H-Ferritin-Regulated MicroRNAs Modulate Gene Expression in K562 Cells

In a previous study, we showed that the silencing of the heavy subunit (FHC) offerritin, the central iron storage molecule in the cell, is accompanied by a modification in global gene expression. In this work, we explored whether different FHC amounts might modulate miRNA expression levels in K562 cells and studied the impact of miRNAs in gene expression profile modifications. To this aim, we performed a miRNA-mRNA integrative analysis in K562 silenced for FHC (K562^shFHC) comparing it with K562 transduced with scrambled RNA (K562^shRNA). Four miRNAs, namely hsa-let-7g, hsa-let-7f, hsa-let-7i and hsa-miR-125b, were significantly up-regulated in silenced cells. The remarkable down-regulation of these miRNAs, following FHC expression rescue, supports a specific relation between FHC silencing and miRNA-modulation. The integration of target predictions with miRNA and gene expression profiles led to the identification of a regulatory network which includes the miRNAs up-regulated by FHC silencing, as well as91 down-regulated putative target genes. These genes were further classified in 9 networks; the highest scoring network, “Cell Death and Survival, Hematological System Development and Function, Hematopoiesis”, is composed by 18 focus molecules including RAF1 and ERK1/2. We confirmed that, following FHC silencing, ERK1/2 phosphorylation is severely impaired and that RAF1 mRNA is significantly down-regulated. Taken all together, our data indicate that, in our experimental model, FHC silencing may affect RAF1/pERK1/2 levels through the modulation of a specific set of miRNAs and add new insights in to the relationship among iron homeostasis and miRNAs.     

Purine receptors are required for DHA-mediated neuroprotection against oxygen and glucose deprivation in hippocampal slices

Docosahexaenoic acid (DHA) is important for central nervous system function during pathological states such as ischemia. DHA reduces neuronal injury in experimental brain ischemia; however, the underlying mechanisms are not well understood. In the present study, we investigated the effects of DHA on acute hippocampal slices subjected to experimental ischemia by transient oxygen and glucose deprivation (OGD) and re-oxygenation and the possible involvement of purinergic receptors as the mechanism underlying DHA-mediated neuroprotection. We observed that cellular viability reduction induced by experimental ischemia as well as cell damage and thiobarbituric acid reactive substances (TBARS) production induced by glutamate (10 mM) were prevented by hippocampal slices pretreated with DHA (5 μM). However, glutamate uptake reduction induced by OGD and re-oxygenation was not prevented by DHA. The beneficial effect of DHA against cellular viability reduction induced by OGD and re-oxygenation was blocked with PPADS (3 μM), a nonselective P2X_1–5 receptor antagonist as well as with a combination of TNP-APT (100 nM) plus brilliant blue (100 nM), which blocked P2X₁, P2X₃, P2X_2/3, and P2X₇ receptors, respectively. Moreover, adenosine receptors blockade with A₁ receptor antagonist DPCPX (100 nM) or with A_2B receptor antagonist alloxazine (100 nM) inhibited DHA-mediated neuroprotection. The addition of an A_2A receptor antagonist ZM241385 (50 nM), or A₃ receptor antagonist VUF5574 (1 μM) was ineffective. Taken together, our results indicated that neuroprotective actions of DHA may depend on P2X, A₁, and A_2B purinergic receptors activation. Our results reinforce the notion that dietary DHA may act as a local purinergic modulator in order to prevent neurodegenerative diseases.     

Trend of Narratives in the Age of Misinformation

Social media enabled a direct path from producer to consumer of contents changing the way users get informed, debate, and shape their worldviews. Such a disintermediation might weaken consensus on social relevant issues in favor of rumors, mistrust, or conspiracy thinking—e.g., chem-trails inducing global warming, the link between vaccines and autism, or the New World Order conspiracy. Previous studies pointed out that consumers of conspiracy-like content are likely to aggregate in homophile clusters—i.e., echo-chambers. Along this path we study, by means of a thorough quantitative analysis, how different topics are consumed inside the conspiracy echo-chamber in the Italian Facebook. Through a semi-automatic topic extraction strategy, we show that the most consumed contents semantically refer to four specific categories: environment, diet, health, and geopolitics. We find similar consumption patterns by comparing users activity (likes and comments) on posts belonging to these different semantic categories. Finally, we model users mobility across the distinct topics finding that the more a user is active, the more he is likely to span on all categories. Once inside a conspiracy narrative users tend to embrace the overall corpus.     

Evolution of Skin Temperature after the Application of Compressive Forces on Tendon,Muscle and Myofascial Trigger Point

Some assessment and diagnosis methods require palpation or the application of certain forces on the skin, which affects the structures beneath, we highlight the importance of defining possible influences on skin temperature as a result of this physical contact. Thus, the aim of the present study is to determine the ideal time for performing thermographic examination after palpation based on the assessment of skin temperature evolution. Randomized and crossover study carried out with 15 computer-user volunteers of both genders, between 18 and 45 years of age, who were submitted to compressive forces of 0, 1, 2 and 3 kg/cm² for 30 seconds with a washout period of 48 hours using a portable digital dynamometer. Compressive forces were applied on the following spots on the dominant upper limb: myofascial trigger point in the levator scapulae, biceps brachii muscle and palmaris longus tendon. Volunteers were examined by means of infrared thermography before and after the application of compressive forces (15, 30, 45 and 60 minutes). In most comparisons made over time, a significant decrease was observed 30, 45 and 60 minutes after the application of compressive forces (p < 0.05) on the palmaris longus tendon and biceps brachii muscle. However, no difference was observed when comparing the different compressive forces (p > 0.05). In conclusion, infrared thermography can be used after assessment or diagnosis methods focused on the application of forces on tendons and muscles, provided the procedure is performed 15 minutes after contact with the skin. Regarding to the myofascial trigger point, the thermographic examination can be performed within 60 minutes after the contact with the skin.     

Dysregulated Immune Activation in Second-Line HAART HIV+ Patients Is Similar to That of Untreated Patients

Background

Successful highly active antiretroviral therapy (HAART) has changed the outcome of AIDS patients worldwide because the complete suppression of viremia improves health and prolongs life expectancy of HIV-1+ patients. However, little attention has been given to the immunological profile of patients under distinct HAART regimens. This work aimed to investigate the differences in the immunological pattern of HIV-1+ patients under the first- or second-line HAART in Brazil.

Methods

CD4+ T cell counts, Viral load, and plasma concentration of sCD14, sCD163, MCP-1, RANTES, IP-10, IL-1β, IL-6, TNF-α, IL-12, IFN-α, IFN-γ, IL-4, IL-5, and IL-10 were assessed for immunological characterization of the following clinical groups: Non-infected individuals (NI; n = 66), HIV-1+ untreated (HIV; n = 46), HIV-1+ treated with first-line HAART (HAART 1; n = 15); and HIV-1+ treated with second-line HAART (HAART 2; n = 15).

Results

We found that the immunological biosignature pattern of HAART 1 is similar to that of NI individuals, especially in patients presenting slow progression of the disease, while patients under HAART 2 remain in a moderate inflammatory state, which is similar to that of untreated HIV patients pattern. Network correlations revealed that differences in IP-10, TNF-α, IL-6, IFN-α, and IL-10 interactions were primordial in HIV disease and treatment. Heat map and decision tree analysis identified that IP-10>TNF-α>IFN-α were the best respective HAART segregation biomarkers.

Conclusion

HIV patients in different HAART regimens develop distinct immunological biosignature, introducing a novel perspective into disease outcome and potential new therapies that consider HAART patients as a heterogeneous group.     

Waterborne Risperidone Decreases Stress Response in Zebrafish

The presence of drugs and their metabolites in surface waters and municipal effluents has been reported in several studies, but its impacts on aquatic organisms are not yet well understood. This study investigated the effects of acute exposure to the antipsychotic risperidone on the stress and behavioral responses in zebrafish. It became clear that intermediate concentration of risperidone inhibited the hypothalamic-pituitary-interrenal axis and displayed anxiolytic-like effects in zebrafish. The data presented here suggest that the presence of this antipsychotic in aquatic environments can alter neuroendocrine and behavior profiles in zebrafish.