Hyperlipidemia Increases Nalbuphine Brain Accumulation with Multiple Dosing without Affecting Its Analgesic Response-Its Respiratory Depression Potential Should Be Investigated in Future Studies.

Nalbuphine is associated with a significant risk of respiratory depression. Its central nervous system entry is hindered by P-glycoproteins, and lower P-glycoprotein activity is a risk factor for respiratory depression. We assessed the effect of hyperlipidemia on nalbuphine pharmacokinetics, brain and liver uptake, and analgesic response following single (2.

Novel Bis(2-cyanoacrylamide) Linked to Sulphamethoxazole: Synthesis, DNA Interaction, Anticancer, ADMET, Molecular Docking, and DFT Studies.

In the light of advancement and potential extensive use of medication design and therapy, new bis(cyanoacrylamides) incorporating sulphamethoxazole derivatives (7 a-7 f) were synthesized and confirmed by different spectral tools. In vitro anticancer activity towards different human cancer cells (HCT116, MDA-MB-231 and A549) was assessed using MTT assay. Among all derivatives, 4C- and 6C-spacer derivatives (7 e and 7 f) had the most potent growth inhibitory activities against HCT116 cells with IC values of 39.

The regulatory role of long non- coding RNAs as a novel controller of immune response against cancer cells.

Immunotherapy has been established as a promising therapy for different cancer types. However, many patients experience primary or secondary resistance to treatment. Immune cells and anti-inflammatory factors are regulated by long noncoding RNAs (lncRNAs).

Myoglobin: From physiological roles to potential implications in cancer.

Myoglobin (MB) belongs to the well-studied globin proteins superfamily. It has been extensively studied for its physiological roles in oxygen storage and transport for about a century now. However, the last two decades shed the light on unexpected aspects for MB research.

Sleep/wake calcium dynamics, respiratory function, and ROS production in cardiac mitochondria.

Introduction: Incidents of myocardial infarction and sudden cardiac arrest vary with time of the day, but the mechanism for this effect is not clear. We hypothesized that diurnal changes in the ability of cardiac mitochondria to control calcium homeostasis dictate vulnerability to cardiovascular events.

Objectives: Here we investigate mitochondrial calcium dynamics, respiratory function, and reactive oxygen species (ROS) production in mouse heart during different phases of wake versus sleep periods.

Expression of Myoglobin in Normal and Cancer Brain Tissues: Correlation With Hypoxia Markers.

Background: Myoglobin (MB) is increasingly recognized as a key player in cancer growth and metastasis. Low oxygen tensions, commonly associated with highly aggressive and recurrent cancers, have been shown to regulate its expression in several cancers such as lung, neck, prostate and breast cancer. However, it is not yet known whether it contributes to the growth and spread of brain cancers especially Glioblastoma multiforme (GBM).

Autism spectrum disorder (ASD)-associated mitochondrial deficits are revealed in children's platelets but unimproved by hyperbaric oxygen therapy.

Mitochondrial and immune dysfunctions are often implicated in the aetiology of autism spectrum disorder (ASD). Here, we studied for the first time the relationship between ASD severity measures and mitochondrial respiratory rates in freshly isolated platelets as well as the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in isolated neutrophils. We also verified the impact of hyperbaric oxygen therapy (HBOT) on mitochondrial and immune functions as well as on ASD severity measures.

ATR-IR and EPR spectroscopy for following the membrane restoration of isolated cortical synaptosomes in aluminium-induced Alzheimer's disease - Like rat model.

Synaptosomal membrane peroxidation and alteration in its biophysical properties are associated with Aluminium (Al) toxicity that may lead to cognitive dysfunction and Alzheimer's disease (AD) like pathogenesis. Here we investigated the therapeutic potential of Lepedium sativum (LS) as a natural anti-inflammatory, antioxidant and as acetyl cholinesterase inhibitor in treating Al induced AD-like in rat model. We utilized ATR-IR spectroscopy to follow the restoration in the damaged membrane structure of isolated rat cortical synaptosomes and its biophysical properties, electron paramagnetic resonance (EPR) spin trapping to follow NADPH oxidase activity (NOX), and EPR spin labelling in response to LS treatment after Al intoxication.

Human-stimulated oocyte extract induces genetic and mitochondrial reprogramming of mesenchymal stromal cells.

Summary: Reprogramming autologous adult cells to pluripotent cells allows for relatively safe cell replacement therapy. This can be achieved by nuclear transfer, cell fusion, or induced pluripotent stem cell technology However, the epigenetic memory of the cell is considered as a great challenge facing the complete reprograming of cells by these methods. Introducing oocyte-specific factors into differentiated cells may present a promising approach by mimicking cellular reprogramming during fertilization.

Insights About Circadian Clock and Molecular Pathogenesis in Gliomas.

The circadian clock is an endogenous time-keeping system that has been discovered across kingdoms of life. It controls and coordinates metabolism, physiology, and behavior to adapt to variations within the day and the seasonal environmental cycles driven by earth rotation. In mammals, although circadian rhythm is controlled by a set of core clock genes that are present in both in suprachiasmatic nucleus (SCN) of the hypothalamus and peripheral tissues, the generation and control of the circadian rhythm at the cellular, tissue, and organism levels occurs in a hierarchal fashion.

Dual-Ligand Functionalized Core-Shell Chitosan-Based Nanocarrier for Hepatocellular Carcinoma-Targeted Drug Delivery.

Introduction: Hepatocellular carcinoma represents a major health problem with the related death numbers still increasing. Active targeting is considered an attractive choice for the development of selective therapeutics with limited side effects and improved efficiency. In this study, we report the design, development and evaluation of a novel dual-ligand functionalized core-shell chitosan-based nanocarrier for the selective delivery of doxorubicin (DOX) for treatment of hepatocellular carcinoma (HCC).

Myoglobin variants are expressed in human glioblastoma cells‑hypoxia effect?

Glioblastoma multiforme (GBM) is the most aggressive human brain cancer. Little is known regarding how these cells adapt to the harsh tumor microenvironment, and consequently survive and resist various treatments. Myoglobin (MB), the oxygen‑binding hemoprotein, has been shown to be ectopically expressed in different human cancers and cell lines, and its expression is hypothesized to be an adaptation mechanism to hypoxia.

ATR-IR and EPR spectroscopy for detecting the alterations in cortical synaptosomes induced by aluminium stress.

Aluminium (Al) is reported to promote free radical production, decrease the antioxidant enzyme status and disturb the enzyme activity involved in acetylcholine metabolism leading to cognitive dysfunction that are strongly associated with Alzheimer's disease (AD) pathogenesis. This work aimed at investigating the effect of Al-toxicity on synaptosomal membrane biophysical properties and lipid peroxidation during 65 days. We utilized ATR-IR spectroscopy to study the changes in membrane biochemical structure and biophysical properties of isolated rat cortical synaptosomes, and EPR spin trapping and labeling to follow NADPH oxidase activity and changes of membrane order parameter, respectively.

Role of mitochondria in rescuing glycolytically inhibited subpopulation of triple negative but not hormone-responsive breast cancer cells.

Triple-negative breast cancer (TNBC) subtype is among the most aggressive cancers with the worst prognosis and least therapeutic targetability while being more likely to spread and recur. Cancer transformations profoundly alter cellular metabolism by increasing glucose consumption via glycolysis to support tumorigenesis. Here we confirm that relative to ER-positive cells (MCF7), TNBC cells (MBA-MD-231) rely more on glycolysis thus providing a rationale to target these cells with glycolytic inhibitors.

Updates on Aptamer Research.

For many years, different probing techniques have mainly relied on antibodies for molecular recognition. However, with the discovery of aptamers, this has changed. The science community is currently considering using aptamers in molecular targeting studies because of the many potential advantages they have over traditional antibodies.

ω-3 and ω-6 Fatty Acids Modulate Conventional and Atypical Protein Kinase C Activities in a Brain Fatty Acid Binding Protein Dependent Manner in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is a highly infiltrative brain cancer with a dismal prognosis. High levels of brain fatty acid binding protein (B-FABP) are associated with increased migration/infiltration in GBM cells, with a high ratio of arachidonic acid (AA) to docosahexaenoic acid (DHA) driving B-FABP-mediated migration. Since several protein kinase Cs (PKCs) are overexpressed in GBM and linked to migration, we explored a possible relationship between B-FABP and levels/activity of different PKCs, as a function of AA and DHA supplementation.

Corrigendum to "Resolving Contributions of Oxygen-Consuming and ROS-Generating Enzymes at the Synapse".

[This corrects the article DOI: 10.1155/2016/1089364.].

The diabetic brain and cognition.

The prevalence of both Alzheimer's disease (AD) and vascular dementia (VaD) is increasing with the aging of the population. Studies from the last several years have shown that people with diabetes have an increased risk for dementia and cognitive impairment. Therefore, the authors of this consensus review tried to elaborate on the role of diabetes, especially diabetes type 2 (T2DM) in both AD and VaD.

Hypoxia-inducible factor-1α activation improves renal oxygenation and mitochondrial function in early chronic kidney disease.

The pathophysiology of chronic kidney disease (CKD) is driven by alterations in surviving nephrons to sustain renal function with ongoing nephron loss. Oxygen supply-demand mismatch, due to hemodynamic adaptations, with resultant hypoxia, plays an important role in the pathophysiology in early CKD. We sought to investigate the underlying mechanisms of this mismatch.

Sex-specific differences in mitochondria biogenesis, morphology, respiratory function, and ROS homeostasis in young mouse heart and brain.

Sex-specific differences in mitochondrial function and free radical homeostasis are reported in the context of aging but not well-established in pathogeneses occurring early in life. Here, we examine if sex disparity in mitochondria function, morphology, and redox status starts early and hence can be implicated in sexual dimorphism in cardiac as well as neurological disorders prevalent at young age. Although mitochondrial activity in the heart did not significantly vary between sexes, female brain exhibited enhanced respiration and higher reserve capacity.

Immunological alteration & toxic molecular inductions leading to cognitive impairment & neurotoxicity in transgenic mouse model of Alzheimer's disease.

Aims: Inflammation is considered to be one of the crucial pathological factors associated with the development of Alzheimer's disease, although supportive experimental evidence remains undiscovered. Therefore, the current study was carried out to better understand and establish the pathophysiological involvement of chronic inflammation in a double transgenic mouse model of Alzheimer's disease.

Main Methods: We analyzed amyloid-beta deposition, oxidative stress, biochemical, neurochemical and immunological markers in a 10month old (APΔE9) mouse model.

Design, synthesis and cytotoxic activity of water-soluble quinones with dibromo--benzoquinone cores and amino oligo(ethylene glycol) side chains against MCF-7 breast cancer cells.

A series of novel quinones was synthesized by reacting tetrabromo--benzoquinone with amino oligo(ethylene glycol) dendrons of generation numbers = 0-2. According to the performed shake-flask experiments, their aqueous solubility ( = 18 mg l-1.6 g ml) and partition coefficients (log  = 2.

Calcium, a Cell Cycle Commander, Drives Colon Cancer Cell Diffpoptosis.

The story of the cell commonder, calcium, reaches into all corners of the cell and controls cell proliferation, differentiation, function, and even death. The calcium-driven eukaryotic revolution is one of the great turning points in the life history, happened about two billion years later when it was converted from a dangerous killer that had to be kept out of cell into the cell master which drives the cell. This review article will take the readers to a tour of tissues chosen to best show the calcium's many faces (proliferator, differentiator, and killer).

Resolving Contributions of Oxygen-Consuming and ROS-Generating Enzymes at the Synapse.

Disruption of cellular redox homeostasis is implicated in a wide variety of pathologic conditions and aging. A fundamental factor that dictates such balance is the ratio between mitochondria-mediated complete oxygen reduction into water and incomplete reduction into superoxide radical by mitochondria and NADPH oxidase (NOX) enzymatic activity. Here we determined mitochondrial as well as NOX-dependent rates of oxygen consumption in parallel with HO generation in freshly isolated synaptosomes using high resolution respirometry combined with fluorescence or electrochemical sensory.

Investigation of the Immunomodulatory effect of Berberis vulgaris on core-pulsed dendritic cell vaccine.

Background: Virus-induced dendritic cells (DCs) functional deficiency leads to sub-optimal initiation of adaptive immune responses and consequently chronic infection establishment. The present study reports an advanced hepatitis C virus (HCV) therapeutic vaccine model based on In vivo enrichment of DCs with barberry ethanolic crude extract (BCE) then pulsing them with HCV core protein.

Methods: DCs were enriched by BCE intravenous injection in BALB/c mice.