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Mitra Nadali, Rille Pullerits, Karin M E Andersson, Sofia Töyrä Silfverswärd, Malin C Erlandsson, Maria I Bokarewa
Despite the predominance of female patients and uncommon obesity, rheumatoid arthritis (RA) is tightly connected to increased cardiovascular morbidity. The aim of this study was to investigate transcriptional activity in the subcutaneous white adipose tissue (WAT) with respect to this disproportionate cardiovascular risk (CVR) in RA. CVR was estimated in 182 female patients, using the modified Systematic Coronary Risk Evaluation scale, and identified 93 patients with increased CVR. The overall transcriptional activity in WAT was significantly higher in patients with CVR and was presented by higher serum levels of WAT products leptin, resistin and IL-6 (all, p < 0...
November 13, 2017: International Journal of Molecular Sciences
Yuan Zhang, Lu Luo, Chao Han, Handeng Lv, Di Chen, Guoliang Shen, Kaiqi Wu, Suwei Pan, Faqing Ye
We designed and synthesized 26 prototype compounds and studied their anti-inflammatory activity and underlying molecular mechanisms. The inhibitory effects of the compounds on the production of nitric oxide (NO), cytokines, inflammatory-related proteins, and mRNAs in lipopolysaccharide (LPS)-stimulated macrophages were determined by the Griess assay, Enzyme linked immunosorbent assay (ELISA), Western blot analysis, and Reverse transcription-Polymerase Chain Reaction (RT-PCR), respectively. Our results indicated that treatment with A2, A6 and B7 significantly inhibited the secretion of NO and inflammatory cytokines in RAW264...
November 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Ana do Vale, Cassilda Pereira, Carlos R Osorio, Nuno M S Dos Santos
AIP56 (apoptosis-inducing protein of 56 kDa) is a key virulence factor of Photobacterium damselae subsp. piscicida (Phdp), the causative agent of a septicaemia affecting warm water marine fish species. Phdp-associated pathology is triggered by AIP56, a short trip AB toxin with a metalloprotease A domain that cleaves the p65 subunit of NF-κB, an evolutionarily conserved transcription factor that regulates the expression of inflammatory and anti-apoptotic genes and plays a central role in host responses to infection...
November 14, 2017: Toxins
Zsolt Czimmerer, Attila Horvath, Bence Daniel, Gergely Nagy, Ixchelt Cuaranta-Monroy, Mate Kiss, Zsuzsanna Kolostyak, Szilard Poliska, Laszlo Steiner, Nikolas Giannakis, Tamas Varga, Laszlo Nagy
MicroRNAs are important components of the post-transcriptional fine-tuning of macrophage gene expression in physiological and pathological conditions. However, the mechanistic underpinnings and the cis-acting genomic factors of how macrophage polarizing signals induce miRNA expression changes are not well characterized. Therefore, we systematically evaluated the transcriptional basis underlying the inflammation-mediated regulation of macrophage microRNome using the combination of different next generation sequencing datasets...
November 10, 2017: Biochimica et Biophysica Acta
Keila Lopes Mendes, Deborah de Farias Lelis, Sérgio Henrique Sousa Santos
The regulation of chronic inflammation has received considerable research attention in recent years because of its contribution to the pathogenesis of chronic diseases such as arthritis, diabetes, metabolic syndrome and obesity. Thus, strategies that inhibit the inflammatory state may be beneficial in improving the pathophysiology of several inflammation-related disorders. Sirtuins are a family of histone deacetylases that contain seven enzymatic activities in mammals (SIRT1-SIRT7) and function to suppress gene transcription by epigenetic mechanisms...
November 7, 2017: Cytokine & Growth Factor Reviews
Yue Yang, Ronge Xing, Song Liu, Yukun Qin, Kecheng Li, Huahua Yu, Pengcheng Li
To investigate the immunostimulatory effects of chitosan sulfates, we prepared α- and β-chitosan sulfates with different molecular weights and compared their immunostimulatory activities in RAW 264.7 macrophages. Results suggest that β-chitosan sulfates were more active than α-chitosan in promoting nitric oxide (NO) production. Further study show that β-chitosan sulfate significantly promoted the production of NO, prostaglandin E2, tumor necrosis factor (TNF)-α, interleukin-6 and interleukin-1β at the levels of transcription and translation...
November 9, 2017: International Journal of Biological Macromolecules
Kenta Saito, Yoichi Matsuo, Hiroyuki Imafuji, Tomotaka Okubo, Yuzo Maeda, Takafumi Sato, Tomoya Shamoto, Ken Tsuboi, Mamoru Morimoto, Hiroki Takahashi, Hideyuki Ishiguro, Shuji Takiguchi
Xantohumol, a prenylated chalcone from hops (Humulus lupulus L.), has been shown to inhibit proliferation in some cancers. However, little is known regarding the effects of xanthohumol in pancreatic cancer. We have previously reported that activation of the transcription factor nuclear factor-κB (NF-κB) plays a key role in angiogenesis in pancreatic cancer. In this study, we investigated whether xanthohumol inhibited angiogenesis by blocking NF-κB activation in pancreatic cancer in vitro and in vivo. We initially confirmed that xanthohumol significantly inhibited proliferation and NF-κB activation in pancreatic cancer cell lines...
November 9, 2017: Cancer Science
Christine M Gross, Manuela Kellner, Ting Wang, Qing Lu, Xutong Sun, Evgeny A Zemskov, Satish Noonepalle, Archana Kangath, Sanjiv Kumar, Manuel Gonzalez-Garay, Ankit A Desai, Saurabh Aggarwal, Boris Gorshkov, Christina Klinger, Alexander D Verin, John D Catravas, Jeffrey R Jacobson, Jason X-J Yuan, Ruslan Rafikov, Joe G N Garcia, Stephen M Black
One of the early events in the progression of lipopolysaccharide (LPS)-mediated acute lung injury (ALI) in mice is the disruption of the pulmonary endothelial barrier resulting in lung edema. However, the molecular mechanisms by which the endothelial barrier becomes compromised remain unresolved. The SRY-related High Mobility Group box (Sox) group-F family member, Sox18, is a barrier- protective protein through its ability to increase the expression of the tight junction protein, Claudin-5. Thus, the purpose of this study was to determine if down-regulation of the Sox18-Claudin-5 axis plays a role in the pulmonary endothelial barrier disruption associated with LPS exposure...
November 8, 2017: American Journal of Respiratory Cell and Molecular Biology
Yali Zhang, Mimi Wang, Huanhuan Dong, Xiaomin Yu, Jingfang Zhang
The development of diabetes mellitus (DM) is accompanied by hyperglycemia-induced oxidative stress. Hyperoside is a major bioactive component in Zanthoxylum bungeanum leaves (HZL) and is a natural antioxidant. However, the effects of HZL on DM and its mechanisms of action remain undefined. The present study evaluated the anti-hypoglycemic and hepatocyte-protective effects of HZL in mice with diabetes induced by a high-carbohydrate/high-fat diet (HFD) and alloxan. We also aimed to eludicate the underlying mechanisms...
October 25, 2017: International Journal of Molecular Medicine
In-Hye Kim, Mi-Jin Kwon, Jae-Hun Jung, Taek-Jeong Nam
Acute renal failure is a serious complication of treatment with the anticancer drug cisplatin. Cisplatin exerts a cytotoxic effect on renal cells by inducing apoptosis through activating the tumor suppressor p53, nuclear factor‑κB (NF‑κB) and mitogen‑activated protein kinase (MAPK)/p38 pathways. Effects of protein extracts of the brown seaweed Porphyra yezoensis (P. yezoensis) on cytotoxicity, inflammation and cell proliferation have been reported; however, the effects of P. yezoensis protein (PYP) extract on cisplatin‑induced renal injury have remained elusive...
October 26, 2017: International Journal of Molecular Medicine
Ge Hu, Dong Hong, Tao Zhang, Huiqin Duan, Panying Wei, Xinxin Guo, Xiang Mu
The present study was conducted to isolate anti-inflammatory compound from Cynanchum atratum and investigate the molecular mechanisms of active compound against lipopolysaccharide (LPS)-induced mastitis in mice. Bioassay-guided fractionations and isolation (via ex vivo tests) of compounds with anti-inflammatory activity were performed on roots of C. atratum yielding a pure bioactive compound: Cynatratoside-C, identified by comparing spectral data (EI-MS, (1)H NMR and (13)C NMR) with literature values. Ex vivo tests showed that Cynatratoside-C inhibited the expression of TLR4 and pro-inflammatory cytokine (TNF-α, IL-6 and IL-1β) production in LPS-stimulated primary mouse mammary epithelial cells...
November 4, 2017: Chemico-biological Interactions
Jingjing Hou, Shihao Jiang, Jiabao Zhao, Dong Zhu, Xinmeng Zhao, Jian-Chun Cai, Si Qing Zhang
NF-κB is a major regulator of gene transcription involved in immune, inflammation, apoptosis and stress responses. However, the regulation of NF-κB is not completely understood. Here, we report that the N-Myc and STATs Interactor (NMI), an IFN-inducible protein, is an important negative regulator of NF-κB activity. We found that NMI negatively regulates TNF-α-induced IL-6 and IL-1β production in HeLa cells. Overexpression of NMI inhibits NF-κB transcriptional activity, in contrast, depletion of NMI by shRNA increases NF-κB transcriptional activity...
November 6, 2017: Scientific Reports
Xiao-Yan Bai, Shujing Li, Miao Wang, Xiahui Li, Yangyang Yang, Zhaowei Xu, Bowen Li, Yanan Li, Kangkai Xia, Huan Chen, Huijian Wu
Krüppel-like factor 9 (KLF9) plays critical roles in several types of tumor. However, the biological functions and the underlying mechanisms of KLF9 in breast cancer metastasis are still unknown. Here, we found the expression of KLF9 was significantly down-regulated in breast cancer and was inversely correlated with the expression of matrix metalloproteinase 9 (MMP9) in breast cancer patients. Functionally, KLF9 transcriptionally down-regulated MMP9 expression and inhibited the metastasis of breast cancer cells...
October 26, 2017: Cancer Letters
Basile Siewe, Allison J Nipper, Haewon Sohn, Jack T Stapleton, Alan Landay
In autoimmune diseases, toll-like receptor (TLR)-stimulated pro-inflammatory IL-6-secreting B cells exert pathogenic roles. Similarly, B cell Fc receptor-like 4 (FcRL4) expression amplifies TLR stimulation, and in rheumatoid arthritis patients, FcRL4 expression identifies a pro-inflammatory B cell subset. B cells from HIV-infected subjects also express heightened levels of FcRL4 and secrete high levels of IL-6: a critical mediator of HIV disease progression. In this study, we sought to determine if FcRL4 identifies a pro-inflammatory B cell subset in HIV-infected subjects and further elucidate the mechanisms underlying FcRL4 amplification of TLR stimulation...
2017: Frontiers in Immunology
Ahmed M Kabel, Aliaa Atef, Remon S Estfanous
The aim of this study was to assess the effect of sitagliptin with or without resveratrol on carcinogen-induced clear cell renal cell carcinoma. Sixty male Wistar rats were divided into 6 equal groups as follows: control; clear cell renal cell carcinoma group; clear cell renal cell carcinoma+sitagliptin group; clear cell renal cell carcinoma+resveratrol group; clear cell renal cell carcinoma+carboxymethyl cellulose group and clear cell renal cell carcinoma+sitagliptin+resveratrol group. Blood urea, serum creatinine, creatinine clearance, urinary N-acetyl beta-d-glucosaminidase (NAG), gamma glutamyl transpeptidase (GGT) and urinary albumin excretion rate (UAER) were determined...
November 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Changwei Li, Kaizhe Chen, Hui Kang, Yufei Yan, Kewei Liu, Changjun Guo, Jin Qi, Kai Yang, Fei Wang, Lei Guo, Chuan He, Lianfu Deng
Pattern recognition receptors (PRRs), including Toll-like receptor 3 (TLR3), are involved in arthritic responses; however, whether interleukin-33 (IL-33) is involved in TLR3-mediated cartilage degeneration is unknown. Here, we found that IL-33 was abundantly increased in chondrocytes of osteoarthritis, especially the chondrocytes of weight-bearing cartilage. Furthermore, double-stranded RNA (dsRNA) released from damaged articular chondrocytes induced by mechanical stretching upregulated IL-33 expression to a greater degree than IL-1β and tumor necrosis factor-α...
November 2, 2017: Cell Death & Disease
Zi'ang Xie, Hejun Yu, Xuewu Sun, Pan Tang, Zhiwei Jie, Shuai Chen, Jiying Wang, An Qin, Shunwu Fan
Osteoporosis develops due to impaired bone formation and/or excessive bone resorption. Although the pharmacological treatment of osteoporosis has been extensively developed, alternative treatments are still needed. Here, we showed that oridonin (ORI), a diterpenoid isolated from Rabdosia rubescens, can suppress osteoclastogenesis and enhance osteogenesis. ORI inhibited the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast formation and bone resorption through the inhibition of p65 nuclear translocation...
November 1, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Honghai Hong, Yingmin Zeng, Wenxuan Jian, Lei Li, Liying Lin, Yousheng Mo, Meiling Liu, Shuhuan Fang, Yong Xia
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, joint tenderness and destruction of synovial joints, leading to severe disability. Anti-inflammatory drugs and disease-modifying anti-rheumatic drugs (DMARDs) may improve RA process. However, in most patients the treatment effect is still not satisfactory. Cyclin-dependent kinase 7 (CDK7) plays a well-established role in the regulation of the eukaryotic cell division cycle, and recent studies indicated that it exerted anti-inflammatory effect...
October 30, 2017: Journal of Cellular and Molecular Medicine
Xianglian Liu, Deyu Huang, Pu Guo, Qinghua Wu, Menghong Dai, Guyue Cheng, Haihong Hao, Shuyu Xie, Zonghui Yuan, Xu Wang
Chronic exposure to low dose of T-2 toxin causes growth retardation and reduced body weight, resulting in economic losses. Excessive inflammatory cytokines and GH deficiency are important mechanisms that contribute to growth inhibition induced by T-2 toxin. However, the regulation of the inflammatory cytokines expecially IL-6, IL-1β, and TNF-α induced by T-2 toxin still remained unclear. The new transcription factor AKNA, belonging to AT-hook protein family, is closely associated with inflammation. However, it was unclear how AKNA regulate the expression of inflammatory cytokines, and there was no report on the role of AKNA in T-2 toxin mediated toxicity...
October 25, 2017: Toxicology
Byungki Jang, Akihito Ishigami, Yong-Sun Kim, Eun-Kyoung Choi
The conversion of peptidylarginine into peptidylcitrulline by calcium-dependent peptidylarginine deiminases (PADs) has been implicated in the pathogenesis of a number of diseases, identifying PADs as therapeutic targets for various diseases. The PAD inhibitor Cl-amidine ameliorates the disease course, severity, and clinical manifestation in multiple disease models, and it also modulates dendritic cell (DC) functions such as cytokine production, antigen presentation, and T cell proliferation. The beneficial effects of Cl-amidine make it an attractive compound for PAD-targeting therapeutic strategies in inflammatory diseases...
October 27, 2017: International Journal of Molecular Sciences
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