Histopathological evaluation of zebrafish (Danio rerio) larvae following embryonic exposure to MgO nanoparticles

The aim of this study was to investigate the histopathological changes in zebrafish larvae following embryonic exposure to nanoparticles of magnesium oxide (MgONPs). The toxicity of metal oxide nanoparticles is attracting increasing attention. Among these nanomaterials, MgONPs are particularly interesting as a low cost and environmentally-friendly material. Histological investigations are used as a highly sensitive method for detecting the morphological features of disease and abnormal gene function. We evaluated the histopathological changes in zebrafish larval tissues following embryonic exposure to MgONPs for a period of 4-96 h post fertilization (hpf). To this end; fixation, tissue processing, sectioning and general staining of the whole-larvae were performed. Histopathological evaluations showed some changes including psoriasis-like epithelial hyperproliferation, muscle cell degeneration, neurodegeneration in the spinal cord, swelling and edematous changes in pericardium, swelling and edematous changes in yolk sac, severe edema within the eyes, smaller retina, disruption of retinal lamination and impaired retinal differentiation. In summary, the results of this study enhance our understanding about the potential hazards of MgONPs to the environment

Effect of bee venom on human acute T-cell lymphoblastic leukemia cell line apoptosis

Background: Recent studies indicate the potential role of bee venom (BV) in cancer therapy. Moreover, many evidences suggest that the regulation of apoptosis plays an important role in tumorigenesis. Considering the apoptosis-inducing and anti-tumor effect of BV, this study aimed to determine the type of the cell death induced by BV on MOLT-4 cancer cell line.Materials and Methods: In this experimental study, MOLT-4 cells were first cultured in RPMI-1640 medium in plate, then the cells were treated with different concentrations (1, 3, 6 and 8 μg/ml) of BV for 24 and 48 h. Morphology of cells, cell viability and type of the cell death were induced by BV were evaluated using inverted microscopy, the MTT assay and flow cytometry, respectively.Results: Cell survival findings showed the BV CC50 values of 6.3 and 0.6 μg/ ml for the cell line in 24 and 48 h, respectively. Moreover, Morphological and Annexin-V antibody analyses indicated that the BV-induced cell death might be an apoptosis. Conclusion: As BV can induce the apoptosis in MOLT-4 cancer cells. Thus, it would bring hope for designing novel drugs for cancer-therapy in future

The effect of curcumin on the estradiol valerate-induced polycystic ovary in rats

Background: Polycystic ovary syndrome (PCOS) is a syndrome with complex endocrine and metabolic disorders, which is characterized by chronic anovulation, polycystic ovary and hyperandrogenism. Curcumin is a substance with antioxidant and anti-inflammatory effects. This study aimed to examine the therapeutic effect of curcumin on polycystic ovary syndrome in adult rats. Materials and Methods: In this experimental study, PCOS was induced in adult female Wistar rats (170 g) by subcutaneous injection of estradiol valerate (2 mg/kg). The control group received no injection. At the end of 60th day, the rats were divided into control, PCOS and curcumin-treated PCOS (100, 200, 300 and 400 mg/kg) groups. After 14 days of intraperitoneal curcumin treatment, blood and ovary samples of all groups were taken for histological and serological studies. Results: The thickness of the theca layer, primordial follicles and number of cysts were significantly decreased in high-dose curcumin treated ovaries compared to the PCOS group. Moreover, the appearance of corpus luteums as the main sign of recurrent ovulation was established. The serological analyses showed an increase in FSH and progesterone and a decrease in LH, estradiol and testosterone compared to the PCOS. Conclusion: The results indicate that curcumin may be a useful agent for improving the PCOS and initiation of ovulation through its various antioxidant and anti-inflammatory effects

In Vitro Effects of Wistar Rat Prenatal and Postnatal Cerebrospinal Fluid on Neural Differentiation and P roliferation of Mesenchymal Stromal Cells Derived from Bone Marrow.

Objective: Cerebrospinal fluid (CSF) plays an important role in cortical development during the fetal stages. Embryonic CSF (E-CSF) consists of numerous neurotrophic and growth factors that regulate neurogenesis, differentiation, and proliferation. Mesenchymal stem cells (MSCs) are multi-potential stem cells that can differentiate into mesenchymal and non-mesenchymal cells, including neural cells. This study evaluates the prenatal and postnatal effects of CSF on proliferation and neural differentiation of bone marrow MSCs (BM-MSCs) at gestational ages E19, E20, and the first day after birth (P1). Materials and Methods: In this experimental study, we confirmed the mesenchymal nature of BM-MSCs according to their adherence properties and surface markers (CD44, CD73 and CD45). The multi-potential characteristics of BMMSCs were verified by assessments of the osteogenic and adipogenic potentials of these cells. Under appropriate in vitro conditions, the BM-MSCs cultures were incubated with and without additional pre- and postnatal CSF. The MTT assay was used to quantify cellular proliferation and viability. Immunocytochemistry was used to study the expression of MAP-2 and β-III tubulin in the BM-MSCs. We used ImageJ software to measure the length of the neurites in the cultured cells. Results: BM-MSCs differentiated into neuronal cell types when exposed to basic fibroblast growth factor (b-FGF). Viability and proliferation of the BM-MSCs conditioned with E19, E20, and P1 CSF increased compared to the control group. We observed significantly elevated neural differentiation of the BM-MSCS cultured in the CSF-supplemented medium from E19 compared to cultures conditioned with E20 and P1 CSF group. Conclusion: The results have confirmed that E19, E20, and P1 CSF could induce proliferation and differentiation of BM-MSCs though they are age dependent factors. The presented data support a significant, conductive role of CSF components in neuronal survival, proliferation, and differentiation

Gestational diabetes leads to down-regulation of CDK4-pRB-E2F1 pathway genes in pancreatic islets of rat offspring

Objective(s): The link between a hyperglycemic intrauterine environment and the development of diabetes later in life has been observed in offspring exposed to gestational diabetes mellitus (GDM), but the underlying mechanisms for this phenomenon are still not clear. Reduced β-cells mass is a determinant in the development of diabetes (type 1 and type 2 diabetes). Some recent studies have provided evidence that the CDK4-pRB-E2F1 regulatory pathway is involved in β-cells proliferation. Therefore, we postulated that GDM exposure impacts the offspring’s β-cells by disruption in the CDK4-pRB-E2F1 pathway. Materials and Methods: Adult Wistar rats were randomly allocated in control and diabetic group. The experimental group received 40 mg/kg/body weight of streptozotocin (STZ) on day zero of gestation. After delivery, diabetic offspring of GDM mothers and control dams at the age of 15 week were randomly scarified and pancreases were harvested. Langerhans islets of diabetic and control groups were digested by collagenase digestion technique. After RNA extraction, we investigated the expressions of the kir 6.2 and CDK4-pRB-E2F1 pathway genes by quantitative real-time PCR. Results: GDM reduced the expression of CDK4-pRB-E2F1 pathway genes in Langerhans islets cells of offspring. CDK4, pRB and E2F1 pathway genes were downregulated in diabetic islets by 51, 35 and 84, respectively. Also, the expression of Kir 6.2 was significantly decreased in diabetic islets by 88. Conclusion: We suggest that the effect of gestational diabetes on offspring’s β-cells may be primarily caused by the suppression of CDK4-pRB-E2F1 pathway. © 2017, Mashhad University of Medical Sciences. All rights reserved

Bee venom treatment reduced C-reactive protein and improved follicle quality in a rat model of estradiol valerate-induced polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) is a low grade inflammatory disease characterized by hyperandrogenemia and chronic anovulation. C-reactive protein (CRP), released by adipocytes, plays a key role in PCOS. Apis mellifera honeybee venom (HBV) contains a variety of biologically active components with various pharmaceutical properties. This study was designed to assess the possibility of HBV application as an anti-inflammatory therapeutic agent. To induce PCOS, 1 mg/100 g body weight estradiol valerate (EV) was subcutaneously (SC) injected into eight-week-old rats. After 60 days, 0.5 mg/kg HBV was administered SC for 14 consecutive days, and the results of PCOS treatment were investigated. Rats were then anesthetized with chloroform, and their ovaries and livers were surgically removed to determine histomorphometrical changes. Testosterone and 17-β-estradiol were detected by chemiluminescence immunoassay. In order to detect serum CRP, ELISA kit was used in three groups of EV-induced PCOS, HBV-treated PCOS and control animals. Thickness of the theca layer, number of cysts and the level of serum CRP significantly decreased in HBV group in comparison with PCOS group. Moreover, corpus luteum, as a sign of ovulation, was observed in HBV-treated ovaries which were absent in PCOS group. Our results suggest that the beneficial effect of HBV may be mediated through its inhibitory effect on serum CRP levels

Effect of Bumble Bee Venom in the Treatment of Polycystic Ovary Syndrome, the Relationship Between Tissue Factor Affecting the Level of TNFα in the Wistar Rat Model

Abstract Background & aim: Polycystic ovary syndrome (PCOS) is an endocrine failure leading to anovulation. TNFα is an effective factor in the regulation of normal functioning of the ovaries. High levels of TNFα causes PCOS is further. In this study, the effects of bumble bee venom (HBV) on TNFα and other symptoms of ovarian PCOS were studied. Methods: In this experimental study, 60 female Wistar rats were divided into three groups: control, sham and experimental groups. The experimental group was injected with estradiol valerate-induced PCOS direction. Induced rats (PCOS) were divided into two groups and treated with HBV. The treatment Group received 0.2mg of HBV for 10 consecutive days. Serum and ovarian tissue was collected from each of the four groups to compare the histological and changes in blood sugar levels. Results: A significant increase in ovarian PCOS weight was observed in the control group , whereas in the treated group with HBV rate fell (15.5 mg) Glucose levels in PCOS was 256.5, the control group138, and the treatment group 158. Thickness of the theca layer of antral follicles in the treated group compared with PCOS showed a significant decrease (110 μm and 150 μm respectively). Immunohistochemical results showed increased TNFα factor in PCOS group than in the control group, whereas these levels in samples treated with HBV Reduced. Conclusion: The results of this study revealed that the beneficial effects of HBV in PCOS may be due to the inhibitory effect on factor TNFα. Key words: Polycystic ovary syndrome, Bumble bee venom, Tumor necrosis factor, Immunohistochemistr

In vitro comparative survey of cell adhesion and proliferation of human induced pluripotent stem cells on surfaces of polymeric electrospun nanofibrous and solution-cast film scaffolds

Extracellular matrix (ECM) components play a critical role in regulating cell behaviors. Interactions between ECM components and cells are important in various biological processes, including cell attachment, survival, morphogenesis, spreading, proliferation, and gene expression. In this study the in vitro responses of human induced pluripotent stem cells (hiPSCs) on polycaprolactone (PCL) electrospun nanofibrous scaffold were reported in comparison with those of the cells on corresponding solution-cast film scaffold. Our results demonstrated that the nanofibrous scaffold showed better support for the attachment and proliferation of hiPSCs than their corresponding film scaffold. Consequently, we emphasize that hiPSCs can sense the physical properties and chemical composition of the materials and regulate their behaviors accordingly. © 2015 Wiley Periodicals, Inc

Changes in the Expression of Cyclooxygenase-2 in Polycystic Ovary Syndrome in Wistar Rats

Background: Cyclooxygenase 2 is a key enzyme which converts arachidonic acid into prostaglandins. Cyclooxygenase 2 is triggered by inflammatory stimuli, such as cytokines. Its expression increases in tumors and Alzheimer's disease and ovarian hyperstimulation syndrome. Polycystic ovarian syndrome is a heterogeneous disease characterized by pathological angiogenesis and chronic anovulation. In the present study, the probable role of cyclooxygenase 2 in Wistar rats with polycystic ovarian syndrome was investigated.Methods: Thirty female Wistar rats (170-200 gr) were equally divided into three groups: 2 mg estradiol valerate was intramuscularly administered to each rat in the experiment group or group 1; the rats in group 2 were regarded as the sham group and received sesame oil injections and group 3 or the control group received no injections. After 60 days of treatment, animals were anaesthetized with chloroform and killed by decapitation. Ovaries were collected for histological and immunohistochemical evaluations. All the experiments were repeated three times.Results: Morphologically, ovaries from the control group exhibited follicles in various stages of development and many fresh corpus luteum. In estradiol valerate group small follicles in early development were observed in addition to follicles showing evidence of atresia and many large cysts with thickened theca cell layer. Corpus luteum was rare or absent in group 2. The immunohistochemical analysis for cyclooxygenase 2 expression showed an increased expression of cyclooxygenase 2 enzyme in group 1.Conclusion: The results suggested the involvement of cyclooxygenase 2 in the progression to polycystic ovarian syndrome in a rat model