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https://www.readbyqxmd.com/read/29793058/the-transcription-factor-skn-1-and-detoxification-gene-ugt-22-alter-albendazole-efficacy-in-caenorhabditis-elegans
#1
Pauline Fontaine, Keith Choe
Parasitic nematodes infect over 1/4 th of the human population and are a major burden on livestock and crop production. Benzimidazole class anthelmintics are widely used to treat infections, but resistance is a widespread problem. Mutation of genes encoding the benzimidazole target β-tubulin is a well-established mechanism of resistance, but recent evidence suggests that metabolism of the drugs may also occur. Our objective was to investigate contributions of the detoxification-response transcription factor SKN-1 to anthelmintic drug resistance using C...
April 25, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29793055/fatty-acid-activation-in-thermogenic-adipose-tissue
#2
REVIEW
Sandra Steensels, Baran A Ersoy
Channeling carbohydrates and fatty acids to thermogenic tissues, including brown and beige adipocytes, have garnered interest as an approach for the management of obesity-related metabolic disorders. Mitochondrial fatty acid oxidation (β-oxidation) is crucial for the maintenance of thermogenesis. Upon cellular fatty acid uptake or following lipolysis from triglycerides (TG), fatty acids are esterified to coenzyme A (CoA) to form active acyl-CoA molecules. This enzymatic reaction is essential for their utilization in β-oxidation and thermogenesis...
May 21, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29793019/factors-predicting-non-compliance-with-follow-up-after-endovascular-aneurysm-repair
#3
Timothy P Shiraev, Elif Durur, David A Robinson
PURPOSE: Although the potential for complications following endovascular aneurysm repair (EVAR) mandates lifetime follow-up, non-compliance with follow-up has been shown to be as high as 57%. We sought to investigate the incidence of non-compliance with follow up in our patient population and to identify risk factors associated with this, in order to allow implementation of targeted strategies to prevent loss to follow up. METHODOLOGY: We carried out a review of consecutive patients undergoing EVAR at two Sydney hospitals between 1995 and 2015...
May 21, 2018: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/29792879/astragaloside-suppresses-apoptosis-of-the-podocytes-in-rats-with-diabetic-nephropathy-via-mir-378-traf5-signaling-pathway
#4
Xiao Lei, Bo-da Zhang, Ji-Gang Ren, Fang-Li Luo
AIMS: Apoptosis of podocytes plays a crucial role in diabetic nephropathy (DN) development, and astragaloside (AS-IV) has a significant impact on podocyte apoptosis. This study aims to explore the effect of AS-IV on diabetic nephropathy progression. MATERIALS AND METHODS: The diabetic nephropathy model was established in rats with streptozotocin (STZ) injection. The albuminuria was examined by using the enzyme linked immunosorbent assay (ELISA). The expression of miR-378, tumor-necrosis factor (TNF) receptor (TNFR)-associated factor 5 (TRAF5) mRNA and protein was analyzed by qRT-PCR and western blot, respectively...
May 21, 2018: Life Sciences
https://www.readbyqxmd.com/read/29792857/tgf-%C3%AE-plays-a-vital-role-in-triple-negative-breast-cancer-tnbc-drug-resistance-through-regulating-stemness-emt-and-apoptosis
#5
Xiaodan Xu, Lu Zhang, Xiaogang He, Ping Zhang, Caihong Sun, Xiaojun Xu, Yaojuan Lu, Feifei Li
Triple negative breast cancer (TNBC) is the most malignant subtype of breast cancer in which the cell surface lacks usual targets for drug to exhibit its effects. Epirubicin (Epi) is widely used for TNBC, but a substantial number of patients develop Epi resistance that is usually associated with poor prognosis. Transforming growth factor (TGF-β) is a multifunctional cytokine. In recent study, it appears that TGF-β influences the cancer stem cell population, thus, the drug resistance of cancer may also be affected...
May 21, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29792808/eradication-of-established-tumors-by-chemically-self-assembled-nanoring-csan-targeted-t-cells
#6
Jacob Petersburg, Jingjing Shen, Clifford M Csizmar, Katherine A Murphy, Justin Spanier, Kari Gabrielse, Thomas S Griffith, Brian Fife, Carston R Wagner
Our laboratory has developed chemically self-assembled nanorings (CSANs) as prosthetic antigen receptors (PARs) for the non-genetic modification of T-cell surfaces. PARs have been successfully employed in vitro to activate T cells for the selective killing of leukemia cells. However, PAR efficacy has yet to be evaluated in vivo or against solid tumors. Therefore, we developed bispecific PARs that selectively target the human CD3 receptor and human Epithelial Cell Adhesion Molecule (EpCAM), which is overexpressed on multiple carcinomas and cancer stem cells...
May 24, 2018: ACS Nano
https://www.readbyqxmd.com/read/29792703/structure-based-design-of-inhibitors-with-improved-selectivity-for-steroidogenic-cytochrome-p450-17a1-over-cytochrome-p450-21a2
#7
Charlie Fehl, Caleb D Vogt, Rahul Yadav, Kelin Li, Emily E Scott, Jeffrey Aubé
Inhibition of androgen biosynthesis is clinically effective for treating androgen-responsive prostate cancer. Abiraterone is a clinical first-in-class inhibitor of cytochrome P450 17A1 (CYP17A1) required for androgen biosynthesis. However, abiraterone also causes hypertension, hypokalemia, and edema, likely due in part to off-target inhibition of another steroidogenic cytochrome P450, CYP21A2. Abiraterone analogs were designed based on structural evidence that B-ring substituents may favorably interact with polar residues in binding CYP17A1 and sterically clash with residues in the CYP21A2 active site...
May 24, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29792572/galnac-sirna-conjugates-leading-the-way-for-delivery-of-rnai-therapeutics
#8
Aaron D Springer, Steven F Dowdy
Short-interfering RNA (siRNA)-induced RNAi responses have great potential to treat a wide variety of human diseases from cancer to pandemic viral outbreaks to Parkinson's Disease. However, before siRNAs can become drugs, they must overcome a billion years of evolutionary defenses designed to keep invading RNAs on the outside cells from getting to the inside of cells. Not surprisingly, significant effort has been placed in developing a wide array of delivery technologies. Foremost of these has been the development of N-acetylgalactosamine (GalNAc) siRNA conjugates for delivery to liver...
May 24, 2018: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/29792404/culotte-stenting-for-coronary-bifurcation-lesions-with-2nd-and-3rd-generation-everolimus-eluting-stents-the-celtic-bifurcation-study
#9
Simon J Walsh, Colm G Hanratty, Stuart Watkins, Keith G Oldroyd, Niall T Mulvihill, Mark Hensey, Alex Chase, Dave Smith, Nick Cruden, James C Spratt, Darren Mylotte, Tom Johnson, Jonathan Hill, Hafiz M Hussein, Kris Bogaerts, Marie-Claude Morice, David P Foley
AIMS: The aim of this study was to provide contemporary outcome data for patients with de novo coronary disease and Medina 1,1,1 lesions who were treated with a culotte two-stent technique, and to compare the performance of two modern-generation drug-eluting stent (DES) platforms, the 3-connector XIENCE and the 2-connector SYNERGY. METHODS AND RESULTS: Patients with Medina 1,1,1 bifurcation lesions who had disease that was amenable to culotte stenting were randomised 1:1 to treatment with XIENCE or SYNERGY DES...
May 24, 2018: EuroIntervention
https://www.readbyqxmd.com/read/29792395/how-are-patients-with-heart-failure-treated-in-primary-care
#10
Hélène Vaillant-Roussel, Bruno Pereira, Sylvaine Gibot-Boeuf, Romain Eschalier, Claude Dubray, Rémy Boussageon, Philippe Vorilhon
OBJECTIVE: The aim of this study was to assess the adherence of general practitioners (GPs) to guidelines in patients with heart failure with reduced ejection fraction (HFrEF) and to describe GPs' prescribing behavior regarding patients with heart failure with preserved ejection fraction (HFpEF). MATERIALS AND METHODS: Cross-sectional study as part of the ETIC trial. Five classes of drugs were described: angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs); β-blockers (BBs); mineralocorticoid receptor antagonists (MRAs); diuretics (thiazide or loop diuretics); and digoxin...
May 24, 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29792227/integrated-time-course-omics-analysis-distinguishes-immediate-therapeutic-response-from-acquired-resistance
#11
Genevieve Stein-O'Brien, Luciane T Kagohara, Sijia Li, Manjusha Thakar, Ruchira Ranaweera, Hiroyuki Ozawa, Haixia Cheng, Michael Considine, Sandra Schmitz, Alexander V Favorov, Ludmila V Danilova, Joseph A Califano, Evgeny Izumchenko, Daria A Gaykalova, Christine H Chung, Elana J Fertig
BACKGROUND: Targeted therapies specifically act by blocking the activity of proteins that are encoded by genes critical for tumorigenesis. However, most cancers acquire resistance and long-term disease remission is rarely observed. Understanding the time course of molecular changes responsible for the development of acquired resistance could enable optimization of patients' treatment options. Clinically, acquired therapeutic resistance can only be studied at a single time point in resistant tumors...
May 23, 2018: Genome Medicine
https://www.readbyqxmd.com/read/29792216/hiv-1-tat-phosphorylation-on-ser-16-residue-modulates-hiv-1-transcription
#12
Andrey Ivanov, Xionghao Lin, Tatiana Ammosova, Andrey V Ilatovskiy, Namita Kumari, Hatajai Lassiter, Nowah Afangbedji, Xiaomei Niu, Michael G Petukhov, Sergei Nekhai
BACKGROUND: HIV-1 transcription activator protein Tat is phosphorylated in vitro by CDK2 and DNA-PK on Ser-16 residue and by PKR on Tat Ser-46 residue. Here we analyzed Tat phosphorylation in cultured cells and its functionality. RESULTS: Mass spectrometry analysis showed primarily Tat Ser-16 phosphorylation in cultured cells. In vitro, CDK2/cyclin E predominantly phosphorylated Tat Ser-16 and PKR-Tat Ser-46. Alanine mutations of either Ser-16 or Ser-46 decreased overall Tat phosphorylation...
May 23, 2018: Retrovirology
https://www.readbyqxmd.com/read/29792176/anti-neutrophil-cytoplasmic-antibody-associated-glomerulonephritis-with-detection-of-myeloperoxidase-and-phospholipase-a-2-receptor-in-membranous-nephropathy-lesions-report-of-two-patients-with-microscopic-polyangiitis
#13
Kenta Tominaga, Takahiro Uchida, Toshihiko Imakiire, Kenji Itoh, Hideyuki Shimazaki, Kuniaki Nakanishi, Hiroo Kumagai, Naoki Oshima
BACKGROUND: Podocyte phospholipase A2 receptor (PLA2 R) is a major target antigen in idiopathic adult membranous nephropathy (MN). Histological PLA2 R staining in the renal tissue has proven to be useful for the detection of idiopathic MN. However, glomerular PLA2 R deposits have also been recently observed in several patients with secondary MN, such as hepatitis B virus-associated, hepatitis C virus-associated, and neoplasm-associated MN. Certain inflammatory environments have been suggested to lead to abnormal expression of PLA2 R epitopes, with the resulting production of PLA2 R autoantibodies...
May 23, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29792023/fern-9-11-ene-2%C3%AE-3%C3%AE-diol-action-on-insulin-secretion-in-hyperglycemic-conditions
#14
Allisson Jhonatan Gomes Castro, Luisa Helena Cazarolli, Gabrielle Da Luz, Delsi Altenhofen, Hemily Batista Da Silva, Francieli Kanumfre Carvalho, Moacir Geraldo Pizzolatti, Fátima Rmb Silva
The objective of this study was to investigate the effect and the mechanism of action of fernenediol as insulin secretagogue. Wistar rats were treated with 0.1; 1 and 10 mg/kg fernenediol and then induced hyperglycemia by oral glucose. The glycaemia, insulin, LDH, calcium and hepatic glycogen were analyzed. Considering the intestine and pancreas as targets for the triterpene action, the duodenum was used to verify the influence of fernenediol on intestinal glycosidases. Additionally, pancreatic islets were used for studies of 14 C-deoxyglucose uptake and influx of 45 Ca2+ in hyperglycemic medium with/without fernenediol in the presence/absence of an inhibitor/activator of KATP channels, glibenclamide, diazoxide, nifedipine, calcium chelator (BAPTA- AM) and H-89 and ST the inhibitors of the PKA and PKC enzymes...
May 24, 2018: Biochemistry
https://www.readbyqxmd.com/read/29791834/molecular-and-functional-sex-differences-of-noradrenergic-neurons-in-the-mouse-locus-coeruleus
#15
Bernard Mulvey, Dionnet L Bhatti, Sandeep Gyawali, Allison M Lake, Skirmantas Kriaucionis, Christopher P Ford, Michael R Bruchas, Nathaniel Heintz, Joseph D Dougherty
Preclinical work has long focused on male animals, though biological sex clearly influences risk for certain diseases, including many psychiatric disorders. Such disorders are often treated by drugs targeting the CNS norepinephrine system. Despite roles for noradrenergic neurons in behavior and neuropsychiatric disease models, their molecular characterization has lagged. We profiled mouse noradrenergic neurons in vivo, defining over 3,000 high-confidence transcripts expressed therein, including druggable receptors...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29791258/licorice-root-extract-and-magnesium-isoglycyrrhizinate-protect-against-triptolide-induced-hepatotoxicity-via-up-regulation-of-the-nrf2-pathway
#16
Qin-You Tan, Qian Hu, Sheng-Nan Zhu, Lu-Lu Jia, Juan Xiao, Hua-Zhen Su, Shao-Yuan Huang, Jing Zhang, Junfei Jin
Triptolide, the predominant biologically active component of the Chinese herb Tripterygium wilfordii Hook f., possesses numerous pharmacological activities, including anti-inflammatory, anti-fertility, anti-neoplastic, and immunosuppressive effects. However, toxicity and severe adverse effects, particularly hepatotoxicity, limit the clinical application of triptolide. Licorice root extract contains various bioactive compounds and is potent hepatoprotective. Magnesium isoglycyrrhizinate, a magnesium salt of the 18α-glycyrrhizic acid stereoisomer of glycyrrhizic acid, is used clinically in China to treat chronic viral hepatitis and acute drug-induced liver injury...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29791175/-dyslipidemia-and-hypertension-what-to-worry-about-more
#17
Jan Václavík
Dyslipidemia is present in every other patient with arterial hypertension. With increasing blood pressure and cholesterol levels, the risk of cardiovascular events increases proportionally. Treatment of dyslipidemia appears to lower cardiovascular mortality to a greater extent than treatment of hypertension. A significant proportion of patients with dyslipidemia indicated for drug therapy are not treated at all or treated insufficiently and do not reach the target values. Concurrent treatment of hypertension and dyslipidemia reduces the incidence of cardiovascular events significantly more than treating only one of these diseases...
2018: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29790803/ultrasound-guided-delivery-of-thymidine-kinase-nitroreductase-dual-therapeutic-genes-by-pegylated-plga-pie-nanoparticles-for-enhanced-triple-negative-breast-cancer-therapy
#18
Rammohan Devulapally, Taehwa Lee, Aarohi Barghava-Shah, Thillai V Sekar, Kira Foygel, Sunitha V Bachawal, Jürgen K Willmann, Ramasamy Paulmurugan
AIM: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype. Since no targeted therapy is available, gene-directed enzyme prodrug therapy (GDEPT) could be an attractive strategy for treating TNBC. MATERIALS & METHODS:  Polyethylene glycol (PEG)ylated-poly(lactic-co-glycolic acid)/polyethyleneimine nanoparticles (PLGA/PEI NPs) were synthesized and complexed with TK-NTR fusion gene. Ultrasound (US) and microbubble (MB) mediated sonoporation was used for efficient delivery of the TK-NTR-DNA-NP complex to TNBC tumor in vivo for cancer therapy...
May 2018: Nanomedicine
https://www.readbyqxmd.com/read/29790778/survey-of-family-related-factors-of-children-treated-under-dental-general-anaesthesia
#19
P Rajavaara, M-L Laitala, H Vähänikkilä, V Anttonen
AIM: Treatment under general anaesthesia (DGA) is a rising trend in Finland. There is a great need to investigate the causes leading to it. Our purpose was to examine family-related factors reported by parents, such as the family size and favoring DGA in the family, and their influence on children being treated under DGA. This survey was based on a questionnaire targeted to parents of children whose dental treatment could not be performed in a conventional setting. MATERIALS AND METHODS: Guardians of 87 healthy children treated under DGA at a municipal health center in the city of Oulu, Finland, between November 2014 and December 2015 answered the questionnaire on family-related background factors and on the respondent's own as well as their child's presumed dental fear...
June 2018: European Journal of Paediatric Dentistry: Official Journal of European Academy of Paediatric Dentistry
https://www.readbyqxmd.com/read/29790727/pathophysiology-of-severe-traumatic-brain-injury-overview
#20
Ruth A O'leary, Alistair D Nichol
Traumatic brain injury is a leading cause of morbidity and mortality globally, particularly among young people, with significant social and economic effects. The World Health Organization (WHO) estimates that more than five million people die each year from traumatic injuries worldwide. While public health initiative such as seatbelts and airbags have had a major impact, it will be impossible to prevent traumatic brain injury, it is therefore that we understand the pathophysiology of secondary brain injury to be able to effectively treat our patient but aloes to develop novel targets of future interventions...
May 22, 2018: Journal of Neurosurgical Sciences
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