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https://www.readbyqxmd.com/read/30551086/designing-luminescent-ruthenium-prodrug-for-precise-cancer-therapy-and-rapid-clinical-diagnosis
#1
Zhennan Zhao, Xiang Zhang, Chang-E Li, Tianfeng Chen
The effective design of a targeted drug delivery system could improve the therapeutic efficacy of anticancer drugs by reducing their undesirable adsorption and toxic side effects. Here, an RGD-peptide functionalized and bioresponsive ruthenium prodrug (Ru-RGD) was designed for both cancer therapy and clinical diagnosis. This prodrug can be selectively delivered to cervical tumor sites to enhance theranostic efficacy. The benzimidazole-based ligand of the complex is susceptible to acidic conditions so, after reaching the tumor microenvironment, ligand substitution occurs and the therapeutic drug is released...
December 5, 2018: Biomaterials
https://www.readbyqxmd.com/read/30550999/near-infrared-aiegens-as-transformers-to-enhance-tumor-treatment-efficacy-with-controllable-self-assembled-redox-responsive-carrier-free-nanodrug
#2
Wei Zhang, Yan Wen, Dong-Xuan He, Yi-Feng Wang, Xiao-Li Liu, Chan Li, Xing-Jie Liang
Nanosized drug delivery systems (nDDS) have been extensively exploited to achieve improved therapeutic performance of chemotherapeutic drugs in cancer treatment. Carrier-free nanodrugs have recently emerged as a promising generation of nDDS. In this work, a carrier-free theranostic nanodrug was fabricated by incorporating near-infrared (NIR) emission AIEgens (NPAPF) with redox responsive camptothecin-gemcitabine amphiphilic prodrug (CPT-ss-GEM) to form self-assembled nanoparticles (NCssG NPs). The introducing of AIEgens is designed to not only endow the nDDS with NIR imaging ability but also to act as transformers to modulate the geometry of the self-assembled nanostructures from nanowires to spherical nanoparticles...
December 10, 2018: Biomaterials
https://www.readbyqxmd.com/read/30550980/identification-of-b-cell-epitopes-enhanced-by-protein-unfolding-and-aggregation
#3
Timothy J Eyes, James I Austerberry, Rebecca J Dearman, Linus O Johannissen, Ian Kimber, Noel Smith, Angela Thistlethwaite, Jeremy P Derrick
Aggregation of therapeutic proteins is a key factor in the generation of unwanted immunogenicity, and can result in reduced serum half-life, neutralization of function and adverse health effects. There is currently little information regarding how aggregates interact with B-cell receptors or cognate antibodies at the protein sequence level, or whether non-native, aggregate-induced epitopes predominate in these interactions. Using an antibody fragment (single chain antibody variable fragment; scFv) that forms aggregates readily at low temperature, anti-scFv IgG antibody responses were generated by intraperitoneal injection of BALB/c strain mice with monomer or aggregate preparations...
December 11, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/30550953/targeting-stats-in-neuroinflammation-the-road-less-traveled
#4
REVIEW
Seyed Mohammad Nabavi, Touqeer Ahmed, Maheen Nawaz, Kasi Pandima Devi, Devasahayam Jaya Balan, Valeria Pittalà, Sandro Argüelles-Castilla, Lara Testai, Haroon Khan, Antoni Sureda, Marcos Roberto de Oliveira, Rosa Anna Vacca, Suowen Xu, Bahman Yousefi, Valeria Curti, Maria Daglia, Eduardo Sobarzo-Sánchez, Rosanna Filosa, Seyed Fazel Nabavi, Maryam Majidinia, Ahmad Reza Dehpour, Samira Shirooie
JAK/STAT transduction pathway is a highly conserved pathway implicated in regulating cellular proliferation, differentiation, survival and apoptosis. Dysregulation of this pathway is involved in the onset of autoimmune, haematological, oncological, metabolic and neurological diseases. Over the last few years, the research of anti-neuroinflammatory agents has gained considerable attention. The ability to diminish the STAT-induced transcription of inflammatory genes is documented for both natural compounds (such as polyphenols) and chemical drugs...
December 11, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30550941/microfluidic-assembly-of-hydrogel-based-immunogenic-tumor-spheroids-for-evaluation-of-anticancer-therapies-and-biomarker-release
#5
Pooja Sabhachandani, Saheli Sarkar, Seamus Mckenney, Ravi Dashnamoorthy, Andrew M Evens, Tania Konry
Diffuse large B cell lymphoma (DLBCL), the most common subtype of Non-Hodgkin lymphoma, exhibits pathologic heterogeneity and a dynamic immunogenic tumor microenvironment (TME). However, the lack of preclinical in vitro models of DLBCL TME hinders optimal therapeutic screening. This study describes the development of an integrated droplet microfluidics-based platform for high-throughput generation of immunogenic DLBCL spheroids. The spheroids consist of three cell types (cancer, fibroblast and lymphocytes) in a novel hydrogel combination of alginate and puramatrix, which promoted cell adhesion and aggregation...
December 11, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30550940/carrier-free-nanoparticles-of-cathepsin-b-cleavable-peptide-conjugated-doxorubicin-prodrug-for-cancer-targeting-therapy
#6
Man Kyu Shim, Jooho Park, Hong Yeol Yoon, Sangmin Lee, Wooram Um, Jong-Ho Kim, Sun-Woong Kang, Joung-Wook Seo, Soo-Wang Hyun, Jae Hyung Park, Youngro Byun, Ick Chan Kwon, Kwangmeyung Kim
Cancer nanomedicine using nanoparticle-based delivery systems has shown outstanding promise in recent decades for improving anticancer treatment. However, limited targeting efficiency, low drug loading efficiency and innate toxicity of nanoparticles have caused severe problems, leaving only a few available in the clinic. Here, we newly developed carrier-free nanoparticles of cathepsin B-cleavable peptide (Phe-Arg-Arg-Gly; FRRG)-conjugated doxorubicin (DOX) prodrug (FRRG-DOX) that formed a stable nanoparticle structure with an average diameter of 213 nm in aqueous condition...
December 11, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30550888/dimethyl-fumarate-ameliorates-acetaminophen-induced-hepatic-injury-in-mice-dependent-of-nrf-2-ho-1-pathway
#7
Rehab S Abdelrahman, Noha Abdel-Rahman
Drug-induced liver toxicity is the most frequent cause of acute liver failure worldwide. Hepatotoxicity caused by acetaminophen (ACT) overdose is mediated by its metabolic product promoting oxidative stress and activation of inflammatory mediators. Nuclear factor erythroid-related factor-2 (Nrf-2) induces the release of cytoprotective enzymes in response to electrophilic or oxidative stress and is considered a promising therapeutic target. Dimethyl fumarate (DMF) is a potent activator of (Nrf-2), its anti-inflammatory and antioxidant properties of DMF have been highlighted recently...
December 11, 2018: Life Sciences
https://www.readbyqxmd.com/read/30550846/identification-of-putative-non-host-essential-genes-and-novel-drug-targets-against-acinetobacter-baumannii-by-in-silico-comparative-genome-analysis
#8
Reaz Uddin, Fareha Masood, Syed Sikander Azam, Abdul Wadood
Acinetobacter baumannii, the gram-negative bacteria emerged as an extremely critical pathogen causing nosocomial and different kinds of infections. A. baumannii exhibit resistivity towards various classes of antibiotics that shows that there is a dire need to search more drug targets by exploiting the full genome of the bacteria. In doing so, a strategy is made with the combination of computational biology, pathogen informatics and cheminformatics. Comparative genomics analysis, modeling and docking studies have been performed for the prediction of non-host essential genes and novel drug candidates against A...
December 11, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/30550797/modulation-of-the-unfolded-protein-response-pathway-as-an-antiviral-approach-in-airway-epithelial-cells
#9
Aline Schögler, Oliver Caliaro, Melanie Brügger, Blandina I Oliveira Esteves, Izabela Nita, Amiq Gazdhar, Thomas Geiser, Marco P Alves
INTRODUCTION: Rhinovirus (RV) infection is a major cause of cystic fibrosis (CF) lung morbidity with limited therapeutic options. Various diseases involving chronic inflammatory response and infection are associated with endoplasmic reticulum (ER) stress and subsequent activation of the unfolded protein response (UPR), an adaptive response to maintain cellular homeostasis. Recent evidence suggests impaired ER stress response in CF airway epithelial cells, this might be a reason for recurrent viral infection in CF...
December 11, 2018: Antiviral Research
https://www.readbyqxmd.com/read/30550765/novel-aspects-of-pcsk9-and-lipoprotein-receptors-in-renal-disease-related-dyslipidemia
#10
Pragyi Shrestha, Bart van de Sluis, Robin P F Dullaart, Jacob van den Born
Chronic kidney disease (CKD) is a global health problem with a profound impact on quality of life. Cardiovascular disease is established as a major cause of morbidity and mortality in patients with CKD. Dyslipidemia is frequently observed in CKD patients, suggesting a causal relation between dyslipidemia and cardiovascular disease in CKD patients. Currently, lipid-lowering drugs such as statins, are the primary choice for lipid lowering therapy in high-risk populations. Despite many studies showing CVD risk reduction with statins, CVD still remains the leading cause of the death in CKD...
December 11, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/30550405/combination-of-%C3%AF-3-fatty-acids-and-cisplatin-as-a-potential-alternative-strategy-for-personalized-therapy-of-metastatic-melanoma-an-in-vitro-study
#11
Renata Ottes Vasconcelos, Simona Serini, Ana Paula de Souza Votto, Gilma Santos Trindade, Caterina Fanali, Alessandro Sgambato, Gabriella Calviello
The recently developed therapeutic strategies have led to unprecedented improvements in the control of metastatic melanoma and in the survival of specific subgroups of patients. However, drug resistance, low response rates, and undesired side effects make these treatments not suitable or tolerable for all the patients, and chemotherapeutic treatments appear still indispensable, at least for subgroups of patients. New combinatory strategies are also under investigation as tailored treatments or salvage therapies, including combined treatments of immunotherapy with conventional chemotherapy...
December 13, 2018: Melanoma Research
https://www.readbyqxmd.com/read/30550348/pulmonary-hypertension-in-patients-with-a-history-of-intravenous-drug-use
#12
Michael McGee, Nicholas Whitehead, Scott Twadell, Nicholas Collins
OBJECTIVE: Pulmonary hypertension may be a consequence of intrinsic elevation in pulmonary vasculature resistance or complicate numerous other conditions affecting the cardiac and respiratory systems. In this review we sought to explore the relationship between pulmonary hypertension and intravenous drug use. METHODS: A narrative review was conducted using PubMed MeSH search with further papers were identified using a standard PubMed search with relevant key terms and various synonyms...
December 14, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/30550295/f8-il10-a-new-potential-anti-rheumatic-drug-evaluated-by-a-pet-guided-translational-approach
#13
Stefan T G Bruijnen, Durga M S H Chandrupatla, Leonardo Giovanonni, Dario Neri, Danielle J Vugts, Marc C Huisman, Otto S Hoekstra, Rene J P Musters, Adriaan A Lammertsma, Guus Ams van Dongen, Gerrit Jansen, Carla F M Molthoff, Conny J van der Laken
Antibody fragment F8- mediated Interleukin 10 (IL10) delivery is a novel treatment for rheumatoid arthritis (RA). F8 binds to the extra-domain-A of fibronectin (ED-A). In this study, in-vivo biodistribution and arthritis targeting of radiolabeled F8-IL10 were investigated in RA patients, followed by further animal studies. Therefore, three RA patients (DAS28 >3.2) received 0.4 mg, 30-74 megabecquerel [124I]I-F8-IL10 for PET-CT and blood sampling. In visually identified PET-positive joints target-to-background were calculated...
December 14, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/30550209/-therapeutic-effect-of-nasal-corticosteroids-combined-with-nasal-antihistamine-on-vasomotor-rhinitis
#14
K Song, Z P Gong, Y F Ma, Y Chen
Objective: To observe the clinical efficacy of nasal corticosteroids combined with nasal antihistamine in the treatment of vasomotor rhinitis. Method: One hundred and twenty vasomotor rhinitis patients were randomly divided into three groups including budesonide group, azelastine group, and budesonide and azelastine group with 40 cases in each. Nasal spray with nasal corticosteroids and nasal antihistamines was applied for combined treatment group, while the patients in budesonide group and azelastine group were given only nasal corticosteroids and nasal antihistamines, respectively...
December 5, 2018: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
https://www.readbyqxmd.com/read/30549489/a-double-blind-randomized-placebo-controlled-study-of-aspirin-and-n-acetylcysteine-as-adjunctive-treatments-for-bipolar-depression
#15
Isabelle E Bauer, Charles Green, Gabriela D Colpo, Antonio L Teixeira, Sudhakar Selvaraj, Katherine Durkin, Giovana B Zunta-Soares, Jair C Soares
OBJECTIVE: Neuroinflammation has been implicated in the pathophysiology of bipolar disorder. Some evidence shows that nonsteroidal anti-inflammatory drugs (NSAIDs) have promising antidepressant effects. The antioxidant N-acetylcysteine (NAC) may enhance the effects of NSAIDs. No study has, however, tested the adjunctive therapeutic benefits of an NSAID and NAC in bipolar disorder. METHODS: The sample included 24 medicated patients diagnosed with DSM-IV-TR bipolar disorder who were aged 18-65 years and had a Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 20...
December 4, 2018: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/30549486/abrupt-symptom-improvements-in-antidepressant-clinical-trials-transient-placebo-effects-or-therapeutic-reality
#16
Sigal Zilcha-Mano, Steven P Roose, Patrick J Brown, Bret R Rutherford
BACKGROUND: According to prevailing models and classical reports, abrupt responses to antidepressant medication are not true drug responses but rather transient placebo effects. By contrast, recent reports suggest that early sudden improvements have a lasting effect and appear in most patients receiving medication. Clinical guidelines influenced by these contradictory findings are mixed and confusing. OBJECTIVE: To evaluate the occurrence and effects of abrupt improvements in symptoms in placebo vs antidepressant conditions in individuals with late-life depression, using a rigorous method of identifying sudden gains, developed and tested in scores of studies in psychotherapy research...
December 4, 2018: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/30549424/extracellular-vesicle-mimetic-ghost-nanovesicles-for-delivering-anti-inflammatory-drugs-to-mitigate-gram-negative-bacterial-outer-membrane-vesicle-induced-systemic-inflammatory-response-syndrome
#17
Gyeongyun Go, Jaewook Lee, Dong-Sic Choi, Sang Soo Kim, Yong Song Gho
Sepsis is one of the major causes of death in hospital patients and is represented by systemic inflammatory response syndrome (SIRS) associated with infection. Gram-negative bacteria including Escherichia coli can provoke sepsis by stimulating the immune systems. Outer membrane vesicles (OMVs), nanosized vesicular structures derived from Gram-negative bacteria, contain several pathogen-associated molecular patterns, and are demonstrated to mediate SIRS. Here, extracellular vesicle-mimetic ghost nanovesicles loaded with dexamethasone, an anti-inflammatory drug, are developed using alkaline solution, sonication, and buoyant density gradient ultracentrifugation...
December 14, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/30549068/determination-of-olanzapine-for-therapeutic-drug-monitoring-in-schizophrenia-patients-by-lc-ms-method
#18
Mevlut Albayrak, Yucel Kadioglu, Mehmet Emrah Yaman, Onur Senol, Elif Oral
Olanzapine is an atypical antipsychotic drug from thienobenzodiazepine family which displays efficacy in patients with schizophrenia and related psychoses. A novel LC/MS method was developed and validated for determination of olanzapine in schizophrenia patients plasma. A liquid-liquid extraction procedure carried out by using 5 mL diethyl ether-diisopropyl ether mixture (1:1, v/v). Average recovery of the extraction procedure was found as 94.8 %. Chromatographic separation was performed on reversed-phase C18 column (250x2...
December 13, 2018: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/30548527/poly-allylamine-hydrochloride-and-fucoidan-based-self-assembled-polyelectrolyte-complex-nanoparticles-for-cancer-therapeutics
#19
Pei Wang, Ranjith Kumar Kankala, Biaoqi Chen, Ruimin Long, Duanhua Cai, Yuangang Liu, Shibin Wang
Herein, we fabricated the novel drug delivery system based on the self-assembly of two polyelectrolytes, poly-allylamine hydrochloride (PAH) and fucoidan, as the polycation and polyanion, respectively, under mild conditions for cancer therapeutics. Furthermore, the designed polyelectrolyte complex nanoparticles as well as the methotrexate (MTX) disodium salt-loaded composites were systematically characterized using various techniques. The MTX loading in the nanoparticles was confirmed by zeta potential values that changed from -36...
December 12, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/30547858/nonconventional-therapeutics-against-staphylococcus-aureus
#20
Caroline M Grunenwald, Monique R Bennett, Eric P Skaar
Staphylococcus aureus is one of the most important human pathogens that is responsible for a variety of diseases ranging from skin and soft tissue infections to endocarditis and sepsis. In recent decades, the treatment of staphylococcal infections has become increasingly difficult as the prevalence of multi-drug resistant strains continues to rise. With increasing mortality rates and medical costs associated with drug resistant strains, there is an urgent need for alternative therapeutic options. Many innovative strategies for alternative drug development are being pursued, including disruption of biofilms, inhibition of virulence factor production, bacteriophage-derived antimicrobials, anti-staphylococcal vaccines, and light-based therapies...
November 2018: Microbiology Spectrum
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