Cloning and expression profile of FLT3 gene during progenitor cell-dependent liver regeneration

Background and Aim: The liver has a unique capacity to regenerate upon exposure to viral infections, toxic reactions and cancer formation. Liver regeneration is a complex phenomenon in which several factors participate during its onset. Cellular proliferation is an important component of this process and the factors that regulate this proliferation have a vital role. FLT3, a well-known hematopoietic stem cell and hepatic lineage surface marker, is involved in proliferative events of hematopoietic stem cells. However, its contribution to liver regeneration is not known. Therefore, the aim of this study was to clone and examine the role of FLT3 during liver regeneration in rats. Methods: Partial cDNA of rat homolog of FLT3 gene was cloned from thymus and the tissue specific expression of this gene at mRNA and protein levels was examined by RT-PCR and Western blot. After treating with 2-AAF and performing hepatectomy in rats to induce progenitor-dependent liver regeneration, the mRNA and protein expression profile of FLT3 was investigated by real-time PCR and Western blot during liver regeneration. In addition, cellular localization of FLT3 protein was determined by immunohistochemistry. Results: The results indicated that rat FLT3 cDNA has high homology with mouse and human FLT3 cDNA. It was also found that FLT3 is expressed in most of the rat tissues and during liver regeneration. In addition, its intracellular localization is altered during the late stages of liver regeneration. Conclusion: The FLT3 receptor is activated at the late stages of liver regeneration and participates in the proliferation response that is observed during progenitor-dependent liver regeneration. © 2006 The Authors

The effect of telomerase template antagonist GRN163L on Bone-Marrow-Derived rat mMesenchymal stem cells is reversible and associated with altered expression of cyclin d1, cdk4 and cdk6

Telomerase activity is essential for the continued growth and survival of malignant cells, therefore inhibition of this activity presents an attractive target for anti-cancer therapy. The telomerase inhibitor GRN163L, was shown to inhibit the growth of cancer cells both in vitro and in vivo. Mesenchymal stem cells (MSCs) also show telomerase activity in maintaining their self-renewal; therefore the effects of telomerase inhibitors on MSCs may be an issue of concern. MSCs are multipotent cells and are important for the homeostasis of the organism. In this study, we sought to demonstrate in vitro effects of GRN163L on rat MSCs. When MSCs were treated with 1 μM GRN163L, their phenotype changed from spindle-shaped cells to rounded ones and detached from the plate surface, similar to cancer cells. Quantitative-RT-PCR and immunoblotting results revealed that GRN163L holds MSCs at the G1 state of the cell cycle, with a drastic decrease in mRNA and protein levels of cyclin D1 and its cdk counterparts, cdk4 and cdk6. This effect was not observed when MSCs were treated with a mismatch control oligonucleotide. One week after GRN163L was removed, mRNA and protein expressions of the genes, as well as the phenotype of MSCs returned to those of untreated cells. Therefore, we concluded that GRN163L does not interfere with the self-renewal and differentiation of MSCs under short term in vitro culture conditions. Our study provides additional support for treating cancers by administrating GRN163L without depleting the body's stem cell pools. © 2010 Springer Science+Business Media, LLC

Migraine in women: the role of hormones and their impact on vascular diseases

Migraine is a predominantly female disorder. Menarche, menstruation, pregnancy, and menopause, and also the use of hormonal contraceptives and hormone replacement treatment may influence migraine occurrence. Migraine usually starts after menarche, occurs more frequently in the days just before or during menstruation, and ameliorates during pregnancy and menopause. Those variations are mediated by fluctuation of estrogen levels through their influence on cellular excitability or cerebral vasculature. Moreover, administration of exogenous hormones may cause worsening of migraine as may expose migrainous women to an increased risk of vascular disease. In fact, migraine with aura represents a risk factor for stroke, cardiac disease, and vascular mortality. Studies have shown that administration of combined oral contraceptives to migraineurs may further increase the risk for ischemic stroke. Consequently, in women suffering from migraine with aura caution should be deserved when prescribing combined oral contraceptives

Sweet plasmonics: Sucrose macrocrystals of metal nanoparticles

Cataloged from PDF version of article.The realization of plasmonic structures generally necessitates expensive fabrication techniques, such as electron beam and focused ion beam lithography, allowing for the top-down fabrication of low-dimensional structures. Another approach to make plasmonic structures in a bottom-up fashion is colloidal synthesis, which is convenient for liquid-state applications or very thin solid films where aggregation problems are an important challenge. The architectures prepared using these methods are typically not robust enough for easy handling and convenient integration. Therefore, developing a new plasmonic robust platform having large-scale dimensions without adversely affecting the plasmonic features is in high demand. As a solution, here we present a new plasmonic composite structure consisting of gold nanoparticles (Au NPs) incorporated into sucrose macrocrystals on a large scale, while preserving the plasmonic nature of the Au NPs and providing robustness in handling at the same time. As a proof of concept demonstration, we present the fluorescence enhancement of green CdTe quantum dots (QDs) via plasmonic coupling with these Au NPs in the sucrose crystals. The obtained composite material exhibits centimeter scale dimensions and the resulting quantum efficiency (QE) is enhanced via the interplay between the Au NPs and CdTe QDs by 58% (from 24% to 38%). Moreover, a shortening in the photoluminescence lifetime from 11.0 to 7.40 ns, which corresponds to a field enhancement factor of 2.4, is observed upon the introduction of Au NPs into the QD incorporated macrocrystals. These results suggest that such "sweet" plasmonic crystals are promising for large-scale robust platforms to embed plasmonic nanoparticles

Detection of metastases in patients with cutaneous melanoma using FDG-PET/CT

This study aimed to detect metastases in patients with stage III or IV cutaneous melanoma by F-18-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT). Thirty-nine patients with clinically evident stage III or IV melanoma underwent whole-body FDG-PET/CT scans for metastatic disease and these results were compared with those of biopsy. Scans for 38 of the patients were evaluated; one patient's scan could not be evaluated. There were 11 true-positive, two false-positive, 24 true-negative and one false-negative scans for the detection of melanoma metastases, with sensitivity 91%, specificity 92%, accuracy 92%, and positive and negative predictive values 84% and 96%, respectively. False-positive FDG-PET/CT scans were due to sarcoidosis in the lung and infected cyst in the liver. It is concluded that FDG-PET/CT scanning has high sensitivity and specificity for detecting stage III or IV metastatic melanoma

Mesenchymal stem cells: Possibilities of new treatment options

Stem cell research evolved as a new hope and has gained tremendous interest during the last two decades in developing potential strategies for many debilitating diseases. Mesenchymal stem cells (MSCs) are bone marrow-derived multipotent stem cells capable of self-renewal and of differentiating into multiple lineages, such as osteocytes, adipocytes, chondrocytes, myoblasts, cardiomyocytes, and hepatocytes. MSCs are an important source for cellular therapies. They can easily be obtained and expanded in vitro in large numbers without significantly altering their properties. MSCs not only migrate to the injured site in vivo but also have immunomodulatory effects that make their use attractive for allogeneic grafting. MSCs can also be frozen for preservation; and when thawed, they retain their normal physiological function, allowing future ''off-the-shelf'' therapy approaches. Because of these features, MSCs have high therapeutic value in tissue engineering and regenerative medicine. In this chapter, the contribution of the MSCs to cardiovascular repair and liver regeneration are summarized. © Springer Science+Business Media, LLC 2012. All rights reserved

Primary thyroid lymphoma: report of two cases

Primary thyroid Iymphoma is a rare disease. Most of the patients have a history of Hashimoto's thyroiditis. Main histopathologic subtypes are either mucosa-associated lymphoid tissue (MALT) or diffuse large cell lymphomas. Treatment options are surgical resection in localised, low-grade MALT lymphomas or systemic chemotherapy in aggressive, diffuse large cell lymphomas. But, sometimes other histopathologic subtypes can be seen and therapeutic approaches must be done. We report two patients who have primary thyroid lymphoma. There was no history of Hashimoto's thyroiditis in either case, and neither of them had MALT histologic subtype. First patient a sixty four year old woman, admitted to hospital because of bilateral thyroid nodules. Histological subtype was B cell follicular lymphoma. Subtotal thyroidectomy was performed and radiotherapy was administered to the entire neck region. Second patient, a 50 year old man, presented with complaints of a left thyroid mass and dyspnoea. Total thyroidectomy was carried out and chemotherapy was given. Histological diagnosis was diffuse large B cell lymphoma. Thyroid lymphomas had heterogenous histological and clinical characteristics. In localised, non-aggressive subtypes, surgical treatment must be considered. Postoperative chemotherapy or radiotherapy may be necessary in some patients. East African Medical Journal Vol.81(7) 2004: 378-38

The Effect of Estrogen on Bone Marrow-Derived Rat Mesenchymal Stem Cell Maintenance: Inhibiting Apoptosis Through the Expression of Bcl-x L and Bcl-2

Mesenchymal Stem Cells (MSCs) have high therapeutic value for regenerative medicine and tissue engineering due to their differentiation potential and non-immunogenic characteristics. They are also considered as an effective in vivo delivery agent because of their ability to migrate to the site of injury. A major roadblock in their use for cell-based therapies is their rareness in vivo. Therefore, it is important to obtain increased number of functional MSCs in vitro in order to have adequate numbers for therapeutic regiments. We aimed to investigate the role of estrogen and its mechanism in obtaining more MSCs. MSCs were isolated from female and ovariectomized rats and cultured in the presence and absence of 10 -7 M estrogen. In the presence of estrogen, not only their CFU-F activity increased but also apoptotic rate decreased as shown by TUNEL staining leading to obtain more MSCs. Also the number of the cells in the colonies increased upon estrogen treatment. To reveal the mechanism of this effect, we focused on Bcl-2 family of proteins. Our immunoblotting experiments combined with knockdown studies suggested a critical role for anti-apoptotic Bcl-x L and Bcl-2. Estrogen treatment up regulated the expression Bcl-x L and Bcl-2. When we knocked down the expression of bcl-x L and bcl-2, MSCs lacking these genes showed an increase in the apoptotic rate in contrast to normal MSCs following estrogen treatment. Therefore, estrogen treatment will be of great advantage for cell-based therapies in order to get more functional MSCs and may provide opportunities to develop new strategies for debilitating diseases. © 2011 Springer Science+Business Media, LLC