Umbilical cord-derived mesenchymal stem cells preconditioned with isorhamnetin: potential therapy for burn wounds

BACKGROUNDImpaired wound healing can be associated with different pathological states. Burn wounds are the most common and detrimental injuries and remain a major health issue worldwide. Mesenchymal stem cells (MSCs) possess the ability to regenerate tissues by secreting factors involved in promoting cell migration, proliferation and differentiation, while suppressing immune reactions. Preconditioning of MSCs with small molecules having cytoprotective properties can enhance the potential of these cells for their use in cell-based therapeutics.AIMTo enhance the therapeutic potential of MSCs by preconditioning them with isorhamnetin for second degree burn wounds in rats.METHODSHuman umbilical cord MSCs (hU-MSCs) were isolated and characterized by surface markers, CD105, vimentin and CD90. For preconditioning, hU-MSCs were treated with isorhamnetin after selection of the optimized concentration (5 µmol/L) by cytotoxicity analysis. The migration potential of these MSCs was analyzed by the in vitro scratch assay. The healing potential of normal, and preconditioned hU-MSCs was compared by transplanting these MSCs in a rat model of a second degree burn wound. Normal, and preconditioned MSCs (IH + MSCs) were transplanted after 72 h of burn injury and observed for 2 wk. Histological and gene expression analyses were performed on day 7 and 14 after cell transplantation to determine complete wound healing.RESULTSThe scratch assay analysis showed a significant reduction in the scratch area in the case of IH + MSCs compared to the normal untreated MSCs at 24 h, while complete closure of the scratch area was observed at 48 h. Histological analysis showed reduced inflammation, completely remodeled epidermis and dermis without scar formation and regeneration of hair follicles in the group that received IH + MSCs. Gene expression analysis was time dependent and more pronounced in the case of IH + MSCs. Interleukin (IL)-1β, IL-6 and Bcl-2 associated X genes showed significant downregulation, while transforming growth factor β, vascular endothelial growth factor, Bcl-2 and matrix metallopeptidase 9 showed significant upregulation compared to the burn wound, showing increased angiogenesis and reduced inflammation and apoptosis.CONCLUSIONPreconditioning of hU-MSCs with isorhamnetin decreases wound progression by reducing inflammation, and improving tissue architecture and wound healing. The study outcome is expected to lead to an improved cell-based therapeutic approach for burn wounds.     

Changes in Phyto-Chemical Status upon Viral Infections in Plant: A Critical Review

Most damaging plant diseases have been caused by viruses in the entire world. In tropical and subtropical areas, the damage caused by plant virus leads to great economic and agricultural losses. Single stranded DNA viruses (geminiviruses) are the most perilous pathogens which are responsible for major diseases in agronomic and horticultural crops. Significantly begomoviruses and mastreviruses are the biggest genus of plant infecting viruses, transmitted though Bemisia tabaci and members of Cicadellidae respectively. Plants possesses some naturally existing chemicals term as phyto-chemicals which perform important functions in the plant. Some antioxidant enzymes are used by plants for self-defense upon foreign invasion of infection. This review explains the present perceptive of influence of viral infections on phyto-chemicals, oxidative enzymes and biochemical changes occurring in the plant. Viral infection mediated phyto-chemical changes in plants mainly includes: up and down regulation of photosynthetic pigment, increase in the concentration of phenolic compounds, elevation of starch content in the leaf and up & down regulation of anti-oxidative enzymes including (GPX) guaiacol peroxidase, (PPO) polyphenol oxidase, (APX) ascorbate peroxidase, (SOD) superoxide dismutase and (CTA) catalase. These changes lead to initiation of hypersensitive response, by thicken of the leaf lamina, lignification under the leaf surface, blocking to stomatal openings, systematic cell death, generation of reactive oxidative species (ROS), activation of pathogen mediated resistance pathways i.e., production of salicylic acid and jasmonic acid. Collectively all the physiological changes in the plant due to viral infection supports the activation of defense mechanism of the plant to combat against viral infection by limiting virus in specific area, followed with the production of barriers for pathogen, accumulation of starch in the leaf and excess production of (ROS). These strategies used by the plant to prevent the spread of virus in whole plant and to minimize the risk of severe yield loss.     

Synthesis,anticancer activity,and β‐lactoglobulin binding interactions of multitargeted kinase inhibitor sorafenib tosylate (SORt) using spectroscopic and molecular modelling approaches

Sorafenib tosylate (SORt) is an oral multikinase inhibitor used for treatment of advanced renal cell, liver, and thyroid cancers. In this study, this drug was synthesized and its antiproliferative activities against HCT116 and CT26 cells were assessed. The interaction of SORt with β‐lactoglobulin (BLG) was studied using different fluorescence techniques, circular dichroism (CD), zeta potential measurements, and docking simulation. The results of infrared (IR), mass, ^HNMR, and ^CNMR spectra demonstrated that the drug was produced with high quality, purity, and efficiency. SORt showed potent cytotoxicity against HCT116 and CT26 cells with IC₅₀ of 8.12 and 5.42 μM, respectively. For BLG binding of SORt, the results showed that static quenching was the cause of the high affinity drug–protein interaction. Three‐dimensional fluorescence and synchronous spectra indicated that SORt conformation was changed at different levels. CD suggested that the α‐helix content remained almost constant in the BLG–SORt complex, whereas random coil content decreased. Zeta potential values of BLG were more positive after binding with SORt, due to electrostatic interactions between BLG and SORt. Thermodynamic parameters confirmed van der Waals and hydrogen bond interactions in the complex formation. Molecular modelling predicted the presence of hydrogen bonds and electrostatic forces in the BLG–SORt system, which was consistent with the experimental results.     

Pathogen Presence in Wild Birds Inhabiting Landfills in Central Iran

EcoHealth - Wild birds are important in the transmission of many zoonotic pathogens such as salmonella and avian influenza virus (AIV). The current study investigated the presence of bacterial and...     

Correction to: In Silico Evaluation of Food Derived Bioactive Peptides as Inhibitors of Angiotensin Converting Enzyme (ACE)

International Journal of Peptide Research and Therapeutics - The original version of the article unfortunately contained a typo in co-author name.     

Aberrant expression of lncRNAs SNHG6, TRPM2-AS1, MIR4435-2HG,and hypomethylation of TRPM2-AS1 promoter in colorectal cancer

Accumulating evidence has indicated that deregulation of lncRNAs plays essential roles in colorectal cancer (CRC) carcinogenesis. The goal of this study was to analyze the expression of lncRNAs in colorectal cancer and their association with clinicopathological variables. Bioinformatics analysis of published CRC microarray data was performed to identify the important lncRNAs. The expression levels of candidate genes were assessed in the human colon cancer/normal cell lines, CRC, adenomatous colorectal polyps, and their marginal tissues by qRT-PCR. Moreover, the methylation status of the TRPM2-AS1 promoter was studied using qMSP assay. Furthermore, we investigated the molecular mechanisms of these lncRNAs in CRC progression using in silico analysis. Microarray analysis revealed that lncRNAs SNHG6, MIR4435-2HG, and TRPM2-AS1 were upregulated in CRC. These results were validated in colon cell lines. Moreover, qRT-PCR showed that the expression levels of SNHG6 and TRPM2-AS1 were upregulated in the colorectal tumor tissues compared with their paired tissues. Nonetheless, there was no significant increase in MIR4435-2HG expression in CRC samples. Furthermore, we observed a significant hypomethylation of TRPM2-AS1 promoter and its activation in CRC tissues. By in silico analysis, we found that the lncRNAs upregulation could promote proliferation and drug resistance of colorectal cancer cells via miRNAs sponging and modulation of their targets expression. In conclusion, based on our results upregulation of SNHG6 and TRPM2-AS1, and hypomethylation of TRPM2-AS1 promoter might be considered as potential diagnostic biomarkers for CRC initiation and development.     

Supplementation of Taurine Insulates Against Oxidative Stress,Confers Neuroprotection and Attenuates Memory Impairment in Noise Stress Exposed Male Wistar Rats

Noise has always been an important environmental factor that induces health problems in the general population. Due to ever increasing noise pollution, humans are facing multiple auditory and non-auditory problems including neuropsychiatric disorders. In modern day life it is impossible to avoid noise due to the rapid industrialization of society. Continuous exposure to noise stress creates a disturbance in brain function which may lead to memory disorder. Therefore, it is necessary to find preventive measures to reduce the deleterious effects of noise exposure. Supplementation of taurine, a semi essential amino acid, is reported to alleviate psychiatric disorders. In this study noise-exposed (100 db; 3 h daily for 15 days) rats were supplemented with taurine at a dose of 100 mg/kg for 15 days. Spatial and recognition memory was assessed using the Morris water maze and novel object recognition task, respectively. Results of this study showed a reversal of noise-induced memory impairment in rats. The derangements of catecholaminergic and serotonergic levels in the hippocampus and altered brain antioxidant enzyme activity due to noise exposure were also restored by taurine administration. This study highlights the importance of taurine supplementation to mitigate noise-induced impaired memory via normalizing the neurochemical functions and reducing oxidative stress in rat brain.

     

Microsporum fulvum, an Ignored Pathogenic Dermatophyte: A New Clinical Isolation from Iran

Misidentifying with Microsporum gypseum has for a long time been accounted for less prevalence of the geophilic species, Microsporum fulvum in human dermatophytosis. We describe a new case of infection with the species in an Iranian young man. Direct examination of skin scrapings revealed a tinea corporis, and morphological study of the recovered isolate from the culture resulted in the identification of M. gypseum. However, PCR amplification of ITS1-5.8S rDNA-ITS2 region and subsequent ITS-RFLP and sequencing were indicative of M. fulvum as the true causative agent. To recognize M. fulvum in human infections and to validate the morphologically distinguished isolates of M. gypseum, the genetic-based identification is strongly recommended.