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https://www.readbyqxmd.com/read/29149944/management-of-sepsis-induced-immunosuppression
#1
REVIEW
Fabienne Venet, Thomas Rimmelé, Guillaume Monneret
It is now well established that profound immunosuppression develops within a few days after sepsis onset in patients. This should be considered additional organ failure because it is associated with increased rate of nosocomial infections, mortality, and long-term complications, thus constituting the rationale for immunomodulation in patients. Nevertheless, the demonstration of the efficacy of such therapeutic strategy in improving deleterious outcomes in sepsis remains to be made. Results from clinical trials based on interleukin 7 and granulocyte macrophage colony-stimulating factor immunoadjuvant therapies in septic shock patients are expected for 2018...
January 2018: Critical Care Clinics
https://www.readbyqxmd.com/read/29149221/dietary-protein-sources-differentially-affect-microbiota-mtor-activity-and-transcription-of-mtor-signaling-pathways-in-the-small-intestine
#2
Soumya K Kar, Alfons J M Jansman, Nirupama Benis, Javier Ramiro-Garcia, Dirkjan Schokker, Leo Kruijt, Ellen H Stolte, Johanna J Taverne-Thiele, Mari A Smits, Jerry M Wells
Dietary protein sources can have profound effects on host-microbe interactions in the gut that are critically important for immune resilience. However more knowledge is needed to assess the impact of different protein sources on gut and animal health. Thirty-six wildtype male C57BL/6J mice of 35 d age (n = 6/group; mean ± SEM body weight 21.9 ± 0.25 g) were randomly assigned to groups fed for four weeks with semi synthetic diets prepared with one of the following protein sources containing (300 g/kg as fed basis): soybean meal (SBM), casein, partially delactosed whey powder, spray dried plasma protein, wheat gluten meal and yellow meal worm...
2017: PloS One
https://www.readbyqxmd.com/read/29147627/stat1-gene-deficient-mice-develop-accelerated-breast-cancer-growth-and-metastasis-which-is-reduced-by-il-17-blockade
#3
Sanjay Varikuti, Steve Oghumu, Mohamad Elbaz, Greta Volpedo, Dinesh K Ahirwar, Pablo C Alarcon, Rachel H Sperling, Ellen Moretti, Marissa S Pioso, Jennifer Kimble, Mohd W Nasser, Ramesh K Ganju, Cesar Terrazas, Abhay R Satoskar
Signal transducer and activator of transcription 1 (STAT1) mediates interferon gamma signaling which activates the expression of various genes related to apoptosis, inflammation, cell cycle and angiogenesis. Several experimental and clinical studies have investigated the role of STAT1 in primary tumor growth in breast cancer; however, its role in tumor metastasis remains to be determined. To determine the role of STAT1 in breast cancer metastasis, we analyzed growth and metastasis in WT or STAT1(-/-) mice orthotopically implanted with metastatic 4T1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147617/phase-i-trial-of-anti-gd2-monoclonal-antibody-hu3f8-plus-gm-csf-impact-of-body-weight-immunogenicity-and-anti-gd2-response-on-pharmacokinetics-and-survival
#4
Irene Y Cheung, Brian H Kushner, Shakeel Modak, Ellen M Basu, Stephen S Roberts, Nai-Kong V Cheung
Fifty-seven stage 4 patients with refractory/relapsed neuroblastoma were enrolled in a phase I trial (Clinicaltrials.gov NCT01757626) using humanized anti-GD2 monoclonal antibody hu3F8 in combination with granulocyte-macrophage colony-stimulating factor. The influence of body weight and human anti-human antibody (HAHA) on the pharmacokinetics (PK) of hu3F8, and the effect of de novo anti-GD2 response on patient outcome were explored. Serum samples before hu3F8 infusion, and serially up to day 12 during treatment cycle #1, and at 5 min after each hu3F8 infusion for all subsequent cycles were collected...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147615/tumor-associated-neutrophils-induce-apoptosis-of-non-activated-cd8-t-cells-in-a-tnf%C3%AE-and-no-dependent-mechanism-promoting-a-tumor-supportive-environment
#5
Janna Michaeli, Merav E Shaul, Inbal Mishalian, Avi-Hai Hovav, Liran Levy, Lidia Zolotriov, Zvi Granot, Zvi G Fridlender
The role of neutrophils in tumor progression has become in recent years a subject of growing interest. Tumor-associated neutrophils (TANs), which constitute an important portion of the tumor microenvironment, promote immunosuppression in advanced tumors by modulating the proliferation, activation and recruitment of a variety of immune cell types. Studies which investigated the consequences of manipulating TAN polarization suggest that the impact of these neutrophils on tumor progression is considerably mediated by and dependent on the presence of CD8 T-cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147612/low-dose-post-transplant-cyclophosphamide-can-mitigate-gvhd-and-enhance-the-g-csf-atg-induced-gvhd-protective-activity-and-improve-haploidentical-transplant-outcomes
#6
Yu Wang, Ying-Jun Chang, Lu Chen, Lan-Ping Xu, Zhi-Lei Bian, Xiao-Hui Zhang, Chen-Hua Yan, Kai-Yan Liu, Xiao-Jun Huang
Use of high-dose, post-transplant cyclophosphamide (PTCy) results in low rates of graft-versus-host-disease (GVHD) and favorable immune reconstitution, although with higher rates of relapse and somewhat high rates of graft failure. We hypothesized that permissible dose reduction of PTCy might be feasible. The current study attempts to establish a murine model and focus on regulatory T cells (Tregs) to clarify the immunological mechanisms for GVHD prevention by low-dose PTCy. In addition, a prospective, clinical cohort study in haploidentical, T-cell replete transplantation is initiated to support the rational...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29146994/usefulness-of-the-delta-neutrophil-index-to-predict-30-day-mortality-in-patients-with-st-segment-elevation-myocardial-infarction
#7
Taeyoung Kong, Tae Hoon Kim, Yoo Seok Park, Sung Phil Chung, Hye Sun Lee, Jung Hwa Hong, Jong Wook Lee, Je Sung You, Incheol Park
This study aimed to evaluate the association between the delta neutrophil index (DNI), which reflects immature granulocytes, and the severity of ST-elevation myocardial infarction (STEMI), as well as to determine the significance of the DNI as a prognostic marker for early mortality and other clinical outcomes in patients with STEMI who underwent reperfusion. This retrospective, observational cohort study was conducted using patients prospectively integrated in a critical pathway program for STEMI. We included 842 patients diagnosed with STEMI who underwent primary percutaneous coronary intervention (pPCI)...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146453/cellular-and-biochemical-parameters-following-autotomy-and-ablation-mediated-cheliped-loss-in-the-chinese-mitten-crab-eriocheir-sinensis
#8
Xiao-Zhen Yang, Cong Zhang, Gen-Yong Huang, Min-Jie Xu, Yong-Xu Cheng, Zhi-Gang Yang, Qian Zhang, Yi-Yue Wang
In the pond culture of juvenile Eriocheir sinensis, various factors have frequently led to a high rate of autotomy and limb impairments. This study evaluated the differential effects of cheliped loss with autotomy and ablation on the short-term cellular and biochemical parameters of juvenile E. sinensis. In this study, compared with the crabs before treatment, the total hemocyte counts (THC), granulocyte counts (GC), hemocyte agglutination, phosphatase activity and glucose metabolism levels were significantly increased, while hyalinocyte counts (HC) and total antioxidant capacity (T-AOC) were significantly decreased within 3 h...
November 13, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29143796/angelica-sinensis-polysaccharides-ameliorate-stress-induced-premature-senescence-of-hematopoietic-cell-via-protecting-bone-marrow-stromal-cells-from-oxidative-injuries-caused-by-5-fluorouracil
#9
Hanxianzhi Xiao, Lirong Xiong, Xiaoying Song, Pengwei Jin, Linbo Chen, Xiongbin Chen, Hui Yao, Yaping Wang, Lu Wang
Myelosuppression is the most common complication of chemotherapy. Decline of self-renewal capacity and stress-induced premature senescence (SIPS) of hematopoietic stem cells (HSCs) induced by chemotherapeutic agents may be the cause of long-term myelosuppression after chemotherapy. Whether the mechanism of SIPS of hematopoietic cells relates to chemotherapeutic injury occurred in hematopoietic microenvironment (HM) is still not well elucidated. This study explored the protective effect of Angelica sinensis polysaccharide (ASP), an acetone extract polysaccharide found as the major effective ingredients of a traditional Chinese medicinal herb named Chinese Angelica (Dong Quai), on oxidative damage of homo sapiens bone marrow/stroma cell line (HS-5) caused by 5-fluorouracil (5-FU), and the effect of ASP relieving oxidative stress in HM on SIPS of hematopoietic cells...
October 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29142459/a-phase-i-study-of-different-doses-and-frequencies-of-pegylated-recombinant-human-granulocyte-colony-stimulating-factor-peg-rhg-csf-in-patients-with-standard-dose-chemotherapy-induced-neutropenia
#10
Yan Qin, Xiaohong Han, Lin Wang, Ping Du, Jiarui Yao, Di Wu, Yuanyuan Song, Shuxiang Zhang, Le Tang, Yuankai Shi
Objective: The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy. However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy. Methods: Eligible patients received 3-cycle chemotherapy every 3 weeks...
October 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/29142211/the-microbiota-protects-against-respiratory-infection-via-gm-csf-signaling
#11
Rebecca L Brown, Richard P Sequeira, Thomas B Clarke
The microbiota promotes resistance to respiratory infection, but the mechanistic basis for this is poorly defined. Here, we identify members of the microbiota that protect against respiratory infection by the major human pathogens Streptococcus pneumoniae and Klebsiella pneumoniae. We show that the microbiota enhances respiratory defenses via granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, which stimulates pathogen killing and clearance by alveolar macrophages through extracellular signal-regulated kinase signaling...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29141868/geographic-clonal-tracking-in-macaques-provides-insights-into-hspc-migration-and-differentiation
#12
Chuanfeng Wu, Diego A Espinoza, Samson J Koelle, E Lake Potter, Rong Lu, Brian Li, Di Yang, Xing Fan, Robert E Donahue, Mario Roederer, Cynthia E Dunbar
The geographic distribution of hematopoiesis at a clonal level is of interest in understanding how hematopoietic stem and progenitor cells (HSPCs) and their progeny interact with bone marrow (BM) niches during regeneration. We tagged rhesus macaque autologous HSPCs with genetic barcodes, allowing clonal tracking over time and space after transplantation. We found marked geographic segregation of CD34(+) HSPCs for at least 6 mo posttransplantation, followed by very gradual clonal mixing at different BM sites over subsequent months to years...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29141715/clinical-isolation-of-anaplasma-phagocytophilum-in-south-korea
#13
Seung Hun Lee, Se Yoon Park, Mi Jin Jang, Ki Ju Choi, Hae Kyung Lee, Young-Uk Cho, Yeong Seon Lee, Sung-Han Kim, Seon Do Hwang
We report the first isolation of Anaplasma phagocytophilum in South Korea. A 61-year-old woman presented with a 6-day history of fever, headache, and myalgia. Initial investigation showed neutropenia and thrombocytopenia. We diagnosed human granulocytic anaplasmosis by microscopic examination and serologic testing. The patient recovered fully without antibiotic therapy. The isolate was obtained from the patient's blood by cell culture and mouse inoculation. Its identity was confirmed by an immunofluorescence assay, sequencing of the 16S rRNA gene, msp2 (p44), and ankA genes, and staining and electron microscopy of morulae of A...
October 30, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29141666/intron-retention-enhances-gene-regulatory-complexity-in-vertebrates
#14
Ulf Schmitz, Natalia Pinello, Fangzhi Jia, Sultan Alasmari, William Ritchie, Maria-Cristina Keightley, Shaniko Shini, Graham J Lieschke, Justin J-L Wong, John E J Rasko
BACKGROUND: While intron retention (IR) is now widely accepted as an important mechanism of mammalian gene expression control, it remains the least studied form of alternative splicing. To delineate conserved features of IR, we performed an exhaustive phylogenetic analysis in a highly purified and functionally defined cell type comprising neutrophilic granulocytes from five vertebrate species spanning 430 million years of evolution. RESULTS: Our RNA-sequencing-based analysis suggests that IR increases gene regulatory complexity, which is indicated by a strong anti-correlation between the number of genes affected by IR and the number of protein-coding genes in the genome of individual species...
November 16, 2017: Genome Biology
https://www.readbyqxmd.com/read/29141152/tm-values-and-unfolded-fraction-can-predict-aggregation-rates-for-gcsf-variant-formulations-but-not-under-predominantly-native-conditions
#15
Mathew J Robinson, Paul Matejtschuk, Adrian F Bristow, Paul A Dalby
Protein engineering and formulation optimisation strategies can be taken to minimise protein aggregation in the biopharmaceutical industry. Short-term stability measures such as the mid-point transition temperature (Tm) for global unfolding provide convenient surrogates for longer-term (eg 2-year) degradation kinetics, with which to optimise formulations on practical time-scales. While successful in some cases, their limitations have not been fully evaluated or understood. Tm values are known to correlate with chemical degradation kinetics for wild-type granulocyte colony stimulating factor (GCSF) at pH 4-5...
November 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29141087/effect-of-granulocyte-macrophage-colony-stimulating-factor-with-or-without-supervised-exercise-on-walking-performance-in-patients-with-peripheral-artery-disease-the-propel-randomized-clinical-trial
#16
Mary M McDermott, Luigi Ferrucci, Lu Tian, Jack M Guralnik, Donald Lloyd-Jones, Melina R Kibbe, Tamar S Polonsky, Kathryn Domanchuk, James H Stein, Lihui Zhao, Doris Taylor, Christopher Skelly, William Pearce, Harris Perlman, Walter McCarthy, Lingyu Li, Ying Gao, Robert Sufit, Christina L Bloomfield, Michael H Criqui
Importance: Benefits of granulocyte-macrophage colony-stimulating factor (GM-CSF) for improving walking ability in people with lower extremity peripheral artery disease (PAD) are unclear. Walking exercise may augment the effects of GM-CSF in PAD, since exercise-induced ischemia enhances progenitor cell release and may promote progenitor cell homing to ischemic calf muscle. Objectives: To determine whether GM-CSF combined with supervised treadmill exercise improves 6-minute walk distance, compared with exercise alone and compared with GM-CSF alone; to determine whether GM-CSF alone improves 6-minute walk more than placebo and whether exercise improves 6-minute walk more than an attention control intervention...
November 15, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/29139571/human-prosthetic-joint-infections-are-associated-with-myeloid-derived-suppressor-cells-mdscs-implications-for-infection-persistence
#17
Cortney E Heim, Debbie Vidlak, Jessica Odvody, Curtis W Hartman, Kevin L Garvin, Tammy Kielian
Prosthetic joint infection (PJI) is a devastating complication of joint arthroplasty surgery typified by biofilm formation. Currently, mechanisms whereby biofilms persist and evade immune-mediated clearance in immune competent patients remain largely ill-defined. Therefore, the current study characterized leukocyte infiltrates and inflammatory mediator expression in tissues from patients with PJI compared to aseptic loosening. CD33(+) HLA-DR(-) CD66b(+) CD14(-/low) granulocytic myeloid-derived suppressor cells (G-MDSCs) were the predominant leukocyte population at sites of human PJI compared to aseptic tissues...
November 15, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/29138752/the-effect-of-granulocyte-colony-stimulating-factor-on-the-progression-of-atherosclerosis-in-animal-models-a-meta-analysis
#18
REVIEW
Manli Liu, Kejian Liu, Dongdong Chen, Hongzhi Chen, Kunming Sun, Xinxin Ju, Jiaojiao Lan, Yang Zhou, Weishan Wang, Lijuan Pang
Background: Atherosclerosis is a common inflammatory disease. Stem cell and endothelial progenitor cell treatments can improve cardiac function after myocardial infarction. Granulocyte colony-stimulating factor (G-CSF) is a mobilisation agent, mobilising stem cells from the bone marrow to circulation in the blood. G-CSF may constitute a treatment of atherosclerosis. We have conducted meta-analysis to evaluate the current evidence for the effect of G-CSF on the progression of atherosclerosis in animal models and to provide reference for preclinical experiments and future human clinical trials of atherosclerosis treatment...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29137362/an-optimized-hmgb1-expressed-by-recombinant-rabies-virus-enhances-immunogenicity-through-activation-of-dendritic-cells-in-mice
#19
Zhao Wang, Qian Liang, Yajing Zhang, Jie Yang, Mingming Li, Kunlun Wang, Min Cui, Huanchun Chen, Zhen F Fu, Ling Zhao, Ming Zhou
Rabies remains an important public health threat, killing approximately 59,000 people worldwide annually, most of which are from the developing countries of Africa and Asia where dog rabies are endemic. Therefore, developing an affordable and efficacious vaccine for dog-mediated rabies control is needful in these countries. Our previous studies indicated that over-expression of granulocyte-macrophage colony stimulating factor (GM-CSF) or macrophage inflammatory protein-1 (MIP-1α or CCL3) by recombinant rabies virus (rRABV) could enhance the immunogenicity by activating dendritic cells (DCs)...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137226/the-neglected-avian-hepatotropic-virus-induces-acute-and-chronic-hepatitis-in-ducks-an-alternative-model-for-hepatology
#20
Xumin Ou, Sai Mao, Jingyu Cao, Yunchao Ma, Guangpeng Ma, Anchun Cheng, Mingshu Wang, Dekang Zhu, Shun Chen, Renyong Jia, Mafeng Liu, Kunfeng Sun, Qiao Yang, Ying Wu, Xiaoyue Chen
Duck Hepatitis A Virus (DHAV) belongs to the Avihepatovirus, which is also classified into Picornaviridae with Hepatovirus, Hepatitis A Virus (HAV). In humans, the pathogenesis of HAV is not well understood because of limited work with animal models. Here, we investigated the progress of duck viral hepatitis caused by DHAV and their potential for dissecting the pathogenesis of HAV. During the course of infection, the duck model had undergone hepatocellular lesions (vacuolation, acidophilic degeneration and steatosis), lymphocytes recruitment (neutrophil granulocytes, heterophilic granulocytes and T cells or plasm cells) and repair (activation of hepatic stellate cells, fibrosis and regeneration)...
October 10, 2017: Oncotarget
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