Cytotoxic cobalt (III) Schiff base complexes: in vitro anti-proliferative,oxidative stress and gene expression studies in human breast and lung cancer cells

BioMetals - Increasing cancer drug chemo-resistance, especially in the treatment of breast and lung cancers, alarms the immediate need of newer and effective anticancer drugs. Until now,...     

Comparative investigation of the differentiation capability of bone-marrow- and adipose-derived mesenchymal stem cells by qualitative and quantitative analysis

Mesenchymal stem cells (MSCs) hold promise for cell-based therapy in regenerative medicine. To date, MSCs have been obtained from conventional bone marrow via a highly invasive procedure. Therefore, MSCs are now also isolated from sources such as adipose tissue, cord blood and cord stroma, a subject of growing interest. As the characterization and differentiation potential of adipose-derived MSCs (AD-MSCs) and bone-marrow-derived MSCs (BM-MSCs) have not been documented, we have evaluated and compared the characteristics of both MSC types by qualitative and quantitative analyses. Both cell types show similar morphology and surface protein expression, being positive for stromal-associated markers and negative for hematopoietic and endothelial markers. The colony-forming potential of AD-MSCs is distinctly higher than that of BM-MSCs. Nonetheless, similar adipogenic and osteogenic differentiation is observed in both groups of MSCs. Cytochemical qualitative analysis and calcium mineralization demonstrate higher levels toward osteogenic differentiation in BM-MSCs than in AD-MSCs. On the contrary, the percentage of Nile red oil staining for differentiated adipocytes is higher in AD-MSCs than in BM-MSCs. Quantitative real-time polymerase chain reaction shows similar patterns of osteogenic- and adipogenic-associated gene expression in both cell types. Each of the MSCs respond in functional analysis by exhibiting unique properties at the differentiation level according to their micro-environmental niche. Thus, quantitative analysis might be a valuable means of describing stem cell multipotency, in addition to qualitative investigation.     

Verrucarin A, a protein synthesis inhibitor, induces growth inhibition and apoptosis in breast cancer cell lines MDA-MB-231 and T47D

Verrucarin A (VA), a protein synthesis inhibitor, derived from the pathogen fungus Myrothecium verrucaria, inhibits growth of leukemia cell lines and activates caspases and apoptosis and inflammatory signaling in macrophages. We have investigated VA-induced growth inhibition in breast cancer cells MDA-MB-231 and T47D and, particularly, the mechanism of VA-induced apoptosis. VA treatment brought about apoptotic cell death in a dose- and time-dependent manner which was associated with chromatin condensation, cell shrinkage, nuclear fragmentation and intracellular ROS production. Mitochondrial membrane depolarization, activation of caspase-3, down-regulation of Bcl-2 expression and up-regulation of Bax and p53 expression were observed. VA thus affects the viability of both the breast cancer cells by triggering ROS-mediated intrinsic mechanism of apoptosis.     

Skin-derived multipotent stromal cells – an archrival for mesenchymal stem cells

Progenitor stem cells have been identified, isolated and characterized in numerous tissues and organs. However, their therapeutic potential and the use of these stem cells remain elusive except for a few progenitor cells from bone marrow, umbilical cord blood, eyes and dental pulp. The use of bone marrow-derived hematopoietic stem cells (HSC) or mesenchymal stem cells (MSCs) is restricted due to their extreme invasive procedures, low differentiation potential with age and rejection. Thus, we need a clinical grade alternative to progenitor stem cells with a high potential to differentiate, na?ve and is relatively easy in in vitro propagation. In this review, we summarize cell populations of adherent and floating spheres derived from different origins of skin, or correctly foreskin, by enzymatic digestion compared with established MSCs. The morphology, phenotype, differentiation capability and immunosuppressive property of the adherent cell populations are comparable with MSCs. Serum-free cultured floating spheres have limited mesodermal but higher neurogenic differentation potential, analogous to neural crest stem cells. Both the populations confirmed their plethora potential in in vitro. Together, it may be noted that the skin-derived adherent cell populations and floating cells can be good alternative sources of progenitor cells especially in cosmetic, plastic and sports regenerative medicine.     

In vitro differentiation of human skin-derived multipotent stromal cells into putative endothelial-like cells

Background  

Multipotent stem cells have been successfully isolated from various tissues and are currently utilized for tissue-engineering and cell-based therapies. Among the many sources, skin has recently emerged as an attractive source for multipotent cells because of its abundance. Recent literature showed that skin stromal cells (SSCs) possess mesoderm lineage differentiation potential; however, the endothelial differentiation and angiogenic potential of SSC remains elusive. In our study, SSCs were isolated from human neonatal foreskin (hNFSSCs) and adult dermal skin (hADSSCs) using explants cultures and were compared with bone marrow (hMSC-TERT) and adipose tissue-derived mesenchymal stem cells (hADMSCs) for their potential differentiation into osteoblasts, adipocytes, and endothelial cells.     

Possible Existence of the Hypothalamic-Pituitary-Hippocampal (HPH) Axis: A Reciprocal Relationship Between Hippocampal Specific Neuroestradiol Synthesis and Neuroblastosis in Ageing Brains with Special Reference to Menopause and Neurocognitive Disorders

The hippocampus-derived neuroestradiol plays a major role in neuroplasticity, independent of circulating estradiol that originates from gonads. The response of hypothalamus-pituitary regions towards the synthesis of neuroestradiol in the hippocampus is an emerging scientific concept in cognitive neuroscience. Hippocampal plasticity has been proposed to be regulated via neuroblasts, a major cellular determinant of functional neurogenesis in the adult brain. Defects in differentiation, integration and survival of neuroblasts in the hippocampus appear to be an underlying cause of neurocognitive disorders. Gonadotropin receptors and steroidogenic enzymes have been found to be expressed in neuroblasts in the hippocampus of the brain. However, the reciprocal relationship between hippocampal-specific neuroestradiol synthesis along neuroblastosis and response of pituitary based feedback regulation towards regulation of estradiol level in the hippocampus have not completely been ascertained. Therefore, this conceptual article revisits (1) the cellular basis of neuroestradiol synthesis (2) a potential relationship between neuroestradiol synthesis and neuroblastosis in the hippocampus (3) the possible involvement of aberrant neuroestradiol production with mitochondrial dysfunctions and dyslipidemia in menopause and adult-onset neurodegenerative disorders and (4) provides a hypothesis for the possible existence of the hypothalamic-pituitary-hippocampal (HPH) axis in the adult brain. Eventually, understanding the regulation of hippocampal neurogenesis by abnormal levels of neuroestradiol concentration in association with the feedback regulation of HPH axis might provide additional cues to establish a neuroregenerative therapeutic management for mood swings, depression and cognitive decline in menopause and neurocognitive disorders.

     

Contribution of the secretory material of caecilian (amphibia: Gymnophiona) male Mullerian gland to motility of sperm: a study in Uraeotyphlus narayani

Caecilians are a unique group of limbless burrowing amphibians with discontinuous distribution. Several caecilian species are viviparous, and all practice internal fertilization. In amniotic vertebrates the sperm undergo post-testicular physiological maturation when they are initiated into motility under the influence of an epididymal secretion. Further, during ejaculation mammalian sperm are suspended in a fluid secreted by the male accessory sex glands, viz., prostate gland and seminal vesicles. Caecilians lack comparable glands, but still practice internal fertilization. Uniquely, male caecilians retain the Mullerian ducts in the adults as a pair of functional glands. It has long been hypothesized, based on indirect evidence, that the Mullerian gland would be a male accessory sex gland, secreting a fluid in which sperm are suspended during ejaculation and which would also provide nutritional support to the ejaculated sperm. In the present study, the secretory material of the Mullerian gland of Uraeotyphlus narayani was mixed with sperm obtained from the testis, and the changes in motility were recorded. Uraeotyphlus narayani sperm possess a perforatorium of the acrosome proceeding deep into the endonuclear canal of the nucleus. The midpiece is characterized by closely applied centrioles, the anterior ends of the axoneme and axial fiber, and a mitochondrial sheath. The long tail has an undulating membrane on one side, supported by the axoneme and an axial fiber. The live sperm possess a mitochondrial vesicle, also known as the cytoplasmic droplet, anywhere along the head and the midpiece, as in anuran sperm, which is shed from sperm that have ceased motility. Uraeotyphlus narayani sperm are motile the moment they are released directly from the testis, indicating that the sperm do not require post-testicular physiological maturation. On being mixed with the secretory material of the Mullerian gland, the spermatozoa are enhanced in speed as well as duration of motility. Therefore, the caecilian male Mullerian gland is considered to be the male accessory sex gland.