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https://www.readbyqxmd.com/read/28209901/vitamin-b3-modulates-mitochondrial-vulnerability-and-prevents-glaucoma-in-aged-mice
#1
Pete A Williams, Jeffrey M Harder, Nicole E Foxworth, Kelly E Cochran, Vivek M Philip, Vittorio Porciatti, Oliver Smithies, Simon W M John
Glaucomas are neurodegenerative diseases that cause vision loss, especially in the elderly. The mechanisms initiating glaucoma and driving neuronal vulnerability during normal aging are unknown. Studying glaucoma-prone mice, we show that mitochondrial abnormalities are an early driver of neuronal dysfunction, occurring before detectable degeneration. Retinal levels of nicotinamide adenine dinucleotide (NAD(+), a key molecule in energy and redox metabolism) decrease with age and render aging neurons vulnerable to disease-related insults...
February 17, 2017: Science
https://www.readbyqxmd.com/read/28204842/the-effect-of-nonsurgical-periodontal-therapy-on-hnp1-3-level-in-gingival-crevicular-fluid-of-chronic-periodontitis-patients
#2
Ewa Dolińska, Anna Skurska, Małgorzata Pietruska, Violetta Dymicka-Piekarska, Robert Milewski, Jan Pietruski, Anton Sculean
The rich bacterial flora of oral cavity is controlled by innate immune response, including antibacterial peptides and among them human neutrophil peptides 1-3 (HNP1-3). The knowledge of the involvement of HNPs in innate and acquired immunity of the periodontium is fragmentary. The aim of the study was to assess alterations in HNP1-3 levels in the gingival crevicular fluid (GCF) of chronic periodontitis patients before and after nonsurgical periodontal therapy. Nineteen patients with chronic periodontitis were qualified to the study...
February 15, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28199020/gemfibrozil-food-and-drug-administration-approved-lipid-lowering-drug-increases-longevity-in-mouse-model-of-late-infantile-neuronal-ceroid-lipofuscinosis
#3
Arunava Ghosh, Suresh Babu Rangasamy, Khushbu K Modi, Kalipada Pahan
Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL) is a rare neurodegenerative disease caused by mutations in the Cln2 gene that leads to deficiency or loss of function of the tripeptidyl peptidase 1 (TPP1) enzyme. TPP1 deficiency is known to cause the accumulation of autofluoroscent lipid-protein pigments in brain. Similar to other neurodegenerative disorders, LINCL is also associated with neuroinflammation and neuronal damage. Despite investigations, no effective therapy is currently available for LINCL...
February 15, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28193778/ag-221-a-first-in-class-therapy-targeting-acute-myeloid-leukemia-harboring-oncogenic-idh2-mutations
#4
Katharine Yen, Jeremy Travins, Fang Wang, Muriel D David, Erin Artin, Kim Straley, Anil Padyana, Stefan Gross, Byron DeLaBarre, Erica Tobin, Yue Chen, Raj Nagaraja, Sung Choe, Lei Jin, Zenon Konteatis, Giovanni Cianchetta, Jeffrey O Saunders, Francesco G Salituro, Cyril Quivoron, Paule Opolon, Olivia Bawa, Véronique Saada, Angelo Paci, Sophie Broutin, Olivier A Bernard, Stéphane de Botton, Benoît S Marteyn, Monika Pilichowska, YingXia Xu, Cheng Fang, Fan Jiang, Wentao Wei, Shengfang Jin, Lee Silverman, Wei Liu, Hua Yang, Lenny Dang, Marion Dorsch, Virginie Penard-Lacronique, Scott A Biller, Shin-San Michael Su
Somatic gain-of-function mutations in isocitrate dehydrogenase (IDH) 1 and 2 are found in multiple hematologic and solid tumors, leading to accumulation of the oncometabolite, (R)-2-hydroxyglutarate (2HG). 2HG competitively inhibits α-ketoglutarate-dependent dioxygenases, including histone demethylases and methylcytosine dioxygenases of the Tet family, causing epigenetic dysregulation and a block in cellular differentiation. In vitro studies have provided proof of concept for mutant IDH inhibition as a therapeutic approach...
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28192475/adverse-cardiac-effects-of-exogenous-angiotensin-1-7-in-rats-with-subtotal-nephrectomy-are-prevented-by-ace-inhibition
#5
Louise M Burrell, Daniel Gayed, Karen Griggs, Sheila K Patel, Elena Velkoska
We previously reported that exogenous angiotensin (Ang) 1-7 has adverse cardiac effects in experimental kidney failure due to its action to increase cardiac angiotensin converting enzyme (ACE) activity. This study investigated if the addition of an ACE inhibitor (ACEi) to Ang 1-7 infusion would unmask any beneficial effects of Ang 1-7 on the heart in experimental kidney failure. Male Sprague-Dawley rats underwent subtotal nephrectomy (STNx) and were treated with vehicle, the ACEi ramipril (oral 1mg/kg/day), Ang 1-7 (subcutaneous 24 μg/kg/h) or dual therapy (all groups, n = 12)...
2017: PloS One
https://www.readbyqxmd.com/read/28191770/stem-cell-based-tissue-engineered-laryngeal-replacement
#6
Tahera Ansari, Peggy Lange, Aaron Southgate, Karin Greco, Carla Carvalho, Leanne Partington, Anthony Bullock, Sheila MacNeil, Mark W Lowdell, Paul D Sibbons, Martin A Birchall
Patients with laryngeal disorders may have severe morbidity relating to swallowing, vocalization, and respiratory function, for which conventional therapies are suboptimal. A tissue-engineered approach would aim to restore the vocal folds and maintain respiratory function while limiting the extent of scarring in the regenerated tissue. Under Good Laboratory Practice conditions, we decellularized porcine larynges, using detergents and enzymes under negative pressure to produce an acellular scaffold comprising cartilage, muscle, and mucosa...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28190975/reduced-platelet-hyper-reactivity-and-platelet-leukocyte-aggregation-after-periodontal-therapy
#7
Efthymios Arvanitidis, Sergio Bizzarro, Elena Alvarez Rodriguez, Bruno G Loos, Elena A Nicu
BACKGROUND: Platelets from untreated periodontitis patients are hyper-reactive and form more platelet-leukocyte complexes compared to cells from individuals without periodontitis. It is not known whether the improvement of the periodontal condition achievable by therapy has beneficial effects on the platelet function. We aimed to assess the effects of periodontal therapy on platelet reactivity. METHODS: Patients with periodontitis (n = 25) but unaffected by any other medical condition or medication were included and donated blood before and after periodontal therapy...
2017: Thrombosis Journal
https://www.readbyqxmd.com/read/28185054/identification-of-new-lead-molecules-against-ube2nl-enzyme-for-cancer-therapy
#8
Vishwanath Ramatenki, Ramakrishna Dumpati, Rajender Vadija, Santhiprada Vellanki, Sarita Rajender Potlapally, Rohini Rondla, Uma Vuruputuri
Cancer is characterized by abnormal growth of cells. Targeting ubiquitin proteins in the discovery of new anticancer therapeutics is an attractive strategy. The present study uses the structure-based drug discovery methods to identify new lead structures, which are selective to the putative ubiquitin-conjugating enzyme E2N-like (UBE2NL). The 3D structure of the UBE2NL was evaluated using homology modeling techniques. The model was validated using standard in silico methods. The hydrophobic pocket of UBE2NL that aids in binding with its natural receptor ubiquitin-conjugating enzyme E2 variant (UBE2V) was identified through protein-protein docking study...
February 9, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28135601/interaction-of-quercetin-and-its-metabolites-with-warfarin-displacement-of-warfarin-from-serum-albumin-and-inhibition-of-cyp2c9-enzyme
#9
Miklós Poór, Gabriella Boda, Paul W Needs, Paul A Kroon, Beáta Lemli, Tímea Bencsik
Flavonoids are ubiquitous molecules in nature with manifold pharmacological effects. Flavonoids interact with several proteins, and thus potentially interfere with the pharmacokinetics of various drugs. Though much is known about the protein binding characteristics of flavonoid aglycones, the behaviour of their metabolites, which are extensively formed in the human body has received little attention. In this study, the interactions of the flavonoid aglycone quercetin and its main metabolites with the albumin binding of the oral anticoagulant warfarin were investigated by fluorescence spectroscopy and ultrafiltration...
January 27, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28134775/chrysin-protects-rat-kidney-from-paracetamol-induced-oxidative-stress-inflammation-apoptosis-and-autophagy-a-multi-biomarker-approach
#10
Fatih Mehmet Kandemir, Sefa Kucukler, Eyup Eldutar, Cuneyt Caglayan, İlhami Gülçin
Paracetamol (PC) is a safe analgesic and antipyretic drug at therapeutic doses, and it is widely used in clinics. However, at high doses, it can induce hepatotoxicity and nephrotoxicity. Chrysin (CR) is a natural flavonoid that has biological activities that include being an antioxidant, an anti-inflammatory, and an anti-cancer agent. The main objective of this study was to investigate the efficacy of CR against PC-induced nephrotoxicity in rats. CR was given orally via feeding needle to male Sprague Dawley rats as a single daily dose of 25 or 50 mg/kg for six days...
January 26, 2017: Scientia Pharmaceutica
https://www.readbyqxmd.com/read/28129335/reduction-of-aflatoxin-b1-toxicity-by-lactobacillus-plantarum-c88-a-potential-probiotic-strain-isolated-from-chinese-traditional-fermented-food-tofu
#11
Li Huang, Cuicui Duan, Yujuan Zhao, Lei Gao, Chunhua Niu, Jingbo Xu, Shengyu Li
In this study, we investigated the potential of Lactobacillus plantarum isolated from Chinese traditional fermented foods to reduce the toxicity of aflatoxin B1 (AFB1), and its subsequent detoxification mechanism. Among all the investigated L. plantarum strains, L. plantarum C88 showed the strongest AFB1 binding capacity in vitro, and was orally administered to mice with liver oxidative damage induced by AFB1. In the therapy groups, the mice that received L. plantarum C88, especially heat-killed L. plantarum C88, after a single dose of AFB1 exposure, showed an increase in unabsorbed AFB1 in the feces...
2017: PloS One
https://www.readbyqxmd.com/read/28125922/ace-inhibitor-induced-angioedema-of-the-small-bowel
#12
Kent L Wilin, Michael J Czupryn, Richard Mui, Anas Renno, Julie A Murphy
Angiotensin-converting enzyme (ACE) inhibitors are known to cause angioedema. Most ACE inhibitor-induced angioedema cases describe swelling in the periorbital region, tongue, and pharynx. We describe a case of a 62-year-old female with presumed angioedema of the small bowel after more than a 2-year history of lisinopril use (with no recent changes in her dose of 40 mg orally twice daily). The patient presented with nausea and intermittent left middle and upper quadrant abdominal pain and denied history of angioedema or swelling with any medications or any history of abdominal pain...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/28123123/-acute-phase-reaction-following-bisphosphonates
#13
Hiroshi Tsurukami
Bisphosphonates are effective in decreasing bone resorption, the incidence of fragility fracure, and pain from bone metastases. Although relatively well tolerated, the initial dose(s)of intravenous or oral monthly aminobisphosphonates can be associated with an acute phase response, a nonspecific physiologic reaction associated with increased levels of inflammatory cytokines, fever, and flu like symptoms including fatigue, nausea, and myalgia within 3 days of dosing and lasting 7 days or less. Nitrogen-BPs(N-BPs)inhibit osteoclast function by acting as potent inhibitors of the enzyme farnesyl diphosphate(FPP)synthase in the mevalonate biosynthetic pathway...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28120922/microencapsulation-with-alginate-caco3-a-strategy-for-improved-phage-therapy
#14
Joan Colom, Mary Cano-Sarabia, Jennifer Otero, Javier Aríñez-Soriano, Pilar Cortés, Daniel Maspoch, Montserrat Llagostera
Bacteriophages are promising therapeutic agents that can be applied to different stages of the commercial food chain. In this sense, bacteriophages can be orally administered to farm animals to protect them against intestinal pathogens. However, the low pH of the stomach, the activities of bile and intestinal tract enzymes limit the efficacy of the phages. This study demonstrates the utility of an alginate/CaCO3 encapsulation method suitable for bacteriophages with different morphologies and to yield encapsulation efficacies of ~100%...
January 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28120013/secretory-expression-and-surface-display-of-a-new-and-biologically-active-single-chain-insulin-sci-59-analog-by-lactic-acid-bacteria
#15
Ruifeng Mao, Dongli Wu, Shimeng Hu, Kangping Zhou, Man Wang, Yefu Wang
Insulin plays an important role in drug therapies for diabetes mellitus and as the main route of insulin delivery, subcutaneous injection may cause local discomfort, hypoglycemia, hyperinsulinemia, and patient non-compliance. Therefore, oral delivery of insulin is more preferred. However, there is a low bioavailability due to insulin degradation by proteolytic enzymes and severe pH conditions along the gastrointestinal tract. In order to use the food-grade bacteria lactic acid bacteria (LAB) as oral delivery vehicles, a new and bioactive single-chain insulin (SCI-59) analog, containing the insulin B- and A-chains connected by an eight-residue linker (RSRGLPFR), was secretory expressed in Lactococcus lactis NZ3900 without using an antibiotic resistance gene and displayed onto the surface of various non-viable bacteria (NVBs) without genetic modification...
January 24, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28116598/enterolactone-glucuronide-and-%C3%AE-glucuronidase-in-antibody-directed-enzyme-prodrug-therapy-for-targeted-prostate-cancer-cell-treatment
#16
Yunyun Di, Shaoping Ji, Philipp Wolf, Ed S Krol, Jane Alcorn
Evidence from preclinical and animal studies demonstrated an anticancer effect of flaxseed lignans, particularly enterolactone (ENL), against prostate cancer. However, extensive first-pass metabolism following oral lignan consumption results in their systemic availability primarily as glucuronic acid conjugates (ENL-Gluc) and their modest in vivo effects. To overcome the unfavorable pharmacokinetics and improve their effectiveness in prostate cancer, antibody-directed enzyme prodrug therapy (ADEPT) might offer a novel strategy to allow for restricted activation of ENL from circulating ENL-Gluc within the tumor environment...
January 23, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28115286/new-aspects-on-the-hepatoprotective-potential-associated-with-the-antioxidant-hypocholesterolemic-and-anti-inflammatory-activities-of-vernonia-condensata-baker
#17
Jucélia Barbosa da Silva, Renata de Freitas Mendes, Vívian Tomasco, Nícolas de Castro Campos Pinto, Luiz Gustavo de Oliveira, Matheus Nehrer Rodrigues, Danielle Maria de Oliveira Aragão, Jair Adriano Kopke de Aguiar, Maria Silvana Alves, Maria Christina Nogueira Marques Castañon, Antônia Ribeiro, Elita Scio
ETHNOPHARMACOLOGICAL RELEVANCE: Vernonia condensata Baker (Asteraceae) is traditionally used in South American Countries as an anti-inflammatory, analgesic and hepatoprotective. AIM OF THE STUDY: This study aimed to investigate the in vivo hepatoprotective and antioxidant, and the in vitro anti-inflammatory activities of the ethyl acetate partition (EAP) from the ethanolic extract of this medicinal plant leaves. MATERIALS AND METHODS: For the in vivo hepatoprotective activity, rats were pretreated orally for seven days with vehicle, silymarin 100mg/kg or EAP 50, 100 and 200mg/kg...
January 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28108235/the-use-of-bacteriophages-to-biocontrol-oral-biofilms
#18
Szymon P Szafrański, Andreas Winkel, Meike Stiesch
Infections induced by oral biofilms include caries, as well as periodontal, and peri-implant disease, and may influence quality of life, systemic health, and expenditure. As bacterial biofilms are highly resistant and resilient to conventional antibacterial therapy, it has been difficult to combat these infections. An innovative alternative to the biocontrol of oral biofilms could be to use bacteriophages or phages, the viruses of bacteria, which are specific, non-toxic, self-proliferating, and can penetrate into biofilms...
January 17, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28107795/adherence-to-therapies-in-cystic-fibrosis-a-targeted-literature-review
#19
Siva Narayanan, Jochen G Mainz, Smeet Gala, Harold Tabori, Daniel Grossoehme
Cystic fibrosis (CF) is a life-shortening condition with no cure. Available therapies relieving the symptoms of CF are complex and time-consuming. A comprehensive review assessing adherence to different CF therapies, association of adherence with outcomes, and factors influencing adherence could inform optimal patient management strategies. Areas covered: A targeted literature review of studies published from 2010-2016 assessed adherence to CF therapies. Nineteen studies qualified for inclusion. Adherence to CF therapies was sub-optimal, and varied by treatment, mode of treatment administration, age, season, time and method of adherence measurement...
January 20, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28107533/improvement-of-therapeutic-efficacy-of-oral-immunotherapy-in-combination-with-regulatory-t-cell-inducer-kakkonto-in-a-murine-food-allergy-model
#20
Yuka Nagata, Takeshi Yamamoto, Michie Hayashi, Shusaku Hayashi, Makoto Kadowaki
Oral immunotherapy (OIT) has been considered a promising approach for food allergies (FAs). However, the current OIT strategy is limited in terms of the long-term efficacy and safety. We have previously demonstrated that kakkonto, a traditional Japanese herbal medicine, suppresses the occurrence of allergic symptoms in a murine model of ovalbumin (OVA)-induced FA, which is attributed to the induction of the Foxp3+ CD4+ regulatory T cells. In this study, we established an OIT model using the FA mice with already established allergic symptoms and determined whether kakkonto could improve the efficacy of OIT...
2017: PloS One
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