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https://www.readbyqxmd.com/read/28636189/discovery-of-alkyl-bis-oxy-dibenzimidamide-derivatives-as-novel-protein-arginine-methyltransferase-1-prmt1-inhibitors
#1
Wei-Yao Zhang, Wen-Chao Lu, Hao Jiang, Zheng-Bing Lv, Yi-Qian Xie, Fu-Lin Lian, Zhong-Jie Liang, Yu-Xi Jiang, Da-Jin Wang, Cheng Luo, Jia Jin, Fei Ye
Protein arginine methylation, a post-translational modification critical for a variety of biological processes, is catalyzed by protein arginine N-methyltransferases (PRMTs). In particular, PRMT1 is responsible for over 85% of the arginine methylation in mammalian cells. Dysregulation of PRMT1 is involved in diverse pathological diseases including cancers. However, most current PRMT1inhibitors are lack of specificity, efficacy, and bioavailability. Herein, a series of alkyl bis(oxy)dibenzimidamide derivatives were identified as selective PRMT1 inhibitors...
June 21, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28636123/sem-imaging-of-the-stimulatory-response-of-raw264-7-cells-against-porphyromonas-gingivalis-using-a-simple-technique-employing-new-conductive-materials
#2
Chisato Takahashi, Yoshiki Umemura, Ayako Naka, Hiromitsu Yamamoto
In the medical biology, it is essential to understand not only biological morphology but also the interaction between biological materials and agents. To study these, electron microscopy (EM) is often utilized. However, sample preparation techniques for EM require a high level of skill and a considerable time. Here, we conducted EM using a simple technique employing a conductive liquid, BEL-1, and compared the results with another simple technique employing an ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4 ])...
June 21, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28635653/virtual-screening-against-phosphoglycerate-kinase-1-in-quest-of-novel-apoptosis-inhibitors
#3
Jie Xia, Bo Feng, Qianhang Shao, Yuhe Yuan, Xiang Simon Wang, Naihong Chen, Song Wu
Inhibition of apoptosis is a potential therapy to treat human diseases such as neurodegenerative disorders (e.g., Parkinson's disease), stroke, and sepsis. Due to the lack of druggable targets, it remains a major challenge to discover apoptosis inhibitors. The recent repositioning of a marketed drug (i.e., terazosin) as an anti-apoptotic agent uncovered a novel target (i.e., human phosphoglycerate kinase 1 (hPgk1)). In this study, we developed a virtual screening (VS) pipeline based on the X-ray structure of Pgk1/terazosin complex and applied it to a screening campaign for potential anti-apoptotic agents...
June 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28635639/immune-checkpoints-as-a-target-for-colorectal-cancer-treatment
#4
REVIEW
Alessandro Passardi, Matteo Canale, Martina Valgiusti, Paola Ulivi
Anti-tumor immunity is a new line of research for the treatment of patients with solid tumors. In this field, negative regulators of the immune system called immune checkpoints play a key role in limiting antitumor immunologic responses. For this reason, immune checkpoint-inhibiting agents, such as those directed against cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 receptor (PD1) and its ligand PD-L1, have been developed as antitumor drugs, producing interesting results in preclinical and clinical studies...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28635307/synthesis-evaluation-and-modeling-of-some-triazolothienopyrimidinones-as-anti-inflammatory-and-antimicrobial-agents
#5
Adnan A Bekhit, Ahmed M Farghaly, Ragab M Shafik, Mona Ma Elsemary, Mai S El-Shoukrofy, Alaa El-Din A Bekhit, Tamer M Ibrahim
AIM: New triazolotetrahydrobenzothienopyrimidinone derivatives were synthesized. EXPERIMENTAL: Their structures were confirmed, and their anti-inflammatory, antimicrobial activities and ulcerogenic potentials were evaluated. RESULTS: Compounds 7a, 10a and 11a showed minimal ulcerogenic effect and high selectivity toward human recombinant COX-2 over COX-1 enzyme with IC50 values of 1.39, 1.22 and 0.56 μM, respectively. Their docking outcome correlated with their biological activity and confirmed the high selectivity binding toward COX-2...
June 21, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28634718/mite-communities-acari-mesostigmata-in-young-and-mature-coniferous-forests-after-surface-wildfire
#6
Jacek Kamczyc, Cezary Urbanowski, Emilia Pers-Kamczyc
Density, diversity and assemblage structure of Mesostigmata (cohorts Gamasina and Uropodina) were investigated in Scots pine forests differing in forest age (young: 9-40 years and mature: 83-101 years) in which wildfire occurred. This animal group belongs to the dominant acarine predators playing a crucial role in soil food webs and being important as biological control agents. In total, six forests (three within young and three within mature stands) were inspected in Puszcza Knyszyńska Forest Complex in May 2015...
June 20, 2017: Experimental & Applied Acarology
https://www.readbyqxmd.com/read/28634478/transcriptional-and-antagonistic-responses-of-biocontrol-strain-lysobacter-enzymogenes-oh11-to-the-plant-pathogenic-oomycete-pythium-aphanidermatum
#7
Yangyang Zhao, Guoliang Qian, Yuan Chen, Liangcheng Du, Fengquan Liu
Lysobacter enzymogenes is a ubiquitous, beneficial, plant-associated bacterium emerging as a novel biological control agent. It has the potential to become a new source of antimicrobial secondary metabolites such as the Heat-Stable Antifungal Factor (HSAF), which is a broad-spectrum antimycotic with a novel mode of action. However, very little information about how L. enzymogenes detects and responds to fungi or oomycetes has been reported. An in vitro confrontation bioassay between the pathogenic oomycete Pythium aphanidermatum and the biocontrol bacterial strain L...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28634338/coumarin-benzimidazole-hybrids-as-a-potent-antimicrobial-agent-synthesis-and-biological-elevation
#8
L Ravithej Singh, Srinivasa Rao Avula, Sneha Raj, Akanksha Srivastava, Gopala Reddy Palnati, C K M Tripathi, Mukesh Pasupuleti, Koneni V Sashidhara
Molecular hybridization approach is an emerging tool in drug discovery for designing new pharmacophores with biological activity. A novel, new series of coumarin-benzimidazole hybrids were designed, synthesized and evaluated for their broad spectrum antimicrobial activity. Among all the synthesized molecules, compound (E)-3-(2-1H-benzo[d]imidazol-1-yl)-1-((4-chlorobenzyl)oxy)imino)ethyl)-2H-chromen-2-one showed the most promising broad spectrum antibacterial activity against Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis and Proteus vulgaris...
June 21, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28634103/undetectable-mannose-binding-lectin-and-corticosteroids-increase-serious-infection-risk-in-rheumatoid-arthritis
#9
Graeme J Carroll, Krista Makin, Maxine Garnsey, Max Bulsara, Bronwyn V Carroll, Shona M Curtin, Erin M Allan, Andrew McLean-Tooke, Christine Bundell, Monica L Kemp, Pooja Deshpande, Dana Ihdayhid, Sophie Coleman, Tracie Easter, James Triplett, Timothy Disteldorf, C Helen Marsden, Michaela Lucas
BACKGROUND: Infection is the leading cause of death in rheumatoid arthritis (RA). Corticosteroid (CS) use is a known and important risk factor for serious infections (SIs). Mannose binding lectin (MBL) is a genetically determined component of the innate immune system implicated in neonatal infections. OBJECTIVE: Our aim was to determine whether MBL deficiency is a risk factor for SIs in RA and to compare it with CS use and also synthetic and biologic disease-modifying antirheumatic drug (DMARD) therapy...
June 17, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28634084/drug-delivery-to-melanoma-brain-metastases-can-current-challenges-lead-to-new-opportunities
#10
Gautham Gampa, Shruthi Vaidhyanathan, Jann N Sarkaria, William F Elmquist
Melanoma has a high propensity to metastasize to the brain, and patients with melanoma brain metastases (MBM) have an extremely poor prognosis. The recent approval of several molecularly-targeted agents (e.g., BRAF, MEK inhibitors) and biologics (anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies) has brought new hope to patients suffering from this formerly untreatable and lethal disease. Importantly, there have been recent reports of success in some clinical studies examining the efficacy of both targeted agents and immunotherapies that show similar response rates in both brain metastases and extracranial disease...
June 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28633560/bioinspired-hydrogels-to-engineer-cancer-microenvironments
#11
Kyung Min Park, Daniel Lewis, Sharon Gerecht
Recent research has demonstrated that tumor microenvironments play pivotal roles in tumor development and metastasis through various physical, chemical, and biological factors, including extracellular matrix (ECM) composition, matrix remodeling, oxygen tension, pH, cytokines, and matrix stiffness. An emerging trend in cancer research involves the creation of engineered three-dimensional tumor models using bioinspired hydrogels that accurately recapitulate the native tumor microenvironment. With recent advances in materials engineering, many researchers are developing engineered tumor models, which are promising platforms for the study of cancer biology and for screening of therapeutic agents for better clinical outcomes...
June 21, 2017: Annual Review of Biomedical Engineering
https://www.readbyqxmd.com/read/28632451/prolyl-oligopeptidase-and-its-role-in-the-organism-attention-to-the-most-promising-and-clinically-relevant-inhibitors
#12
Katerina Babkova, Jan Korabecny, Ondrej Soukup, Eugenie Nepovimova, Daniel Jun, Kamil Kuca
Prolyl oligopeptidase (POP), also called prolyl endopeptidase, is a cytosolic enzyme investigated by several research groups. It has been proposed to play an important role in physiological processes such as modulation of the levels of several neuronal peptides and hormones containing a proline residue. Due to its proteolytic activity and physiological role in cell signaling pathways, inhibition of POP offers an emerging approach for the treatment of Alzheimer's and Parkinson's diseases as well as other diseases related to cognitive impairment...
June 20, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28632415/synthesis-and-biological-evaluation-of-tanshinone-iia-derivatives-as-novel-endothelial-protective-agents
#13
Xiaoling Bi, Kuojun Zhang, Long He, Biao Gao, Qinlan Gu, Xueyan Li, Jun Chen, Jinxin Wang
AIM: Oxidative stress-induced endothelial injury is a main risk factor in the pathogenesis of cardiovascular diseases. Tanshinone IIA (Tan IIA) exerts protective functions on endothelial cells in response to oxidative stress. To exploit new bioactive compounds from this natural product, 12 derivatives were first synthesized and evaluated for endothelial protective activities. MATERIALS & METHODS: Title compounds were prepared according to high-yielded synthetic routes, and their protective effects on human endothelial EA...
June 20, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28632379/an-intracellular-delivery-platform-for-recalcitrant-cells-when-polymeric-carrier-marries-photoporation
#14
Jingxian Wu, Hui Xue, Zhonglin Lyu, Zhenhua Li, Yangcui Qu, Yajun Xu, Lei Wang, Qian Yu, Hong Chen
The intracellular delivery of exogenous macromolecules is of great interest for both fundamental biological research and clinical applications. Although traditional delivery systems based on either carrier mediation or membrane disruption have some advantages, however, they are generally limited with respect to delivery efficiency and cytotoxicity. Herein, a collaborative intracellular delivery platform with excellent comprehensive performance is developed using polyethylenimine of low molecular weight (LPEI) as a gene carrier in conjunction with a gold nanoparticle layer (GNPL) acting as a photoporation agent...
June 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28631740/radiotherapy-for-renal-cell-carcinoma-renaissance-of-an-overlooked-approach
#15
REVIEW
Shankar Siva, Gargi Kothari, Alexander Muacevic, Alexander V Louie, Ben J Slotman, Bin S Teh, Simon S Lo
Conventional radiotherapy previously had a limited role in the definitive treatment of renal cell carcinoma (RCC), owing to the disappointing outcomes of several trials and the perceived radioresistance of this type of cancer. In this context, radiotherapy has been relegated largely to the palliation of symptoms in patients with metastatic disease, with variable rates of response. Following the availability of newer technologies that enable safe delivery of high-dose radiotherapy, stereotactic ablative radiotherapy (SABR) has become increasingly used in patients with RCC...
June 20, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28631708/-new-horizons-in-the-use-of-biological-agents-during-pregnancy-in-patients-with-rheumatic-disease
#16
P A Shesternya, M M Petrova, A O Vasilyeva
Pregnancy in the presence of rheumatic diseases (RD) and adequate therapy before planned conception, during gestation, and after delivery during lactation is challenging. Advances in the treatment of RD are largely due to the clinical introduction of a new class of biological agents (BAs). There are less than two decades of experience in using BAs in rheumatology and to date there are no unified standards and accepted rules governing their use during pregnancy. According to the current requirements, information on a medicine should be given in three sections: 1) pregnancy; 2) lactation, and 3) use in men and women who are planning concept (the latter section has appeared for the first time)...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28631707/-chondroprotectors-a-range-of-application-in-general-somatic-practice
#17
O A Shavlovskaya
Chondroprotectors (CP) are biological agents that contribute to the regeneration of the cartilage surfaces and articular capsule, participating in the metabolic processes of the articular cartilage. Progressive loss of hyaline cartilage and lower levels of chondroitin sulfate were observed in osteoarthritis (OA) at different sites, including dorsopathy. OA therapy is aimed at slowing disease progression, relieving pain symptoms, and reducing functional disorders. For this purpose, oral or injectable CPs (Chondroguard, Sustaguard) are prescribed...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28631695/-chronic-stress-and-mental-disorders-in-patients-with-systemic-scleroderma-results-of-an-interdisciplinary-study
#18
O F Seravina, T A Lisitsyna, M N Starovoytova, O V Desinova, O B Kovalevskaya, D Yu Veltishchev
AIM: To analyze of the prevalence of stressful factors and mental disorders (MDs), as well as their clinical psychopathological and clinical psychological characteristics to improve the comprehensive diagnosis and treatment of systemic scleroderma (SSD). SUBJECTS AND METHODS: Examinations were performed in 110 patients (predominantly women (n=97 (88.2%); mean age, 49.9±2.47 years) with a documented diagnosis of SSD (its mean duration, 7.25±0.42 years). 62 (56...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28630047/update-on-anti-tumor-necrosis-factor-agents-and-other-new-drugs-for-inflammatory-bowel-disease
#19
REVIEW
Benjamin L Cohen, David B Sachar
The treatment of inflammatory bowel disease (IBD)-ulcerative colitis (UC) and Crohn's disease (CD)-has evolved beyond surgery with the introduction of biologic agents, primarily antibodies against mediators of inflammation and cell attraction. Anti-tumor necrosis factor (TNF) agents have been the first line treatment for moderate to severe ulcerative colitis and Crohn's disease for more than 15 years. During that time much has been learnt about how best to use these agents. This review will assess the evidence on how to optimize the use of anti-TNF agents; when and how to start treatment; how to monitor treatment and when to de-escalate it; and the potential adverse effects of these drugs...
June 19, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28629905/2017-american-college-of-rheumatology-american-association-of-hip-and-knee-surgeons-guideline-for-the-perioperative-management-of-antirheumatic-medication-in-patients-with-rheumatic-diseases-undergoing-elective-total-hip-or-total-knee-arthroplasty
#20
Susan M Goodman, Bryan Springer, Gordon Guyatt, Matthew P Abdel, Vinod Dasa, Michael George, Ora Gewurz-Singer, Jon T Giles, Beverly Johnson, Steve Lee, Lisa A Mandl, Michael A Mont, Peter Sculco, Scott Sporer, Louis Stryker, Marat Turgunbaev, Barry Brause, Antonia F Chen, Jeremy Gililland, Mark Goodman, Arlene Hurley-Rosenblatt, Kyriakos Kirou, Elena Losina, Ronald MacKenzie, Kaleb Michaud, Ted Mikuls, Linda Russell, Alexander Sah, Amy S Miller, Jasvinder A Singh, Adolph Yates
OBJECTIVE: This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA)...
June 8, 2017: Journal of Arthroplasty
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