Showing papers in "American Journal of Physiology-cell Physiology in 2019"
TL;DR: This review discusses the current knowledge of how neuroinflammation contributes to BBB damage in ischemic stroke and provides an updated overview of the role of cytokines, chemokines, oxidative and nitrosative stress, adhesion molecules, matrix metalloproteinases, and vascular endothelial growth factor.
Abstract: As part of the neurovascular unit, the blood-brain barrier (BBB) is a unique, dynamic regulatory boundary that limits and regulates the exchange of molecules, ions, and cells between the blood and ...
390 citations
TL;DR: It is shown that the m6A-catalytic enzyme METTL3 is specifically upregulated following the M1 polarization of mouse macrophages, and drives M1 macrophage polarization by directly methylating STAT1 mRNA, potentially serving as an anti-inflammatory target.
Abstract: Compelling evidence indicates that epigenetic regulations orchestrate dynamic macrophage polarization. N6-methyladenosine (m6A) methylation is the most abundant epigenetic modification of mammalian...
123 citations
TL;DR: The ability of antioxidants to protect against the oxidative stress induced by hyperglycemia and elevated free fatty acid levels in vitro, suggests a causative role of oxidative stress in mediating the latter clinical conditions.
Abstract: It is now accepted that nutrient abundance in the blood, especially glucose, leads to the generation of reactive oxygen species (ROS), ultimately leading to increased oxidative stress in a variety ...
111 citations
TL;DR: OSCC-derived exosomes promote M2 subtype macrophage polarization mediated by exosome-enclosed miR-29a-3p, and the mechanism by miR+3p is the activity of SOCS1/STAT6 signals in macrophages.
Abstract: This study aims to explore the mechanism of the signal transmission between oral squamous cell carcinoma (OSCC) and unpolarized stromal immune macrophages mediated by OSCC-derived exosomes (OSCC-Ex...
89 citations
TL;DR: Results showed that exogenous H2O2 inhibited pTr cell viability, arrested the cell cycle at S and G2/M phases, and increased cell apoptosis and autophagy protein light chain 3B and Beclin-1, whereas these effects were reversed by different concentrations of N-acetyl-l-cysteine (NAC) posttreatment.
Abstract: Significant embryo loss remains a serious problem in pig production. Reactive oxygen species (ROS) play a critical role in embryonic implantation and placentation. However, the potential mechanism ...
89 citations
TL;DR: It is suggested that both mechanical and biochemical stimuli trigger Piezo1-mediated Ca2+ influx and thereby activate matrix metalloproteinase-2 and membrane type 1 matrix metalop Proteinase and synergistically facilitate sprouting angiogenesis.
Abstract: Angiogenesis is initiated in response to a variety of external cues, including mechanical and biochemical stimuli; however, the underlying signaling mechanisms remain unclear. Here, we investigated...
76 citations
TL;DR: The severe phenotype seen in RPEΔGlut1h mice indicates that glucose transport via the GLUT1 transporter in the RPE is required to meet the anabolic and catabolic requirements of photoreceptors and maintain Müller glial cells in a quiescent state.
Abstract: The retina is one of the most metabolically active tissues in the body and utilizes glucose to produce energy and intermediates required for daily renewal of photoreceptor cell outer segments. Gluc...
67 citations
TL;DR: The development of organoid models of intestinal biology and the applications of organoids for study of the pathophysiology of intestinal diseases and cancer are described.
Abstract: In vitro, cell cultures are essential tools in the study of intestinal function and disease. For the past few decades, monolayer cellular cultures, such as cancer cell lines or immortalized cell li...
67 citations
TL;DR: The hypothesis is proposed that the α7β1 integrin can contribute to mechanical-load induced skeletal muscle growth via an mTORC1-independent mechanism.
Abstract: The α7β1-integrin is a transmembrane adhesion protein that connects laminin in the extracellular matrix (ECM) with actin in skeletal muscle fibers. The α7β1-integrin is highly expressed in skeletal...
66 citations
TL;DR: The potential application of ncRNAs as biomarkers of AKI as well as therapeutic targets for treating AKI and impeding AKI-CKD transition are discussed, and the future research directions of n cRNAs in kidney injury and repair are highlighted.
Abstract: Acute kidney injury (AKI) is a major kidney disease featured by a rapid decline of renal function. Pathologically, AKI is characterized by tubular epithelial cell injury and death. Besides its acut...
63 citations
TL;DR: This review covers CD73 functions in multiple organ systems and cell types, with a particular focus on novel findings from the last 5 years.
Abstract: Ecto-5′-nucleotidase [cluster of differentiation 73 (CD73)] is a ubiquitously expressed glycosylphosphatidylinositol-anchored glycoprotein that converts extracellular adenosine 5′-monophosphate to ...
TL;DR: PoWeR is a novel, practical, and easy-to-deploy approach for eliciting robust hypertrophy in mice, and its findings can inform future research on the mechanisms underlying skeletal muscle adaptive potential and muscle memory.
Abstract: Myonuclei gained during exercise-induced skeletal muscle hypertrophy may be long-lasting and could facilitate future muscle adaptability after deconditioning, a concept colloquially termed “muscle ...
TL;DR: These findings provide direct evidence that uremic metabolites negatively impact skeletal muscle mitochondrial energetics, resulting in decreased energy transfer, impaired complex III and IV enzyme activity, and elevated oxidant production.
Abstract: Chronic kidney disease (CKD) leads to increased skeletal muscle fatigue, weakness, and atrophy. Previous work has implicated mitochondria within the skeletal muscle as a mediator of muscle dysfunct...
TL;DR: The molecular mechanisms underlying abnormal mitochondrial morphology in HF and their contributions to the development of cardiac diseases are discussed, highlighting the crucial roles of PTMs of mitochondrial fission and fusion proteins.
Abstract: Mitochondrial fragmentation frequently occurs in chronic pathological conditions as seen in various human diseases. In fact, abnormal mitochondrial morphology and mitochondrial dysfunction are hall...
TL;DR: It is demonstrated that ANXA4 expression is downregulated in PE and may promote trophoblast invasion via the PI3K/Akt/eNOS pathway.
Abstract: The inadequate trophoblast invasion is associated with the development of preeclampsia (PE). Considering that annexin A4 (ANXA4) enhances tumor invasion, we aimed to explore the functional role of ...
TL;DR: The effect that various integrins and extracellular matrix components have in embryonic brain development, and how this changes in both maturity and in the poststroke environment are described are described.
Abstract: Ischemicstroke is a leading cause of death and disability in the United States, but recent advances in treatments [i.e., endovascular thrombectomy and tissue plasminogen activator (t-PA)] that targ...
TL;DR: Findings indicate that blocking the REDD1/TXNIP axis repressed the inflammation-mediated vascular injury process, which may be closely related to oxidative stress and apoptosis in HUVECs, implying that the REDd1/Texas Instruments axis may be a new target for preventing the endothelial cell injury process.
Abstract: The aim of the present study was to investigate the potential role of regulated in development and DNA damage response 1 (REDD1) in LPS-induced vascular endothelial injury by using human umbilical ...
TL;DR: It is suggested that under basal conditions apical NKCC1 is continuously active and works in the net inward flux mode maintaining [Cl-]i and CWV needed for CSF secretion.
Abstract: Choroid plexus epithelial cells (CPECs) secrete cerebrospinal fluid (CSF). They express Na+-K+-ATPase and Na+-K+-2Cl− cotransporter 1 (NKCC1) on their apical membrane, deviating from typical basola...
TL;DR: The data suggest that platelet-cancer cell interactions and perhaps platelet procoagulant EVs may contribute to the prothrombotic phenotype of colon cancer patients, and may provide rationale for targeting platelets with PAR4 antagonists together with aspirin and/or ADP receptor antagonists as a potential intervention to limit cancer-associated thrombosis.
Abstract: Cancer-associated thrombosis is a common first presenting sign of malignancy and is currently the second leading cause of death in cancer patients after their malignancy. However, the molecular mec...
TL;DR: Given the growing understanding of how specific changes at the cellular level impact whole-organism physiology, there is an equally growing interest in pharmacological manipulation of apoptosis and/or autophagy for altering human physiology and health.
Abstract: Apoptosis and autophagy are processes resulting from the integration of cellular stress and death signals. Their individual importance is highlighted by the lethality of various mouse models missin...
TL;DR: Evidence regarding which of these mechanisms may be implicated in age-related skeletal muscle anabolic resistance is summarized, and recommendations for future avenues of research which can expand the knowledge of this area are provided.
Abstract: Skeletal muscle mass, a strong predictor of longevity and health in humans, is determined by the balance of two cellular processes, muscle protein synthesis (MPS) and muscle protein breakdown. MPS ...
TL;DR: Results support that activation of both cytosolic and mitochondrial calpains impairs mitochondria during cardiac ISC-REP, and contributes to mitochondrial dysfunction by impairing removal of the impaired mitochondria through depletion of a key component of the mitophagy process.
Abstract: Activation of calpain 1 (CPN1) and calpain 2 (CPN2) contributes to cardiac injury during ischemia (ISC) and reperfusion (REP). Complex I activity is decreased in heart mitochondria following ISC-RE...
TL;DR: The paracrine action of EVs released by stem cells and their potential involvement in the activation of regenerative programs in injured cells are addressed.
Abstract: The extracellular vesicles (EVs) are membrane vesicles carrying proteins, nucleic acids, and bioactive lipids of the cell of origin. These vesicles released within the extracellular space and enter...
TL;DR: It is demonstrated that 12 wk of exercise training significantly altered skeletal muscle gene expression of transcription factors and gene expression related to the kynurenine pathway, but not circulating kynuranine metabolites in older men.
Abstract: Exercise positively impacts mood and symptoms of depression; however, the mechanisms underlying these effects are not fully understood. Recent evidence highlights a potential role for skeletal musc...
TL;DR: It is shown that Ang Ⅱ promotes MerTK shedding via AT1R/ROS/p38MAPK/ADAM17 pathway in macrophages, which led to defective efferocytosis and atherosclerosis progression, which may provide promising diagnosis and therapies for ACS patients.
Abstract: Vulnerable plaques in advanced atherosclerosis have defective efferocytosis. The role of ANG II in the progression of atherosclerosis is not fully understood. Herein, we investigated the effects an...
TL;DR: The impact of sex and hypertension as modifiable and nonmodifiable risk factors and the underlying cellular mechanisms that may underlie heterogeneous stroke outcomes are explored.
Abstract: A functional neurovascular unit (NVU) is central to meeting the brain’s dynamic metabolic needs. Poststroke damage to the NVU within the ipsilateral hemisphere ranges from cell dysfunction to compl...
TL;DR: The current knowledge regarding the role of miRNAs in brain development and cerebrovascular pathophysiology is summarized and recent progress of the miRNA-based mechanisms in neuronal and cerebrvascular development as well as their role in hypoxic-ischemic brain injury are reviewed.
Abstract: MicroRNAs (miRNAs) are a class of highly conserved non-coding RNAs with 21–25 nucleotides in length and play an important role in regulating gene expression at the posttranscriptional level via bas...
TL;DR: Exposure to both high- and low-pH media decreased basal mitochondrial respiration, ATP turnover, and maximum mitochondrial respiratory capacity, indicating that muscle pH affects several metabolic signaling pathways, including those required for mitochondrial function.
Abstract: Exercise stimulates mitochondrial biogenesis and increases mitochondrial respiratory function and content. However, during high-intensity exercise muscle pH can decrease below pH 6.8 with a concomi...
TL;DR: Findings show that beclin 1 plays a constitutive, autophagy-independent role in the regulation of intestinal TJ barrier function via endocytosis of occludin.
Abstract: A defective tight junction (TJ) barrier is a key pathogenic factor for inflammatory bowel disease. Previously, we have shown that autophagy, a cell survival mechanism, enhances intestinal epithelia...
TL;DR: It is concluded that SIRT3 silencing in SW620 cancer cells leads to decreased mitochondrial biogenesis and mitochondrial dysfunction, ultimately affecting cell viability, and could be a therapeutic strategy to render cells more sensitive to treatment.
Abstract: Sirtuin 3 (SIRT3) is the main mitochondrial deacetylase and targets several crucial enzymes against oxidative stress. Recent reports suggest that SIRT3 could also participate in the quality and qua...