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https://www.readbyqxmd.com/read/28441731/polyphenolic-compounds-and-digestive-enzymes-in-vitro-non-covalent-interactions
#1
REVIEW
Alejandra I Martinez-Gonzalez, Ángel G Díaz-Sánchez, Laura A de la Rosa, Claudia L Vargas-Requena, Ismael Bustos-Jaimes, And Emilio Alvarez-Parrilla
The digestive enzymes-polyphenolic compounds (PCs) interactions behind the inhibition of these enzymes have not been completely studied. The existing studies have mainly analyzed polyphenolic extracts and reported inhibition percentages of catalytic activities determined by UV-Vis spectroscopy techniques. Recently, pure PCs and new methods such as isothermal titration calorimetry and circular dichroism have been applied to describe these interactions. The present review focuses on PCs structural characteristics behind the inhibition of digestive enzymes, and progress of the used methods...
April 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28441717/dexmedetomidine-relieves-formaldehyde-induced-pain-in-rats-through-both-%C3%AE-2-adrenoceptor-and-imidazoline-receptor
#2
Hong Zhang, Xiang Yan, De-Gui Wang, Yu-Fang Leng, Zhan-Hai Wan, Yong-Qiang Liu, Yan Zhang
Dexmedetomidine (DEX) is a highly selective α2 adrenergic receptor agonist. In this study, we investigated the analgesic effect and the underlying mechanisms of DEX on inflammatory visceral pain in rats. Twenty-five male Sprague Dawley (SD) rats were randomly divided into 5 groups, including control, sham, low dose DEX, medium dose DEX and high dose DEX group. Pain was induced with 10% formalin and scored every 15min till 2 h-post the induction. Hematoxylin-eosin (HE) staining was used to evaluate the toxicity of DEX on spinal cord neurons...
April 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28441582/synthesis-and-antiproteasomal-activity-of-novel-o-benzyl-salicylamide-based-inhibitors-built-from-leucine-and-phenylalanine
#3
Radek Jorda, Jan Dušek, Eva Řezníčková, Karel Pauk, Pratibha P Magar, Aleš Imramovský, Vladimír Kryštof
Inhibition of protein degradation is one of strategies for suppression of uncontrolled proliferation of cancer cells. Proteolytic degradation in cells is mainly ensured by proteasome and its inhibition by bortezomib showed benefit in clinical use for the treatment of multiple myeloma. We report here the library of antiproteasomal O-benzyl salicylamides built from leucine and phenylalanine. Prepared compounds displayed antiproliferative activity on K562, CEM and U266 cancer cell lines, ranging from high micromolar to submicromolar GI50 values...
April 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28441565/gut-microbiota-small-molecules-modulate-host-cellular-functions
#4
Jacob M Luber, Aleksandar D Kostic
The human gut metagenome was recently discovered to encode vast collections of biosynthetic gene clusters with diverse chemical potential, almost none of which are yet functionally validated. Recent work elucidates common microbiome-derived biosynthetic gene clusters encoding peptide aldehydes that inhibit human proteases.
April 24, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28440887/microrna-regulation-of-extracellular-matrix-components-in-the-process-of-atherosclerotic-plaque-destabilization
#5
REVIEW
Michal Kowara, Agnieszka Cudnoch-Jedrzejewska, Grzegorz Opolski, Pawel Wlodarski
The process of atherosclerotic plaque destabilization, leading to myocardial infarction, is still not fully understood. The pathway - composed of structural and regulatory proteins of the extracellular matrix (ECM) such as collagen, elastin, small leucine-rich proteoglycans, metalloproteinases, cathepsins and serine proteases - is one potential way of atherosclerotic plaque destabilization. The expression of these proteins is controlled by different microRNA molecules. The goal of this paper is to summarize the current investigations and knowledge about ECM in the process of atherosclerotic plaque destabilization, giving special attention to epigenetic expression regulation by microRNA...
April 25, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28440480/palmitate-impairs-angiogenesis-via-suppression-of-cathepsin-activity
#6
Jin Zhang, Ying Shan, Yong Li, Xinping Luo, Haiming Shi
Angiogenesis requires the interaction of multiple variable factors to promote endothelial cell adhesion, migration and survival. Palmitate, a free fatty acid, exhibits an anti‑angiogenic effect via interference with endothelial cell function, whereas cysteine proteases are important in protein turnover and are termed positive modulators of neovascularization. However, the association between these two factors regarding the regulation of human endothelial cell function remains to be elucidated. By using cell counting kit‑8, the Transwell method and an annexin V‑fluorescein isothiocyanate/propidium iodide apoptosis detection kit, the present study reported that high levels of palmitate result in a significant decrease in endothelial cell proliferation and invasion, and induced cell apoptosis; cathepsin L and S inhibitors may suppress palmitate‑induced apoptosis...
April 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440429/cathepsin%C3%A2-b-expression-in-colorectal-cancer-in-a-middle-east-population-potential-value-as-a-tumor-biomarker-for-late-disease-stages
#7
Maha-Hamadien Abdulla, Mansoor-Ali Valli-Mohammed, Khayal Al-Khayal, Abdulmalik Al Shkieh, Ahmad Zubaidi, Rehan Ahmad, Khalid Al-Saleh, Omar Al-Obeed, James McKerrow
Cathepsin B (CTSB), is a cysteine protease belonging to the cathepsin (Clan CA) family. The diagnostic and prognostic significance of increased CTSB in the serum of cancer patients have been evaluated for some tumor types. CTSB serum and protein levels have also been reported previously in colorectal cancer (CRC) with contradictory results. The aim of the present study was to investigate CTSB expression in CRC patients and the association of CTSB expression with various tumor stages in a Middle East population...
April 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440198/the-role-of-neutrophil-proteases-in-lps-induced-production-of-regulatory-rheumatoid-factor-that-suppresses-autoimmunity
#8
Elena Stolyarova, Liubov Beduleva, Alexandr Sidorov, Igor Menshikov, Alexey Terentiev, Kseniya Vachrusheva
BACKGROUND: We recently identified a regulatory rheumatoid factor (regRF), the production of which is associated with autoimmune disease resistance and remission. In studies of regRF in the blood of healthy rats, spontaneous increases in the regRF level were noted. We suggest that in the normal state, a mechanism exists for maintaining the activity of the pool of regRF-producing lymphocytes at a level that makes it possible to control the expansion of autoreactive lymphocytes. OBJECTIVE: The purpose of this study was to test the hypothesis that the endogenous stimulator of regRF production is Fc fragments of IgG that are formed upon exposure to the proteases of neutrophils...
April 24, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28440185/a-therapeutic-potential-of-animal-%C3%AE-hairpin-antimicrobial-peptides
#9
Tatiana V Ovchinnikova, Pavel V Panteleev, Sergey V Balandin, Vadim T Ivanov
Endogenous antimicrobial peptides (AMPs) are evolutionary ancient molecular factors of innate immunity that play the key role in host defense. Because of the low resistance rate, AMPs have caught extensive attention as possible alternatives to conventional antibiotics. Over the last years, it has become evident that biological functions of AMPs are beyond direct killing of microbial cells. This review focuses on a relatively small family of animal host defense peptides with the β-hairpin structure stabilized by disulfide bridges...
April 24, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28439671/tobacco-etch-virus-protease-mediating-cleavage-of-the-cellulose-binding-module-tagged-colored-proteins-immobilized-on-the-regenerated-amorphous-cellulose
#10
Xuelian Yu, Jiaqi Sun, Weiyu Wang, Li Jiang, Ruyue Wang, Wenjun Xiao, Beijiu Cheng, Jun Fan
In this study, four fusion proteins were designed, in which the N-terminal cellulose-binding module as the affinity tag was immobilized on the regenerated amorphous cellulose (RAC), and the release of the C-terminal colored proteins was detected easily and rapidly after on-resin cleavage using the free tobacco etch virus protease (TEVp) variant, or the immobilized cognate protease with a binding capacity of up to 220 mg protein per gram of RAC. The enhanced stability and repetitive use of the immobilized TEVp compensated slight loss of the catalytic efficiency toward the soluble protein substrate...
April 24, 2017: Bioprocess and Biosystems Engineering
https://www.readbyqxmd.com/read/28439287/rattlesnake-crotalus-molossus-nigrescens-venom-induces-oxidative-stress-on-human-erythrocytes
#11
David Meléndez-Martínez, Juan Manuel Muñoz, Guillermo Barraza-Garza, Martha Sandra Cruz-Peréz, Ana Gatica-Colima, Emilio Alvarez-Parrilla, Luis Fernando Plenge-Tellechea
BACKGROUND: Globally, snake envenomation is a well-known cause of death and morbidity. In many cases of snakebite, myonecrosis, dermonecrosis, hemorrhage and neurotoxicity are present. Some of these symptoms may be provoked by the envenomation itself, but others are secondary effects of the produced oxidative stress that enhances the damage produced by the venom toxins. The only oxidative stress effect known in blood is the change in oxidation number of Fe (from ferrous to ferric) in hemoglobin, generating methemoglobin but not in other macromolecules...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/28439090/slc10a4-regulates-ige-mediated-mast-cell-degranulation-in-vitro-and-mast-cell-mediated-reactions-in-vivo
#12
Hanna Pettersson, Behdad Zarnegar, Annika Westin, Viktor Persson, Christiane Peuckert, Jörgen Jonsson, Jenny Hallgren, Klas Kullander
Mast cells act as sensors in innate immunity and as effector cells in adaptive immune reactions. Here we demonstrate that SLC10A4, also referred to as the vesicular aminergic-associated transporter, VAAT, modifies mast cell degranulation. Strikingly, Slc10a4 (-/-) bone marrow-derived mast cells (BMMCs) had a significant reduction in the release of granule-associated mediators in response to IgE/antigen-mediated activation, whereas the in vitro development of mast cells, the storage of the granule-associated enzyme mouse mast cell protease 6 (mMCP-6), and the release of prostaglandin D2 and IL-6 were normal...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28439009/estrogen-receptor-%C3%AE-a-regulator-of-androgen-receptor-signaling-in-the-mouse-ventral-prostate
#13
Wan-Fu Wu, Laure Maneix, Jose Insunza, Ivan Nalvarte, Per Antonson, Juha Kere, Nancy Yiu-Lin Yu, Virpi Tohonen, Shintaro Katayama, Elisabet Einarsdottir, Kaarel Krjutskov, Yu-Bing Dai, Bo Huang, Wen Su, Margaret Warner, Jan-Åke Gustafsson
As estrogen receptor β(-/-) (ERβ(-/-)) mice age, the ventral prostate (VP) develops increased numbers of hyperplastic, fibroplastic lesions and inflammatory cells. To identify genes involved in these changes, we used RNA sequencing and immunohistochemistry to compare gene expression profiles in the VP of young (2-mo-old) and aging (18-mo-old) ERβ(-/-) mice and their WT littermates. We also treated young and old WT mice with an ERβ-selective agonist and evaluated protein expression. The most significant findings were that ERβ down-regulates androgen receptor (AR) signaling and up-regulates the tumor suppressor phosphatase and tensin homolog (PTEN)...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438975/galectin-3-is-a-target-for-proteases-involved-in-the-virulence-of-staphylococcus-aureus
#14
Jonas Elmwall, Jakub Kwiecinski, Manli Na, Abukar Ahmed Ali, Veronica Osla, Lindsey Shaw, Wanzhong Wang, Karin Sävman, Elisabet Josefsson, Johan Bylund, Tao Jin, Amanda Welin, Anna Karlsson
Staphylococcus aureus is a major cause of skin and soft-tissue infection. The bacterium expresses four major proteases emerging as virulence factors; aureolysin (Aur), V8 protease (SspA), staphopain A (ScpA), and staphopain B (SspB). We hypothesized that human galectin-3, a β-galactoside-binding lectin involved in immune regulation and antimicrobial defense, is a target for these proteases, and that proteolysis of galectin-3 is a novel immune evasion mechanism. Indeed, supernatants from laboratory strains and clinical isolates of S...
April 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28438633/structural-insights-into-the-interaction-of-coronavirus-papain-like-proteases-and-interferon-stimulated-gene-product-15-from-different-species
#15
Courtney M Daczkowski, John V Dzimianski, Jozlyn R Clasman, Octavia Goodwin, Andrew D Mesecar, Scott D Pegan
Severe Acute and Middle East Respiratory syndrome coronaviruses (SARS-CoV and MERS-CoV) encode multifunctional papain-like proteases (PLPs) that have the ability to process the viral polyprotein to facilitate RNA replication as well as antagonize the host innate-immune response. The latter function involves reversing post-translational modification of cellular proteins conjugated with either ubiquitin (Ub) or Ub-like interferon stimulated gene product 15 (ISG15). Ubiquitin is known to be highly conserved among eukaryotes but surprisingly ISG15 is highly divergent among animals...
April 21, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28438620/expression-of-protease-activated-receptor-2-par-2-is-related-to-advanced-clinical-stage-and-adverse-prognosis-in-ovarian-clear-cell-carcinoma
#16
Murasaki Aman, Yoshihiro Ohishi, Hiroko Imamura, Tomoko Shinozaki, Nobuko Yasutake, Kiyoko Kato, Yoshinao Oda
Recent studies demonstrated that Protease-activated receptor-2 (PAR-2) correlates with tumor progression in various tissues. On the other hand, oxidative stress arising from endometriosis has been considered a cause of carcinogenesis in ovarian clear cell carcinoma (OCCC). We previously demonstrated that oxidative stress upregulates PAR-2 expression, and we conducted the present study to investigate the PAR-2 expression and its relation to clinicopathological factors and oxidative stress in OCCC. We performed an immunohistochemical evaluation in 95 cases of OCCC...
April 21, 2017: Human Pathology
https://www.readbyqxmd.com/read/28438120/transcriptomic-analysis-links-gene-expression-to-unilateral-pollen-pistil-reproductive-barriers
#17
Amanda K Broz, Rafael F Guerrero, April M Randle, You Soon Baek, Matthew W Hahn, Patricia A Bedinger
BACKGROUND: Unilateral incompatibility (UI) is an asymmetric reproductive barrier that unidirectionally prevents gene flow between species and/or populations. UI is characterized by a compatible interaction between partners in one direction, but in the reciprocal cross fertilization fails, generally due to pollen tube rejection by the pistil. Although UI has long been observed in crosses between different species, the underlying molecular mechanisms are only beginning to be characterized...
April 24, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28437463/relationship-of-the-crebc-two-component-regulatory-system-and-inner-membrane-protein-cred-with-swimming-motility-in-stenotrophomonas-maltophilia
#18
Hsin-Hui Huang, Wei-Ching Chen, Cheng-Wen Lin, Yi-Tsung Lin, Hsiao-Chen Ning, Yi-Chih Chang, Tsuey-Ching Yang
The CreBC two-component system (TCS) is a conserved regulatory system found in Escherichia coli, Aeromonas spp., Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. In this study, we determined how CreBC TCS regulates secreted protease activities and swimming motility using creB, creC, and creBC in-frame deletion mutants (KJΔCreB, KJΔCreC, and KJΔBC) of S. maltophilia KJ. Compared to wild-type KJ, KJΔCreB had a comparable secreted protease activity; however, the secreted protease activities were obviously reduced in KJΔCreC and KJΔBC, suggesting that CreC works together with another unidentified response regulator (not CreB) to regulate secreted protease activity...
2017: PloS One
https://www.readbyqxmd.com/read/28437250/ionizing-radiation-reduces-adam10-expression-in-brain-microvascular-endothelial-cells-undergoing-stress-induced-senescence
#19
Lucinda S McRobb, Matthew J McKay, Jennifer R Gamble, Michael Grace, Vaughan Moutrie, Estevam D Santos, Vivienne S Lee, Zhenjun Zhao, Mark P Molloy, Marcus A Stoodley
Cellular senescence is associated with aging and is considered a potential contributor to age-associated neurodegenerative disease. Exposure to ionizing radiation increases the risk of developing premature neurovascular degeneration and dementia but also induces premature senescence. As cells of the cerebrovascular endothelium are particularly susceptible to radiation and play an important role in brain homeostasis, we investigated radiation-induced senescence in brain microvascular endothelial cells (EC). Using biotinylation to label surface proteins, streptavidin enrichment and proteomic analysis, we analyzed the surface proteome of stress-induced senescent EC in culture...
April 17, 2017: Aging
https://www.readbyqxmd.com/read/28434781/design-of-novel-hiv-1-protease-inhibitors-incorporating-isophthalamide-derived-p2-p3-ligands-synthesis-biological-evaluation-and-x-ray-structural-studies-of-inhibitor-hiv-1-protease-complex
#20
Arun K Ghosh, Margherita Brindisi, Prasanth R Nyalapatla, Jun Takayama, Jean-Rene Ella-Menye, Sofiya Yashchuk, Johnson Agniswamy, Yuan-Fang Wang, Manabu Aoki, Masayuki Amano, Irene T Weber, Hiroaki Mitsuya
Based upon molecular insights from the X-ray structures of inhibitor-bound HIV-1 protease complexes, we have designed a series of isophthalamide-derived inhibitors incorporating substituted pyrrolidines, piperidines and thiazolidines as P2-P3 ligands for specific interactions in the S2-S3 extended site. Compound 4b has shown an enzyme Ki of 0.025nM and antiviral IC50 of 69nM. An X-ray crystal structure of inhibitor 4b-HIV-1 protease complex was determined at 1.33Å resolution. We have also determined X-ray structure of 3b-bound HIV-1 protease at 1...
April 9, 2017: Bioorganic & Medicinal Chemistry
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