scholarly journals Toxicity of chlordane at early developmental stage of zebrafish

2017 ◽  
Author(s):  
Jingxuan Xiong
Keyword(s):  
Early Stage ◽  
Real Life ◽  
Potential Effect ◽  
Early Developmental Stage ◽  
Dependent Manner ◽  
Lower Survival Rate ◽  
Zebrafish Larvae ◽  
Hatching Time ◽  
Early Developmental ◽  
Dose Dependent

AbstractChlordane is highly toxic organochlorine pesticides that have been widely used throughout the world for decades and posing adverse effects on the environment. Contents detected in tissue and blood samples have resulted in a raising concern for their potential effects on wildlife and humans. In this study, we investigate the potential effect of chlordane on the development of zebrafish embryos. Zebrafish larvae were treated with different concentrations (0, 25, 50, 100, 200 ng/L) of chlordane from 12 hours postfertilization (hpf). Different early stage parameters were observed at 1, 2, 3 and 4 day post-fertilization (dpf). Chlordane-exposed zebrafish larvae appeared significant lower survival rate, developmental and hatching time delay and decreased embryo productivity. The heartbeat rate and blood flow were decreased in a dose dependent manner. These results suggested that exposure to real life of chlordane led to direct morphological and phenotypic changes and effects systems related to development and reproduction even in short-term manner.

Oral Supplementation with Omega3 Fatty Acids Inhibits NFkB Activation In Chronic Lymphocytic Leukemia (CLL) Cells.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4607-4607
Author(s):  
Oscar F. F Ballester ◽  
Johannes Fahrmann ◽  
Theodore Witte ◽  
Gabriela Ballester ◽  
W. Elaine Hardman
Keyword(s):  
Conflicts Of Interest ◽  
Early Stage ◽  
Gradient Centrifugation ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Dependent Manner ◽  
Red Cell ◽  
Omega 3 ◽  
Dose Dependent

Abstract Abstract 4607 Introduction: Nuclear factor kappa B (NFkB) is a critical transcription factor involved in the growth and survival of CLL cells. NFkB is recognized as an important target for the development of novel therapies for the treatment of various malignancies. In vitro and in experimental animal models, OMEGA-3 fatty acid (O3FA) supplementation has been shown to inhibit NFkB activity. Patients and Methods: Patients with early stage CLL (Rai stages 0-II) who required no therapy, where accrued to this phase I-II trial. O3FA supplements were given for a total of 12 months at doses ranging from 2250 mg (EPA plus DHA), escalated to 4500 mg and 6750 mg per day as tolerated. NFkB activity was measured in peripheral blood samples after separation of mononuclear cell by gradient centrifugation and expressed as luminescence units/μ g of protein. Baseline and multiple serial samples were obtained during the study period. In-vitro cytotoxicity assays to doxorubicin were conducted using standard LD50 methods. Compliance was monitored by analysis of red cell and lymphocyte membrane lipid composition by gas chromatography. Results: Fifteen patients have been accrued to the trial, 8 of them have currently completed the planned 12 months of the study period. No significant clinical changes in disease activity were noted. O3FA was well tolerated. Supplementation resulted in a dose-dependent increase of O3FA composition of red cell and lymphocyte membranes in a dose dependent manner. At baseline, CLL patients had NFkB above the range observed in normal controls (2.05 × 104 to 2.32 × 105 NFkB lum units/μ g). The median value in CLL patients at baseline was 11.60 × 106 NFkB lum units/μ g (range 0.9 × 105 to 23.12 × 106). Among 5 patients with the highest baseline levels of NFkB, a decrease in NFkB activity ranging from 0.02 to 0.19 of the baseline value, was noted at the 2 higher doses of O3FA supplementation. Similar results were seen in patients with relatively lower levels of baseline NFkB activity (0.9 × 105 to 2.96 × 106 lum units/μ g). In vitro, significant doxorubicin cytotoxicity (>50%) was noted in samples obtained during supplementation, at μ gM concentrations which produced no detectable cell kill in baseline samples. Conclusions: O3FA supplementation resulted in significant inhibition of NFkB activity in leukemic cells from patients with CLL. In-vitro, after O3FA supplementation CLL cells became more sensitive to doxorubicin. Preliminary analysis of whole genome micro arrays revealed significant down-regulation of multiple genes associated with O3FA supplementation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Activation Effects of Polysaccharides ofFlammulina velutipesMycorrhizae on the T Lymphocyte Immune Function

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Zheng-Fei Yan ◽  
Nai-Xu Liu ◽  
Xin-Xin Mao ◽  
Yu Li ◽  
Chang-Tian Li
Keyword(s):  
Immune Function ◽  
T Lymphocyte ◽  
Interleukin 2 ◽  
Potential Effect ◽  
Dependent Manner ◽  
Health Products ◽  
Immune Health ◽  
Spleen Lymphocytes ◽  
Dose Dependent

Flammulina velutipesmycorrhizae have increasingly been produced with increasing ofF. velutipesproduction. A mouse model was thus used to examine potential effect ofF. velutipesmycorrhizae on the immune function. Fifty female Wistar mice (5-weeks-old) weighed 15–20 g were randomly allocated into five groups. Polysaccharide ofF. velutipesmycorrhizae were treated with mice and mice spleen lymphocytes. The levels of CD3+, CD4+, and CD8+T lymphocyte, interleukin-2 (IL-2), and tumor necrosis factor-a (TNF-α) were determined. The results showed that the proportions of CD3+, and CD4+T lymphocyte, the ratio of CD4+/CD8+, and the levels of IL-2 and TNF-a were significantly increased in polysaccharide ofF. velutipesmycorrhizae, while the proportion of CD8+T lymphocyte was decreased in polysaccharide ofF. velutipesmycorrhizae-dose dependent manner. Our findings indicated that a long term exposure of polysaccharide ofF. velutipesmycorrhizae could activate the T lymphocyte immune function. Polysaccharide ofF. velutipesmycorrhizae was expected to develop into the immune health products.

scholarly journals In-Vivo Toxicity Studies and In-Vitro Inactivation of SARS-CoV-2 by Povidone-iodine In-situ Gel Forming Formulations

2020 ◽  
Author(s):  
Bo Liang ◽  
Xudong Yuan ◽  
Gang Wei ◽  
Wei Wang ◽  
Ming Zhang ◽  
...  
Keyword(s):  
Povidone Iodine ◽  
Early Stage ◽  
Etiologic Agent ◽  
Dependent Manner ◽  
Forming Technology ◽  
Long Acting ◽  
Dose Dependent

AbstractTo curb the spread of SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, we characterize the virucidal activity of long-acting Povidone Iodine (PVP-I) compositions developed using an in-situ gel forming technology. The PVP-I gel forming nasal spray (IVIEW-1503) and PVP-I gel forming ophthalmic eye drop (IVIEW-1201) rapidly inactivated SARS-CoV-2, inhibiting the viral infection of VERO76 cells. No toxicity was observed for the PVP-I formulations. Significant inactivation was noted with preincubation of the virus with these PVP-I formulations at the lowest concentrations tested. It has been demonstrated that both PVP-I formulations can inactivate SARS-CoV-2 virus efficiently in both a dose-dependent and a time-dependent manner. These results suggest IVIEW-1503 and IVIEW-1201 could be potential agents to reduce or prevent the transmission of the virus through the nasal cavity and the eye, respectively. Further studies are needed to clinically evaluate these formulations in early-stage COVID-19 patients.

Fibroblast growth factor during mesoderm induction in the early chick embryo

Development ◽  
1990 ◽  
Vol 109 (2) ◽  
pp. 387-393 ◽  
Author(s):  
E. Mitrani ◽  
Y. Gruenbaum ◽  
H. Shohat ◽  
T. Ziv
Keyword(s):  
Developmental Stages ◽  
Culture Conditions ◽  
Mesoderm Induction ◽  
Dependent Manner ◽  
Chick Embryogenesis ◽  
Defined Culture ◽  
High Degree ◽  
Early Developmental ◽  
Dose Dependent

A chick genomic clone that reveals a high degree of homology to the mammalian and Xenopus bFGF gene has been isolated. The pattern of expression of bFGF has been examined during early chick embryogenesis. RNA blot analysis revealed that chick bFGF is already transcribed at pregastrula stages. Immunolabeling analysis indicated that bFGF protein is present at these early developmental stages and is distributed evenly in the epiblast, hypoblast and marginal zone of the chick blastula. Substances that can inhibit FGF action were applied to early chick blastoderms grown in vitro under defined culture conditions (DCM). Both heparin and suramin were capable of blocking the formation of mesodermal structures in a dose-dependent manner. Our results indicate that FGF-like substances may need to be present for axial structures to develop although they may be acting earlier during the induction of non-axial mesoderm.

A patient with medulloblastoma in its early developmental stage

2014 ◽  
Vol 14 (6) ◽  
pp. 615-620 ◽  
Author(s):  
Naoki Shinojima ◽  
Hideo Nakamura ◽  
Masayoshi Tasaki ◽  
Kouki Kameno ◽  
Shigeo Anai ◽  
...  
Keyword(s):  
Developmental Stage ◽  
Early Stage ◽  
Expression Patterns ◽  
Immunohistochemical Analysis ◽  
Sudden Onset ◽  
Early Developmental Stage ◽  
Chromosome 6 ◽  
Group 4 ◽  
The Individual ◽  
Early Developmental

Medulloblastoma is the most frequent malignant brain tumor of the posterior fossa in children and is considered an embryonal tumor. It has been suggested that medulloblastomas be categorized into 4 distinct molecular subgroups— WNT (DKK1), SHH (SFRP1), Group 3 (NPR3), or Group 4 (KCNA1)—since each subgroup is distinct and there is no overlap. The authors report on a 13-year-old boy with medulloblastoma. He presented with sudden-onset nausea and vomiting due to intratumoral hemorrhage. The medulloblastoma was thought to be in an early developmental stage because the tumor volume was extremely small. Immunohistochemical analysis showed that the tumor was mainly composed of DKK1- and NPR3-positive areas. The individual areas of the tumor stained only for DKK1 or NPR3, with no overlap—that is, DKK1 and NPR3 expression were mutually exclusive. Samples obtained by laser microdissection of individual areas and subjected to mass spectrometry confirmed that the expression patterns of proteins were different. Fluorescence in situ hybridization for chromosome 6 showed there were 2 distinct types of cells that exhibited monosomy or disomy of chromosome 6. These results demonstrated that distinct subtypes of medulloblastoma may be present within a single tumor, an observation that has not been previously reported. Our findings in this case indicate that early-stage medulloblastoma may include more than 1 distinct subtype and hint at factors involved in the origin and development of medulloblastomas.

scholarly journals The PI3K/Akt pathway is involved in early infection of some exogenous avian leukosis viruses

2011 ◽  
Vol 92 (7) ◽  
pp. 1688-1697 ◽  
Author(s):  
Shao-zhen Feng ◽  
Wei-sheng Cao ◽  
Ming Liao
Keyword(s):  
Viral Entry ◽  
Early Stage ◽  
Dependent Manner ◽  
Phosphatidylinositol 3 Kinase ◽  
Akt Phosphorylation ◽  
Akt Activation ◽  
Pi3k Inhibitors ◽  
Cellular Factors ◽  
Dose Dependent

Avian leukosis virus (ALV) is an enveloped and oncogenic retrovirus. Avian leukosis caused by the members of ALV subgroups A, B and J has become one of the major problems challenging the poultry industry in China. However, the cellular factors such as signal transduction pathways involved in ALV infection are not well defined. In this study, our data demonstrated that ALV-J strain NX0101 infection in primary chicken embryo fibroblasts or DF-1 cells was correlated with the activity and phosphorylation of Akt. Akt activation was initiated at a very early stage of infection independently of NX0101 replication. The specific phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 or wortmannin could suppress Akt phosphorylation, indicating that NX0101-induced Akt phosphorylation is PI3K-dependent. ALV-A strain GD08 or ALV-B strain CD08 infection also demonstrated a similar profile of PI3K/Akt activation. Treatment of DF-1 cells with the drug 5-(N, N-hexamethylene) amiloride that inhibits the activity of chicken Na+/H+ exchanger type 1 significantly reduced Akt activation induced by NX0101, but not by GD08 and CD08. Akt activation triggered by GD08 or CD08 was abolished by clathrin-mediated endocytosis inhibitor chlorpromazine. Receptor-mediated endocytosis inhibitor dansylcadaverine had a negligible effect on all ALV-induced Akt phosphorylation. Moreover, viral replication of ALV was suppressed by LY294002 in a dose-dependent manner, which was due to the inhibition of virus infection by LY294002. These data suggest that the activation of the PI3K/Akt signalling pathway by exogenous ALV infection plays an important role in viral entry, yet the precise mechanism remains under further investigation.

scholarly journals Nitrendipine-Treatment Increases Cork Spot Disorder Incidence in Pear ‘Akituki’ (Pyrus pyrifolia Nakai.) by Altering Calcium Distribution Inside the Fruit

Plants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 994
Author(s):  
Zhenhua Cui ◽  
Nannan Wang ◽  
Dingli Li ◽  
Ran Wang ◽  
Chunhui Ma
Keyword(s):  
Developmental Stage ◽  
Early Stage ◽  
Growth Period ◽  
Calcium Content ◽  
Early Developmental Stage ◽  
Pyrus Pyrifolia ◽  
Mineral Contents ◽  
Pyrus Pyrifolia Nakai ◽  
Expression Of Genes ◽  
Early Developmental

‘Akituki’ (Pyrus pyrifolia Nakai.) is a very popular and profitable pear cultivar in China. However, its high susceptibility to cork spot disorder has limited its expansion of cultivated area. The mechanisms of cork spot disorder have been discussed extensively, focusing on Ca2+ deficiency, yet no consensus has been made. In this study, we applied nitrendipine (NI) as a Ca2+ uptake inhibitor to explore the role of calcium in cork spot disorder occurrence. Results showed that NI treatment on the fruit remarkably increased the incidence of cork spot disorder; alteration of mineral contents happened at the early developmental stage of the fruit, especially on the outer flesh and the peel of the fruit; and this gap was filled gradually along with the expansion of the fruit. Significant differences in the expression levels of Ca2+ transport-related genes were found in the inner flesh, outer flesh and peel during the fruit growth period. The observation of free Ca2+ localization indicated the intracellular imbalance of Ca2+ in the NI-treated fruit. In conclusion, NI treatment reduced the calcium content in the fruit at an early developmental stage, altered the related expression of genes and influenced the cellular Ca2+ balance in the fruit, which prompted the occurrence of cork spot disorder. Measures for the prevention and control of cork spot disorder should be taken at the early stage of the fruit development in the field.

Circulatory GSK-3β: Blood-Based Biomarker and Therapeutic Target for Alzheimer’s Disease

2021 ◽  
pp. 1-12
Author(s):  
Shiwani Kumari ◽  
Ambica Singh ◽  
Abhinay Kumar Singh ◽  
Yudhishthir Yadav ◽  
Swati Bajpai ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Memory Loss ◽  
Amyloid Β ◽  
Clear Understanding ◽  
Dependent Manner ◽  
Brain Disorder ◽  
Gsk 3Β ◽  
Dose Dependent

Background: Alzheimer’s disease (AD) is the progressive brain disorder which degenerates brain cells connection and causes memory loss. Although AD is irreversible, it is not impossible to arrest or slow down the progression of the disease. However, this would only be possible if the disease is diagnosed at an early stage, and early diagnosis requires clear understanding of the pathogenesis at molecular level. Overactivity of GSK-3β and p53 accounts for tau hyperphosphorylation and the formation of amyloid-β plaques. Objective: Here, we explored GSK-3β and p53 as blood-based biomarkers for early detection of AD. Methods: The levels of GSK-3β, p53, and their phosphorylated states were measured using surface plasmon resonance and verified using western blot in serum from AD, mild cognitive impairment (MCI), and geriatric-control (GC) subjects. The neurotoxic SH-SY5Y cell line was treated with antioxidant Emblica Officinalis (EO) for rescue effect. Results: GSK-3β, p53, and their phosphorylated states were significantly over expressed (p >  0.001) in AD and MCI compared to GC and can differentiate AD and MCI from GC. The expression level of GSK-3β and p53 proteins were found to be downregulated in a dose-dependent manner after the treatment with EO in amyloid-b-induced neurotoxic cells. Conclusion: These proteins can serve as potential blood markers for the diagnosis of AD and EO can suppress their level. This work has translational value and clinical utility in the future.

scholarly journals An Oleanolic Acid Derivative Inhibits Hemagglutinin-Mediated Entry of Influenza A Virus

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 225 ◽  
Author(s):  
Mengdie Ye ◽  
Yixian Liao ◽  
Li Wu ◽  
Wenbao Qi ◽  
Namrta Choudhry ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Conformational Changes ◽  
Influenza A ◽  
Dissociation Constants ◽  
Early Stage ◽  
Dependent Manner ◽  
Influenza A Viruses ◽  
Endosomal Membrane ◽  
Chicken Erythrocytes ◽  
Dose Dependent

Influenza A viruses (IAV) have been a major public health threat worldwide, and options for antiviral therapy become increasingly limited with the emergence of drug-resisting virus strains. New and effective anti-IAV drugs, especially for highly pathogenic influenza, with different modes of action, are urgently needed. The influenza virus glycoprotein hemagglutinin (HA) plays critical roles in the early stage of virus infection, including receptor binding and membrane fusion, making it a potential target for the development of anti-influenza drugs. In this study, we show that OA-10, a newly synthesized triterpene out of 11 oleanane-type derivatives, exhibited significant antiviral activity against four different subtypes of IAV (H1N1, H5N1, H9N2 and H3N2) replications in A549 cell cultures with EC50 ranging from 6.7 to 19.6 μM and a negligible cytotoxicity (CC50 > 640 μM). It inhibited acid-induced hemolysis in a dose-dependent manner, with an IC50 of 26 µM, and had a weak inhibition on the adsorption of H5 HA to chicken erythrocytes at higher concentrations (≥40 µM). Surface plasmon resonance (SPR) analysis showed that OA-10 interacted with HA in a dose-dependent manner with the equilibrium dissociation constants (KD) of the interaction of 2.98 × 10−12 M. Computer-aided molecular docking analysis suggested that OA-10 might bind to the cavity in HA stem region which is known to undergo significant rearrangement during membrane fusion. Our results demonstrate that OA-10 inhibits H5N1 IAV replication mainly by blocking the conformational changes of HA2 subunit required for virus fusion with endosomal membrane. These findings suggest that OA-10 could serve as a lead for further development of novel virus entry inhibitors to prevent and treat IAV infections.

Modification by Su-10'603 of the response to histamine on the production of cortisol and corticosterone in isolated canine adrenocortical cells

1982 ◽  
Vol 101 (4) ◽  
pp. 586-591 ◽  
Author(s):  
T. Hirose ◽  
I. Matsumoto ◽  
T. Aikawa
Keyword(s):  
Biosynthetic Pathway ◽  
Early Stage ◽  
Dependent Manner ◽  
Adrenocortical Cell ◽  
Concomitant Increase ◽  
Adrenocortical Cells ◽  
Corticosterone Response ◽  
Dose Dependent ◽  
Predominant Product

Abstract. The effect of Su-10'603 on the cortisol and corticosterone response to histamine in dispersed canine adrenocortical cells was examined. The production of cortisol and corticosterone in isolated dog adrenocortical cell incubations increased in a dose-dependent manner at concentrations of histamine between 0.01 and 10.0 μg/ml medium, with the predominant production of cortisol. When Su-10'603 (0.005 to 5.0 μg/ml medium), an inhibitor of 17α-hydroxylation on corticosteroidogenesis, was added in cell incubations with histamine (1.0 μg/ml medium), the production of cortisol decreased in a reciprocal fashion, with a concomitant increase of corticosterone production. At the concentration between 0.05 and 0.1 μg Su-10'603/ml medium, there was a shift from cortisol to corticosterone as the predominant product. These results indicate that in the dog, histamine at pathophysiological concentration stimulates steroidogenesis and acts at a relatively early stage in the biosynthetic pathway.

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