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https://www.readbyqxmd.com/read/30102858/a-small-molecule-compound-has-anti-influenza-a-virus-activity-by-acting-as-a-pb2-inhibitor
#1
Teng Liu, Miaomiao Liu, Feimin Chen, Fangzhao Chen, Yuanxin Tian, Qi Huang, Shu-Wen Liu, Jie Yang
With regular influenza epidemics and the emergence of drug-resistant virus strains, it is extremely crucial to develop effective and low-toxicity anti-influenza A virus drugs that act on conserved sites of novel targets. Here, we identified a novel anti-influenza compound, 1,3-dihydroxy-6-benzo [c] chromene (D715-2441), from a library of 8,026 small molecule compounds using cell-based influenza A infection assays and explored the underlying mechanisms. Our results revealed that D715-2441 possessed antiviral activities against multiple subtypes of influenza A viruses, including H1N1, H3N2, H5N1, H7N9, the clinical isolate 690 (H3 subtype) and oseltamivir-resistant strains with an NA-H274Y mutation, and suppressed the early steps in the virus replication cycle...
August 13, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/30101644/apalutamide-for-the-treatment-of-prostate-cancer
#2
Dana E Rathkopf, Howard I Scher
Five new agents have been shown to prolong survival in patients with metastatic castration-resistant prostate cancer, including two targeting androgen receptor signaling (abiraterone acetate plus prednisone; enzalutamide). Recognition that these tumors remain driven by androgen receptor signaling has prompted clinical evaluation of these agents at earlier states in the prostate cancer disease continuum, along with the continued development of new agents targeting this pathway. Areas covered: This article focuses on apalutamide, a next-generation nonsteroidal antiandrogen, with current literature queried in PubMed/Medline...
September 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/30099198/multicellular-spheroid-based-on-a-triple-co-culture-a-novel-3d-model-to-mimic-pancreatic-tumor-complexity
#3
Gianpiero Lazzari, Valerie Nicolas, Michiya Matsusaki, Mitsuru Akashi, Patrick Couvreur, Simona Mura
The preclinical drug screening of pancreatic cancer treatments suffers from the absence of appropriate models capable to reproduce in vitro the heterogeneous tumor microenvironment and its stiff desmoplasia. Driven by this pressing need, we describe in this paper the conception and the characterization of a novel 3D tumor model, consisting of a triple co-culture of pancreatic cancer cells (PANC-1), fibroblasts (MRC-5) and endothelial cells (HUVEC), which assembled to form a hetero-type multicellular tumor spheroid (MCTS)...
August 9, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/30099048/association-of-serum-sestrin2-level-with-metabolic-risk-factors-in-newly-diagnosed-drug-na%C3%A3-ve-type-2-diabetes
#4
Hye Soo Chung, Hwan-Jin Hwang, Soon Young Hwang, Nam Hoon Kim, Ji-A Seo, Sin Gon Kim, Nan Hee Kim, Sei Hyun Baik, Kyung Mook Choi, Hye Jin Yoo
AIMS: Previous in-vitro and in-vivo experimental studies have shown that Sestrin2 attenuates oxidative stress and the pro-inflammatory pathway, resulting in improving metabolic homeostasis. However, the relationship between circulating Sestrin2 concentration and cardiometabolic risks in humans has not been explored. METHODS: Sestrin2 concentration was measured in 240 subjects (46 without diabetes and 194 with diabetes), and the associations between Sestrin2 level and various cardiometabolic risk factors including body composition, insulin resistance, and atherosclerosis was assessed...
August 9, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/30097614/nutrient-scavenging-in-cancer
#5
REVIEW
Brendan T Finicle, Vaishali Jayashankar, Aimee L Edinger
While cancer cell proliferation depends on access to extracellular nutrients, inadequate tumour perfusion means that glucose, amino acids and lipids are often in short supply. To overcome this obstacle to growth, cancer cells utilize multiple scavenging strategies, obtaining macromolecules from the microenvironment and breaking them down in the lysosome to produce substrates for ATP generation and anabolism. Recent studies have revealed four scavenging pathways that support cancer cell proliferation in low-nutrient environments: scavenging of extracellular matrix proteins via integrins, receptor-mediated albumin uptake and catabolism, macropinocytic consumption of multiple components of the tumour microenvironment and the engulfment and degradation of entire live cells via entosis...
August 10, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/30094570/the-roles-of-the-cox2-pge2-ep-axis-in-therapeutic-resistance
#6
Dali Tong, Qiuli Liu, Lin-Ang Wang, Qiubo Xie, Jian Pang, Yiqiang Huang, Luofu Wang, Gaolei Liu, Dianzheng Zhang, Weihua Lan, Jun Jiang
Therapeutic resistance has been and remains to be the major challenge in developing successful treatments for different cancers and therefore, understanding the underlying mechanisms in the development of therapeutic resistance is crucial in combating cancers. Multiple mechanisms underlie the development of therapeutic resistance, and the signaling pathways involved in cancer stem cell repopulation, enhanced epithelial-mesenchymal transition (EMT), inflammatory infiltration, and immunosuppression play pivotal roles in this process...
August 10, 2018: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/30094089/microrna-regulation-of-liver-cancer-stem-cells
#7
REVIEW
Weiyang Lou, Jingxing Liu, Yanjia Gao, Guansheng Zhong, Bisha Ding, Liang Xu, Weimin Fan
MicroRNAs (miRNAs), a class of emerging small non-coding RNAs, serve as vital players in modulating multiple biological processes via the post-transcriptional regulation of gene expression. Dysregulated expression of miRNAs in liver cancer is well documented, and the involvement of miRNAs in liver cancer initiation and progression has also been described. Cancer stem cells (CSCs) are a subset of cells known to be at the root of cancer recurrence and resistance to therapy. In this review, we highlight recent reports indicating that miRNAs participate in the regulation of liver cancer stem cells (LCSCs)...
2018: American Journal of Cancer Research
https://www.readbyqxmd.com/read/30093886/study-the-features-of-57-confirmed-crispr-loci-in-38-strains-of-staphylococcus-aureus
#8
Xihong Zhao, Zhixue Yu, Zhenbo Xu
Staphylococcus aureus is a foodborne pathogen that causes food contamination and food poisoning, which poses great harm to health, agriculture and other hosts. Clustered regularly interspaced short palindromic repeats (CRISPR) are a recently discovered bacterial immune system that resists foreign genes such as phage DNA. This system inhibits the transfer of specific movable genetic elements that match the CRISPR spacer sequences, thereby preventing the spread of drug-resistant genes between pathogens. In this study, 57 CRISPR loci were screened from 38 strains of S...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/30093677/bifidobacterium-adolescentis-is-intrinsically-resistant-to-antitubercular-drugs
#9
Dhanashree Lokesh, Raman Parkesh, Rajagopal Kammara
Multiple mutations in the β subunit of the RNA polymerase (rpoβ) of Mycobacterium tuberculosis (Mtb) are the primary cause of resistance to rifamycin (RIF). In the present study, bifidobacterial rpoβ sequences were analyzed to characterize the mutations that contribute to the development of intrinsic resistance to RIF, isoniazid, streptomycin and pyrazinamide. Sequence variations, which mapped to cassettes 1 and 2 of the rpoβ pocket, are also found in multidrug-resistant Mtb (MDR Mtb). Growth curves in the presence of osmolytes and different concentrations of RIF showed that the bacteria adapted rapidly by shortening the growth curve lag time...
August 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30089632/optimizing-drug-combinations-against-multiple-myeloma-using-a-quadratic-phenotypic-optimization-platform-qpop
#10
Masturah Bte Mohd Abdul Rashid, Tan Boon Toh, Lissa Hooi, Aleidy Silva, Yanzhou Zhang, Pei Fang Tan, Ai Ling Teh, Neerja Karnani, Sudhakar Jha, Chih-Ming Ho, Wee Joo Chng, Dean Ho, Edward Kai-Hua Chow
Multiple myeloma is an incurable hematological malignancy that relies on drug combinations for first and secondary lines of treatment. The inclusion of proteasome inhibitors, such as bortezomib, into these combination regimens has improved median survival. Resistance to bortezomib, however, is a common occurrence that ultimately contributes to treatment failure, and there remains a need to identify improved drug combinations. We developed the quadratic phenotypic optimization platform (QPOP) to optimize treatment combinations selected from a candidate pool of 114 approved drugs...
August 8, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/30089463/lc-ms-based-sphingolipidomic-study-on-a549-human-lung-adenocarcinoma-cell-line-and-its-taxol-resistant-strain
#11
Hao Huang, Tian-Tian Tong, Lee-Fong Yau, Cheng-Yu Chen, Jia-Ning Mi, Jing-Rong Wang, Zhi-Hong Jiang
BACKGROUND: Resistance to chemotherapy drugs (e.g. taxol) has been a major obstacle in successful cancer treatment. In A549 human lung adenocarcinoma, acquired resistance to the first-line chemotherapy taxol has been a critical problem in clinics. Sphingolipid (SPL) controls various aspects of cell growth, survival, adhesion, and motility in cancer, and has been gradually regarded as a key factor in drug resistance. To better understand the taxol-resistant mechanism, a comprehensive sphingolipidomic approach was carried out to investigate the sphingolipid metabolism in taxol-resistant strain of A549 cell (A549T)...
August 8, 2018: BMC Cancer
https://www.readbyqxmd.com/read/30088909/engineering-anticancer-amphipathic-peptide-dendronized-compounds-for-highly-efficient-plasma-organelle-membrane-perturbation-and-multidrug-resistance-reversal
#12
Xiao Zhang, Yachao Li, Cheng Hu, Yahui Wu, Dan Zhong, Xianghui Xu, Zhongwei Gu
Discovering new strategies for combating drug-resistant tumors becomes a worldwide challenge. Thereinto, stubborn drug-resistant tumor membrane is a leading obstacle on chemotherapy. Herein, we report a novel tumor-activatable amphipathic peptide-dendronized compound, which could form nanoaggregates in aqueous solutions, for perturbing tumor plasma/organelle membrane and reversing multidrug resistance. Distinguished from classical linear amphipathic peptide drugs for membrane disturbance, dendritic lysine-based architecture is designed as a multivalent scaffold to amplify the supramolecular interactions of cationic compound with drug-resistant tumor membrane...
August 8, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/30087741/tuberculosis-in-the-prisons-in-the-republic-of-macedonia-2008-2017
#13
Biljana Ilievska-Poposka, Maja Zakoska, Karolina Pilovska-Spasovska, Ljiljana Simonovska, Vladimir Mitreski
BACKGROUND: Tuberculosis (TB) is a major health problem in penitentiary institutions (prisons), and its prevalence was reported to be multiple times higher compared to that of the general population. Conditions such as overcrowding, malnutrition and limited access to medical care which often exist in prisons increase the risk of reactivation, transmission and poor prognosis of tuberculosis disease among inmates. AIM: The main objective of this study was to present the epidemiological situation of TB in the prisons from 2008 till 2017 in the Republic of Macedonia (RM)...
July 20, 2018: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/30087562/antimycobacterial-susceptibility-evaluation-of-rifampicin-and-isoniazid-benz-hydrazone-in-biodegradable-polymeric-nanoparticles-against-mycobacterium-tuberculosis-h37rv-strain
#14
Sushruta S Hakkimane, Vishnu Prasad Shenoy, Santosh L Gaonkar, Indira Bairy, Bharath Raja Guru
Introduction: Tuberculosis (TB) is the single largest infectious disease which requires a prolonged treatment regime with multiple drugs. The present treatment for TB includes frequent administration of a combination of four drugs for a duration of 6 months. This leads to patient's noncompliance, in addition to developing drug-resistant strains which makes treatment more difficult. The formulation of drugs with biodegradable polymeric nanoparticles (NPs) promises to overcome this problem...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/30086517/the-role-of-glutamatergic-modulation-in-the-mechanism-of-action-of-ketamine-a-prototype-rapid-acting-antidepressant-drug
#15
REVIEW
Agnieszka Pałucha-Poniewiera
Over the past decade, ketamine has been one of the most commonly studied potential antidepressants. This is because it produces a spectacularly rapid and persistent therapeutic effect in people suffering from severe treatment-resistant depression (TRD), for which classical drugs are ineffective. Similar efficacy was demonstrated for scopolamine, a drug belonging to a completely different pharmacological group. This interesting coincidence piqued the interest of psychopharmacologists and prompted them to search for a possible common mechanism of these rapid acting antidepressant drugs (RAADs)...
February 9, 2018: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/30086337/comparison-of-antiviral-resistance-across-acute-and-chronic-viral-infections
#16
REVIEW
Stephen Mason, John Devincenzo, Stephen Toovey, Jim Z Wu, Richard J Whitley
Antiviral therapy can lead to drug resistance, but multiple factors determine the frequency of drug resistance mutations and the clinical consequences. When chronic infections caused by Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV) are compared with acute infections such as influenza virus, respiratory syncytial virus (RSV), and other respiratory viruses, there are similarities in how and why antiviral resistance substitutions occur, but the clinical significance can be quite different...
August 4, 2018: Antiviral Research
https://www.readbyqxmd.com/read/30085270/candida-auris-the-recent-emergence-of-a-multidrug-resistant-fungal-pathogen
#17
Kaitlin Forsberg, Kate Woodworth, Maroya Walters, Elizabeth L Berkow, Brendan Jackson, Tom Chiller, Snigdha Vallabhaneni
Candida auris is an emerging multidrug-resistant yeast that causes serious invasive infections with high mortality. It was first discovered in 2009, and since then, individual cases or outbreaks have been reported from over 20 countries on five continents. Controlling C. auris is challenging for several reasons: (1) it is resistant to multiple classes of antifungals, (2) it can be misidentified as other yeasts by commonly available identification methods, and (3) because of its ability to colonize patients perhaps indefinitely and persist in the healthcare environment, it can spread between patients in healthcare settings...
July 31, 2018: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/30083262/targeting-s1pr1-stat3-loop-abrogates-desmoplasia-and-chemosensitizes-pancreatic-cancer-to-gemcitabine
#18
Manendra Babu Lankadasari, Jayasekharan S Aparna, Sabira Mohammed, Shirley James, Kazunori Aoki, Valsalakumari S Binu, Sindhu Nair, Kuzhuvelil B Harikumar
Rationale: Pancreatic cancer is associated with poor prognosis with a 5-year survival rate of less than 6%. Approximately 90% of pancreatic cancer patients harbor somatic mutations in the KRAS gene. Multiple lines of evidence suggest a persistent activation of STAT3 in KRAS-driven oncogenesis contributing to desmoplasia and gemcitabine resistance. Sphingosine 1-phosphate receptor 1 (S1PR1) is an integral component of tumor progression and maintains an activated state of STAT3. FTY720 is an approved drug for multiple sclerosis and acts as a functional antagonist for S1PR1...
2018: Theranostics
https://www.readbyqxmd.com/read/30082743/dbc1-regulates-wnt-%C3%AE-catenin-mediated-expression-of-macc1-a-key-regulator-of-cancer-progression-in-colon-cancer
#19
Hwa Jin Kim, Sue Jin Moon, Seok-Hyung Kim, Kyu Heo, Jeong Hoon Kim
Metastasis-associated in colon cancer 1 (MACC1) has been reported to be overexpressed in multiple cancers and promote proliferation, metastasis, cancer stem cell-like properties, and drug resistance of cancer cells. Despite its significance and the considerable knowledge accumulated on the function of MACC1 in various types of human malignancies, regulatory mechanisms underlying MACC1 expression remain unclear. Here we report that MACC1 is a direct target of Wnt/β-catenin signaling pathway in colon cancer cells and that DBC1 functions as a coactivator for Wnt-mediated MACC1 expression by promoting the activity of a LEF1/β-catenin-dependent enhancer located in intron 1 of MACC1 gene...
August 6, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/30082559/antibiotic-adjuvant-combinations-ceftriaxone-sulbactam-adjuvant-disodium-edetate-as-an-alternative-empiric-therapy-for-the-treatment-of-nosocomial-infections-results-of-a-retrospective-study
#20
Saibal Chakravorty, Prashant Arun
OBJECTIVE: Carbapenems are one of the last therapeutic options to treat various bacterial infections including multidrug resistant (MDR) nosocomial infections. However, excessive and inappropriate prescription of this drug has recently led to an epidemic rise in carbapenem resistance. Optimizing antibiotic utilization and exploring alternate options can be a potential way to control carbapenem resistance. The aim of this study was to assess the clinical efficacy of novel antibiotic adjuvant entity (ceftriaxone + sulbactam + ethylenediaminetetraacetic acid [EDTA] [CSE-1034]) in the treatment of various nosocomial infections...
October 2017: Indian Journal of Cancer
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