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Molecular Medicine

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https://www.readbyqxmd.com/read/28079229/the-transcription-factor-xbp1-in-memory-and-cognition-implications-in-alzheimer-disease
#1
Moustapha Cissé, Eric Duplan, Frédéric Checler
X-box binding protein 1 (XBP1) is a unique basic region leucine zipper transcription factor isolated two decades ago in a search for regulators of major histocompatibility complex class II gene expression. XBP1 is a very complex protein regulating many physiological functions, including immune system, inflammatory responses, and lipid metabolism. Evidence over the past few years suggests that XBP1 also plays important roles in pathological settings since its activity as transcription factor has profound effects on the prognosis and progression of diseases such as cancer, neurodegeneration, and diabetes...
January 4, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/27999842/reduced-skin-blistering-in-experimental-epidermolysis-bullosa-acquisita-after-anti-tnf-treatment
#2
Misa Hirose, Anika Kasprick, Foteini Beltsiou, Katharina Schulze Dieckhoff, Franziska Sophine Schulze, Unni Kjsrl Samavedam, Jennifer E Hundt, Hendri H Pas, Marcel F Jonkman, Enno Schmidt, Kathrin Kalies, Detlef Zillikens, Ralf J Ludwig, Katja Bieber
Epidermolysis bullosa acquisita (EBA) is a difficult-to-treat subepidermal autoimmune blistering skin disease (AIBD) with circulating and tissue-bound anti-type VII collagen antibodies. Different reports have indicated an increased concentration of tumor necrosis factor alpha (TNF) in the serum and blister fluid of patients with subepidermal AIBDs. Furthermore, successful anti-TNF treatment has been reported for individual patients with AIBDs. Here, we show that in mice, induction of experimental EBA by repeated injections of rabbit-anti mouse type VII collagen antibodies led to increased expression of TNF in skin, as determined by real-time PCR and immunohistochemistry...
December 20, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/28079228/attenuated-recovery-of-contractile-function-in-aging-hearts-following-global-ischemia-reperfusion-role-of-extracellular-hsp27-and-tlr4
#3
Lihua Ao, Yufeng Zhai, Chunhua Jin, Joseph C Cleveland, David A Fullerton, Xianzhong Meng
BACKGROUND: While cardiac functional recovery is attenuated in the elderly following cardiac surgery with obligatory global myocardial ischemia/reperfusion (I/R), the underlying mechanism remains incompletely understood. We observed previously that human and mouse myocardium releases heat shock protein (HSP) 27 during global I/R. Extracellular HSP27 induces myocardial inflammatory response and plays a role in post-ischemic cardiac dysfunction in adult mouse hearts. OBJECTIVE: This study was to determine the role of extracellular HSP27 and Toll-like receptor 4 (TLR4) in the attenuated functional recovery in aging mouse hearts following global I/R...
December 19, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27925633/shock-wave-enhances-angiogenesis-through-vegfr2-activation-and-recycling
#4
Tien-Hung Huang, Cheuk-Kwan Sun, Yi-Ling Chen, Ching-Jen Wang, Tsung-Cheng Yin, Mel S Lee, Hon-Kan Yip
Although low-energy shock wave (SW) is adopted to treat ischemic diseases because of its pro-angiogenic properties, the underlying mechanism remains unclear. This study aimed at testing whether SW-induced angiogenesis may be through endothelial vascular endothelial growth factor receptor 2 (VEGFR2) signaling and trafficking. Phosphorylation of VEGFR2-Akt-eNOS axis and production of nitric oxide (NO) were determined in human umbilical vein endothelial cells (HUVECs) treated with SW. Carotid artery in ob/ob mice was treated with SW before evaluation with sprouting assay...
December 6, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27925632/sepsis-induces-telomere-shortening-a-potential-mechanism-responsible-for-delayed-pathophysiological-events-in-sepsis-survivors
#5
Naara Mendes Oliveira, Ester C S Rios, Thais Martins de Lima, Vanessa Jacob Victorino, Hermes Barbeiro, Fabiano Pinheiro da Silva, Csaba Szabo, Francisco Garcia Soriano
Sepsis survivors suffer from additional morbidities, including higher disk of readmissions, nervous system disturbances and cognitive dysfunction, and increased mortality, even several years after the initial episode of sepsis. In many ways, the phenotype of sepsis survivors resembles the phenotype associated with accelerated aging. Since telomere shortening is a hallmark of aging, we investigated whether sepsis also leads to telomere shortening. Male balb/c mice were divided into two groups: the control group received 100 μl of normal saline intraperitoneally; the sepsis group received 15 mg/kg of bacterial lipopolysaccharide i...
December 5, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27900387/a-modification-specific-peptide-based-immunization-approach-using-crm197-carrier-protein-development-of-a-selective-vaccine-against-pyroglutamate-a%C3%AE-peptides
#6
Valérie Vingtdeux, Haitian Zhao, Pallavi Chandakkar, Christopher M Acker, Peter Davies, Philippe Marambaud
Strategies aimed at reducing cerebral accumulation of the amyloid-β (Aβ) peptides have therapeutic potential in Alzheimer's disease (AD). Aβ immunization has proven to be effective at promoting Aβ clearance in animal models but adverse effects have hampered its clinical evaluation. The first anti-Aβ immunization clinical trial, which assessed a full-length Aβ1-42 vaccine, increased the risk of encephalitis most likely because of autoimmune pro-inflammatory T helper 1 (Th1) response against all forms of Aβ...
November 28, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27900389/the-clearance-of-cell-remnants-and-the-regeneration-of-the-injured-muscle-depend-on-soluble-pattern-recognition-receptor-ptx3
#7
Michela Vezzoli, Clara Sciorati, Lara Campana, Antonella Monno, Maria Giulia Doglio, Elena Rigamonti, Gianfranca Corna, Thierry Touvier, Alessandra Castiglioni, Annalisa Capobianco, Alberto Mantovani, Angelo A Manfredi, Cecilia Garlanda, Patrizia Rovere-Querini
OBJECTIVE: The signals causing the resolution of muscle inflammation are only partially characterized. The long pentraxin PTX3, which modulates leukocyte recruitment and activation, could contribute. METHODS: We analysed the expression of ptx3 after muscle injury and verified whether hematopoietic precursors are a source of the protein. The kinetics of regeneration and leukocytes infiltration, the accumulation of cell remnants and anti-histidyl-t-RNA synthetase autoantibodies were compared in wild-type and ptx3-deficient mice...
November 23, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27900388/data-driven-modeling-for-precision-medicine-in-pediatric-acute-liver-failure
#8
Ruben Zamora, Yoram Vodovotz, Qi Mi, Derek Barclay, Jinling Yin, Simon Horslen, David Rudnick, Kathleen M Loomes, Robert H Squires
Absence of early outcome biomarkers for Pediatric Acute Liver Failure (PALF) hinders medical and liver transplant decisions. We sought to define dynamic interactions among circulating inflammatory mediators to gain insights into PALF outcome sub-groups. Serum samples from 101 participants in the PALF study, collected over the first 7 days following enrollment, were assayed for 27 inflammatory mediators. Outcomes (Spontaneous survivors [S, n=61], Non-survivors [NS, n=12], and liver transplant patients [LTx, n=28]) were assessed at 21 days post-enrollment...
November 23, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27878210/t-regulatory-cell-mediated-immunotherapy-for-solid-organ-transplantation-a-clinical-perspective
#9
Mohammad Afzal Khan
T regulatory cells (Tregs) play a vital role in suppressing heightened immune responses, and thereby promote a state of immunological tolerance. Tregs modulate both innate and adaptive immunity, which make them a potential candidate for cell-based immunotherapy to suppress uncontrolled activation of graft specific inflammatory cells and their toxic mediators. These grafts specific inflammatory cells (T effector cells) and other inflammatory mediators (Immunoglobulins, active complement mediators) are mainly responsible for graft vascular deterioration followed by acute/chronic rejection...
November 22, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27878211/liraglutide-enhances-the-efficacy-of-human-mesenchymal-stem-cells-in-preserving-islet-%C3%AE-cell-function-in-severe-non-obese-diabetic-mice
#10
Li-Rong Li, Xiao-Lei Jia, Hui Hui, Jie Zhang, Ying Liu, Wei-Juan Cui, Qian-Yue Xu, Da-Long Zhu
Glucagon-like peptide 1 (GLP-1) can promote islet β-cell replication and function, and mesenchymal stem cells (MSCs) can inhibit T cell autoimmunity. This study aimed at testing the dynamic distribution of infused human MSCs and therapeutic effect of combined MSCs and Liraglutide, a long-acting GLP-1 analogue, on preserving β-cell function in severe non-obese diabetic (NOD) mice. We found that infused MSCs accumulated in the pancreas at 4 weeks post infusion, which was not affected by Liraglutide treatment...
November 17, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27878209/preclinical-models-of-overwhelming-sepsis-implicate-the-neural-system-that-encodes-contextual-fear-memory
#11
Patricio T Huerta, Sergio Robbiati, Tomás Salvador Huerta, Anchal Sabharwal, Rose A Berlin, Maya Frankfurt, Bruce T Volpe
Long-term sepsis survivors sustain cryptic brain injury that leads to cognitive impairment, emotional imbalance, and increased disability burden. Suitable animal models of sepsis, such as cecal ligation and puncture (CLP), have permitted the analysis of abnormal brain circuits that underlie post-septic behavioral phenotypes. For instance, we have previously shown that CLP-exposed mice exhibit impaired spatial memory together with depleted dendritic arbors and decreased spines in the apical dendrites of pyramidal neurons in the CA1 region of the hippocampus...
November 17, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27878212/obesity-paradox-obesity-orthodox-and-the-metabolic-syndrome-an-approach-to-unity
#12
Jesse Roth, Navneet Sahota, Priya Patel, Syed Faizan Mehdi, Mohammad Masum Wiese, Hafiz B Mahboob, Michelle Bravo, Daniel J Eden, Muhammad A Bashir, Amrat Kumar, Farah Alsaati, Irwin J Kurland, Wunnie Brima, Ann Danoff, Alessandra L Szulc, Valentin A Pavlov, Kevin J Tracey, Huan Yang
Obesity and the accompanying metabolic syndrome are strongly associated with heightened morbidity and mortality in older adults. In our review of more than 20 epidemiologic studies of major infectious diseases, including leaders such as tuberculosis, community-acquired pneumonia, and sepsis, obesity was associated with better outcomes. A cause-and-effect relationship between over-nutrition and survival with infection is suggested by results of two preliminary studies of infections in mice, where high fat feeding for 8-10 weeks provided much better outcomes...
November 16, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27847962/the-multi-target-effects-of-cni-1493-convergence-of-anti-amylodogenic-and-anti-inflammatory-properties-in-animal-models-of-alzheimer-s-disease
#13
Roman Sankowski, Arne Herring, Kathy Keyvani, Kathrin Frenzel, Jinyu Wu, Stephan Röskam, Carmen Noelker, Michael Bacher, Yousef Al-Abed
After several decades of Alzheimer's disease (AD) research and failed clinical trials, one can speculate that targeting a single pathway is not sufficient. However, a cocktail of novel therapeutics will constitute a challenging clinical trial. A more plausible approach will capitalize on a drug that has relevant and synergistic multiple-target effects in AD. We have previously demonstrated the efficacy of CNI-1493 in the CRND8 transgenic AD mouse model. Similar to many anti-inflammatory drugs that were tested in preclinical model of AD, it was speculated that the significant effect of CNI-1493 is due to its established anti-inflammatory properties in rodents and humans...
November 15, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27819109/a-journey-in-science-not-lost-in-translation
#14
Tak Mak
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...
November 1, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27782294/a-novel-role-for-programmed-cell-death-receptor-ligand-1-pd-l1-in-sepsis-induced-intestinal-dysfunction
#15
Youping Wu, Chun-Shiang Chung, Yaping Chen, Sean Farrell Monaghan, Sima Patel, Xin Huang, Daithi Seamus Heffernan, Alfred Ayala
Studies imply that intestinal barrier dysfunction is a key contributor to morbid events associated with sepsis. Recently, co-inhibitory molecule, programmed death-ligand1 (PD-L1) has been shown to be involved in the regulation of intestinal immune tolerance and/or inflammation. Our previous studies showed that PD-L1 gene deficiency reduced sepsis-induced intestinal injury morphologically. However, it isn't known how PD-L1 expression impacts intestinal barrier dysfunction during sepsis. Here we tested the hypothesis that PD-L1 expressed on intestinal epithelial cells (IECs) has a role in sepsis-induced intestinal barrier dysfunction...
October 25, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27782292/n-n-dimethylacetamide-significantly-attenuates-lps-and-tnf%C3%AE-induced-proinflammatory-responses-via-inhibition-of-the-nuclear-factor-kappa-b-pathway
#16
Ryan Pekson, Vladimir Poltoratsky, Samir Gorasiya, Sruthi Sundaram, Charles R Ashby, Ivana Vancurova, Sandra E Reznik
Previously, we have shown that N,N-dimethylacetamide (DMA) prevents inflammation-induced preterm birth in a murine model, inhibits LPS-induced increases in placental pro-inflammatory cytokines and up-regulates the anti-inflammatory cytokine Interleukin-10 (IL-10). However, DMA's mechanism of action remains to be elucidated. In the current study we investigate how DMA produces its anti-inflammatory effect. Using in vitro and ex vivo models, we show that DMA suppresses secretion of pro-inflammatory cytokines in lipopolysaccharide (LPS)-induced RAW 264...
October 24, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/28059429/erratum
#17
(no author information available yet)
This corrects the article DOI: 10.2119/molmed.2013.00122.
October 20, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27782293/peroxisome-proliferator-activated-receptor-gamma-2-modulates-late-pregnancy-homeostatic-metabolic-adaptations
#18
Yurena Vivas, Monica Díez-Hochleitner, Adriana Izquierdo-Lahuerta, Patricia Corrales, Daniel Horrillo, Ismael Velasco, Cristina Martínez-García, Mark Campbell, Julio Sevillano, Mercedes Ricote, Manuel Ros, Maria Pilar Ramos, Gema Medina-Gomez
Pregnancy requires the adaptation of maternal energy metabolism including expansion and functional modifications of adipose tissue. Insulin resistance (IR), predominantly during late gestation, is a physiological metabolic adaptation that serves to support the metabolic demands of fetal growth. The molecular mechanisms underlying these adaptations are not fully understood and may contribute to gestational diabetes mellitus. Peroxisome proliferator-activated receptor gamma (PPARγ) controls adipogenesis, glucose and lipid metabolism and insulin sensitivity...
October 19, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27761584/adenosine-generated-in-the-bone-marrow-niche-through-a-cd38-mediated-pathway-correlates-with-progression-of-human-myeloma
#19
Alberto L Horenstein, Valeria Quarona, Denise Toscani, Federica Costa, Antonella Chillemi, Vito Pistoia, Nicola Giuliani, Fabio Malavasi
Human myeloma cells express CD38 at high levels and grow in hypoxic niches inside the bone marrow. Myeloma cells respond to hypoxia with metabolic changes leading to aerobic glycolysis, thus reducing ATP and increasing NAD(+). Our hypothesis is that these conditions favor the enzymatic pathways involved in the production of adenosine in the niche. Within the niche, NAD(+) is able to activate a discontinuous adenosinergic pathway that relies upon CD38, CD203a, and CD73 or TRACP, according to the environmental pH...
October 13, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27730250/developing-connections-amongst-b-lymphocytes-and-deregulated-pathways-in-autoimmunity
#20
Moncef Zouali, Gregory Tsay
Immunologists have long investigated B lymphocytes as solely antibody producing cells. With further studies, it became clear that B cells are able to exert a variety of functions within the immune system, and beyond. As a result, B cells are considered promising targets for immunotherapy in a variety of disorders. Recently, experts in B cell biology and autoimmunity convened to discuss important stepping stones to decipher the complexity of B lymphocyte-mediated pathways in autoimmune diseases.
October 5, 2016: Molecular Medicine
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