Melatonin regulates CRE-dependent gene transcription underlying osteoblast proliferation by activating Src and PKA in parallel.

Several studies have indicated a relationship between melatonin and idiopathic scoliosis, including our previous work which demonstrated that melatonin can inhibit osteoblast proliferation; however, the mechanism remains unclear. Here, we utilized a MTT assay to show that melatonin significantly reduces osteoblast proliferation in a concentration-and time-dependent manner. Through a combination of techniques, including real-time PCR, MTT assays, immunofluorescence, and luciferase assays, we confirmed that melatonin-induced changes in phosphorylated cAMP response element-binding protein (CREB) reduced transcriptional activity in a melatonin receptor-dependent manner.

Fisetin suppresses malignant proliferation in human oral squamous cell carcinoma through inhibition of Met/Src signaling pathways.

Fisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary flavonoid and has been indicated as a novel anti-cancer agent in several types of cancer cells. However, the mechanisms underlying the effect of fisetin in human oral squamous cell carcinoma (OSCC) remain unclear. Here, we report that fisetin significantly inhibits tumor cell proliferation and induces apoptosis in OSCC (UM-SCC-23 and Tca-8113) cancer cell lines.

Cathepsin D protects renal tubular cells from damage induced by high glucose independent of its enzymatic activity.

Although glomerular and vascular damage have been considered the main characteristics of diabetic kidney disease (DKD), accumulating data now indicate that tubular atrophy also plays a major role. Cathepsin D (CatD) is the major aspartate protease within lysosomes. The current study demonstrated that CatD expression was altered in the renal tubular epithelium in patients with diabetes mellitus (DM).

Transcription Factor NFAT5 Promotes Glioblastoma Cell-driven Angiogenesis via SBF2-AS1/miR-338-3p-Mediated EGFL7 Expression Change.

Glioblastoma (GBM) is the most aggressive primary intracranial tumor of adults and confers a poor prognosis due to high vascularization. Hence anti-angiogenic therapy has become a promising strategy for GBM treatment. In this study, the transcription factor nuclear factor of activated T-cells 5 (NFAT5) was significantly elevated in glioma samples and GBM cell lines, and positively correlated with glioma WHO grades.

Sirtuin 7 plays an oncogenic role in human osteosarcoma via downregulating CDC4 expression.

It is still a controversy whether the role of Sirtuin 7 (SIRT7) is an oncogene or a tumor suppressor gene in cancer as SIRT7 may have different functions in different types of cancer. Particularly, the specific roles of SIRT7 in the progression of osteosarcoma remain undiscovered. The main aim of this study is to identify the expression of SIRT7 in osteosarcoma and explore the biological functions of SIRT7 in regulating cellular processes of osteosarcoma cells.

The role of Dickkopf family in cancers: from Bench to Bedside.

Numerous epidemiological studies indicate that cancer will be responsible for millions of deaths in one year. Although multiple therapeutic strategies exist, and vast research efforts are being focused on developing newer and better regimens, cancer-related morbidity and mortality remain high. Metastasis and recurrence are prominent causes of treatment failure in cancers.

Mouse Anaphylactic Hypotension Is Characterized by Initial Baroreflex Independent Renal Sympathoinhibition Followed by Sustained Renal Sympathoexcitation.

The hemodynamic response to mouse systemic anaphylaxis is characterized by an initial hypertension followed by sustained hypotension. However, the defense mechanisms of the sympathetic nervous system against this circulatory disturbance is not known. Here, we investigated the renal sympathetic nerve activity (RSNA) response to mouse systemic anaphylaxis, along with the roles of carotid sinus baroreceptor, vagal nerves and the transient receptor potential vanilloid type 1 channel (TRPV1).

Integration between Glycolysis and Glutamate-Glutamine Cycle Flux May Explain Preferential Glycolytic Increase during Brain Activation, Requiring Glutamate.

The 1988 observation by Fox et al. (1988) that brief intense brain activation increases glycolysis (pyruvate formation from glucose) much more than oxidative metabolism has been abundantly confirmed. Specifically glycolytic increase was unexpected because the amount of ATP it generates is smaller than that formed by subsequent oxidative metabolism of pyruvate.

Pioglitazone Improves Mitochondrial Function in the Remnant Kidney and Protects against Renal Fibrosis in 5/6 Nephrectomized Rats.

Pioglitazone is a type of peroxisome proliferator-activated receptor γ (PPARγ) agonist and has been demonstrated to be effective in chronic kidney diseases (CKD) treatment. However, the underlying mechanism involved in the renoprotection of pioglitazone has not been fully revealed. In the present study, the renoprotective mechanism of pioglitazone was investigated in 5/6 nephrectomized (Nx) rats and TGF-β1-exposed HK-2 cells.

Cathepsin S Is Involved in Th17 Differentiation Through the Upregulation of IL-6 by Activating PAR-2 after Systemic Exposure to Lipopolysaccharide from .

Positive links have been found between periodontitis and numerous diseases in humans via persistent inflammation throughout the body. However, the main factors responsible for maintaining this pro-inflammatory condition are poorly understood. The spleen, the largest secondary immune organ, is a central hub regulating the immune response/inflammation due to the dendritic cell (DC) response to CD4 T cell subtype differentiation, and lysosomal proteinase cathepsin S (CatS) is known to be involved in DC functions.

Upregulation of Matrix Metalloproteinase-9 in Primary Cultured Rat Astrocytes Induced by 2-Chloroethanol Via MAPK Signal Pathways.

2-Chloroethanol (2-CE) is one of the reactive metabolites of 1,2-DCE , which might contribute to brain edema formation induced by 1,2-dichloroethane (1,2-DCE) poisoning. Thus, the purpose of this study was to explore the roles of mitogen-activated protein kinase (MAPK) signal pathways in upregulation of matrix metalloproteinase-9 (MMP-9) in 2-CE exposed rat astrocytes. Expression of p38 MAPK (p38), extracellular signal regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and MMP-9 at both protein and gene levels in rat astrocytes were determined using western blot and real-time RT-PCR methods.

Adverse Effects of the Apolipoprotein E ε4 Allele on Episodic Memory, Task Switching and Gray Matter Volume in Healthy Young Adults.

Many studies have shown that healthy elderly subjects and patients with Alzheimer's disease (AD) who carry the () ε4 allele have worse cognitive function and more severe brain atrophy than non-carriers. However, it remains unclear whether this polymorphism leads to changes of cognition and brain morphology in healthy young adults. In this study, we used an established model to measure verbal episodic memory and core executive function (EF) components (response inhibition, working memory and task switching) in 32 ε4 carriers and 40 non-carriers between 20 years and 40 years of age.

Glutamate Deregulation in Ketamine-Induced Psychosis-A Potential Role of PSD95, NMDA Receptor and PMCA Interaction.

Ketamine causes psychotic episodes and is often used as pharmacological model of psychotic-like behavior in animals. There is increasing evidence that molecular mechanism of its action is more complicated than just N-methyl-D-aspartic acid (NMDA) receptor antagonism and involves interaction with the components of calcium homeostatic machinery, in particular plasma membrane calcium pump (PMCA). Therefore, in this study we aimed to characterize brain region-specific effects of ketamine on PMCA activity, interaction with NMDA receptor through postsynaptic density protein 95 (PSD95) scaffolding proteins and glutamate release from nerve endings.

Endothelial-Monocyte Activating Polypeptide II Suppresses the Glioblastoma-Induced Angiogenesis by Inducing Autophagy.

The obstacle in delivering therapeutics to glioblastoma (GBM) is tumor-induced angiogenesis which leads to the formation of abnormal vessels and a dysfunctional blood-tumor barrier. Here, we elucidated the effect of endothelial-monocyte activating polypeptide II (EMAP II) on the GBM-induced angiogenesis as well as its potential mechanisms. Our results proved that EMAP II inhibited the viability, mitochondrial membrane potential, migration and tube formation of GBM-induced endothelial cells (GECs) by inducing cell autophagy, demonstrated by cell viability assay, JC-1 staining assay, transwell assay and tube formation assay, respectively.

The Role of HOTAIR/miR-148b-3p/USF1 on Regulating the Permeability of BTB.

Homeobox transcript antisense intergenic RNA (HOTAIR), as a long non-coding RNA (lncRNA), has been considered to play critical roles in the biological properties of various tumors. The purposes of this study were to investigate the role and possible molecular mechanisms of HOTAIR in regulating the permeability of blood tumor barrier (BTB) . Our present study elucidated that the expressions of HOTAIR and upstream stimulatory factor 1 (USF1) was up-regulated, but miR-148b-3p was down-regulated in glioma microvascular endothelial cells (GECs).

LC-0882 targets PAK4 and inhibits PAK4-related signaling pathways to suppress the proliferation and invasion of gastric cancer cells.

Gastric cancer is the most common malignant tumor and globally the third leading cause of cancer-related deaths. Therefore, there exists an urgent need to identify new effective gastric cancer treatments. Given the important roles in tumorigenesis and progression, p21-activated kinase 4 (PAK4) has been regarded as an attractive high-value druggable target.

Elevated Circulating Trimethylamine N-Oxide Levels Contribute to Endothelial Dysfunction in Aged Rats through Vascular Inflammation and Oxidative Stress.

Vascular endothelial dysfunction, a characteristic of the aging process, is an important risk factor for cardiovascular disease in aging. Although, vascular inflammation and oxidative stress are major contributors to endothelial dysfunction in aging, the underlying mechanisms during the aging process are not fully understood. Accumulating evidence reveals that gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) is implicated in the pathogenesis of many cardiovascular diseases.

Maternal Different Degrees of Iodine Deficiency during Pregnant and Lactation Impair the Development of Cerebellar Pinceau in Offspring.

Iodine is critical for synthesis of thyroid hormones (TH). And iodine deficiency (ID) is one of the most significant reasons of intellectual disability and motor memory impairment, although the potential mechanisms are still under investigation. Presently, mild ID and marginal ID are largely ignored problems for women of child bearing age.

Physiological Signal-Based Method for Measurement of Pain Intensity.

The standard method for prediction of the absence and presence of pain has long been self-report. However, for patients with major cognitive or communicative impairments, it would be better if clinicians could quantify pain without having to rely on the patient's self-description. Here, we present a newly pain intensity measurement method based on multiple physiological signals, including blood volume pulse (BVP), electrocardiogram (ECG), and skin conductance level (SCL), all of which are induced by external electrical stimulation.

Molecular Epidemiology and Antifungal Susceptibility of in China (August 2009 to July 2014): A Multi-Center Study.

is an increasingly important cause of invasive candidiasis. In China, relatively little is known of the molecular epidemiology of and of its antifungal susceptibility patterns. Here we studied 411 non-duplicate isolates from 411 patients at 11 hospitals participating in the National China Hospital Invasive Fungal Surveillance Net program (CHIF-NET; 2010-2014).

Functional Network Connectivity Patterns between Idiopathic Generalized Epilepsy with Myoclonic and Absence Seizures.

The extensive cerebral cortex and subcortical structures are considered as the major regions related to the generalized epileptiform discharges in idiopathic generalized epilepsy. However, various clinical syndromes and electroencephalogram (EEG) signs exist across generalized seizures, such as the loss of consciousness during absence seizures (AS) and the jerk of limbs during myoclonic seizures (MS). It is presumed that various functional systems affected by discharges lead to the difference in syndromes of these seizures.

Modes of Effective Connectivity within Cortical Pathways Are Distinguished for Different Categories of Visual Context: An fMRI Study.

Context contributes to accurate and efficient information processing. To reveal the dynamics of the neural mechanisms that underlie the processing of visual contexts during the recognition of color, shape, and 3D structure of objects, we carried out functional magnetic resonance imaging (fMRI) of subjects while judging the contextual validity of the three visual contexts. Our results demonstrated that the modes of effective connectivity in the cortical pathways, as well as the patterns of activation in these pathways, were dynamical depending on the nature of the visual contexts.

Hyperbaric oxygen treatment attenuates neuropathic pain by elevating autophagy flux via inhibiting mTOR pathway.

Peripheral neuropathic pain is a complex disease, and treated based on underlying diseases. Emerging evidences suggest that hyperbaric oxygen alleviates neuropathic pain. However, its cellular and molecular mechanism on pain relief is unknown.

Beneficial Effects of Sulforaphane Treatment in Alzheimer's Disease May Be Mediated through Reduced HDAC1/3 and Increased P75NTR Expression.

Alzheimer's disease is an irreversible, progressive neurodegenerative disorder. The accumulation of Aβ in the brain is thought to play a causative role in the development of cognitive dysfunction in Alzheimer's disease. The p75 neurotrophin receptor is of great importance to protect against the Aβ burden and its expression is regulated by histone acetylation.