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https://www.readbyqxmd.com/read/30121499/lipid-metabolism-disorder-induced-by-up-regulation-of-mir-125b-and-mir-144-following-%C3%AE-diketone-antibiotic-exposure-to-f0-zebrafish-danio-rerio
#1
Xuedong Wang, Yuansi Zheng, Yan Ma, Liyang Du, Fangyu Chu, Haidong Gu, Randy A Dahlgren, Yanyan Li, Huili Wang
β-Diketone antibiotics (DKAs) are widely used in human and veterinary medicine to prevent and treat a large variety of infectious diseases. Long-term DKA exposure to zebrafish can result in lipid metabolism disorders and liver function abnormalities. Based on our previous miRNA-seq analyses, miR-144 and miR-125b were identified as target genes regulating lipid metabolism. DKA-exposure at 12.5 and 25 mg/L significantly increased the expressions of miR-144 and miR-125b. The expression levels for the two miRNAs exhibited an inverse relationship with their lipid-metabolism-related target genes (ppardb, bcl2a, pparaa and pparda)...
August 16, 2018: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/30121491/remission-maintenance-treatment-options-in-chronic-lymphocytic-leukemia
#2
REVIEW
Alexander Egle, Lisa Pleyer, Thomas Melchardt, Tanja Nicole Hartmann, Richard Greil
Chronic lymphocytic leukemia (CLL) treatment has come a long way in the last two decades, producing increases in tumor control to the point of generating sizeable numbers of patients with undetectable minimal residual disease and creating overall survival benefits in randomized comparisons. Most of this has been achieved by limited-term treatment approaches including chemotherapeutic and immune-therapeutic drugs. More recently, novel therapies targeting signaling pathways essential for the survival of the neoplastic clones have opened avenues that provide disease control in long-term treatment designs, mostly without producing deep remissions...
August 10, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/30121124/developments-in-anti-complement-therapy-from-disease-to-clinical-trial
#3
Claire L Harris, Richard B Pouw, David Kavanagh, Ruyue Sun, Daniel Ricklin
The complement system is well known for its role in innate immunity and in maintenance of tissue homeostasis, providing a first line of defence against infection and playing a key role in flagging apoptotic cells and debris for disposal. Unfortunately complement also contributes to pathogenesis of a number of diseases; in some cases driving pathology, and in others amplifying or exacerbating the inflammatory and damaging impact of non-complement disease triggers. The role of complement in pathogenesis of an expanding number of diseases has driven industry and academia alike to develop an impressive arsenal of anti-complement drugs which target different proteins and functions of the complement cascade...
August 15, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/30120962/progression-of-alzheimer-s-disease-tau-propagation-and-its-modifiable-risk-factors
#4
REVIEW
Shuko Takeda
The number of patients with Alzheimer's disease (AD) has been increasing exponentially side by side with aging societies worldwide. Symptoms of AD worsen over time due to progressive neurodegeneration, requiring institutional care at the later stage and resulting in a heavy burden on patients, caregivers, and the public-health system. AD neuropathology is characterized by cerebral accumulation and aggregation of amyloid-β (Aβ) and tau proteins. For decades, Aβ has been a leading target in the therapeutic development for AD, and many drug candidates have been tested in clinical trials; however, most medications have failed to slow the progression of the disease...
August 15, 2018: Neuroscience Research
https://www.readbyqxmd.com/read/30120894/liver-complications-following-treatment-of-hematologic-malignancy-with-anti-cd22-calicheamicin-inotuzumab-ozogamicin
#5
George B McDonald, James W Freston, James L Boyer, Laurie D DeLeve
BACKGROUND AND RATIONALE: Treatment of hematologic malignancy with antibody-drug conjugates (ADC) may cause liver injury. ADCs deliver a toxic moiety into antigen-expressing tumor cells but may also injure hepatic sinusoids (Sinusoidal Obstruction Syndrome, SOS). We studied patients who received an anti-CD22-calicheamicin conjugate (inotuzumab ozogamicin) to gain insight into mechanisms of sinusoidal injury, as there are no CD22+ cells in the normal liver but non-specific uptake of ADCs by liver sinusoidal endothelial cells...
August 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30120623/enhancing-mitochondrial-health-to-treat-hypertension
#6
REVIEW
Alfonso Eirin, Amir Lerman, Lilach O Lerman
PURPOSE OF REVIEW: This review summarizes literature pertaining to the dawning field of therapeutic targeting of mitochondria in hypertension and discusses the potential of these interventions to ameliorate hypertension-induced organ damage. RECENT FINDINGS: In recent years, mitochondrial dysfunction has been reported as an important contributor to the pathogenesis of hypertension-related renal, cardiac, and vascular disease. This in turn prompted development of novel mitochondria-targeted compounds, some of which have shown promising efficacy in experimental studies and safety in clinical trials...
August 17, 2018: Current Hypertension Reports
https://www.readbyqxmd.com/read/30120478/fixed-low-dose-triple-combination-antihypertensive-medication-vs-usual-care-for-blood-pressure-control-in-patients-with-mild-to-moderate-hypertension-in-sri-lanka-a-randomized-clinical-trial
#7
Ruth Webster, Abdul Salam, H Asita de Silva, Vanessa Selak, Sandrine Stepien, Senaka Rajapakse, Stanley Amarasekara, Naomali Amarasena, Laurent Billot, Arjuna P de Silva, Mervyn Fernando, Rama Guggilla, Stephen Jan, Jayanthimala Jayawardena, Pallab K Maulik, Sepalika Mendis, Suresh Mendis, Janake Munasinghe, Nitish Naik, Dorairaj Prabhakaran, Gotabaya Ranasinghe, Simon Thom, Nirmali Tisserra, Vajira Senaratne, Sanjeewa Wijekoon, Santharaj Wijeyasingam, Anthony Rodgers, Anushka Patel
Importance: Poorly controlled hypertension is a leading global public health problem requiring new treatment strategies. Objective: To assess whether a low-dose triple combination antihypertensive medication would achieve better blood pressure (BP) control vs usual care. Design, Setting, and Participants: Randomized, open-label trial of a low-dose triple BP therapy vs usual care for adults with hypertension (systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg; or in patients with diabetes or chronic kidney disease: >130 mm Hg and/or >80 mm Hg) requiring initiation (untreated patients) or escalation (patients receiving monotherapy) of antihypertensive therapy...
August 14, 2018: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/30120413/arrestin-recruitment-to-dopamine-d2-receptor-mediates-locomotion-but-not-incentive-motivation
#8
Prashant Donthamsetti, Eduardo F Gallo, David C Buck, Edward L Stahl, Ying Zhu, J Robert Lane, Laura M Bohn, Kim A Neve, Christoph Kellendonk, Jonathan A Javitch
The dopamine (DA) D2 receptor (D2R) is an important target for the treatment of neuropsychiatric disorders such as schizophrenia and Parkinson's disease. However, the development of improved therapeutic strategies has been hampered by our incomplete understanding of this receptor's downstream signaling processes in vivo and how these relate to the desired and undesired effects of drugs. D2R is a G protein-coupled receptor (GPCR) that activates G protein-dependent as well as non-canonical arrestin-dependent signaling pathways...
August 17, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/30120270/membrane-modulating-drugs-can-affect-the-size-of-amyloid-%C3%AE-25-35-aggregates-in-anionic-membranes
#9
Adree Khondker, Richard J Alsop, Sebastian Himbert, Jennifer Tang, An-Chang Shi, Adam P Hitchcock, Maikel C Rheinstädter
The formation of amyloid-β plaques is one of the hallmarks of Alzheimer's disease. The presence of an amphiphatic cell membrane can accelerate the formation of amyloid-β aggregates, making it a potential druggable target to delay the progression of Alzheimer's disease. We have prepared unsaturated anionic membranes made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine (DMPS) and added the trans-membrane segment Aβ25-35 . Peptide plaques spontaneously form in these membranes at high peptide concentrations of 20 mol%, which show the characteristic cross-β motif (concentrations are relative to the number of membrane lipids and indicate the peptide-to-lipid ratio)...
August 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30120163/fda-approval-summary-pembrolizumab-for-recurrent-locally-advanced-or-metastatic-gastric-or-gastroesophageal-junction-adenocarcinoma-expressing-pd-l1
#10
Lola Fashoyin-Aje, Martha Donoghue, Huanyu Chen, Kun He, Janaki Veeraraghavan, Kirsten B Goldberg, Patricia Keegan, Amy E McKee, Richard Pazdur
On September 22, 2017, the U.S. Food and Drug Administration (FDA) granted accelerated approval for pembrolizumab (Keytruda, Merck & Co., Inc., Whitehouse Station, NJ) for the treatment of patients with recurrent, locally advanced or metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after two or more systemic therapies, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy, and whose tumors express programmed death-ligand 1 (PD-L1), as determined by an FDA-approved test...
August 17, 2018: Oncologist
https://www.readbyqxmd.com/read/30120160/fda-approval-summary-vemurafenib-for-the-treatment-of-patients-with-erdheim-chester-disease-with-the-braf-v600-mutation
#11
Patricia A Oneal, Virginia Kwitkowski, Lola Luo, Yuan Li Shen, Sriram Subramaniam, Stacy Shord, Kirsten B Goldberg, Amy E McKee, Edvardas Kaminskas, Ann Farrell, Richard Pazdur
On November 6, 2017, the U.S. Food and Drug Administration (FDA) granted regular approval to vemurafenib for the treatment of adult patients with Erdheim-Chester disease (ECD) with BRAF V600 mutation. ECD is a type of histiocytosis, a rare disorder characterized by an abnormal accumulation and behavior of cells of the mononuclear phagocytic system, which includes antigen-processing cells, dendritic cells, monocytes, or macrophages. Recently published data confirm a frequency of 54% of BRAF V600E mutations in patients with ECD...
August 17, 2018: Oncologist
https://www.readbyqxmd.com/read/30119911/the-impact-of-microsatellite-stability-status-in-colorectal-cancer
#12
REVIEW
Ruby Gupta, Surajit Sinha, Rabindra N Paul
Several forms of genomic instability are known to drive the development of colorectal cancer (CRC). Chromosomal instability is the most common type found in 85% of the CRC, while 15% patients have microsatellite instability (MSI). MSI tumors are the subset of CRC that are characterized by dysfunction of mismatch repair genes (MMR) causing failure to repair errors in repetitive DNA sequences called microsatellites. Twelve percent of MSI tumors are acquired, caused by methylation-associated silencing of a gene that encodes a DNA MMR protein, while the remaining 3% have germline mutations in one of the MMR genes (Lynch syndrome)...
July 18, 2018: Current Problems in Cancer
https://www.readbyqxmd.com/read/30119227/in-vitro-and-in-vivo-anticancer-efficacy-potential-of-quercetin-loaded-polymeric-nanoparticles
#13
Ruma Baksi, Devendra Pratap Singh, Swapnil P Borse, Rita Rana, Vipin Sharma, Manish Nivsarkar
Quercetin (QCT) is a flavonoid, abundantly present in plants and has gained considerable interest for its antioxidant property and chemo preventive activity. Bioavailability of QCT is very low due to its poor aqueous solubility and instability. Researchers are working on the application of nanotechnology to target chemotherapeutic drugs to the tumour site. The aim of the present study was to develop quercetin loaded chitosan nanoparticles (QCT-CS NPs) with enhanced encapsulation efficiency and sustained release property...
July 24, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30118875/molecular-evolution-and-functional-divergence-of-ispd-homologs-in-malarial-parasites
#14
P Chellapandi, R Prathiviraj, A Prisilla
Malaria, caused by Plasmodium falciparum, continues to be one of the leading parasitic diseases to humans. It is urgent to discover novel targets for the development of antimalarial drugs. The 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (IspD) in 2-C-methyl-D-erythritol-4-phosphate pathway has been considered as a second in vivo off-target to discover novel antimalarial drugs for its essentiality in malarial parasites and devoid in mammals. Our aim is to rationalize the basis of its functional parts by studying molecular diversity, origin and evolution across malarial parasites...
August 14, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/30118857/risk-factors-for-restenosis-after-drug-coated-balloon-angioplasty-for-complex-femoropopliteal-arterial-occlusive-disease
#15
Ji Woong Roh, Young-Guk Ko, Chul-Min Ahn, Sung-Jin Hong, Dong-Ho Shin, Jung-Sun Kim, Byeong-Keuk Kim, Donghoon Choi, Myeong-Ki Hong, Yangsoo Jang
BACKGROUND: Currently, there exists limited data on patient outcome following the use of drug-coated balloons to treat complex femoropopliteal arterial occlusive lesions. The aim of the present study was to investigate the outcomes of patient treated with drug-coated balloons (DCB) and to identify predictors of restenosis. METHODS: We retrospectively investigated medical records from 120 patients (137 limbs) treated with DCBs for femoropopliteal lesions at a single center between 2013 and 2016...
August 14, 2018: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/30118774/neuroprotective-effects-of-bergenin-in-alzheimer-s-disease-investigation-through-molecular-docking-in-vitro-and-in-vivo-studies
#16
Priyal Barai, Nisith Raval, Sanjeev Acharya, Ankit Borisa, Hardik Bhatt, Niyati Acharya
Alzheimer's disease (AD) is an enervating and chronic progressive neurodegenerative disorder, occurring frequently in the elderly and adversely affecting intellectual capabilities and the cognitive processes. Bergenin possesses efficacious antioxidant, antiulcerogenic, anti-HIV, hepatoprotective, neuroprotective, anti-inflammatory and immunomodulatory activity along with antinociceptive effect and wound healing properties. Previous studies have shown that bergenin has in vitro bovine adrenal tyrosine hydroxylase inhibitory activity, mushroom tyrosinase inhibitory activities, β-secretase (BACE-1) enzyme inhibitory activity and prevented neuronal death in the primary culture of rat cortical neurons...
August 14, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/30118769/structure-based-identification-and-biological-evaluation-of-novel-and-potent-inhibitors-of-pcaf-catalytic-domain
#17
Venkatesan Suryanarayanan, Tamilselvam Rajavel, Kasi Pandima Devi, Sanjeev Kumar Singh
p300/CBP Associated Factor (PCAF), a GNAT family member protein, represent a valid target for therapeutic interventions since its dysfunction has implicated in variety of diseases like cancer, diabetes, inflammatory diseases, etc. Despite its potential for therapeutics, only a small number of PCAF inhibitors were reported. Hence, in this study, the catalytic domain of PCAF was explored to screen novel, potent and cell permeable inhibitor from three small molecule databases like Life Chemical, Maybridge and Chembridge by using Structure Based Virtual Screening (SBVS) method...
August 10, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/30118574/fluorescence-based-assay-for-accurate-measurement-of-transcriptional-activity-in-trypanosomatid-parasites
#18
Priscila M Hiraiwa, Alessandra M de Aguiar, Andréa R Ávila
Trypanosomatid parasites are causative agents of neglected human diseases. Their lineage diverged early from the common eukaryotic ancestor, and they evolved singular mechanisms of gene expression that are crucial for their survival. Studies on unusual and essential molecular pathways lead to new drug targets. In this respect, assays to analyze transcriptional activity will provide useful information to identify essential and specific factors. However, the current methods are laborious and do not provide global and accurate measures...
August 17, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/30118354/clinical-management-of-rheumatologic-conditionsco-occurring-with-inflammatory-bowel-diseases
#19
Carla Felice, Daniela Pugliese, Luigi Giovanni Papparella, Fabrizio Pizzolante, Eugenia Onori, Antonio Gasbarrini, Gian Lodovico Rapaccini, Luisa Guidi, Alessandro Armuzzi
Spondyloarthritis (SpA) is the most common extra-intestinal manifestation in patients with inflammatory bowel diseases (IBD). Articular disorders may also appear as "paradoxical" effects during biologic therapy with anti-tumor necrosis factor (TNF). Areas covered: In this narrative review, we report the current knowledge about the pathogenesis, the diagnosis and the therapeutic management of articular diseases occurring in patients with IBD. Expert commentary: Evidence-based recommendations for the management of IBD-associated SpA and paradoxical arthritis are lacking...
August 17, 2018: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/30117592/lipid-lowering-therapy-for-atherosclerotic-cardiovascular-disease-it-is-not-so-simple
#20
EDITORIAL
John Vincent
Plasma levels of atherogenic lipoproteins reflect a key risk factor for atherosclerotic cardiovascular disease ASCVD and treatments that lower these lipoproteins improve CV outcomes. Statins and PCSK9 inhibitors reduce LDL-C remarkably to low levels but do not eliminate residual cardiovascular risk as a result of other atherogenic lipoproteins or pathways for ASCVD, including inflammation, that are independent of LDL-C. Statins and PCSK9 inhibitors have complex mechanisms of action which appear to be additive and hence beneficial...
August 2018: Clinical Pharmacology and Therapeutics
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