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https://www.readbyqxmd.com/read/27903296/factors-affecting-long-term-efficacy-of-t-regulatory-cell-based-therapy-in-type-1-diabetes
#1
Natalia Marek-Trzonkowska, Małgorzata Myśliwiec, Dorota Iwaszkiewicz-Grześ, Mateusz Gliwiński, Ilona Derkowska, Magdalena Żalińska, Maciej Zieliński, Marcelina Grabowska, Hanna Zielińska, Karolina Piekarska, Anna Jaźwińska-Curyłło, Radosław Owczuk, Agnieszka Szadkowska, Krystyna Wyka, Piotr Witkowski, Wojciech Młynarski, Przemysława Jarosz-Chobot, Artur Bossowski, Janusz Siebert, Piotr Trzonkowski
BACKGROUND: Recent studies suggest that immunotherapy using T regulatory cells (Tregs) prolongs remission in type 1 diabetes (T1DM). Here, we report factors that possibly affect the efficacy of this treatment. METHODS: The metabolic and immune background of 12 children with recently diagnosed T1DM, as well as that of untreated subjects, during a 2-year follow-up is presented. Patients were treated with up to 30 × 10(6)/kg b.w. of autologous expanded CD3(+)CD4(+)CD25(high)CD127(-) Tregs...
December 1, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27901481/human-pancreatic-cancer-xenografts-recapitulate-key-aspects-of-cancer-cachexia
#2
Daniel Delitto, Sarah M Judge, Andrea E Delitto, Rachel L Nosacka, Fernanda G Rocha, Bayli B DiVita, Michael H Gerber, Thomas J George, Kevin E Behrns, Steven J Hughes, Shannon M Wallet, Andrew R Judge, Jose G Trevino
Cancer cachexia represents a debilitating syndrome that diminishes quality of life and augments the toxicities of conventional treatments. Cancer cachexia is particularly debilitating in patients with pancreatic cancer (PC). Mechanisms responsible for cancer cachexia are under investigation and are largely derived from observations in syngeneic murine models of cancer which are limited in PC. We evaluate the effect of human PC cells on both muscle wasting and the systemic inflammatory milieu potentially contributing to PC-associated cachexia...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899899/cell-expansion-dependent-inflammatory-and-metabolic-profile-of-human-bone-marrow-mesenchymal-stem-cells
#3
Patricia Prieto, María Fernández-Velasco, María E Fernández-Santos, Pedro L Sánchez, Verónica Terrón, Paloma Martín-Sanz, Francisco Fernández-Avilés, Lisardo Boscá
Stem cell therapy has emerged as a promising new area in regenerative medicine allowing the recovery of viable tissues. Among the many sources of adult stem cells, bone marrow-derived are easy to expand in culture via plastic adherence and their multipotentiality for differentiation make them ideal for clinical applications. Interestingly, several studies have indicated that MSCs expansion in vitro may be limited mainly due to "cell aging" related to the number of cell divisions in culture. We have determined that MSCs exhibit a progressive decline across successive passages in the expression of stem cell markers, in plasticity and in the inflammatory response, presenting low immunogenicity...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27893707/blockade-of-the-il-6-trans-signalling-stat3-axis-suppresses-cachexia-in-kras-induced-lung-adenocarcinoma
#4
A Miller, L McLeod, S Alhayyani, A Szczepny, D N Watkins, W Chen, P Enriori, W Ferlin, S Ruwanpura, B J Jenkins
Lung cancer is the leading cause of cancer death worldwide, and is frequently associated with the devastating paraneoplastic syndrome of cachexia. The potent immunomodulatory cytokine interleukin (IL)-6 has been linked with the development of lung cancer as well as cachexia; however, the mechanisms by which IL-6 promotes muscle wasting in lung cancer cachexia are ill-defined. In this study, we report that the gp130(F/F) knock-in mouse model displaying hyperactivation of the latent transcription factor STAT3 via the common IL-6 cytokine family signalling receptor, gp130, develops cachexia during Kras-driven lung carcinogenesis...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27893460/tgf-%C3%AE-1-modulates-microglial-phenotype-and-promotes-recovery-after-intracerebral-hemorrhage
#5
Roslyn A Taylor, Che-Feng Chang, Brittany A Goods, Matthew D Hammond, Brian Mac Grory, Youxi Ai, Arthur F Steinschneider, Stephen C Renfroe, Michael H Askenase, Louise D McCullough, Scott E Kasner, Michael T Mullen, David A Hafler, J Christopher Love, Lauren H Sansing
Intracerebral hemorrhage (ICH) is a devastating form of stroke that results from the rupture of a blood vessel in the brain, leading to a mass of blood within the brain parenchyma. The injury causes a rapid inflammatory reaction that includes activation of the tissue-resident microglia and recruitment of blood-derived macrophages and other leukocytes. In this work, we investigated the specific responses of microglia following ICH with the aim of identifying pathways that may aid in recovery after brain injury...
November 28, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27889479/ido1-is-an-integral-mediator-of-inflammatory-neovascularization
#6
Arpita Mondal, Courtney Smith, James B DuHadaway, Erika Sutanto-Ward, George C Prendergast, Arturo Bravo-Nuevo, Alexander J Muller
The immune tolerogenic effects of IDO1 (indoleamine 2,3-dioxygenase 1) have been well documented and genetic studies in mice have clearly established the significance of IDO1 in tumor promotion. Dichotomously, the primary inducer of IDO1, the inflammatory cytokine IFNγ (interferon-γ), is a key mediator of immune-based tumor suppression. One means by which IFNγ can exert an anti-cancer effect is by decreasing tumor neovascularization. We speculated that IDO1 might contribute to cancer promotion by countering this anti-neovascular effect of IFNγ, possibly through IDO1-potentiated elevation of the pro-tumorigenic inflammatory cytokine IL6 (interleukin-6)...
November 9, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27888521/cancer-associated-mesenchymal-stroma-fosters-the-stemness-of-osteosarcoma-cells-in-response-to-intratumoral-acidosis-via-nf-%C3%AE%C2%BAb-acivation
#7
Sofia Avnet, Gemma Di Pompo, Tokuhiro Chano, Costantino Errani, Arig Ibrahim-Hashim, Robert J Gillies, Davide Maria Donati, Nicola Baldini
The role of mesenchymal stem cells (MSC) in osteosarcoma (OS), the most common primary tumor of bone, has not been extensively elucidated. We have recently shown that OS is characterized by interstitial acidosis, a microenvironmental condition that is similar to a wound setting, in which mesenchymal reactive cells are activated to release mitogenic and chemotactic factors. We therefore intended to test the hypothesis that, in OS, acid-activated MSC influence tumor cell behavior. Conditioned media or co-culture with normal MSC previously incubated with short-term acidosis (pH 6...
November 26, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27888157/curcumin-use-in-pulmonary-diseases-state-of-the-art-and-future-perspectives
#8
REVIEW
Diana Lelli, Amirhossein Sahebkar, Thomas P Johnston, Claudio Pedone
Curcumin (diferuloylmethane) is a yellow pigment present in the spice turmeric (Curcuma longa). It has been used for centuries in Ayurveda (Indian traditional medicine) for the treatment of several diseases. Over the last several decades, the therapeutic properties of curcumin have slowly been elucidated. It has been shown that curcumin has pleiotropic effects, regulating transcription factors (e.g., NF-kB), cytokines (e.g., IL6, TNF-alpha), adhesion molecules (e.g., ICAM-1), and enzymes (e.g., MMPs) that play a major role in inflammation and cancerogenesis...
November 22, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27888067/allele-and-genotype-frequencies-of-polymorphisms-in-cytokine-genes-in-ethnic-russian-individuals-from-moscow-russia
#9
Alexandra Shadrina, Elena Voronina, Igor Zolotukhin, Maxim Filipenko
Two hundred and twenty eight ethnic Russian individuals from Moscow, Russia, were genotyped at 14 single nucleotide polymorphisms CCL2 A-2578G; VEGFA C-2578A, G-634C, and C+936T; TNF G+419A and G-308A; IL1A G-889A; IL1RN T+1018C; IL6 G-174C and G-572C; IFNG T+874A; IL1B C-511T; IL10 A+1082G; TGFB1 C-509T. Genotypes were determined using real-time polymerase chain reaction with TaqMan probes and polymerase chain reaction followed by melting analysis of dual-labeled probe. Genotype distribution was in accordance with Hardy-Weinberg equilibrium for all studied polymorphisms...
November 22, 2016: Human Immunology
https://www.readbyqxmd.com/read/27876617/canagliflozin-a-sodium-glucose-cotransporter-2-inhibitor-attenuates-obesity-induced-inflammation-in-the-nodose-ganglion-hypothalamus-and-skeletal-muscle-of-mice
#10
Farhana Naznin, Hideyuki Sakoda, Tadashi Okada, Hironobu Tsubouchi, T M Zaved Waise, Kenji Arakawa, Masamitsu Nakazato
Chronic inflammation in systemic organs, such as adipose tissue, nodose ganglion, hypothalamus, and skeletal muscles, is closely associated with obesity and diabetes mellitus. Because sodium glucose cotransporter 2 (SGLT2) inhibitors exert both anti-diabetic and anti-obesity effects by promoting urinary excretion of glucose and subsequent caloric loss, we investigated the effect of canagliflozin, an SGLT2 inhibitor, on obesity-induced inflammation in neural tissues and skeletal muscles of mice. High-fat diet (HFD)-fed male C57BL/6J mice were treated with canagliflozin for 8 weeks...
November 19, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27875309/rna-sequencing-reveals-a-role-of-tonebp-in-regulation-of-pro-inflammatory-genes-in-response-to-hyperosmolarity-in-healthy-nucleus-pulposus-cells-a-homeostatic-response
#11
Zariel I Johnson, Irving M Shapiro, Makarand V Risbud
Transcription factor Tonicity-Responsive Enhancer-Binding Protein (TonEBP/NFAT5) is critical for osmo-adaptation and extracellular matrix homeostasis of nucleus pulposus (NP) cells in their hypertonic tissue niche. Recent studies implicate TonEBP signaling in inflammatory disease and rheumatoid arthritis pathogenesis. However, broader functions of TonEBP in the disc remain unknown. RNA-sequencing was performed on NP cells with TonEBP knockdown under hypertonic conditions. 1140 TonEBP-dependent genes were identified and categorized using Ingenuity Pathway Analysis...
November 8, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27873461/human-peripheral-blood-mononuclear-cell-in-vitro-system-to-test-the-efficacy-of-food-bioactive-compounds-effects-of-polyunsaturated-fatty-acids-and-their-relation-with-bmi
#12
Margalida Cifre, Rubén Díaz-Rúa, Rubén Varela-Calviño, Bàrbara Reynés, Jordi Pericás-Beltrán, Andreu Palou, Paula Oliver
SCOPE: To analyse usefulness of isolated human peripheral blood mononuclear cells (PBMC) to rapidly/easily reflect n-3 long-chain polyunsaturated fatty acid (LCPUFA) effects on lipid metabolism/inflammation gene profile, and evaluate if these effects are BMI-dependent. METHODS AND RESULTS: PBMC from normoweight (NW) and overweight/obese (OW/OB) subjects were incubated with physiological doses of docosahexaenoic (DHA), eicosapentaenoic acid (EPA), or their combination...
November 22, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27871023/association-of-a-novel-gabrg2-splicing-variation-and-a-ptgs2-cox-2-single-nucleotide-polymorphism-with-taiwanese-febrile-seizures
#13
Kun-Long Hung, Jao-Shwann Liang, Jinn-Shyan Wang, Hui-Ju Chen, Li-Ju Lin, Jyh-Feng Lu
Febrile seizure (FS) is the most common type of convulsion in infants and young children. The occurrence of FS in a subset of children with febrile illness suggested genetic factors may have an important effect on the predisposition of the disease. Using targeted next generation sequencing (NGS), a novel splicing variation (NM_198903.2:c.1249-1G>T) was identified in the γ-aminobutyric acid type A (GABA-A) receptor γ2 subunit (GABRG2) gene of a FS patient. To investigate possible association of FS with single nucleotide polymorphisms (SNPs) in prostaglandin-endoperoxide synthase-2 (prostaglandin G/H synthase-2; PTGS2/cyclooxygenase-2; COX2) gene involving in thermoregulatory pathway, eight SNPs, rs689465, rs689466, rs20417, rs13306038, rs201931599, rs689470, rs4648306 and rs4648308, along with 2 previously reported variations in IL1RN (86-bp VNTR) and IL10 (rs1900872) were genotyped and utilized for case-control association studies on 35 FS and 31 non-FS controls...
November 14, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/27870860/gene-expression-profile-of-high-ifn-%C3%AE-producers-stimulated-with-leishmania-braziliensis-identifies-genes-associated-with-cutaneous-leishmaniasis
#14
Marcia W Carneiro, Kiyoshi F Fukutani, Bruno B Andrade, Rebecca P Curvelo, Juqueline R Cristal, Augusto M Carvalho, Aldina Barral, Johan Van Weyenbergh, Manoel Barral-Netto, Camila I de Oliveira
BACKGROUND: The initial response to Leishmania parasites is essential in determining disease development or resistance. In vitro, a divergent response to Leishmania, characterized by high or low IFN-γ production has been described as a potential tool to predict both vaccine response and disease susceptibility in vivo. METHODS AND FINDINGS: We identified uninfected and healthy individuals that were shown to be either high- or low IFN-γ producers (HPs and LPs, respectively) following stimulation of peripheral blood cells with Leishmania braziliensis...
November 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27870582/markers-of-islet-endothelial-dysfunction-occur-in-male-db-db-mice-and-may-contribute-to-reduced-insulin-release
#15
Meghan F Hogan, Amy W Liu, Michael J Peters, Joshua R Willard, Zaheen Rabbani, Erik C Bartholomew, Adam Ottley, Rebecca L Hull
Islet endothelial cells produce paracrine factors that support β-cell function and growth. Endothelial dysfunction underlies diabetic microvascular complications; thus we hypothesized that in diabetes, islet endothelial cells become dysfunctional and this may contribute to β-cell secretory dysfunction. Islets/islet endothelial cells were isolated from diabetic db/db mice, treated with or without the glucose-lowering agent phlorizin, or C57BL/6J mice fed a high fat diet for 18 weeks (and appropriate controls)...
November 21, 2016: Endocrinology
https://www.readbyqxmd.com/read/27866912/investigation-of-candidate-genes-for-osteoarthritis-based-on-gene-expression-profiles
#16
Shuanghai Dong, Tian Xia, Lei Wang, Qinghua Zhao, Jiwei Tian
OBJECTIVE: To explore the mechanism of osteoarthritis (OA) and provide valid biological information for further investigation. METHODS: Gene expression profile of GSE46750 was downloaded from Gene Expression Omnibus database. The Linear Models for Microarray Data (limma) package (Bioconductor project, http://www.bioconductor.org/packages/release/bioc/html/limma.html) was used to identify differentially expressed genes (DEGs) in inflamed OA samples. Gene Ontology function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were performed based on Database for Annotation, Visualization and Integrated Discovery data, and protein-protein interaction (PPI) network was constructed based on the Search Tool for the Retrieval of Interacting Genes/Proteins database...
November 17, 2016: Acta Orthopaedica et Traumatologica Turcica
https://www.readbyqxmd.com/read/27866224/the-beneficial-effects-of-empagliflozin-an-sglt2-inhibitor-on-atherosclerosis-in-apoe-mice-fed-a-western-diet
#17
Ji Hye Han, Tae Jung Oh, Ghayoung Lee, Hyo Jin Maeng, Dong Hwa Lee, Kyoung Min Kim, Sung Hee Choi, Hak Chul Jang, Hye Seung Lee, Kyong Soo Park, Young-Bum Kim, Soo Lim
AIMS/HYPOTHESIS: A recent large clinical study has shown that empagliflozin has a lower rate of cardiovascular and all-cause mortality when compared with placebo in patients with type 2 diabetes. We investigated the effect of empagliflozin (compared with glimepiride) on the progression of atherosclerosis, and its possible mechanisms of action. METHODS: Forty-eight 5-week-old male ApoE (-/-) mice were fed a western diet for 20 weeks and divided into four groups: control (saline, 154 mmol/l NaCl), glimepiride 0...
November 19, 2016: Diabetologia
https://www.readbyqxmd.com/read/27865949/lost-in-translation-the-potential-psychobiotic-lactobacillus-rhamnosus-jb-1-fails-to-modulate-stress-or-cognitive-performance-in-healthy-male-subjects
#18
John R Kelly, Andrew P Allen, Andriy Temko, William Hutch, Paul J Kennedy, Niloufar Farid, Eileen Murphy, Geraldine Boylan, John Bienenstock, John F Cryan, Gerard Clarke, Timothy G Dinan
BACKGROUND: Preclinical studies have identified certain probiotics as psychobiotics - live microorganisms with a potential mental health benefit. Lactobacillus rhamnosus (JB-1) has been shown to reduce stress-related behaviour, corticosterone release and alter central expression of GABA receptors in an anxious mouse strain. However, it is unclear if this single putative psychobiotic strain has psychotropic activity in humans. Consequently, we aimed to examine if these promising preclinical findings could be translated to healthy human volunteers...
November 16, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27863449/il6-mediated-inflammatory-loop-reprograms-normal-to-emt-metastatic-cscs-in-pre-neoplastic-liver-of-tgf%C3%AE-deficient-%C3%AE-2sp-mice
#19
Abhisek Mitra, Jun Yan, Xueqing Xia, Shouhao Zhou, Jian Chen, Lopa Mishra, Shulin Li
Hepatocellular carcinoma (HCC) is the second-leading cause of cancer-related deaths world-wide with poor survival rate. As many as 40% of HCCs are clonal, with alteration of key tumor suppressor pathways in stem cells is the primary cause of HCC initiation. However, mechanisms that generate metastatic stem cells in pre-neoplastic liver tissue are not well understood. We hypothesized that chronic inflammation is a major driver of the transformation of genetically defective liver stem cells (LSCs) into highly metastatic liver cancer cells in premalignant liver tissue...
November 18, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27862254/hk2-proximal-tubule-epithelial-cells-synthesize-and-secrete-plasma-proteins-predominantly-through-the-apical-surface
#20
Ke-Wei Zhao, Elsa J Brochmann Murray, Samuel S Murray
Renal proximal tubule epithelial cells (PTECs) are known to reabsorb salts and small plasma proteins filtered through Bowman's capsule. Following acute kidney injury, PTECs assume some characteristics of hepatocytes in producing various plasma proteins. We now demonstrate that even at a resting state, a PTEC cell line, HK2 expresses mRNAs for and synthesizes and secretes plasma proteins in a complex with complement C3, an α2 -macroglobulin family chaperone, including albumin, transferrin, α1 -antitrypsin, α1 -antichymotrypsin, α2 -HS-glycoprotein, ceruloplasmin, haptoglobin, C1-inhibitor, secreted phosphoprotein-24, and insulin-like growth factor-1...
November 9, 2016: Journal of Cellular Biochemistry
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