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Robert A Sandhaus
Alpha-1 antitrypsin deficiency (AATD) is a condition caused by the inheritance of two mutated SERPINA1 gene alleles. Individuals with AATD are at increased risk of injury to the liver and lungs. The pulmonary manifestations include precocious onset of pulmonary emphysema and bronchiectasis. For nearly three decades, treatment has been available to individuals with emphysema caused by AATD, but this therapy-augmentation of plasma and tissue alpha-1 antitrypsin levels by intravenous administration of human plasma-derived protein-was approved by regulatory authorities based on its biochemical efficacy...
August 2016: Annals of the American Thoracic Society
Manfred Relle, Bernd Föhr, Federica Fasola, Andreas Schwarting
Granulomatosis with polyangiitis (GPA) is a severe autoimmune disease and one of the small vessel anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Although its etiology and pathophysiology are still widely unknown, it is accepted that infections, environmental factors, epigenetic modifications, and a genetic predisposition provide the basis for this systemic disorder. GPA typically evolves into two phases: an initial phase characterized by ear, nose and throat (ENT) manifestations, such as chronic sinusitis and otitis, ulceration of the oral cavity and pharynx, as well as pulmonary nodules and a severe generalized phase, defined by the occurrence of rapidly progressive glomerulonephritis, pulmonary hemorrhage, and arthritis...
August 21, 2016: Molecular and Cellular Probes
Kelsey Brooks, Gregory W Burns, Joao G N Moraes, Thomas E Spencer
Available studies support the idea that the uterine epithelia and their secretions have important biological roles in conceptus survival, elongation and implantation in sheep. The present study evaluated the transcriptome of the uterine luminal epithelium (LE), glandular epithelium (GE) and conceptus, and proteome of the uterine luminal fluid (ULF) during the peri-implantation period of pregnancy. Transcriptome (RNA-sequencing) analysis was conducted on LE and GE isolated from uteri of Day 10, 12, 14, 16, and 20 pregnant sheep by laser capture microdissection...
August 17, 2016: Biology of Reproduction
Andrea Di Francesco, Clara Di Germanio, Amaresh C Panda, Phu Huynh, Robert Peaden, Ignacio Navas-Enamorado, Paul Bastian, Elin Lehrmann, Alberto Diaz-Ruiz, David Ross, David Siegel, Jennifer L Martindale, Michel Bernier, Myriam Gorospe, Kotb Abdelmohsen, Rafael de Cabo
NAD(P)H: quinone oxidoreductase (NQO1) is essential for cell defense against reactive oxidative species, cancer, and metabolic stress. Recently, NQO1 was found in ribonucleoprotein (RNP) complexes, but NQO1-interacting mRNAs and the functional impact of such interactions are not known. Here, we used ribonucleoprotein immunoprecipitation (RIP) and microarray analysis to identify comprehensively the subset of NQO1 target mRNAs in human hepatoma HepG2 cells. One of its main targets, SERPINA1 mRNA, encodes the serine protease inhibitor α-1-antitrypsin, A1AT, which is associated with disorders including obesity-related metabolic inflammation, chronic obstructive pulmonary disease (COPD), liver cirrhosis and hepatocellular carcinoma...
August 8, 2016: Free Radical Biology & Medicine
Vanessa Sauer, Tatyana Tchaikovskaya, Xia Wang, Yanfeng Li, Wei Zhang, Krisztina Tar, Zsuzsanna Polgar, Jianqiang Ding, Chandan Guha, Ira J Fox, Namita Roy-Chowdhury, Jayanta Roy-Chowdhury
Although several types of somatic cells have been reprogrammed to induced pluripotent stem cells (iPSC) and then differentiated to hepatocyte-like cells (iHep), the method for generating such cells from renal tubular epithelial cells shed in human urine and transplanting them in animal livers has not been described systematically. We report reprogramming of human urinary epithelial cells to iPSCs and subsequent hepatic differentiation, followed by a detailed characterization of the newly generated iHeps. The epithelial cells were reprogrammed into iPSCs by delivering the pluripotency factors OCT3/4, SOX2, KLF4 and MYC using methods that do not involve transgene integration, such as nucleofection of episomal (oriP/EBNA-1) plasmids or infection with recombinant Sendai viruses...
June 9, 2016: Cell Transplantation
Wenjuan Wu, Qi Wang, Fuqiang Yin, Zhijun Yang, Wei Zhang, Hani Gabra, Li Li
Emerging drug resistance in epithelial ovarian cancer (EOC) thwarted progress in platinum‑based chemotherapy, resulting in increased mortality, morbidity and healthcare costs. The aim of this study was to detect the responses induced by chemotherapy at protein and metabolite levels, and to search for new plasma markers that can predict resistance to platinum‑based chemotherapy in EOC patients, leading to improved clinical response rates. Serum samples were collected and subjected to proteomic relative quantitation analysis and metabolomic analysis...
October 2016: International Journal of Oncology
Arif Bashir, Naveed Nazir Shah, Younis Mohammad Hazari, Mudasir Habib, Samirul Bashir, Nazia Hilal, Mariam Banday, Syed Asrafuzzaman, Khalid Majid Fazili
Alpha1-antitrypsin (AAT) is one of the major circulating anti-protease whose levels in circulation are raised during excessive amount of proteases, especially neutrophil elastase (NE) released during the course of inflammation. Proteolytic attack of NE on peripheral organs, more exclusively on lung parenchyma has severe consequence that may precipitate pulmonary emphysema. Normally, human body has its own molecular and physiological mechanisms to synthesize and regulate the production of anti-protease like AAT to mitigate the extent of inflammatory damage...
August 2016: Respiratory Medicine
Julien Peltier, Jean-Pierre Roperch, Stéphane Audebert, Jean-Paul Borg, Luc Camoin
UNLABELLED: Colorectal cancer (CRC) remains a major cause of cancer related-death in developed countries. The mortality risk is correlated with the stage of CRC determined at the primary diagnosis and early diagnosis is associated with enhanced survival rate. Currently, only faecal occult blood tests are used to screen for CRC. Consequently, there is an incentive to identify specific markers of CRC. We used quantitative proteomic analysis of serum samples to characterize protein profiles in adenoma, CRC and healthy control samples...
October 4, 2016: Journal of Proteomics
W J Wu, Q Wang, W Zhang, L Li
OBJECTIVE: To identified differentially expressed proteins associated with platinum resistance in platinum resistance epithelial oarian cancer(EOC)patients in serum and investigate their clinical value. METHODS: A total of 106 patients withoverian tumor in affiliated tumor hospital of Guangxi Medical University from August 1998 to September 2013 were enrolled in this study, which include 52 cases od platinum-sensitive(PTS), 44 cases of platinum-resistant(PTR)and 10 cases of benign ovarian cyst(BOC)...
July 25, 2016: Zhonghua Fu Chan Ke za Zhi
Catherine M Greene, Stefan J Marciniak, Jeffrey Teckman, Ilaria Ferrarotti, Mark L Brantly, David A Lomas, James K Stoller, Noel G McElvaney
α1-Antitrypsin deficiency (A1ATD) is an inherited disorder caused by mutations in SERPINA1, leading to liver and lung disease. It is not a rare disorder but frequently goes underdiagnosed or misdiagnosed as asthma, chronic obstructive pulmonary disease (COPD) or cryptogenic liver disease. The most frequent disease-associated mutations include the S allele and the Z allele of SERPINA1, which lead to the accumulation of misfolded α1-antitrypsin in hepatocytes, endoplasmic reticulum stress, low circulating levels of α1-antitrypsin and liver disease...
2016: Nature Reviews. Disease Primers
Nupur Aggarwal, Elena Korenbaum, Ravi Mahadeva, Stephan Immenschuh, Veronika Grau, Charles A Dinarello, Tobias Welte, Sabina Janciauskiene
Alpha1-antitrypsin (A1AT, SERPINA1), a major circulating inhibitor of neutrophil elastase (NE) and proteinase-3 (PRN3), has been proposed to reduce the processing and release of IL-1β. Since the anti-inflammatory properties of A1AT are influenced by the presence of polyunsaturated fatty acids, we compared effects of fatty acid-free (A1AT-0) and α-linoleic acid-bound (A1AT-LA) forms of A1AT on lipopolysaccharide (LPS)-induced synthesis of IL-1β precursor and the release of IL-1β from human blood neutrophils...
July 13, 2016: Molecular Medicine
Natalia L Starodubtseva, Alexey S Kononikhin, Anna E Bugrova, Vitaliy Chagovets, Maria Indeykina, Ksenia N Krokhina, Irina V Nikitina, Yury I Kostyukevich, Igor A Popov, Irina M Larina, Leila A Timofeeva, Vladimir E Frankevich, Oleg V Ionov, Dmitry N Degtyarev, Eugene N Nikolaev, Gennady T Sukhikh
A serious problem during intensive care and nursing of premature infants is the invasiveness of many examination methods. Urine is an excellent source of potential biomarkers due to the safety of the collection procedure. The purpose of this study was to determine the features specific for the urine proteome of preterm newborns and their changes under respiratory pathologies of infectious and non-infectious origin. The urine proteome of 37 preterm neonates with respiratory diseases and 10 full-term newborns as a control group were investigated using the LC-MS/MS method...
June 14, 2016: Journal of Proteomics
Deolinda Silva, Maria João Oliveira, Miguel Guimarães, Ricardo Lima, Sílvia Gomes, Susana Seixas
BACKGROUND: Alpha-1-antitrypsin deficiency (AATD) is a genetic condition caused by SERPINA1 mutations, which culminates into lower protease inhibitor activity in the serum and predisposes affected individuals to emphysema. Clinical manifestations of AATD are often associated to ZZ (p.Glu342Lys) and SZ (p.Glu264Val) genotypes and less frequently to rare deficiency or null alleles in heterozygous and homozygous states. METHODS: We sequenced SERPINA1 (approximately 8 kb) and genotyped two microsatellites located upstream and downstream of the gene (195 and 5...
July 2016: Respiratory Medicine
Luiz Gustavo Gardinassi
Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in children, elderly, and immunocompromised individuals. Despite of advances in diagnosis and treatment, biomarkers of RSV infection are still unclear. To understand the host response and propose signatures of RSV infection, previous studies evaluated the transcriptional profile of the human bronchial epithelial cell line-BEAS-2B-infected with different strains of this virus. However, the evolution of statistical methods and functional analysis together with the large amount of expression data provide opportunities to uncover novel biomarkers of inflammation and infections...
2016: Advances in Virology
Cong Li, Wentao Cai, Chenghao Zhou, Hongwei Yin, Ziqi Zhang, Juan J Loor, Dongxiao Sun, Qin Zhang, Jianfeng Liu, Shengli Zhang
Paired-end RNA sequencing (RNA-Seq) was used to explore the bovine transcriptome from the mammary tissue of 12 Chinese Holstein cows with 6 extremely high and 6 low phenotypic values for milk protein percentage. We defined the differentially expressed transcripts between the two comparison groups, extremely high and low milk protein percentage during the peak lactation (HP vs LP) and during the non-lactating period (HD vs LD), respectively. Within the differentially expressed genes (DEGs), we detected 157 at peak lactation and 497 in the non-lactating period with a highly significant correlation with milk protein concentration...
2016: Scientific Reports
Xinxin Zhang, Dehua Ma, Wei Zou, Yibing Ding, Chengchu Zhu, Haiyan Min, Bin Zhang, Wei Wang, Baofu Chen, Minhua Ye, Minghui Cai, Yanqing Pan, Lei Cao, Yueming Wan, Yu Jin, Qian Gao, Long Yi
BACKGROUND: Primary spontaneous pneumothorax (PSP) or pulmonary cysts is one of the manifestations of Birt-Hogg-Dube syndrome (BHDS) that is caused by heterozygous mutations in FLCN gene. Most of the mutations are SNVs and small indels, and there are also approximately 10 % large intragenic deletions and duplications of the mutations. These molecular findings are generally obtained by disparate methods including Sanger sequencing and Multiple Ligation-dependent Probe Amplification in the clinical laboratory...
2016: Respiratory Research
Pasi Huuskonen, Maria R Amezaga, Michelle Bellingham, Lucy H Jones, Markus Storvik, Merja Häkkinen, Leea Keski-Nisula, Seppo Heinonen, Peter J O'Shaughnessy, Paul A Fowler, Markku Pasanen
Detrimental effects of maternal smoking on the term placental proteome and steroid-metabolizing activities, and maternal hormone levels, were studied by using seven non-smoker and seven smoker placentae. Smoking significantly affected 18% of protein spots. The functional networks affected were i) cell morphology, cellular assembly and organization, cellular compromise (15 hits) and ii) DNA replication, recombination, and repair, energy production, nucleic acid metabolism (6 hits). Smoking significantly up-regulated such proteins as, SERPINA1, EFHD1 and KRT8; and down-regulated SERPINB2, FGA and HBB...
August 2016: Reproductive Toxicology
Steffen Halbgebauer, Magdalena Nagl, Hans Klafki, Ute Haußmann, Petra Steinacker, Patrick Oeckl, Jan Kassubek, Elmar Pinkhardt, Albert C Ludolph, Hilkka Soininen, Sanna-Kaisa Herukka, Jens Wiltfang, Markus Otto
Early detection of dementia in Parkinson disease is a prerequisite for preventive therapeutic approaches. Modified serpinA1 in cerebrospinal fluid (CSF) was suggested as an early biomarker for differentiation between Parkinson patients with (PDD) or without dementia (PD). Within this study we aimed to further explore the diagnostic value of serpinA1. We applied a newly developed nanoscale method for the detection of serpinA1 based on automated capillary isoelectric focusing (CIEF). A clinical sample of 102 subjects including neurologically healthy controls (CON), PD and PDD patients was investigated...
2016: Scientific Reports
Kuniaki Seyama, Toyohiro Hirai, Michiaki Mishima, Koichiro Tatsumi, Masaharu Nishimura
BACKGROUND: Alpha1-antitrypsin (ΑAT) deficiency (AATD), a condition of little or no AAT in the serum, is believed to be extremely rare in Japan. However, no such nationwide epidemiological survey has been conducted. The Respiratory Research Failure Group and Japanese Respiratory Society (JRS) cooperated to conduct this survey. METHODS: The survey questionnaire was sent by post to 1598 hospitals that have 200 or more beds (excluding mental hospitals), and by e-mail to members of the JRS...
May 2016: Respiratory Investigation
Vineela Kadiyala, Sarah K Sasse, Mohammed O Altonsy, Reena Berman, Hong W Chu, Tzu L Phang, Anthony N Gerber
Antagonism of pro-inflammatory transcription factors by monomeric glucocorticoid receptor (GR) has long been viewed as central to glucocorticoid (GC) efficacy. However, the mechanisms and targets through which GCs exert therapeutic effects in diseases such as asthma remain incompletely understood. We previously defined a surprising cooperative interaction between GR and NF-κB that enhanced expression of A20 (TNFAIP3), a potent inhibitor of NF-κB. Here we extend this observation to establish that A20 is required for maximal cytokine repression by GCs...
June 10, 2016: Journal of Biological Chemistry
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