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https://www.readbyqxmd.com/read/28641100/bruton-s-tyrosine-kinase-btk-as-a-promising-target-in-solid-tumors
#1
REVIEW
J Molina-Cerrillo, T Alonso-Gordoa, P Gajate, E Grande
Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells...
June 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28635255/characterization-and-immunomodulatory-activity-of-a-novel-peptide-ecfsta-from-wheat-germ-globulin
#2
Wenjia Wu, Mengmeng Zhang, Yao Ren, Xinze Cai, Zhina Yin, Xiaoai Zhang, Tian Min, Hui Wu
A novel peptide was extracted from wheat germ globulin and purified using ion-exchange chromatography, gel filtration chromatography and semi-preparative reverse phase-high performance liquid chromatography (RP-HPLC). The sequence of the peptide was found to be Glu-Cys-Phe-Ser-Thr-Ala (ECFSTA). Its immunomodulatory effects were evaluated, and the results showed that ECFSTA could enhance phagocytosis of RAW 264.7 cells and significantly increase their secretion of nitric oxide (NO), interleukins-6 (IL-6), tumor necrosis factors-α (TNF-α), and reactive oxygen species (ROS)...
June 21, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28632753/mait-cells-launch-a-rapid-robust-and-distinct-hyperinflammatory-response-to-bacterial-superantigens-and-quickly-acquire-an-anergic-phenotype-that-impedes-their-cognate-antimicrobial-function-defining-a-novel-mechanism-of-superantigen-induced-immunopathology
#3
Christopher R Shaler, Joshua Choi, Patrick T Rudak, Arash Memarnejadian, Peter A Szabo, Mauro E Tun-Abraham, Jamie Rossjohn, Alexandra J Corbett, James McCluskey, John K McCormick, Olivier Lantz, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28631997/expression-and-purification-of-a-functional-porcine-soluble-triggering-receptor-expressed-on-myeloid-cells-1
#4
Hui Li, Shuangshuang Guo, Leyan Yan, Chunhua Meng, Yiyi Hu, Kongwang He, Zhendan Shi
Triggering receptor expressed on myeloid cells 1 (TREM-1) plays a vital role in the pathogen-triggered amplification loop required for proinflammatory responses. Blockade of TREM-1 signaling may inhibit expansion of sepsis and prolong survival of animals. In the present study, the gene of porcine soluble TREM-1 was cloned and expressed in E. coli. After purification, the bioactivity of recombinant porcine soluble TREM-1 was tested in vitro on porcine alveolar macrophages. The results showed that supplementation with the recombinant porcine sTREM-1 protein rapidly and dose-dependently attenuated the upregulation of cytokines (IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12, IL-16, IL-18, and TNF-α) caused by LPS stimulation in the cultured porcine alveolar macrophages...
February 10, 2017: Animal Biotechnology
https://www.readbyqxmd.com/read/28631886/nlrp3-expression-and-urinary-hsp72-in-relation-to-biomarkers-of-inflammation-and-oxidative-stress-in-diabetic-nephropathy-patients
#5
Hemat El-Sayed El-Horany, Rania Nagi Abd-Ellatif, Mona Watany, Yasser M Hafez, Hanaa Ibrahim Okda
Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease. Nod-like receptors nucleotide-binding domain and leucine-rich repeat pyrin-3 domain (NLRP3) inflammasome displays a considerable role in the chronic inflammatory state observed in diabetic patients. Urinary heat shock protein 72 (uHSP72) is a sensitive and specific biomarker for the early detection of acute kidney injury. The aim of this study was to evaluate NLRP3 relative gene expression, its correlation with inflammatory and oxidative stress markers, and to assess the value of uHSP72 in the early detection of DN in type 2 diabetic patients with different degrees of DN...
June 20, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28631819/protective-effects-of-tannic-acid-on-pressure-overload-induced-cardiac-hypertrophy-and-underlying-mechanisms-in-rats
#6
Li Chu, Pinya Li, Tao Song, Xue Han, Xuan Zhang, Qiongtao Song, Tao Liu, Yuanyuan Zhang, Jianping Zhang
OBJECTIVES: The aim of this study was to examine the cardioprotective effects and latent mechanism of tannic acid (TA) on cardiac hypertrophy. METHODS: Abdominal aortic banding (AAB) was used to induce pressure overload-induced cardiac hypertrophy in male Wistar rats, sham-operated rats served as controls. AAB rats were treated with TA (20 and 40 mg/kg) or captoril. KEY FINDINGS: Abdominal aortic banding rats that received TA showed ameliorated pathological changes in cardiac morphology and coefficients, decreased cardiac hypertrophy and apoptosis, a reduction in over expressions of angiotensin type 1 receptor (AT1 R), angiotensin type 2 receptor (AT2 R), phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and transforming growth factor-β (TGF-β) mRNA, and modified expression of matrix metal proteinase-9 (MMP-9) mRNA in AAB rat hearts...
June 20, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28630305/multiple-layers-of-heterogeneity-and-subset-diversity-in-human-mait-cell-responses-to-distinct-microorganisms-and-to-innate-cytokines
#7
Joana Dias, Edwin Leeansyah, Johan K Sandberg
Mucosa-associated invariant T (MAIT) cells are a large innate-like T-cell subset in humans defined by invariant TCR Vα7.2 use and expression of CD161. MAIT cells recognize microbial riboflavin metabolites of bacterial or fungal origin presented by the monomorphic MR1 molecule. The extraordinary level of evolutionary conservation of MR1 and the limited known diversity of riboflavin metabolite antigens have suggested that MAIT cells are relatively homogeneous and uniform in responses against diverse microbes carrying the riboflavin biosynthesis pathway...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630066/porphyromonas-gulae-activates-unprimed-and-ifn%C3%AE-primed-macrophages-via-the-pattern-recognition-receptors-tlr-2-tlr-4-and-nod2
#8
James A Holden, Neil M O'Brien-Simpson, Jason C Lenzo, Rebecca K H Orth, Ashley Mansell, Eric C Reynolds
Porphyromonas gulae is an anaerobic, Gram-negative coccobacillus that has been associated with periodontal disease in companion animals. The aims of this study were to analyse the ligation of pattern recognition receptors by P. gulae and the subsequent activation of macrophages. Exposure of HEK cells transfected with Toll-like receptors or NOD-like receptors to P. gulae resulted in the ligation of TLR2, TLR4 and NOD2. The effect of this engagement of receptors was investigated by measuring the synthesis of nitric oxide, CD86 expression and inflammatory cytokine production using wild type, TLR2-/- and TLR4-/- macrophages...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28628927/curcumin-promotes-apoptosis-of-activated-hepatic-stellate-cells-by-inhibiting-protein-expression-of-the-myd88-pathway
#9
Ya-Jun He, Kenny Kuchta, Yan-Mei Deng, Silke Cameron, Yu Lin, Xu-You Liu, Guo-Ron Ye, Xia Lv, Yuta Kobayashi, Jian-Chang Shu
Activation and proliferation of hepatic stellate cells (HSC) play an important role in the progress of liver fibrosis. HSC activation occurs in response to inflammatory cytokines, cellular interactions with immune cells, and morphogenetic signals. The literature hints to a role of the adaptor protein MyD88 in fibrosis. Although curcumin has been shown to exert inhibitory effects on the proliferation of HSC in vitro, its influence on the MyD88 pathway in HSC has remained unclear. Here, we investigated whether curcumin accelerates apoptosis of HSC through the MyD88 pathway...
June 19, 2017: Planta Medica
https://www.readbyqxmd.com/read/28627583/deoxyactein-protects-pancreatic-%C3%AE-cells-against-methylglyoxal-induced-oxidative-cell-damage-by-the-upregulation-of-mitochondrial-biogenesis
#10
Kwang Sik Suh, Eun Mi Choi, Woon-Won Jung, Yu Jin Kim, Soo Min Hong, So Yong Park, Sang Youl Rhee, Suk Chon
Methylglyoxal (MG) is one of the major precursors of advanced glycation end products (AGEs), which are considered to be one of the causes of diabetes and its complications. The root and rhizomes of black cohosh (Cimicifuga racemosa) have long been used medicinally, and deoxyactein is one of its major constituents. In the present study, the protective effects of deoxyactein against MG-induced oxidative cell damage were investigated in insulin-producing pancreatic β-cells. We found that deoxyactein protected the pancreatic β-cells against MG-induced cell death...
June 12, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28625979/intestine-specific-homeobox-gene-isx-integrates-interleukin-6-signaling-tryptophan-catabolism-and-immune-suppression
#11
Li-Ting Wang, Shyh-Shin Chiou, Chee-Yin Chai, Edward Hsi, Kazunari K Yokoyama, Shen-Nien Wang, Shau-Ku Huang, Shih-Hsien Hsu
The intestine-specific homeobox transcription factor ISX is an IL-6-inducible proto-oncogene implicated in the development of hepatocellular carcinoma (HCC), but its mechanistic contributions to this process are undefined. In this study, we provide evidence that ISX mediates a positive feedback loop integrating inflammation, tryptophan cataboism and immune suppression. We found that ISX mediated IL-6-induced expression of the tryptophan catabolic enzymes IDO1 and TDO2 in HCC cells, resulting in an ISX-dependent increase in the tryptophan catabolite kynurenine and its receptor aryl hydrocarbon receptor (AHR)...
June 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28625263/-bacterial-endotoxin-induced-endothelial-cell-injury-and-calcium-overload-associated-with-toll-like-receptor-and-calcium-signal
#12
Jianguo Xiao, Qing Song, Tanshi Li, Rongju Sun
OBJECTIVE: To explore the effect of toll-like receptor 4 (TLR4), myeloid differentiation protein-2 (MD2), and stromal interaction molecular 1 (STIM1) for regulating human vascular endothelial calcium overload injury and inflammatory reaction induced by bacterial endotoxin (LPS). METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured in Dulbecco's modification of Eagle's medium (DMEM). (1) The levels of TLR4, MD2 and nuclear factor-κB (NF-κB) were detected by reverse transcriotion-polymerase chain reaction (RT-PCR) before and 0...
February 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28621526/orthogonal-mass-spectrometry-based-footprinting-for-epitope-mapping-and-structural-characterization-the-il-6-receptor-upon-binding-of-protein-therapeutics
#13
Ke Sherry Li, Guodong Chen, Jingjie Mo, Richard Y-C Huang, Ekaterina G Deyanova, Brett R Beno, Steve O'Neil, Adrienne A Tymiak, Michael L Gross
Higher order structure (HOS) is a crucial determinant for the biological functions and quality attributes of protein therapeutics. Mass spectrometry (MS)-based protein footprinting approaches play an important role in elucidating the relationship between protein biophysical properties and structure. Here, we describe the use of a combined method including hydrogen-deuterium exchange (HDX), fast photochemical oxidation of proteins (FPOP) and site-specific carboxyl group footprinting to investigate the HOS of protein and protein complexes...
June 16, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28621212/methamphetamine-causes-neurotoxicity-by-promoting-polarization-of-macrophages-and-inflammatory-response
#14
X Li, F Wu, L Xue, B Wang, J Li, Y Chen, T Chen
Macrophages, especially their activation state, are closely related to the progression of neurotoxicity. Classically activated macrophages (M1) are proinflammatory effectors, while alternatively activated macrophages (M2) exhibit anti-inflammatory properties. As a powerful addictive psychostimulant drug, coupled with its neurotoxicity, methamphetamine (Meth) abuse may lead to long-lasting abnormalities in the neuronal system. The present study investigated the effect of Meth at subtoxic concentration on macrophage activation state and its underlying toxicity to neuronal cells...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28619762/impaired-tnf-tnfr2-signaling-enhances-th2-and-th17-polarization-and-aggravates-allergic-airway-inflammation
#15
Xiao-Ming Li, Xi Chen, Wen Gu, Yi-Jia Guo, Yi Cheng, Juan Peng, Xue-Jun Guo
CD4+T cell differentiation plays an important role in allergic airway diseases. Tumor necrosis factor receptor 2 (TNFR2) has been shown to regulate CD4+T lymphocyte differentiation, but its role in allergic airway inflammation is not clear. Here we investigated the role of TNFR2 in allergic airway inflammation. Mouse model was generated by immunization with OVA and intranasal administration of TNFR2 antibody. Airway inflammation and CD4+T cell differentiation were measured in vivo and in vitro. Inhibited TNFR2 signaling aggravated airway inflammation and increased the expression of inflammatory cytokines (IL-4, IL-5, IL-17, and TNF-α) in serum and bronchoalveolar lavage fluid (BALF)...
June 15, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28619384/risk-stratification-to-determine-the-impact-of-induction-therapy-on-survival-rejection-and-adverse-events-after-pediatric-heart-transplant-a-multi-institutional-study
#16
Chesney Castleberry, Elizabeth Pruitt, Rebecca Ameduri, Kenneth Schowengerdt, Erik Edens, Nancy Hagin, James K Kirklin, David Naftel, Simon Urschel
BACKGROUND: Induction therapy is increasingly being used in pediatric heart transplantation. General versus risk-adapted use remains controversial. We aimed to determine the impact of induction therapy on outcomes after stratifying patients by diagnosis and risk. METHODS: The Pediatric Heart Transplant Study (PHTS) database was used to identify patients (age ≤18 years) who underwent transplantation between January 1, 2001 and December 31, 2014. Patients were excluded if they survived <48 hours or received multiple induction agents...
May 11, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28619064/protective-effect-of-rutin-supplementation-against-cisplatin-induced-nephrotoxicity-in-rats
#17
Ali R Alhoshani, Mohamed M Hafez, Sufia Husain, Abdel Malek Al-Sheikh, Moureq R Alotaibi, Salim S Al Rejaie, Musaad A Alshammari, Mashal M Almutairi, Othman A Al-Shabanah
BACKGROUND: Cisplatin (CP) is commonly used in the treatment of different types of cancer but nephrotoxicity has been a major limiting factor. Therefore, the present study aimed to study the possible protective effect of rutin against nephrotoxicity induced by cisplatin in rats. METHODS: Forty male Wistar albino rats were randomly divided into 4 groups. Rats of group 1 control group intraperitoneal (i.p.) received 2.5 ml/kg, group 2 CP group received single dose 5 mg/kg cisplatin i...
June 15, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28618867/human-articular-chondrocytes-induce-interleukin-2-nonresponsiveness-to-allogeneic-lymphocytes
#18
Satomi Abe, Hitoshi Nochi, Hiroshi Ito
Introduction We previously showed that articular chondrocytes (ACs) have immune privilege and immunomodulatory functions like those of mesenchymal stem cells. To elucidate these mechanisms, we focused on interleukin-2 (IL-2), which plays critical roles in lymphocyte mitogenic activity. The purpose of this study was to explore whether ACs affect the role of IL-2 underlying immunomodulatory functions. Material and Methods Irradiated human ACs from osteoarthritis donors were used. Third-party ACs were added to the mixed lymphocyte reaction (MLR) with or without recombinant human IL-2 (rhIL-2), and the levels of IL-2 and the soluble form of the IL-2 receptor α (sIL-2Rα) protein in supernatant were measured by enzyme-linked immunosorbent assay...
July 2017: Cartilage
https://www.readbyqxmd.com/read/28618089/crh-promotes-human-colon-cancer-cell-proliferation-via-il-6-jak2-stat3-signaling-pathway-and-vegf-induced-tumor-angiogenesis
#19
Xianjun Fang, Yali Hong, Li Dai, Yuanyuan Qian, Chao Zhu, Biao Wu, Shengnan Li
Corticotrophin-releasing hormone (CRH) has been demonstrated to participate in various diseases. Our previous study showed that its receptor CRHR1 mediated the development of colitis-associated cancer in mouse model. However, the detailed mechanisms remain unclear. In this study, we explored the oncogenetic role of CRH/CRHR1 signaling in colon cancer cells. Cell proliferation and colony formation assays revealed that CRH contributed to cell proliferation. Moreover, tube formation assay showed that CRH-treated colon cancer cell supernatant significantly promoted tube formation of human umbilical vein endothelial cells (HUVECs)...
June 15, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28618071/histamine-receptor-2-modifies-inkt-cell-activity-within-the-inflamed-lung
#20
R Ferstl, R Frei, W Barcik, E Schiavi, K Wanke, M Ziegler, N Rodriguez-Perez, D Groeger, P Konieczna, S Zeiter, D Nehrbass, Roger Lauener, C A Akdis, L O'Mahony
BACKGROUND: Histamine is a key immunoregulatory mediator and can dampen proinflammatory responses via activation of histamine receptor 2 (H2 R). The aim of this study was to determine the role of H2 R in modulating lung inflammatory responses. METHODS: H2 R was blocked using famotidine or activated using dimaprit in both the ovalbumin (OVA) and house dust mite extract (HDM) murine models of respiratory inflammation. H2 R-deficient animals and CD1d/ H2 R-deficient animals were utilized to examine the CD1d presentation of lipid antigens (αGal-Cer or OCH) to invariant Natural Killer T (iNKT) cells...
June 15, 2017: Allergy
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