Extracellular micro/nanovesicles rescue kidney from ischemia-reperfusion injury

Acute renal failure (ARF) is a clinical challenge that is highly resistant to treatment, and its high rate of mortality is alarming. Ischemia–reperfusion injury (IRI) is the most common cause of ARF. Especially IRI is implicated in kidney transplantation and can determine graft survival. Although the exact pathophysiology of renal IRI is unknown, the role of inflammatory responses has been elucidated. Because mesenchymal stromal cells (MSCs) have strong immunomodulatory properties, they are under extensive investigation as a therapeutic modality for renal IRI. Extracellular vesicles (EVs) play an integral role in cell-to-cell communication. Because the regenerative potential of the MSCs can be recapitulated by their EVs, the therapeutic appeal of MSC-derived EVs has dramatically increased in the past decade. Higher safety profile and ease of preservation without losing function are other advantages of EVs compared with their producing cells. In the current review, the preliminary results and potential of MSC-derived EVs to alleviate kidney IRI are summarized. We might be heading toward a cell-free approach to treat renal IRI.     

Cytoplasmic SIR2 homologue overexpression promotes survival of Leishmania parasites by preventing programmed cell death

The Silent Information Regulator (SIR2) family of genes have been cloned from a variety of species ranging from bacteria to man. In previous studies, we reported the characterization of a Leishmania major gene encoding a protein with extensive homology to yeast SIR2p and expressed by different Leishmania species and parasite developmental stages and thus termed LmSIR2. Unlike the yeast SIR2p, LmSIR2p is mainly localized within the cytoplasm. In the present study, sequencing of a homologue encoding gene in another Leishmania species, Leishmania infantum, revealed 93% overall amino acid identity with L. major SIR2 gene. Further, using L. infantum as a recipient for a plasmid vector (pTEX) which allows overexpression of LmSIR2p led to the accumulation of the protein in the parasite cytoplasm of both promastigote and amastigote forms and a striking increase in the survival of amastigotes, the vertebrate stage of the parasite, when maintained under normal axenic culture conditions. This phenotype was also observed when L. infantum parasites were transfected with a cosmid vector (CLHyg), isolated from a L. infantum cosmid library, carrying the L. infantum SIR2 gene (CLHyg-LiSIR2). In contrast, no effect was observed on survival of the promastigote forms (insect stage) under similar culture conditions. However, when the glucose was used as a unique source of energy under starvation conditions, the viability of promastigotes was significantly enhanced. Moreover, we showed that amastigote forms in the stationary phase of culture died with a feature of apoptosis as revealed by the appearance of YOPRO-1 positive cells and that expression of LmSIR2 protein substantially delays this phenomenon. Taken together, these results demonstrate the existence of SIR2-related proteins encoding genes in different Leishmania species and suggest that LmSIR2p could participate among other factors in the control of cell death.     

Diffusion of MRI and CT Contrast Agents in Articular Cartilage under Static Compression

Cartilage has a limited capacity for self-repair and focal damage can eventually lead to complete degradation of the tissue. Early diagnosis of degenerative changes in cartilage is therefore essential. Contrast agent-based computed tomography and magnetic resonance imaging provide promising tools for this purpose. However, the common assumption in clinical applications that contrast agents reach steady-state distributions within the tissue has been of questionable validity. Characterization of nonequilibrium diffusion of contrast agents rather than their equilibrium distributions may therefore be more effective for image-based cartilage assessment. Transport of contrast agent through the extracellular matrix of cartilage can be affected by tissue compression due to matrix structural and compositional changes including reduced pore size and fluid content. We therefore investigate the effects of static compression on diffusion of three common contrast agents: sodium iodide, sodium diatrizoate, and gadolinium diethylenetriamine-pentaacid (Gd-DTPA). Results showed that static compression was associated with significant decreases in diffusivities for sodium iodide and Gd-DTPA, with similar (but not significant) trends for sodium diatrizoate. Molecular mass of contrast agents affected diffusivities as the smallest one tested, sodium iodide, showed higher diffusivity than sodium diatrizoate and Gd-DTPA. Compression-associated cartilage matrix alterations such as glycosaminoglycan and fluid contents were found to correspond with variations in contrast agent diffusivities. Although decreased diffusivity was significantly correlated with increasing glycosaminoglycan content for sodium iodide and Gd-DTPA only, diffusivity significantly increased for all contrast agents by increasing fluid fraction. Because compounds based on iodine and gadolinium are commonly used for computed tomography and magnetic resonance imaging, present findings can be valuable for more accurate image-based assessment of variations in cartilage composition associated with focal injuries.     

Synthesis and in vitro evaluation of novel 1,2,4-triazine derivatives as neuroprotective agents

The role of novel triazine derivatives against oxidative stress exerted by hydrogen peroxide on differentiated rat pheochromocytoma (PC12) cell line was examined and a consistent protection from H₂O₂-induced cell death, associated with a marked reduction in caspase-3 activation, was observed. Moreover, activation of NF-κB, a known regulator of a host of genes that involves in specific stress and inflammatory responses by H₂O₂, was greatly impaired by triazine pretreatment in differentiated PC12 cells. Neuroprotective effect of such compounds may represent a promising approach for treatment of neurodegenerative diseases.     

Leishmania species: Detection and identification by nested PCR assay from skin samples of rodent reservoirs

Many rodent species act as reservoir hosts of zoonotic cutaneous leishmaniasis in endemic areas. In the present study a simple and reliable assay based on nested PCR was developed for the detection and identification of Leishmania parasites from rodent skin samples. We designed Leishmania-specific primers that successfully amplified ITS regions of Leishmania major, Leishmania gerbilli and Leishmania turanica using nested PCR. Out of 95 field collected Rhombomys opimus, 21 were positive by microscopic examination and 48 by nested PCR. The percentage of gerbils infected with L. major, L. gerbilli and L. turanica was 3.2%, 1.1% and 27.4%, respectively. In 15.8% of the rodents, we found mixed natural infections by L. major and L. turanica, 1.1% by L. major and L. gerbilli, and 2.1% by the three species. We concluded that this method is simple and reliable for detecting and identifying Leishmania species circulating in rodent populations.     

Salicylic acid changes morpho-physiological attributes of feverfew (Tanacetum parthenium L.) under salinity stress

Feverfew (Tanacetum parthenium) (TP) is a valuable medicinal plant from Asteraceae family with various pharmaceutical and therapeutic properties. A pot experiment was conducted to evaluate the effect of salicylic acid (SA) on the physiological and morphological responses of TP under salinity stress. Salinity was induced by NaCl and CaCl₂ (2:1) at 30, 60, 90, 120, 150 and 180 mM levels. SA was applied as foliar application at 0, 200 and 300 ppm concentrations. Plant height, leaf and shoot number, fresh and dry weight and essential oil, starch, sugar, protein, proline, catalase (CAT), peroxidase (POD), and ascorbic peroxidase (APX) contents were as measured morpho-physiological traits. The results showed that SA significantly (P ≤ 0.05) improved the measured traits and caused higher tolerance in TP plants under salinity stress. The essential oil content increased with increasing the salinity level up to 90 mM, which was more significant when combined with SA application. All of the measured traits except proline content, antioxidant enzymes, essential oil and sugar decreased at high salinity levels.