Potential Link Between Proprotein Convertase Subtilisin/Kexin Type 9 and Alzheimer's Disease.

Alzheimer's disease [AD] is not only the most common neurodegenerative disease but is also currently incurable. Proprotein convertase subtilisin/kexin-9 [PCSK9] is an indirect regulator of plasma low density lipoprotein [LDL] levels controlling LDL receptor expression at the plasma membrane. PCSK9 also appears to regulate the development of glucose intolerance, insulin resistance, abdominal obesity, inflammation, and hypertension, conditions that have been identified as risk factors for AD.

Thyroid Hormone Enhances Neurite Outgrowth in Neuroscreen 1 Cells.

Objectives: Alzheimer's disease (AD) is a neurodegenerative disorder that affects millions of individuals. Moreover, hypothyroidism has been identified as one of the risk factors that may contribute to the development of AD. Here, we investigated whether there was a correlation among expression levels of proteins involved in the formation of AD lesions, neurite outgrowth, and thyroid hormone levels.

Cytokine signaling through Mthl10 ties lifespan to environmental stress.

A systems-level understanding of cytokine-mediated, intertissue signaling is one of the keys to developing fundamental insight into the links between aging and inflammation. Here, we employed , a routine model for analysis of cytokine signaling pathways in higher animals, to identify a receptor for the growth-blocking peptide (GBP) cytokine. Having previously established that the phospholipase C/Ca signaling pathway mediates innate immune responses to GBP, we conducted a dsRNA library screen for genes that modulate Ca mobilization in S3 cells.

Correlation of Carbon Dots' Light-Activated Antimicrobial Activities and Fluorescence Quantum Yield.

This study investigated the photo-activated antibacterial function of a series of specifically prepared carbon dots with 2,2'-(ethylenedioxy)bis(ethylamine) as the surface functionalization molecule (EDA-CDots), whose fluorescence quantum yields (Φ) ranged from 7.5% to 27%. The results revealed that the effectiveness of CDots' photo-activated bactericidal function was correlated with their observed Φ values.

Modified Facile Synthesis for Quantitatively Fluorescent Carbon Dots.

A simple yet consequential modification was made to the popular carbonization processing of citric acid - polyethylenimine precursor mixtures to produce carbon dots (CDots). The modification was primarily on pushing the carbonization processing a little harder at a higher temperature, such as the hydrothermal processing condition of around 330 °C for 6 hours. The CDots thus produced are comparable in spectroscopic and other properties to those obtained in other more controlled syntheses including the deliberate chemical functionalization of preprocessed and selected small carbon nanoparticles, demonstrating the consistency in CDots and reaffirming their general definition as carbon nanoparticles with surface passivation by organic or other species.

Data on peptides identified by mass spectrometry analysis of in vitro DYRK1A-mediated phosphorylation sites on GLI1.

The data presented in this article support the accompanying research article "Identification of a DYRK1A-mediated phosphorylation site within the nuclear localization sequence of the hedgehog transcription factor GLI1" (Ehe et al., 2017) [1]. Although it has been demonstrated that DYRK1A (dual-specificity tyrosine-regulated kinase 1A) can phosphorylate the hedgehog pathway transcription factor GLI1 (GLIoma-associated oncogene homolog 1) and promote its nuclear localization, the DYRK1A-mediated sites of phosphorylation on GLI1 involved were not fully known.

Pharmacological targeting of GLI1 inhibits proliferation, tumor emboli formation and in vivo tumor growth of inflammatory breast cancer cells.

Activation of the Hedgehog (Hh) pathway effector GLI1 is linked to tumorigenesis and invasiveness in a number of cancers, with targeting of GLI1 by small molecule antagonists shown to be effective. We profiled a collection of GLI antagonists possessing distinct mechanisms of action for efficacy in phenotypic models of inflammatory and non-inflammatory breast cancer (IBC and non-IBC) that we showed expressed varying levels of Hh pathway mediators. Compounds GANT61, HPI-1, and JK184 decreased cell proliferation, inhibited GLI1 mRNA expression and decreased the number of colonies formed in TN-IBC (SUM149) and TNBC (MDA-MB-231 and SUM159) cell lines.

Antibacterial effects of carbon dots in combination with other antimicrobial reagents.

This study was designed to investigate the antimicrobial effects of CDots in combination with other antimicrobial reagents, including H2O2, Na2CO3, and AcOH (acetic acid). CDots were synthesized and passivated with 2,2'-(ethylenedioxy)bis(ethylamine) (EDA). The minimal inhibitory concentration (MIC) of CDots was 64 μg/mL on both Gram negative bacteria E.

Atorvastatin and lovastatin, but not pravastatin, increased cellular complex formation between PCSK9 and the LDL receptor in human hepatocyte-like C3A cells.

Statins are the first-line treatment for hypercholesterolemic patients. Herein, the effects of three statins on complex formation between proprotein convertase subtilisin-kexin 9 (PCSK9) and the low density lipoprotein receptor (LDLR), a critical step for the PCSK9-dependent degradation of LDLR in the lysosome, were examined. Human hepatocyte-like C3A cells grown in control (containing 10% fetal bovine serum) or MITO+ (supplemented with BD™ MITO + serum extender) medium were also treated with atorvastatin (Atorv), lovastatin (Lov), or pravastatin (Prav) for 24 h.

Identification of a DYRK1A-mediated phosphorylation site within the nuclear localization sequence of the hedgehog transcription factor GLI1.

GLI1 is a key downstream transcription effector of the Hedgehog (Hh) signaling pathway that is involved in promoting cell growth, differentiation and tissue patterning in embryonic development. GLI1 over-activation and its nuclear localization has also been linked to the increased aggressiveness of a number of cancers. It has previously been demonstrated that DYRK1A (dual-specificity tyrosine-regulated kinase 1A) can phosphorylate GLI1 and promote GLI1 nuclear localization and its transcriptional activity.

Discovery of small molecule inhibitors for the C. elegans caspase CED-3 by high-throughput screening.

C. elegans has been widely used as a model organism for programmed cell death and apoptosis. Although the CED-3 caspase is the primary effector of cell death in C.

Hypercholesterolemia: The role of PCSK9.

Heart disease ends the life of more people than any other disease in the United States. High levels of low density lipoprotein (LDL)-cholesterol cause heart diseases by increasing the formation of atherosclerotic plaques. Proprotein convertase subtilisin/kexin-9 (PCSK9) indirectly regulates plasma LDL levels by controlling the LDL receptor expression at the plasma membrane.

Plant-Produced Asialo-Erythropoietin Restores Pancreatic Beta-Cell Function by Suppressing Mammalian Sterile-20-like Kinase (MST1) and Caspase-3 Activation.

Pancreatic beta-cell death adversely contributes to the progression of both type I and II diabetes by undermining beta-cell mass and subsequently diminishing endogenous insulin production. Therapeutics to impede or even reverse the apoptosis and dysfunction of beta-cells are urgently needed. Asialo-rhuEPO, an enzymatically desialylated form of recombinant human erythropoietin (rhuEPO), has been shown to have cardioprotective and neuroprotective functions but with no adverse effects like that of sialylated rhuEPO.

Inflammatory breast cancer tumor emboli express high levels of anti-apoptotic proteins: use of a quantitative high content and high-throughput 3D IBC spheroid assay to identify targeting strategies.

Inflammatory breast cancer (IBC) is one of the most lethal breast cancer variants; with existing therapy, 5-yr survival rate is only 35%. Current barriers to successful treatment of IBC include frequent infiltration and the presence of tumor cell clusters, termed tumor emboli, within the breast parenchyma and lymphatics. Prior studies have identified the role of anti-apoptotic signaling, in particular hyperactivation of NFκB and its target genes, in IBC pathobiology and therapeutic resistance.

Carbonic anhydrase III (Car3) is not required for fatty acid synthesis and does not protect against high-fat diet induced obesity in mice.

Carbonic anhydrases are a family of enzymes that catalyze the reversible condensation of water and carbon dioxide to carbonic acid, which spontaneously dissociates to bicarbonate. Carbonic anhydrase III (Car3) is nutritionally regulated at both the mRNA and protein level. It is highly enriched in tissues that synthesize and/or store fat: liver, white adipose tissue, brown adipose tissue, and skeletal muscle.

Bisphenol A activates EGFR and ERK promoting proliferation, tumor spheroid formation and resistance to EGFR pathway inhibition in estrogen receptor-negative inflammatory breast cancer cells.

Emerging evidence from epidemiological studies suggests a link between environmental chemical exposure and progression of aggressive breast cancer subtypes. Of all clinically distinct types of breast cancers, the most lethal phenotypic variant is inflammatory breast cancer (IBC). Overexpression of epidermal growth factor receptors (EGFR/HER2) along with estrogen receptor (ER) negativity is common in IBC tumor cells, which instead of a solid mass present as rapidly proliferating diffuse tumor cell clusters.

Carbon Dots' Antiviral Functions Against Noroviruses.

This study reported the first assessment of carbon dots' (CDots) antiviral activity to human norovirus virus-like-particles (VLPs), GI.1 and GII.4 VLPs.

A Novel Role of Silibinin as a Putative Epigenetic Modulator in Human Prostate Carcinoma.

Silibinin, extracted from milk thistle ( L.), has exhibited considerable preclinical activity against prostate carcinoma. Its antitumor and chemopreventive activities have been associated with diverse effects on cell cycle, apoptosis, and receptor-dependent mitogenic signaling pathways.

Photoexcited State Properties of Carbon Dots from Thermally Induced Functionalization of Carbon Nanoparticles.

Carbon dots are small carbon nanoparticles with various surface passivation schemes, in which more effective has been the deliberate chemical functionalization of the nanoparticles for brighter fluorescence emissions, though the synthesis method is more tedious and subject to some limitations in the selection of functionalization molecules. Another more popular synthesis method has been the carbonization of organic species, with the method being more efficient and versatile, but less controllable in the synthesis and for the desired dot structure and performance. In this work, a hybrid approach combining the advantageous characteristics of the two synthesis methods was applied to the preparation of carbon dots with polyethyleneimine (PEI) for surface passivation, where pre-processed and selected small carbon nanoparticles were functionalized with PEI in microwave-induced thermal reactions.

Approved Glycopeptide Antibacterial Drugs: Mechanism of Action and Resistance.

The glycopeptide antimicrobials are a group of natural product and semisynthetic glycosylated peptides that show antibacterial activity against Gram-positive organisms through inhibition of cell-wall synthesis. This is achieved primarily through binding to the d-alanyl-d-alanine terminus of the lipid II bacterial cell-wall precursor, preventing cross-linking of the peptidoglycan layer. Vancomycin is the foundational member of the class, showing both clinical longevity and a still preferential role in the therapy of methicillin-resistant Staphylococcus aureus and of susceptible Enterococcus spp.

Influence of Matrices on 3D-Cultured Prostate Cancer Cells' Drug Response and Expression of Drug-Action Associated Proteins.

This study investigated the effects of matrix on the behaviors of 3D-cultured cells of two prostate cancer cell lines, LNCaP and DU145. Two biologically-derived matrices, Matrigel and Cultrex BME, and one synthetic matrix, the Alvetex scaffold, were used to culture the cells. The cell proliferation rate, cellular response to anti-cancer drugs, and expression levels of proteins associated with drug sensitivity/resistance were examined and compared amongst the 3D-cultured cells on the three matrices and 2D-cultured cells.

Ubisol-Q10 Prevents Glutamate-Induced Cell Death by Blocking Mitochondrial Fragmentation and Permeability Transition Pore Opening.

Mitochondrial dysfunction and oxidative stress are the major events that lead to the formation of mitochondrial permeability transition pore (mPTP) during glutamate-induced cytotoxicity and cell death. Coenzyme Q10 (CoQ10) has widely been used for the treatment of mitochondrial disorders and neurodegenerative diseases. Comparing to traditional lipid-soluble CoQ10, water soluble CoQ10 (Ubisol-Q10) has high intracellular and intra-mitochondrial distribution.

Visible-Light-Activated Bactericidal Functions of Carbon "Quantum" Dots.

Carbon dots, generally defined as small carbon nanoparticles with various surface passivation schemes, have emerged as a new class of quantum-dot-like nanomaterials, with their optical properties and photocatalytic functions resembling those typically found in conventional nanoscale semiconductors. In this work, carbon dots were evaluated for their photoinduced bactericidal functions, with the results suggesting that the dots were highly effective in bacteria-killing with visible-light illumination. In fact, the inhibition effect could be observed even simply under ambient room lighting conditions.

The Chemical Molecule B355252 is Neuroprotective in an In Vitro Model of Parkinson's Disease.

6-Hydroxydopamine (6-OHDA) is a neurotoxin frequently used to create in vitro and in vivo experimental models of Parkinson's disease (PD), a chronic neurodegenerative disorder largely resulting from damage to the nigrostriatal dopaminergic pathway. No effective drugs or therapies have been developed for this devastating disorder, and current regimens of symptomatic therapeutics only alleviate symptoms temporarily. Therefore, effective treatments that reverse or cure this disorder are urgently needed.

Development of a Cell-Based Fluorescence Polarization Biosensor Using Preproinsulin to Identify Compounds That Alter Insulin Granule Dynamics.

Diabetes currently affects 9.3% of the U.S.