Role of Forkhead Transcription Factors in Diabetes-Induced Oxidative Stress

Diabetes is a chronic metabolic disorder, characterized by hyperglycemia resulting from insulin deficiency and/or insulin resistance. Recent evidence suggests that high levels of reactive oxygen species (ROS) and subsequent oxidative stress are key contributors in the development of diabetic complications. The FOXO family of forkhead transcription factors including FOXO1, FOXO3, FOXO4, and FOXO6 play important roles in the regulation of many cellular and biological processes and are critical regulators of cellular oxidative stress response pathways. FOXO1 transcription factors can affect a number of different tissues including liver, retina, bone, and cell types ranging from hepatocytes to microvascular endothelial cells and pericytes to osteoblasts. They are induced by oxidative stress and contribute to ROS-induced cell damage and apoptosis. In this paper, we discuss the role of FOXO transcription factors in mediating oxidative stress-induced cellular response

Thermodynamic analysis and system design of a novel split cycle engine concept

AbstractThe split cycle engine is a new reciprocating internal combustion engine with a potential of a radical efficiency improvement. In this engine, the compression and combustion–expansion processes occur in different cylinders. In the compression cylinder, the charge air is compressed through a quasi-isothermal process by direct cooling of the air. The high pressure air is then heated in a recuperator using the waste heat of exhaust gas before induction to the combustion cylinder. The combustion process occurs during the expansion stroke, in a quasi-isobaric process. In this paper, a fundamental theoretical cycle analysis and one-dimensional engine simulation of the split cycle engine was undertaken. The results show that the thermal efficiency (η) is mainly decided by the CR (compression ratio) and ER (expansion ratio), the regeneration effectiveness (σ), and the temperature rising ratio (N). Based on the above analysis, a system optimization of the engine was conducted. The results showed that by increasing CR from 23 to 25, the combustion and recuperation processes could be improved. By increasing the expansion ratio to 26, the heat losses during the gas exchange stroke were further reduced. Furthermore, the coolant temperatures of the compression and expansion chambers can be controlled separately to reduce the wall heat transfer losses. Compared to a conventional engine, a 21% total efficiency improvement was achieved when the split cycle was applied. It was concluded that through the system optimization, a total thermal efficiency of 53% can be achieved on split cycle engine

Real-time energy management for diesel heavy duty hybrid electric vehicles

In this paper, a fuzzy-tuned equivalent consumption minimization strategy (F-ECMS) is proposed as an intelligent real-time energy management solution for a conceptual diesel engine-equipped heavy duty hybrid electric vehicle (HEV). In the HEV, two electric motors/generators are mounted on the turbocharger shaft and engine shaft, respectively, which can improve fuel efficiency by capturing and storing energy from both regenerative braking and otherwise wasted engine exhaust gas. The heavy duty HEV frequently involved in duty cycles characterized by start-stop events, especially in off-road applications, whose dynamics is analyzed in this paper. The on-line optimization problem is formulated as minimizing a cost function in terms of weighted fuel power and electric power. In the cost function, a cost factor is defined for both improving energy transmission efficiency and maintaining the battery energy balance. To deal with the nonexplicit relationship between HEV fuel economy, battery state of charge (SOC), and control variables, the cost factor is fuzzy tuned using expert knowledge and experience. In relation to the fuel economy, the air-fuel ratio is an important factor. An online search for capable optimal variable geometry turbocharger (VGT) vane opening and exhaust gas recirculation (EGR) valve opening is also necessary. Considering the exhaust emissions regulation in diesel engine control, the boundary values of VGT and EGR actuators are identified by offline design-of-experiment tests. An online rolling method is used to implement the multivariable optimization. The proposed method is validated via simulation under two transient driving cycles, with the fuel economy benefits of 4.43% and 6.44% over the nonhybrid mode, respectively. Compared with the telemetry equivalent consumption minimization strategy, the proposed F-ECMS shows better performance in the sustainability of battery SOC under driving conditions with the rapid dynamics often associated with off-road applications

Effect of Bacteria on the Wound Healing Behavior of Oral Epithelial Cells

Wounded tissue offers opportunity to microflora to adhere, colonize, invade and infect surrounding healthy tissue. The bacteria of the oral cavity have the potential to alter the wound healing process by interacting with keratinocytes. The aim of this study was to investigate mechanisms through which oral bacteria may influence re-epithelialization by interacting with gingival keratinocytes. By an in vitro scratch assay we demonstrate that primary gingival keratinocytes have impaired closure when exposed to two well characterized oral bacteria, P. gingivalis, and to a lesser extent, F. nucleatum. P. gingivalis reduced wound closure by ~40%, which was partially dependent on proteolytic activity, and bacteria was still present within infected cells 9 days later despite exposure to bacteria for only 24 h. Both oral bacteria caused keratinocyte apoptosis at the wound site with cell death being greatest at the wound edge. P. gingivalis and F. nucleatum adversely affected cell proliferation and the effect also had a spatial component being most striking at the edge. The impact of the bacteria was long lasting even when exposure was brief. Cell migration was compromised in bacteria challenged keratinocytes with P. gingivalis having more severe effect (pF. nucleatum. Quantitative real time PCR of bacteria challenged cells showed that P. gingivalis and to a lesser extent F. nucleatum significantly downregulated cell cycle genes cyclin1, CDK1, and CDK4 (pP. gingivalis (p\u3c0.05)

A comparative study between a Rankine cycle and a novel intra-cycle based waste heat recovery concepts applied to an internal combustion engine

AbstractA novel intra-cycle waste heat recovery (ICWHR) methodology, applied to an internal combustion engine is presented in this study. Through a split type thermodynamic cycle design, quasi-isothermal compression of the charge air and isobaric combustion of the air/fuel mixture can be performed separately in two chambers. Within such a design, the exhaust heat can be recovered to the intake air flow between the compression chamber and combustion chamber. Consequently, the recovered energy can be re-utilized in the combustor directly, and an intra-cycle waste heat recovery process can be achieved. To investigate the fundamental aspects of this new methodology, a comparative study between the conventional Rankine based WHR and the new ICWHR was undertaken. Both theoretical and numerical analysis were applied to evaluate the performance characteristics of these two technologies. The ICWHR cycle differs from the Rankine cycle in that an energy conversion subsystem is not necessary since the recovered energy is sent back to the combustion chamber directly, and then the system efficiency is improved significantly. Furthermore, the theoretical results indicate that the full cycle efficiency of ICWHR system is determined by the regeneration effectiveness, the compression ratio and the fuel equivalence ratio, then the limitations of Rankine cycle, such as working fluid selection and system parameter calibration can be avoided mechanically. Finally, through a one dimensional system model, analysis of optimal operation range, system efficiency and the heat transfer behaviours of ICWHR system are discussed in this paper and comparisons made with a Rankine cycle WHR system

\u3cem\u3eP. gingivalis\u3c/em\u3e Modulates Keratinocytes Through FOXO Transcription Factors

P. gingivalis is a prominent periodontal pathogen that has potent effects on host cells. In this study we challenged gingival epithelial cells with P. gingivalis with the aim of assessing how mRNA levels of key target genes were modulated by P. gingivalis via the transcription factors FOXO1 and FOXO3. Primary mono- and multi-layer cultures of gingival epithelial cells were challenged and barrier function was examined by fluorescent dextran and apoptosis was measured by cytoplasmic histone associated DNA. Gene expression levels were measured by real-time PCR with and without FOXO1 and FOXO3 siRNA compared to scrambled siRNA. P. gingivalis induced a loss of barrier function and stimulated gingival epithelial cell apoptosis in multilayer cultures that was in part gingipain dependent. P. gingivalis stimulated an increase in FOXO1 and FOXO3 mRNA, enhanced mRNA levels of genes associated with differentiated keratinocyte function (keratin-1, -10, -14, and involucrin), increased mRNA levels of apoptotic genes (BID and TRADD), reduced mRNA levels of genes that regulate inflammation (TLR-2 and -4) and reduced those associated with barrier function (integrin beta-1, -3 and -6). The ability of P. gingivalis to modulate these genes was predominantly FOXO1 and FOXO3 dependent. The results indicate that P. gingivalis has pronounced effects on gingival keratinocytes and modulates mRNA levels of genes that affect host response, differentiation, apoptosis and barrier function. Moreover, this modulation is dependent upon the transcription factors FOXO1 or FOXO3. In addition, a new function for FOXO1 was identified, that of suppressing TLR-2 and TLR-4 and maintaining integrin beta -1, beta -3 and beta -6 basal mRNA levels in keratinocytes

Clearance of damaged mitochondria via mitophagy is important to the protective effect of ischemic preconditioning in kidneys

<p>Ischemic preconditioning (IPC) affords tissue protection in organs including kidneys; however, the underlying mechanism remains unclear. Here we demonstrate an important role of macroautophagy/autophagy (especially mitophagy) in the protective effect of IPC in kidneys. IPC induced autophagy in renal tubular cells in mice and suppressed subsequent renal ischemia-reperfusion injury (IRI). The protective effect of IPC was abolished by pharmacological inhibitors of autophagy and by the ablation of <i>Atg7</i> from kidney proximal tubules. Pretreatment with BECN1/Beclin1 peptide induced autophagy and protected against IRI. These results suggest the dependence of IPC protection on renal autophagy. During IPC, the mitophagy regulator PINK1 (PTEN induced putative kinase 1) was activated. Both IPC and BECN1 peptide enhanced mitolysosome formation during renal IRI in mitophagy reporter mice, suggesting that IPC may protect kidneys by activating mitophagy. We further established an in vitro model of IPC by inducing ‘chemical ischemia’ in kidney proximal tubular cells with carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Brief treatment with CCCP protected against subsequent injury in these cells and the protective effect was abrogated by autophagy inhibition. In vitro IPC increased mitophagosome formation, enhanced the delivery of mitophagosomes to lysosomes, and promoted the clearance of damaged mitochondria during subsequent CCCP treatment. IPC also suppressed mitochondrial depolarization, improved ATP production, and inhibited the generation of reactive oxygen species. Knockdown of <i>Pink1</i> suppressed mitophagy and reduced the cytoprotective effect of IPC. Together, these results suggest that autophagy, especially mitophagy, plays an important role in the protective effect of IPC.</p> <p><b>Abbreviations</b>: ACTB: actin, beta; ATG: autophagy related; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2 interacting protein 3 like; BUN: blood urea nitrogen; CASP3: caspase 3; CCCP: carbonyl cyanide 3-chlorophenylhydrazone; COX4I1: cytochrome c oxidase subunit 4I1; COX8: cytochrome c oxidase subunit 8; DAPI: 4ʹ,6-diamidino-2-phenylindole; DNM1L: dynamin 1 like; EGFP: enhanced green fluorescent protein; EM: electron microscopy; ER: endoplasmic reticulum; FC: floxed control; FIS1: fission, mitochondrial 1; FUNDC1: FUN14 domain containing 1; H-E: hematoxylin-eosin; HIF1A: hypoxia inducible factor 1 subunit alpha; HSPD1: heat shock protein family D (Hsp60) member 1; IMMT/MIC60: inner membrane mitochondrial protein; IPC: ischemic preconditioning; I-R: ischemia-reperfusion; IRI: ischemia-reperfusion injury; JC-1: 5,5ʹ,6,6ʹ-tetrachloro-1,1ʹ,3,3ʹ-tetraethylbenzimidazolylcarbocyanine iodide; KO: knockout; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; mito-QC: mito-quality control; mRFP: monomeric red fluorescent protein; NAC: N-acetylcysteine; PINK1: PTEN induced putative kinase 1; PPIB: peptidylprolyl isomerase B; PRKN: parkin RBR E3 ubiquitin protein ligase; ROS: reactive oxygen species; RPTC: rat proximal tubular cells; SD: standard deviation; sIPC: simulated IPC; SQSTM1/p62: sequestosome 1; TOMM20: translocase of outer mitochondrial membrane 20; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling</p