Psoriasis and Gut Microbiome—Current State of Art

Psoriasis is a chronic, immune-mediated inflammatory disease that affects around 125 million people worldwide. Several studies concerning the gut microbiota composition and its role in disease pathogenesis recently demonstrated significant alterations among psoriatic patients. Certain parameters such as Firmicutes/Bacteroidetes ratio or Psoriasis Microbiome Index were developed in order to distinguish between psoriatic and healthy individuals. The “leaky gut syndrome” and bacterial translocation is considered by some authors as a triggering factor for the onset of the disease, as it promotes chronic systemic inflammation. The alterations were also found to resemble those in inflammatory bowel diseases, obesity and certain cardiovascular diseases. Microbiota dysbiosis, depletion in SCFAs production, increased amount of produced TMAO, dysregulation of the pathways affecting the balance between lymphocytes populations seem to be the most significant findings concerning gut physiology in psoriatic patients. The gut microbiota may serve as a potential response-to-treatment biomarker in certain cases of biological treatment. Oral probiotics administration as well as fecal microbial transplantation were most reported in bringing health benefits to psoriatic patients. However, the issue of psoriatic bacterial gut composition, its role and healing potential needs further investigation. Here we reviewed the literature on the current state of the relationship between psoriasis and gut microbiome.     

Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models

1,25-Dihydroxycholecalciferol, the hormonally active vitamin D₃ metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)₂D₃ analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study. Both the vitamin D active metabolite and synthetic analog regulated the growth of not only estrogen receptor-positive cells (T47D and MCF-7, in vitro and in vivo), but also hormone-independent cancer cells such as SKBR-3 (HER-2-positive) and MDA-MB-231 (triple-negative), despite their relatively low VDR expression. Combined with An, PRI-2191 and PRI-2205 significantly inhibited the tumor growth of MCF-7 cells. Potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase by both An (enzyme inhibition) and vitamin D compounds (switched off/decreased aromatase gene expression, decreased expression of other genes related to estrogen signaling) and by regulation of the expression of the estrogen receptor ERα and VDR.     

The influence of pacing rate and autonomic blockade on human primary and secondary atrial pacemakers

Current gene therapy protocols designed to treat adenosine deaminase (ADA) deficiency and other metabolic disorders suffer from low-efficiency delivery to target cells and a lack of long-term stability in expression of the therapeutic proteins. These problems may be resolved by use of an in vivo dominant selection. The multidrug transporter (MDR1) has been suggested as a useful selective marker for gene therapy. In this work, we co-expressed ADA and MDR1 cDNA in a retroviral vector using an internal ribosome entry site (IRES) from encephalomyocarditis virus. This system produced a bicistronic mRNA containing both ADA and MDR1, which enables co-expression of ADA and MDR1, and also allows the two proteins to be translated separately. After in vitro selection using a cytotoxic MDR1 substrate, vincristine, we demonstrated that functional ADA was co-expressed with MDR1 in proportion to the expression level of MDR1, whereas MDR1 expression was proportional to the stringency of the vincristine selection. Because the efficiency of IRES-dependent translation was much lower than that of cap-dependent translation in this system, we observed lower expression of the genes positioned after the IRES. This asymmetric expression caused a lower viral titer when MDR1 was placed downstream from the IRES, but it also provided a way of modulating the relative expression of ADA and MDR1. The retroviral system described in this work may serve as a useful tool to evaluate the strategies involving in vivo dominant selection for gene therapy of ADA-deficient patients.     

Solid state reactions in the Fe2O3-CaCO3-In2O3 system

The kinetics of solid-state reactions of powdered reactants were investigated by X-ray and by differential thermogravimetry in a magnetic field. Measurements revealed mutual diffusion of the Fe³⁺ and In³⁺ ions in the Fe₂O₃-In₂O₃ system heat treated for 3 h at 700 to 1400° C. Diffusion of indium into the Fe₂O₃ lattice caused a shift of the Curie temperature of the antiferromagnetic iron oxide towards lower temperatures. Only Caln₂O₄ was found between CaCO₃ and In₂O₃ up to 1400° C. Also, in the Fe₂O₃-CaCO₃-In₂O₃in system, the reaction started with the mutual diffusion of iron and indium and the forming of CaFe₂O₄. End-products were the magnetic -Ca₄Fe₁₄O₂₅ and CaFe₄O₇, and the non-magnetic CaFe₅O₇, depending on the In³⁺ concentration. Indium stabilized the magnetic calcium-iron oxide structures, shifting their Curie temperatures towards lower values.     

PACAP-38 in Acute ST-Segment Elevation Myocardial Infarction in Humans and Pigs: A Translational Study

Acute myocardial infarction (MI) is one of the most common causes of death worldwide. Pituitary adenylate cyclase activating polypeptide (PACAP) is a cardioprotective neuropeptide expressing its receptors in the cardiovascular system. The aim of our study was to examine tissue PACAP-38 in a translational porcine MI model and plasma PACAP-38 levels in patients with ST-segment elevation myocardial infarction (STEMI). Significantly lower PACAP-38 levels were detected in the non-ischemic region of the left ventricle (LV) in MI heart compared to the ischemic region of MI-LV and also to the Sham-operated LV in porcine MI model. In STEMI patients, plasma PACAP-38 level was significantly higher before percutaneous coronary intervention (PCI) compared to controls, and decreased after PCI. Significant negative correlation was found between plasma PACAP-38 and troponin levels. Furthermore, a significant effect was revealed between plasma PACAP-38, hypertension and HbA1c levels. This was the first study showing significant changes in cardiac tissue PACAP levels in a porcine MI model and plasma PACAP levels in STEMI patients. These results suggest that PACAP, due to its cardioprotective effects, may play a regulatory role in MI and could be a potential biomarker or drug target in MI.     

Ethanol combustion over strontium- and cerium-doped LaCoO3 catalysts

Ce- or Sr-doped LaCoO₃ bulk perovskites were prepared by citric acid method as well as 10 wt.% of LaCoO₃ was deposited on alumina carrier stabilized with lanthanum. Properties of prepared materials were characterized by determination of surface area, acid-basic properties and XRD, XPS, TPDO₂, H₂-TPR measurements as well as catalytic activity and selectivity for ethanol combustion was tested. It was found that substitution of La in LaCoO₃ with either Sr or Ce has only small effect on its activity in ethanol combustion. Strontium inserted into LaCoO₃ structure increases basic character of the perovskite surface as well as selectivity to acetaldehyde (ACA). Substitution of La with cerium has no effect on the concentration of basic sites and does not affect the selectivity to ACA. Activity of LaCoO₃-based catalysts in ethanol combustion and their selectivity to ACA formation can be explained on the basis of the presence of both -oxygen species and sites with basic character on the material surface.

Acid-basic properties of supported LaCoO₃ are dominated by acidic character of the carrier. Results of XPS and H₂-TPR measurements of LaCoO₃ supported on La–Al₂O₃ suggest that perovskite remains in strong interaction with carrier and probably is partially decomposed. Deposition of perovskite on stabilized carrier significantly increases the rate of ethanol combustion.     

Clonal variation in reproductive response to temperature by a potential bulking control agent, Lecane inermis (Rotifera)

The novel idea of using rotifers Lecane inermis (Rotifera, Monogononta) as a tool to overcome activated sludge bulking generates an on-going need to study rotifer biology. The results of biological research on rotifers can serve to improve the method so that it can be most effective when applied in treatment plants. The aim of this study was to test the effect of temperature on four selected rotifer clones originating from different treatment plants. The rate of population development from a single individual (parthenogenetic female) during a 10-day experiment was measured at three temperatures: 8, 15 and 20 degrees C. The temperatures used reflect the annual temperature distribution in the majority of municipal wastewater treatment plants in the temperate zone. The growth rate coefficient (r) and doubling time (tD) were calculated for each clone. Under the most favourable conditions (20 degrees C), rvalues varied between 0.41 and 0.47 d and doubling time between 1.5 and 1.7 d. At a temperature of 15 degrees C, the doubling time was approximately two times longer (2.5-3.4 d). The strongest intraspecific variations were observed at the lowest temperature of 8 degrees C. At this temperature, one of the clones almost failed to proliferate, and another exhibited a doubling time of 7.9 d. The doubling times were a few times greater for the remaining two clones (60 d for Lk1, 33.3 d for Lk4). These results could be very useful in predicting the chances that the rotifers would survive in a biological reactor in a wastewater treatment plant at the temperatures used in these reactors.