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Madeline Y Wong, Ngoc Duc Doan, Andrew S DiChiara, Louis J Papa, Jaime H Cheah, Christian K Soule, Nicki Watson, John D Hulleman, Matthew D Shoulders
Collagen overproduction is a feature of fibrosis and cancer, while insufficient deposition of functional collagen molecules and/or the secretion of malformed collagen are common in genetic disorders like osteogenesis imperfecta. Collagen secretion is an appealing therapeutic target in these and other diseases, as secretion directly connects intracellular biosynthesis to collagen deposition and biological function in the extracellular matrix. However, small molecule and biological methods to tune collagen secretion are severely lacking...
April 20, 2018: Biochemistry
Helga Holm Schultz, Svend Aage Engelholm, Eva Harder Brix, Ulrik Pedersen-Bjergaard, Peter Lommer Kristensen
BACKGROUND: The risk of developing diabetes mellitus (DM) during treatment with high dose glucocorticoids is unknown and monitoring of glucose is random in many settings. OBJECTIVE: To determine incidence of and risk factors for induction of DM during high dose glucocorticoid therapy of metastatic spinal cord compression in patients referred to radiotherapy. Furthermore, to describe the time course of development of DM. SUBJECTS AND METHODS: 140 patients were recruited (131 were included in the analysis) with metastatic spinal cord compression receiving high dose glucocorticoid, ≥100 mg prednisolone per day were included in a prospective, observational cohort study...
April 18, 2018: Endocrine Connections
Mohammad Rehan Ajmal, Fahad Almutairi, Nida Zaidi, Parvez Alam, Mohammad Khursheed Siddiqi, MohsinVahid Khan, Masih Uzzaman, Mohd Ishtikhar, Rizwan Hasan Khan
Alpha1-acid glycoprotein (AAG) is a major acute phase protein of human plasma. Binding of clofazimine to AAG is investigated using optical spectroscopy and molecular docking tools. We found significant quenching of intrinsic fluorescence of AAG upon the binding of clofazimine, binding mode is static with binding constant of 3.52x104 at 298K. The Gibbs free energy change is found to be negative for the interaction of clofazimine with AAG indicating spontaneity of the binding process. Binding of clofazimine induced ordered structure in protein and lead to molecular compaction...
April 19, 2018: Journal of Biomolecular Structure & Dynamics
Jon C Svendsen, Aage K O Alstrup, Lasse F Jensen
No abstract text is available yet for this article.
April 2018: Nature
Suleyman Vural, Richard Simon, Julia Krushkal
BACKGROUND: The APOBEC gene family of cytidine deaminases plays important roles in DNA repair and mRNA editing. In many cancers, APOBEC3B increases the mutation load, generating clusters of closely spaced, single-strand-specific DNA substitutions with a characteristic hypermutation signature. Some studies also suggested a possible involvement of APOBEC3A, REV1, UNG, and FHIT in molecular processes affecting APOBEC mutagenesis. It is important to understand how mutagenic processes linked to the activity of these genes may affect sensitivity of cancer cells to treatment...
April 11, 2018: Human Genomics
Nata Kermanian, Kaj Aage Hansen
Venous thromboembolism is a very common complication of nephrotic syndrome (NS). This case report concerns a 19-year-old male, who had known NS and was admitted two times in a short period, first presenting with recurrent symptoms of NS and later with an acute abdomen, which was diagnosed as renal venous thrombosis (RVT) and pulmonary thromboembolism. The patient was treated with prednisolone and therapeutic doses of dalteparin and warfarin. Venous thrombosis, particularly RVT and pulmonary thromboembolism, should be considered in patients with NS...
April 2, 2018: Ugeskrift for Laeger
Hassan Mellatyar, Sona Talaei, Younes Pilehvar-Soltanahmadi, Abolfazl Barzegar, Abolfazl Akbarzadeh, Arman Shahabi, Mazyar Barekati-Mowahed, Nosratollah Zarghami
Heat shock protein 90 (Hsp90) is an evolutionary preserved molecular chaperone which mediates many cellular processes such as cell transformation, proliferation, and survival in normal and stress conditions. Hsp90 plays an important role in folding, maturation, stabilization and activation of Hsp90 client proteins which all contribute to the development, and proliferation of cancer as well as other inflammatory diseases. Functional inhibition of Hsp90 can have a massive effect on various oncogenic and inflammatory pathways, and will result in the degradation of their client proteins...
March 27, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jing Wang, Yun Li, Wei Sun, Jing Liu, Wenming Chen
OBJECTIVE: This study aimed to investigate synergistic effects of recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) and heat-shock protein 90 (HSP90) inhibitor (geldanamycin derivative 17 -allylamino- 17-demethoxy -geldanamycin, 17-AAG) on the proliferation and apoptosis of multiple myeloma (MM) cells. METHODS: MTT assays evaluated inhibitory effects of rmhTRAIL and 17-AAG in different concentrations and treatment durations on the proliferation of RPMI8226 and U266 cells...
March 22, 2018: Hematology (Amsterdam, Netherlands)
Kinga A Kocemba-Pilarczyk, Barbara Ostrowska, Sonia Trojan, Ecce Aslan, Dorota Kusior, Małgorzata Lasota, Claire Lenouvel, Joanna Dulińska-Litewka
Multiple myeloma (MM) is characterized as a clonal expansion of malignant plasma cells in the bone marrow, which is often associated with pancytopenia and osteolytic bone disease. Interestingly, myeloma-infiltrated bone marrow is considered to be hypoxic, providing selection pressure for a developing tumour. Since HSP90 was shown to participate in stabilization of the subunit of the key transcription factor HIF-1, which controls the hypoxic response, the aim of this study was to investigate the influence of a HSP90 inhibitor 17-Allylamino-17-demethoxygeldanamycin (17-AAG), on MM cells cultured under low oxygenation conditions...
March 15, 2018: Acta Biochimica Polonica
Aage Kristian Olsen Alstrup, Nora Elisabeth Zois, Mette Simonsen, Ole Lajord Munk
BACKGROUND: Positron emission tomography (PET) imaging of anaesthetized pig brains is a useful tool in neuroscience. Stable cerebral blood flow (CBF) is essential for PET, since variations can affect the distribution of several radiotracers. However, the effect of physiological factors regulating CBF is unresolved and therefore knowledge of optimal anaesthesia and monitoring of pigs in PET studies is sparse. The aim of this study was therefore to determine if and how physiological variables and the duration of anaesthesia affected CBF as measured by PET using [15 O]-water in isoflurane-N2 O anaesthetized domestic female pigs...
March 12, 2018: Acta Veterinaria Scandinavica
Guo-Fu Li, Guo Yu, Yanfei Li, Yi Zheng, Qing-Shan Zheng, Hartmut Derendorf
Quantitative prediction of unbound drug fraction (fu ) is essential for scaling pharmacokinetics through physiologically-based approaches. However, few attempts have been made to evaluate the projection of fu values under pathological conditions. The primary objective of this study was to predict fu values (n=105) of 56 compounds with or without the information of predominant binding protein in patients with varying degrees of hepatic insufficiency by accounting for quantitative changes in molar concentrations of either the major binding protein or albumin plus alpha 1-acid glycoprotein (AAG) associated with differing levels of hepatic dysfunction...
March 5, 2018: Journal of Pharmaceutical Sciences
Catherine J A Williams, Aage K O Alstrup, Mads F Bertelsen, Heidi M Jensen, Cleo A C Leite, Tobias Wang
Alfaxalone is becoming a popular anesthetic for nonmammalian vertebrates, but the physiological effects of its administration remain largely unknown in these taxa. Therefore, the cardiovascular responses to a clinically relevant dose of alfaxalone (10 mg/kg) are reported in the bullfrog ( Lithobates catesbeianus), following intramuscular (IM) and intravascular (IV) administration (via a femoral artery catheter) and compared with an IV dose of propofol, another parenteral GABA (γ-aminobutyric acid) agonist in common veterinary use as an induction agent...
March 2018: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
Line Engel Clasen, Anne Bruun Blauert, Svend Aage Madsen
Being exposed to sexual assaults has numerous psychological and social consequences, which may interfere with the adolescent's still-ongoing development. This article focuses on social consequences for adolescents exposed to sexual assault by someone from their peer group. Participants were 148 in number and 15-18 year olds (M = 16.34 years, 90.5% female) from Centre for Victims of Sexual Assault's "Youth Programme." A mixed methods design combined extensive survey data collected from the 148 adolescents and five case stories...
February 28, 2018: Journal of Child Sexual Abuse
Sandeep S Joshi, Shunlin Jiang, Emmanual Unni, Stephen R Goding, Tao Fan, Paul A Antony, Thomas J Hornyak
Heat shock protein 90 (HSP90) is a molecular chaperone which stabilizes client proteins with important roles in tumor growth. 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90 ATPase activity, occupies the ATP binding site of HSP90 causing a conformational change which destabilizes client proteins and directs them towards proteosomal degradation. Malignant melanomas have active RAF-MEK-ERK signaling which can occur either through an activating mutation in BRAF (BRAFV600E) or through activation of signal transduction upstream of BRAF...
2018: PloS One
Doo Young Bae, Sang Mi Eum, Sang Woo Lee, Jin-Hyub Paik, Soo-Yong Kim, Mihyun Park, Changyoung Lee, The Bach Tran, Van Hai Do, Jae-Yun Heo, Eun-Soo Seong, Il-Seop Kim, Ki-Young Choi, Jin Sung Hong, Rahul Vasudeo Ramekar, Sangho Choi, Jong-Kuk Na
To broaden and delve into the genomic information of Clausena excavata , an important medicinal plant in many Asian countries, RNA sequencing (RNA-seq) analysis was performed and a total of 16,638 non-redundant unigenes (≥ 300 bp) with an average length of 755 bp were generated by de novo assembly from 17,580,456 trimmed clear reads. The functional categorization of the identified unigenes by a gene ontology (GO) term resulted in 2305 genes in the cellular component, 5577 in the biological processes, and 8056 in the molecular functions, respectively...
March 2018: 3 Biotech
Olga A Kladova, Milena Bazlekowa-Karaban, Sonia Baconnais, Olivier Piétrement, Alexander A Ishchenko, Bakhyt T Matkarimov, Danila A Iakovlev, Andrey Vasenko, Olga S Fedorova, Eric Le Cam, Barbara Tudek, Nikita A Kuznetsov, Murat Saparbaev
The base excision repair (BER) pathway consists of sequential action of DNA glycosylase and apurinic/apyrimidinic (AP) endonuclease necessary to remove a damaged base and generate a single-strand break in duplex DNA. Human multifunctional AP endonuclease 1 (APE1, a.k.a. APEX1, HAP-1, or Ref-1) plays essential roles in BER by acting downstream of DNA glycosylases to incise a DNA duplex at AP sites and remove 3'-blocking sugar moieties at DNA strand breaks. Human 8-oxoguanine-DNA glycosylase (OGG1), methyl-CpG-binding domain 4 (MBD4, a...
February 11, 2018: DNA Repair
Bui Thi Kim Ly, Hoang Thanh Chi
FMS-like tyrosine kinase-3 fragments from exon 14 to the end without any mutations or deletions has been reported to fuse to ETV6 (TEL) in a few cases of myeloid/lymphoid neoplasms with eosinophilia carrying a translocation t(12;13)(p13;q12). This fusion protein confers constitutive activation on FLT3 fragment and induces factor-independent growth in transfected Ba/F3 cells indicating that it is an oncoprotein. However, the mechanism controlling the stability of this oncoprotein is unknown. In this study, we focus on finding factors controlling the stability of ETV6/FLT3...
February 22, 2018: Oncology Research
Bin Yang, Junlong Zhang, Xinle Liu, Zhuochun Huang, Zhenzhen Su, Yun Liao, Lanlan Wang
IgA nephropathy (IgAN) is the most common chronic glomerular disease worldwide. Genetic factors are thought to be crucial in the pathogenesis of IgAN. However, few data are available on the relationship between human leucocyte antigen (HLA) and signal transducer and activator of transcription 4 (STAT4) polymorphisms and IgAN susceptibility in the Chinese population. Therefore, we examined HLA-DP/DQ and STAT4 polymorphisms (rs3077, rs9277535, rs7453920 and rs7574865) in a total of 630 subjects including 140 IgAN and 490 healthy controls in Chinese...
January 23, 2018: Oncotarget
Na Ling, Jumei Zhang, Chengsi Li, Haiyan Zeng, Wenjing He, Yingwang Ye, Qingping Wu
Cronobacter species are foodborne pathogens that can cause neonatal meningitis, necrotizing enterocolitis, and sepsis; they have unusual abilities to survive in environmental stresses such as acid stress. However, the factors involved in acid stress responses and biofilm formation in Cronobacter species are poorly understood. In this study, we investigated the role of grxB on cellular morphology, acid tolerance, surface hydrophobicity, auto-aggregation (AAg), motility, and biofilm formation in Cronobacter sakazakii ...
2018: Frontiers in Microbiology
Selma Becherirat, Fatemeh Valamanesh, Mojgan Karimi, Anne-Marie Faussat, Jean-Marie Launay, Cynthia Pimpie, Amu Therwath, Marc Pocard
Antiangiogenics administration in colorectal cancer patients seemed promising therapeutic approach. Inspite of early encouraging results, it however gave only modest clinical benefits. When AAG was administered with discontinuous schedule, the disease showed acceleration in certain cases. Though resistance to AAG has been extensively studied, it is not documented for discontinuous schedules. To simulate clinical situations, we subjected a patient-derived CRC subcutaneous xenograft in mice to three different protocols: 1) AAG (bevacizumab) treatment for 30 days (group A) (group B was the control), 2) bevacizumab treatment for 50 days (group C) and bevacizumab for 30 days and 20 without treatment (group D), and 3) bevacizumab treatment for 70 days (group E) and 70 days treatment with a drug-break period between day 30 and 50 (group F)...
February 16, 2018: Translational Oncology
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