Increase In Mitotic Activity Research Articles

Immunodetection of selected pancreatic hormones under intragastric administration of apelin-13, a novel endogenous ligand for an angiotensin-like orphan G-protein coupled receptor, in unweaned rats.

This study investigated the effects of intragastric administration of apelin-13 on the secretion of critical pancreatic hormones in a cohort of three-week-old Wistar rats. The research aimed to uncover apelin's modulatory roles in endocrine interactions dictating metabolic homeostasis during early life. Rats were randomly assigned to control or experimental groups, receiving apelin-13 or saline for 14 days. The study population consisted of three-week-old Wistar rats of both sexes, weighing between 20 and 25 grams. Histological examination, analysis of variance and t-tests were employed to assess significant differences. Distinctive alterations in large islet morphology were observed, indicating a notable reduction in size. Additionally, an increase in alpha- and beta-cell density within specific islet sizes was noted, suggesting significant changes in cell populations. The study found a substantial increase in mitotic activity and a decrease in apoptosis in small and medium-sized islets post apelin-13 administration, indicating its potential role in regulating cell survival and proliferation. The notable reduction in large islet size coupled with increased alpha and beta cell density implies a targeted impact of apelin-13 on pancreatic cell dynamics. Also, the observed increase in mitotic activity and decrease in apoptosis in small and medium-sized islets suggest its potential regulatory role in cell survival and proliferation within the pancreatic microenvironment.

Insight into JNK Inhibition-based Strategy for the Treatment of Alzheimer's Disease

Background: Existing drugs for the treatment of Alzheimer's disease do not meet the basic requirements. Therefore, it is necessary to search for fundamentally new targets for the discovery of drugs for Alzheimer's disease (AD). When creating approaches to stimulate neurogenesis, such a search is promising to conduct as part of the development of a strategy for targeted regulation of intracellular signal transduction in regeneration-competent cells (RCCs). Moreover, the participation of c-Jun Nterminal kinases (JNK) in the regulation of the functions of the nervous tissue and neuroglial cells is known. Objective: The aim of the work was to study the effect of the JNK inhibitor (IQ-1S) on exploratory behavior and cognitive functions in aged mice (16-month-old male C57BL/6 mice as a model of AD) in combination with the dynamics of shifts in the RCCs functioning (nervous tissue progenitors: neural stem cells (NSCs) and neuronal-committed progenitors (NCPs); neuroglial cells: astrocytes, oligodendrocytes, microglial cells). Methods: The studies were carried out on male C57BL/6 mice aged 16 months as model of Alzheimer's disease. We studied the effect of the JNK inhibitor on exploratory behavior, conditioned reflex activity, and on the functioning of RCCs in the subventricular zone of the cerebral hemispheres (SVZ). NCPs and neuroglial cells of different types were obtained by immunomagnetic separation. Results: We observed significant changes in exploratory behavior and impaired conditioned reflex activity in aged C57BL/6 mice. The administration of the JNK inhibitor led to a significant correction of age-related behavioral and memory disorders in aged mice. At the same time, against the background of JNK inhibition-based therapy, an increase in mitotic activity and the content of both NSCs and NCPs in the SVZ was noted. However, these shifts were more pronounced in committed precursors. The phenomenon of the inhibition of NSC specialization under the influence of a pharmacological agent was also revealed. In addition, the JNK inhibitor caused an increase in the secretion of neurotrophic growth factors by oligodendrocytes and microglial cells. Conclusion: The findings open up prospects for the development of JNK targeting-based approaches for the treatment of AD.

Morphologic and Cellular Changes Induced by Selective Laser Trabeculoplasty.

PurposeSelective laser trabeculoplasty is a safe and effective procedure for reducing IOP, but its mechanism of action is not fully elucidated. We evaluated the morphologic and cellular changes as well as DNA synthesis after SLT treatment of human trabecular meshwork (TM) tissue explants.MethodsCorneoscleral rim tissues that underwent SLT treatment were compared to control segments that had no laser treatment. Light microscopy (LM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) were used to assess cell morphology. The Click-iT 5-ethynyl-2’-deoxyuridine (EdU) imaging kit was used to compare DNA synthesis/cell proliferation with a confocal microscope. All tissues were assessed for vitality.ResultsSLT treatment does not reveal notable cell damage in the juxtacanalicular (JCT) region, but mildly disrupts superficial trabecular beams and uveal TM, ablates TM endothelial cells from the undamaged beams as detected by both LM and TEM. This superficial destruction was not observed in some SLT treatment spots on higher magnification by SEM. SLT treatment increased mitotic activity and DNA synthesis near the lining of Schlemm’s canal after several days.ConclusionSLT treatment disrupts endothelial cells in the corneoscleral TM and causes superficial ultrastructural changes to the uveal TM. SLT treatment also shows a trend towards dynamic time-dependent changes in (DNA synthesis) with an increase in mitotic activity at 7 days cell proliferation.

UNUSUAL PATHWAY OF DIAGNOSIS OF A RARE CASE: PERIPHERAL AMELOBLASTOMA

<h3>Background</h3> This case report highlights the varying differential diagnoses that finally led to the diagnosis of the peripheral ameloblastoma. It goes through the unexpected journey in reaching the diagnosis of this particular patient owing to varying presentations and unexpected findings. <h3>Discussion</h3> A 75-year-old woman was referred to the Royal Lancaster Infirmary maxillofacial surgery under the 2-week wait pathway for a right buccal swelling. The patient was referred by her general dental practitioner for a lump adjacent to the upper right maxillary tuberosity. The patient had bleeding from the lesion intermittently, raising suspicion of a possible malignancy. An incisional biopsy was performed and the initial impression for histology was cylindroma or eccrine spiral adenoma; however, the histopathologist confirmed the specimen was from the oral mucosa and a working diagnosis of low-grade salivary type neoplasm was reached. An excisional right buccal sulcus biopsy of the lesion was performed and showed infiltration of a basaloid tumor arising from squamous epithelium. The tumor islands were composed of basaloid tumor cells with peripheral palisading. There was no increase in mitotic activity. The overall appearance was consistent with an extraosseous ameloblastoma. Because of the differences between histology results, the sample was sent for further analysis and confirmation to Newcastle University, where it was confirmed to be a peripheral ameloblastoma. <h3>Conclusions</h3> The case highlights the difficult histologic appearance of a peripheral ameloblastoma and shows the need for thorough history and investigations to ensure the correct diagnosis and treatment.

Assessment of Genotoxicity and Cytotoxicity of Leached Chemicals from HDPE Plastic Commonly Used by Ambulant Vendors

Plasticizers and additives in plastics like polyethylene terephthalate (PET) bottles have been found to leach – especially when exposed to certain stresses, including temperature. Frequent exposure to these chemicals is associated with a higher risk of developing developmental and reproductive disorders and cancer. In this study, water at varying temperatures (28, 65, 75, and 85 °C) was contained in high-density polyethylene (HDPE) plastic “labo,” a food packaging material common in the Philippines. Gas chromatography–mass spectrometry (GC-MS) analysis showed that the leached chemicals were derivatives of plastic additives and compounds or degradation compounds of these chemicals. Notable leachates include dimethyl sulfoxide, isosorbide, and cyclohexene derivatives. Different compounds leached at different temperatures. The Allium cepa test revealed chromosomal aberrations such as anaphase with bridge, sticky chromosomes, and chromosomal breaks. These signify that the compounds may be genotoxic to Allium cepa root tip cells. The Allium cepa test, brine shrimp lethality assay, and MTT assay on MCF-7 cells were also conducted as preliminary cytotoxicity tests. Results showed an increase in mitotic activity for Allium cepa root tip cells and induced proliferation of MCF-7 cells. Moreover, the mortality rates of Artemia salina were low after 24 h of exposure. These findings provide additional information regarding the leaching from plastic labo – the identity of leached chemicals and the effects of exposure on various cell lines and organisms. These findings may be used as a basis for existing policies regarding the use of plastic as food packaging material.

Influence of monosodium glutamate consumption by albino rats during pregnancy and lactation on their offspring

The consequences of dietary intake of significant amounts of monosodium glutamate (MSG) are the excess body weight; structural and functional disorders of the central nervous system, liver, kidneys. We have not found information about the influence of excessive using of the MSG by a woman during pregnancy and lactation on the fetus and infants. The aim of the study was the experimental evaluation of the MSG consumption consequences during pregnancy and lactation to the offspring health. Material and methods. The offspring of 3-month old pregnant female white Wistar rats, who received 1% MSG solution (200 mg per kg of body weight per day) ad libitum as the source of liquid during the pregnancy and lactation, have been studied (MSG group). The control group included offspring of pregnant female rats that received water as the source of liquid. In 25-day-old offspring histological examination and morphometry of the nucleo-nucleolar apparatus of neurons in the neocortex of the proper parietal lobe, cardiomyocytes of the subendocardial zones of the left and right ventricles have been performed. Gravimetry have been also carried out (body weight and weight of brain, heart, liver, kidney, thymus and spleen); mitotic activity of anterior corneal epithelium has been evaluated, the state of erythrocyte membranes have been analyzed by the method of acid erythrograms; behavioral tests "Open field", "The elevated plus-maze test", "Hanging on a horizontal wire" have been performed. Results. MSG consumption during pregnancy and lactation led to an increase of brain (by 19.1%) and kidneys (by 7.8%) relative masses; masses of thymus and spleen were decreased. Significant decrease of locomotor activity and increase of time of hanging in "horizontal wire test" were registered. A histological study showed an increase in the number of nucleoli in the neurons of the V layer of the neocortex of the proper parietal lobe (control - 1.56±0.09; MSG group - 1.81±0.07, р=0.03); decrease of the nucleolar parameters of cardiomyocytes; increase of mitotic activity of anterior corneal epithelium (control - 4.021±0.612‰; MSG group - 6.985±0.889‰, р=0.019). A decrease of the resistance of erythrocyte membranes to acid hemolysis was also registered. Conclusion. The results obtained indicate the effect of oral consumption of MSG food additive during pregnancy and lactation on the organism of the offspring.

Change of Quercus robur L. acorns seedlings cytogenetic parameters under anthropogenic impact

Long-term dynamic of cytogenetic parameters of the seedlings apical root meristem was analyzed for the Quercus robur for Central Black-Soil region. Central Black-Soil region located in the European part of Russia (geographical coordinates for Voronezh city: 51.660781; 39.200269) in the temperate climate zone. Annual climate indicators were analyzed to determine the possible influence of precipitation amount and temperature fluctuations during pollination and seed formation in the parent trees. Seed progeny cytogenetic parameters of trees growing in urban and suburban conditions were characterized by an increase in mitotic activity and the proportion of cells with mitotic pathologies, the appearance of micronucleus and residual nucleoli in mitosis. There was possible consequence of the complex technosphere negative factors impact on populations. The mitotic index for urban populations (from 6.8% to 9.5 %) was approximately at the same level for all years in long-term dynamics. There was a sharp decrease in mitotic activity (4.6 %) for the control area in 2019 compared with the data for 2008 (10.5%). The proportion of cells with mitosis pathologies in the meristems of urban seedlings was increased. There was a significant prophase-cells proportion increase among the seedlings. The reduction of number of pathologies may indicate the check-point repair system operation.

A Rare Case of Atypical Pleomorphic Neoplasm of Pineal Region in a Child: A Case Report

A 10-year-old boy with no past medical history presented with complaints of nausea and vomiting associated with morning headache for the last month. Ophthalmic nerve and eye exam showed diplopia and strabismus with no other significant findings on physical and neurological examination. Magnetic resonance imaging (MRI) of the brain revealed a homogenous hyperdense and enhancing mass in the pineal region. The endoscopic biopsy of the pineal region demonstrated the cells with highly pleomorphic and hyperchromatic nuclei with an increase in mitotic activity. There were many vessels but no area of vascular proliferation and necrosis. Granular bodies with eosinophilia were identified. Immunohistochemistry was positive for class III b-tubulin with epidermal growth factor receptor (EGFR) staining and glial fibrillary acidic protein (GFAP). Immunostaining was positive for p53, Phosphatase and Tensin homolog (PTEN), and oligodendrocyte transcription factor (OLIG2), while staining for cluster of differentiation (CD)34, cytokeratin (CK), human melanoma black (HMB)45, and isocitrate dehydrogenase (IDH)-R132H mutation was negative, consistent with atypical pleomorphic neoplasm of the pineal region. The patient underwent tumor resection via a sub-occipital trans-tentorial approach, followed by one dose of chemotherapy. The patient experienced a resolution of the symptom and was doing well on his bi-monthly follow up.

Controlling osteoblast morphology and proliferation via surface micro-topographies of implant biomaterials

Current research on surface modifications has yielded advanced implant biomaterials. Various implant surface modifications have been shown to be promising in improving bone target cell response, but more comprehensive studies whether certain implant surface modifications can directly target cell behavioural features such as morphogenesis and proliferation are needed. Here, we studied the response of primary alveolar bone cells on various implant surface modifications in terms of osteoblast morphology and proliferation in vitro. Analyses of surface modifications led to surface-related test parameters including the topographical parameters micro-roughness, texture aspect and surface enlargement as well as the physicochemical parameter surface wettability. We compared osteoblast morphology and proliferation towards the above-mentioned parameters and found that texture aspect and surface enlargement but not surface roughness or wettability exhibited significant impact on osteoblast morphology and proliferation. Detailed analysis revealed osteoblast proliferation as a function of cell morphology, substantiated by an osteoblast size- and morphology-dependent increase in mitotic activity. These findings show that implant surface topography controls cell behavioural morphology and subsequently cell proliferation, thereby opening the road for cell instructive biomaterials.

Evaluation of mutagenic and anti-mutagenic potential of alpha-lipoic acid by chromosomal aberration assay in mice

This study investigated both the mutagenicity and anti-mutagenicity of alpha-lipoic acid (ALA) in the bone marrow cells of mice using a chromosomal aberration assay. Cyclophosphamide (CP) 40 mg/kg was used as a clastogen in the positive control, and a vehicle-treated negative control group was also included. Multiple dose levels (15, 30, and 100 mg/kg of ALA) were given by intraperitoneal injection (IP) alone and in combination with CP (CP was administered 1 h prior to ALA). Bone marrow samples were collected 12 and 24 h after drug administration. The results demonstrated a significant increase in the frequency of chromosomal aberrations (CA) in bone marrow cells with depressions in the mitotic index (MI) of the positive control group of mice. However, in the groups of mice treated with different doses of ALA in the presence of CP, the percentages of CA decreased significantly with increases in mitotic activity. The results also indicate that ALA given alone in different doses had no mutagenic effect on mouse bone marrow cells. ALA has a dose and time-dependent protective effect against the mutagenicity induced by CP.

Effects of Carvacrol in an Experimentally Induced Esophageal Burn Model: Expression of VEGF and Caspase-3 Proteins

Introduction We investigated the therapeutic effects of carvacrol in an experimental esophageal burn rat model with immunohistochemical techniques. Materials and Methods: Three groups were included in this study, composed of eight Wistar albino rats each. The control group was given 1 mL 0.9% (wt/vol) NaCl; esophageal burns were induced in groups 2 and 3 by administration of 1 mL 40% NaOH in the distal 2 cm of the esophagus. The treatment group was administered 75 mg/kg carvacrol in 2 mL 0.9% NaCl for 10 days. After a routine histological examination of the tissues, sections were stained with vascular endothelial growth factor (VEGF) and caspase-3 for immunohistochemical analysis and were examined under a light microscope. Results: In the control group, there were regular cells in the cornified epithelial tissue and cylindrical cells in the basal layer, which faced toward the apical surface in the mitotic phase. The burn group displayed wide degeneration, necrosis, and abundant apoptotic cells in the epithelial tissue as well as intense inflammatory cell infiltration. In the treatment group, there was an increase in mitotic activity in the basal cells of the epithelial layer and degenerative changes, but a preserved epithelial layer and significant cornified structures. The treatment group showed positive caspase-3 expression in some apoptotic cells within the epithelial layer and in connective tissue, and there were only a small number of degenerated cells in the muscle layer. Additionally, in the treatment group, VEGF expression was evident in small numbers of inflammatory cells in the papillary region of the epithelium, and in dilated vascular endothelial cells. Conclusions: Carvacrol may contribute to a reduction in fibrosis by decreasing inflammation and preventing cell apoptosis.

Induction of bystander effect in root meristem of soybean seedlings after γ-irradiation

The bystander effect refers to the non-target effects of ionizing radiation and it is the occurrence of radiation damages in the cells that have not been exposed to direct action of ionizing radiation. The aim of the study is to investigate the possibility of forming the “bystander effect” during the germination of irradiated and intact seeds of some soybean Glycine max (L.) Mer. varieties in the common aquatic environment. The soybean seeds of the Raiduga and Sprytna varieties (obtained by selection) and the genetically modified Apollo variety had been exposed to γ-radiation at a dose of 40 Gy. The mitotic activity of the seedlings root meristem cells of irradiated (IR) and intact (IN) seeds, as well as intact seeds, which were germinated in the same aqueous medium together with irradiated (INIR), was analyzed. The similar levels of mitotic activity were observed in seedlings of breeding varieties in “IN” variant, while cells in genetically modified variety divided more intensively. Radiation exposure in a dose of 40 Gy increased the level of mitotic activity in all varieties. The values of the mitotic indices increased 2 times in the varieties of Raiduga and Sprytna. The increase in Apollo variety was less significant, but this may be due to a high level of mitotic activity in the control variant. Irradiation also contributed to the appearance of chromosomal aberrations: fragments and bridges. The increase in mitotic activity in the meristem of the studied varieties to the mentioned levels may indicate the presence of a pool of meristem cells that can accelerate the passage of phases of the mitotic cycle under extreme conditions. Mitotic activity increased in the “INIR” variant in all investigated varieties. The largest excess over the “IN” was in Sprytna, a little less in the variety Raiduga. The proliferative activity in the Apollo variety meristem remained almost unchanged. Thus, the work shows the possibility of a “bystander effect” forming under the condition of joint germination of irradiated and intact seeds in the common aquatic environment. The intensity of “bystander effect” formation depends on the genotype and start mitotic potential.

Bystander effect formation in the sprout root meristem in condition of irradiated and non-irradiated seeds joint growing

Aim. To study the possibility of bystander effect inducing in the joint germination in a common aqueous environment of irradiated and non-irradiated seeds. Methods. Cytogenetic methods including mitotic activity level estimation, accounting for the number of nucleoli, and methods for statistical analysis of the data. Results. The effect of radiation stimulation with a dose of 40 Gy was dependent on the variety, and the effect of gamma radiation at a dose of 200 Gy reduced the level of mitotic activity in comparison with the control in both varieties. Mitotic indices increase in the meristem of non-irradiated seeds while growing with irradiated one. Conclusions. The bystander effect is formed on the organismic level under condition of growing of irradiated and non-irradiated seeds in a common aquatic environment and it is ma-nifested as an increase in the level of meristem cells proliferation and in the intensification of synthetic processes. The addition of irradiated with a high dose of gamma radiation seeds to the non-irradiated seeds induces an increase in mitotic activity largely than the addition of seeds irradiated with a relatively small dose.&#x0D; Keywords: bystander effect, radiation stimulation, mitotic activity, nucleoli.

Mitotic and apoptotic activity in colorectal neoplasia

BackgroundColorectal cancer (CRC) is third most commonly diagnosed cancer worldwide. The aim of the prospective study was to evaluate mitosis and apoptosis of epithelial cells at each stage of colorectal neoplasia.MethodsA total of 61 persons were enrolled into the study: 18 patients with non-advanced colorectal adenoma (non-a-A), 13 patients with advanced colorectal adenoma (a-A), 13 patients with CRC and 17 controls: individuals with normal findings on colonoscopy. Biopsy samples were taken from pathology (patients) and healthy mucosa (patients and healthy controls). Samples were formalin-fixed paraffin-embedded and stained with haematoxylin-eosin. Mitotic and apoptotic activity were evaluated in lower and upper part of the crypts and in the superficial compartment. Apoptotic activity was also assessed using detection of activated caspase-3.ResultsIn controls, mitotic activity was present in lower part of crypts, accompanied with low apoptotic activity. Mitotic and apoptotic activity decreased (to almost zero) in upper part of crypts. In superficial compartment, increase in apoptotic activity was observed. Transformation of healthy mucosa into non-a-A was associated with significant increase of mitotic activity in lower and upper part of the crypts and with significant increase of apoptotic activity in all three compartments; p < 0.05. Transformation of non-a-A into a-A did not lead to any further significant increase in apoptotic activity, but was related to significant increase in mitotic activity in upper part of crypts and superficial compartment. A significant decrease in apoptotic activity was detected in all three comparments of CRC samples compared to a-A; p < 0.05. No differences in mitotic and apoptotic activity between biopsies in healthy controls and biopsy samples from healthy mucosa in patients with colorectal neoplasia were observed. Detection of activated caspase-3 confirmed the above findings in apoptotic activity.ConclusionsSignificant dysregulation of mitosis and apoptosis during the progression of colorectal neoplasia, corresponding with histology, was confirmed. In patients with sporadic colorectal neoplasia, healthy mucosa does not display different mitotic and apoptotic activity compared to mucosa in healthy controls and therefore adequate endoscopic/surgical removal of colorectal neoplasia is sufficient.

Doxorubicin-provoked increase of mitotic activity and concomitant drain of G0-pool in therapy-resistant BE(2)-C neuroblastoma.

In this study chemotherapy response in neuroblastoma (NB) was assessed for the first time in a transplantation model comprising non-malignant human embryonic microenvironment of pluripotent stem cell teratoma (PSCT) derived from diploid bona fide hESC. Two NB cell lines with known high-risk phenotypes; the multi-resistant BE(2)-C and the drug sensitive IMR-32, were transplanted to the PSCT model and the tumour growth was exposed to single or repeated treatments with doxorubicin, and thereafter evaluated for cell death, apoptosis, and proliferation. Dose dependent cytotoxic effects were observed, this way corroborating the experimental platform for this type of analysis. Notably, analysis of doxorubicin-resilient BE(2)-C growth in the PSCT model revealed an unexpected 1,5-fold increase in Ki67-index (p<0.05), indicating that non-cycling (G0) cells entered the cell cycle following the doxorubicin exposure. Support for this notion was obtained also in vitro. A pharmacologically relevant dose (1μM) resulted in a marked accumulation of Ki67 positive BE(2)-C cells (p<0.0001), as well as a >3-fold increase in active cell cycle (i.e. cells positive staining for PH3 together with incorporation of EdU) (p<0.01). Considering the clinical challenge for treating high-risk NB, the discovery of a therapy-provoked growth-stimulating effect in the multi-resistant and p53-mutated BE(2)-C cell line, but not in the drug-sensitive p53wt IMR-32 cell line, warrants further studies concerning generality and clinical significance of this new observation.

Photobiomodulation therapy action in wound repair skin induced in aged rats old: time course of biomarkers inflammatory and repair.

Previous studies have discussed an inverse correlation between age and wound healing, because it relates to the association of aging with a gradual decrease in healing capacity. Treatment with photobiomodulation therapy (PBMT) improves wound healing by inducing increases in mitotic activity, numbers of fibroblasts, collagen synthesis, and neovascularization. Therefore, this study aimed to evaluate the effects of PBMT in cutaneous wound healing in aged rats. A punch biopsy of 8mm in diameter was performed to produce a skin wound. The study included 45 male rats, of which 15 were young (30days) and 30 were elderly (500days). The 45 animals were distributed into 3 experimental groups, which were subjected to skin wounds and 1 aged group received PBMT, with a 30-mW laser beam (power density of 1.07W/cm2), beam area of 0.028cm2, and λ660nm produced through active phosphide Gallium-Aluminum-Indio (InGaAIP). The PBMT application took the form of a single-point transcutaneous method, with a total energy of 2 joules per wound site, energy density of 72J/cm2, and time of 1min and 7s. Analysis was performed to verify the effect of PBMT on the quantity of collagen I and III, metalloproteinase 3 and 9 (MMP-3 and MMP-9), tissue inhibitor of metalloproteinase-2 (TIMP-2) and of vascular endothelial growth factor (VEGF) at the wound site by immunohistochemistry, cytokine-induced neutrophil chemoattractant (CINC)-1, by enzyme-linked immunosorbent assay (ELISA) and interleukin (IL)-6 real-time polymerase chain reaction (RT-PCR). That we conclude LLLT is effective in the modulation of inflammatory mediators IL-6, CINC-1, VEGF, MMP-3, MMP-9 and TIMP-2 as well as increased collagen production in aged animals during different phases of the tissue regeneration process. However, the effects of PBMT obtained in the aged animals (aged LLLT group) suggest that new dosimetries should be tested to achieve better results.

Temporal lobe epilepsy and adult hippocampal neurogenesis

Temporal lobe epilepsy (TLE) is a common and severe neurological disorder which is often intractable. It can not only damage the normal structure and function of hippocampus, but also affect the neurogenesis in dentate gyrus (DG). It is well documented from researches on the animal models of TLE that after a latent period of several days, prolonged seizure activity leads to a dramatic increase in mitotic activity in the hippocampal DG. However, cell proliferation returns to baseline levels within 3-4 weeks after status epilepticus (SE). Meanwhile, there are two major abnormalities of DG neurogenesis, including the formation of hilar basal dendrites and the ectopic migration of newborn granule cells into the polymorphic cell layer, which may affect epileptogenesis and seizure onset. However, the specific contribution of these abnormalities to seizures is still unknown. In other words, whether they are anti-epileptic or pro-epileptic is still under heated discussion. This article systematically reviews current knowledge on neurogenesis and epilepsy based on the results of studies in recent years and discusses the possible roles of neurogenesis in epileptogenesis and pathologic mechanisms, so as to provide information for the potential application of neurogenesis as a new clinical therapeutic target for temporal lobe epilepsy.

Differential regulation of meristem size, morphology and organization by the ERECTA, CLAVATA and class III HD-ZIP pathways.

ABSTRACTThe shoot apical meristem (SAM) of angiosperm plants is a small, highly organized structure that gives rise to all above-ground organs. The SAM is divided into three functional domains: the central zone (CZ) at the SAM tip harbors the self-renewing pluripotent stem cells and the organizing center, providing daughter cells that are continuously displaced into the interior rib zone (RZ) or the surrounding peripheral zone (PZ), from which organ primordia are initiated. Despite the constant flow of cells from the CZ into the RZ or PZ, and cell recruitment for primordium formation, a stable balance is maintained between the distinct cell populations in the SAM. Here we combined an in-depth phenotypic analysis with a comparative RNA-Seq approach to characterize meristems from selected combinations of clavata3 (clv3), jabba-1D (jba-1D) and erecta (er) mutants of Arabidopsis thaliana. We demonstrate that CLV3 restricts meristem expansion along the apical-basal axis, whereas class III HD-ZIP and ER pathways restrict meristem expansion laterally, but in distinct and possibly perpendicular orientations. Our k-means analysis reveals that clv3, jba-1D/+ and er lead to meristem enlargement by affecting different aspects of meristem function; for example, clv3 displays an increase in the stem cell population, whereas jba-1D/+ er exhibits an increase in mitotic activity and in the meristematic cell population. Our analyses demonstrate that a combined genetic and mRNA-Seq comparative approach provides a precise and sensitive method to identify cell type-specific transcriptomes in a small structure, such as the SAM.

5-Fluorouracil Treatment Leads to Activation of Stem Cell Niche By Reconstructing Mesenchymal Stromal Cells and Exert a Distinct Microenvironmental Impact on Normal and Leukemic Cells

Reactivation of endogenous hematopoietic stem cells (HSCs) are initiated by stimulation of bone marrow niche triggered by various injury signals. Here, we show that treatment with 5-fluorouracil (5-FU) leads to reconstruction of bone marrow (BM) microenvironment to establish an activated niche stimulating hematopoietic stem cells (HSCs). First, we show that pre-treatment with 5-FU leads to engraftment of donor cells in non-irradiated recipient mice without affecting the homing efficiency of HSCs into BM. The HSC activation effects were reproduced in-vitro by co-culturing hematopoietic cells with CD45-Ter119- stromal cells derived from 5-FU treated BM, but not by co-culture with CD45+ cells or stromal cells obtained from enzymatic digestion of bone from the same mice. Examination of BM mesenchymal cells after 5-FU treatment revealed a rapid emergence of high-proliferating mesenchymal progenitors exhibiting large size colony (CFU-F) and higher self-renewal of colonogenic cells 3-5 days after 5-FU treatment, which was concomitantly associated with regeneration of CD34+Lin-Sca-1+c-kit+ (LSK) cells in the same BM. The cellular changes in mesenchymal stroma was associated with rapid emergence of characteristic mesenchymal cell populations (PDGFR-a+/Leptin receptor+/SSEA-3+: PLS) with 650-folds increase of the PLS cells in BM in 3 days after 5-FU treatment. However, the increase of these PLS mesenchymal cells were not associated with increase in mitotic activity of mesenchymal cells (<5% BrdU+ cells), indicating phenotypic conversion of subpopulation in BM. Moreover, cellular changes in mesenchymal niche were associated with rapid increase of mesenchymal cells expressing cross-talk molecules such as CXCL-12 (20-folds), Jagged-1 (13-folds) and DLL-1 (15-folds). Furthermore, in-vivo administration of chemicals blocking CXCL-12 and notch signaling during the recovery from the 5-FU treatment led to the significant loss of LSK-SLAM cells in the regenerated BM. Interestingly, the BM niche activated by 5-FU exerted a distinct effect on normal and leukemic cells in a manner that it provide higher support on the primitive state of normal HSCs than for MN-1 induced leukemia cells. Thus, leukemic mice engrafted with MN-1 cells exhibited a decrease in primitive leukemic cell (Lin-c-kit+) and higher survival by 5-FU treatment than those treated by radiation. Taken together, our study reveals the cellular reconstruction of mesenchymal niche in BM during stimulus-induced niche activation and provides an insight on the selective niche targeting as a novel therapeutic strategies for hematological diseases. DisclosuresNo relevant conflicts of interest to declare.

English

Magnetic field is considered a simple and cheap method for stimulation of germination process compared to traditional chemical processes. In this research, laboratory experiment was conducted at Seed Technology Unit, Mansoura, Egypt to evaluate the effect of magnetic field on germination, seedling growth and cytogenetic characters of fresh and carry over (old) onion seeds (c.v.Giza Red). Seeds were magnetically pretreated by different magnetic field (0.03 or 0.06 T) using static magnetic device for different periods time (30, 60 and 90 mint). The obtained results indicated that magnetic field treatment increased all germination and seedling growth characters compared with control. Exposed fresh and carry over seeds to 0.06 T with 30 mint gave the heights values of germination percentage, germination rate, speed germination index and seedling growth parameters, that is, seedling length, seedling dry weight, seedling vigor I and seedling vigor II. Whereas, mean germination time was decreased using 0.03 T with 60 mint gave maximum values in carry over seeds and with 60 min in new seeds. Also, the results showed significant increase in mitotic activity and chromosomal aberration after 30 min treatments for both doses of fresh seeds and with 0.06 T of carry over seeds, while relative division rate (RDR) gave positive values and little disturbance in mitotic phase index. However, the percentage of mitotic abnormalities increased after all exposure treatments. It could be concluded that utilization of magnetic field could enhancement of germination of onion seeds but we need to be carry out more experiments to make magnetic map for all varieties of onion. Key words: Magnetic field, germination, mitotic activity, phase index, relative division rate, mitotic aberrations.