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Therapeutic Drug* AND anti*

Seungwha Paik, Jin Kyung Kim, Chaeuk Chung, Eun-Kyeong Jo
Tuberculosis (TB), which is primarily caused by the major etiologic agent Mycobacterium tuberculosis (Mtb), remains a serious infectious disease worldwide. Recently, much effort has been made to develop novel/improved therapies by modulating host responses to TB (i.e., host-directed therapy). Autophagy is an intracellular catabolic process that helps maintain homeostasis or the removal of invading pathogens via a lysosomal degradation process. The activation of autophagy by diverse drugs or agents may represent a promising treatment strategy against Mtb infection, even to drug-resistant strains...
October 15, 2018: Virulence
Juhi Singh, Pooja Mittal, Gunjan Vasant Bonde, Gufran Ajmal, Brahmeshwar Mishra
Quercetin (Qu), is a flavonoid known to have anti-diabetic effects owing to its antioxidant property, thus promoting regeneration of the pancreatic islets, ultimately increasing insulin secretion. But the therapeutic application of Qu is hampered by its low oral bioavailability and its unfavourable physicochemical characteristics. The present work aimed at formulation of Quercetin loaded Soluplus® micelles (SMs) so as to enhance its bioavailability and provide prolonged release for the management of diabetes...
October 16, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Li Yan Chan, Joshua Ding Wei Teo, Kevin Shyong-Wei Tan, Keitaro Sou, Wei Lek Kwan, Chi-Lik Ken Lee
Chloroquine was among the first of several effective drug treatments against malaria until the onset of chloroquine resistance. In light of diminished clinical efficacy of chloroquine as an antimalarial therapeutic, there is potential in efforts to adapt chloroquine for other clinical applications, such as in combination therapies and in diagnostics. In this context, we designed and synthesized a novel asymmetrical squaraine dye coupled with chloroquine (SQR1-CQ). In this study, SQR1-CQ was used to label live Plasmodium falciparum ( P...
October 14, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Iman Fatemi, Fatemeh Delrobaee, Maryam Bahmani, Ali Shamsizadeh, Mohammad Allahtavakoli
The aim of this study was to evaluate the anti-diabetic drug metformin (Met) effects on the anxiety and cognitive impairment in ovariectomized mice. Thirty-two female adult mice were distributed into four groups: control, sham ovariectomy, ovariectomy + Met 7 mg/kg and ovariectomy + Met 15 mg/kg. The vaginal cytology was used to confirm the ovariectomy surgery. Anxiety was monitored using elevated plus maze test and cognitive function was assessed by novel object recognition task. Animal's brains were analyzed for the brain-derived neurotrophic factor (BDNF)...
October 12, 2018: Neuroscience Letters
Aimei Liu, Qinghua Wu, Jingchao Guo, Irma Ares, José-Luis Rodríguez, María-Rosa Martínez-Larrañaga, Zonghui Yuan, Arturo Anadón, Xu Wang, María-Aránzazu Martínez
Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are currently the most effective lipid-lowering drugs, effectively reducing the plasma total cholesterol and low-density lipoprotein, while also decreasing three triacylglycerols and increasing plasma high-density lipoprotein to a certain extent. However, the excessive or long-term use of statins can cause in vitro cytotoxicity, in vivo liver injury, liver necrosis, kidney damage, and myopathy in both human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with statins, and various antioxidants have been evaluated to investigate their protective roles against statin-induced liver, kidney, and muscle toxicities...
October 12, 2018: Pharmacology & Therapeutics
Caroline Murphy, Edwina Stack, Svetlana Krivelo, Mark Breheny, Hui Ma, Richard O'Kennedy
Antibody-based sensors are now widely used in therapeutics, diagnostics, and in environmental monitoring. Recombinant antibodies are becoming integral parts of such devices due to their reported high affinities, their capacity for engineering to achieve highly defined performance characteristics and the fact that their production can be optimized to a significant degree. To aid as a model for the identification of important analyte binding residues within the antibody sub-structure and elucidate the docking characteristics of small molecules such as metabolites, illicit drugs, biotherapeutics (proteins, peptides and nucleic acids) or toxins towards the antibody, herein we report the binding of the harmful cyanobacterial-toxin, microcystin-leucine-arginine (MC-LR) to a single chain fragment variable (scFv) antibody fragment...
October 12, 2018: Journal of Immunological Methods
Aaron J Wyble, Steven C Moore, Sean G Yates
Thyroid storm is a severe manifestation of thyrotoxicosis characterized by systemic organ dysfunction secondary to a hypermetabolic state. Although antithyroid drugs, steroids, beta-blockers, antipyretics, and cholestyramine are the standard of care, some patients inadequately respond to these conventional therapies. Therapeutic plasma exchange has been previously utilized as a treatment modality in patients with a poor response to routine therapies or with contraindications to them. Herein, we report our experience with the management of a case of thyroid storm refractory to conventional treatment but responsive to therapeutic plasma exchange...
October 15, 2018: Journal of Clinical Apheresis
Nathiya Ranganathan, Gayathri Mahalingam
Endophytic fungi, especially from mangrove plants, are rich source of secondary metabolites, which plays a major role in various pharmacological actions preferably in cancer and bacterial infections. To perceive its role in antidiabetic activity we isolated and tested the metabolites derived from a novel strain Alternaria longipes strain VITN14G obtained from mangrove plant Avicennia officinalis. The crude extract was analyzed for antidiabetic activity and subjected to column chromatography. The isolated fractions were screened in vitro for α-glucosidase and α-amylase inhibitory activities...
October 15, 2018: Journal of Cellular Biochemistry
Jane Harper, Katherine J Adams, Giovanna Bossi, Debbie E Wright, Andrea R Stacey, Nicole Bedke, Ruth Martinez-Hague, Dan Blat, Laure Humbert, Hazel Buchanan, Gabrielle S Le Provost, Zoe Donnellan, Ricardo J Carreira, Samantha J Paston, Luise U Weigand, Martina Canestraro, Joseph P Sanderson, Sophie Botta Gordon-Smith, Kate L Lowe, Karolina A Rygiel, Alex S Powlesland, Annelise Vuidepot, Namir J Hassan, Brian J Cameron, Bent K Jakobsen, Joseph Dukes
Robust preclinical testing is essential to predict clinical safety and efficacy and provide data to determine safe dose for first-in-man studies. There are a growing number of examples where the preclinical development of drugs failed to adequately predict clinical adverse events in part due to their assessment with inappropriate preclinical models. Preclinical investigations of T cell receptor (TCR)-based immunotherapies prove particularly challenging as these biologics are human-specific and thus the conventional testing in animal models is inadequate...
2018: PloS One
Parisa Hasanein, Abbasali Emamjomeh, Nasibeh Chenarani, Mussa Bohlooli
OBJECTIVES: Cognitive impairment and hyperalgesia are among the common manifestations of diabetes. Hyperglycemia may contribute to their developments but the exact pathophysiology underlying these complications is not fully understood. Flavonoids from plants original have beneficial effects on diabetes by improving glycemic control. Rutin (RUT) is a bioflavonoid found in many plants and foods with many biological activities including neuroprotective and antidiabetic effects. In this study, we hypothesized that administration of RUT (10, 25 and 50 mg/kg, i...
October 15, 2018: Nutritional Neuroscience
Sophie Neugebauer, Christina Wichmann, Sibylle Bremer-Streck, Stefan Hagel, Michael Kiehntopf
BACKGROUND: Adequate antibiotic treatment is a prerequisite for the successful treatment of systemic infections. Based on accumulating scientific evidence, a fixed dosage regimen can lead to insufficient and ineffective antibiotic therapy. Thus, the aim of this study was to develop and validate a simplified, but sensitive method for the simultaneous quantification of antimicrobials by using liquid chromatography with tandem mass spectrometry (LC-MS/MS) for the development of personalized therapy regimens using therapeutic drug monitoring (TDM)...
October 12, 2018: Therapeutic Drug Monitoring
Jesús Valencia-Cervantes, Sara Huerta-Yepez, Guillermo Aquino-Jarquín, Sara Rodríguez-Enríquez, Daniel Martínez-Fong, José-Antonio Arias-Montaño, Víctor Manuel Dávila-Borja
Medulloblastomas are among the most frequently diagnosed pediatric solid tumors, and drug resistance remains as the principal cause of treatment failure. Hypoxia and the subsequent activation of hypoxia‑inducible factor 1α (HIF‑1α) are considered key factors in modulating drug antitumor effectiveness, but the underlying mechanisms in medulloblastomas have not yet been clearly understood. The aim of the present study was to determine whether hypoxia induces resistance to cyclophosphamide (CPA) and ifosfamide (IFA) in DAOY medulloblastoma cells, whether the mechanism is dependent on HIF‑1α, and whether involves the modulation of the expression of cytochromes P450 (CYP)2B6, 3A4 and 3A5 and the control of cell proliferation...
October 12, 2018: Oncology Reports
Su-Hyun Nho, Goo Yoon, Ji-Hye Seo, Ha-Na Oh, Seung-Sik Cho, Hangun Kim, Hyun Woo Choi, Jung-Hyun Shim, Jung-Il Chae
Licochalcone H (LCH) is a chemical compound that is a positional isomer of licochalcone C (LCC), a chalconoid isolated from the root of Glycyrrhiza inflata, which has various pharmacological properties including anti‑inflammatory, antioxidant, antitumor, and anticancer effects. However, the efficacy of LCH on cancer cells has not been investigated. The present study examined the effects of LCH on cell proliferation, induction of apoptosis, and the regulation of matrin 3 (Matr3) protein in oral squamous cell carcinoma (OSCC) cells by Annexin V/propidium iodide (PI) staining and western blot analysis...
October 11, 2018: Oncology Reports
Upashi Goswami, Raghuram Kandimalla, Sanjeeb Kalita, Arun Chattopadhyay, Siddhartha Sankar Ghosh
Combination drug therapy has become an effective clinical practice for cancer treatment because of low cytotoxicity by the synergistic effect of each medicine. Luminescent Au nanoclusters (Au NCs) were formulated into spherical polyethylene glycol (PEG)-Au NC-encapsulated drug-sodium butyrate (NaB) composite nanoparticles (PEG-Au NC-NaB-NPs) in the presence of PEG and NaB. Their effect on cancer cells was investigated using bio imaging, unravelling the mechanism of the endocytosis pathway and combination therapeutic interventions with a plant-based antimalarial drug artesunate (ART)...
September 30, 2018: ACS Omega
Damayanti Bagchi, V S Sharan Rathnam, Peter Lemmens, Indranil Banerjee, Samir Kumar Pal
Nanomaterials with antimicrobial properties triggered by external stimuli appear to be a promising and innovative substitute for the destruction of antibiotic-resistant superbugs as they can induce multiple disruptions in the cellular mechanism. This study demonstrates the use of squaraine (SQ) dye as the photosensitive material, activated in the near-infrared tissue-transparent therapeutic window. The dye has been covalently attached to the ZnO nanoparticle surface, forming ZnO-SQ nanohybrids. The formation of the nanohybrids is confirmed using Fourier transform infrared and other optical spectroscopic methods...
September 30, 2018: ACS Omega
Annette C Dolphin
This review will first describe the importance of Ca2+ entry for function of excitable cells, and the subsequent discovery of voltage-activated calcium conductances in these cells. This finding was rapidly followed by the identification of multiple subtypes of calcium conductance in different tissues. These were initially termed low- and high-voltage activated currents, but were then further subdivided into L-, N-, PQ-, R and T-type calcium currents on the basis of differing pharmacology, voltage-dependent and kinetic properties, and single channel conductance...
October 2, 2018: Brain and Neuroscience Advances
Pavimol Angsantikul, Soracha Thamphiwatana, Qiangzhe Zhang, Kevin Spiekermann, Jia Zhuang, Ronnie H Fang, Weiwei Gao, Marygorret Obonyo, Liangfang Zhang
Inspired by the natural pathogen-host interactions and adhesion, this study reports on the development of a novel targeted nanotherapeutics for the treatment of Helicobacter pylori ( H. pylori ) infection. Specifically, plasma membranes of gastric epithelial cells (e.g. AGS cells) are collected and coated onto antibiotic-loaded polymeric cores, the resulting biomimetic nanoparticles (denoted AGS-NPs) bear the same surface antigens as the source AGS cells and thus have inherent adhesion to H. pylori bacteria...
June 2018: Adv Ther (Weinh)
Yeping Sun, Shanshan Wang, Yong Yi, Jing Zhang, Zhongping Duan, Kehu Yuan, Wenjun Liu, Jing Li, Yiping Zhu
Hepatitis B virus (HBV) infection is a leading cause of liver cirrhosis, liver cancer, and liver failure, affecting 350 million people worldwide. Currently available anti-HBV drugs include (PEGylated-) interferon-α and nucleos(t)ide analogs, which can cause significant side effects and drug-resistance in many cases of long-term treatment. The lack of a reliable and robust in vitro infection system is a major barrier for understanding the HBV life cycle and discovering novel therapeutic targets. In the present study, we demonstrate that overexpression of the hepatitis B surface antigen binding protein (SBP) in HepG2 cells (HepG2-SBP) resulted in their susceptibility to HBV infection...
2018: Frontiers in Cellular and Infection Microbiology
Harry Menon, Adip Pillai, Jeanine Aussenberg-Rodriguez, John Ambrose, Irini Youssef, Elizabeth A Griffiths, Omar Al Ustwani
Background: Most hospitals still use unfractionated heparin (UFH) as the primary agent for venous thromboembolism (VTE) prophylaxis in the hospital setting due to ease of use and insignificant cost. However, the risk of heparin-induced thrombocytopenia (HIT) has led some groups to favor other options for therapeutic and prophylactic anticoagulation. This is particularly relevant in light of recent data demonstrating a lower rate of HIT in patients receiving enoxaparin compared with UFH...
October 2018: Avicenna Journal of Medicine
Q Liu, D Wang, M Yuan, B F He, J Li, C Mao, G S Wang, H Qian
Aberrantly overexpressed oncogenic microRNAs (miRNAs, miRs) are excellent targets for therapeutic interventions. Nevertheless, thus far, little progress has been made in developing miRNA-based drugs and techniques for clinical applications, especially for overexpressed miRNAs. In this study, we demonstrate that self-assembled DNA nanostructures bearing multiple DNA sequences that are complementary to a target miRNA can effectively capture the overexpressed oncogenic miRNA and subsequently inhibit cancer cell proliferation...
October 14, 2018: Chemical Science
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