Band 401, Heft 10

Metabolic disorders, including obesity, diabetes, and hyperlipidemia, as well as cardiovascular diseases (CVD), particularly atherosclerosis, are still leading causes of death worldwide. Plasma levels of low-density lipoprotein (LDL) are currently being considered as a critical risk factor for the diseases mentioned above, especially atherosclerosis. Because of the heterogeneous nature of LDL, many studies have already been conducted on its subclasses, especially small dense LDL (sdLDL). According to available evidence, sdLDL levels can be considered as an ideal alternative to LDL levels for monitoring CVD and early diagnosis of atherosclerosis. Recently, several researchers have focused on factors that are able to decrease sdLDL levels and improve health quality. Therefore, the purpose of this study is to describe the production process of sdLDL particles and review the effects of pharmaceutical and dietary agents as well as lifestyle on sdLDL plasma levels. In brief, their mechanisms of action are discussed. Apparently, cholesterol and LDL-lowering compounds are also effective in the reduction of sdLDL levels. In addition, improving lipid profile, especially the reduction of triglyceride levels, appropriate regimen, and lifestyle can decrease sdLDL levels. Therefore, all the aforementioned parameters should be taken into consideration simultaneously in sdLDL levels reducing strategies.

PIWI-interacting RNAs (piRNAs) are small regulatory RNAs that associate with members of the PIWI clade of the Argonaute superfamily of proteins. piRNAs are predominantly found in animal gonads. There they silence transposable elements (TEs), regulate gene expression and participate in DNA methylation, thus orchestrating proper germline development. Furthermore, PIWI proteins are also indispensable for the maintenance and differentiation capabilities of pluripotent stem cells in free-living invertebrate species with regenerative potential. Thus, PIWI proteins and piRNAs seem to constitute an essential molecular feature of somatic pluripotent stem cells and the germline. In keeping with this hypothesis, both PIWI proteins and piRNAs are enriched in neoblasts, the adult stem cells of planarian flatworms, and their presence is a prerequisite for the proper regeneration and perpetual tissue homeostasis of these animals. The piRNA pathway is required to maintain the unique biology of planarians because, in analogy to the animal germline, planarian piRNAs silence TEs and ensure stable genome inheritance. Moreover, planarian piRNAs also contribute to the degradation of numerous protein-coding transcripts, a function that may be critical for neoblast differentiation. This review gives an overview of the planarian piRNA pathway and of its crucial function in neoblast biology.

α -Synuclein fibrillation is now regarded as a major pathogenic process in Parkinson’s disease and its proteinaceous deposits are also detected in other neurological disorders including Alzheimer's disease. Therefore anti-amyloidegenic compounds may delay or prevent the progression of synucleinopathies disease. Molecular chaperones are group of proteins which mediate correct folding of proteins by preventing unsuitable interactions which may lead to aggregation. The objective of this study was to investigate the anti-amyloidogenic effect of molecular chaperone artemin on α -synuclein. As the concentration of artemin was increased up to 4 μg/ml, a decrease in fibril formation of α -synuclein was observed using thioflavin T (ThT) fluorescence and congo red (CR) assay. Transmission electron microscopy (TEM) images also demonstrated a reduction in fibrils in the presence of artemin. The secondary structure of α -synuclein was similar to its native form prior to fibrillation when incubated with artemin. A cell-based assay has shown that artemin inhibits α -synuclein aggregation and reduce cytotoxicity, apoptosis and reactive oxygen species (ROS) production. Our results revealed that artemin has efficient chaperon activity for preventing α -synuclein fibril formation and toxicity.

Pancreatic ductal adenocarcinoma is one of the most aggressive tumors with a microenvironment marked by hypoxia and starvation. Galectin-3 has been evaluated in solid tumors and seems to present both pro/anti-tumor effects. So, this study aims to characterize the expression of Galectin-3 from pancreatic tumor cells and analyze its influence for cell survive and motility in mimetic microenvironment. For this, cell cycle and cell death were accessed through flow cytometry. Characterization of inside and outside Galectin-3 was performed through Real-Time Quantitative Reverse Transcription PCR (qRT-PCR), immunofluorescence, Western blot, and ELISA. Consequences of Galectin-3 extracellular inhibition were investigated using cell death and scratch assays. PANC-1 showed increased Galectin-3 mRNA expression when cultivated in hypoxia for 24 and 48 h. After 24 h in simultaneously hypoxic/deprived incubation, PANC-1 shows increased Galectin-3 protein and secreted levels. For Mia PaCa-2, cultivation in deprivation was determinant for the increasing in Galectin-3 mRNA expression. When cultivated in simultaneously hypoxic/deprived condition, Mia PaCa-2 also presented increasing for the Galectin-3 secreted levels. Treatment of PANC-1 cells with lactose increased the death rate when cells were incubated simultaneously hypoxic/deprived condition. Therefore, it is possible to conclude that the microenvironmental conditions modulate the Galectin-3 expression on the transcriptional and translational levels for pancreatic cancer cells.

The proliferation and migration of endothelial cells are vascular events of inflammation, a process which can also potentiate the effects of promigratory factors. With the aim of investigating possible modifications in the activity of erythropoietin (Epo) in an inflammatory environment, we found that Epo at a non-promigratory concentration was capable of stimulating EA.hy926 endothelial cell migration when TNF- α was present. VCAM-1 and ICAM-1 expression, as well as adhesion of monocytic THP-1 cells to endothelial layers were also increased. Structurally modified Epo (carbamylation or N -homocysteinylation) did not exhibit these effects. The sensitizing effect of TNF- α on Epo activity was mediated by the Epo receptor. Inhibition assays targeting the PI3K/mTOR/NF-κB pathway, shared by Epo and TNF- α , show a cross-talk between both cytokines. As observed in assays using antioxidants, cell migration elicited by TNF-α + Epo depended on TNF- α -generated reactive oxygen species (ROS). ROS-mediated inactivation of protein tyrosine phosphatase 1B (PTP1B), involved in Epo signaling termination, could explain the synergistic effect of these cytokines. Our results suggest that ROS generated by inflammation inactivate PTP1B, causing the Epo signal to last longer. This mechanism, along with the cross-talk between both cytokines, could explain the sensitizing action of TNF- α on the migratory effect of Epo.

Extracellular Hsp70 (eHsp70) is elevated in blood of patients with inflammatory diseases (e.g. chronic obstructive pulmonary disease), prone to bacterial infections. It stimulates pro-inflammatory effects in cells via TLR2 and TLR4. The main hypothesis was that eHsp70 induces inflammation and alters inflammatory responses to lipopolysaccharide (LPS) and lipoteichoic acid (LTA). We assessed pro-inflammatory cytokines concentrations, TLR2 , TLR4 and Hsp70 mRNA expressions, NF-κB and MAPKs activation, and viability after treatment of monocyte-derived macrophages (MDMs) and THP-1 cells with recombinant human (rh) Hsp70, LPS and LTA. rhHsp70, LPS, LTA and their combinations induced IL-6, IL-8 and TNF-α from MDMs. LPS, LTA, and combinations with rhHsp70 increased TLR2 and decreased TLR4 in both cells. rhHsp70 increased TLR2 and TLR4 in THP-1 cells, and TLR2 in MDMs. rhHsp70, LPS and their combinations up-regulated Hsp70 in MDMs, while down-regulated it in THP-1. LPS and its combinations with rhHsp70 lowered cell viability in THP-1 cells and activated caspases-8 and -9. Involvement of NF-κB and MAPKs in inflammatory and survival mechanisms stimulated by rhHsp70 was demonstrated. eHsp70 alone and in combination with bacterial components could provoke inflammation and affect viability of MDMs and THP-1 cells leading to disturbed inflammatory responses in diseases accompanied with bacterial colonisations or infections.

It has been reported that high-mobility group box 3 is overexpressed in various cancers. This study aimed to explore its function in non-small cell lung cancer (NSCLC). A546 and H460 cell lines were used for in vivo experiments, scratch healing tests, transwell migration and invasion experiments. It was first found that HMGB3 was highly expressed in tumor tissues in the patients and associated with NSCLC stage. Silencing of HMGB3 significantly slowed the growth, proliferation and invasion of NSCLC in vitro , and repressed cell growth in vivo . Mechanistic studies suggest that the observed effects were mediated by inhibiting the expression of β-catenin/MMP7/c-Myc in Wnt pathway. Our study highlights the role of HMGB3 in NSCLC, which may provide a therapeutic target for the treatment of NSCLC.