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International Journal of Molecular Sciences

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https://www.readbyqxmd.com/read/28218733/integrating-pharmacoproteomics-into-early-phase-clinical-development-state-of-the-art-challenges-and-recommendations
#1
REVIEW
Savita Nandal, Tal Burt
Pharmacoproteomics is the study of disease-modifying and toxicity parameters associated with therapeutic drug administration, using analysis of quantitative and temporal changes to specific, predetermined, and select proteins, or to the proteome as a whole. Pharmacoproteomics is a rapidly evolving field, with progress in analytic technologies enabling processing of complex interactions of large number of unique proteins and effective use in clinical trials. Nevertheless, our analysis of clinicaltrials.gov and PubMed shows that the application of proteomics in early-phase clinical development is minimal and limited to few therapeutic areas, with oncology predominating...
February 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218729/exhaled-breath-metabolomics-for-the-diagnosis-of-pneumonia-in-intubated-and-mechanically-ventilated-intensive-care-unit-icu-patients
#2
Pouline M P van Oort, Sanne de Bruin, Hans Weda, Hugo H Knobel, Marcus J Schultz, Lieuwe D Bos, On Behalf Of The Mars Consortium
The diagnosis of hospital-acquired pneumonia remains challenging. We hypothesized that analysis of volatile organic compounds (VOCs) in exhaled breath could be used to diagnose pneumonia or the presence of pathogens in the respiratory tract in intubated and mechanically-ventilated intensive care unit patients. In this prospective, single-centre, cross-sectional cohort study breath from mechanically ventilated patients was analysed using gas chromatography-mass spectrometry. Potentially relevant VOCs were selected with a p-value < 0...
February 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218726/biomarkers-in-pediatric-community-acquired-pneumonia
#3
REVIEW
Nicola Principi, Susanna Esposito
Community-acquired pneumonia (CAP) is an infectious disease caused by bacteria, viruses, or a combination of these infectious agents. The severity of the clinical manifestations of CAP varies significantly. Consequently, both the differentiation of viral from bacterial CAP cases and the accurate assessment and prediction of disease severity are critical for effectively managing individuals with CAP. To solve questionable cases, several biomarkers indicating the etiology and severity of CAP have been studied...
February 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218720/time-concentration-and-ph-dependent-transport-and-uptake-of-anthocyanins-in-a-human-gastric-epithelial-nci-n87-cell-line
#4
Allison A Atnip, Gregory T Sigurdson, Joshua Bomser, M Mónica Giusti
Anthocyanins are the largest class of water soluble plant pigments and a common part of the human diet. They may have many potential health benefits, including antioxidant, anti-inflammatory, anti-cancer, and cardioprotective activities. However, anthocyanin metabolism is not well understood. Studies suggest that anthocyanins absorption may occur in the stomach, in which the acidic pH favors anthocyanin stability. A gastric epithelial cell line (NCI-N87) has been used to study the behavior of anthocyanins at a pH range of 3...
February 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218709/pet-imaging-for-initial-staging-and-therapy-assessment-in-multiple-myeloma-patients
#5
REVIEW
Clément Bailly, Rodolphe Leforestier, Bastien Jamet, Thomas Carlier, Mickael Bourgeois, François Guérard, Cyrille Touzeau, Philippe Moreau, Michel Chérel, Françoise Kraeber-Bodéré, Caroline Bodet-Milin
Multiple myeloma (MM) is a hematological neoplasm characterized by the clonal proliferation of malignant plasma cells in the bone marrow. MM results in diffuse or focal bone infiltration and extramedullary lesions. Over the past two decades, advances have been made with regard to the diagnosis, staging, treatment, and imaging of MM. Computed tomography (CT) and magnetic resonance imaging (MRI) are currently recommended as the most effective imaging modalities at diagnostic. Yet, recent data from the literature suggest that positron emission tomography combined with computed tomography (PET/CT) using (18)F-deoxyglucose (FDG) is a promising technique for initial staging and therapeutic monitoring in this pathology...
February 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218707/fkbp51-immunohistochemical-expression-a-new-prognostic-biomarker-for-oscc
#6
Daniela Russo, Francesco Merolla, Massimo Mascolo, Gennaro Ilardi, Simona Romano, Silvia Varricchio, Virginia Napolitano, Angela Celetti, Loredana Postiglione, Pier Paolo Di Lorenzo, Luigi Califano, Giovanni Orabona Dell'Aversana, Fabio Astarita, Maria Fiammetta Romano, Stefania Staibano
Up-to-date, several molecular markers of prognosis have been studied in Oral Squamous Cell Carcinoma (OSCC), but none entered in the clinical setting. Therapy of OSCC tumors mainly relies on surgery, radiotherapy and partially on chemotherapy; there is an urgent need for biomarkers able to better stratify OSCC patients' risk to address targeted therapeutic strategies. The role of immune response in the pathogenesis and biological behavior of OSCC has been investigated by several authors, and promising results have been obtained with immune checkpoint inhibitors...
February 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218669/a-review-of-gaucher-disease-pathophysiology-clinical-presentation-and-treatments
#7
REVIEW
Jérôme Stirnemann, Nadia Belmatoug, Fabrice Camou, Christine Serratrice, Roseline Froissart, Catherine Caillaud, Thierry Levade, Leonardo Astudillo, Jacques Serratrice, Anaïs Brassier, Christian Rose, Thierry Billette de Villemeur, Marc G Berger
Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. In the general population, its incidence is approximately 1/40,000 to 1/60,000 births, rising to 1/800 in Ashkenazi Jews. The main cause of the cytopenia, splenomegaly, hepatomegaly, and bone lesions associated with the disease is considered to be the infiltration of the bone marrow, spleen, and liver by Gaucher cells...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218667/essential-roles-of-e3-ubiquitin-ligases-in-p53-regulation
#8
REVIEW
Sanam Sane, Khosrow Rezvani
The ubiquitination pathway and proteasomal degradation machinery dominantly regulate p53 tumor suppressor protein stability, localization, and functions in both normal and cancerous cells. Selective E3 ubiquitin ligases dominantly regulate protein levels and activities of p53 in a large range of physiological conditions and in response to cellular changes induced by exogenous and endogenous stresses. The regulation of p53's functions by E3 ubiquitin ligases is a complex process that can lead to positive or negative regulation of p53 protein in a context- and cell type-dependent manner...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218665/matrix-metalloproteinases-as-regulators-of-periodontal-inflammation
#9
REVIEW
Cavalla Franco, Hernández-Ríos Patricia, Sorsa Timo, Biguetti Claudia, Hernández Marcela
Periodontitis are infectious diseases characterized by immune-mediated destruction of periodontal supporting tissues and tooth loss. Matrix metalloproteinases (MMPs) are key proteases involved in destructive periodontal diseases. The study and interest in MMP has been fuelled by emerging evidence demonstrating the broad spectrum of molecules that can be cleaved by them and the myriad of biological processes that they can potentially regulate. The huge complexity of MMP functions within the 'protease web' is crucial for many physiologic and pathologic processes, including immunity, inflammation, bone resorption, and wound healing...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218664/determination-of-vegfr-2-kdr-604a-g-polymorphism-in-pancreatic-disorders
#10
Vlad Pădureanu, Mihail Virgil Boldeanu, Ioana Streaţă, Mihai Gabriel Cucu, Isabela Siloşi, Lidia Boldeanu, Maria Bogdan, Anca Ştefania Enescu, Maria Forţofoiu, Aurelia Enescu, Elena Mădălina Dumitrescu, Dragoş Alexandru, Valeriu Marian Şurlin, Mircea Cătălin Forţofoiu, Ileana Octavia Petrescu, Florin Petrescu, Mihai Ioana, Marius Eugen Ciurea, Adrian Săftoiu
Pancreatic disorders have a high prevalence worldwide. Despite the fact that screening methods became more effective and the knowledge we have nowadays about pancreatic diseases has enhanced, their incidence remains high. Our purpose was to determine whether single nucleotide polymorphism (SNP) of VEGFR-2/KDR (vascular endothelial growth factor receptor 2/kinase insert domain receptor) influences susceptibility to develop pancreatic pathology. Genomic DNA was extracted from blood samples collected from patients diagnosed with acute pancreatitis (n = 110), chronic pancreatitis (n = 25), pancreatic cancer (n = 82) and healthy controls (n = 232)...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218663/advanced-glycation-end-products-inhibit-the-proliferation-of-human-umbilical-vein-endothelial-cells-by-inhibiting-cathepsin-d
#11
Yuan Li, Ye Chang, Ning Ye, Dongxue Dai, Yintao Chen, Naijin Zhang, Guozhe Sun, Yingxian Sun
We aimed to investigate the effect of advanced glycation end products (AGEs) on the proliferation and migration ability of human umbilical vein endothelial cells (HUVECs). Cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) assay, real-time cell analyzer and 5-Ethynyl-2'-deoxyuridine (EdU) staining. Cell migration was detected by wound-healing and transwell assay. AGEs significantly inhibited the proliferation and migration of HUVECs in a time-and dose-dependent way. Western blotting revealed that AGEs dramatically increased the expression of microtubule-associated protein 1 light chain 3 (LC3) II/I and p62...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218659/effects-of-remote-ischemic-preconditioning-on-heme-oxygenase-1-expression-and-cutaneous-wound-repair
#12
Niels A J Cremers, Kimberley E Wever, Ronald J Wong, René E M van Rheden, Eline A Vermeij, Gooitzen M van Dam, Carine E Carels, Ditte M S Lundvig, Frank A D T G Wagener
Skin wounds may lead to scar formation and impaired functionality. Remote ischemic preconditioning (RIPC) can induce the anti-inflammatory enzyme heme oxygenase-1 (HO-1) and protect against tissue injury. We aim to improve cutaneous wound repair by RIPC treatment via induction of HO-1. RIPC was applied to HO-1-luc transgenic mice and HO-1 promoter activity and mRNA expression in skin and several other organs were determined in real-time. In parallel, RIPC was applied directly or 24h prior to excisional wounding in mice to investigate the early and late protective effects of RIPC on cutaneous wound repair, respectively...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218655/taste-receptors-mediate-sinonasal-immunity-and-respiratory-disease
#13
REVIEW
Jennifer E Douglas, Noam A Cohen
The bitter taste receptor T2R38 has been shown to play a role in the pathogenesis of chronic rhinosinusitis (CRS), where the receptor functions to enhance upper respiratory innate immunity through a triad of beneficial immune responses. Individuals with a functional version of T2R38 are tasters for the bitter compound phenylthiocarbamide (PTC) and exhibit an anti-microbial response in the upper airway to certain invading pathogens, while those individuals with a non-functional version of the receptor are PTC non-tasters and lack this beneficial response...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218653/proteomic-analysis-of-mitochondria-enriched-fraction-isolated-from-the-frontal-cortex-and-hippocampus-of-apolipoprotein-e-knockout-mice-treated-with-alda-1-an-activator-of-mitochondrial-aldehyde-dehydrogenase-aldh2
#14
Aneta Stachowicz, Rafał Olszanecki, Maciej Suski, Katarzyna Głombik, Agnieszka Basta-Kaim, Dariusz Adamek, Ryszard Korbut
The role of different genotypes of apolipoprotein E (apoE) in the etiology of Alzheimer's disease is widely recognized. It has been shown that altered functioning of apoE may promote 4-hydroxynonenal modification of mitochondrial proteins, which may result in mitochondrial dysfunction, aggravation of oxidative stress, and neurodegeneration. Mitochondrial aldehyde dehydrogenase (ALDH2) is an enzyme considered to perform protective function in mitochondria by the detoxification of the end products of lipid peroxidation, such as 4-hydroxynonenal and other reactive aldehydes...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218651/proteome-characteristics-of-non-alcoholic-steatohepatitis-liver-tissue-and-associated-hepatocellular-carcinomas
#15
Anna Kakehashi, Vasily E Stefanov, Naomi Ishii, Takahiro Okuno, Hideki Fujii, Kazuaki Kawai, Norifumi Kawada, Hideki Wanibuchi
To uncover mechanisms of nonalcoholic steatohepatitis (NASH) associated hepatocarcinogenesis, we compared the proteomes of human NASH-associated liver biopsies, resected hepatocellular carcinomas (HCCs) and HCCs of HCV⁺ patients with normal liver tissue of patients with gastrointestinal tumor metastasis, in formalin-fixed paraffin-embedded samples obtained after surgery in our hospital during the period from 2006 to 2011. In addition, proteome analysis of liver tumors in male STAM NASH-model mice was performed...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212334/transfer-of-anti-rotavirus-antibodies-during-pregnancy-and-in-milk-following-maternal-vaccination-with-a-herpes-simplex-virus-type-1-amplicon-vector
#16
Anita F Meier, Mark Suter, Elisabeth M Schraner, Bruno M Humbel, Kurt Tobler, Mathias Ackermann, Andrea S Laimbacher
Rotaviruses (RVs) are important enteric pathogens of newborn humans and animals, causing diarrhea and in rare cases death, especially in very young individuals. Rotavirus vaccines presently used are modified live vaccines that lack complete biological safety. Previous work from our laboratory suggested that vaccines based on in situ produced, non-infectious rotavirus-like particles (RVLPs) are efficient while being entirely safe. However, using either vaccine, active mucosal immunization cannot induce protective immunity in newborns due to their immature immune system...
February 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212331/analysis-of-epidermal-growth-factor-receptor-related-gene-expression-changes-in-a-cellular-and-animal-model-of-parkinson-s-disease
#17
In-Su Kim, Sushruta Koppula, Shin-Young Park, Dong-Kug Choi
We employed transcriptome analysis of epidermal growth factor receptor related gene expression changes in cellular and animal models of Parkinson's disease (PD). We used a well-known Parkinsonian toxin 1-methyl-4-phenylpyridine (MPP⁺) to induce neuronal apoptosis in the human neuroblastoma SH-SY5Y cell line. The MPP⁺-treatment of SH-SY5Y cells was capable of inducing neuro-apoptosis, but it remains unclear what kinds of transcriptional genes are affected by MPP⁺ toxicity. Therefore the pathways that were significantly perturbed in MPP⁺ treated human neuroblastoma SH-SY5Y cells were identified based on genome-wide gene expression data at two time points (24 and 48 h)...
February 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212330/synthesis-of-8-aryl-o-methylcyanidins-and-their-usage-for-dye-sensitized-solar-cell-devices
#18
Yuki Kimura, Kin-Ichi Oyama, Yasujiro Murata, Atsushi Wakamiya, Kumi Yoshida
Anthocyanins as natural pigments are colorful and environmentally compatible dyes for dye-sensitized solar cells (DSSCs). To increase the efficiency, we designed and synthesized unnatural O-methylflavonols and O-methylcyanidins that possess an aryl group at the 8-position. We synthesized per-O-methylquercetin from quercetin, then using selective demethylation prepared various O-methylquercetins. Using the Suzuki-Miyaura coupling reaction, 8-arylation of per-O-methylquercetin was achieved. Using a LiAlH₄ reduction or Clemmensen reduction, these flavonols were transformed to the corresponding cyanidin derivatives in satisfactory yields...
February 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212324/differential-gene-expression-in-the-meristem-and-during-early-fruit-growth-of-pisum-sativum-l-identifies-potential-targets-for-breeding
#19
Annu Smitha Ninan, Anish Shah, Jiancheng Song, Paula E Jameson
For successful molecular breeding it is important to identify targets to the gene family level, and in the specific species of interest, in this case Pisum sativum L. The cytokinins have been identified as a key breeding target due to their influence on plant architecture, and on seed size and sink activity. We focused on the cytokinin biosynthetic gene family (the IPTs) and the gene family key to the destruction of cytokinins (the CKXs), as well as other gene families potentially affected by changing cytokinin levels...
February 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212323/low-intensity-extracorporeal-shock-wave-therapy-enhances-brain-derived-neurotrophic-factor-expression-through-perk-atf4-signaling-pathway
#20
Bohan Wang, Hongxiu Ning, Amanda B Reed-Maldonado, Jun Zhou, Yajun Ruan, Tie Zhou, Hsun Shuan Wang, Byung Seok Oh, Lia Banie, Guiting Lin, Tom F Lue
Low-intensity extracorporeal shock wave therapy (Li-ESWT) is used in the treatment of erectile dysfunction, but its mechanisms are not well understood. Previously, we found that Li-ESWT increased the expression of brain-derived neurotrophic factor (BDNF). Here we assessed the underlying signaling pathways in Schwann cells in vitro and in penis tissue in vivo after nerve injury. The result indicated that BDNF were significantly increased by the Li-ESWT after nerve injury, as well as the expression of BDNF in Schwann cells (SCs, RT4-D6P2T) in vitro...
February 16, 2017: International Journal of Molecular Sciences
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