Although neutrophil extracellular traps (NETs) form to prevent dissemination of pathogenic microorganisms, excessive release DNA and DNA-associated proteins can also perpetuate sterile inflammation. In this study, we found that the danger-associated molecular pattern protein high-mobility group box 1 (HMGB1) induce NET formation. formation was after exposure wild-type receptor for advanced glycation end products-deficient HMGB1, whereas deficiency Toll-like (TLR)4 diminished ability...

Although resistin was recently found to modulate insulin resistance in preclinical models of type II diabetes and obesity, recent studies also suggested that has proinflammatory properties. We examined whether the human-specific variant affects neutrophil activation severity LPS-induced acute lung injury. Because human mouse have distinct patterns tissue distribution, experiments were performed using humanized mice exclusively express (hRTN(+/-)(/-)) but are deficient resistin. Enhanced...

Abstract An inability of neutrophils to eliminate invading microorganisms is frequently associated with severe infection and may contribute the high mortality rates sepsis. In present studies, we examined whether metformin other 5′ adenosine monophosphate-activated protein kinase (AMPK) activators affect neutrophil motility, phagocytosis bacterial killing. We found that activation AMPK enhanced chemotaxis in vitro vivo , also counteracted inhibition induced by exposure lipopolysaccharide...

Although AMP-activated protein kinase (AMPK) is involved in regulating carbohydrate and lipid metabolism, activated AMPK also plays an anti-inflammatory role many cell populations. However, despite the ability of activation to diminish severity inflammatory responses, previous studies have found that activity diminished LPS-treated neutrophils lungs mice with LPS-induced acute lung injury (ALI). Since GSK3β participates activity, we examined potential roles for modulating macrophages...

We aimed to identify miRNAs whose expression levels in fetal tissues are altered by exposure a diabetic milieu and elucidate the impact on target protein expression. Gestational diabetes mellitus (GDM) affects both immediate future disease risk offspring. hypothesized that GDM alters miRNA human umbilical vein endothelial cells (HUVECs) may influence metabolic processes. A cross-sectional design compared differences HUVECs abundance placentae between infants of women with (IGDM) born...

Defective clearance of apoptotic cells is frequently associated with perpetuation inflammatory conditions. Our results show a rapid activation AMP-activated kinase (AMPK) in macrophages upon exposure to or lysophosphatidylcholine, specific phospholipid that produced and released from dying cells. AMPK resulted inhibition mitochondrial oxygen consumption ATP production further depended on Ca(2+) mobilization reactive species generation. Once activated, increased microtubule synthesis...

Alterations in metabolic and bioenergetic homeostasis contribute to sepsis-mediated organ injury. However, how AMP-activated protein kinase (AMPK), a major sensor regulator of energy expenditure production, affects development injury loss innate capacity during polymicrobial sepsis remains unclear. In the present experiments, we found that cross-talk between AMPK GSK3β signaling pathways controls chemotaxis ability neutrophils macrophages kill bacteria ex vivo. mice with abdominal or more...

Objective This study aimed to investigate cellular sources of microRNAs (miRNA) within adipose tissue and the impact obesity on miRNA expression, as well examine targets miRNAs. Methods expression by quantitative polymerase chain reaction was examined in adipocytes, macrophages (ATM), peripheral blood mononuclear cells from individuals with normal weight obesity. Differentiated 3T3‐L1 adipocytes were cocultured macrophages, differentiated human mesenchymal stem transfected miR‐155,...

Abstract Adverse maternal environments, such as diabetes and obesity, impair placental mitochondrial function, which affects fetal development offspring long-term health. The underlying mechanisms effective interventions to abrogate effect remain unclear. Our previous studies demonstrated impaired biogenesis in male human placenta of diabetic mothers. In the present studies, epigenetic marks possibly related placentae women with (n = 23) controls were analyzed. Effects metformin examined...

Background The molecular backgrounds that determine therapeutic effectiveness in esophageal cancer remain largely unknown. Breast susceptibility gene 1 (BRCA1) expression has been found to switch the response cisplatin- or paclitaxel-based chemotherapy. It remains unclear how variations BRCA1 influence clinical outcomes cancer. Patients and Methods Quantitative real-time polymerase chain reaction (qPCR) was performed examine mRNA expressions paraffin-embedded specimens from 144 patients with...

Abstract Effective removal of apoptotic cells, particularly neutrophils, is essential for the successful resolution acute inflammatory conditions. In these experiments, we found that whereas interaction between vitronectin and integrins diminished ability macrophages to ingest with urokinase-type plasminogen activator receptor (uPAR) on surface cells also had equally important inhibitory effects efferocytosis. Preincubation inhibitor-1 eliminated its inhibit phagocytosis cells. Similarly,...

Hyperglycemia and insulin resistance induced by acute injuries or critical illness are associated with increased mortality morbidity, as well later development of type 2 diabetes. The molecular mechanisms underlying the onset following remain poorly understood. In present studies, roles serine kinases, inhibitory κB kinase (IKK) c-Jun NH -terminal (JNK), in hepatic were investigated. our animal model diabetes, activation IKK JNK was observed early 15 min, concomitant rapid impairment...

Thermogenic brown or beige adipocytes dissipate energy in the form of heat and thereby counteract obesity related metabolic complications. The miRNA cluster miR-130b/301b is highly expressed adipose tissues has been implicated diseases as a posttranscriptional regulator mitochondrial biogenesis lipid metabolism. We investigated roles regulating adipogenesis vivo vitro. declined progenitor cells during adipogenesis, while forced overexpression miR-130b-3p miR-301b-3p suppressed uncoupling...

Adverse intrauterine environments can cause persistent changes in epigenetic profiles of stem cells, increasing susceptibility the offspring to developing metabolic diseases later life. Effective approaches restore landscape and function cells remain be determined. In this study, we investigated effects pharmaceutical activation AMP-activated protein kinase (AMPK), an essential regulator energy metabolism, on mitochondrial programming Wharton's Jelly mesenchymal (WJ-MSCs) from women with...

Abstract Metabolic and bioenergetic plasticity of immune cells is essential for optimal responses to bacterial infections. AMPK Parkin ubiquitin ligase are known regulate mitochondrial quality control mitophagy that prevents unwanted inflammatory responses. However, it not if this evolutionarily conserved mechanism has been coopted by the host defense eradicate pathogens influence post-sepsis immunosuppression. Parkin, levels, effects activators were investigated in human leukocytes from...

Recombinant adenovirus (Ad) vectors can initiate an inflammatory response, limiting its use in gene therapy and basic research. Despite increased efforts to better understand Ad infection, little is known about how it affects cellular metabolic responses. In the current studies, we explored effects of on insulin signaling molecules glucose homeostasis. Nonreplicative were injected into rats through tail vein, at 4-13 days postinjection tolerance examined. vector infection significantly...

Macrophage-derived factors, including TNF-α, are known as important inducers of insulin resistance. However, the role macrophages in resistance liver is unclear. Hyperglycemia and commonly occur following acute injuries or critical illness, referred to “critical illness diabetes.” In present studies, roles hepatic surgical trauma hemorrhage were investigated. Intravenous administration gadolinium chloride clodronate-liposome resulted depletion both spleen rats. Macrophage by either did not...

Abstract Background Diabetes during pregnancy affects placental mitochondrial content and function, which has the potential to impact fetal development long-term health of offspring. Resistin is a peptide hormone originally discovered in mice as an adipocyte-derived factor that induced insulin resistance. In humans, resistin primarily secreted by monocytes or macrophages. The regulation roles human diabetes remain unclear. Methods Fetal levels were measured cord blood from pregnancies with (...

( Aust N Z J Obstet Gynaecol . 2016;56(4):352–357) The occurrence of type 1 (T1DM) and 2 diabetes (T2DM) during pregnancy is increasing around the world. An understanding differences in insulin requirements between groups may have vital clinical consequences enabling clinicians to respond effectively gestation-specific glycemic alterations, avoid hypoglycemia, identify subgroups for whom additional intervention would be beneficial. This study was a retrospective review conducted examine...

Impaired insulin receptor (IR) activity has been found in various models of resistance, including injury or critical illness and Type 2 diabetes. However, mechanisms that modulate IR function remain unclear. With an animal model critical-illness diabetes, we insulin-induced tyrosine phosphorylation the liver was impaired as early 15 min following trauma hemorrhage. Possible for this defect were examined, protein levels posttranslational modifications. The total amounts hepatic IRα IRβ...