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Rui Santos, Catarina Costa, Dalila Mil-Homens, Daniela Romão, Carla C C R de Carvalho, Pedro Pais, Nuno P Mira, Arsénio M Fialho, Miguel C Teixeira
The mechanisms of persistence and virulence associated to Candida glabrata infections are poorly understood, limiting the ability to fight this fungal pathogen. In this study, the multidrug resistance transporters CgTpo1_1 and CgTpo1_2 are shown to play a role in C. glabrata virulence. The survival of the infection model Galleria mellonella, infected with C. glabrata, was found to increase upon the deletion of either CgTPO1_1 or CgTPO1_2. The underlying mechanisms were further explored. In the case of CgTpo1_1, this phenotype was found to be consistent with the observation that it confers resistance to antimicrobial peptides (AMP), such as the human AMP histatin-5...
October 25, 2016: Cellular Microbiology
Hua-Qiang Zhu, Jin-Ben Ma, Xie Song, Heng-Jun Gao, Chao-Qun Ma, Hong Chang, Hong-Guang Li, Fang-Feng Liu, Jun Lu, Xu Zhou
Metformin, an oral biguanide drug used to treat type 2 diabetes, has displayed anticancer activities in several types of cancer cells. The combination of gemcitabine and cisplatin is the standard chemotherapy regimen for cholangiocarcinoma, but its benefit is limited. The present study aimed to investigate whether metformin could enhance the activities of gemcitabine and cisplatin against cholangiocarcinoma, and the underlying mechanisms. Metformin inhibited the proliferation of human cholangiocarcinoma RBE and HCCC-9810 cells and induced cell cycle arrest at the G0/G1 phase by increasing the activation of AMP-activated protein kinase (AMPK) pathways...
October 20, 2016: Oncology Reports
Wenjie Li, Fei Cao, Juan Li, Zhixin Wang, Yu Ren, Zheyong Liang, Peijun Liu
Simvastatin (SIM), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been reported to inhibit the activity of hepatitis B virus (HBV), however, the mechanism underlying its antiviral function remains unknown. Minichromosome maintenance (MCM) 7, a component of the MCM complex, has been reported to act as an important host factor aiding virus genome replication in host cells. The present study demonstrated that downregulation of MCM7 inhibited the expression of proteins transferred by adenoviral vectors...
October 20, 2016: Molecular Medicine Reports
Luka Dobovišek, Marko Hojnik, Polonca Ferk
The physiological and pathophysiological roles of sex hormones have been well documented and the modulation of their effects is applicable in many current treatments. On the other hand, the physiological role of endocannabinoids is not yet clearly understood and the endocannabinoid system is considered a relatively new therapeutic target. The physiological association between sex hormones and cannabinoids has been investigated in several studies; however, its involvement in the pathophysiology of common human diseases has been studied separately...
October 17, 2016: International Journal of Molecular Medicine
Mahendra Rai, Raksha Pandit, Swapnil Gaikwad, György Kövics
Antimicrobial peptides (AMPs) are diverse group of natural proteins present in animals, plants, insects and bacteria. These peptides are responsible for defense of host from pathogenic organisms. Chemical, enzymatic and recombinant techniques are used for the synthesis of antimicrobial peptides. These peptides have been found to be an alternative to the chemical preservatives. Currently, nisin is the only antimicrobial peptide, which is widely utilized in the preservation of food. Antimicrobial peptides can be used alone or in combination with other antimicrobial, essential oils and polymeric nanoparticles to enhance the shelf-life of food...
September 2016: Journal of Food Science and Technology
Randa Abdel Malik, Nina Zippel, Timo Frömel, Juliana Heidler, Sven Zukunft, Barbara Walzog, Nariman Ansari, Francesco Pampaloni, Susanne Wingert, Michael A Rieger, Ilka Wittig, Beate Fisslthaler, Ingrid Fleming
RATIONALE: The AMP-activated protein kinase (AMPK) is stimulated by hypoxia and while the AMPKα1 catalytic subunit has been implicated in angiogenesis, little is known about the role played by the AMPKα2 subunit in vascular repair. OBJECTIVE: To determine the role of the AMPKα2 subunit in vascular repair. METHODS AND RESULTS: Recovery of blood flow after femoral artery ligation was impaired (>80%) in AMPKα2(-/-) versus wild-type mice, a phenotype reproduced in mice lacking AMPKα2 in myeloid cells (AMPKα2(ΔMC))...
October 24, 2016: Circulation Research
Mark A Hanson, Phineas T Hamilton, Steve J Perlman
BACKGROUND: Drosophila is an important model for studying the evolution of animal immunity, due to the powerful genetic tools developed for D. melanogaster. However, Drosophila is an incredibly speciose lineage with a wide range of ecologies, natural histories, and diverse natural enemies. Surprisingly little functional work has been done on immune systems of species other than D. melanogaster. In this study, we examine the evolution of immune genes in the speciose subgenus Drosophila, which diverged from the subgenus Sophophora (that includes D...
October 24, 2016: BMC Evolutionary Biology
M Mezzelani, S Gorbi, D Fattorini, G d'Errico, M Benedetti, M Milan, L Bargelloni, F Regoli
The aim of the present investigation was to provide new insights on accumulation and possible adverse effects of various non-steroidal anti-inflammatory drugs (NSAIDs) in mussels, Mytilus galloprovincialis, exposed to an environmentally realistic concentration (0.5μg/L) of individual compounds, Acetaminophen (AMP), Diclofenac (DIC), Ibuprofen (IBU), Ketoprofen (KET) or Nimesulide (NIM). The measurement of drugs in mussel tissues was integrated with both functional alterations at cellular level and transcriptomic responses...
October 11, 2016: Aquatic Toxicology
A Blomme, B Costanza, P de Tullio, M Thiry, G Van Simaeys, S Boutry, G Doumont, E Di Valentin, T Hirano, T Yokobori, S Gofflot, O Peulen, A Bellahcène, F Sherer, C Le Goff, E Cavalier, A Mouithys-Mickalad, F Jouret, P G Cusumano, E Lifrange, R N Muller, S Goldman, P Delvenne, E De Pauw, M Nishiyama, V Castronovo, A Turtoi
Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as overexpressed in several cancers and shown to contribute to proliferation, migration and invasion of cancer cells. We have previously demonstrated that myoferlin regulates epidermal growth factor receptor activity in breast cancer. In the current study, we report a consistent overexpression of myoferlin in triple-negative breast cancer cells (TNBC) over cells originating from other breast cancer subtypes...
October 24, 2016: Oncogene
Yongcheng Pan, Lusi Zhang, Qiong Liu, Ying Li, Hui Guo, Yu Peng, Hexiang Peng, Beisha Tang, Zhengmao Hu, Jingping Zhao, Kun Xia, Jia-Da Li
AMPD1 is an adenosine monophosphate deaminase that catalyzes the deamination of AMP to IMP. To understand the physiological function of AMPD1, we obtained a strain of Ampd1 mutant mice from KOMP repository, which was generated by a knockout-first strategy. An elevated AMP level and almost complete lack of IMP was detected in the skeletal muscle of E18.5 Ampd1(tm1a/tm1a) mice. However, Ampd1(tm1a/tm1a) mice died in 2 days postnatally, which was contradicting to previous reports. After removal of the knockout-first cassette and critical exon, mice homozygous for the Ampd1(tm1c/tm1c) and Ampd1(tm1d/tm1d) alleles survived to adulthood...
October 24, 2016: Scientific Reports
Laura Evangelista, Maria Vittoria Dieci, Valentina Guarneri, Pier Franco Conte
PURPOSE: The aim of the study was to determine the correlation between 16α-18F-fluoro-17β-estradiol (18F-FES) uptake and the expression and functionality of estrogen receptors (ERs), as well as to evaluate the ability of 18F-FES PET to predict the response to hormonal therapy (HT) in patients with locally advanced or metastatic breast cancer (BC). METHODS: Literature searches in the major literature databases were carried out in order to select English-language articles dealing with 18F-FES PET and BC...
October 19, 2016: Current Radiopharmaceuticals
Joel E Gallant, Graeme Moyle, Juan Berenguer, Peter Shalit, Huyen Cao, Ya-Pei Liu, Joel Myers, Lisa Rosenblatt, Lingfeng Yang, Javier Szwarcberg
OBJECTIVES: Cobicistat (COBI) enhances atazanavir (ATV) pharmacokinetic parameters similarly to ritonavir (RTV) in both healthy volunteers and HIV-infected adults. Primary efficacy and safety outcomes of this Phase 3, international, randomized, double-blind, double-dummy, active-controlled trial in HIV-1-infected treatment-naïve adults (GS-US-216-0114/NCT01108510) demonstrated that ATV+COBI was non-inferior to ATV+RTV, each in combination with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), at Weeks 48 and 144, with high rates of virologic success for both regimens (85...
October 21, 2016: Current HIV Research
Liliana F Iannucci, Jingfeng Sun, Brijesh K Singh, Jin Zhou, Vincent A Kaddai, Antonia Lanni, Paul M Yen, Rohit A Sinha
Short-chain fatty acids (SCFAs) are gut microbial fermentation products derived from dietary fiber sources. Although depletion of gut microflora has been linked to the development of liver disease, the direct effects of SCFAs on intracellular hepatic processes are not well understood. In this study, we demonstrated that the SCFAs, propionate and butyrate, regulated autophagic flux in hepatic cells in a cell-autonomous manner. Induction of autophagy by SCFAs required PPARγ stimulation of Uncoupling Protein 2 (UCP2) expression that was associated with reduced intracellular ATP levels and activation of PRKAA1/AMPK (protein kinase, AMP-activated, alpha 1 catalytic subunit)...
October 20, 2016: Biochemical and Biophysical Research Communications
Chatchai Muanprasat, Varanuj Chatsudthipong
Chitosan oligosaccharide (COS) is an oligomer of β-(1➔4)-linked D-glucosamine. COS can be prepared from the deacetylation and hydrolysis of chitin, which is commonly found in the exoskeletons of arthropods and insects and the cell walls of fungi. COS is water soluble, non-cytotoxic, readily absorbed through the intestine and mainly excreted in the urine. Of particular importance, COS and its derivatives have been demonstrated to possess several biological activities including anti-inflammation, immunostimulation, anti-tumor, anti-obesity, anti-hypertension, anti-Alzheimer's disease, tissue regeneration promotion, drug and DNA delivery enhancement, anti-microbial, anti-oxidation and calcium-absorption enhancement...
October 20, 2016: Pharmacology & Therapeutics
Wanxing Duan, Ke Chen, Zhengdong Jiang, Xin Chen, Liankang Sun, Jiahui Li, Jianjun Lei, Qinhong Xu, Jiguang Ma, Xuqi Li, Liang Han, Zheng Wang, Zheng Wu, Fengfei Wang, Erxi Wu, Qingyong Ma, Zhenhua Ma
Emerging evidence suggests that metformin, as an activator of AMP-activated protein kinase (AMPK), may be useful in preventing and treating PDAC. However, whether metformin has an effect on the stromal reaction of PDAC remains unknown. In this study, we first evaluated the expression of AMPK and phosphorylated-AMPK (P-AMPK) in normal and PDAC tissues, our data indicate that reduced P-AMPK expression is a frequent event in PDAC and correlated with poor prognosis and the dense stromal reaction. We then determined the efficacy of metformin on PDAC growth in vitro and in vivo...
October 20, 2016: Cancer Letters
Shin Morizane, Kazuko Mizuno, Tetsuya Takiguchi, Saeko Sugimoto, Keiji Iwatsuki
Here we report that psoriatic inflammation increases serum amyloid A (SAA) expression in epidermal keratinocytes, and that SAA also induces cytokines, chemokines, and AMPs in the cells.
October 20, 2016: Journal of Investigative Dermatology
Stephan M Caucheteux, Vincent Piguet
Cutaneous vaccination can be a challenge because the development of local skin inflammation is often unavoidable. Thus, it is important to identify and validate new vaccine adjuvants that enhance immunization without the burden of inflammation. Wang et al. now report on a cyclic GMP-AMP adjuvant, the natural stimulator of interferon genes agonist, providing evidence for potent immune responses without inflammation.
November 2016: Journal of Investigative Dermatology
Chao Han, Shuke Nie, Guiqin Chen, Kai Ma, Nian Xiong, Zhentao Zhang, Yan Xu, Tao Wang, Stella M Papa, Xuebing Cao
Long-term L-DOPA treatment of Parkinson's disease is accompanied with fluctuations of motor responses and L-DOPA-induced dyskinesia (LID). Phosphorylation of the dopamine and c-AMP regulated phosphoprotein of 32 kDa (DARPP-32) plays a role in the pathogenesis of LID, and thus dephosphorylation of this protein by activated calcineurin may help reduce LID. One important activator of calcineurin is the Ca(2+) ionophore ionomycin. Here, we investigated whether intrastriatal injection of ionomycin to hemiparkinsonian rats produced changes in L-DOPA responses including LID...
October 19, 2016: Neuroscience
Olena Odnokoz, Kyle Nakatsuka, Vladimir I Klichko, Jacqueline Nguyen, Liz Calderon Solis, Kaitlin Ostling, Marziyeh Badinloo, William C Orr, Svetlana N Radyuk
Previously, we have shown that flies under-expressing the two mitochondrial peroxiredoxins (Prxs), dPrx3 and dPrx5, display increases in tissue-specific apoptosis and dramatically shortened life span, associated with a redox crisis, manifested as changes in GSH:GSSG and accumulation of protein mixed disulfides. To identify specific pathways responsible for the observed biological effects, we performed a transcriptome analysis. Functional clustering revealed a prominent group enriched for immunity-related genes, including a considerable number of NF-kB-dependent antimicrobial peptides (AMP) that are up-regulated in the Prx double mutant...
October 19, 2016: Biochimica et Biophysica Acta
Yufeng Li, Zheng Li, Dan Wang, Xiang Zhang, Jia Li, Sher Ali, Jingze Lu, Hao Zong, Xiaolan Xu
Insulin-stimulated GLUT4 translocation from GLUT4 storage vesicles (GSVs) to the plasma membrane (PM) constitutes a key process for blood glucose control. Therefore, compounds that could promote GLUT4 translocation into the PM represent potential drugs for the treatment of diabetes. In this research, we screened for agonists that induce GLUT4 translocation by using a novel pH-sensitive fluorescent probe, insulin-regulated aminopeptidase (IRAP)-mOrange2. We identified as well as validated one agonist, staurosporine, from a 64,000 compound library...
October 18, 2016: Biochemical and Biophysical Research Communications
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