Crosstalk between E2f1 and c-Myc mediates hepato-protective effect of royal jelly on taxol-induced damages

2016 ◽  
Vol 36 (6) ◽  
pp. 626-637 ◽  
Author(s):  
H Malekinejad ◽  
M Fani ◽  
S Kh Shafiee-Roodbari ◽  
F Delkhosh-Kasmaie ◽  
A Rezaei-Golmisheh
Keyword(s):  
Protective Effect ◽  
Messenger Rna ◽  
Royal Jelly ◽  
Mrna Level ◽  
Dependent Manner ◽  
Protective Effects ◽  
Elevated Alkaline Phosphatase ◽  
Liver Growth ◽  
Histopathological Studies

Previous histopathological studies have shown the hepatotoxicity of paclitaxel (TXL). However, there is little known about the molecular pathway(s) of TXL-induced hepatotoxicity. Therefore, this study aimed to uncover the role of two transcription factors in the TXL-induced hepatotoxicity. Moreover, the hepato-protective effect of royal jelly (RJ) on TXL-induced toxicity was investigated. Wistar rats were divided into control and test groups. The test groups along with TXL received various doses of RJ (0, 50, 100 and 150 mg/kg, body weight). Biochemical hepatic functional assays, histopathological studies and hepatic superoxide dismutase level were determined. Additionally, the expression of E2f1 and cellular-myelocytomatosis (c-Myc) at messenger RNA (mRNA) level in the liver was evaluated. The hepatic functional biomarkers showed a significant ( p < 0.05) elevation in the TXL-received animals, while RJ administration for 28 days resulted in a remarkable reduction in TXL-elevated alkaline phosphatase, alanine transaminase and lactate dehydrogenase levels. The TXL-treated animals showed a significant ( p < 0.05) up-regulation of E2f1 and down-regulation of c-Myc at mRNA level, respectively. RJ lowered the expression of E2f1 while enhanced the expression of c-Myc in a dose-dependent manner. Our data suggest the hepato-protective effects of RJ on TXL-induced toxicity, which may attribute to a clear crosstalk between E2f1 and c-Myc as two regulators of liver growth.

scholarly journals THE ROLE OF THE NEONATAL FC RECEPTOR IN THE UNCOATING OF ECHOVIRUSES AND COXSACKIEVIRUS A9

2019 ◽  
Vol 64 (3) ◽  
pp. 132-139
Author(s):  
P. S. Usoltseva ◽  
A. V. Alimov ◽  
A. V. Rezaykin ◽  
A. G. Sergeev ◽  
A. V. Novoselov
Keyword(s):  
Protective Effect ◽  
Cellular Receptor ◽  
Protective Effects ◽  
Neonatal Fc Receptor ◽  
Receptor Specificity ◽  
Cellular Receptors ◽  
Coxsackievirus A9 ◽  
Rd Cells ◽  
Adenovirus Receptor

The aim of this study was to determine the role of the human neonatal receptor for the Fc fragment of IgG (hFcRn) as a common uncoating cellular receptor for echoviruses and coxsackievirus A9 during infection of human rhabdomyosarcoma (RD) cells. Material and methods. The protective effect of the human serum albumin, purified from globulins, (HSA-GF) and antibodies to hFcRn was studied in RD cells infected with several strains and clones of species B enteroviruses possessing different receptor specificity (echoviruses 3, 9, 11, 30 and coxsackieviruses A9, B4, B5). Results. It was shown that HSA-GF at concentrations of 4% or less protected RD cells from infection with echoviruses 3, 9, 11 and coxsackievirus A9. The antibodies to hFcRn at concentrations of 2.5 ug/mL or less demonstrated the similar spectrum of protective activity in RD cells against infection with echoviruses 3, 9, 11, 30 and coxsackievirus A9. The protective effect of HSA-GF or the antibodies to hFcRn was not observed in RD cells infected with coxsackieviruses B4 and B5 that need coxsackievirus-adenovirus receptor for uncoating. Discussion. The usage of the previously characterized echovirus 11 clonal variants with different receptor specificity allowed us to define the function of hFcRn as a canyon-binding uncoating receptor in RD cells. The kinetics and magnitude of the observed protective effects correlated with receptor specificity of the enteroviruses used in this work supporting the two-step interaction of DAF-dependent echoviruses with the cellular receptors. Conclusions. In this study, the function of hFcRn was defined in RD cells as a canyon-binding and uncoating receptor for echoviruses and coxsackievirus A9. The two-step interaction of DAF-dependent echoviruses during entry into the cells was confirmed: initially with the binding receptor DAF and subsequently with the uncoating receptor hFcRn.

Protective effect of the dimer of 16,16-diMePGB1 against KCN-induced mitochondrial failure in hepatocytes

1992 ◽  
Vol 263 (2) ◽  
pp. C405-C411 ◽  
Author(s):  
Y. Park ◽  
T. M. Devlin ◽  
D. P. Jones
Keyword(s):  
Membrane Potential ◽  
Protective Effect ◽  
Ion Transport ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Time Dependent ◽  
Dependent Manner ◽  
Protective Effects ◽  
Cellular Swelling

The dimer and trimer of 16,16-dimethyl-15-dehydroprostaglandin B1 (16,16-diMePGB1) previously have been shown to have protective effects on mitochondrial function. To examine the potential mechanisms involved in protection against mitochondrial failure, we have studied the effects of the dimer of 16,16-diMe-PGB1 (dicalciphor) on mitochondrial function in hepatocytes exposed to KCN. Addition of micromolar concentrations of dicalciphor provided substantial protection against KCN-induced toxicity in a concentration- and time-dependent manner. Dicalciphor, however, had no effect on total or mitochondrial ATP losses in KCN-treated cells. The dimer prevented the marked loss of mitochondrial membrane potential (delta psi) and delta pH that occurs as a result of KCN treatment and prevented KCN-induced loading of phosphate in mitochondria. Furthermore, the dimer of 16,16-diMePGB1 also prevented KCN-induced mitochondrial and cellular swelling. These results demonstrate that dicalciphor protects against KCN-induced damage and that this protection is associated with regulation of specific mitochondrial ion transport functions.

Zymogen Protein C as a Novel Modulator of Cancer Progression In Murine Models

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 718-718
Author(s):  
Geerte L. Van Sluis ◽  
Paris Margaritis ◽  
Michael Sliozberg ◽  
Jenna Mauer ◽  
Armida Faella ◽  
...  
Keyword(s):  
Protective Effect ◽  
Tumor Progression ◽  
Lung Metastasis ◽  
Protein C ◽  
Tumor Metastasis ◽  
Minimal Risk ◽  
Dependent Manner ◽  
Molecular Therapeutics ◽  
Dose Dependent

Abstract Abstract 718 Recent evidence on the role of the protein C (PC) pathway in tumor progression of the experimental mouse melanoma model has revealed that inhibition of the cytoprotective effects of endogenous activated PC (aPC) enhances tumor cell extravasation, whereas exogenous administration of recombinant human APC has a protective effect. Moreover transgenic mice overexpressing endothelial PC receptor (EPCR) in tissue endothelium exhibit low rates of tumor metastasis. Here we report our findings in C57Bl/6 mice expressing murine forms of APC or zymogen PC by viral-mediated gene transfer. Vector-injected mice resulted in continuous expression of murine APC (mAPC) or PC (mPC), which reached plateau levels after week 2. On week 3, we administered B16F10 murine melanoma cells (3.5×10^5) intravascularly and analyzed the rates of lung metastasis 21 days later compared to age and gender matched saline-injected groups (control cohort=26 mice). We observed a dose-dependent protective effect of mAPC. Mice expressing mAPC at levels of 7.3 ± 1.5 ng/ml (n=8) or lower (determined by a functional ELISA-capture assay) did not differ from saline injected mice (that had baseline mAPC levels < 3 ng/ml). By increasing the vector dose, mAPC levels of 25.6 ± 4.8 ng/ml (n=16) to 118 ±6 ng/ml (n=10) reduced the numbers of lung metastasis compared to saline injected mice (p<0.05). To investigate the contribution of the cytoprotective/anticoagulant role of mAPC, we injected mice with a variant form of mAPC with reduced anticoagulant but intact cytoprotective activity (mAPC-5A). Following melanoma cell infusion, animals expressing levels of mAPC-5A ranging from 15.2 ± 3.2 ng/ml (n=16) to 80.4 ± 4.7 ng/ml (n=10) exhibited rates of lung metastasis similar to controls. To further explore the anticoagulant pathway in this metastasis model, we injected mice with AAV expressing zymogen mPC. There was a dose-dependent increase in the mPC levels measured by a chromogenic assay resulting in 3–4 fold of normal levels. However, this was not associated with increased levels of mAPC compared to saline-injected mice. Notably, in the mPC expressing mice (n=26), the rates of tumor metastasis were significantly reduced compared to controls (p<0.005). The protective effect of zymogen mPC remained even in the absence of protease-activated receptor (PAR-1), one main cellular receptor for the APC-mediated cytoprotective effect. In particular, the lung metastasis rates in PAR-1 null mice expressing mPC (n=21) were lower than PAR-1 null mice injected with saline (n=15) (p<0.01). Lastly, the hemostatic effects of the expressed transgenes (mPC, mAPC and mAPC-5A) in all mice were investigated. Prolongation of the activated partial prothrombin time and increase blood loss following tail clipping assay was restricted to animals expressing APC-WT in a dose-dependent manner but not in APC-5A or zymogen PC compared to controls. These findings support a novel and important role of zymogen PC in modulating tumor progression with minimal risk of bleeding. Disclosures: High: Genzyme, Inc: Consultancy, Patents & Royalties; Third Rock Ventures: Consultancy; PTC Therapeutics:; Amsterdam Molecular Therapeutics:; Sangamo Biosciences:; Novo-Nordisk: Consultancy; Shire, Inc.: Consultancy.

Protective effect of Fragarria ananassa and Vaccinium corymbosum fruit extracts against L-arginine induced acute pancreatitis in rats

2019 ◽  
Author(s):  
Siva Reddy Challa ◽  
Veena Gadicherla ◽  
Mandava V. Basaveswara Rao ◽  
P. Ramakrishna ◽  
K.Pavan Kumar
Keyword(s):  
Acute Pancreatitis ◽  
Protective Effect ◽  
Dna Fragmentation ◽  
Antioxidant Properties ◽  
Vaccinium Corymbosum ◽  
Pancreatic Tissue ◽  
Protective Effects ◽  
Tissue Samples ◽  
Fruit Extracts ◽  
Histopathological Studies

The study was aimed to evaluate the protective effects of alcoholic extracts of Strawberry and Blueberry fruits [AESF and AEBF] in acute pancreatitis in rats. Treatment groups received AESF and AEBF at doses of 200 and 400 mg/kg for 7 days with prior injections of L-arginine on 5th day. Biochemical parameters were estimated in serum and pancreatic tissue samples. Histopathological studies and DNA fragmentation assay were carried out in isolated pancreatic tissue. The results of the study indicated that treatment of AESF and AEBF exhibited a significant dose dependent protective effect. Upon the treatment, anti-oxidant enzymes were significantly (*pless than 0.05) increased. Biochemical results were correlated with the histopathological findings. In addition, the DNA fragmentation assay showed an intact DNA in pancreatic cells of treated groups. In conclusion, berry fruit extracts exerted a potential protective effect against L-arginine induced damage in rat pancreas, at least in part, due to its antioxidant properties.

scholarly journals miR-135b Plays a Neuroprotective Role by Targeting GSK3β in MPP+-Intoxicated SH-SY5Y Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Jianlei Zhang ◽  
Wei Liu ◽  
Yabo Wang ◽  
Shengnan Zhao ◽  
Na Chang
Keyword(s):  
Cell Proliferation ◽  
Glycogen Synthase ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Protective Effects ◽  
Inflammatory Cytokine Production ◽  
Protein Levels

miR-135a-5p was reported to play a crucial role in the protective effects of hydrogen sulfide against Parkinson’s disease (PD) by targeting rho-associated protein kinase 2 (ROCK2). However, the role of another member of miR-135 family (miR-135b) and the underlying mechanism in PD are still unclear. qRT-PCR and western blot showed that miR-135 was downregulated and glycogen synthase kinase 3β (GSK3β) was upregulated at mRNA and protein levels in MPP+-intoxicated SH-SY5Y cells in a dose- and time-dependent manner. MTT, TUNEL, and ELISA assays revealed that miR-135b overexpression significantly promoted cell proliferation and inhibited apoptosis and production of TNF-α and IL-1β in SH-SY5Y cells in the presence of MPP+. Luciferase reporter assay demonstrated that GSK3β was a direct target of miR-135b. Moreover, sodium nitroprusside (SNP), a GSK3β activator, dramatically reversed the effects of miR-135b upregulation on cell proliferation, apoptosis, and inflammatory cytokine production in MPP+-intoxicated SH-SY5Y cells. Taken together, miR-135b exerts a protective role via promotion of proliferation and suppression of apoptosis and neuroinflammation by targeting GSK3β in MPP+-intoxicated SH-SY5Y cells, providing a potential therapeutic target for the treatment of PD.

Hesperidin protects against cyclophosphamide-induced hepatotoxicity by upregulation of PPARγ and abrogation of oxidative stress and inflammation

2014 ◽  
Vol 92 (9) ◽  
pp. 717-724 ◽  
Author(s):  
Ayman M. Mahmoud
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Protective Effect ◽  
Liver Lipid ◽  
Inos Mrna ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Intraperitoneal Dose

The most important reason for the non-approval and withdrawal of drugs by the Food and Drug Administration is hepatotoxicity. Therefore, this study was undertaken to evaluate the protective effects of hesperidin against cyclophosphamide (CYP)-induced hepatotoxicity in Wistar rats. The rats received a single intraperitoneal dose of CYP of 200 mg/kg body mass, followed by treatment with hesperidin, orally, at doses of 25 and 50 mg/kg for 11 consecutive days. CYP induced hepatic damage, as evidenced by the significantly elevated levels of serum pro-inflammatory cytokines, serum transaminases, liver lipid peroxidation, and nitric oxide. As a consequence, there was reduced glutathione content, and the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, were markedly reduced. In addition, CYP administration induced a considerable downregulation of peroxisome proliferator activated receptor gamma (PPARγ) and upregulation of nuclear factor-kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) mRNA expression. Hesperidin, in a dose-dependent manner, rejuvenated the altered markers to an almost normal state. In conclusion, hesperidin showed a potent protective effect against CYP-induced oxidative stress and inflammation leading to hepatotoxicity. The study suggests that hesperidin exerts its protective effect against CYP-induced hepatotoxicity through upregulation of hepatic PPARγ expression and abrogation of inflammation and oxidative stress.

scholarly journals Platycodon grandiflorum Saponins Ameliorate Cisplatin-Induced Acute Nephrotoxicity through the NF-κB-Mediated Inflammation and PI3K/Akt/Apoptosis Signaling Pathways

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1328 ◽  
Author(s):  
Weizhe Zhang ◽  
Jingang Hou ◽  
Xiaotong Yan ◽  
Jing Leng ◽  
Rongyan Li ◽  
...  
Keyword(s):  
Protective Effect ◽  
Signaling Pathways ◽  
Kidney Injury ◽  
Dependent Manner ◽  
Protective Effects ◽  
Phosphatidylinositol 3 Kinase ◽  
Platycodon Grandiflorum ◽  
Tnf Α ◽  
Factor Α ◽  
Oxide Synthase

Although cisplatin is a potent chemotherapeutic agent against cancers, its clinical application is seriously limited by its severe side effects of nephrotoxicity. Previous studies reported that saponins isolated from the roots of Platycodon grandiflorum (PGS) exerted protective effects in various animal models of renal injury, with no confirmation on cisplatin-induced injury. This study was designed to investigate the protective effect of PGS (15 and 30 mg/kg) on cisplatin-induced kidney injury in mice. The levels of serum creatinine (CRE) and blood urea nitrogen (BUN), and renal histopathology demonstrated the protective effect of PGS against cisplatin-induced kidney injury. PGS exerted anti-inflammation effects via suppressing nuclear factor-kappa B (NF-κB) activation and alleviating the cisplatin-induced increase in inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in kidney tissues. The expressions of phosphorylation of phosphatidylinositol 3-kinase/protein kinase B and its downstream apoptotic factors, such as Bcl-2 and caspase families were regulated by PGS in a dose-dependent manner. In conclusion, PGS exerted kidney protection effects against cisplatin-induced kidney injury by inhibiting the activation of NF-κB and regulating PI3K/Akt/apoptosis signaling pathways in mice.

scholarly journals Significant passive protective effect against anthrax by antibody to Bacillus anthracis inactivated spores that lack two virulence plasmids

Microbiology ◽  
2006 ◽  
Vol 152 (10) ◽  
pp. 3103-3110 ◽  
Author(s):  
Jargalsaikhan Enkhtuya ◽  
Keiko Kawamoto ◽  
Yoshiyasu Kobayashi ◽  
Ikuo Uchida ◽  
Neeraj Rana ◽  
...  
Keyword(s):  
Protective Effect ◽  
Bacillus Anthracis ◽  
Protective Antigen ◽  
Lethal Dose ◽  
Dependent Manner ◽  
Protective Effects ◽  
Virulence Plasmids ◽  
Somatic Antigens ◽  
Dose Dependent ◽  
Formalin Fixed

The protective-antigen (PA)-based cell-free vaccine is the only vaccine licensed for use against Bacillus anthracis infection in humans. Although the PA shows strong immunogenicity, the capsule or spore-associated somatic antigens may be important as additional vaccine targets for full protection against anthrax. In this study, the protective effect of spore-associated antigens against B. anthracis infection was determined. Rabbits were immunized with formalin-fixed spores of a non-toxigenic unencapsulated B. anthracis strain that lacked the two virulence plasmids pXO1 and pXO2, and the protective effects of the immune antibody were evaluated. Immunostaining and Western blot analysis revealed that the anti-B. anthracis (anti-BA)-spore IgG specifically bound to the surface of spores or endospores of B. anthracis, but not to vegetative cells, or closely related Bacillus species, such as Bacillus cereus, Bacillus subtilis and Bacillus thuringiensis. Passively transferred anti-BA-spore IgG protected mice from intraperitoneal challenge with a lethal dose of fully virulent B. anthracis spores, and increased the survival rate in a dose-dependent manner. Pre-incubation of spores with antibody also reduced their infectivity in a dose-dependent manner. The number of bacteria (c.f.u.) in spleens and livers of infected mice was significantly lower in antibody-treated mice than in untreated mice. Treatment with anti-BA-spore IgG also inhibited the germination of spores in J774.1 macrophages, suggesting that opsonization of spores promotes phagocytosis and subsequent killing by macrophages. These results indicate the usefulness of spore surface antigens as vaccine targets. In combination with major virulence factors such as the PA, spore-associated antigens may offer a safer and more effective multicomponent vaccine for B. anthracis infection.

Role of delta-like ligand-4 in chemoresistance against docetaxel in MCF-7 cells

2016 ◽  
Vol 36 (4) ◽  
pp. 328-338 ◽  
Author(s):  
Q Wang ◽  
Y Shi ◽  
HJ Butler ◽  
J Xue ◽  
G Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Expression Vectors ◽  
Dependent Manner ◽  
Protective Effects ◽  
Promising Target ◽  
Cancer Cell Survival ◽  
Mcf 7

As Notch receptors have been shown to induce chemoresistance, we hypothesized that delta-like ligand-4 (DLL4), a central Notch signalling ligand, might also participate in chemoresistance in breast cancer. To investigate this issue, overexpression of DLL4 was induced by transfection with expression vectors for DLL4 in the human breast cancer cell line Michigan cancer foundation-7 (MCF-7). It was found that DLL4 could be adaptively upregulated by docetaxel (DOC) treatment in a dose-dependent manner, but Notch1 was unaffected. Overexpression of DLL4 could significantly attenuate the cytotoxic effects of DOC by increasing Bcl-2 expression, while decreasing Bax expression, apoptosis rate and DNA damage. The protective effects of DLL4 made cells acquire chemoresistance against DOC and resulted in cancer cell survival. DLL4 is normally regarded as a regulator of vascular development. Our results expanded the understanding of DLL4. Since DLL4 may play an important role in the process of acquiring chemoresistance, it may be a promising target in overcoming chemoresistance in breast cancer.

scholarly journals Positive components of mental health provide significant protection against likelihood of falling in older women over a 13-year period

2012 ◽  
Vol 24 (9) ◽  
pp. 1419-1428 ◽  
Author(s):  
Richard A. Burns ◽  
Julie Byles ◽  
Paul Mitchell ◽  
Kaarin J. Anstey
Keyword(s):  
Mental Health ◽  
Protective Effect ◽  
Physical Health ◽  
Well Being ◽  
Poor Mental Health ◽  
Protective Effects ◽  
Logistic Regression Models ◽  
Random Intercept ◽  
Psychological Risk

ABSTRACTBackground:In late life, falls are associated with disability, increased health service utilization and mortality. Physical and psychological risk factors of falls include falls history, grip strength, sedative use, stroke, cognitive impairment, and mental ill-health. Less understood is the role of positive psychological well-being components. This study investigated the protective effect of vitality on the likelihood of falls in comparison to mental and physical health.Methods:Female participants were drawn from the Dynamic Analyses to Optimise Ageing (DYNOPTA) harmonization project. Participants (n= 11,340) were aged 55–95 years (Mean = 73.68; SD = 4.31) at baseline and observed on up to four occasions for up to 13 years (Mean = 5.30; SD = 2.53).Results:A series of random intercept logistic regression models consistently identified vitality's protective effects on falls as a stronger effect in the reduction of the likelihood of falls than the effect of mental health. Vitality is a significant predictor of falls likelihood even after adjusting for physical health, although the size of effect is substantially explained by its covariance with mental and physical heath.Conclusions:Vitality has significant protective effects on the likelihood of falls. In comparison with mental health, vitality reported much stronger protective effects on the likelihood to fall in comparison with the risk associated with poor mental health in a large sample of older female adults. Both physical health and mental health account for much of the variance in vitality, but vitality still reports a protective effect on the likelihood of falls.

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