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Therapeutic target

Felipe Del Valle Batalla, Ana-María Lennon-Dumenil, María-Isabel Yuseff
The capacity of B lymphocytes to produce specific antibodies, particularly broadly neutralizing antibodies that provide immunity to viral pathogens has positioned them as valuable therapeutic targets for immunomodulation. To become competent as antibody secreting cells, B cells undergo a series of activation steps, which are triggered by the recognition of antigens frequently displayed on the surface of other presenting cells. Such antigens elicit the formation of an immune synapse (IS), where local cytoskeleton rearrangements coupled to mechanical forces and membrane trafficking orchestrate the extraction and processing of antigens in B cells...
June 20, 2018: Molecular Immunology
Qing Ou-Yang, Bo Yan, Ang Li, Zhi-Song Hu, Jian-Nan Feng, Xin-Xin Lun, Ming-Ming Zhang, Meng-De Zhang, Kai-Chun Wu, Fang-Fang Xue, An-Gang Yang, Jing Zhao
As HER2 is frequently overexpressed in various malignancies, targeting HER2 is considered an efficient, highly selective antitumor therapy. HER2-targeted immunoconjugates are being developed and result in persistent remission of HER2-overexpressing tumors. However, many of the antibodies used as the targeting moiety are of murine origin and exhibit risk of inducing immunogenicity, limiting their antitumor therapeutic efficacy. Here, we humanized e23sFv, an HER2-targeting murine scFv with excellent affinity and specificity, using a human antibody consensus sequence engraftment strategy...
June 14, 2018: Biomaterials
Anna M Trier, Brian S Kim
Atopic dermatitis (AD) is an inflammatory skin disease characterized by two primary features: relapsing skin lesions and chronic itch. Major advances in our understanding of type 2 immunity have led to new insights into the critical factors that promote the development and persistence of AD-associated skin inflammation. Although inflammation is strongly associated with the development of atopic itch, the precise mechanisms by which itch arises in AD are poorly understood. In this review, we highlight recent studies that have started to unveil how various proinflammatory factors released within the skin can elicit sensations of itch and discuss the therapeutic potential of targeting these neuroimmunologic processes...
June 20, 2018: Current Opinion in Immunology
Charline Ogier, Pierre-Emmanuel Colombo, Corinne Bousquet, Lucile Canterel-Thouennon, Pierre Sicard, Véronique Garambois, Gaëlle Thomas, Nadège Gaborit, Marta Jarlier, Nelly Pirot, Martine Pugnière, Nadia Vie, Céline Gongora, Pierre Martineau, Bruno Robert, André Pèlegrin, Thierry Chardès, Christel Larbouret
Neuregulin 1 (NRG1), a ligand for HER3 and HER4 receptors, is secreted by both pancreatic tumor cells (PC) and cancer-associated fibroblasts (CAFs), the latter representing the most abundant compound of pancreatic stroma. This desmoplastic stroma contributes to Pancreatic Ductal Adenocarcinoma (PDAC) aggressiveness and therapeutic failure by promoting tumor progression, invasion and resistance to chemotherapies. In the present work, we aimed at disrupting the complex crosstalk between PC and CAF in order to prevent tumor cell proliferation...
June 20, 2018: Cancer Letters
Xu Jianping, Wei Kunhua, Zhang Guojun, Lei Lujing, Yang Dawei, Wang Wenle, Han Qiheng, Xia Yuan, Bi Yaqiong, Yang Min, Li Minhui
ETHNOPHARMACOLOGICAL RELEVANCE: The genus Salvia is one of the largest genera of the Lamiaceae family. In China, about 40 Salvia species have been used as medicinal plants for treatment of various diseases, specifically hepatic and renal diseases and those of the cardiovascular and immune systems. AIM OF THIS REVIEW: This review aims to provide systematically organized information on the ethnopharmacology, phytochemistry, pharmacology, and toxicology of medicinal Salvia species in China to support their therapeutic potential in the treatment of human diseases...
June 20, 2018: Journal of Ethnopharmacology
Reema Banarjee, Akshay Sharma, Shakuntala Bai, Arati Deshmukh, Mahesh Kulkarni
Endothelial dysfunction is one of the primary steps in the development of diabetes associated cardiovascular diseases. Hyperglycemic condition in diabetes promotes accumulation of advanced glycation end products (AGEs) in the plasma, that interact with the receptor for AGEs (RAGE) present on the endothelial cells and negatively affect their function. Using Human umbilical vascular endothelial cells (HUVECs) in culture, the effect of glycated human serum albumin on global proteomic changes was studied by SWATH-MS, a label free quantitative proteomic approach...
June 20, 2018: Journal of Proteomics
Xu Qian, Xiaobo Nie, Wenhao Yao, Konrad Klinghammer, Holger Sudhoff, Andreas M Kaufmann, Andreas E Albers
One of the greatest challenges in systemic treatment of head and neck squamous cell carcinoma (HNSCC) is a small tumor cell population, namely, cancer stem-like cells (CSC). CSC can regenerate and maintain a heterogenic tumor by their self-renewal capacity. Their potential ability to be more resistant to and survival after chemo- and radiation therapy was also identified. Further studies have shown that reactive oxygen species (ROS) contribute to this CSC-associated resistance. In this review, we focus on the current knowledge of HNSCC-CSC, with regard to ROS as a possible and novel therapeutic approach in targeting CSC...
June 20, 2018: Seminars in Cancer Biology
Rindert Missiaen, Massimiliano Mazzone, Gabriele Bergers
Tumor angiogenesis and escape of immunosurveillance are two cancer hallmarks that are tightly linked and reciprocally regulated by paracrine signaling cues of cell constituents from both compartments. Formation and remodeling of new blood vessels in tumors is abnormal and facilitates immune evasion. In turn, immune cells in the tumor, specifically in context with an acidic and hypoxic environment, can promote neovascularization. Immunotherapy has emerged as a major therapeutic modality in cancer but is often hampered by the low influx of activated cytotoxic T-cells...
June 20, 2018: Seminars in Cancer Biology
Hiroyuki Mizoguchi, Tian Wang, Mizuki Kusaba, Kazuya Fukumoto, Kiyofumi Yamada
Patients suffering from neuropsychiatric disorders such as substance use and addiction disorders show impaired decision-making, which may be associated with their psychiatric disorders. Previously, using a gambling test for rodents, we demonstrated that methamphetamine-dependent rats showed alterations in their decision-making strategy. In this study, we investigated the effect of nicotine on impaired decision-making strategy in rats which have been treated repeatedly with methamphetamine. Nicotine has previously been shown to have therapeutic effects on attentional and cognitive abnormalities in psychosis...
June 20, 2018: Behavioural Brain Research
Min Li, Yuetao Wen, Rongrong Zhang, Fei Xie, Gang Zhang, Xinyue Qin
BACKGROUND: Repulsive guidance molecule A (RGMa) is implicated in focal cerebral ischemia-reperfusion (I/R) injury, but its mechanisms are still largely unknown. This work focused on the effects of RGMa on the blood-brain barrier (BBB) after focal cerebral I/R injury. METHODS: Sprague-Dawley (SD) rats were randomly divided into four groups: sham, middle cerebral artery occlusion (MCAO)/reperfusion (I/R), MCAO/reperfusion administered recombinant adenovirus expressing sh-con (I/R + sh-con) and MCAO/reperfusion administered recombinant adenovirus expressing sh-RGMa (I/R + sh-RGMa) groups...
June 20, 2018: Brain Research Bulletin
Andrea Giacomini, Fiorenza Stagni, Marco Emili, Sandra Guidi, Maria Elisa Salvalai, Mariagrazia Grilli, Veronica Vidal-Sanchez, Carmen Martinez-Cué, Renata Bartesaghi
Individuals with Down syndrome (DS), a genetic condition due to triplication of Chromosome 21, are characterized by intellectual disability that worsens with age. Since impairment of neurogenesis and dendritic maturation are very likely key determinants of intellectual disability in DS, interventions targeted to these defects may translate into a behavioral benefit. While most of the neurogenesis enhancers tested so far in DS mouse models may pose some caveats due to possible side effects, substances naturally present in the human diet may be regarded as therapeutic tools with a high translational impact...
June 20, 2018: Brain Research Bulletin
Theodore A Slotkin, Ashley Ko, Frederic J Seidler
Glucocorticoids are given in preterm labor to prevent respiratory distress but these agents evoke neurobehavioral deficits in association with reduced brain region volumes. To determine whether the neurodevelopmental effects are distinct from growth impairment, we gave developing rats dexamethasone at doses below or within the therapeutic range (0.05, 0.2 or 0.8 mg/kg) at different stages: gestational days (GD) 17-19, postnatal days (PN) 1-3 or PN7-9. In adolescence and adulthood, we assessed the impact on noradrenergic systems in multiple brain regions, comparing the effects to those on somatic growth or on brain region growth...
June 20, 2018: Toxicology
Yingbin Huang, Guangyu Chen, Yang Wang, Rui He, Jun Du, Xingyuan Jiao, Qiang Tai
Hepatocellular carcinoma (HCC) is a common malignant tumor usually resistant to chemotherapy. MicroRNAs play important roles in modulation of carcinogenesis and chemoresistance, which miR-16 has been reported to mediate chemoresistance in many types of cancers. However, the role of miR-16 in HCC remains unknown. The aim of this study was to investigate whether miR-16 is participated in chemoresistance in HCC and shed light on the underlying molecular mechanisms. The findings of the current study discover that miR-16 is down-regulated in HCC tissue and cell lines...
June 20, 2018: Biochemical and Biophysical Research Communications
Shashank Shekhar, Mark W Cunningham, Mallikarjuna R Pabbidi, Shaoxun Wang, George W Booz, Fan Fan
Ischemic stroke is a devastating and debilitating medical condition with limited therapeutic options. However, accumulating evidence indicates a central role of inflammation in all aspects of stroke including its initiation, the progression of injury, and recovery or wound healing. A central target of inflammation is disruption of the blood brain barrier or neurovascular unit. Here we discuss recent developments in identifying potential molecular targets and immunomodulatory approaches to preserve or protect barrier function and limit infarct damage and functional impairment...
June 20, 2018: European Journal of Pharmacology
Yuichi Hattori, Kohshi Hattori, Tokiko Suzuki, Sailesh Palikhe, Naoyuki Matsuda
Despite advances in overall medical care, sepsis and its sequelae continue to be an embarrassing clinical entity with an unacceptably high mortality rate. The central reason for high morbidity and high mortality of sepsis and its sequelae is the lack of an effective treatment. Previous clinical trials have largely failed to identify an effective therapeutic target to improve clinical outcomes in sepsis. Thus, the key goal favoring the outcome of septic patients is to devise innovative and evolutionary therapeutic strategies...
June 20, 2018: European Journal of Pharmacology
János G Filep, Meriem Shekeri, Driss El Kebir
The formyl peptide receptors (FPRs) are G protein coupled receptors that recognize a broad range of structurally distinct pathogen and danger-associated molecular patterns and mediate host defense to infection and tissue injury. It became evident that the cellular distribution and biological functions of FPRs extend beyond myeloid cells and governing their activation and trafficking. In recent years, significant progress has been made to position FPRs at check points that control the resolution of inflammation, tissue repair and return to homeostasis...
June 20, 2018: European Journal of Pharmacology
Aleksandar Jovanović
A few decades ago, cardiac muscle was discovered to possess signalling pathways that, when activated, protect the myocardium against the damage induced by ischaemia-reperfusion. The ability of cardiac muscle to protect itself against injury has been termed 'cardioprotection'. Many compounds and procedures can trigger cardioprotection including conditionings (exposure to brief episodes of ischaemia-reperfusion to protect against sustained ischaemia-reperfusion), hypoxia, adenosine, acetylcholine, adrenomedullin, angiotensin, bradykinin, catecholamines, endothelin, estrogens, phenylephrine, opioids, testosterone, and many more...
June 20, 2018: European Journal of Pharmacology
Mark G Swain, David E J Jones
The management of fatigue associated with chronic liver disease is a complex and major clinical challenge. Although fatigue can complicate many chronic diseases, it is particularly common in diseases with an inflammatory component. Fatigue can have both peripheral (i.e., neuromuscular) and central (i.e., resulting from changes in neurotransmission within the brain) causes. However, fatigue in chronic liver disease has strong social/contextual components and is often associated with behavioural alterations including depression and anxiety...
June 23, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Marwa Daghsni, Mohamad Rima, Ziad Fajloun, Michel Ronjat, Juan L Brusés, Ridha M'rad, Michel De Waard
BACKGROUND: Autism spectrum disorder (ASD) comprises a group of neurodevelopmental psychiatric disorders characterized by deficits in social interactions, interpersonal communication, repetitive and stereotyped behaviors and may be associated with intellectual disabilities. The description of ASD as a synaptopathology highlights the importance of the synapse and the implication of ion channels in the etiology of these disorders. METHODS: A narrative and critical review of the relevant papers from 1982 to 2017 known by the authors was conducted...
June 22, 2018: Brain and Behavior
Mehak Zahoor Khan, Prabhjot Kaur, Vinay Kumar Nandicoori
The emergence of increasingly drug-resistant Mycobacterium tuberculosis strains has become a crucial public health concern. In order to effectively treat tuberculosis, it is imperative to find newer drug targets, which are important for the in vivo bacterial survival and persistence. Phosphorylation based signaling cascades modulated by eukaryotic-like serine/threonine protein kinases and phosphatase in M. tuberculosis, transduce extracellular stimuli to a cellular response ensuing pathogen's growth, persistence and pathogenesis...
June 22, 2018: IUBMB Life
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