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macrophage and diabetes

Meiling Zhang, Long Pan, Dong Xu, Chuanwu Cao, Rongfeng Shi, Shilong Han, Junping Liu, Xue Li, Maoquan Li
The incidence of Klebsiella pneumoniae liver abscess (KPLA) has increased in a number of Asian countries over the past 30 years. Diabetes mellitus (DM) is a risk factor for KPLA. The prevalence and clinical features of KPLA in patients with and without DM have been well described; however, the underlying molecular mechanism responsible for the increased incidence of KPLA in patients with DM remains unclear. In the present study, a mouse model of DM was constructed and mice were infected with K. pneumoniae ...
June 2018: Experimental and Therapeutic Medicine
Leonardo Roever, Elmiro Santos Resende, Angélica Lemos Debs Diniz, Nilson Penha-Silva, João Lucas O'Connell, Paulo Fernando Silva Gomes, Hugo Ribeiro Zanetti, Anaisa Silva Roerver-Borges, Fernando César Veloso, Fernanda Rodrigues de Souza, Poliana Rodrigues Alves Duarte, Thiago Montes Fidale, Antonio Casella-Filho, Paulo Magno Martins Dourado, Antonio Carlos Palandri Chagas, Sadeq Ali-Hasan-Al-Saegh, Paulo Eduardo Ocke Reis, Rogério de Melo Costa Pinto, Gustavo B F Oliveira, Álvaro Avezum, Mansueto Neto, André Rodrigues Durães, Rose Mary Ferreira Lisboa da Silva, Antonio José Grande, Celise Denardi, Renato Delascio Lopes, Nitesh Nerlekar, Shahab Alizadeh, Adrian V Hernandez, Maria Inês da Rosa, Giuseppe Biondi-Zoccai
INTRODUCTION: The prevalence of metabolic syndrome (MetS) and MetS-related stroke is set to increase dramatically in coming decades. MetS is a complex disease that includes endothelial dysfunction, insulin resistance, diabetes, hypertension, ectopic obesity, and dyslipidaemia and an increased risk of cardiovascular events. One function of high-density lipoprotein (HDL) cholesterol (HDL-C) is the cholesterol-efflux pathway, which is the pathway where cholesterol is removed from macrophages within the arterial walls back into the bloodstream and out to the liver...
June 2018: Medicine (Baltimore)
Vishnu Jayakumar Sunandhakumari, Arun Sadasivan, Elizabeth Koshi, Aswathy Krishna, Aneesh Alim, Aneesh Sebastian
For years the pathogenesis of periodontitis was under an immunological Th1/Th2 paradigm. Th1 cells are considered to afford protection against the intracellular pathogens. These cells produce the interferons (IFN) that are involved in macrophage activation, which, in turn, plays an important role in phagocytosis, complement fixation, and opsonization. Th2 cells are thought to have evolved as a form of protection against parasitic helminthes. Th17 subset of CD4Not Necessary+ T cells was identified in the year 2005, which added greater complexity to Th function and are pro inflammatory in nature...
June 13, 2018: Dentistry journal
Erin D Giles, Sonali Jindal, Elizabeth A Wellberg, Troy Schedin, Steven M Anderson, Ann D Thor, Dean P Edwards, Paul S MacLean, Pepper Schedin
BACKGROUND: Obesity and type II diabetes are linked to increased breast cancer risk in postmenopausal women. Patients treated with the antidiabetic drug metformin for diabetes or metabolic syndrome have reduced breast cancer risk, a greater pathologic complete response to neoadjuvant therapy, and improved breast cancer survival. We hypothesized that metformin may be especially effective when targeted to the menopausal transition, as this is a lifecycle window when weight gain and metabolic syndrome increase, and is also when the risk for obesity-related breast cancer increases...
June 14, 2018: Breast Cancer Research: BCR
Tao Yan, Poornima Venkat, Michael Chopp, Alex Zacharek, Peng Yu, Ruizhuo Ning, Xiaoxi Qiao, Mark R Kelley, Jieli Chen
APX3330 is a selective inhibitor of APE1/Ref-1 redox activity. In this study, we investigate the therapeutic effects and underlying mechanisms of APX3330 treatment in type one diabetes mellitus (T1DM) stroke rats. Adult male Wistar rats were induced with T1DM and subjected to transient middle cerebral artery occlusion (MCAo) and treated with either PBS or APX3330 (10mg/kg, oral gavage) starting at 24h after MCAo, and daily for 14 days. Rats were sacrificed at 14 days after MCAo and, blood brain barrier (BBB) permeability, ischemic lesion volume, immunohistochemistry, cell death assay, Western blot, real time PCR, and angiogenic ELISA array were performed...
June 2018: Aging and Disease
Hung-Wen Liu, Sue-Joan Chang
The clear mechanism of moderate exercise training (Ex) in attenuating muscle loss remains elusive in diabetes. We investigated the effects of moderate exercise training on diabetes-induced nuclear factor-κB (NF-κB) activation and mitochondrial dysfunction. Skeletal muscle size and atrophy signaling pathways were examined in type 2 diabetic db/db mice with or without moderate exercise training (5.2 m/min, 1 h/day, and 5 days/week for a total of 8 weeks). Exercise training decreased serum leptin, MCP-1, and resistin levels in db/db +Ex mice, but it did not reduce symptoms of insulin resistance including hyperglycemia, hyperinsulinemia, and impaired glucose tolerance...
2018: Frontiers in Physiology
Ryutaro Iwabuchi, Shota Ikeno, Mie Kobayashi-Ishihara, Haruko Takeyama, Manabu Ato, Yasuko Tsunetsugu-Yokota, Kazutaka Terahara
Two cytokines, fms-related tyrosine kinase 3 ligand (Flt3-L) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are considered to be the essential regulators of dendritic cell (DC) development in vivo . However, the combined effect of Flt3-L and GM-CSF on human DCs has not been evaluated in vivo . In this study, we, therefore, aimed at evaluating this using a humanized mouse model. Humanized non-obese diabetic/SCID/Jak3null (hNOJ) mice were constructed by transplanting hematopoietic stem cells from human umbilical cord blood into newborn NOJ mice, and in vivo transfection (IVT) was performed by hydrodynamic injection-mediated gene delivery using plasmids encoding human Flt3-L and GM-CSF...
2018: Frontiers in Immunology
Chujun Yuan, Jiyuan Hu, Saj Parathath, Lisa Grauer, Courtney Blachford Cassella, Svetlana Bagdasarov, Ira J Goldberg, Ravichandran Ramasamy, Edward A Fisher
Guidelines to reduce cardiovascular risk in diabetes include aggressive LDL lowering, but benefits are attenuated compared to those in patients without diabetes. Consistent with this, we have reported in mice that hyperglycemia impaired atherosclerosis regression. Aldose reductase (AR) is thought to contribute to clinical complications of diabetes by directing glucose into pathways producing inflammatory metabolites. Mice have low levels of AR, thus, raising them to human levels would be a more clinically relevant model to study changes in diabetes under atherosclerosis regression conditions...
June 11, 2018: Diabetes
Ming Wu, Ruoyu Li, Yanjuan Hou, Shan Song, Weixia Han, Nan Chen, Yunxia Du, Yunzhuo Ren, Yonghong Shi
Thioredoxin-interacting protein (TXNIP) is associated with inflammation, tubulointerstitial fibrosis, and oxidative stress in diabetic kidney disease, yet the potential role of TXNIP in nondiabetic renal injury is not well known. This study aimed to investigate the effect of TXNIP on renal injury by creating a unilateral ureteral obstruction (UUO) model in TXNIP knockout (TKO) mice. We performed sham or UUO surgery in 8-week-old TXNIP KO male mice and age and sex-matched wild-type (WT) mice. Animals were killed at 3, 5, 7, or 14 days after surgery, and renal tissues were obtained for RNA, protein, and other analysis...
June 8, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Florian Kahles, Ana Liberman, Constantin Halim, Matthias Rau, Julia Möllmann, Robert Werner Mertens, Marcia Rückbeil, Irmgard Diepolder, Benedikt Walla, Sebastian Diebold, Mathias Burgmaier, Corinna Lebherz, Nikolaus Marx, Michael Lehrke
OBJECTIVE: The incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) are secreted by the gut after food intake leading to pancreatic insulin secretion and glucose lowering. Beyond its role in glucose control, GLP-1 was found in mice and men to beneficially modulate the process of atherosclerosis, which has been linked to improved cardiovascular outcome of patients with diabetes at high cardiovascular risk treated with GLP-1 receptor agonists...
May 23, 2018: Molecular Metabolism
Junfei Jin, Zhongyang Lu, Yanchun Li, Ji Hyun Ru, Maria F Lopes-Virella, Yan Huang
It has been well established that patients with diabetes or metabolic syndrome (MetS) have increased prevalence and severity of periodontitis, an oral infection initiated by bacteria and characterized by tissue inflammation and destruction. To understand the underlying mechanisms, we have shown that saturated fatty acid (SFA), which is increased in patients with type 2 diabetes or MetS, and LPS, an important pathogenic factor for periodontitis, synergistically stimulate expression of proinflammatory cytokines in macrophages by increasing ceramide production...
June 8, 2018: Journal of Leukocyte Biology
Alicia J Jenkins, Paul Welsh, John R Petrie
PURPOSE OF REVIEW: We provide an overview of recent publications that extend clinically relevant knowledge relating to metformin's effects on lipids and atherosclerotic vascular disease and/or provide insights into the drug's mechanisms of action on the heart and vasculature. RECENT FINDINGS: We focus on original research in humans or in human tissues. Several recently completed randomized clinical trials have reported effects of metformin on surrogate measures of atherosclerotic vascular disease, including carotid-intima media thickness, vascular reactivity and calcification in people with Type 1 (T1D) and Type 2 (T2D) diabetes as well as nondiabetic dysglycaemia...
June 6, 2018: Current Opinion in Lipidology
Catherine A Reardon, Amulya Lingaraju, Kelly Q Schoenfelt, Guolin Zhou, Chang Cui, Hannah Jacobs-El, Ilona Babenko, Andrew Hoofnagle, Daniel Czyz, Howard Shuman, Tomas Vaisar, Lev Becker
Type 2 diabetes (T2D) is associated with increased risk for atherosclerosis; however, the mechanisms underlying this relationship are poorly understood. Macrophages, which are activated in T2D and causatively linked to atherogenesis, are an attractive mechanistic link. Here, we use proteomics to show that diet-induced obesity and insulin resistance (obesity/IR) modulate a pro-atherogenic "macrophage-sterol-responsive-network" (MSRN), which, in turn, predisposes macrophages to cholesterol accumulation...
June 5, 2018: Cell Reports
Mengqi Guo, Jie Xiao, Xi Sheng, Xinyu Zhang, Yuanyuan Tie, Lei Wang, Lang Zhao, Xiaoping Ji
Atherosclerosis (AS) in diabetic patients is often associated with low stability, which might be largely attributed to unfavorable macrophage polarization and increased inflammatory response induced by hyperglycaemia. Ginsenoside Rg3 is one of the main active principles of Panax Ginseng, which has been reported to be a natural ligand of peroxisome proliferator-activated receptor-gamma (PPARγ), a key nuclear transcriptional factor involved in inflammation and macrophage differentiation. However, it remains unclear if Rg3 could exert protective effects on plaque stability in diabetes...
2018: Frontiers in Pharmacology
Lijun Wang, Xiao Ye, Yanyin Hua, Yingxiang Song
Adipose tissue fibrosis is a novel mechanism for the development of obesity related insulin resistance. Berberine (BBR) has been shown to relieve several metabolic disorders, including obesity and type 2 diabetes. However, the effects of BBR on obesity related adipose fibrosis remain poorly understood. The objective of this study was to assess the effects of BBR on adipose tissue fibrosis in high fat diet (HFD)-induced obese mice. The results showed that BBR reduced animal body weight and significantly improved glucose tolerance in HFD mice...
May 28, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Hui Li, Han-Ying Luo, Qing Liu, Yang Xiao, Lin Tang, Feng Zhong, Gan Huang, Jun-Mei Xu, Ai-Min Xu, Zhi-Guang Zhou, Ru-Ping Dai
Background: Glucose fluctuation confers additional risks on diabetes-related vascular diseases, but the underlying mechanisms are unknown. Macrophage activation mediated by TLR4-JNK signaling plays an important role during the progress of diabetes. In the present study, we hypothesize that glucose fluctuation results in macrophage inflammation through TLR4-JNK signaling pathways. Methods: THP-1 cells were treated with normal glucose (5 mM), constant high glucose (25 mM), and intermittent high glucose (rotation per 6 h in 5 mM or 25 mM) for 24 h...
2018: Journal of Immunology Research
Jingyuan Sun, Hongping Deng, Zhen Zhou, Xiaoxing Xiong, Ling Gao
Abdominal aortic aneurysm (AAA) was previously ascribed to weaken defective medial arterial/adventitial layers, for example, smooth muscle/fibroblast cells. Therefore, besides surgical repair, medications targeting the medial layer to strengthen the aortic wall are the most feasible treatment strategy for AAA. However, so far, it is unclear whether such drugs have any beneficial effect on AAA prognosis, rate of aneurysm growth, rupture, or survival. Notably, clinical studies have shown that AAA is highly associated with endothelial dysfunction in the aged population...
2018: Oxidative Medicine and Cellular Longevity
Anant Jaiswal, Sukka Santosh Reddy, Mohita Maurya, Preeti Maurya, Manoj Kumar Barthwal
In human adipose tissue and obesity, miR-99a expression is negatively correlated with inflammation. Therefore, the present study investigated the role of miR-99a in macrophage phenotype activation and adipose tissue inflammation. M2 BMDMs showed a significant increase in miR-99a expression when compared to the M0 and M1 phenotypes. Phenotype-switching experiments established an association between upregulated miR-99a expression and the M2 phenotype. Overexpression of miR-99a prevented M1 phenotype activation and attenuated bactericidal activity...
May 30, 2018: Cellular & Molecular Immunology
Liang Tao, Hongfa Lin, Jingjing Wen, Qi Sun, Yan Gao, Xi Xu, Junsong Wang, Jianfa Zhang, Dan Weng
Endoplasmic reticulum (ER) stress contributes to the development and progression of many chronic inflammatory diseases, including type 2 diabetes, obesity, atherosclerosis, neurodegenerative diseases, and cancer. ER stress has been reported to induce inflammasome activation and release of mature IL-1β, which contributes to many inflammatory diseases. The molecular mechanisms that activate the inflammasome during ER stress are still poorly understood. Here we report that the kinase receptor-interacting protein 1 (RIP1) plays an important role in ER stress-induced activation of inflammasome...
May 29, 2018: Cell Death & Disease
Joan Domingo-Espín, Oktawia Nilsson, Katja Bernfur, Rita Del Giudice, Jens O Lagerstedt
Prolonged hyperglycemia in poorly controlled diabetes leads to an increase in reactive glucose metabolites that covalently modify proteins by non-enzymatic glycation reactions. Apolipoprotein A-I (apoA-I) of high-density lipoprotein (HDL) is one of the proteins that becomes glycated in hyperglycemia. The impact of glycation on apoA-I protein structure and function in lipid and glucose metabolism were investigated. ApoA-I was chemically glycated by two different glucose metabolites (methylglyoxal and glycolaldehyde)...
May 23, 2018: Biochimica et Biophysica Acta
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