochondria increasing oxidative phosphorylation (OXPHOS). In several animal models, DCA decreases plasma cholesterol and triglycerides. Thus, DCA was used in the 70 s to treat diabetes mellitus, hyperlipoproteinemia and hypercholesterolemia with satisfactory results. However, the mechanism of action remained unknown and we describe it here. DCA increases LDLR mRNA and protein levels as well as LDL intake in several cell lines, primary human hepatocytes and two different mouse models. This effect is mediated by transcriptional activation as evidenced by H3 acetylation on lysine 27 on the LDLR promoter. DCA induces expression of the MAPK ERK5 that turns on the transcription factor MEF2. Inhibition of this ERK5/MEF2 pathway by genetic or pharmacological means decreases LDLR expression and LDL intake. In summary, our results indicate that DCA, by inducing OXPHOS, promotes ERK5/MEF2 activation leading to LDLR expression. The ERK5/MEF2 pathway offers an interesting pharmacological target for drug development.
MAP kinase-interacting serine/threonine kinase 2 promotes proliferation, metastasis, and predicts poor prognosis in non-small cell lung cancer
Authors: Guo Zhihua , Peng Guilin , Li Ermao , Xi Shaoyan , Zhang Yu , Li Yong , Lin Xiaodong , Li Guangqiu , Wu Qinian , He Jianxing 
Published: August 2017

AbstractWe hypothesized that MAP kinase-interacting serine/threonine kinase 2 (MNK2) may contribute to non-small cell lung cancer (NSCLC) development, and serve as a new therapeutic target. Immunohistochemical staining evaluated the correlation between MNK2 expression and clinicopathological features in 367 NSCLC cancer tissues. We determined the effects of MNK2 silencing in NSCLC cell lines in vitro and in vivo. RT-PCR and western blotting was used to examine the impact of MNK2 on ERK and AKT pathways. MNK2 was overexpressed in NSCLC cell lines and tumor tissues. Patients with MNK2 overexpression had lower OS rates (P < 0.001). High expression of MNK2 was correlated with lymph node metastasis (P = 0.008). MNK2 functioned as an independent prognostic factor for poor survival in patients with NSCLC (P = 0.003). MNK2 down-regulation inhibited proliferation, migration and invasion in vitro (P < 0.001), and reduced tumor growth and invasion in nude mice (P < 0.05). MNK2 enhanced phosphorylation of eIF4E, a downstream target of ERK and AKT pathways, which promoted NSCLC proliferation and invasion. We conclude that MNK2 overexpression in NSCLC is associated with proliferation, migration, invasion, and lower survival rates in patients via the phosphorylated eIF4E-mediated signaling pathway.
Carbonyl reductase 1 catalyzes 20β-reduction of glucocorticoids, modulating receptor activation and metabolic complications of obesity
Authors: Morgan Ruth A. , Beck Katharina R. , Nixon Mark , Homer Natalie Z. M. , Crawford Andrew A. , Melchers Diana , Houtman René , Meijer Onno C. , Stomby Andreas , Anderson Anna J. , Upreti Rita , Stimson Roland H. , Olsson Tommy , Michoel Tom , Cohain Ariella , Ruusalepp Arno , Schadt Eric E. , Björkegren Johan L. M. , Andrew Ruth , Kenyon Christopher J. , Hadoke Patrick W. F. , Odermatt Alex , Keen John A. , Walker Brian R. 
Published: August 2017

AbstractCarbonyl Reductase 1 (CBR1) is a ubiquitously expressed cytosolic enzyme important in exogenous drug metabolism but the physiological function of which is unknown. Here, we describe a role for CBR1 in metabolism of glucocorticoids. CBR1 catalyzes the NADPH- dependent production of 20β-dihydrocortisol (20β-DHF) from cortisol. CBR1 provides the major route of cortisol metabolism in horses and is up-regulated in adipose tissue in obesity in horses, humans and mice. We demonstrate that 20β-DHF is a weak endogenous agonist of the human glucocorticoid receptor (GR). Pharmacological inhibition of CBR1 in diet-induced obesity in mice results in more marked glucose intolerance with evidence for enhanced hepatic GR signaling. These findings suggest that CBR1 generating 20β-dihydrocortisol is a novel pathway modulating GR activation and providing enzymatic protection against excessive GR activation in obesity.
Mild intracellular acidification by dexamethasone attenuates mitochondrial dysfunction in a human inflammatory proximal tubule epithelial cell model
Authors: Schirris T. J. J. , Jansen J. , Mihajlovic M. , van den Heuvel L. P. , Masereeuw R. , Russel F. G. M. 
Published: August 2017

AbstractSeptic acute kidney injury (AKI) associates with poor survival rates and often requires renal replacement therapy. Glucocorticoids may pose renal protective effects in sepsis via stimulation of mitochondrial function. Therefore, we studied the mitochondrial effects of dexamethasone in an experimental inflammatory proximal tubule epithelial cell model. Treatment of human proximal tubule epithelial cells with lipopolysaccharide (LPS) closely resembles pathophysiological processes during endotoxaemia, and led to increased cytokine excretion rates and cellular reactive oxygen species levels, combined with a reduced mitochondrial membrane potential and respiratory capacity. These effects were attenuated by dexamethasone. Dexamethasone specifically increased the expression and activity of mitochondrial complex V (CV), which could not be explained by an increase in mitochondrial mass. Finally, we demonstrated that dexamethasone acidified the intracellular milieu and consequently reversed LPS-induced alkalisation, leading to restoration of the mitochondrial function. This acidification also provides an explanation for the increase in CV expression, which is expected to compensate for the inhibitory effect of the acidified environment on this complex. Besides the mechanistic insights into the beneficial effects of dexamethasone during renal cellular inflammation, our work also supports a key role for mitochondria in this process and, hence, provides novel therapeutic avenues for the treatment of AKI.
Lactoferrin-derived Peptides Active towards Influenza: Identification of Three Potent Tetrapeptide Inhibitors
Authors: Scala Maria Carmina , Sala Marina , Pietrantoni Agostina , Spensiero Antonia , Di Micco Simone , Agamennone Mariangela , Bertamino Alessia , Novellino Ettore , Bifulco Giuseppe , Gomez-Monterrey Isabel M. , Superti Fabiana , Campiglia Pietro 
Published: August 2017

AbstractBovine lactoferrin is a biglobular multifunctional iron binding glycoprotein that plays an important role in innate immunity against infections. We have previously demonstrated that selected peptides from bovine lactoferrin C-lobe are able to prevent both Influenza virus hemagglutination and cell infection. To deeper investigate the ability of lactoferrin derived peptides to inhibit Influenza virus infection, in this study we identified new bovine lactoferrin C-lobe derived sequences and corresponding synthetic peptides were synthesized and assayed to check their ability to prevent viral hemagglutination and infection. We identified three tetrapeptides endowed with broad anti-Influenza activity and able to inhibit viral infection in a concentration range femto- to picomolar. Our data indicate that these peptides may constitute a non-toxic tool for potential applications as anti-Influenza therapeutics.
Inhibition of SHIP2 in CD2AP-deficient podocytes ameliorates reactive oxygen species generation but aggravates apoptosis
Authors: Saurus Pauliina , Tolvanen Tuomas A. , Lindfors Sonja , Kuusela Sara , Holthöfer Harry , Lehtonen Eero , Lehtonen Sanna 
Published: August 2017

AbstractLack of CD2-associated protein (CD2AP) in mice increases podocyte apoptosis and leads to glomerulosclerosis and renal failure. We showed previously that SHIP2, a negative regulator of the PI3K/AKT signalling pathway, interacts with CD2AP. Here, we found that the expression level and activity of SHIP2 and production of reactive oxygen species (ROS) are increased in cultured CD2AP knockout (CD2AP−/−) mouse podocytes. Oxidative stress was also increased in CD2AP−/− mouse glomeruli in vivo. We found that puromycin aminonucleoside (PA), known to increase ROS production and apoptosis, increases SHIP2 activity and reduces CD2AP expression in cultured human podocytes. PDK1 and CDK2, central regulators of AKT, were downregulated in CD2AP−/− or PA-treated podocytes. Downregulation of PDK1 and CDK2, ROS generation and apoptosis were prevented by CD2AP overexpression in both models. Notably, inhibition of SHIP2 activity with a small molecule inhibitor AS1949490 ameliorated ROS production in CD2AP−/− podocytes, but, surprisingly, further reduced PDK1 expression and aggravated apoptosis. AKT- and ERK-mediated signalling was diminished and remained reduced after AS1949490 treatment in the absence of CD2AP. The data suggest that inhibition of the catalytic activity of SHIP2 is beneficial in reducing oxidative stress, but leads to deleterious increase in apoptosis in podocytes with reduced expression of CD2AP.
Effects of biochar, waste water irrigation and fertilization on soil properties in West African urban agriculture
Authors: Häring Volker , Manka’abusi Delphine , Akoto-Danso Edmund K. , Werner Steffen , Atiah Kofi , Steiner Christoph , Lompo Désiré J. P. , Adiku Samuel , Buerkert Andreas , Marschner Bernd 
Published: August 2017

AbstractIn large areas of sub-Saharan Africa crop production must cope with low soil fertility. To increase soil fertility, the application of biochar (charred biomass) has been suggested. In urban areas, untreated waste water is widely used for irrigation because it is a nutrient-rich year-round water source. Uncertainty exists regarding the interactions between soil properties, biochar, waste water and fertilization over time. The aims of this study were to determine these interactions in two typical sandy, soil organic carbon (SOC) and nutrient depleted soils under urban vegetable production in Tamale (Ghana) and Ouagadougou (Burkina Faso) over two years. The addition of biochar at 2 kg m−2 made from rice husks and corn cobs initially doubled SOC stocks but SOC losses of 35% occurred thereafter. Both biochar types had no effect on soil pH, phosphorous availability and effective cation exchange capacity (CEC) but rice husk biochar retained nitrogen (N). Irrigation with domestic waste water increased soil pH and exchangeable sodium over time. Inorganic fertilization alone acidified soils, increased available phosphorous and decreased base saturation. Organic fertilization increased SOC, N and CEC. The results from both locations demonstrate that the effects of biochar and waste water were less pronounced than reported elsewhere.
Caveolin-1 Protects Retinal Ganglion Cells against Acute Ocular Hypertension Injury via Modulating Microglial Phenotypes and Distribution and Activating AKT pathway
Authors: Zhang Liwei , Xu Jiazhou , Liu Ran , Chen Wei , Chen Qishan , Hu Wenjie , Zhou Lan , Zhang Ruting , Xu Hongping , Lin Dongyue , Li Xuri , Tang Zhongshu 
Published: August 2017

AbstractGlaucoma, a group of eye diseases, causes gradual loss of retinal ganglion cells (RGCs) and ultimately results in irreversible blindness. Studies of the underlying mechanisms of glaucoma and clinical trial are far from satisfactory. Results from a genome-wide association study have suggested that the CAV1/CAV2 locus is associated with glaucoma, but this association and its potential underlying mechanisms need to be confirmed and further explored. Here, we studied the function of caveolin-1 (Cav1) in an acute ocular hypertension glaucoma model. Cav1 deficiency caused an aggregated lesion in the retina. In addition, treatment with cavtratin, a membrane permeable Cav1 scaffolding domain peptide, enhanced RGC survival. After cavtratin treatment, microglial numbers decreased significantly, and the majority of them migrated from the inner retinal layer to the outer retinal layers. Furthermore, cavtratin promoted a change in the microglia phenotype from the neurotoxic pro-inflammatory M1 to the neuroprotective anti-inflammatory M2. In a molecular mechanism experiment, we found that cavtratin activated the phosphorylation of both AKT and PTEN in cultured N9 cells. Our data highlights the neuroprotective effect of Cav1 on acute ocular hypertension and suggests that Cav1 may serve as a novel therapeutic target for the treatment of glaucoma. We further propose that cavtratin is a therapeutic candidate for glaucoma clinical trials.
Scatter-plate microscope for lensless microscopy with diffraction limited resolution
Authors: Singh Alok Kumar , Pedrini Giancarlo , Takeda Mitsuo , Osten Wolfgang 
Published: August 2017

AbstractScattering media have always been looked upon as an obstacle in imaging. Various methods, ranging from holography to phase compensation as well as to correlation techniques, have been proposed to cope with this obstacle. We, on the other hand, have a different understanding about the role of the diffusing media. In this paper we propose and demonstrate a ‘scatter-plate microscope’ that utilizes the diffusing property of the random medium for imaging micro structures with diffraction-limited resolution. The ubiquitous property of the speckle patterns permits to exploit the scattering medium as an ultra-thin lensless microscope objective with a variable focal length and a large working distance. The method provides a light, flexible and cost effective imaging device as an alternative to conventional microscope objectives. In principle, the technique is also applicable to lensless imaging in UV and X-ray microscopy. Experiments were performed with visible light to demonstrate the microscopic imaging of USAF resolution test target and a biological sample with varying numerical aperture (NA) and magnifications.
Calaxin establishes basal body orientation and coordinates movement of monocilia in sea urchin embryos
Authors: Mizuno Katsutoshi , Shiba Kogiku , Yaguchi Junko , Shibata Daisuke , Yaguchi Shunsuke , Prulière Gérard , Chenevert Janet , Inaba Kazuo 
Published: August 2017

AbstractThrough their coordinated alignment and beating, motile cilia generate directional fluid flow and organismal movement. While the mechanisms used by multiciliated epithelial tissues to achieve this coordination have been widely studied, much less is known about regulation of monociliated tissues such as those found in the vertebrate node and swimming planktonic larvae. Here, we show that a calcium sensor protein associated with outer arm dynein, calaxin, is a critical regulator for the coordinated movements of monocilia. Knockdown of calaxin gene in sea urchin embryos results in uncoordinated ciliary beating and defective directional movement of the embryos, but no apparent abnormality in axoneme ultrastructure. Examination of the beating cycle of individual calaxin-deficient cilia revealed a marked effect on the waveform and spatial range of ciliary bending. These findings indicate that calaxin-mediated regulation of ciliary beating is responsible for proper basal body orientation and ciliary alignment in fields of monociliated cells.
A novel role of the soybean clock gene LUX ARRHYTHMO in male reproductive development
Authors: Liew Lim Chee , Singh Mohan B. , Bhalla Prem L. 
Published: August 2017

AbstractThe evening complex of ELF4-ELF3-LUX proteins is an integral component of a plant circadian clock. LUX ARRHYTHMO (LUX) is one of the key components of the evening complex, and that play a key role in circadian rhythms and flowering. Here, we report that diverged soybean LUX has the additional role in male reproductive development. We studied diurnal and circadian rhythms of soybean LUX (GmLUXa, GmLUXb, and GmLUXc) using qRT-PCR, and show its nuclear localisation by particle bombardment. Yeast-two hybrid (Y2H) studies indicate that both GmLUXb and GmLUXc form an evening complex with GmELF4b and GmELF3a, respectively. Ectopic expression of GmLUXb in Arabidopsis lux mutants can complement functions of AtLUX, whereas GmLUXc generates novel phenotypes of serrated leaves, stunted plants, shortened anther filament, and low seed set. Overall, our results suggest that the LUX gene has diverged in soybean where GmLUXb and GmLUXc share the role to control flowering time, but GmLUXc has evolved to regulate anther filament growth and seed set by regulating the Gibberellin hormone biosynthesis pathway.
Peptide-mediated delivery of donor mitochondria improves mitochondrial function and cell viability in human cybrid cells with the MELAS A3243G mutation
Authors: Chang Jui-Chih , Hoel Fredrik , Liu Ko-Hung , Wei Yau-Huei , Cheng Fu-Chou , Kuo Shou-Jen , Tronstad Karl Johan , Liu Chin-San 
Published: August 2017

AbstractThe cell penetrating peptide, Pep-1, has been shown to facilitate cellular uptake of foreign mitochondria but further research is required to evaluate the use of Pep-1-mediated mitochondrial delivery (PMD) in treating mitochondrial defects. Presently, we sought to determine whether mitochondrial transplantation rescue mitochondrial function in a cybrid cell model of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) disease. Following PMD, recipient cells had internalized donor mitochondria after 1 h, and expressed higher levels of normal mitochondrial DNA, particularly at the end of the treatment and 11 days later. After 4 days, mitochondrial respiratory function had recovered and biogenesis was evident in the Pep-1 and PMD groups, compared to the untreated MELAS group. However, only PMD was able to reverse the fusion-to-fission ratio of mitochondrial morphology, and mitochondria shaping proteins resembled the normal pattern seen in the control group. Cell survival following hydrogen peroxide-induced oxidative stress was also improved in the PMD group. Finally, we observed that PMD partially normalized cytokine expression, including that of interleukin (IL)-7, granulocyte macrophage–colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF), in the MELAS cells. Presently, our data further confirm the protective effects of PMD as well in MELAS disease.
The influence of the mating type on virulence of Mucor irregularis
Authors: Xu Wenqi , Liang Guanzhao , Peng Jingwen , Long Zhimin , Li Dongmei , Fu Meihua , Wang Qiong , Shen Yongnian , Lv Guixia , Mei Huan , Tsui Clement K. M. , Liu Weida 
Published: August 2017

AbstractMucor irregularis is an emerging fungal pathogen that cause cutaneous infection and could cause death. However, little is known about its mechanism of pathogenesis. There is evidence suggesting virulence vary with mating types in fungi, including the Mucorales. Here, we characterized the mating type locus of M. irregularis and the mating type ratio of 17 clinical isolates in China. Genomic data indicated M. irregularis is heterothallic having two mating types – bearing either SexP or SexM allele. Also, we employed a mice model to study the inflammation and pathological effects of different mating types. The comparison of the inflammatory response, cytokine profiles and Th-1, Th-2 and Th-17 cells numbers in each mating type treated mice showed that the severity and disease progress were enhanced in (+) mating type treated mice. One (+/0) mutant strain, with multiple mutations at the mating locus, had defects in sexual mating ability but appeared to be more virulent than the (−) mating type. Although (+) mating type appeared to be more virulent, most of our clinical isolates presented belonged to (−) mating type. Our findings support the involvement of MAT genes in sexual fertility, and the influence of mating type on the severity of cutaneous infection.
RETRACTED ARTICLE: Accelerated oral wound healing using a pre-vascularized mucosal cell sheet
Authors: Lee Jaewang , Kim Eun Hye , Shin Daiha , Roh Jong-Lyel 
Published: August 2017

AbstractCell sheets with pre-vascularization have recently been developed but remain relatively untested in oral wound healing. Therefore, we examined the potential utility of our newly developed pre-vascularized mucosal cell sheets in oral wound healing. Mucosal keratinocytes, fibroblasts, and endothelial progenitor cells were primarily cultured for in vitro cell expansion from mucosa and blood of Sprague-Dawley rats. Mucosal cell sheets were generated using cultured keratinocytes and plasma fibrin (K sheet) or keratinocytes and a mixture of fibrin, fibroblasts, and endothelial cells (PV sheet). Autologous sheets were transplanted on deep wounds in the buccal region of rats. The gross and histological characteristics of wound healing were compared among control wound, K sheet, and PV sheet groups. We successfully cultured and expanded keratinocytes, fibroblasts, and endothelial progenitor cells in vitro for generating mucosal cell sheets with or without pre-vascularization. In the in vivo oral wound model, compared with the control wound, the PV sheet group exhibited rapid wound closure more prominently than the K sheet group. The histological healing in the PV sheet group was similar to that in rat normal buccal mucosa without fibrosis. The pre-vascularized mucosal cell sheet exhibited in vivo efficacy in oral wound healing by promoting accelerated healing.
Impact of phenolic compounds in the acyl homoserine lactone-mediated quorum sensing regulatory pathways
Authors: Hossain Md. Akil , Lee Seung-Jin , Park Na-Hye , Mechesso Abraham Fikru , Birhanu Biruk Tesfaye , Kang JeongWoo , Reza Md. Ahsanur , Suh Joo-Won , Park Seung-Chun 
Published: August 2017

AbstractQuorum sensing (QS) is a cell density-dependent regulation of virulent bacterial gene expression by autoinducers that potentially pertains in the epidemic of bacterial virulence. This study was initially designed to evaluate the effect of 5 phenolic compounds in the modulation of QS and virulence factors of Chromobacterium violaceum and Pseudomonas aeruginosa, and to determine the mechanisms of their effects. Biosensor strains were used to assess antibacterial and anti-QS effect of these compounds. Only methyl gallate (MG) among these compounds demonstrated profound anti-QS effect in the preliminary study, and thus only MG was utilized further to evaluate the effects on the synthesis and activity of acyl homoserine lactone (AHL) in C. violaceum and on the modulation of biofilm, motility, proteolytic, elastase, pyocyanin, and rhamnolipid activity in P. aeruginosa. Finally, the effect of MG on the expression of QS-regulated genes of P. aeruginosa was verified. MG suppressed both the synthesis and activity of AHL in C. violaceum. It also restricted the biofilm formation and other QS-associated virulence factor of P. aeruginosa. MG concentration-dependently suppressed the expression of lasI/R, rhlI/R, and pqsA of P. aeruginosa and was non-toxic in in vitro study. This is the first report of the anti-QS mechanism of MG.