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Parkinson’s disease (PD) is considered as a high prevalence neurodegenerative disorders worldwide. Pathologically, the demise of dopamine-producing cells, in large part due to an abnormal accumulation of the α-synuclein in the substantia nigra, is one of the main causes of the disease. Up until now, many de novo investigations have been conducted to disclose the mechanisms underlying in PD. Among them, impacts of non-coding RNAs (ncRNAs) on the pathogenesis and/or progression of PD need to be highlighted. microRNAs (miRNAs) and long ncRNAs (lncRNAs) are more noteworthy in this context. miRNAs are small ncRNAs (with 18–25 nucleotide in length) that control the expression of multiple genes at post-transcriptional level, while lncRNAs have longer size (over 200 nucleotides) and are involved in some key biological processes through various mechanisms. Involvement of miRNAs has been well documented in the development of PD, particularly gene expression. Hence, in this current review, we will discuss the impacts of miRNAs in regulation of the expression of PD-related genes and the role of lncRNAs in the pathogenesis of PD.
Molecular Biology Reports pp 1–12
Mehdi Hassanpour, Omid Cheraghi, Vahid Siavashi, Reza Rahbarghazi, Mohammad Nori
A large number of cardiovascular disorders and abnormalities, notably accelerated vascular deficiencies could be related to aging changes and increased length of life. During the past decades, the discovery of different stem cells facilitates ongoing attempts for attenuating many disorders, especially in vascular beds. Endothelial progenitor cells (EPCs) are a subtype of stem cells that have potent capacity to differentiate into mature endothelial cells (ECs). However , some documented studies reported an age-related decline in proliferation and function of many stem cells. There is no data on aging effect upon proliferation and morphological feature of EPCs .To show aging effect on EPCs proliferation and multipotentiality, bone marrow samples were provided from old and young cases in three different species; human, mouse and dog. After 7 days of culture, the cell morphology and clonogenic capacity were evaluated. We also calculated the mean number of colonies both in bone marrow samples from old and young subjects. To confirm the cell phenotype, isolated cells were immune-phenotyped by a panel of antibodies against Tie-2, CD133 and CD309 markers . Our results showed that EPCs exhibited prominent spindle form in all bone marrow samples from young cases while the cell shape became more round by aging. Notably, the number of colonies was reduced in aged samples as compared to parallel young subject samples (P < 0.05) . We also detected that the expression of endothelial related markers diminished by aging . The results of this study suggest that the age-related vascular abnormalities could be presumably related to the decline in stemness capacity of EPCs. Available: Journal of Cardiovasc Thorac Res, 2016, 8
Potent anti-angiogenic and cytotoxic effect of conferone on human colorectal adenocarcinoma HT-29 cells
Cancer is one of the leading causes of death worldwide, both in developed and developing countries. Of note, colorectal adenoma encompasses a high rate of gastrointestinal-associated cancer death in human being. Today, different strategies, including surgery approaches, photodynamic therapy, radiation and particularly natural compounds have been extensively used to manage tumor behavior in human body . The objective of the present study was to elucidate the multilateral effect of conferone on HT-29 cell lines. In addition to cell cytotoxicity analysis, the extent of lipid peroxidation, MDA formation, catalase, superoxide dismutase and intracellular ROS levels, as markers of oxidative stress, were also studied. P-glycoprotein-mediated cellular efflux effectiveness, anti-angiogenic and finally anti-migratory capacities of conferone-exposed HT-29 cells were monitored over a course of 72 h . It was found that, conferone mediated cell proliferation arrest and induced cell death through both apoptosis and necrosis phenomena. HT-29 cells, exposed to 20 µM conferone, under gone oxidative stress and total content of reactive oxygen species was increased in a time-dependent manner. Intracellular accumulation of rhodamine 123 and cell's swelling under iso- and hypo-osmotic conditions could be related to P-glycoprotein incorrect performance in the presence of conferone. A significant reduction in CD31 positive cells population and in vitro tubulogenesis of endothelial cells was also observed after incubation with conditioned medium collected from 72 h conferone-treated HT-29 cells. Conferone also precluded angiogenesis capability of treated HT-29 cells through an altered secretome profile, including vascular endothelial growth factor, Angiopoietin-1 and -2 factors. In addition to anti-angiogenic properties of conferone, a profound decrease in migration capability of HT-29 cells was also evident.
Source: Omid Cheraghi et al. Phytomedicine 21 February 2016
In accordance to experimental work by Feizy et al. it was found that morphine exerts adverse effects on neural stem cells. They previously acclaimed that:
Up to present, a large number of reports unveiled exacerbating effects of both long- and short-term administration of morphine, as a potent analgesic agent, on opium-addicted individuals and a plethora of cell kinetics, although contradictory effect of morphine on different cells have been introduced until yet. To address the potent modulatory effect of morphine on neural multipotent precursors with emphasis on endogenous sex-related neurosteroids biosynthesis, we primed the rat neural stem cells isolated from embryonic rat telencephalon to various concentrations of morphine including 10, 20, 50 and 100 µM alone or in combination with naloxone (100 µM) over period of 72 h. Flow cytometric Ki-67 expression and Annexin-V/PI based necrosis and apoptosis of exposed cells were evaluated. The total content of dihydrotestosterone and estradiol in cell supernatant was measured by ELISA. According on obtained data, both concentration- and time-dependent decrement of cell viability were orchestrated thorough down-regulation of ki-67 and simultaneous up-regulation of Annexin-V. On the other hand, the addition of naloxone (100 µM), as Mu opiate receptor antagonist, could blunt the morphine-induced adverse effects. It also well established that time-course exposure of rat neural stem cells with morphine potently could accelerate the endogenous dihydrotestosterone and estradiol biosynthesis. Interestingly, naloxone could consequently attenuate the enhanced neurosteriodogenesis time-dependently. It seems that our results discover a biochemical linkage between an accelerated synthesis of sex-related steroids and rat neural stem cells viability.
This research was further published on Journal of Neurochemical Research. 2016 Jan 30
Glycosylation or addition of sugar chains to protein is a highly conserved form of protein modifications cellular metabolism. There are two major abundant and well-known forms of glycosylation that occur on the many proteins; N-linked and mucin-type O-linked. Mucin-type O- glycosylation is a conserved protein modification present on membrane-bound and secreted proteins. One of the most important molecular alterations in cancer cells is the aberrant expression of antigens resulting from an incomplete O-glycosylation. It was well-established that an abnormal Mucin-type O-glycan associated with cancer and several human disorders is Tn-antigen. This glycan has a simple structure composed of N-acetyl-d-galactosamine with a glycosidic α linkage to Serine/Threonine residues in glycoproteins. This type of glycosylation is initiated with a large family of enzymes called UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferases (GALNTs) in mammals. Each member of the family is capable of catalyzing the addition of GalNAc to the hydroxyl group of Serines or Threonines in protein substrate. There are 20 ppGalNAc-Ts in humans that all family members are type II- transmembrane proteins that have a short N-terminal cytoplasmic tail and a hydrophobic region that spans the Golgi membrane, and a conserved catalytic region that lies within the Golgi lumen. In addition, in vitro studies have demonstrated that certain members of this family have unique protein substrate preferences as well as specific sites of GalNAc addition within those substrates. The following scheme illustrates mucin-type O-glycan biosynthesis:
In one of the recent studies the expression of 14 GALNT genes were analyzed in normal and cancerous B and C lymphocytes of either in patients with AML or CLL. In conclusion, it was found that GALNT11 was expressed in Jukart, T and CLL cells while little or no expression was found in normal B and Daudi cells. Conclusively, GALNT11 enzyme is presumably introduced as a new marker in Chronic Lymphocytic Leukemia. It reasonable to focus about the possible role of this enzyme during maturation of hematopoietic stem cell into end stage cells like lymphocyte.
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By: Sh. Mozaffari