Abnormal inflammation and accelerated decline in lung function occur patients with chronic obstructive pulmonary disease (COPD). Human sirtuin (SIRT1), an antiaging antiinflammatory protein, is a metabolic NAD(+)-dependent protein/histone deacetylase that regulates proinflammatory mediators by deacetylating histone nonhistone proteins.To determine the expression of SIRT1 lungs smokers COPD, to elucidate regulation response cigarette smoke macrophages, its impact on nuclear factor (NF)-kappaB...

The silent information regulator 2 (Sir2) family of proteins (sirtuins or SIRTs), which belong to class III histone/protein deacetylases, have been implicated in calorie restriction, aging, and inflammation. We hypothesized that cigarette smoke-mediated proinflammatory cytokine release is regulated by SIRT1 its interaction with NF-kappaB a monocyte-macrophage cell line (MonoMac6) inflammatory cells rat lungs. Cigarette smoke extract (CSE) exposure MonoMac6 caused dose- time-dependent...

A variety of mouse models have been used to study the pathogenesis pulmonary emphysema/chronic obstructive disease. The effect cigarette smoke (CS) is believed be strain dependent, because certain strains are more susceptible or resistant development emphysema. However, molecular basis susceptibility effects CS not known. We investigated on lungs most commonly mechanism CS. C57BL/6J, A/J, AKR/J, CD-1, and 129SvJ mice were exposed for 3 consecutive days, various parameters inflammatory...

Liver transplantation is the last resort for liver failure patients. However, due to shortage of donor organs, bioengineered generated from decellularized whole scaffolds and induced pluripotent stem cell (iPSC)-derived hepatocytes (iPSC-Heps) being studied as an alternative approach treat disease. Nevertheless, there has been no report on both interaction iPSC-Heps with a extracellular matrix (ECM) analysis recellularized into scaffolds. In this study, we produced porcine iPSC-Heps, which...

Toll-like receptors (TLRs) and Nod-like (NLRs) are known to trigger an innate immune response against microbial infection. Although studies suggest that activation of TLRs modulate the function mesenchymal stem cells (MSCs), little is about role NLRs on MSC function. In this study, we investigated whether NOD1 NOD2 regulate functions human umbilical cord blood-derived MSCs (hUCB-MSCs). The genes TLR2, TLR4, NOD1, were expressed in hUCB-MSCs. Stimulation with each agonist (Pam(3)CSK(4) for...

Abstract Whole kidney decellularization is a promising approach in regenerative medicine for engineering functional organ. The reaction of the potential host depends on biocompatibility these decellularized constructs. Despite proven ability scaffolds to guide cell attachment and growth, little known about hemocompatibility scaffolds. Our aim prepare kidneys clinically relevant size evaluate its hemocompatibility. Porcine were cannulated via renal artery, then perfused with 0.1% sodium...

The cyclin-dependent kinase inhibitor p21(CIP1/WAF1/SDI1) (p21) is an important inhibitory checkpoint regulator of cell cycle progression in response to oxidative and genotoxic stresses. It known that p21 potentiates inflammatory inhibits apoptosis proliferation, leading cellular senescence. However, the role endogenous regulation lung injurious responses by cigarette smoke (CS) or other pro-inflammatory stimuli not known. We hypothesized modifier inflammation injury, genetic ablation will...

Niemann Pick disease type C1 (NPC) is an autosomal recessive characterized by progressive neurological deterioration leading to premature death. In this study, we hypothesized that human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have the multifunctional abilities ameliorate NPC symptoms in brain. To test hypothesis, hUCB-MSCs were transplanted into hippocampus of mice early asymptomatic stage. This transplantation resulted recovery motor function Rota Rod and impaired...

The receptor for advanced glycan end products (RAGE) has been identified as a susceptibility gene chronic obstructive pulmonary disease (COPD) in genome-wide association studies (GWASs). However, less is known about how RAGE involved the pathogenesis of COPD. To determine molecular mechanism by which influences COPD experimental models, we investigated efficacy RAGE-specific antagonist FPS-ZM1 administration vivo and vitro models. We injected elastase intratracheally mice, infiltrated...

The tripeptide-copper complex glycyl-l-histidyl-l-lysine-Cu (II) (GHK-Cu) is involved in wound healing and tissue remodeling. Although GHK-Cu exhibits anti-aging renewing properties, its roles acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are still unknown. Therefore, we examined the effects of lipopolysaccharide (LPS)-induced RAW 264.7 macrophages vitro ALI mice vivo. treatment reduced reactive oxygen species (ROS) production, increased superoxide dismutase (SOD)...

Growing evidence links prenatal exposure to particulate matter (PM2.5) with reduced lung function and incidence of pulmonary diseases in infancy childhood. However, the underlying biological mechanisms how PM2.5 affects lungs are incompletely understood, which explains lack an ideal vitro development model. Human pluripotent stem cells (hPSCs) have been successfully employed for developmental toxicity evaluations due their unique ability differentiate into any type cell body. In this study,...

Cadmium (Cd), a major component of cigarette smoke, disrupts the normal functions airway cells and can lead to development various pulmonary diseases such as chronic obstructive disease (COPD). However, molecular mechanisms involved in Cd-induced are poorly understood. Here, we identified cluster genes that altered response Cd exposure human bronchial epithelial (BEAS-2B) demonstrated ER stress inflammation mediated via CCAAT-enhancer-binding proteins (C/EBP)-DNA-damaged-inducible transcript...

The oxidative stress and cellular apoptosis by environmental factor including cigarette smoke induces alveolar airway remodeling leading to chronic obstructive pulmonary disease (COPD). Recently, the receptor for advanced glycan end products (RAGE) which is highly expressed in epithelium emerging as a biomarker COPD susceptibility or progression. However, it still remains unknown how RAGE plays role extract (CSE)-exposed human type II epithelial cell line. Therefore, we determined efficacy...

Nanoparticles (NPs) have been recognized as both useful tools and potentially toxic materials in various industrial medicinal fields. Previously, we found that zinc oxide (ZnO) NPs are neurotoxic to human dopaminergic neuroblastoma SH-SY5Y cells mediated by lipoxygenase (LOX), not cyclooxygenase-2 (COX-2). Here, examined whether bone marrow-derived mesenchymal stem (MSCs), which different from cells, might exhibit COX-2- and/or LOX-dependent cytotoxicity of ZnO NPs. Additionally, changes...

The activation of transcription factor NF-kappaB is controlled by two main pathways: the classical canonical (RelA/p65-p50)- and alternative noncanonical (RelB/p52)-NF-kappaB pathways. RelB has been shown to play a protective role in RelA/p65-mediated proinflammatory cytokine release immune-inflammatory lymphoid cells. Increased infiltration macrophages cells occurs lungs patients with chronic obstructive pulmonary disease, leading abnormal inflammation. We hypothesized that RelB, its...

Abstract Neural stem cells (NSCs) are capable of giving rise to neurons, glia, and astrocytes. Although self-renewal differentiation in NSCs regulated by many genes, such as Notch Numb, little is known about the role defective genes on from developing brain. The Niemann-Pick type C1 (NPC1) disease a neurodegenerative caused mutation NPC1 gene that affects function protein. ability NSC was investigated using model disease. disorder significantly affected NSCs, well differentiation. NPC1−/−...

Abstract Human pluripotent stem cell (hPSC)-derived alveolar epithelial cells (AECs) provide new opportunities for understanding lung development and the treatment of pulmonary diseases. However, toxicity assessments using hPSC-AECs have not been undertaken. In this study, we generated functional AECs from hPSCs evaluated their inflammatory apoptotic responses to cadmium (Cd) exposure (1, 5, 10 μM) 24 h compared with human bronchial line (BEAS-2B) primary as controls. Our data showed that Cd...

Treatment with mesenchymal stem cells (MSC) in spinal cord injury (SCI) has been highlighted as therapeutic candidate for SCI. Although astrogliosis is a major phenomenon after SCI, the role of still controversial. In this study, we determined whether acute transplantation MSC improves outcome SCI through modulating astrogliosis.Bone marrow derived rat MSCs were induced neural differentiation and transplanted rats. Matrix metalloproteinase (MMP) neuro-inflammatory pathway analyzed at 1, 3 7...

Fyn is a tyrosine kinase with multiple roles in variety of cellular processes. Here we report that new involved adipocyte differentiation. Elevated protein detected specifically the adipocytes obese mice. Moreover, expression increases progressively 3T3-L1 cells during vitro adipogenesis, which correlates its activity. Inhibition by either genetic or pharmacological manipulation restrains preadipocytes from fully differentiating into mature adipocytes. Mechanistically, regulates activity...