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https://www.readbyqxmd.com/read/28437885/sesquiterpenes-evaluation-on-schistosoma-mansoni-survival-excretory-system-and-membrane-integrity
#1
Rosimeire Nunes de Oliveira, Karina Rodrigues Dos Santos, Tiago Manuel Fernandes Mendes, Vera Lúcia Garcia, Adriana Silva Santos Oliveira, Veronica de Lourdes Sierpe Jeraldo, Silmara Marques Allegretti
The main challenge in schistosomiasis control has been the emergence of drug-resistant parasites. Since the 1970's, praziquantel (PZQ) is the single drug for treatment. This fact highlights the importance to research news chemotherapeutic agents. In the last years, S. mansoni excretory system and tegument have been major targets for drug development. The purpose of this study was to evaluate the effect of sesquiterpenes, alpha-humulene and trans-caryophyllene on S. mansoni survival, excretory system and membrane integrity, after in vitro exposure...
April 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28437884/regulatory-role-of-mir-211-5p-in-hepatocellular-carcinoma-metastasis-by-targeting-zeb2
#2
Guangbin Jiang, Li Wen, Weiping Deng, Zhiyuan Jian, Hongmei Zheng
Hepatocellular carcinoma (HCC) is the most common type of cancer and the rapid tumor growth, drug resistance and metastasis are the major problems for HCC therapy. MicroRNAs (miRNAs) involve in various cell biological processes in HCC. ZEB2 plays crucial roles in HCC progression. ZEB2 is regulated by some identified miRNAs, but there needs to find new miRNAs regulating ZEB2 expression for better understanding the molecular mechanism of HCC. In the present study, ZEB2 was identified as a direct target of miR-211-5p, which was a potential oncogene in cancer...
April 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28437852/a-diagnostic-microdosing-approach-to-investigate-platinum-sensitivity-in-non-small-cell-lung-cancer
#3
Si-Si Wang, Maike Zimmermann, Hongyong Zhang, Tzu-Yin Lin, Michael Malfatti, Kurt Haack, Kenneth W Turteltaub, George D Cimino, Ralph de Vere White, Chong-Xian Pan, Paul T Henderson
The platinum-based drugs cisplatin, carboplatin and oxaliplatin are often used for chemotherapy, but drug resistance is common. The prediction of resistance to these drugs via genomics is a challenging problem since hundreds of genes are involved. A possible alternative is to use mass spectrometry to determine the propensity for cells to form drug-DNA adducts-the pharmacodynamic drug-target complex for this class of drugs. The feasibility of predictive diagnostic microdosing was assessed in non-small cell lung cancer (NSCLC) cell culture and a pilot clinical trial...
April 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28437620/american-association-of-clinical-endocrinologists-and-american-college-of-endocrinology-guidelines-for-management-of-dyslipidemia-and-prevention-of-cardiovascular-disease
#4
Paul S Jellinger, Yehuda Handelsman, Paul D Rosenblit, Zachary T Bloomgarden, Vivian A Fonseca, Alan J Garber, George Grunberger, Chris K Guerin, David S H Bell, Jeffrey I Mechanick, Rachel Pessah-Pollack, Kathleen Wyne, Donald Smith, Eliot A Brinton, Sergio Fazio, Michael Davidson
OBJECTIVE: The development of these guidelines is mandated by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs). METHODS: Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols...
April 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28437613/evaluating-the-role-of-multidrug-resistance-protein-3-mdr3-inhibition-in-predicting-drug-induced-liver-injury-using-125-pharmaceuticals
#5
Michael D Aleo, Falgun Shah, Kan He, Paul D Bonin, A David Rodrigues
The role of bile salt export protein (BSEP) inhibition in drug-induced liver injury (DILI) has been investigated widely, while inhibition of the canalicular multidrug resistant protein 3 (MDR3) has received less attention. This transporter plays a pivotal role in secretion of phospholipids into bile and functions coordinately with BSEP to mediate the formation of bile acid-containing biliary micelles. Therefore, inhibition of MDR3 in human hepatocytes was examined across 125 drugs (70 of Most- and 55 of No-DILI-concern)...
April 24, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28437447/carbonic-anhydrase-iii-car3-is-not-required-for-fatty-acid-synthesis-and-does-not-protect-against-high-fat-diet-induced-obesity-in-mice
#6
Sarah W Renner, Lauren M Walker, Lawrence J Forsberg, Jonathan Z Sexton, Jay E Brenman
Carbonic anhydrases are a family of enzymes that catalyze the reversible condensation of water and carbon dioxide to carbonic acid, which spontaneously dissociates to bicarbonate. Carbonic anhydrase III (Car3) is nutritionally regulated at both the mRNA and protein level. It is highly enriched in tissues that synthesize and/or store fat: liver, white adipose tissue, brown adipose tissue, and skeletal muscle. Previous characterization of Car3 knockout mice focused on mice fed standard diets, not high-fat diets that significantly alter the tissues that highly express Car3...
2017: PloS One
https://www.readbyqxmd.com/read/28437394/selective-degradation-of-splicing-factor-caper%C3%AE-by-anticancer-sulfonamides
#7
Taisuke Uehara, Yukinori Minoshima, Koji Sagane, Naoko Hata Sugi, Kaoru Ogawa Mitsuhashi, Noboru Yamamoto, Hiroshi Kamiyama, Kentaro Takahashi, Yoshihiko Kotake, Mai Uesugi, Akira Yokoi, Atsushi Inoue, Taku Yoshida, Miyuki Mabuchi, Akito Tanaka, Takashi Owa
Target-protein degradation is an emerging field in drug discovery and development. In particular, the substrate-receptor proteins of the cullin-ubiquitin ligase system play a key role in selective protein degradation, which is an essential component of the anti-myeloma activity of immunomodulatory drugs (IMiDs), such as lenalidomide. Here, we demonstrate that a series of anticancer sulfonamides NSC 719239 (E7820), indisulam, and NSC 339004 (chloroquinoxaline sulfonamide, CQS) induce proteasomal degradation of the U2AF-related splicing factor coactivator of activating protein-1 and estrogen receptors (CAPERα) via CRL4(DCAF15) mediated ubiquitination in human cancer cell lines...
April 24, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28437226/first-report-of-prevalence-of-ctx-m-15-producing-escherichia-coli-o25b-st131-from-iran
#8
Mohammad Hasan Namaei, Masoud Yousefi, Masoud Ziaee, Alireza Salehabadi, Malaknaz Ghannadkafi, Elham Amini, Parvin Askari
The emergence of Escherichia coli sequence type 131 (ST131) as a multidrug-resistant and virulent pathogen represents a major challenge to public health globally. Recently, the O25b/ST131 E. coli producing CTX-M-15 with high virulence potential has been reported worldwide, but has received little attention in Iran. This study is the first in Iran to specifically determine the spread of the O25b/ST131 clone producing CTX-M-15 among E. coli isolates belonging to the B2 phylogenetic group. ST131 clone in phylogenetic group B2 was detected based on PCR detection of ST131-specific single-nucleotide polymorphisms in mdh and gyrB...
February 16, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28437091/speeding-up-early-drug-discovery-in-antiviral-research-a-fragment-based-in-silico-approach-for-the-design-of-virtual-anti-hepatitis-c-leads
#9
Alejandro Speck-Planche, M Natalia Dias Soeiro Cordeiro
Hepatitis C constitutes an unresolved global health problem. This infectious disease is caused by the hepatotropic hepatitis C virus (HCV), and it can lead to the occurrence of life-threatening medical conditions such as cirrhosis and liver cancer. Nowadays, major clinical concerns have arisen due to the appearance of multidrug resistance (MDR), and the side effects especially associated with long-term treatments. In this work, we report the first multitasking model for quantitative structure-biological effect relationships (mtk-QSBER), focused on the simultaneous exploration of anti-HCV activity and in vitro safety profiles related to the absorption, distribution, metabolism, elimination, and toxicity (ADMET)...
April 24, 2017: ACS Combinatorial Science
https://www.readbyqxmd.com/read/28436750/emap-ii-sensitize-u87mg-and-glioma-stem-like-cells-to-temozolomide-via-induction-of-autophagy-mediated-cell-death-and-g2-m-arrest
#10
Qi Yu, Libo Liu, Ping Wang, Yilong Yao, Yixue Xue, Yunhui Liu
Despite the fact that temozolomide (TMZ) has been widely accepted as the key chemotherapeutic agent to prolong the survival of patients with glioblastoma, failure and recurrence cases can still be observed in clinics. Glioma stem-like cells (GSCs) are thought to be responsible for the drug resistance. In this study, we investigate whether endothelial monocyte-activating polypeptide-II (EMAP-II), a pro-inflammatory cytokine, can enhance TMZ cytotoxicity on U87MG and GSCs or not. As described in prior research, GSCs have been isolated from U87MG and maintained in the serum-free DMEM/F12 medium containing EGF, b-FGF, and B27...
April 24, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28436748/disruption-of-tetr-type-regulator-aden-by-mobile-genetic-element-confers-elevated-virulence-in-acinetobacter-baumannii
#11
Rajagopalan Saranathan, Sudhakar Pagal, Ajit R Sawant, Archana Tomar, M Madhangi, Suresh Sah, Annapurna Satti, K P Arunkumar, K Prashanth
Acinetobacter baumannii is an important human pathogen and considered as a major threat due to its extreme drug resistance. In this study, the genome of a hyper-virulent MDR strain PKAB07 of A. baumannii isolated from an Indian patient was sequenced and analysed to understand its mechanisms of virulence, resistance and evolution. Comparative genomics analysis of PKAB07 revealed virulence and resistance related genes scattered throughout the genome, instead of being organized as an island, indicating the highly mosaic nature of the genome...
April 24, 2017: Virulence
https://www.readbyqxmd.com/read/28436655/investigating-the-antibacterial-activity-of-biphenylthiazoles-against-methicillin-and-vancomycin-resistant-staphylococcus-aureus-mrsa-and-vrsa
#12
Mohamed Hagras, Haroon Mohammad, Mohamed S Mandour, Youssef A Hegazy, Adel Ghiaty, Mohamed N Seleem, Abdelrahman S Mayhoub
Phenylthiazoles were reported previously as a new scaffold with antibacterial activity against an array of multidrug-resistant staphylococci. However, their promising antibacterial activity was hampered in large part by their short half-life due to excessive hepatic clearance. Close inspection of the structure-activity-relationships (SAR) of the phenylthiazoles revealed two important structural features necessary for antibacterial activity (a nitrogenous and a lipophilic component). Incorporating the nitrogenous part within a pyrimidine ring resulted in analogues with a prolonged half-life, while the biphenyl moiety revealed the most potent analogue 1b...
April 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28436480/dihydromyricetin-induces-apoptosis-and-reverses-drug-resistance-in-ovarian-cancer-cells-by-p53-mediated-downregulation-of-survivin
#13
Yingqi Xu, Shengpeng Wang, Hon Fai Chan, Huaiwu Lu, Zhongqiu Lin, Chengwei He, Meiwan Chen
Ovarian cancer is one of the leading causes of death in gynecological malignancies, and the resistance to chemotherapeutic agents remains a major challenge to successful ovarian cancer chemotherapy. Dihydromyricetin (DHM), a natural flavonoid derived from Ampeopsis Grossdentata, has been widely applied in food industry and medicine for a long time. However, little is known about the effects of DHM on ovarian cancer and the underlying mechanisms. In this study, we demonstrated that DHM could effectively inhibit the proliferation of ovarian cancer cells and induce cell apoptosis...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436438/spatiotemporally-and-sequentially-controlled-drug-release-from-polymer-gatekeeper-hollow-silica-nanoparticles
#14
L Palanikumar, M T Jeena, Kibeom Kim, Jun Yong Oh, Chaekyu Kim, Myoung-Hwan Park, Ja-Hyoung Ryu
Combination chemotherapy has become the primary strategy against cancer multidrug resistance; however, accomplishing optimal pharmacokinetic delivery of multiple drugs is still challenging. Herein, we report a sequential combination drug delivery strategy exploiting a pH-triggerable and redox switch to release cargos from hollow silica nanoparticles in a spatiotemporal manner. This versatile system further enables a large loading efficiency for both hydrophobic and hydrophilic drugs inside the nanoparticles, followed by self-crosslinking with disulfide and diisopropylamine-functionalized polymers...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436422/rational-design-of-non-resistant-targeted-cancer-therapies
#15
Francisco Martínez-Jiménez, John P Overington, Bissan Al-Lazikani, Marc A Marti-Renom
Drug resistance is one of the major problems in targeted cancer therapy. A major cause of resistance is changes in the amino acids that form the drug-target binding site. Despite of the numerous efforts made to individually understand and overcome these mutations, there is a lack of comprehensive analysis of the mutational landscape that can prospectively estimate drug-resistance mutations. Here we describe and computationally validate a framework that combines the cancer-specific likelihood with the resistance impact to enable the detection of single point mutations with the highest chance to be responsible of resistance to a particular targeted cancer therapy...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436419/nontuberculous-mycobacteria-in-gastrostomy-fed-patients-with-cystic-fibrosis
#16
H Al-Momani, A Perry, R Jones, S Bourke, S Doe, J Perry, A Anderson, T Forrest, I Forrest, M Griffin, M Brodlie, J Pearson, C Ward
Multi-drug resistant Mycobacterium abscessus complex (MABSC) is a form of Nontuberculous mycobacteria (NTM) of special, international concern in Cystic Fibrosis (CF). We hypothesised that gastric juice and percutaneous endoscopic gastrostomy (PEG) feeding devices might yield MABSC isolates. Gastric juice and sputa from sixteen adult PEG fed CF patients and five replaced PEG tubes were studied. Bacterial and fungal isolates were cultured. Mycobacterium were identified by rpoB, sodA and hsp65 gene sequencing and strain typed using variable number tandem repeat...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436164/synthesis-and-sar-study-of-novel-anticancer-protoflavone-derivatives-investigation-of-cytotoxicity-and-interaction-with-the-abcb1-and-abcg2-multidrug-efflux-transporters
#17
Balázs Dankó, Szilárd Tóth, Ana Martins, Vágvölgyi Máté, Norbert Kúsz, Joseph Molnár, Fang-Rong Chang, Yang-Chang Wu, Gergely Szakács, Attila Hunyadi
There is a constant need for new therapies against multidrug resistant (MDR) cancer. Natural compounds represent a promising class of novel anticancer agents. Recently, we have shown that protoflavones display activity in multidrug resistant cancer cell lines overexpressing the drug efflux pump P-glycoprotein. In the present study, 52 protoflavones, including 22 new derivatives were synthesized and tested against a panel of sensitive parental cells and their MDR derivatives obtained by transfection with the human ABCB1 or ABCG2 genes, or by adaptation to chemotherapeutics...
April 23, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28435886/discovery-of-a-novel-antifungal-agent-in-the-pathogen-box
#18
François L Mayer, James W Kronstad
Human fungal pathogens cause over 2 million infections per year and are major drivers of morbidity and mortality. Cryptococcus neoformans and Candida albicans are two of the most common fungal pathogens of humans, together accounting for a staggering 1.4 million infections annually, with very high mortality rates. Patients with dysfunctional immune systems, such as individuals with HIV/AIDS, are particularly susceptible to fungal infections. Unfortunately, relatively few antifungal drugs are currently available and fungi frequently develop resistance, further complicating treatment approaches...
March 2017: MSphere
https://www.readbyqxmd.com/read/28435832/microbiological-biosafety-multiple-drug-resistance-and-functional-diversity-of-bacteria-associated-with-the-surfaces-of-raw-vegetables
#19
Farooq Nisma, Raheem Asif, Ali Basharat
No abstract text is available yet for this article.
March 2017: Iranian Journal of Public Health
https://www.readbyqxmd.com/read/28435679/targeting-the-pro-inflammatory-factor-ccl2-mcp-1-with-bindarit-for-influenza-a-h7n9-treatment
#20
Stefan Wolf, Scott Johnson, Olivia Perwitasari, Suresh Mahalingam, Ralph A Tripp
Influenza A viruses are important human and animal pathogens. Seasonal influenza viruses cause infections every year, and occasionally zoonotic viruses emerge to cause pandemics with significantly higher morbidity and mortality rates. Three cases of laboratory confirmed human infection with avian influenza A (H7N9) virus were reported in 2013, and there have been several cases reported across South East Asia, and recently in North America. Most patients experience severe respiratory illness, with mortality rates approaching 40%...
March 2017: Clinical & Translational Immunology
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