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Immunomodulatory drugs

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https://www.readbyqxmd.com/read/28526605/microevolutionary-response-of-a-gut-nematode-to-intestinal-inflammation
#1
Cédric Lippens, Bruno Faivre, Gabriele Sorci
Parasitic helminths interfere with the immune responses of their hosts to establish long-lasting, chronic infections. While favorable to the parasite, the capacity to dampen the immune response can also provide a benefit to the host in terms of reduced risk of immune disorders and immunopathology. The immunomodulatory role of nematodes has been exploited in clinical trials to treat a number of inflammatory and immune diseases. However, how parasites adapt to an inflammatory environment remains a poorly explored question...
May 16, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28526350/designing-novel-bioconjugates-of-hydroxyethylcellulose-and-salicylates-for-potential-pharmaceutical-and-pharmacological-applications
#2
Khawar Abbas, Muhammad Amin, Muhammad Ajaz Hussain, Muhammad Sher, Syed Nasir Abbas Bukhari, Ibrahim Jantan, Kevin J Edgar
The present study deals with fabrication of macromolecular prodrugs (MPDs) of salicylic acid (SA) and aspirin (ASP) based on a hydrophilic cellulose ether, hydroxyethylcellulose (HEC). Degrees of substitution (DS) of SA and ASP per HEC repeating unit (HEC-RU) were achieved ranging from 0.60-2.18 and 0.53-1.50, respectively. The amphiphilic HEC-SA conjugate 2 assembled into nanowire-like structures, while HEC-ASP conjugate 6 formed nanoparticles (diameter 300-700nm) at a water/DMSO interface. After oral administration in rabbit models, conjugates 2 and 6 showed plasma half-life of 6...
May 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28525891/identification-of-precision-treatment-strategies-for-relapsed-refractory-multiple-myeloma-by-functional-drug-sensitivity-testing
#3
Muntasir Mamun Majumder, Raija Silvennoinen, Pekka Anttila, David Tamborero, Samuli Eldfors, Bhagwan Yadav, Riikka Karjalainen, Heikki Kuusanmäki, Juha Lievonen, Alun Parsons, Minna Suvela, Esa Jantunen, Kimmo Porkka, Caroline A Heckman
Novel agents have increased survival of multiple myeloma (MM) patients, however high-risk and relapsed/refractory patients remain challenging to treat and their outcome is poor. To identify novel therapies and aid treatment selection for MM, we assessed the ex vivo sensitivity of 50 MM patient samples to 308 approved and investigational drugs. With the results we i) classified patients based on their ex vivo drug response profile; ii) identified and matched potential drug candidates to recurrent cytogenetic alterations; and iii) correlated ex vivo drug sensitivity to patient outcome...
May 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28522110/high-dose-gemcitabine-busulfan-and-melphalan-for-autologous-stem-cell-transplant-in-patients-with-relapsed-or-refractory-myeloma-a-phase-2-trial-and-matched-pair-comparison-with-melphalan
#4
Yago Nieto, Benigno C Valdez, Sai R Pingali, Roland Bassett, Ruby Delgado, John Nguyen, Nina Shah, Uday Popat, Roy B Jones, Borje S Andersson, Alison Gulbis, Sairah Ahmed, Qaiser Bashir, Simrit Parmar, Krina Patel, Alan Myers, Gabriela Rondon, Robert Z Orlowski, Richard Champlin, Muzaffar Qazilbash
BACKGROUND: High-dose melphalan is of little benefit as a regimen for patients with relapsed or refractory myeloma undergoing an autologous stem-cell transplant (ASCT). The poor performance of single-agent melphalan in this setting prompted us to study a new high-dose combination of infused gemcitabine, busulfan, and melphalan. METHODS: We did a phase 2 trial at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). We enrolled patients with primary refractory or relapsed myeloma who had received treatment with bortezomib, an immunomodulatory drug, or both, or who were receiving a salvage ASCT...
May 15, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28521337/perspectives-for-clinical-use-of-engineered-human-host-defense-antimicrobial-peptides
#5
María Eugenia Pachón-Ibáñez, Younes Smani, Jerónimo Pachón, Javier Sánchez-Céspedes
Infectious diseases caused by bacteria, viruses or fungi are among the leading causes of death worldwide. The emergence of drug-resistance mechanisms, especially among bacteria, threatens the efficacy of all current antimicrobial agents, some of them already ineffective. As a result, there is an urgent need for new antimicrobial drugs. Host defense antimicrobial peptides (HDPs) are natural occurring and well-conserved peptides of innate immunity, broadly active against Gram-negative and Gram-positive bacteria, viruses and fungi...
May 1, 2017: FEMS Microbiology Reviews
https://www.readbyqxmd.com/read/28505457/molecular-and-biocompatibility-characterization-of-red-blood-cell-membrane-targeted-and-cell-penetrating-peptide-modified-polymeric-nanoparticles
#6
Kaustuv Sahoo, Sriharsha Karumuri, Rangika S Hikkaduwa Koralege, Nicholas H Flynn, Steve Hartson, Jing Liu, Joshua D Ramsey, Kaan Kalkan, Carey Pope, Ashish Ranjan
Red blood cells (RBCs) express a variety of immunomodulatory markers that enable the body to recognize them as self. We have shown that RBC membrane glycophorin A (GPA) receptor can mediate membrane attachment of protein therapeutics. A critical knowledge gap is whether attaching drug encapsulated nanoparticles (NPs) to GPA, and modification with cell penetration peptide (CPP) will impact binding, oxygenation and induce cellular stress. The objective of this study was to formulate copolymer-based NPs containing model fluorescent tagged bovine serum albumin (BSA) with GPA-specific targeting ligands such as ERY1 (ENPs), single chain variable antibody (scFv TER-119, SNPs), and low molecular weight protamine based CPP (LNPs) and determine their biocompatibility using a variety of complementary high-throughput in vitro assays...
May 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28504554/how-is-patient-care-for-multiple-myeloma-advancing
#7
Sonja Genadieva Stavric, Francesca Bonello, Sara Bringhen, Mario Boccadoro, Alessandra Larocca
Treatment of multiple myeloma has undergone profound changes in the past years thanks to the increased understanding of the biology of the disease and the new treatment options. New drugs and effective approaches are currently available for the treatment of multiple myeloma, including immunomodulatory agents, proteasome inhibitors and autologous stem cell transplantation. Areas covered. We have described the recent updated criteria to start treatment in multiple myeloma and summarized clinical data from major studies including most recent agents...
May 15, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28504078/a-review-on-therapeutic-potentials-of-trigonella-foenum-graecum-fenugreek-and-its-chemical-constituents-in-neurological-disorders-complementary-roles-to-its-hypolipidemic-hypoglycemic-and-antioxidant-potential
#8
Saima Zameer, Abul Kalam Najmi, Divya Vohora, Mohd Akhtar
OBJECTIVES: The growing rate of neurological disorders is a major concern in today's scenario. Today's research is focusing on therapeutic interventions providing benefits in these disorders. Presently, drugs of natural origin have gained more interest for the treatment of central nervous system disorders for their efficacy and less/ no side effects. This review is emphasizing the cited roles of Trigonella foenum graecum (fenugreek) and its constituents in different neurological manifestations...
May 15, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28501003/phytochemicals-for-taming-agitated-immune-endocrine-neural-axis
#9
REVIEW
Seema Patel
Homeostasis of immune-endocrine-neural axis is paramount for human health. If this axis gets agitated due to age, genetic variations, environmental exposures or lifestyle assaults, a cascade of adverse reactions occurs in human body. Cytokines, hormones and neurotransmitters, the effector molecules of this axis behave erratically, leading to a gamut of neural, endocrine, autoimmune, and metabolic diseases. Current panel of drugs can tackle some of them but not in a sustainable, benign way as a myriad of side effects, causal of them have been documented...
May 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28500900/treatment-of-refractory-epilepsy-patients-with-autologous-mesenchymal-stem-cells-reduces-seizure-frequency-an-open-label-study
#10
Fedor Hlebokazov, Tatiana Dakukina, Svetlana Ihnatsenko, Svetlana Kosmacheva, Michael Potapnev, Antos Shakhbazau, Natalia Goncharova, Michael Makhrov, Pavel Korolevich, Nikolai Misyuk, Victoria Dakukina, Irina Shamruk, Elena Slobina, Sergei Marchuk
PURPOSE: Existing anti-epileptic drugs (AED) have limited efficiency in many patients, necessitating the search for alternative approaches such as stem cell therapy. We report the use of autologous patient-derived mesenchymal stem cells (MSC) as a therapeutic agent in symptomatic drug-resistant epilepsy in a Phase I open label clinical trial (registered as NCT02497443). PATIENTS AND METHODS: The patients received either standard treatment with AED (control group), or AED supplemented with single intravenous administration of undifferentiated autologous MSC (target dose of 1×10(6)cells/kg), followed by a single intrathecal injection of neurally induced autologous MSC (target dose of 0...
May 10, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28487853/promising-approaches-to-optimize-the-biological-properties-of-the-antimicrobial-peptide-esculentin-1a-1-21-nh2-amino-acids-substitution-and-conjugation-to-nanoparticles
#11
REVIEW
Bruno Casciaro, Floriana Cappiello, Mauro Cacciafesta, Maria Luisa Mangoni
Antimicrobial peptides (AMPs) represent an interesting class of molecules with expanding biological properties which make them a viable alternative for the development of future antibiotic drugs. However, for this purpose, some limitations must be overcome: (i) the poor biostability due to enzymatic degradation; (ii) the cytotoxicity at concentrations slightly higher than the therapeutic dosages; and (iii) the inefficient delivery to the target site at effective concentrations. Recently, a derivative of the frog skin AMP esculentin-1a, named esculentin-1a(1-21)NH2, [Esc(1-21): GIFSKLAGKKIKNLLISGLKG-NH2] has been found to have a potent activity against the Gram-negative bacterium Pseudomonas aeruginosa; a slightly weaker activity against Gram-positive bacteria and interesting immunomodulatory properties...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/28486830/ethnomedicinal-uses-phytochemistry-and-pharmacological-aspects-of-the-genus-premna-a-review
#12
Roza Dianita, Ibrahim Jantan
CONTEXT: The genus Premna (Lamiaceae), distributed throughout tropical and subtropical Asia, Africa, Australia and the Pacific Islands, is used in folk medicine primarily to treat inflammation, immune-related diseases, stomach disorders, wound healing, and skin diseases. OBJECTIVES: This review exhaustively gathers available information on ethnopharmacological uses, phytochemistry, and bioactivity studies on more than 20 species of Premna and critically analyzes the reports to provide the perspectives and directions for future research for the plants as potential source of drug leads and pharmaceutical agents...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28484087/modulation-of-goat-monocyte-function-by-hccyst-2-a-secreted-cystatin-from-haemonchus-contortus
#13
Yujian Wang, Yuling Wen, Shuai Wang, Muhammad Ehsan, RuoFeng Yan, XiaoKai Song, LiXin Xu, XiangRui Li
Modulation and suppression of the host immune response by nematode parasites have been reported extensively and the cysteine protease inhibitor (cystatin) is identified as one of the major immunomodulator. In the present study, we cloned and produced recombinant cystatin protein from nematode parasite Haemonchus contortus (rHCcyst-2) and investigated its immunomodulatory effects on goat monocyte. rHCcyst-2 protein is biologically functional as shown by its ability to inhibit the protease activity of cathepsin L, cathepsin B and papain...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28481421/immunomodulatory-treatment-other-than-corticosteroids-immunoglobulin-and-plasma-exchange-for-chronic-inflammatory-demyelinating-polyradiculoneuropathy
#14
REVIEW
Mohamed Mahdi-Rogers, Ruth Brassington, Angela A Gunn, Pieter A van Doorn, Richard Ac Hughes
BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a disease that causes progressive or relapsing and remitting weakness and numbness. It is probably caused by an autoimmune process. Immunosuppressive or immunomodulatory drugs would be expected to be beneficial. This review was first published in 2003 and has been updated most recently in 2016. OBJECTIVES: To assess the effects of immunomodulatory and immunosuppressive agents other than corticosteroids, immunoglobulin, and plasma exchange in CIDP...
May 8, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28473823/recombinant-human-ifn%C3%AE-2b-response-promotes-vaginal-epithelial-cells-defense-against-candida-albicans
#15
Ting Li, Xiaoxi Niu, Xu Zhang, Suxia Wang, Zhaohui Liu
Classical antifungal drugs have been subjected to restrictions due to drug toxicity, drug resistance, bioavailability, and detrimental drug interactions. Type I interferon (IFN) exerts direct distinct immunostimulatory or immunomodulatory actions; however, little is known regarding the anti-fungal reactions of vaginal epithelial cells (VECs) induced by the type I IFN response. Therefore, in the present study, we evaluated the cytotoxic activity, immunocompetent cytokine responses, and non-B IgG production of the VK2/E6E7 VEC line following recombinant human IFN α-2b (rhIFNα-2b) treatment in response to Candida albicans...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28470884/follow-up-of-patients-with-refractory-or-relapsed-multiple-myeloma-after-allogeneic-hematopoietic-cell-transplantation
#16
Corina Schneidawind, Silke Duerr-Stoerzer, Christoph Faul, Lothar Kanz, Katja Weisel, Wolfgang Bethge, Dominik Schneidawind
BACKGROUND: The role of allogeneic hematopoietic cell transplantation (HCT) for the treatment of multiple myeloma is controversial. However, the introduction of proteasome inhibitors and immunomodulatory drugs might influence outcomes in case of relapse or refractory disease after allogeneic HCT. METHODS: We report 41 consecutive patients that underwent allogeneic HCT for the treatment of relapsed or refractory multiple myeloma. RESULTS: Three-year event-free survival (EFS) and overall survival (OS) of the whole cohort were 15% and 51%, respectively...
May 3, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28462710/endothelial-progenitor-cells-as-mediators-of-the-crosstalk-between-vascular-repair-and-immunity-lessons-from-systemic-autoimmune-diseases
#17
Javier Rodríguez-Carrio, Patricia López, Ana Suárez
From the discovery of Endothelial Progenitor Cells (EPC), these bone marrow-derived precursors have been placed as crucial mediators of the endothelial repair. Accordingly, altered levels and function of EPC have been found in different scenarios of CV risk. Despite the fact that EPC exhibit important characteristics which support a link of this cell subset with a number of inflammatory and immune networks, little is known on the actual mediators involved and the clinical relevance of these features. Systemic diseases are generally hallmarked by a vascular repair failure and increased cardiovascular disease occurrence, EPC impairment having a pivotal role...
April 27, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28456618/protein-tyrosine-phosphatase-conjugated-with-a-novel-transdermal-delivery-peptide-ap-rptp-alleviates-both-atopic-dermatitis-like-and-psoriasis-like-dermatitis
#18
Won-Ju Kim, Ja-Hyun Koo, Hyun-Jung Cho, Jae-Ung Lee, Ji Yun Kim, Hong-Gyun Lee, Sohee Lee, Jong Hoon Kim, Mi Seon Oh, Minah Suh, Eui-Cheol Shin, Joo Yeon Ko, Myung Hyun Sohn, Je-Min Choi
BACKGROUND: Atopic dermatitis and psoriasis are the two most common chronic inflammatory skin diseases. There is an unmet medical need to overcome limitations for transcutaneous drug development posed by the skin barrier. OBJECTIVE: We aimed to identify a novel transdermal delivery peptide and to develop a transcutaneously applicable immunomodulatory protein for treating atopic dermatitis and psoriasis. METHODS: We identified and generated reporter proteins conjugated to AP, a novel transdermal delivery peptide of human origin, and analyzed the intracellular delivery efficiency of these proteins in mouse and human skin cells and tissues using multi-photon confocal microscopy...
April 26, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28452243/evaluation-of-us-2016-0115161-a1-isoindoline-compounds-and-methods-of-their-use
#19
Rok Frlan, Stanislav Gobec
Immunomodulatory drugs (IMIDs®) are small orally available molecules that modulate the immune system and other biological targets through multiple mechanisms of action and have been successfully used in the treatment of myelodysplastic syndrome and multiple myeloma. However, recent studies of their complex mechanism of action revealed their potential in autoimmune diseases and solid tumors, which intensified scientific interest in these compounds. Areas covered: This patent application claims new IMIDs for the treatment of cancer and disorders associated with angiogenesis and inflammation...
June 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28452204/mesenchymal-stem-cells-time-to-change-the-name
#20
Arnold I Caplan
Mesenchymal stem cells (MSCs) were officially named more than 25 years ago to represent a class of cells from human and mammalian bone marrow and periosteum that could be isolated and expanded in culture while maintaining their in vitro capacity to be induced to form a variety of mesodermal phenotypes and tissues. The in vitro capacity to form bone, cartilage, fat, etc., became an assay for identifying this class of multipotent cells and around which several companies were formed in the 1990s to medically exploit the regenerative capabilities of MSCs...
April 28, 2017: Stem Cells Translational Medicine
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