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Experimental therapeutics

L Chen, J-Q Jiang, Y Zhang, H Feng
OBJECTIVE: As an initial step in exploring the feasibility of oral sulfhydryl as an adjuvant for improving nitrate ester tolerance, this study was designed to experimentally test the adjuvant therapy in a rabbit model of atherosclerosis (AS). MATERIALS AND METHODS: New Zealand white rabbits with induced AS were randomly divided into four groups: AS group, AS + nitrate ester group, AS + nitrate ester tolerance group, and AS + drug combination group. Additionally, four equivalent groups with healthy New Zealand white rabbits without AS were also conformed...
March 2018: European Review for Medical and Pharmacological Sciences
Mitul A Mehta, Anne Schmechtig, Vasileia Kotoula, Juliet McColm, Kimberley Jackson, Claire Brittain, Sitra Tauscher-Wisniewski, Bruce J Kinon, Paul D Morrison, Thomas Pollak, Timothy Mant, Steven C R Williams, Adam J Schwarz
BACKGROUND: Aberrant glutamate neurotransmission, and in particular dysfunction of the N-methyl-D-aspartate receptor (NMDAR), has been implicated in psychiatric disorders and represents a novel therapeutic target. Low-dose administration of the NMDA antagonist ketamine in healthy volunteers elicits a strong blood oxygenation level dependent (BOLD) imaging signal that can be attenuated by pretreatment with single, therapeutically effective doses of marketed medicines interacting with the glutamate system...
March 21, 2018: Psychopharmacology
Taoufik Ladhari, Konrad Szafnicki
Usual therapies against malignant tumors, such as surgery, chemotherapy, radiation, is severe and when repeated their efficiency may decrease because tumorous cells may become resistant. Contrarily, hyperthermia has been known for some time as an effective auxiliary treatment, which can be applied repeatedly. In some cases of abdominal carcinomatosis, particularly those of digestive origin, HIPEC is considered as an promising therapeutic option. Chemotherapy and hyperthermia are combined via the perfusion of the abdominal cavity with hot fluids containing chemotherapeutic agents, thus, augmenting the influence of appropriate chemotherapeutic agents with heat...
April 2018: 3 Biotech
Ciriana Orabona, Giada Mondanelli, Maria T Pallotta, Agostinho Carvalho, Elisa Albini, Francesca Fallarino, Carmine Vacca, Claudia Volpi, Maria L Belladonna, Maria G Berioli, Giulia Ceccarini, Susanna Mr Esposito, Raffaella Scattoni, Alberto Verrotti, Alessandra Ferretti, Giovanni De Giorgi, Sonia Toni, Marco Cappa, Maria C Matteoli, Roberta Bianchi, Davide Matino, Alberta Iacono, Matteo Puccetti, Cristina Cunha, Silvio Bicciato, Cinzia Antognelli, Vincenzo N Talesa, Lucienne Chatenoud, Dietmar Fuchs, Luc Pilotte, Benoît Van den Eynde, Manuel C Lemos, Luigina Romani, Paolo Puccetti, Ursula Grohmann
A defect in indoleamine 2,3-dioxygenase 1 (IDO1), which is responsible for immunoregulatory tryptophan catabolism, impairs development of immune tolerance to autoantigens in NOD mice, a model for human autoimmune type 1 diabetes (T1D). Whether IDO1 function is also defective in T1D is still unknown. We investigated IDO1 function in sera and peripheral blood mononuclear cells (PBMCs) from children with T1D and matched controls. These children were further included in a discovery study to identify SNPs in IDO1 that might modify the risk of T1D...
March 22, 2018: JCI Insight
Yang Cao, Xu Shi, Yingmin Liu, Ren Xu, Qing Ai
MicroRNA-338-3p has been reported to be a tumor suppressor in multiple cancer types. However, the biological role of miR-338-3p and underlying mechanism in multiple myeloma (MM) remains unclear. In the present study, we investigate the biological role and potential of miR-338-3p in MM. We found that miR-338-3p was significantly decreased in MM newly diagnosed and relapsed tissues and cell lines. Overexpression of miR-338-3p in MM cells significantly inhibited proliferation and promoted apoptosis, and caspase-3 and caspase-8 activity...
March 21, 2018: Oncology Research
Francesca Pischiutta, Eliana Sammali, Ornella Parolini, Hilary V O Carswell, Elisa R Zanier
Acute brain injury resulting from ischemic/hemorrhagic or traumatic damage is one of the leading causes of mortality and disability worldwide and is a significant burden to society. Neuroprotective options to counteract brain damage are very limited in stroke and traumatic brain injury (TBI). Given the multifaceted nature of acute brain injury and damage progression, several therapeutic targets may need to be addressed simultaneously to interfere with the evolution of the injury and improve the patient's outcome...
January 2018: Cell Transplantation
Lucia Centurione, Francesca Passaretta, Maria Antonietta Centurione, Silvia De Munari, Elsa Vertua, Antonietta Silini, Marco Liberati, Ornella Parolini, Roberta Di Pietro
The human placenta is an important source of stem cells that can be easily collected without ethical concerns since it is usually discarded after childbirth. In this study, we analyzed the amniotic membrane (AM) from the human placenta with the aim of mapping different regions with respect to their morpho-functional features and regenerative potential. AMs were obtained from 24 healthy women, undergoing a caesarean section, and mapped into 4 different regions according to their position in relation to the umbilical cord: the central, intermediate, peripheral, and reflected areas...
January 2018: Cell Transplantation
Ewelina Bratek, Apolonia Ziembowicz, Elzbieta Salinska
Hypoxia-ischemia (H-I) at the time of birth may cause neonatal death or lead to persistent brain damage. The search for an effective treatment of asphyxiated infants has not resulted in an effective therapy, and hypothermia remains the only available therapeutic strategy. Among possible experimental therapies, the induction of ischemic tolerance is promising. Recent investigations have shown that activation of group II metabotropic glutamate receptors (mGluR2/3) can provide neuroprotection against H-I, but the mechanism of this effect is not clear...
March 17, 2018: Brain Sciences
Suzanne M de la Monte, Ming Tong, Jack R Wands
The Journal of Alzheimer's Disease (JAD), founded in 1998, played a pivotal role in broadening the field of research on Alzheimer's disease (AD) by publishing a diverse range of clinical, pathological, molecular, biochemical, epidemiological, experimental, and review articles from its birth. This article recounts my own journey as an author who contributed articles to JAD over the 20 years of the journal's existence. In retrospect, it seems remarkable that a considerable body of work that originated from our group marks a trail that began with studies of vascular, stress, and mitochondrial factors in AD pathogenesis, exploded into the concept of 'Type 3 Diabetes', and continued with the characterization of how environmental, exposure, and lifestyle factors promote neurodegeneration and which therapeutic strategies could reverse the neurodegeneration cascade...
2018: Journal of Alzheimer's Disease: JAD
Gianluigi Forloni, Claudia Balducci
The production of soluble amyloid-β oligomers (AβOs) and the activation of inflammation are two important early steps in the pathogenesis of Alzheimer's disease (AD). The central role of oligomers as responsible for the neuronal dysfunction associated with the clinical features has been extended to the other protein misfolding disorders definable, on this basis, as oligomeropathies. In AD, recent evidence indicates that the mechanism of inflammation as a consequence of neurodegeneration must be assessed in favor of a more direct role of glial activation in the alteration of synaptic function...
2018: Journal of Alzheimer's Disease: JAD
Christian Griñán-Ferré, Rubén Corpas, Dolors Puigoriol-Illamola, Verónica Palomera-Ávalos, Coral Sanfeliu, Mercè Pallàs
Epigenetics is emerging as the missing link among genetic inheritance, environmental influences, and body and brain health status. In the brain, specific changes in nucleic acids or their associated proteins in neurons and glial cells might imprint differential patterns of gene activation that will favor either cognitive enhancement or cognitive loss for more than one generation. Furthermore, derangement of age-related epigenetic signaling is appearing as a significant risk factor for illnesses of aging, including neurodegeneration and Alzheimer's disease (AD)...
2018: Journal of Alzheimer's Disease: JAD
Phuong H Nguyen, Maria P Del Castillo-Frias, Olivia Berthoumieux, Peter Faller, Andrew J Doig, Philippe Derreumaux
Targeting the early oligomers formed by the amyloid-β (Aβ) peptide of 40 and 42 amino acids is considered one promising therapeutic approach for Alzheimer's disease (AD). In vitro experiments and computer simulations are often used in synergy to reveal the modes of interactions of drugs. In this account, we present our contribution to understanding how small molecules bind to Aβ40/Aβ42 peptides, based either on extensive coarse-grained and all-atom simulations, or a variety of experimental techniques. We conclude by offering several perspectives on the future of this field to design more efficient drugs...
March 16, 2018: Journal of Alzheimer's Disease: JAD
Q L Gui, Y S Wang, S Huang, Y Wan, H P Wang, Z G Zhu, M M Li, H Y Zhu, Q S Tao, Y Y Shen, Q Zhang, H Qin
Objective: To investigate the clinical significance of tumor associated macrophages (TAM) in multiple myeloma (MM) and the relationship with angiogenesis and immunosuppression. Methods: Seventy cases of MM patients diagnosed from August 2015 to June 2017 were enrolled in the study as experimental group, 20 cases of benign hematological diseases (13 with iron deficiency anemia and 7 with megaloblastic anemia) patients as control group. Immunohistochemical method was used to detect the expression of CD163, CD34 and VEGF in bone marrow samples, and flow cytometry was used to detect the proportion of regulatory T cell (Treg cells), ELISA was used to detect the level of IL-10, and the clinical features were analyzed...
February 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Mark Sherman, Lydia Contreras
Recent advances in computational and experimental methods have led to novel avenues for therapeutic development. Utilization of nucleic acids as therapeutic agents and/or targets has been recently gaining attention due to their potential as high-affinity, selective molecular building blocks for various therapies. Notably, development of computational algorithms for predicting accessible RNA binding sites, identifying therapeutic target sequences, modeling delivery into tissues, and designing binding aptamers have enhanced therapeutic potential for this new drug category...
March 18, 2018: Current Opinion in Biotechnology
G H Callejas, R L Figueira, F L L Gonçalves, F A P Volpe, A W Zuardi, J A Crippa, J E Hallak, L Sbragia
Gastroschisis (GS) is an abdominal wall defect that results in histological and morphological changes leading to intestinal motility perturbation and impaired absorption of nutrients. Due to its anti-inflammatory, antioxidant, and neuroprotective effects, cannabidiol (CBD) has been used as a therapeutic agent in many diseases. Our aim was to test the effect of maternal CBD in the intestine of an experimental model of GS. Pregnant rats were treated over 3 days with CBD (30 mg/kg) after the surgical induction of GS (day 18...
March 15, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Chrysovalantis Voutouri, Triantafyllos Stylianopoulos
Hyaluronan is abundant in the extracellular matrix of many desmoplastic tumors and determines in large part the tumor biochemical and mechanical microenvironment. Additionally, it has been identified as one of the major physiological barriers to the effective delivery of drugs to solid tumors and its targeting with the use of pharmaceutical agents has shown to decompress tumor blood vessels, and thus improve tumor perfusion and efficacy of cytotoxic drugs. In this study, we investigated the contribution of hyaluronan to the accumulation of mechanical forces in tumors...
2018: PloS One
Alberto Zullo, Emanuela Simone, Maddalena Grimaldi, Vincenzina Musto, Francesco Paolo Mancini
Fighting diseases and controlling the signs of ageing are the major goals of biomedicine. Sirtuins, enzymes with mainly deacetylating activity, could be pivotal targets of novel preventive and therapeutic strategies to reach such aims. Scientific proofs are accumulating in experimental models, but, to a minor extent, also in humans, that the ancient practice of calorie restriction could prove an effective way to prevent several degenerative diseases and to postpone the detrimental signs of ageing. In the present review, we summarize the evidence about the central role of sirtuins in mediating the beneficial effects of calorie restriction in skeletal and cardiac muscle since these tissues are greatly damaged by diseases and advancing years...
March 21, 2018: International Journal of Molecular Sciences
Katarzyna Kaczmarek, Tomasz Hornowski, Martina Kubovcíkova, Milan Timko, Marceli Koralewski, Arkadiusz Józefczak
The efficiency of ultrasound hyperthermia for anti-cancer treatments such as radiotherapy or chemotherapy can be improved by using sonosensitizers, which are materials that enhance the attenuation and dissipation of acoustic energy. We propose the use of magnetic nanoparticles as sonosensitizers because of their biocompatibility, non-toxicity, and common use in several medical applications. A magnetic material was synthetized and then incorporated in the form of a magnetic fluid in agar tissue-mimicking phantoms...
March 21, 2018: ACS Applied Materials & Interfaces
Skanda Rajasundaram
Our increasing appreciation of adenosine as an endogenous signaling molecule that terminates inflammation has generated excitement regarding the potential to target adenosine receptors (ARs) in the treatment of multiple sclerosis (MS), a disease of chronic neuroinflammation. Of the four G protein-coupled ARs, A2ARs are the principal mediator of adenosine's anti-inflammatory effects and accordingly, there is a growing body of evidence surrounding the role of A2ARs in experimental autoimmune encephalomyelitis (EAE), the dominant animal model of MS...
2018: Frontiers in Immunology
Laura Hidalgo-Garcia, Julio Galvez, M Elena Rodriguez-Cabezas, Per O Anderson
Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions of the gastrointestinal tract characterized by an exacerbated mucosal immune response. Macrophages play pivotal roles in the maintenance of gut homeostasis but they are also implicated in the pathogenesis of IBD. They are highly plastic cells and their activation state depends on the local environment. In the healthy intestine, resident macrophages display an M2 phenotype characterized by inflammatory energy, while inflammatory M1 macrophages dominate in the inflamed intestinal mucosa...
2018: Frontiers in Pharmacology
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