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https://www.readbyqxmd.com/read/28107624/tocilizumab-alendronate-conjugate-for-treatment-of-rheumatoid-arthritis
#1
Hwiwon Lee, Suk Ho Bhang, Jeong Ho Lee, Hyemin Kim, Sei Kwang Hahn
An autoimmune disease of rheumatoid arthritis (RA) causes severe inflammation on the synovial membrane, which results in the destruction of articular cartilage and bone. Here, Tocilizumab (TCZ) - Alendronate (ALD) conjugate is synthesized for the early intervention of RA. A humanized monoclonal antibody of TCZ shows an immunosuppressive effect, targeting interleukin-6 (IL-6) receptor in the RA pathogenesis. ALD is an anti-inflammatory bisphosphonate drug which can bind to the exposed bone surface. ALD is conjugated selectively to N-glycan on Fc region of TCZ using a chemical linker of 3-(2-pyridyldithio) propionyl hydrazide (PDPH) - poly(ethylene glycol) - N-hydroxysuccinimide (PDPH-PEG-NHS)...
January 20, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28107509/development-of-combining-of-human-bronchial-mucosa-models-with-xposeali%C3%A2-for-exposure-of-air-pollution-nanoparticles
#2
Jie Ji, Anna Hedelin, Maria Malmlöf, Vadim Kessler, Gulaim Seisenbaeva, Per Gerde, Lena Palmberg
BACKGROUND: Exposure to agents via inhalation is of great concerns both in workplace environment and in the daily contact with particles in the ambient air. Reliable human airway exposure systems will most likely replace animal experiment in future toxicity assessment studies of inhaled agents. METHODS: In this study, we successfully established a combination of an exposure system (XposeALI) with 3D models mimicking both healthy and chronic bronchitis-like mucosa by co-culturing human primary bronchial epithelial cells (PBEC) and fibroblast at air-liquid interface (ALI)...
2017: PloS One
https://www.readbyqxmd.com/read/28107387/neuronal-cell-death-and-degeneration-through-increased-nitroxidative-stress-and-tau-phosphorylation-in-hiv-1-transgenic-rats
#3
Young-Eun Cho, Myoung-Hwa Lee, Byoung-Joon Song
The underlying mechanisms for increased neurodegeneration and neurocognitive deficits in HIV-infected people are unclear. Therefore, this study was aimed to investigate the mechanisms of increased neurodegeneration in 5-month old male HIV-1 Transgenic (Tg) rats compared to the age- and gender-matched wild-type (WT) by evaluating histological changes and biochemical parameters of the key proteins involved in the cell death signaling and apoptosis. Histological and immunohistochemical analyses revealed decreased neuronal cells with elevated astrogliosis in HIV-1 Tg rats compared to WT...
2017: PloS One
https://www.readbyqxmd.com/read/28107277/suppressive-effect-of-1%C3%AE-25-dihydroxyvitamin-d3-on-th17-immune-responses-in-kidney-transplant-recipients-with-tacrolimus-based-immunosuppression
#4
Byung Ha Chung, Bo-Mi Kim, Kyoung Chan Doh, Ji-Won Min, Mi-La Cho, Kyoung Woon Kim, Chul Woo Yang
BACKGROUND: The aim of this study was to investigate whether 1α,25-dihydroxyvitamin D3 can regulate Th17-related-immune responses in kidney transplant recipients (KTRs) being treated with tacrolimus (Tac)-based immunosuppression. METHODS: First, we evaluated the effect of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) on Th17-immune responses in an in vitro study using peripheral blood mononuclear cells (PBMCs) from healthy volunteers or KTRs. Next, we investigated mTOR/STAT3 signaling as a mechanism by which 1,25(OH)2D3 exerted its effect on T cells using the Jurkat cell line...
October 6, 2016: Transplantation
https://www.readbyqxmd.com/read/28107179/nuclear-prmt5-cyclin-d1-and-il-6-are-associated-with-poor-outcome-in-oropharyngeal-squamous-cell-carcinoma-patients-and-is-inversely-associated-with-p16-status
#5
Bhavna Kumar, Arti Yadav, Nicole V Brown, Songzhu Zhao, Michael J Cipolla, Paul E Wakely, Alessandra C Schmitt, Robert A Baiocchi, Theodoros N Teknos, Matthew Old, Pawan Kumar
Protein arginine methyltransferase-5 (PRMT5) plays an important role in cancer progression by repressing the expression of key tumor suppressor genes via the methylation of transcriptional factors and chromatin-associated proteins. However, very little is known about the expression and biological role of PRMT5 in head and neck cancer. In this study, we examined expression profile of PRMT5 at subcellular levels in oropharyngeal squamous cell carcinoma (OPSCC) and assessed its correlation with disease progression and patient outcome...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28106785/ketamine-analog-methoxetamine-induced-inflammation-and-dysfunction-of-bladder-in-rats
#6
Qiang Wang, Qinghui Wu, Junpeng Wang, Yang Chen, Guihao Zhang, Jiawei Chen, Jie Zhao, Peng Wu
The novel synthetic psychoactive ketamine analog methoxetamine is reportedly being used for recreational purposes. As ketamine use can result in urinary dysfunction, we conducted the present study to investigate how methoxetamine affects the bladder. A cystometry investigation showed that female Sprague-Dawley rats experienced increased micturition frequency bladder dysfunction after receiving a daily intraperitoneal injection of 30 mg/kg methoxetamine or ketamine for periods of 4 or 12 weeks. Histologic examinations of rat bladder tissue revealed damaged urothelium barriers, as well as evidence of inflammatory cell infiltration and matrix deposition...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106783/extract-of-polygala-tenuifolia-alleviates-stress-exacerbated-atopy-like-skin-dermatitis-through-the-modulation-of-protein-kinase-a-and-p38-mitogen-activated-protein-kinase-signaling-pathway
#7
Bongjun Sur, Bombi Lee, Ye Seul Yoon, Pooreum Lim, Riwon Hong, Mijung Yeom, Hyang Sook Lee, Hijoon Park, Insop Shim, Hyejung Lee, Young Pyo Jang, Dae-Hyun Hahm
Atopic dermatitis (AD) and stress create a vicious cycle: stress exacerbates atopic symptoms, and atopic disease elicits stress and anxiety. Targeting multiple pathways including stress and allergic inflammation is, therefore, important for treating AD. In this study, we investigated the remedial value of Polygala tenuifolia Willd. (PTW) for treating immobilization (IMO) stress-exacerbated atopy-like skin dermatitis and its underlying mechanism. Trimellitic anhydride (TMA) was applied to dorsal skin for sensitization and subsequently both ears for eliciting T-cell-dependent contact hypersensitivity in mice, which underwent 2 h-IMO stress and PTW administration for the latter 6 and 9 days in the ear exposure period of TMA, respectively...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106546/a-common-variant-of-il-6r-is-associated-with-elevated-il-6-pathway-activity-in-alzheimer-s-disease-brains
#8
Patrick C G Haddick, Jessica L Larson, Nisha Rathore, Tushar R Bhangale, Qui T Phung, Karpagam Srinivasan, David V Hansen, Jennie R Lill, Margaret A Pericak-Vance, Jonathan Haines, Lindsay A Farrer, John S Kauwe, Gerard D Schellenberg, Carlos Cruchaga, Alison M Goate, Timothy W Behrens, Ryan J Watts, Robert R Graham, Joshua S Kaminker, Marcel van der Brug
The common p.D358A variant (rs2228145) in IL-6R is associated with risk for multiple diseases and with increased levels of soluble IL-6R in the periphery and central nervous system (CNS). Here, we show that the p.D358A allele leads to increased proteolysis of membrane bound IL-6R and demonstrate that IL-6R peptides with A358 are more susceptible to cleavage by ADAM10 and ADAM17. IL-6 responsive genes were identified in primary astrocytes and microglia and an IL-6 gene signature was increased in the CNS of late onset Alzheimer's disease subjects in an IL6R allele dependent manner...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106354/adding-dexmedetomidine-to-ropivacaine-for-femoral-nerve-block-inhibit-local-inflammatory-response
#9
Jing Li, Hanghui Wang, Buhuai Dong, Jianbing Ma, Xucai Wu
BACKGROUND: Peripheral nerve block has an anti-inflammatory effect that is confirmed in animal studies, while inconclusive in human studies. Dexmedetomidine (DEX), a highly selective α2-adenoceptor agonist, has a potent anti-inflammatory effect. The aim of this study was to evaluate the effect of DEX added to ropivacaine for femoral nerve block (FNB) on local inflammatory response after total knee arthroplasty (TKA). METHODS: Sixty patients scheduled for TKA were randomized into two equal groups in a prospective randomized study...
January 20, 2017: Minerva Anestesiologica
https://www.readbyqxmd.com/read/28106314/role-of-cytokine-changes-in-clozapine-induced-fever-a-cohort-prospective-study
#10
Yuan-Pin Hung, Carol Sheei-Meei Wang, Chia-Nan Yen, Hsun-Cheng Chang, Po See Chen, I Hui Lee, Kao Chin Chen, Yen Kuang Yang, Ru-Band Lu, Tzu-Yun Wang
AIM: Clozapine-associated fever is common but the specific cytokine changes and treatment durations that may cause fever remain unknown. We investigate the association between inflammatory cytokine changes and clozapine-induced fever in patients who were treated with clozapine. METHODS: Forty-three patients with schizophrenia or schizoaffective disorder, diagnosed by using the Chinese Version of the Mini International Neuropsychiatric Interview, were treated with clozapine for the first time (first-time use group, n = 22) or more than 6 months (long-term use group, n = 21)...
January 20, 2017: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/28106157/tlr4-antagonist-fp7-inhibits-lps-induced-cytokine-production-and-glycolytic-reprogramming-in-dendritic-cells-and-protects-mice-from-lethal-influenza-infection
#11
Laure Perrin-Cocon, Anne Aublin-Gex, Stefania E Sestito, Kari Ann Shirey, Mira C Patel, Patrice André, Jorge C Blanco, Stefanie N Vogel, Francesco Peri, Vincent Lotteau
Dysregulated Toll-like receptor (TLR)-4 activation is involved in acute systemic sepsis, chronic inflammatory diseases, such as atherosclerosis and diabetes, and in viral infections, such as influenza infection. Thus, therapeutic control of the TLR4 signalling pathway is of major interest. Here we tested the activity of the small-molecule synthetic TLR4 antagonist, FP7, in vitro on human monocytes and monocyte-derived dendritic cells (DCs) and in vivo during influenza virus infection of mice. Our results indicate that FP7 antagonized the secretion of proinflammatory cytokines (IL-6, IL-8, and MIP-1β) by monocytes and DCs (IC50 < 1 μM) and prevented DC maturation upon TLR4 activation by ultrapure lipopolysaccharide (LPS)...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28106119/early-secreted-antigenic-target-of-6-kda-of-mycobacterium-tuberculosis-stimulates-il-6-production-by-macrophages-through-activation-of-stat3
#12
Bock-Gie Jung, Xisheng Wang, Na Yi, Justin Ma, Joanne Turner, Buka Samten
As early secreted antigenic target of 6 kDa (ESAT-6) of Mycobacterium tuberculosis (Mtb) is an essential virulence factor and macrophages are critical for tuberculosis infection and immunity, we studied ESAT-6 stimulated IL-6 production by macrophages. ESAT-6 stimulated significantly higher IL-6 secretion by murine bone marrow derived macrophages (BMDM) compared to culture filtrate protein 10 kDa (CFP10) and antigen 85A. Polymyxin B, an LPS blocker, did not affect ESAT-6 stimulated macrophage IL-6 production...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105603/resuscitation-fluid-composition-affects-hepatic-inflammation-in-a-murine-model-of-early-sepsis
#13
Amanda L Patrick, Peter M Grin, Nicole Kraus, Michelle Gold, Matthew Berardocco, Patricia C Liaw, Alison E Fox-Robichaud
BACKGROUND: Fluid resuscitation is a crucial therapy for sepsis, and the use of balanced fluids and/or isotonic albumin may improve patient survival. We have previously demonstrated that resuscitation with normal saline results in increased hepatic leukocyte recruitment in a murine model of sepsis. Given that clinical formulations of albumin are in saline, our objectives were to develop a novel balanced electrolyte solution specifically for sepsis and to determine if supplementing this solution with albumin would improve the inflammatory response in sepsis...
December 2017: Intensive Care Medicine Experimental
https://www.readbyqxmd.com/read/28105508/euterpe-oleracea-mart-seed-extract-protects-against-renal-injury-in-diabetic-and-spontaneously-hypertensive-rats-role-of-inflammation-and-oxidative-stress
#14
Viviane da Silva Cristino Cordeiro, Graziele Freitas de Bem, Cristiane Aguiar da Costa, Izabelle Barcellos Santos, Lenize Costa Reis Marins de Carvalho, Dayane Teixeira Ognibene, Ana Paula Machado da Rocha, Jorge José de Carvalho, Roberto Soares de Moura, Angela Castro Resende
PURPOSE: Euterpe oleracea Mart. (açaí) seed extract (ASE), through its anti-hypertensive, antioxidant and anti-inflammatory properties, may be useful to treat or prevent human diseases. Several evidences suggest that oxidative stress and inflammation contribute to the pathogenesis of diabetic nephropathy; therefore, we tested the hypothesis that ASE (200 mg/kg(-1)day(-1)) prevents diabetes and hypertension-related oxidative stress and inflammation, attenuating renal injury. METHODS: Male rats with streptozotocin (STZ)-induced diabetes (D), and spontaneously hypertensive rats with STZ-induced diabetes (DH) were treated daily with tap water or ASE (D + ASE and DH + ASE, respectively) for 45 days...
January 20, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28105362/pre-treatment-serum-inflammatory-cytokines-as-survival-predictors-of-patients-with-nasopharyngeal-carcinoma-receiving-chemoradiotherapy
#15
Adel F Al-Kholy, Omminea A Abdullah, Mamdouh Z Abadier, Manal M Hassaan, Mohamed F Shindy, Dalia M Nor El-Dien, Ali Hasaneen
The present study aimed to examine the predictability of pre-treatment serum levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α for determining the outcome of patients with nasopharyngeal carcinoma (NPC) assigned for chemoradiotherapy. A total of 35 patients with NPC were subjected to clinical examination and evaluation of performance status using Karnofsky scoring. Nasopharyngoscopy was performed for evaluation and to obtain a biopsy. Blood samples were obtained pre- and post-treatment for polymerase chain reaction quantitative estimation of Epstein-Barr virus (EBV) DNA plasma load and enzyme-linked immunosorbent assay for estimation of serum cytokines...
December 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28105173/interleukin-6-promotes-tumor-progression-in-colitis-associated-colorectal-cancer-through-hif-1%C3%AE-regulation
#16
Jun Han, Qiulei Xi, Qingyang Meng, Jingzheng Liu, Yongxian Zhang, Yusong Han, Qiulin Zhuang, Yi Jiang, Qiurong Ding, Guohao Wu
Interleukin-6 (IL-6) is a well-known etiological factor of colitis-associated colorectal cancer (CAC) and has a significant role in CAC progression. In addition, hypoxia-inducible factor 1α (HIF-1α) serves a primary role in the progression of CAC. However, the association between IL-6 and HIF-1α during the progression of CAC remains unclear. To investigate this association, the present study induced CAC in a mouse model using azoxymethane and dextran sulfate sodium. In addition, an anti-IL-6 receptor antibody was used to inhibit IL-6...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105083/effects-of-glutamine-on-markers-of-intestinal-inflammatory-response-and-mucosal-permeability-in-abdominal-surgery-patients-a-meta-analysis
#17
Xiao-Liang Shu, Ting-Ting Yu, Kai Kang, Jian Zhao
The present meta-analysis was carried out to determine whether supplementation with glutamine (Gln) would reduce the intestinal inflammatory response and mucosal permeability in patients undergoing abdominal surgery. The PubMed, EMBASE, Web of Science, and The Cochrane Library databases were searched for randomized controlled trials on the effects of supplementation with Gln, and published from August, 1966 to June 2014. Inclusion criteria for the meta-analysis were: i) Study design was a randomized controlled trial, ii) study included patients undergoing abdominal surgery, iii) study patients received a supplementation with Gln peptide (Ala-Gln or Gly-Gln) whereas control patients did not use any supplements, and iv) study outcomes included inflammatory markers [C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6, and IL-2 receptor] and markers of intestinal permeability [lactulose/mannitol, diamine oxidase, D(-)lactic acid, and endotoxin]...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28104982/mirna-133a-ucp2-pathway-regulates-inflammatory-bowel-disease-progress-by-influencing-inflammation-oxidative-stress-and-energy-metabolism
#18
Xi Jin, Dong Chen, Ruo-Heng Zheng, Hong Zhang, Yi-Peng Chen, Zun Xiang
AIM: To investigate the role of the miR-133a-UCP2 pathway in the pathogenesis of inflammatory bowel disease (IBD) and to explore the potential downstream mechanisms with respect to inflammation, oxidative stress and energy metabolism. METHODS: C57BL/6 mice were fed dextran sulfate sodium (DSS) liquid for 7 consecutive days, followed by the administration of saline to the DSS group, UCP2 siRNA to the UCP2 group and a miR-133a mimic to the miR-133a group on days 8 and 11...
January 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28104981/sodium-butyrate-attenuates-high-fat-diet-induced-steatohepatitis-in-mice-by-improving-gut-microbiota-and-gastrointestinal-barrier
#19
Da Zhou, Qin Pan, Feng-Zhi Xin, Rui-Nan Zhang, Chong-Xin He, Guang-Yu Chen, Chang Liu, Yuan-Wen Chen, Jian-Gao Fan
AIM: To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. METHODS: Male C57BL/6J mice were divided into three groups, normal control were fed standard chow and model group were fed a high-fat diet (HFD) for 16 wk, the intervention group were fed HFD for 16 wk and treated with NaB for 8 wk. Gut microbiota from each group were detected at baseline and at 16 wk, liver histology were evaluated and gastrointestinal barrier indicator such as zonula occluden-1 (ZO-1) were detected by immunohistochemistry and realtime-PCR, further serum or liver endotoxin were determined by ELISA and inflammation- or metabolism-associated genes were quantified by real-time PCR...
January 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28104778/probiotic-strains-modulate-cytokine-production-and-the-immune-interplay-between-human-peripheral-blood-mononucear-cells-and-colon-cancer-cells
#20
Meir Djaldetti, Hanna Bessler
BACKGROUND: Human health is tightly connected with a great number of gut microbial cells designated as microbiome or microbiota. We have examined the effect of six microbial strains (MS) included in a commercial probiotic on cytokine production by human peripheral blood mononuclear cells (PBMC) and on their immune dialog with colon carcinoma cells. METHODS: Non-stimulated and lipopolysaccharide (LPS) stimulated PBMC were incubated for 24 hours with MS. The secretion of tumor necrosis factor alpha (TNFα), IL-1β, IL-6, interferon gamma (IFNγ), IL-10, and IL-1ra, as well as the effect of MS on the immune interplay between PBMC and cells from HT-29 and RKO colon carcinoma lines were evaluated...
January 18, 2017: FEMS Microbiology Letters
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