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Immunomodulatory therapy

Soo-Hwan Kim, Jieun Jung, Kyung Jin Cho, Jong-Ho Choi, Hyeong Seon Lee, Gi Jin Kim, Seung Gwan Lee
The immunomodulatory effects of mesenchymal stem cells (MSCs) are an important mediator of their therapeutic effects in stem cell therapy and regenerative medicine. The regulation mechanism of MSCs is orchestrated by several factors in both intrinsic and extrinsic events. Recent studies have shown that the dynamic expression of cytokines secreted from MSCs control T cell function and maturation by regulating the expression of FoxP3, which figures prominently in T cell differentiation. However, there is no evidence that placenta-derived mesenchymal stem cells (PD-MSCs) have strong immunomodulatory effects on T cell function and maturation via FoxP3 expression...
October 31, 2018: International Journal of Stem Cells
Günter Päth, Nikolaos Perakakis, Christos S Mantzoros, Jochen Seufert
Diabetes mellitus type 1 and type 2 have become a global epidemic with dramatically increasing incidences. Poorly controlled diabetes is associated with severe life-threatening complications. Beside traditional treatment with insulin and oral anti-diabetic drugs, clinicians try to improve patient's care by cell therapies using embryonic stem cells (ESC), induced pluripotent stem cells (iPSC) and adult mesenchymal stem cells (MSC). ESC display a virtually unlimited plasticity, including the differentiation into insulin producing β-cells, but they raise ethical concerns and bear, like iPSC, the risk of tumours...
October 17, 2018: Metabolism: Clinical and Experimental
Małgorzata Woźniewicz, Paulina M Nowaczyk, Anna Kurhańska-Flisykowska, Marzena Wyganowska-Świątkowska, Małgorzata Lasik-Kurdyś, Jarosław Walkowiak, Joanna Bajerska
Periodontal disease is highly prevalent worldwide, and consumption of certain foods, such as fruits, seem to improve the effectiveness of periodontal therapy (PT) due to their antiadhesive, immunomodulatory, and antioxidative properties. We hypothesized that the cranberry functional beverage (CFB) consumed for eight weeks improves gingival inflammation indices via inhibition of dental plaque, and alterations in antioxidant status, and systemic inflammation in patients with gingivitis. In this two-arm randomized controlled study, fifty participants were divided into an experimental group (CFB), administered daily with 750 ml CFB, or a control group administered the same amount of water...
October 2018: Nutrition Research
Lu Zhang, Di Jing, Lei Wang, Yuan Sun, Jian Jian Li, Brianna Hill, Fan Yang, Yuanpei Li, Kit S Lam
Sophisticated self-assembly may endow materials with a variety of unique functions that are highly desirable for therapeutic nanoplatform. Herein, we report the co-assembly of two structurally-defined telodendrimers, each comprised of hydrophilic linear PEG and hydrophobic cholic acid cluster as a basic amphiphilic molecular subunit. One telodendrimer has four added indocyanine green derivatives, leading to excellent photothermal properties; the other telodendrimer has four sulfhydryl groups designed for efficient inter-subunit cross-linking, contributing to superior stability during circulation...
October 19, 2018: Nano Letters
Yiming Bi, Han Li, Dazhuang Yi, Yuxue Sun, Yang Bai, Sheng Zhong, Yang Song, Gang Zhao, Yong Chen
Glioblastoma multiforme (GBM) is the most commonly encountered subtype of deadly brain cancer in human adults. It has a high recurrence rate and shows aggressive proliferation. The novel cytotoxic agent temozolomide (TMZ) is now frequently applied as the first-line chemotherapeutic treatment for GBM; however, a considerable number of patients treated with TMZ turn out to be refractory to this drug. Hence, a more effective therapeutic approach is urgently required to overcome this critical issue. Accumulating evidence has shown that both AMPK and AKT are activated by TMZ, while only AMPK contributes to apoptosis via mammalian target of rapamycin (mTOR) inhibition...
October 17, 2018: Molecular Pharmaceutics
Rachela Bleuel, Bernadette Eberlein
Affecting 0.5 % of the world's population, vitiligo is an acquired skin disorder that poses major challenges in terms of dermatological care. Characterized by patchy depigmentation, the disease is frequently associated with cosmetic disfigurement and considerable psychological distress. The primary pathophysiological causes for the loss of functional melanocytes are thought to include genetic predisposition, autoimmune mechanisms, and oxidative stress. The present article highlights treatment recommendations contained in the European guidelines as well as those provided by recent reviews on vitiligo...
October 18, 2018: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
Janusz K Rybakowski
The use of lithium for the prevention of recurrences in mood disorders has a 55-year history. Nowadays, lithium is universally accepted as the first-choice mood-stabilizer (MS) for maintenance treatment of bipolar disorder. In addition to its mood-stabilizing properties, lithium exerts anti-suicidal, immunomodulatory and neuroprotective action which may further substantiate its clinical usefulness. Despite these facts, the use of lithium in mood disorders has been greatly underutilized. The reasons include the introduction and promoting other MS as well as a perception of lithium as a "toxic drug" due to its side effects, mainly thyroid, renal and cognitive disturbances...
2018: Frontiers in Molecular Neuroscience
Andrea Ghiroldi, Marco Piccoli, Federica Cirillo, Michelle M Monasky, Giuseppe Ciconte, Carlo Pappone, Luigi Anastasia
Despite considerable improvements in the treatment of cardiovascular diseases, heart failure (HF) still represents one of the leading causes of death worldwide. Poor prognosis is mostly due to the limited regenerative capacity of the adult human heart, which ultimately leads to left ventricular dysfunction. As a consequence, heart transplantation is virtually the only alternative for many patients. Therefore, novel regenerative approaches are extremely needed, and several attempts have been performed to improve HF patients' clinical conditions by promoting the replacement of the lost cardiomyocytes and by activating cardiac repair...
October 16, 2018: International Journal of Molecular Sciences
Muhammed Razmi T, T P Afra, Davinder Parsad
Depigmented patches in vitiligo, a common dermatosis, cause a great psychological distress to the patients. Hence, apart from halting the disease process, the strategies to impart normal skin color to these white patches carry an important role in the management of vitiligo. Surgical procedures are often required for stable vitiligo lesions not responding to medical therapies. It involves 'shuffling' of melanocytes from the pigmented skin to the depigmented areas. During the last fifty years, the vitiligo surgery has evolved from tissue transplantation via cellular transplantation to reach a stage where the use of stem cells or immunomodulatory cells is contemplating...
October 17, 2018: Experimental Dermatology
Roberto Mina, Nisha S Joseph, Jonathan L Kaufman, Vikas A Gupta, Leonard T Heffner, Craig C Hofmeister, Lawrence H Boise, Madhav V Dhodapkar, Charise Gleason, Ajay K Nooka, Sagar Lonial
BACKGROUND: Primary plasma cell leukemia (pPCL) is an aggressive plasma cell disorder characterized by circulating plasma cells and a poor prognosis. Although patients who have pPCL benefit from the use of stem cell transplantation (SCT) and novel agents, their prognosis remains inferior to that of patients who have myeloma. METHODS: This was a retrospective analysis of 38 consecutive patients with pPCL who were diagnosed between October 2005 and July 2016 and were registered in the Winship Cancer Institute of Emory University database...
October 17, 2018: Cancer
Rajkumar Cheluvappa
The appendix contains copious lymphoid tissue and is constantly exposed to gut flora. Appendicitis followed by appendectomy (AA), when done at a young age, prevents or significantly ameliorates inflammatory bowel diseases (IBDs) in later life. Inflammatory bowel disease comprises Crohn's disease and ulcerative colitis. Our unique murine AA model is the only existing experimental model of AA. Herein, the appendiceal pathology closely resembles the pathological features of human appendicitis. Our AA model protects against experimental colitis in an age-, bacteria- and antigen-dependent manner...
October 16, 2018: Inflammatory Bowel Diseases
Patrick Cherin, Abir Tadmouri, Christophe de Jaeger, Taylor Pindi Sala, Jean-Charles Crave
Immunoglobulin (Ig) therapy is used to treat a wide range of immunodeficiencies and autoimmune diseases; While, its clinical benefit has been demonstrated in several studies, Ig therapy is associated with a risk of systemic adverse effects. As such, Onset of renal impairment, including acute renal failure, osmotic nephrosis and renal insufficiency, after immunoglobulin administration is rare, but is one of the most significant concerns related to intravenous Ig use at immunomodulatory doses. However, only few studies have investigated the safety of subcutaneous Ig (SCIg) in relation to these rare conditions...
October 2018: Therapeutic Advances in Musculoskeletal Disease
Dass S Vinay, Byoung S Kwon
Immunomodulatory antibodies that directly trigger and reawaken suppressed T-cell effector function are termed 'checkpoint inhibitors'. CTLA-4 and PD-1/PD-L1 molecules are the most studied inhibitory immune check points against cancer and because of this therapeutic property have entered the clinic for treating a variety of tumor types. The results so far demonstrate a positive impact on cancer remission. Preclinical studies have demonstrated that targeting a number of other T-cell surface molecules including both positive and negative immune regulators, also possesses strong antitumor activity...
October 2018: Immunotherapy
Bożena Adamczyk, Dorota Koziarska, Sławomir Kasperczyk, Monika Adamczyk-Sowa
So far little has been known about antioxidant properties of immunomodulatory drugs. The aim of the study was to evaluate the antioxidant status in serum of relapsing-remitting multiple sclerosis (RRMS) patients treated with II-line immunomodulatory therapy compared to de novo diagnosed patients, subjects treated with interferon (IFN) beta and healthy controls. We analyzed the relationships depending on the gender, age, disease duration, the Expanded Disability Status Scale (EDSS), the Annualized Relapse Rate (ARR) and MRI lesions in patients treated with II-line...
October 16, 2018: Free Radical Research
Eran Zimran, Alla Keyzner, Camelia Iancu-Rubin, Ronald Hoffman, Marina Kremyanskaya
Despite the dramatic progress made in the treatment of patients with myelofibrosis since the introduction of the JAK1/2 inhibitor ruxolitinib, a therapeutic option that can modify the natural history of the disease and prevent evolution to blast-phase is still lacking. Recent investigational treatments including immunomodulatory drugs and histone deacetylase inhibitors benefit some patients but these effects have proven modest at best. Several novel agents do show promising activity in preclinical studies and early-phase clinical trials...
October 16, 2018: Expert Review of Hematology
Mariangela Garofalo, Alessandro Villa, Nicoletta Rizzi, Lukasz Kuryk, Vincenzo Mazzaferro, Paolo Ciana
Oncolytic viruses (OV) are engineered to infect, replicate in and kill cancer cells. Currently, the OV therapeutic approach is mainly restricted to neoplasia amenable to direct local administration of viral particles, while the possibility of a systemic delivery of cancer-tropic viruses would extend the OV application to the treatment of metastatic neoplasia. Herein, we applied in vivo/ex vivo imaging to demonstrate that cancer tropism is achieved when OV are encapsulated inside extracellular vesicles (EV) administered intravenously (i...
October 13, 2018: Viruses
Alejandro A Gru, Eli Williams, Jacqueline M Junkins-Hopkins
Iatrogenic lymphoproliferative disorders have been described in patients receiving immunosuppressive/immunomodulatory agents outside the transplantation setting. Novel biological agents such as TNF-α blockers and JAK-inhibitors have also proven to be effective in many disorders including rheumatoid arthritis, inflammatory bowel disease (ulcerative colitis and Crohn disease), psoriasis, and others. A significant dilemma exists in those lymphoproliferative disorders associated with immunosuppressants and rheumatologic conditions, that relies on whether the association of the process is with the medication or the underlying autoimmune condition...
October 12, 2018: American Journal of Surgical Pathology
Bernardino Miñana López, Felipe Villacampa Aubá, Fernando Ramón de Fata Chillón, Francisco Javier Ancizu Markert, Angel García Cortés, Pablo Doménech López, Santiago Chiva San Román, José María Velis Campillo, Fernando Díez-Caballero Alonso, José Enrique Robles García, David Rosell Costa, Juan Ignacio Pascual Piédrola
We review the role of immunotherapy in castration resistant prostate cancer. Two immunotherapeutic strategies have been applied, isolated or in combination, either with each other or with other agents with demonstrated efficacy in this scenario that would play a role as immunomodulators: vaccines or monoclonal antibodies aimed to block immune response checkpoint inhibitors. Although CRPC presents, a priori, characteristics suggesting that immunotherapy may play a relevant role as a therapeutic strategy, its clinical application has demonstrated a limited and heterogeneous activity, in terms of proportion of responders and response intensity...
September 2018: Archivos Españoles de Urología
Cristina Belizna, Francesca Pregnolato, Sebastien Abad, Jaume Alijotas-Reig, Howard Amital, Zahir Amoura, Laura Andreoli, Emmanuel Andres, Achile Aouba, Sule Apras Bilgen, Laurent Arnaud, Boris Bienvenu, Viktoria Bitsadze, Patrick Blanco, Miri Blank, Maria Orietta Borghi, Antonia Caligaro, Elisabeta Candrea, Valentina Canti, Laurent Chiche, Jean Marie Chretien, Jan Willem Cohen Tervaert, Laura Damian, Teresa Delross, Emmanuelle Dernis, Katrien Devreese, Aleksandra Djokovic, Enrique Esteve-Valverde, Maria Favaro, Céline Fassot, Raquel Ferer-Oliveras, Alban Godon, Mohamed Hamidou, Milena Hasan, Daniel Henrion, Bernard Imbert, Pierre Yves Jeandel, Pascale Jeannin, Patrick Jego, Noemie Jourde-Chiche, Jamilya Khizroeva, Olivier Lambotte, Cédric Landron, Jose Omar Latino, Estibaliz Lazaro, Karina de Leeuw, Thomas Le Gallou, Kiliç Levent, Maarten Liimper, Laurent Loufrani, Romain Lubin, Nadine Magy-Bertrand, Guillaume Mahe, Alexander Makatsariya, Thierry Martin, Christian Muchardt, Gyorgy Nagy, Loukman Omarjee, Pieter Van Paasen, Gilles Pernod, Florence Perrinet, Gilberto Pires da Rosa, Marc Antoine Pistorius, Amelia Ruffati, Fatma Said, Patrick Saulnier, Damien Sene, Loic Sentilhes, Ova Shovman, Jean Sibilia, Crina Sinescu, Natasa Stanisavljevic, Ljudmila Stojanovitch, Lai Shan Tam, Angela Tincani, Fréderic Tollis, Sebastian Udry, Marie Noelle Ungeheuer, Mathilde Versini, Ricard Cervera, Pier Luigi Meroni
The relapse rate in antiphospholipid syndrome (APS) remains high, i.e. around 20%-21% at 5 years in thrombotic APS and 20-28% in obstetrical APS (Cervera et al., 2009, 2015 [2,3]). Hydroxychloroquine (HCQ) appears as an additional therapy, as it possesses immunomodulatory and anti-thrombotic various effects (Pericleous et al., 2016; Andrade and Tektonidou, 2016; Belizna, 2015; Erkan et al., 2014; Erkan and Lockshin, 2012; De Carolis et al., 2015; Mekinian et al., 2015; Merashli et al., 2015; Galli, 2014; Lopez-Pedrera et al...
October 11, 2018: Autoimmunity Reviews
Gwendoline Montes Diaz, Raymond Hupperts, Judith Fraussen, Veerle Somers
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) in which demyelination and neurodegeneration occurs. The immune system of MS patients is characterized by a dysregulation in the balance between pro- and anti-inflammatory immune cells, whereby both the innate and adaptive immune system are involved. Dimethyl fumarate (DMF) was licensed in 2013 as an oral first-line therapy for relapsing-remitting (RR)MS patients. It has a strong efficacy with neuroprotective and immunomodulatory effects and a favourable benefit-risk profile...
October 12, 2018: Autoimmunity Reviews
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