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https://www.readbyqxmd.com/read/27908864/identification-of-candidate-genes-in-osteoporosis-by-integrated-microarray-analysis
#1
J J Li, B Q Wang, Q Fei, Y Yang, D Li
OBJECTIVES: In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis. METHODS: We searched the Gene Expression Omnibus (GEO) database for microarray studies of peripheral blood mononuclear cells in patients with osteoporosis. Subsequently, we integrated gene expression data sets from multiple microarray studies to obtain differentially expressed genes (DEGs) between patients with osteoporosis and normal controls...
December 2016: Bone & Joint Research
https://www.readbyqxmd.com/read/27899793/bacterial-proteases-untapped-antimicrobial-drug-targets
#2
REVIEW
Elizabeth Culp, Gerard D Wright
Bacterial proteases are an extensive collection of enzymes that have vital roles in cell viability, stress response and pathogenicity. Although their perturbation clearly offers the potential for antimicrobial drug development, both as traditional antibiotics and anti-virulence drugs, they are not yet the target of any clinically used therapeutics. Here we describe the potential for and recent progress in the development of compounds targeting bacterial proteases with a focus on AAA+ family proteolytic complexes and signal peptidases (SPs)...
November 30, 2016: Journal of Antibiotics
https://www.readbyqxmd.com/read/27887857/a-potential-contribution-of-dipeptidyl-peptidase-4-by-the-mediation-of-monocyte-differentiation-in-the-development-and-progression-of-abdominal-aortic-aneurysms
#3
Hsin-Ying Lu, Chun-Yao Huang, Chun-Ming Shih, Yi-Wen Lin, Chein-Sung Tsai, Feng-Yen Lin, Chun-Che Shih
OBJECTIVE: Abdominal aortic aneurysms (AAAs) are characterized by the destruction of elastin and collagen in the media and adventitia. Dipeptidyl peptidase-4 (DPP-4, an adipokine known as CD26) influences cell signaling, cell-matrix interactions, and the regulation of the functional activity of incretins in metabolic and inflammatory disorders. Although the role of DPP-4 in AAA evolution has been demonstrated, the underlying mechanisms of DPP-4-regulated AAA development remains unknown...
November 22, 2016: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/27885461/prevention-and-treatment-effect-of-evogliptin-on-hepatic-steatosis-in-high-fat-fed-animal-models
#4
Mi-Kyung Kim, Yu Na Chae, Gook-Jun Ahn, Chang Yell Shin, Song-Hyen Choi, Eun Kyoung Yang, Yong Sung Sohn, Moon-Ho Son
Dipeptidyl peptidase 4 (DPP4) is an adipokine that interrupts insulin signaling. The resulting insulin resistance exacerbates hepatic steatosis. We previously reported that the novel DPP4 inhibitor evogliptin improves insulin resistance. This study aimed to verify the therapeutic potential of evogliptin for fatty liver. Evogliptin treatment was initiated simultaneously with a high-fat diet (HFD) feeding in normal mice and in a post-24 week HFD-fed rats. In a prevention study, insulin sensitivity was preserved in evogliptin-treated mice after a 16-week treatment...
November 24, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27855227/evidence-that-processing-of-the-severe-fever-with-thrombocytopenia-syndrome-virus-gn-gc-polyprotein-is-critical-for-viral-infectivity-and-requires-an-internal-gc-signal-peptide
#5
Teresa Plegge, Heike Hofmann-Winkler, Martin Spiegel, Stefan Pöhlmann
The severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging, highly pathogenic bunyavirus against which neither antivirals nor vaccines are available. The SFTSV glycoproteins, Gn and Gc, facilitate viral entry into host cells. Gn and Gc are generated from a precursor protein, Gn/Gc, but it is currently unknown how the precursor is converted into the single proteins and whether this process is required for viral infectivity. Employing a rhabdoviral pseudotyping system, we demonstrate that a predicted signal sequence at the N-terminus of Gc is required for Gn/Gc processing and viral infectivity while potential proprotein convertase cleavage sites in Gc are dispensable...
2016: PloS One
https://www.readbyqxmd.com/read/27849360/robust-reductions-of-excess-weight-and-hyperphagia-by-beloranib-in-rat-models-of-genetic-and-hypothalamic-obesity
#6
Clinton T Elfers, Christian L Roth
Hypothalamic lesions or deficient melanocortin (MC) signaling via MC4 receptor (MC4r) mutations often lead to hyperphagia and severe treatment resistant obesity. We tested the methionine amino peptidase 2-inhibitor beloranib (ZGN-440) in two male rat models of obesity, one modeling hypothalamic obesity (HO) with combined medial hypothalamic lesions (CMHL), and the other modeling a monogenic form of obesity with MC4r mutations (MC4rKO). In CMHL rats (age 3 months), post-surgery excess weight gain was significantly inhibited (ZGN-440 0...
November 16, 2016: Endocrinology
https://www.readbyqxmd.com/read/27829551/role-of-tripeptidyl-peptidase-ii-in-mhc-class-i-antigen-presentation-biological-characteristics-cellular-crosstalk-and-signaling
#7
REVIEW
Quanhui Tan, Siyuan Ma, Jianjun Hu, Xiaohua Chen, Yongsheng Yu, Guoqing Zang, Zhenghao Tang
Tripeptidyl peptidase II (TPPII) is a multifunctional cytoplasmic serine protease. The main function of TPPII is to cleave proteasome-generated peptides into tripeptides, which can then be further degraded into free amino acids. Recent evidence suggests that TPPII plays an important role in epitope generation, but the mechanisms of TPPII in MHC class I antigen presentation remain unclear. Recent research has shed new light on the mechanisms and functions of TPPII in MHC class I antigen presentation. We therefore provide an updated review of the biological characteristics of TPPII and explore its role in MHC class I antigen presentation...
November 6, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27809302/multiple-functions-of-usp18
#8
REVIEW
Nadine Honke, Namir Shaabani, Dong-Er Zhang, Cornelia Hardt, Karl S Lang
Since the discovery of the ubiquitin system and the description of its important role in the degradation of proteins, many studies have shown the importance of ubiquitin-specific peptidases (USPs). One special member of this family is the USP18 protein (formerly UBP43). In the past two decades, several functions of USP18 have been discovered: this protein is not only an isopeptidase but also a potent inhibitor of interferon signaling. Therefore, USP18 functions as 'a' maestro of many biological pathways in various cell types...
November 3, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27799556/precise-gene-editing-paves-the-way-for-derivation-of-mannheimia-haemolytica-leukotoxin-resistant-cattle
#9
Sudarvili Shanthalingam, Ahmed Tibary, Jonathan E Beever, Poothapillai Kasinathan, Wendy C Brown, Subramaniam Srikumaran
Signal peptides of membrane proteins are cleaved by signal peptidase once the nascent proteins reach the endoplasmic reticulum. Previously, we reported that, contrary to the paradigm, the signal peptide of ruminant CD18, the β subunit of β2 integrins, is not cleaved and hence remains intact on mature CD18 molecules expressed on the surface of ruminant leukocytes. Leukotoxin secreted by Mannheimia (Pasteurella) haemolytica binds to the intact signal peptide and causes cytolysis of ruminant leukocytes, resulting in acute inflammation and lung tissue damage...
October 31, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27797115/inhibitory-effect-of-presenilin-inhibitor-ly411575-on-maturation-of-hepatitis-c-virus-core-protein-production-of-the-viral-particle-and-expressions-of-host-proteins-involved-in-pathogenicity
#10
Teruhime Otoguro, Tomohisa Tanaka, Hirotake Kasai, Atsuya Yamashita, Kohji Moriishi
Hepatitis C virus (HCV) core protein is responsible for the formation of an infectious viral particle and induction of pathogenicity. The C-terminal transmembrane region of the immature core protein is cleaved by signal peptide peptidase (SPP) for maturation of the core protein. SPP is classified into the family of presenilin-like aspartic proteases. Some presenilin inhibitors are expected to suppress HCV infection and production, but this anti-HCV effect has not been investigated in detail. In this study, we screened presenilin inhibitors in order to identify the anti-HCV compound...
October 31, 2016: Microbiology and Immunology
https://www.readbyqxmd.com/read/27795298/fabp4-ap2-regulates-macrophage-redox-signaling-and-inflammasome-activation-via-control-of-ucp2
#11
Kaylee A Steen, Hongliang Xu, David A Bernlohr
Obesity-linked metabolic disease is mechanistically associated with the accumulation of proinflammatory macrophages in adipose tissue leading to increased reactive oxygen species (ROS) production and low-grade, chronic inflammation. Previous work has demonstrated that deletion of the adipocyte fatty acid-binding protein (FABP4/aP2) uncouples obesity from inflammation via up-regulation of the uncoupling protein 2 (UCP2). Herein we demonstrate that ablation of FABP4/aP2 regulates systemic redox capacity, reduces cellular protein sulfhydryl oxidation and in particular, oxidation of mitochondrial protein cysteine residues...
October 17, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27790089/proteomic-substrate-identification-for-membrane-proteases-in-the-brain
#12
REVIEW
Stephan A Müller, Simone D Scilabra, Stefan F Lichtenthaler
Cell-cell communication in the brain is controlled by multiple mechanisms, including proteolysis. Membrane-bound proteases generate signaling molecules from membrane-bound precursor proteins and control the length and function of cell surface membrane proteins. These proteases belong to different families, including members of the "a disintegrin and metalloprotease" (ADAM), the beta-site amyloid precursor protein cleaving enzymes (BACE), membrane-type matrix metalloproteases (MT-MMP) and rhomboids. Some of these proteases, in particular ADAM10 and BACE1 have been shown to be essential not only for the correct development of the mammalian brain, but also for myelination and maintaining neuronal connections in the adult nervous system...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27771154/incretin-treatment-and-atherosclerotic-plaque-stability-role-of-adiponectin-appl1-signaling-pathway
#13
Michelangela Barbieri, Raffaele Marfella, Antonietta Esposito, Maria Rosaria Rizzo, Edith Angellotti, Ciro Mauro, Mario Siniscalchi, Fabio Chirico, Pasquale Caiazzo, Fulvio Furbatto, Alessandro Bellis, Nunzia D'Onofrio, Milena Vitiello, Franca Ferraraccio, Giuseppe Paolisso, Maria Luisa Balestrieri
AIMS: Glucagon like peptide 1 (GLP-1) analogues and dipeptidyl peptidase IV (DPP-4) inhibitors reduce atherosclerosis progression in type 2 diabetes mellitus (T2DM) patients and are associated with morphological and compositional characteristics of stable plaque phenotype. GLP-1 promotes the secretion of adiponectin which exerts anti-inflammatory effects through the adaptor protein PH domain and leucine zipper containing 1 (APPL1). The potential role of APPL1 expression in the evolution of atherosclerotic plaque in TDM2 patients has not previously evaluated...
October 5, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/27769673/not-just-an-antibiotic-target-exploring-the-role-of-type-i-signal-peptidase-in-bacterial-virulence
#14
Shawn I Walsh, Arryn Craney, Floyd E Romesberg
The looming antibiotic crisis has prompted the development of new strategies towards fighting infection. Traditional antibiotics target bacterial processes essential for viability, whereas proposed antivirulence approaches rely on the inhibition of factors that are required only for the initiation and propagation of infection within a host. Although antivirulence compounds have yet to prove their efficacy in the clinic, bacterial signal peptidase I (SPase) represents an attractive target in that SPase inhibitors exhibit broad-spectrum antibiotic activity, but even at sub-MIC doses also impair the secretion of essential virulence factors...
September 21, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27768902/regulation-of-proteasome-activity-by-p2y2-receptor-underlies-the-neuroprotective-effects-of-extracellular-nucleotides
#15
Laura de Diego-García, Mercedes Ramírez-Escudero, Álvaro Sebastián-Serrano, Juan Ignacio Diaz-Hernández, Jesús Pintor, José J Lucas, Miguel Díaz-Hernández
The Ubiquitin-Proteasome System (UPS) is essential for the regulation of the cellular proteostasis. Indeed, it has been postulated that an UPS dysregulation is the common mechanism that underlies several neurological disorders. Considering that extracellular nucleotides, through their selective P2Y2 receptor (P2Y2R), play a neuroprotective role in various neurological disorders that course with an UPS impairment, we wonder if this neuroprotective capacity resulted from their ability to modulate the UPS. Using a cellular model expressing two different UPS reporters, we found that the stimulation of P2Y2R by its selective agonist Up4U induced a significant reduction of UPS reporter levels...
October 18, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27732058/vascular-biology-of-glucagon-receptor-superfamily-peptides-complexity-controversy-and-clinical-relevance
#16
Gemma Pujadas, Daniel J Drucker
Regulatory peptides produced in islet and gut endocrine cells, including glucagon, GLP-1, GLP-2, and GIP exert actions with considerable metabolic importance and translational relevance. Although the clinical development of GLP-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4(DPP4) inhibitors has fostered research into how these hormones act on the normal and diseased heart, less is known about the actions of these peptides on blood vessels. Here we review the effects of these peptide hormones on normal blood vessels, and highlight their vascular actions in the setting of experimental and clinical vascular injury...
October 12, 2016: Endocrine Reviews
https://www.readbyqxmd.com/read/27704740/correlation-of-glypican-4-level-with-basal-active-glucagon-like-peptide-1-level-in-patients-with-type-2-diabetes-mellitus
#17
Sang Ah Lee, Gwanpyo Koh, Suk Ju Cho, So Yeon Yoo, Sang Ouk Chin
BACKGROUND: Previous studies have reported that glypican-4 (GPC4) regulates insulin signaling by interacting with insulin receptor and through adipocyte differentiation. However, GPC4 has not been studied with regard to its effects on clinical factors in patients with type 2 diabetes mellitus (T2DM). We aimed to identify factors associated with GPC4 level in T2DM. METHODS: Between January 2010 and December 2013, we selected 152 subjects with T2DM and collected serum and plasma into tubes pretreated with aprotinin and dipeptidyl peptidase-4 inhibitor to preserve active gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1)...
September 2016: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27697835/complement-pathway-amplifies-caspase-11-dependent-cell-death-and-endotoxin-induced-sepsis-severity
#18
Brooke A Napier, Sky W Brubaker, Timothy E Sweeney, Patrick Monette, Greggory H Rothmeier, Nina A Gertsvolf, Andreas Puschnik, Jan E Carette, Purvesh Khatri, Denise M Monack
Cell death and release of proinflammatory mediators contribute to mortality during sepsis. Specifically, caspase-11-dependent cell death contributes to pathology and decreases in survival time in sepsis models. Priming of the host cell, through TLR4 and interferon receptors, induces caspase-11 expression, and cytosolic LPS directly stimulates caspase-11 activation, promoting the release of proinflammatory cytokines through pyroptosis and caspase-1 activation. Using a CRISPR-Cas9-mediated genome-wide screen, we identified novel mediators of caspase-11-dependent cell death...
October 17, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27690016/phenotype-genotype-association-analysis-of-acth-secreting-pituitary-adenoma-and-its-molecular-link-to-patient-osteoporosis
#19
Renzhi Wang, Yakun Yang, Miaomiao Sheng, Dechao Bu, Fengming Huang, Xiaohai Liu, Cuiqi Zhou, Congxin Dai, Bowen Sun, Jindong Zhu, Yi Qiao, Yong Yao, Huijuan Zhu, Lin Lu, Hui Pan, Ming Feng, Kan Deng, Bing Xing, Wei Lian, Yi Zhao, Chengyu Jiang
Adrenocorticotrophin (ACTH)-secreting pituitary adenoma, also known as Cushing disease (CD), is rare and causes metabolic syndrome, cardiovascular disease and osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD is still unclear because of a lack of human cell lines and animal models. Here, we study 106 clinical characteristics and gene expression changes from 118 patients, the largest cohort of CD in a single-center. RNA deep sequencing is used to examine genotypic changes in nine paired female ACTH-secreting pituitary adenomas and adjacent nontumorous pituitary tissues (ANPT)...
September 29, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27642770/a-target-based-whole-cell-screen-approach-to-identify-potential-inhibitors-of-mycobacterium-tuberculosis-signal-peptidase
#20
Shilah A Bonnett, Juliane Ollinger, Susantha Chandrasekera, Stephanie Florio, Theresa O'Malley, Megan Files, Jo-Ann Jee, James Ahn, Allen Casey, Yulia Ovechkina, David Roberts, Aaron Korkegian, Tanya Parish
The general secretion (Sec) pathway is a conserved essential pathway in bacteria and is the primary route of protein export across the cytoplasmic membrane. During protein export, the signal peptidase LepB catalyzes the cleavage of the signal peptide and subsequent release of mature proteins into the extracellular space. We developed a target-based whole cell assay to screen for potential inhibitors of LepB, the sole signal peptidase in Mycobacterium tuberculosis, using a strain engineered to underexpress LepB (LepB-UE)...
September 19, 2016: ACS Infectious Diseases
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