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Molecular Medicine

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https://www.readbyqxmd.com/read/28960227/tolerogenic-dendritic-cells-induced-by-bd750-ameliorate-proinflammatory-t-cell-responses-and-experimental-autoimmune-encephalitis-in-mice
#1
Yan Zhou, Xiao Leng, Hua Li, Shuxia Yang, Tai Yang, Limei Li, Ying Xiong, Qiang Zou, Yang Liu, Yantang Wang
BD750, a novel JAK3/STAT5 inhibitor, can inhibit T cell proliferation. This study aims to evaluate whether BD750 can induce tolerogenic dendritic cells (tolDC) and their function in experimental autoimmune encephalitis (EAE) in mice. Following BD750 treatment, LPS-induced maturation of DC, allogeneic T cell proliferation, Th1 and Th17 cell functional differentiation, the STAT5 and AKT activation were determined. The effect of tolDC loaded with antigen peptide on the development and severity of EAE and their splenic Th1 and Th17 cell responses were determined...
September 27, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28861588/efficient-genome-wide-association-in-biobanks-using-topic-modeling-identifies-multiple-novel-disease-loci
#2
Thomas H McCoy, Victor M Castro, Leslie A Snapper, Kamber L Hart, Roy H Perlis
Biobanks and national registries represent a powerful tool for genomic discovery, but rely on diagnostic codes that may be unreliable and fail to capture the relationship between related diagnoses. We developed an efficient means of conducting genome-wide association studies using combinations of diagnostic codes from electronic health records (EHR) for 10845 participants in a biobanking program at two large academic medical centers. Specifically, we applied latent Dirichilet allocation to fit 50 disease topics based on diagnostic codes, then conducted genome-wide common-variant association for each topic...
August 31, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28853490/interleukin-26-production-in-human-primary-bronchial-epithelial-cells-in-response-to-viral-stimulation-modulation-by-th17-cytokines
#3
Karlhans Fru Che, Riitta Kaarteenaho, Elisa Lappi-Blanco, Bettina Levänen, Jitong Sun, Åsa Wheelock, Lena Palmberg, C Magnus Sköld, Anders Lindén
Interleukin (IL)-26 is abundant in human airways and this cytokine is involved in the local immune response to a bacterial stimulus in vivo. Specifically, local exposure to the toll-like receptor (TLR) 4 agonist endotoxin does increase IL-26 in human airways and this cytokine potentiates chemotactic responses in human neutrophils. In addition to T-helper (Th) 17 cells, alveolar macrophages can produce IL-26, but it remains unknown whether this cytokine can also be produced in the airway mucosa per se in response to a viral stimulus...
August 29, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28850155/adipose-tissue-and-serum-ccdc80-in-obesity-and-its-association-with-related-metabolic-disease
#4
O Osorio-Conles, M Guitart, J M Moreno-Navarrete, X Escoté, X Duran, J M Fernandez-Real, A M Gomez-Foix, S Fernández-Veledo, J Vendrell
Coiled-coil domain-containing 80 (CCDC80) is an adipocyte-secreted protein that modulates glucose homeostasis in response to diet-induced obesity in mice. The objective of this study is to analyze the link between human CCDC80 and obesity. CCDC80 protein expression was assessed in paired visceral (VAT) and subcutaneous (SAT) adipose tissue from 10 subjects (BMI range 22.4-38.8 kg/m(2)). Circulating CCDC80 levels were quantified in serum samples from two independent cross-sectional cohorts comprising 33 lean and 15 obese (cohort 1) and 32 morbid obese (cohort 2) male subjects...
August 23, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28805233/analytic-and-dynamic-secretory-profile-of-patient-derived-cytokine-induced-killer-cells
#5
Giulia Mesiano, Roberta Zini, Giulia Montagner, Nicoletta Bianchi, Rossella Manfredini, Antonella Chillemi, Massimo Aglietta, Giovanni Grignani, Ilaria Lampronti, Erika Fiorino, Fabio Malavasi, Dario Sangiolo, Roberto Gambari, Davide Ferrari
Adoptive immunotherapy with Cytokine Induced Killer (CIK) cells has shown antitumor activity against several kinds of cancers in preclinical models and clinical trials. CIK cells are a subset of ex vivo expanded T lymphocytes with T-NK phenotype and MHC-unrestricted antitumor activity. Literature provides scanty information on cytokines, chemokines and growth factors secreted by CIK cells. Therefore, we investigated the secretory profile of CIK cells generated from tumor patients. The secretome analysis was performed at specific time points (day 1, day 14 and day 21) of CIK cells expansion...
August 9, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28805232/the-protective-effect-of-heme-oxygenase-1-against-intestinal-barrier-dysfunction-in-cholestatic-liver-injury-is-associated-with-nf-%C3%AE%C2%BAb-inhibition
#6
Lijing Zhang, Zhenling Zhang, Bojia Liu, Yanling Jin, Yan Tian, Yi Xin, Zhijun Duan
Heme oxygenase-1 (HO-1) is reported to protect against liver injury, but little is known about its effect on the intestinal barrier in cholestatic liver injury. In this study, we investigated the effects of HO-1 and its enzymatic by-product on intestinal barrier dysfunction in bile duct ligation (BDL) rats and explored the possible mechanism. The HO-1 inducer cobalt protoporphyrin (CoPP) and carbon monoxide-releasing molecule-2 (CORM-2) were used; the expression levels of tight junction (TJ) proteins, intestinal inflammation and NF-κB p65 were measured...
August 9, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28805231/the-histone-methyltransferase-mixed-lineage-leukemia-mll-3-may-play-a-potential-role-on-clinical-dilated-cardiomyopathy
#7
Ding-Sheng Jiang, Xin Yi, Rui Li, Yun-Shu Su, Jing Wang, Min-Lai Chen, Li-Gang Liu, Min Hu, Cai Cheng, Ping Zheng, Xue-Hai Zhu, Xiang Wei
Histone modifications play a critical role in the pathological processes of dilated cardiomyopathy (DCM). While the role and expression pattern of histone methyltransferases (HMTs), especially mixed lineage leukemia (MLL) families on DCM are unclear. To this end, twelve normal and fifteen DCM heart samples were included in the present study. A murine cardiac remodelling model was induced by transverse aortic constriction (TAC). Real-time PCR was performed to detect the expression levels of MLL families in the mouse and human left ventricles...
August 9, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28741645/inflammasome-and-autophagy-regulation-a-two-way-street
#8
Qian Sun, Jie Fan, Timothy R Billiar, Melanie J Scott
Inflammation plays a significant role in protecting hosts against pathogens. Inflammation induced by non-infectious, endogenous agents can be detrimental, and if excessive can result in organ and tissue damage. The inflammasome is a major innate immune pathway that can be activated via both exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs). Inflammasome activation involves formation and oligomerization of a protein complex including a NOD-like receptor (NLR), an adaptor protein (ASC) and procaspase-1...
July 24, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28681901/dense-genotyping-of-immune-related-regions-identifies-loci-for-rheumatoid-arthritis-risk-and-damage-in-african-americans
#9
Maria I Danila, Vincent Albert Laufer, Richard J Reynolds, Qi Yan, Nianjun Liu, Peter K Gregersen, Annette Lee, Marlena Kern, Carl D Langefeld, Donna K Arnett, S Louis Bridges
Over 100 risk loci for rheumatoid arthritis (RA) have been identified in individuals of European and Asian descent, but the genetic basis for RA in African Americans is less well understood. We genotyped 610 African Americans with autoantibody positive RA and 933 African American controls on the ImmunoChip (iChip) array. Using multivariable regression we evaluated the association between iChip markers and the risk of RA and radiographic severity. The single nucleotide polymorphism (SNP) rs1964995 (OR = 1.97, p = 1...
June 29, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28620671/an-oligodeoxynucleotide-with-aaag-repeats-significantly-attenuates-burn-induced-systemic-inflammatory-responses-via-inhibiting-interferon-regulatory-factor-5-pathway
#10
Yue Xiao, Wenting Lu, Xin Li, Peiyan Zhao, Yun Yao, Xiaohong Wang, Ying Wang, Zhipeng Lin, Yongli Yu, Shucheng Hua, Liying Wang
Previously, we showed that an oligodeoxynucleotide with AAAG repeats (AAAG ODN) rescued mice from fatal acute lung injury (ALI) induced by influenza virus and inhibited production of tumor necrosis factor-α (TNF-α) in the injured lungs. However, the underlying mechanisms remain to be elucidated. Upon the bioinformatic analysis revealing that the AAAG ODN is consensus to interferon regulatory factor 5 (IRF5) binding site in the cis-regulatory elements of proinflammatory cytokines, we tried to explore whether the AAAG ODN could attenuate burn injury induced systemic inflammatory responses via inhibiting IRF5 pathway...
June 14, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28598489/nicotinic-acetylcholine-receptor-mediated-protection-of-the-rat-heart-exposed-to-ischemia-reperfusion
#11
Spyros A Mavropoulos, Nayaab S Khan, Asaph C J Levy, Bradley T Faliks, Cristina P Sison, Valentin A Pavlov, Youhua Zhang, Kaie Ojamaa
Reperfusion injury following acute myocardial infarction is associated with significant morbidity. Activation of neuronal or non-neuronal cholinergic pathways in the heart has been shown to reduce ischemic injury and this effect has been attributed primarily to muscarinic acetylcholine receptors. In contrast, the role of nicotinic receptors, specifically alpha-7 subtype (α7nAChR) in the myocardium remains unknown which offers an opportunity to potentially repurpose several agonists/modulators that are currently under development for neurologic indications...
June 8, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28598490/development-of-a-zebrafish-sepsis-model-for-high-throughput-drug-discovery
#12
Anju Mary Philip, Youdong Wang, Antonio Mauro, Suzan El-Rass, John C Marshall, Warren L Lee, Arthur S Slutsky, Claudia C dosSantos, Xiao-Yan Wen
Sepsis is a leading cause of death worldwide. Current treatment modalities remain largely supportive. Intervention strategies focused on inhibiting specific mediators of the inflammatory host response have been largely unsuccessful, a consequence of an inadequate understanding of the complexity and heterogeneity of the innate immune response. Moreover, the conventional drug development pipeline is time consuming and expensive and the low success rates associated with cell-based screens underline the need for whole organism screening strategies, especially for complex pathological processes...
June 7, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28598488/myosin-light-chain-kinase-knockout-improves-gut-barrier-function-and-confers-a-survival-advantage-in-polymicrobial-sepsis
#13
C Adam Lorentz, Zhe Liang, Mei Meng, Ching-Wen Chen, Benyam P Yoseph, Elise R Breed, Rohit Mittal, Nathan J Klingensmith, Alton B Farris, Eileen M Burd, Michael Koval, Mandy L Ford, Craig M Coopersmith
Sepsis-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the peri-junctional actin-myosin ring. Myosin light chain kinase (MLCK) phosphorylates the myosin regulatory light chain, resulting in increased permeability. The purpose of this study was to determine whether genetic deletion of MLCK would alter gut barrier function and survival from sepsis. MLCK(-/-) and wild type (WT) mice were subjected to cecal ligation and puncture and assayed for both survival and mechanistic studies...
June 7, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28695223/a-journey-in-science-cell-cycle-control
#14
Paul Nurse
Real innovations in medicine and science are historic and singular; the stories behind each occurrence are precious. At Molecular Medicine we have established the Anthony Cerami Award in Translational Medicine to document and preserve these histories. The monographs recount the seminal events as told in the voice of the original investigators who provided the crucial early insight. These essays capture the essence of discovery, chronicling the birth of ideas that created new fields of research; and launched trajectories that persisted and ultimately influenced how disease is prevented, diagnosed, and treated...
May 24, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28474731/a-new-gene-expression-signature-for-triple-negative-breast-cancer-using-frozen-fresh-tissue-before-neoadjuvant-chemotherapy
#15
Sandra Karina Santuario-Facio, Servando Cardona-Huerta, Yadira Xitlalli Perez-Paramo, Victor Trevino, Francisco Hernandez-Cabrera, Augusto Rojas-Martinez, Grecia Uscanga-Perales, Jorge Luis Martinez-Rodriguez, Lizeth Martinez-Jacobo, Gerardo Padilla-Rivas, Gerardo Muñoz-Maldonado, Juan Francisco Gonzalez-Guerrero, Javier Valero-Gomez, Ana Lorena Vazquez-Guerrero, Herminia Guadalupe Martinez-Rodriguez, Alvaro Barboza-Quintana, Oralia Barboza-Quintana, Raquel Garza-Guajardo, Rocio Ortiz-Lopez
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer tumors. Comparisons between TNBC and non-triple negative breast cancer (nTNBC) may help to differentiate key components involved in TNBC neoplasms. The purpose of the study was to analyze the expression profile of TNBC versus nTNBC tumors in a homogeneous population from northeastern Mexico. A prospective study of 50 patients was conducted (25 TNBC and 25 nTNBC). Clinic parameters were equally distributed for TNBC and nTNBC: age at diagnosis (51 vs 47 years, p=0...
May 4, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28467518/mutation-spectrum-of-star-and-a-founder-effect-of-the-p-q258-in-korean-patients-with-congenital-lipoid-adrenal-hyperplasia
#16
Eungu Kang, Yoon-Myung Kim, Gu-Hwan Kim, Beom Hee Lee, Han-Wook Yoo, Jin-Ho Choi
Congenital lipoid adrenal hyperplasia (CLAH) is the most severe form of congenital adrenal hyperplasia, caused by defects in the steroidogenic acute regulatory protein (STAR). The STAR p.Q258* mutation is the most common mutation in China, Japan, and Korea, suggesting a founder effect. This study aimed to investigate the phenotypic and mutation spectrum of STAR defects and identify a founder effect of the p.Q258* mutation in Korean patients with CLAH. For 45 patients from 42 independent pedigrees, haplotype analysis was performed in 10 unrelated trio families, including patients with the p...
May 2, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28386621/repurposing-mebendazole-as-a-replacement-for-vincristine-for-the-treatment-of-brain-tumors
#17
Michelle De Witt, Alexander Gamble, Derek Hanson, Daniel Markowitz, Caitlin Powell, Saleh Al Dimassi, Mark Atlas, John Boockvar, Rosamaria Ruggieri, Marc Symons
The microtubule inhibitor vincristine is currently used to treat a variety of brain tumors, including low-grade glioma and anaplastic oligodendroglioma. Vincristine, however, does not penetrate well into brain tumor tissue, and moreover, it displays dose-limiting toxicities, including peripheral neuropathy. Mebendazole, a Food and Drug Administration-approved anthelmintic drug with a favorable safety profile, has recently been shown to display strong therapeutic efficacy in animal models of both glioma and medulloblastoma...
April 5, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28362018/il-37-suppresses-myd88-mediated-inflammatory-responses-in-human-aortic-valve-interstitial-cells
#18
Qiong Zhan, Qingchun Zeng, Rui Song, Yufeng Zhai, Dingli Xu, David A Fullerton, Charles A Dinarello, Xianzhong Meng
BACKGROUND: Calcific aortic valve disease (CAVD) is common among the elderly, and aortic valve interstitial cells (AVICs) exhibit unique inflammatory and osteogenic responses to pro-inflammatory stimulation which play an important role in valvular fibrosis and calcification. Thus, suppression of AVIC pro-inflammatory response may have therapeutic utility for prevention of CAVD progression. Interleukin (IL)-37, an anti-inflammatory cytokine, reduces tissue inflammation. OBJECTIVE: This study was to test the hypothesis that IL-37 suppresses human AVIC inflammatory responses to Toll-like receptor (TLR) agonists...
March 27, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28332698/induction-of-steatohepatitis-nash-with-insulin-resistance-in-wildtype-b6-mice-by-a-western-type-diet-containing-soybean-oil-and-cholesterol
#19
Janin Henkel, Charles Dominic Coleman, Anne Schraplau, Korinna Jӧhrens, Daniela Weber, José Pedro Castro, Martin Hugo, Tim Julius Schulz, Stephanie Krämer, Annette Schürmann, Gerhard Paul Püschel
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are hepatic manifestations of the metabolic syndrome. Many currently used animal models of NAFLD/NASH lack clinical features of either NASH or metabolic syndrome such as hepatic inflammation and fibrosis (e.g. high-fat diets) or overweight and insulin resistance (e.g. methionine-choline-deficient diets) or they are based on monogenetic defects (e.g. ob/ob mice). In the current study, a western-type diet containing soybean oil with high n 6-PUFA and 0...
March 21, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28332697/alpha-1-antitrypsin-inhibits-rankl-induced-osteoclast-formation-and-functions
#20
Mohammad Ahsanul Akbar, David Nardo, Mong-Jen Chen, Ahmed S Elshikha, Rubina Ahamed, Eslam M Elsayed, Claire Bigot, Lexie Shannon Holliday, Sihong Song
Osteoporosis is a global public health problem affecting more than 200 million people worldwide. We previously showed that treatment with alpha-1 antitrypsin (AAT), a multifunctional protein with anti-inflammatory properties, mitigated bone loss in an ovariectomized mouse model. However, the underlying mechanisms of the protective effect of AAT on bone tissue are largely unknown. In this study, we investigated the effect of AAT on osteoclast formation and function in vitro. Our results showed that AAT dose-dependently inhibited the formation of RANKL (receptor activator of nuclear factor κB ligand) induced osteoclasts derived from mouse bone marrow macrophages/monocyte (BMM) lineage cells and the murine macrophage cell line, RAW 264...
March 21, 2017: Molecular Medicine
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