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Biological drugs

Imran Mahmud, Naznin Shahria, Sabina Yeasmin, Asif Iqbal, Emdadul Hasan Mukul, Sudipta Gain, Jamil Ahmad Shilpi, Md Khirul Islam
Ceriops decandra is a mangrove tree species, reputed for its folkloric uses in the treatment of gastrointestinal disorders, infection, snakebites, inflammation, and cancer. Different parts of the plant are rich with various phytoconstituents which include diterpenoids (ceriopsin A-G), triterpenoids (lupeol, α-amyrin, oleanolic acid, ursolic acid), and phenolics (catechin, procyanidins).These phytoconstituents and their derivatives could form a new basis for developing new drugs against various diseases. The objective of the present study is to compile the phytochemical, ethnobotanical, biological, and pharmacological significance of the plant to provide directions for future research to find out therapeutically active lead compounds for developing new drugs against diseases of current interest including diabetes, inflammation, and cancer...
June 22, 2018: Journal of Complementary & Integrative Medicine
Jenny Beebe, Jing-Yuan Liu, Jian-Ting Zhang
Signal transducer and activator of transcription 3 (STAT3) controls many biological processes including differentiation, survival, proliferation, and angiogenesis. In normal healthy cells, STAT3 is tightly regulated to maintain a momentary active state. However, aberrant or constitutively activated STAT3 has been observed in many different cancers and constitutively activated STAT3 has been shown to associate with poor prognosis and tumor progression. For this reason, STAT3 has been studied as a possible target in the treatment of many different types of cancers...
June 19, 2018: Pharmacology & Therapeutics
Vittoria Massafra, Roberto Pellicciari, Antimo Gioiello, Saskia W C van Mil
Bile acids are amphipathic molecules that were previously known to serve as fat solubilizers in the intestine in postprandial conditions. In the last two decades, bile acids have been recognized as signaling molecules regulating energy metabolism pathways via, amongst others, the farnesoid X receptor (FXR). Upon bile acid activation, FXR controls expression of genes involved in bile acid, lipid, glucose and amino acid metabolism. In addition, FXR activation has been shown to limit the inflammatory response...
June 19, 2018: Pharmacology & Therapeutics
Aleksandra Andreevna Ageeva, Ekaterina A Khramtsova, Ilya M Magin, Peter A Purtov, Miguel A Miranda, Tatyana V Leshina
The origin of biomolecules in the pre-biological period is still a matter of debate, as is the unclarified nature of the differences in enantiomer properties, especially the medically important activity of chiral drugs. On the first issue, significant progress has been made in the last decade of the 20th century with the experimental confirmation of Frank's popular theory on chiral catalysis in spontaneous asymmetric synthesis. Prof. Soai examined the chiral catalysis of the alkylation of achiral aldehydes by achiral reagents...
June 22, 2018: Chemistry: a European Journal
K C Nicolaou, Ruofan Li, Zhaoyong Lu, Emmanuel N Pitsinos, Lawrence B Alemany
Namenamicin is a rare natural product possessing potent cytotoxic properties that may prove useful as a lead compound for payloads of antibody-drug conjugates (ADCs). Its scarcity, coupled with the uncertainty of its full absolute configuration, elevates it to an attractive synthetic target. Herein we describe the total synthesis of the two C7'-epimers of namenamicin and assign its complete structure, opening the way for further chemical and biological studies toward the discovery of potent payloads for ADCs directed toward targeted cancer therapies...
June 22, 2018: Journal of the American Chemical Society
Joaquim Aguirre-Plans, Janet Piñero, Jörg Menche, Ferran Sanz, Laura I Furlong, Harald H H W Schmidt, Baldo Oliva, Emre Guney
The past decades have witnessed a paradigm shift from the traditional drug discovery shaped around the idea of “one target, one disease” to polypharmacology (multiple targets, one disease). Given the lack of clear-cut boundaries across disease (endo)phenotypes and genetic heterogeneity across patients, a natural extension to the current polypharmacology paradigm is to target common biological pathways involved in diseases via endopharmacology (multiple targets, multiple diseases). In this study, we present proximal pathway enrichment analysis (PxEA) for pinpointing drugs that target common disease pathways towards network endopharmacology...
June 22, 2018: Pharmaceuticals
Alessandro Isidori, Federica Loscocco, Marilena Ciciarello, Giulia Corradi, Mariangela Lecciso, Darina Ocadlikova, Sarah Parisi, Valentina Salvestrini, Sergio Amadori, Giuseppe Visani, Antonio Curti
Acute myeloid leukemia (AML) is a disease, which mainly affects the elderly population. Unfortunately, the prognosis of patients aged >65 years is dismal, with 1-year overall survival approaching 10% with conventional therapies. The hypothesis of harnessing the immune system against cancer, including leukemia, has been postulated for a long time, and several clinical attempts have been made in this field. In the last years, we increased our knowledge about the interplay between AML and immune cells, but no major improvement has been translated, up to now, from bench to bedside...
June 22, 2018: Cancers
Dimitrios Papadopoulos, Iosif Bader, Efthalia Gkioxari, Vasiliki Petta, Theodoros Tsaras, Nikoletta Galanopoulou, Maria-Anna Archontouli, Filia Diamantea, Emmanouil Kastanakis, Napoleon Karagianidis, Vasiliki Filaditaki
Aspiration pneumonia has a high incidence in hospitalized patients with community-acquired pneumonia and results in high mortality rates. We aimed to evaluate microbiology and assess prognostic factors of aspiration pneumonia in the setting of a tertiary hospital pulmonology department. Community-acquired (CAAP) and healthcare-associated aspiration pneumonia (HCAAP) cases hospitalized over a period of a year were prospectively followed. Demographic, clinical, biological and radiological data were recorded at admission, while sputum, tracheal aspirates or bronchial washing samples were collected within 48 hours of admission...
June 1, 2018: Le Infezioni in Medicina
Eunae Kim, Cheolhee Kim
Rational drug design is accomplished through the complementary use of structural biology and computational biology of biological macromolecules involved in disease pathology. Most of the known theoretical approaches for drug design are based on knowledge of the biological targets to which the drug binds. This approach can be used to design drug molecules that restore the balance of the signaling pathway by inhibiting or stimulating biological targets by molecular modeling procedures as well as by molecular dynamics simulations...
June 22, 2018: Current Medicinal Chemistry
Fernando Alonso, María Josefina Quezada, Gabriel Gola, Victoria Richmond, Gabriela Cabrera, Andrea Barquero, Javier Alberto Ramírez
Over the last decades, much effort has been devoted to the design of the "ideal" library for screening, the most promising strategies being those which draw inspiration from biogenic compounds, as they seek to add biological relevance to such libraries. On the other hand, there is a growing understanding of the role that molecular complexity plays in the discovery of new bioactive small molecules. Nevertheless, the introduction of molecular complexity must be balanced with synthetic accessibility...
June 21, 2018: ChemMedChem
John K Chan, Stephanie Chow, Subasish Bhowmik, Amandeep Mann, Daniel S Kapp, Robert L Coleman
Gynecologic cancers comprise of mostly uterine, ovarian, and cervical malignancies and are responsible for 95,000 new cases annually in the United States. Uterine cancer is the most common and the number of new cases and mortality has been increasing. Cervical cancer has decreased due to screening, early detection, and treatment of pre-invasive cancers. However, ovarian cancer remains the most lethal because of advanced stage at diagnosis and drug resistance. The metastatic spread pattern differs amongst these cancers, with uterine and cervical cancer found mostly in the primary organ and ovarian cancer disseminating throughout the peritoneum and upper abdomen at presentation...
June 21, 2018: Clinical & Experimental Metastasis
Titouan Jaunet-Lahary, Daniel P Vercauteren, Fabrice Fleury, Adèle D Laurent
Disulfonic stilbene (DS) derivatives are a member of the large family of compounds widely employed in medicine and biology as modulators for membrane transporters or inhibitors of a protein involved in DNA repair. They constitute interesting compounds that have not yet been investigated within the bioavailability framework. No crystallographic structures exist involving such compounds embedded in the most common drug carrier, human serum albumin (HSA). The present work studies, for the first time, the physico-chemical features driving the inclusion of three DS derivatives (amino, nitro and acetamido, named DADS, DNDS and DATDS, respectively) within the four common HSA binding sites using combined molecular docking and molecular dynamics simulations...
June 22, 2018: Physical Chemistry Chemical Physics: PCCP
Violeta Claudia Bojinca, Mihai Bojinca, Madalina Gheorghe, Adelina Birceanu, Cristina Ileana Iosif, Serban Mihai Balanescu, Andra Rodica Balanescu
Tumor necrosis factor inhibitors are the first biological agents used in the treatment of rheumatoid arthritis (RA) to have yielded satisfactory results in terms of clinical improvement and radiologic progression, but they are also associated with the possibility of occurrence of a number of autoimmune systemic events [drug-induced lupus (DIL), vasculitis, sarcoidosis] and localized adverse events [uveitis, psoriasis, interstitial lung disease, erythema multiforme including the major form Stevens-Johnson syndrome (SJS)]...
July 2018: Biomedical Reports
Alina D Nikotina, Lidia Koludarova, Elena Y Komarova, Elena R Mikhaylova, Nikolay D Aksenov, Roman Suezov, Viktor G Kartzev, Boris A Margulis, Irina V Guzhova
Combinational anticancer therapy demonstrates increased efficiency, as it targets different cell-survival mechanisms and allows the decrease of drug dosages that are often toxic to normal cells. Inhibitors of the heat shock response (HSR) are known to reduce the efficiency of proteostasis mechanisms in many cancerous cells, and therefore, may be employed as anti-tumor drug complements. However, the application of HSR inhibitors is limited by their cytotoxicity, and we suggested that milder inhibitors may be employed to sensitize cancer cells to a certain drug...
June 5, 2018: Oncotarget
Helin Feng, Heather Tillman, Gang Wu, Andrew M Davidoff, Jun Yang
Osteosarcoma (OS) cell lines are widely used in understanding the biological functions of cancer, identification and validation of therapeutic targets, as well as in vitro or in vivo preclinical drug screening. Here we report there is a frequent loss-of-function of polycomb repressive complex 2 (PRC2) in OS cell lines but it is rare in tumor samples based on genomic sequencing data, western blotting and immunohistochemistry analysis of H3K27me3. U2OS and 143B cell lines have a complete loss of function of PRC2 and several others have partial loss...
June 5, 2018: Oncotarget
Gokhan Yildiz
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the third-leading cause of malignancy-associated mortality worldwide. HCC cells are highly resistant to chemotherapeutic agents. Therefore, there are currently only two US Food and Drug Administration-approved drugs available for the treatment of HCC. The objective of the present study was to analyze the results of previously published high-throughput drug screening, and in vitro genomic and transcriptomic data from HCC cell lines, and to integrate the obtained results to define the underlying molecular mechanisms of drug sensitivity and resistance in HCC cells...
July 2018: Oncology Letters
Ed Madeley, Brett Duane
Data sourcesPubMed, EMBASE, Web of Science, Cochrane library, China Biology Medicine Disc (CBM), China National Knowledge infrastructure (CNKI).Study SelectionThis study included only human randomised controlled trials (RCTs) and clinical controlled trials (CCTs). To be included studies had to include patients prescribed oral anticoagulant therapy (OAT) requiring dental extraction(s). Comparison was made between patients discontinuing OAT for the dental extraction(s) and those continuing with their OAT. The outcome measured was post-operative bleeding identified by clinician or patient...
June 2018: Evidence-based Dentistry
Marco Simonetti, Diego M Cannas, Xavier Just-Baringo, Iñigo J Vitorica-Yrezabal, Igor Larrosa
Biaryls are ubiquitous core structures in drugs, agrochemicals and organic materials that have profoundly improved many aspects of our society. Although traditional cross-couplings have made practical the synthesis of many biaryls, C-H arylation represents a more attractive and cost-effective strategy for building these structural motifs. Furthermore, the ability to install biaryl units in complex molecules via late-stage C-H arylation would allow access to valuable structural diversity, novel chemical space and intellectual property in only one step...
July 2018: Nature Chemistry
Xuan Luo, Chuiwen Deng, Yunyun Fei, Wen Zhang, Yongzhe Li, Xuan Zhang, Yan Zhao, Xiaofeng Zeng, Fengchun Zhang
BACKGROUND: Psoriatic arthritis (PsA) is a chronic and seronegative inflammatory arthritis occurring in patients with psoriasis. The current knowledge about the risk of malignancy associated with psoriatic arthritis (PsA) patients undergoing therapy is controversial. We focused on the relationship between malignancy and therapy and undertook a meta-analysis to address this issue. METHODS: A systematic literature search of the PubMed, EMBASE, and Web of Science databases was performed to identify relevant studies and trials...
May 23, 2018: Seminars in Arthritis and Rheumatism
Shindu C Thomas, Tushar Madaan, Zeenat Iqbal, Sushama Talegaonkar
BACKGROUND: Bendamustine HCl, an antineoplastic drug, has a very short life of about 40 minutes which necessitates administration of large doses which leads to increased side effects as well as costs. OBJECTIVE: The present work describes the fabrication, optimization and evaluation of bioactive hydroxyapatite nanoparticles to achieve sustained delivery of bendamustine HCl. METHODS: Hydroxyapatite nanoparticles (NPs) were prepared by the wet chemical precipitation method by reacting a calcium and phosphate precursor and the reaction was optimized via Box-Behnken DOE...
June 20, 2018: Current Drug Delivery
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