ABSTRACT
With the development of novel treatments for autoimmune disorders, it has become a popular research focus which mesenchymal stem cells (MSCs) have the capacity to counteract with autoimmune diseases progression. One of the underlying mechanisms behind their activities is the release of extracellular vesicles especially exosomes. MSC-derived exosomes are hypoimmunogenic nanocarriers which contain numerous immunoregulatory factors and similar to other exosomes, are able to pass through boundaries like the blood-brain barrier (BBB). Accumulating evidence provided by animal studies has demonstrated that MSC-derived exosomes, as a novel therapy, can re-induce self-tolerance, without subsequent complications reported for other treatments. Therefore, therapeutic applications of MSC-derived exosomes are contributing to core advances in the field of autoimmune diseases. Here, we briefly describe the biological characteristics of MSC-derived exosomes and review the experimentally verified outcomes for autoimmune disease therapy purposes.
ABSTRACT
Mesenchymal stem cells (MSCs) are multipotent stem cells that have multilinear differentiation and self-renewal abilities. These cells are immune-privileged as they express no or low level of class-II major histocompatibility complex (MHC-II) and other costimulatory molecules. Having neuroprotective and regenerative properties, MSCs can be used to ameliorate several intractable neurodegenerative disorders by affecting both innate and adaptive immune systems. Several manipulations like pretreating MSCs with different conditions or agents, and using molecules derived from MSCs or genetically manipulating them, are the common and practical ways that can be used to strengthen MSCs survival and potency. Improved MSCs can have significantly enhanced impacts on diseases compared to MSCs not manipulated. In this review, we describe some of the most important manipulations that have been exerted on MSCs to improve their therapeutic functions and their applications in ameliorating three prevalent neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease.
ABSTRACT
Several studies have pointed out that certain snake venoms contain compounds presenting cytotoxic activities that selectively interfere with cancer cell metabolism. In this study, Pseudocerastes persicus venom and its fractions were investigated for their anticancer potential on lung cancer cells. Methods: Lung cancer cells (A549) and normal fibroblast cells (Hu02) were treated with the P. persicus venom and its HPLC fractions and the cell cytotoxic effects were analyzed using MTT and lactate dehydrogenase release assays. Apoptosis was determined in venom-treated cell cultures using caspase-3 and caspase-9 assay kits. Results: The treatment of cells with HPLC fraction 21 (25-35 kDa) of P. persicus venom resulted in high LDH release in normal fibroblast cells and high caspase-3 and caspase-9 activities in lung cancer cells. These results indicate that fraction 21 induces apoptosis in cancer cells, whereas necrosis is predominantly caused by cell death in the normal cells. Fraction 21 at the final concentration of 10 μg/mL killed approximately 60% of lung cancer cells, while in normal fibroblast cells very low cell cytotoxic effect was observed. Conclusion: HPLC fraction 21 at low concentrations displayed promising anticancer properties with apoptosis induction in the lung cancer cells. This fraction may, therefore, be considered a promising candidate for further studies.(AU)
Subject(s)
Animals , Snake Venoms/chemical synthesis , Apoptosis , Cell Culture Techniques , Cytotoxins/analysis , Lung NeoplasmsABSTRACT
Sickle-cell disease [SCD] is an inherited hemoglobin childhood disorder, frequently complicated by pulmonary hypertension and cardiac involvement. Cardiovascular events and complications are the leading cause of mortality and morbidity in patients with SCD. Tissue Doppler imaging and the myocardial performance index [Tei index], are simple indices for the assessment of the cardiac function. The purpose of this study was to assess the left ventricular function in children with SCD. Sixty-four patients with SCD [mean age = 11.7 +/- 5.5 years] were compared with 50 age matched healthy controls [mean age = 11.2 +/- 5.20 years]. Myocardial wall motion velocities at the lateral mitral annulus and the junction between the medial mitral annulus and the interventricular septum were assessed during systole [Sa], early diastole [Ea], and late diastole [Aa] through a four-chamber view using pulsed Doppler echocardiography. The ejection fraction and shortening fraction were estimated. The Tei index was estimated via tissue Doppler echocardiography. The results showed that Ea and Aa velocity in the mitral annulus and interventricular septum had no difference between the patients and controls [p value > 0.05], and nor was there any difference between the two groups as regards the Tei index, Ea/Aa, ejection fraction, and shortening fraction [p value > 0.05]. Sam wave velocity, however, had a significant difference between the two groups [p value < 0.038]. The Tei index is a sensitive indicator for the cardiac function in chronic diseases and the right ventricular function in some disorders such as SCD
ABSTRACT
Complete root canal seal is one of the most important aims of root canal treatment. The aim of this study was to compare the sealing ability of three resin-based sealers [AH26, AH Plus Jet and TG Adseal] against microbial microleakage. In this in vitro study, 87 single-rooted extracted human teeth were decoronated maintaining a root length of 15 mm. Apical preparation and coronal flaring of the root canals were carried out up to #40 and #80 K-files, respectively, using the step-back technique. After cleaning and shaping, the teeth were randomly divided to 5 groups: Three experimental groups of 25 teeth, a positive control group of 3 teeth and a negative control group of 9 teeth. The experimental groups were obturated with gutta-percha and AH26 sealer, gutta-percha and AH Plus Jet sealer, and gutta-percha and TG Adseal sealer. The samples were evaluated daily for 90 days and the time of culture contamination with Enterococcus faecalis was registered in each case. The results were statistically analyzed by Kaplan-Meier, Chi-square and Mann-Whitney tests. All the samples in the positive control group were infected after 24 hours. None of the negative control samples were infected after 90 days. Time of contamination between experimental groups showed no significant differences [p value = 0.611]. TG Adseal can be recommended for root canal therapy due to its sealability which is comparable to AH26 and AH Plus Jet root canal sealers and its appropriate cost
ABSTRACT
The clavulanic acid regulatory gene [claR] is in the clavulanic acid biosynthetic gene cluster that encodes ClaR. This protein is a putative regulator of the late steps of clavulanic acid biosynthesis. The aim of this research is the molecular cloning of claR, isolated from the Iranian strain of Streptomyces clavuligerus [S. clavuligerus]. In this experimental study, two different strains of S. clavuligerus were used [PTCC 1705 and DSM 738], of which there is no claR sequence record for strain PTCC 1705 in all three main gene banks. The specific designed primers were subjected to a few base modifications for introduction of the recognition sites of BamHI and ClaI. The claR gene was amplified by polymerase chain reaction [PCR] using DNA isolated from S. clavuligerus PTCC 1705. Nested-PCR, restriction fragment length polymorphism [PCR-RFLP], and sequencing were used for molecular analysis of the claR gene. The confirmed claR was subjected to double digestion with BamHI and ClaI. The cut claR was ligated into a pBluescript [pBs] vector and transformed into E. coli. The entire sequence of the isolated claR [Iranian strain] was identified. The presence of the recombinant vector in the transformed colonies was confirmed by the colony-PCR procedure. The correct structure of the recombinant vector, isolated from the transformed E. coli, was confirmed using gel electrophoresis, PCR, and double digestion with restriction enzymes. The constructed recombinant cassette, named pZSclaR, can be regarded as an appropriate tool for site directed mutagenesis and sub-cloning. At this time, claR has been cloned accompanied with its precisely selected promoter so it could be used in expression vectors. Hence the ClaR is known as a putative regulatory protein. The overproduced protein could also be used for other related investigations, such as a mobility shift assay