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Xiaolan Zhang, Chunmei Lu, Fengmin Zhang, Yingli Song, Minghui Cai, Hui Zhu
Streptococcal heme binding protein (Shp) is involved in the process of heme acquisition in group A Streptococcus (GAS). However, no research thus far has examined the contribution of Shp to the virulence of GAS. To this end, we generated an isogenic strain lacking the shp gene (Δshp) and its complemented strain (Δshp-c) using the parent strain MGAS5005 (WT). Deletion of shp increased survival rates and neutrophil recruitment and reduced skin lesion sizes and GAS loads in the blood and the liver, lung, kidney and spleen in subcutaneous infections of mice...
September 29, 2017: Pathogens and Disease
Hae-Young Lopilly Park, Jie Hyun Kim, Younhea Jung, Chan Kee Park
Purpose: We investigated the extracellular matrix (ECM) of the lamina cribrosa (LC) and peripapillary sclera (PPS) and compared histone acetylation and related enzymes to identify racial differences between Korean and Caucasian donor eyes. Methods: Posterior segment tissues were obtained from 30 Caucasian donors and 42 age and axial length-matched Korean donors. Histone modification was assessed for histone deacetylase (HDAC) 2, HDAC3, and acetylated histone H3...
August 1, 2017: Investigative Ophthalmology & Visual Science
Cristina Pellegrini, Augusto Orlandi, Gaetana Costanza, Alessandro Di Stefani, Antonella Piccioni, Antonella Di Cesare, Andrea Chiricozzi, Amedeo Ferlosio, Ketty Peris, Maria Concetta Fargnoli
Several immune-related markers have been implicated in basal cell carcinoma (BCC) pathogenesis. The BCC inflammatory infiltrate is dominated by Th2 cytokines, suggesting a specific state of immunosuppression. In contrast, regressing BCC are characterized by a Th1 immune response with IFN-γ promoting a tumor suppressive activity. IL-23/Th17-related cytokines, as interleukin (IL)-17, IL-23 and IL-22, play a significant role in cutaneous inflammatory diseases, but their involvement in skin carcinogenesis is controversial and is poorly investigated in BCC...
2017: PloS One
Fwu-Shan Shieh, Patrick Jongeneel, Jamin D Steffen, Selena Lin, Surbhi Jain, Wei Song, Ying-Hsiu Su
Identification of viral integration sites has been important in understanding the pathogenesis and progression of diseases associated with particular viral infections. The advent of next-generation sequencing (NGS) has enabled researchers to understand the impact that viral integration has on the host, such as tumorigenesis. Current computational methods to analyze NGS data of virus-host junction sites have been limited in terms of their accessibility to a broad user base. In this study, we developed a software application (named ChimericSeq), that is the first program of its kind to offer a graphical user interface, compatibility with both Windows and Mac operating systems, and optimized for effectively identifying and annotating virus-host chimeric reads within NGS data...
2017: PloS One
D C Anderson, Stacey A Lapp, John W Barnwell, Mary R Galinski
Plasmodium vivax is a complex protozoan parasite with over 6,500 genes and stage-specific differential expression. Much of the unique biology of this pathogen remains unknown, including how it modifies and restructures the host reticulocyte. Using a recently published P. vivax reference genome, we report the proteome from two biological replicates of infected Saimiri boliviensis host reticulocytes undergoing transition from the late trophozoite to early schizont stages. Using five database search engines, we identified a total of 2000 P...
2017: PloS One
Chester J Joyner, The MaHPIC Consortium, Jennifer S Wood, Alberto Moreno, Anapatricia Garcia, Mary R Galinski
Histopathological data collected from patients with severe malaria have been instrumental for studying malaria pathogenesis. Animal models of malaria are critical to complement such studies. Here, the histopathological changes observed in a rhesus macaque with severe and complicated Plasmodium cynomolgi malaria are reported. The animal presented with thrombocytopenia, severe anemia, and hyperparasitemia during the acute infection. The macaque was given subcurative antimalarial treatment, fluid support, and a blood transfusion to treat the clinical complications, but at the time of transfusion, kidney function was compromised...
August 2017: American Journal of Tropical Medicine and Hygiene
Juan Juan Zhang, Hiroyuki Yano, Takako Sasaki, Noritaka Matsuo, Hidekatsu Yoshioka
AIMS: Col5a1 encodes the α1 chain of type V collagen, a quantitatively minor fibrillar collagen that is critical for the formation and function of the organs in the body. MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate biological functions by binding to the 3'- untranslated region (3'UTR) of specific target mRNA. In this study, we investigated the post-transcriptional regulation of miRNAs on the Col5a1 gene expression. MATERIALS AND METHODS: We cultured osteoblasts and fibroblasts of cell lines...
August 22, 2017: Connective Tissue Research
Bo Gong, Yi Shi, Chao Qu, Zimeng Ye, Yilin Yin, Chang Tan, Ping Shuai, Jing Li, Xiaoxin Guo, Yilian Cheng, Zhenglin Yang, Ying Lin, Xiaoqi Liu
PURPOSE: Many genes have been associated with primary open-angle glaucoma (POAG). This study was conducted to investigate whether catalase (CAT) polymorphisms play a significant role in POAG in a Chinese population. METHODS: A cohort of 416 unrelated POAG patients and 997 unrelated control subjects was included in this case-control association study. CAT functional single-nucleotide polymorphisms (SNPs), including rs1001179, rs7943316, and rs769217, were genotyped by SNaPshot method...
August 22, 2017: Ophthalmic Genetics
Michael Zeller, Jacob C Koella
Defense against parasites can be divided into resistance, which limits parasite burden, and tolerance, which reduces pathogenesis at a given parasite burden. Distinguishing between the two and understanding which defense is favored by evolution in different ecological settings are important, as they lead to fundamentally different evolutionary trajectories of host-parasite interactions. We let the mosquito Aedes aegypti evolve under different food levels and with either no parasite, a constant parasite, or a coevolving parasite (the microsporidian Vavraia culicis)...
September 2017: American Naturalist
H Liu, S-R Li, Q Si
OBJECTIVE: HGF/c-met signal pathway exerts important roles in tumor pathogenesis. The study of c-met related regulatory mechanism provides the basis for finding anti-tumor molecular drugs. MiRNAs can effectively regulate gene expression and work as gene therapy. The identification of miRNAs for c-met regulation and study of related mechanism are of critical importance. MATERIALS AND METHODS: Bioinformatics approach was used to search for possible miRNAs with regulatory functions on c-met gene...
August 2017: European Review for Medical and Pharmacological Sciences
Y-D Wang, Z-L Sun
OBJECTIVE: Migration and proliferation of kidney cancer cells are critical factors affecting effective treatment. Abnormal gene expression exists during cancer pathogenesis. The study showed certain effects of PIK3R1 gene on migration and proliferation of kidney cancer cells, although a few studies have been performed regulatory mechanism of microRNA on PIK3R1 gene. Previous sequencing of PIK3R1 gene found the existence of mir-455 binding site. This study confirmed the regulation of PIK3R1 gene expression in kidney cancer cells of mir-455 by in vitro assay, and analyzed its effects on migration or proliferation of kidney cancer cells...
August 2017: European Review for Medical and Pharmacological Sciences
Federica Begalli, Jason Bennett, Daria Capece, Daniela Verzella, Daniel D'Andrea, Laura Tornatore, Guido Franzoso
Transcription factors of the nuclear factor κB (NF-κB) family are central coordinating regulators of the host defence responses to stress, injury and infection. Aberrant NF-κB activation also contributes to the pathogenesis of some of the most common current threats to global human health, including chronic inflammatory diseases, autoimmune disorders, diabetes, vascular diseases and the majority of cancers. Accordingly, the NF-κB pathway is widely considered an attractive therapeutic target in a broad range of malignant and non-malignant diseases...
August 22, 2017: Biomedicines
Panagiotis V S Vasileiou, Iordanis Mourouzis, Constantinos Pantos
Mitochondria have emerged as key players regarding cellular homeostasis not only due to their contribution regarding energy production through oxidative phosphorylation, but also due to their involvement in signaling, ion regulation, and programmed cell death. Indeed, current knowledge supports the notion that mitochondrial dysfunction is a hallmark in the pathogenesis of various diseases. Mitochondrial biogenesis and function require the coordinated action of two genomes: nuclear and mitochondrial. Unfortunately, both intrinsic and environmental genotoxic insults constantly threaten the integrity of nuclear as well as mitochondrial DNA...
August 22, 2017: International Journal of Molecular Sciences
Fatjon Leti, Johanna K DiStefano
Protein-coding genes represent only a small fraction of the human genome. In the past, the majority of the genomic sequence has been considered transcriptionally silent, but recent large-scale studies have uncovered an array of functionally significant elements, including non-protein-coding transcripts, within these noncoding regions of the human genome. Long noncoding RNAs (lncRNAs), a class of noncoding transcripts with lengths >200 nucleotides, are pervasively transcribed in the genome and function as signals, decoys, guides, or scaffolds to regulate gene expression...
August 22, 2017: Genes
Gregory L Dignon, Gül H Zerze, Jeetain Mittal
Amyloid aggregates are characteristic of many serious diseases such as Alzheimer's Disease, Parkinson's and Type II Diabetes, and commonly involve intrinsically disordered proteins (IDPs), those that populate an ensemble of conformations rather than a single folded structure in isolation. Human Islet Amyloid Polypeptide (hIAPP or amylin) is an amyloidogenic IDP implicated in pancreatic $\beta$-cell death during the pathogenesis of Type II Diabetes. The target of amylin's toxic activity is thought to be the cell's lipid membrane, which may also act as a catalyst for aggregation...
August 22, 2017: Journal of Physical Chemistry. B
Kenjiro Ono
Lewy bodies and Lewy neurites in the brain constitute the main histopathological features of Parkinson's disease (PD) and dementia with Lewy bodies. They comprise amyloid-like fibrils composed of α-synuclein (αS), a small protein (~14 kDa). Because the aggregation of αS in the brain has been implicated as a critical step in the development of these diseases, the research for disease-modifying drugs has focused on modification of the αS aggregation process in the brain. Recent studies using synthetic αS peptides, a cell culture model, transgenic mice models, and human samples such as cerebrospinal fluids and the blood of PD patients have suggested that pre-fibrillar forms of αS (i...
August 21, 2017: Neurochemical Research
Smart Mbagwu, Michael Walch, Luis Filgueira, Pierre-Yves Mantel
Growing attention is drawn toward the role of extracellular vesicles (EVs) in infectious diseases. EVs, which are small vesicles released by cells, are involved in cellular communication, immune regulation, and pathogenesis. EVs act as messenger carrying functional cargoes, including RNA, DNA, lipids and proteins from a donor cell to regulate the function of a recipient cell. In malaria, EVs play a key role in regulating the progression from the blood to the transmission stage by promoting the switch between asexual and sexual stages that are taken up by mosquitoes...
2017: Methods in Molecular Biology
Jinxia Han, Dongwei Chen, Dayi Liu, Yanan Zhu
Modafinil, an FDA approved wakefulness drug prescribed to narcolepsy patients, has recently been shown to have anti-inflammatory effects and provides protection against neuroinflammation. It is unknown if modafinil can also protect against atherosclerosis, pathogenesis of which implicates inflammation. Using an apoE-deficient mouse model, we tried to elucidate the effects of modafinil treatment on the development of atherosclerosis. We tested serum levels of cytokines. We isolated mouse bone marrow-derived macrophages (BMDMs), detected effect of modafinil on the viability and proliferation of BMDMs, and on oxidized low-density lipoprotein-induced IL-6 and TNF-α, and supernatant level of IFN-γ as well as NF-κB activity in BMDMs...
August 21, 2017: Inflammopharmacology
Lauren Taylor Rosenblum, Davide Trotti
Amyotrophic lateral sclerosis (ALS) is a rapid and fatal neurodegenerative disease, primarily affecting upper and lower motor neurons. It is an extremely heterogeneous disease in both cause and symptom development, and its mechanisms of pathogenesis remain largely unknown. Excitotoxicity, a process caused by excessive glutamate signaling, is believed to play a substantial role, however. Excessive glutamate release, changes in postsynaptic glutamate receptors, and reduction of functional astrocytic glutamate transporters contribute to excitotoxicity in ALS...
2017: Advances in Neurobiology
Ho Chan Kim, Ji Youn Lim, Seoyeon Kim, Ji Heui Kim, Yong Ju Jang
One subtype of chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by the development of a T-helper type 2 (Th2) response and eosinophilic infiltration. Here, we aimed to establish an eosinophilic CRSwNP murine model, which would be essential to understand the underlying pathogenesis and establish a treatment strategy. C57BL/6 mice were challenged intranasally with a mixture of an Aspergillus oryzae-derived protease (AP) and ovalbumin (OVA) for 6, 8, or 12 consecutive weeks (12 mice/group); control mice received the same volume of phosphate-buffered saline for 12 weeks (n = 12)...
August 21, 2017: European Archives of Oto-rhino-laryngology
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