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https://www.readbyqxmd.com/read/28733143/mechanisms-of-nlrp1-mediated-autoinflammatory-disease-in-humans-and-mice
#1
REVIEW
Chien-Hsiung Yu, Jonas Moecking, Matthias Geyer, Seth L Masters
NLRP1 was the first NLR protein described to form an inflammasome, recruiting ASC to activate caspase-1, which processes interleukin-1β and interleukin-18 to their active form. A wealth of new genetic information has now redefined our understanding of this innate immune sensor. Specifically, rare loss-of-function variants in the N-terminal pyrin domain (PYD) indicate that this part of NLRP1 is autoinhibitory, and normally acts to prevent a familial autoinflammatory skin disease associated with cancer. In the absence of a ligand to trigger human NLRP1, these mutations have now confirmed the requirement of NLRP1 autolytic cleavage within the FIIND domain, which had previously been implicated in NLRP1 activation...
July 18, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28731182/il%C3%A2-6-stat3-mir%C3%A2-34a-protects-against-neonatal-lung-injury-patients
#2
Huajun Liu, Wenbin Liu, Xueqing Tang, Taisen Wang, Xianlin Sun, Jie Lv
The present study aimed to investigate the protective role of the interleukin (IL)‑6/signal transducer and activator of transcription 3 (STAT3)/microRNA (miR)‑34a signaling pathway in patients with neonatal lung injury (NLI) and the underlying molecular mechanisms of these effects. It was demonstrated that miR‑34a serum expression was significantly upregulated in patients and mice with NLI. Meanwhile, IL‑6 and phosphorylated‑STAT3 protein expression, and tumor necrosis factor (TNF)‑α, IL‑1β and IL‑18 activity levels in NLI mice were significantly induced compared with the normal control group...
July 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28727231/nulliparity-is-associated-with-subtle-adverse-metabolic-outcomes-in-overweight-obese-mothers-and-their-offspring
#3
Sumudu N Seneviratne, José G B Derraik, Yannan Jiang, Lesley M E McCowan, Silmara Gusso, Janene B Biggs, Graham K Parry, Valentina Chiavaroli, Wayne S Cutfield, Paul L Hofman
BACKGROUND: We aimed to evaluate metabolic outcomes in overweight/obese nulliparous and multiparous women and their offspring. STUDY DESIGN: Seventy-two overweight and obese women who participated in a randomized controlled trial of exercise in pregnancy were included in the study, comparing 18 nulliparous and 54 multiparous women and their singleton offspring. Women were assessed at 19 and 36 weeks of gestation. Fetal growth was measured using standard obstetric ultrasound techniques...
July 20, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28723869/chronic-disseminated-salmonellosis-in-a-patient-with-interleukin-12p40-deficiency
#4
Emadia Mohammad Alaki, Fahad Aljobair, Faisal Alaklobi, Mobarak Al Shamrani, Fahad Al-Zahim, Aziza Dongues, Jean-Laurent Casanova
Interleukin (IL)-12 is composed of p35 and p40 subunit, in this case IL-12p40 deficiency is a rare genetic etiology of Mendelian susceptibility to mycobacterial disease (MSMD). Salmonellosis has been reported in almost half of these patients and mostly present in recurrent extra intestinal form. In this report, we described an 18 month old boy with absence of IL12p40 production suffering from chronic disseminated non-typhoidal salmonellosis. To the best of our knowledge this is the first reported case.
July 18, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28723688/trigonelline-inhibits-inflammation-and-protects-%C3%AE-cells-to-prevent-fetal-growth-restriction-during-pregnancy-in-a-mouse-model-of-diabetes
#5
Ji-Yin Zhou, Xiao-Huang Du, Zuo Zhang, Gui-Sheng Qian
BACKGROUND: As an active component from traditional Chinese medicine, trigonelline has a protective effect on diabetes. This study evaluated the protective effects of trigonelline on diabetic mice during pregnancy. METHODS: Diabetes was induced in female mice by intraperitoneal injection for continuous 5-day of 40 mg/kg/day streptozotocin. Female mice were divided into 4 groups after they were allowed to mate with normal male mice: nondiabetic, nondiabetic treated with trigonelline (70 mg/kg) for 18 days, diabetic, and diabetic treated with trigonelline (70 mg/kg)...
July 20, 2017: Pharmacology
https://www.readbyqxmd.com/read/28723348/central-serotonin-attenuates-lps-induced-systemic-inflammation
#6
Clarissa M D Mota, Caroline Rodrigues-Santos, Rodrigo A R Fernández, Ruither O G Carolino, José Antunes-Rodrigues, Janete A Anselmo-Franci, Luiz G S Branco
Serotonin (5-HT) is a neuromodulator involved in several central-mediated mechanisms, such as endocrine processes, behavior, and sleep. Dysfunction of the serotonergic system is mainly linked to psychiatric disorders, but emerging evidence suggests that immune system activation may also alter brain 5-HT signaling. However, whether central 5-HT modulates systemic inflammation (SI) remains unknown. For this purpose, male Wistar rats (280-350 g, 8-9 weeks) were submitted to the experimental protocols beginning between 9 and 10 AM with the performance of injections...
July 16, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28722635/early-life-inflammation-and-neurodevelopmental-outcome-in-bangladeshi-infants-growing-up-in-adversity
#7
Nona M Jiang, Fahmida Tofail, Jennie Z Ma, Rashidul Haque, Beth Kirkpatrick, Charles A Nelson, William A Petri
Exposure to profound adversity can negatively affect the neurodevelopment of children, but biologic mechanisms that underlie this association remain unknown. We sought to determine whether elevated levels of the inflammatory markers C-reactive protein (CRP) and soluble CD14 (sCD14) are associated with neurodevelopmental outcomes in Bangladeshi children. A total of 422 infant-mother pairs from an urban slum in Dhaka, Bangladesh, were enrolled at birth and followed prospectively. Inflammation was measured with sCD14, interleukin (IL)-1β, and IL-6 at 18 weeks, and CRP at 6, 18, 40, and 53 weeks...
July 17, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28722170/activation-of-the-b-cell-receptor-successively-activates-nf-%C3%AE%C2%BAb-and-stat3-in-chronic-lymphocytic-leukemia-cells
#8
Uri Rozovski, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Ivo Veletic, Alessandra Ferrajoli, Jan Burger, Philip Thompson, Nitin Jain, William Wierda, Michael J Keating, Zeev Estrov
In chronic lymphocytic leukemia (CLL) cells, both interleukin-6 (IL-6) and the B-cell receptor (BCR) activate Janus kinase 2 (JAK2) and induce the phosphorylation of signal transduction and activator of transcription 3 (STAT3) on tyrosine 705 residues. However, whereas IL-6 phosphorylates STAT3 within 15 minutes, stimulation of the BCR with anti-immunoglobulin M (IgM) antibodies phosphorylates STAT3 in 2-4 hours. Here we show that this process takes longer because it requires transcriptional activity of NF-κB...
July 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28721449/role-of-regulatory-t-cells-in-acute-myeloid-leukemia-patients-undergoing-relapse-preventive-immunotherapy
#9
Frida Ewald Sander, Malin Nilsson, Anna Rydström, Johan Aurelius, Rebecca E Riise, Charlotta Movitz, Elin Bernson, Roberta Kiffin, Anders Ståhlberg, Mats Brune, Robin Foà, Kristoffer Hellstrand, Fredrik B Thorén, Anna Martner
Regulatory T cells (Tregs) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re:Mission Trial, NCT01347996, http://www.clinicaltrials.gov ) 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of leukemia in the post-consolidation phase. This study aimed at defining the features, function and dynamics of Foxp3(+)CD25(high)CD4(+) Tregs during immunotherapy and to determine the potential impact of Tregs on relapse risk and survival...
July 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28720358/prognostic-significance-of-neutrophilic-infiltration-in-benign-lymph-nodes-in-patients-with-muscle-invasive-bladder-cancer
#10
Sumanta K Pal, Anh Pham, Winston Vuong, Xueli Liu, Yulan Lin, Nora Ruel, Bertram E Yuh, Kevin Chan, Timothy Wilson, Seth P Lerner, David McConkey, Richard Jove, Wei Liang
BACKGROUND: Preclinical studies suggest that signal transducer and activator of transcription 3 (STAT3)-mediated recruitment of neutrophils to premetastatic tissue occurs prior to metastatic progression. OBJECTIVE: We sought to determine if neutrophilic infiltration in benign nodal tissue is associated with poor clinical outcome in patients with muscle-invasive bladder cancer. DESIGN, SETTING, AND PARTICIPANTS: Formalin-fixed, paraffin-embedded tissue was secured from 55 patients with muscle-invasive bladder cancer who had undergone cystectomy at our institution...
February 2017: European Urology Focus
https://www.readbyqxmd.com/read/28720318/immunogenicity-and-protective-efficacy-of-a-newly-developed-tri-component-diphtheria-tetanus-and-acellular-pertussis-vaccine-in-a-murine-model
#11
Dong Ho Huh, Seung Beom Han, Hye Jo Shin, Dong Ho Ahn, Gi Sub Choi, Kyu Ri Kang, Bo Ram Kim, Jin Han Kang
BACKGROUND/PURPOSE: Although assessing the immunogenicity and protective efficacy of acellular pertussis (aP) vaccines via murine model studies faces limitations, preliminary assessments have been achieved by evaluating respiratory challenge and humoral and cellular immunity. METHODS: We performed a long-term intranasal respiratory challenge with reference and clinically isolated strains of Bordetella pertussis. Simultaneously, we assessed humoral and cellular immunity for evaluating the immunogenicity of a newly developed tri-component diphtheria-tetanus-aP (DTaP) vaccine...
June 29, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28719891/serum-interleukin-10-levels-correlate-with-cerebrospinal-fluid-amyloid-beta-deposition-in-alzheimer-disease-patients
#12
Lucio D'Anna, Samir Abu-Rumeileh, Martina Fabris, Cinzia Pistis, Antonio Baldi, Nova Sanvilli, Francesco Curcio, Gian Luigi Gigli, Sebastiano D'Anna, Mariarosaria Valente
BACKGROUND AND OBJECTIVE: In Alzheimer disease (AD) inflammation becomes evident throughout the course of the disease. However, the association between inflammation, cognitive impairment, and cerebrospinal biomarkers (Aβ42, t-tau, p-tau181, and Aβ42/p-tau181 ratio) is poorly understood. METHODS: A large panel of inflammatory cytokines (interleukin [IL]-1β, IL-1ra, IL-2, IL-4, IL-6, IL-10, IL-17, interferon-γ, tumor necrosis factor-α, and vascular endothelial growth factor) was analyzed using a multiplex immunoassay in 27 patients with a diagnosis of AD dementia and in 18 control subjects...
July 19, 2017: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/28717087/pulmonary-intravascular-large-b-cell-lymphoma-ivlbcl-disguised-as-an-asthma-exacerbation-in-a-patient-with-asthma
#13
Tomohito Takeshige, Norihiro Harada, Yasuhito Sekimoto, Ryota Kanemaru, Takeo Tsutsumi, Kei Matsuno, Satomi Shiota, Azuchi Masuda, Akihiko Gotoh, Miki Asahina, Toshimasa Uekusa, Kazuhisa Takahashi
A 62-year-old man with asthma presented with a 1-month history of wheezing and exertional dyspnea. Although the wheezing symptoms disappeared after systemic corticosteroid therapy, the exertional dyspnea and hypoxemia did not improve. A diagnosis of intravascular large B-cell lymphoma (IVLBCL) with pulmonary involvement was suspected because of the increased serum lactic dehydrogenase (LDH) and soluble interleukin-2 receptor (sIL-2R) level, increased alveolar-arterial oxygen difference (AaDO2), decreased pulmonary diffusing capacity for carbon monoxide (DLCO) and scintigraphic, computed tomography (CT) and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT findings...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28717065/comparison-of-postoperative-pain-and-inflammation-reaction-in-dogs-undergoing-preventive-laparoscopic-assisted-and-incisional-gastropexy
#14
Tomoya Haraguchi, Shiho Kimura, Harumichi Itoh, Shinpei Nishikawa, Masato Hiyama, Kenji Tani, Toshie Iseri, Yoshiki Itoh, Munekazu Nakaichi, Yasuho Taura, Kazuhito Itamoto
This study compared the effects of postoperative pain and inflammation reaction after preventive laparoscopic-assisted gastropexy (LAG) and incisional gastropexy (IG) in 10 clinically normal Beagles. Surgical time, incision length, visual analog scale (VAS) score, University of Melbourne Pain Scale (UMPS) score, and plasma C-reactive protein (CRP), plasma cortisol (COR), and serum interleukin-6 (IL-6) levels were evaluated. The VAS and UMPS scores and COR and IL-6 levels were recorded at 0.5, 1, 2, 4, 8, 12, 18 and 24 hr after surgery...
July 17, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28716390/impact-of-cytokine-genetic-polymorphisms-on-the-risk-of-renal-parenchymal-infection-in-children
#15
Almontaser Hussein, Eman Askar, Ahlam Badawy, Khaled Saad, Asmaa Zahran, Ahmad A Elderwy
BACKGROUND: Acute pyelonephritis is associated with renal scarring in up to 30% of patients. Renal scarring may cause significant long-term morbidity. The pathogenesis of acute pyelonephritis remains unclear, although it involves interaction among uroepithelium, the immune system cells, and the locally produced cytokines. That some UTI-prone children develop acute pyelonephritis, and eventually renal parenchymal scarring, suggests a genetic role. Interleukin-6, interleukin-8, chemokine receptor-1 (CXCR1), and tumor necrosis factor-alpha (TNFα), the key regulators of the host immune responses, are proteins whose secretion is controlled by genes...
July 3, 2017: Journal of Pediatric Urology
https://www.readbyqxmd.com/read/28715807/amniotic-fluid-angiogenic-and-inflammatory-factor-profiling-in-foetal-down-syndrome
#16
Monika Zbucka-Kretowska, Karol Charkiewicz, Jan Czerniecki, Joanna Goscik, Slawomir Wolczynski, Piotr Laudanski
OBJECTIVES: Angiogenic factors are proteins that can potentially be related to certain foetal chromosomal abnormalities. The goal of this study was to determine the concentrations of 60 angiogenic factors in the amniotic fluid of women carrying foetuses with Down syndrome (DS). METHODS: After analysis of the karyotyping results, for the purpose of this study, we chose 12 women with foetal DS. For the control group, we selected 12 healthy patients with uncomplicated pregnancies (15-18 weeks of gestation) who delivered healthy newborns at term...
July 15, 2017: Fetal Diagnosis and Therapy
https://www.readbyqxmd.com/read/28713995/bioinformatic-analysis-of-computational-identified-differentially-expressed-genes-in-tumor-stoma-of-pregnancy%C3%A2-associated-breast-cancer
#17
Qian Zhou, Erhu Sun, Lijun Ling, Xiaofeng Liu, Min Zhang, Hong Yin, Cheng Lu
The present study aimed to screen the differentially expressed genes (DEGs) in tumor‑associated stroma of pregnancy‑associated breast cancer (PABC). By analyzing Affymetrix microarray data (GSE31192) from the Gene Expression Omnibus database, DEGs between tumor asso-ciated stromal cells and normal stromal cells in PABC were identified. Gene Ontology (GO) function and pathway enrichment analyses for the DEGs were then performed, followed by construction of a protein‑protein interaction (PPI) network. A total of 94 upregulated and 386 downregulated DEGs were identified between tumor associated stromal cells and normal stromal cells in patients with PABC...
July 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28712670/production-and-regulation-of-interleukin-1-family-cytokines-at-the-materno-fetal-interface
#18
Louis M Scott, Aled H Bryant, April Rees, Billy Down, Ruth H Jones, Catherine A Thornton
IL-1 family members regulate innate immune responses, are produced by gestation-associated tissues, and have a role in healthy and adverse pregnancy outcomes. To better understand their role at the materno-fetal interface we used a human tissue explant model to map lipopolysaccharide (LPS)-stimulated production of IL-1α, IL-1β, IL-18, IL-33, IL-1Ra, IL-18BPa, ST2 and IL-1RAcP by placenta, choriodecidua and amnion. Caspase-dependent processing of IL-1α, IL-1β, IL-18, and IL-33 and the ability of IL-1α, IL-1β, IL-18, and IL-33 to regulate the production of IL-1RA, IL-18BPa, ST2 and IL-1RAcP was also determined...
July 13, 2017: Cytokine
https://www.readbyqxmd.com/read/28710563/an-observational-study-examining-the-effects-of-a-surgically-induced-inflammatory-response-on-the-distribution-of-morphine-and-its-metabolites-into-cerebrospinal-fluid
#19
Yan Wang, Kerry B Goralski, Derek J Roberts, Kathryn Landry, Mark E Issa, Lekha Sleno, Lisa C Julien, Jeremy Wood, Richard I Hall
PURPOSE: Morphine is administered intravenously for pain management in the perioperative period. The effect of the inflammatory response to surgery on morphine distribution across the blood-brain barrier (BBB) in humans was investigated. We hypothesized that a graded surgically induced, systemic inflammatory response alters cerebrospinal fluid (CSF) levels of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) through a temporary reduction in BBB drug efflux transporter function...
July 14, 2017: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/28708885/pioglitazone-ameliorates-glomerular-nlrp3-inflammasome-activation-in-apolipoprotein-e-knockout-mice-with-diabetes-mellitus
#20
Yao Wang, Bo Yu, Li Wang, Ming Yang, Zhiyin Xia, Wei Wei, Fengyu Zhang, Xiaochen Yuan
OBJECTIVE: The NLRP3 inflammasome plays an important role in the pathogenesis of inflammation in diabetic nephropathy (DN). Pioglitazone (PIO) has been found to exert an anti-inflammatory effect in patients with diabetes mellitus, but it is still unclear whether PIO exhibits a similar effect in DN. We aimed to explore the effect and underlying mechanism of PIO on DN, as well as investigate if NLRP3 is a pharmacologic target of PIO. METHODS: We divided 48 apolipoprotein E (apoE) (-/-) mice into 4 groups: apoE (-/-), apoE (-/-) with PIO, diabetic apoE (-/-), and diabetic apoE (-/-) with PIO...
2017: PloS One
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