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1.
Curr Issues Mol Biol ; 46(1): 450-460, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38248330

RESUMEN

Developing strategies for the radiosensitization of cancer cells by the inhibition of genes, which harbor low toxicity to normal cells, will be useful for improving cancer radiotherapy. Here, we focused on a ß-site of amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1; ß-secretase, memapsin-2). By functional inhibition of this peptidase by siRNA, it has also recently been shown that the DNA strand break marker, γH2AX foci, increased, suggesting its involvement in DNA damage response. To investigate this possibility, we knocked down BACE1 with siRNA in cancer cell lines, and sensitization to γ-irradiation was examined by a colony formation assay, γH2AX foci and level analysis, and flow cytometry. BACE1 knockdown resulted in the sensitization of HeLa, MDA-MB-231, U2OS, and SAOS cells to γ-irradiation in a diverse range. BACE1 knockdown showed a weak radiosensitization effect in osteosarcoma U2OS cells, which has a normal p53 function. HeLa and SAOS cells, which harbor p53 dysfunction, exhibited a greater level of radiosensitization. These results suggest that BACE1 may be a potential target for the radiosensitization in particular cancer cells.

2.
J Basic Microbiol ; : e2400327, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39021277

RESUMEN

Three strains of Gram-negative bacterium, Rhizobium, were developed by gamma (γ)-irradiation random mutagenesis. The developed strains were evaluated for their augmented features for symbiotic association, nitrogen fixation, and crop yield of three leguminous plants-chickpea, field-pea, and lentil-in agricultural fields of the northern Indian state of Haryana. Crops treated with developed mutants exhibited significant improvement in plant features and the yield of crops when compared to the control-uninoculated crops and crops grown with indigenous or commercial crop-specific strains of Rhizobium. This improvement was attributed to generated mutants, MbPrRz1 (on chickpea), MbPrRz2 (on lentil), and MbPrRz3 (on field-pea). Additionally, the cocultured symbiotic response of MbPrRz1 and MbPrRz2 mutants was found to be more pronounced on all three crops. The statistical analysis using Pearson's correlation coefficients revealed that nodulation and plant biomass were the most related parameters of crop yield. Among the effectiveness of developed mutants, MbPrRz1 yielded the best results for all three tested crops. Moreover, the developed mutants enhanced macro- and micronutrients of the experimental fields when compared with fields harboring the indigenous rhizobial community. These developed mutants were further genetically characterized, predominantly expressing nitrogen fixation marker, nifH, and appeared to belong to Mesorhizobium ciceri (MbPrRz1) and Rhizobium leguminosarum (both MbPrRz2 and MbPrRz3). In summary, this study highlights the potential of developed Rhizobium mutants as effective biofertilizers for sustainable agriculture, showcasing their ability to enhance symbiotic relationships, crop yield, and soil fertility.

3.
Int J Mol Sci ; 25(2)2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38256048

RESUMEN

The stimulation of growth and development of crops using ionising radiation (radiation hormesis) has been reported by many research groups. However, specific genes contributing to the radiation stimulation of plant growth are largely unknown. In this work, we studied the impact of the low-dose γ-irradiation of barley seeds on the growth dynamics and gene expression of eight barley cultivars in a greenhouse experiment. Our findings confirmed that candidate genes of the radiation growth stimulation, previously established in barley seedlings (PM19L-like, CML31-like, and AOS2-like), are significant in radiation hormesis throughout ontogeny. In γ-stimulated cultivars, the expression of these genes was aligned with the growth dynamics, yield parameters, and physiological conditions of plants. We identified contrasting cultivars for future gene editing and found that the γ-stimulated cultivar possessed some specific abiotic stress-responsive elements in the promotors of candidate genes, possibly revealing a new level of radiation hormesis effect execution. These results can be used in creating new productive barley cultivars, ecological toxicology of radionuclides, and eustress biology studies.


Asunto(s)
Hordeum , Hordeum/genética , Hormesis , Productos Agrícolas , Ecotoxicología , Rayos gamma
4.
J Sci Food Agric ; 104(2): 979-992, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-37715570

RESUMEN

BACKGROUND: 60 Co-γ irradiation can simulate the effects of aging and enhance the flavor of distilled spirits. The present study aimed to investigate the effects of 0, 2, 4, 6, 8 and 10 kGy 60 Co-γ irradiation doses on the key aroma components in newly produced navel orange distilled spirits and thus determine the mechanism of their aging distilled spirits. RESULTS: The identification of aroma compounds demonstrated that ethyl hexanoate, d-limonene, ethyl octanoate, 3-methyl-1-butanol and linalool are the key aroma compounds in navel orange distilled spirits, which were increased except for linalool with irradiation doses of 2-6 kGy. Irradiation treatment simulated the effects of the aging of navel orange distilled spirits by promoting the content of total acids, total esters and aldehydes. Irradiation doses of 2-6 kGy increased the aroma intensity of navel orange distilled spirits, reaching an optimum at 6 kGy. However, irradiation doses as high as 8 and 10 kGy decreased the content of esters in navel orange distilled spirits, which led to a deterioration of the spirit flavor. CONCLUSION: Low doses of 60 Co-γ irradiation can simulate the effects of the aging by increasing the content of key aromatic compounds in navel orange distilled spirits. © 2023 Society of Chemical Industry.


Asunto(s)
Citrus sinensis , Citrus sinensis/química , Monoterpenos Acíclicos , Odorantes , Ésteres
5.
Bioorg Chem ; 131: 106310, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36528923

RESUMEN

A set of novel N-substituted-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetamide 3-16 were designed and synthesized from 2-mercapto-3-phenylquinazolinone 2. The targeted compounds were screened for their cytotoxic activity against the hepatocellular carcinoma cell line HepG-2. Compounds 8, 9, 10, and 11 with IC50 values of 1.11, 4.28, 5.70, and 4.69 µM, respectively, showed 5.7- to 28-fold higher activities than the positive control doxorubicin (IC50 32.02 µM). Furthermore, compounds 8 and 9 were tested for EGFR inhibitory activity and demonstrated IC50 values of 73.23 and 58.26  µM, respectively, when compared to erlotinib's IC50 value of 9.79 µM. The most potent compounds, 8 and 9, were subjected to a single dose of 8 Gy of γ-radiation, and their cytotoxic efficacy was found to increase after irradiation, demonstrating the synergistic effect of γ-irradiation. Molecular docking was adopted for the most active compounds to confirm their mode of action.


Asunto(s)
Antineoplásicos , Carcinoma , Humanos , Quinazolinonas/farmacología , Simulación del Acoplamiento Molecular , Receptores ErbB , Modelos Moleculares , Antineoplásicos/farmacología , Estructura Molecular , Relación Estructura-Actividad , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular , Línea Celular Tumoral
6.
Bull Exp Biol Med ; 176(1): 34-37, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38091132

RESUMEN

NOD SCID mice were humanized by transplanting human hematopoietic cells isolated from umbilical cord blood. A dose-dependent death of hematopoietic cells and their subsequent recovery were shown after acute external γ-irradiation in the model of humanized mice. The proposed approach can be used for preclinical studies of radioprotective agents and for assessment of the impact of adverse factors on the survival rate and functional properties of human hematopoietic stem cells in vivo.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Humanos , Animales , Ratones , Ratones SCID , Células Madre Hematopoyéticas , Ratones Endogámicos NOD , Irradiación Corporal Total , Sangre Fetal , Trasplante Heterólogo , Antígenos CD34
7.
J Food Sci Technol ; 60(5): 1621-1632, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37033314

RESUMEN

In recent years, food irradiation using γ-rays is one of the most valuable practices for insect disinfestation in rice grains for extended shelf life. In this study, flours from four pigmented rice cultivars were exposed to γ-irradiation using 60Co at different doses (0, 5, 10, and 15 kGy). The impact of γ-irradiation on the physico-chemical, functional, and morphological characteristics of pigmented rice flours were analyzed. Results revealed that reduction in amylose content, pH, bulk density, tapped density, and syneresis, while solubility, water absorption capacity, and swelling power values increased significantly (p < 0.05). Pasting characteristics of pigmented rice flours also reduced after exposure to γ-irradiation. Morphological features of pigmented rice flour granules revealed no evidence of physical destruction after irradiation except for black kavuni flour. The structural analysis by FTIR confirms no effect of γ-irradiation on pigmented rice flours. Overall, the study revealed that irradiated pigmented rice flours with enhanced functional properties of less than 10 kGy can be effectively used in the development of value-added rice-based food products considering all the beneficial and safety aspects. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05709-z.

8.
Arch Microbiol ; 204(5): 275, 2022 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-35451658

RESUMEN

In this study, we examined the accumulation of trehalose, a stress-responsive substance, upon gamma-ray irradiation by evaluating the cause of trehalose accumulation and the development of gamma-ray resistance through intracellular trehalose accumulation. Saccharomyces cerevisiae cells cultured to the logarithmic growth phase were irradiated with gamma rays, and the intracellular trehalose content was measured. However, trehalose was not detectable. The yeast cells with trehalose accumulation caused by pre-treatment at 40 °C were irradiated with gamma rays, and the resistance of these cells to gamma radiation was compared with that of cells without heat treatment. Trehalose accumulation resulted in gamma-ray resistance and suppressed the increase in reactive oxygen species, lipid peroxidation, and DNA double-strand break production in yeast cells. The tests were also performed with a trehalose-6-phosphate-synthase (TPS1)-deficient mutant strain (Δtps1) unable to synthesize trehalose, and the results revealed that TPS1 was involved in protection against oxidative stress.


Asunto(s)
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Glucosiltransferasas/genética , Glucosiltransferasas/metabolismo , Respuesta al Choque Térmico , Estrés Oxidativo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Trehalosa
9.
Int J Mol Sci ; 23(9)2022 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-35563460

RESUMEN

The radiosensitization of tumor cells is one of the promising approaches for enhancing radiation damage to cancer cells and limiting radiation effects on normal tissue. In this study, we performed a comprehensive screening of radiosensitization targets in human lung cancer cell line A549 using an shRNA library and identified apolipoprotein B mRNA editing enzyme catalytic subunit 3G (APOBEC3G: A3G) as a candidate target. APOBEC3G is an innate restriction factor that inhibits HIV-1 infection as a cytidine deaminase. APOBEC3G knockdown with siRNA showed an increased radiosensitivity in several cancer cell lines, including pancreatic cancer MIAPaCa2 cells and lung cancer A549 cells. Cell cycle analysis revealed that APOBEC3G knockdown increased S-phase arrest in MIAPaCa2 and G2/M arrest in A549 cells after γ-irradiation. DNA double-strand break marker γH2AX level was increased in APOBEC3G-knocked-down MIAPaCa2 cells after γ-irradiation. Using a xenograft model of A549 in mice, enhanced radiosensitivity by a combination of X-ray irradiation and APOBEC3G knockdown was observed. These results suggest that the functional inhibition of APOBEC3G sensitizes cancer cells to radiation by attenuating the activation of the DNA repair pathway, suggesting that APOBEC3G could be useful as a target for the radiosensitization of cancer therapy.


Asunto(s)
Desaminasa APOBEC-3G , Rayos gamma , Tolerancia a Radiación , Desaminasa APOBEC-3G/antagonistas & inhibidores , Desaminasa APOBEC-3G/farmacología , Animales , Apoptosis , Línea Celular Tumoral , Citidina Desaminasa/genética , Citidina Desaminasa/metabolismo , Puntos de Control de la Fase G2 del Ciclo Celular , Rayos gamma/uso terapéutico , Humanos , Neoplasias Pulmonares/radioterapia , Ratones , Tolerancia a Radiación/genética , Tolerancia a Radiación/fisiología
10.
Chem Zvesti ; 76(3): 1777-1787, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35106020

RESUMEN

One of the advanced oxidative processes is gamma irradiation, an efficient technique for removing pesticides and pharmaceutical products. Radiolytic degradation leads to free radical's formation, which facilitates molecular lesion and breaks the chemical bonds. The use of pharmaceutical compounds, such as hydroxychloroquine (HCQ), is increasing nowadays due to the Covid 19 pandemic situation. This study focused on gamma radiation-induced degradation of HCQ in aqueous solution. The degradation was monitored by High-Performance Liquid Chromatography (HPLC) using an Eclipse XDB-C18 column (150 × 3.0 mm, 3.5 µm) and a mobile phase composed of 94% water (phosphate buffer at pH = 3.6) and 6% acetonitrile, with a DAD detection at λ = 343 nm. The effect of different gamma radiation doses (from 0.05 to 3 kGy) was investigated. Chromatographic analysis shows that 1 kGy dose is effective to degrade completely HCQ at 20 ppm and following a first-pseudo-kinetic order with a dose constant corresponding to 4.2 kGy-1. A comparison was done between gamma degradation and other methods. LC-QToF-MS/MS identified the intermediate products, and their kinetic constants were determined. A mechanism pathway was proposed for HCQ degradation under gamma irradiation.

11.
Cancer Invest ; 39(1): 98-113, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33251876

RESUMEN

Glioblastomas are the primary malignant tumors of brain tissues with poor prognosis and highly invasive phenotypes. Till now Ki-67 LI has emerged as a well-studied proliferation marker that aids in tumor grading, but labeling index alone cannot predict overall survival in gliomas. P21 activated kinase 1 (PAK1) - a serine/threonine kinase has been shown to function as downstream nodule for various oncogenic signaling pathways that promote neoplastic changes. This study is designed to evaluate the expression of PAK1 across various grades and its correlation with Ki-67 LI and overall survival rates among a total number of 140 clinical brain tumors of glioma patients. We also studied the activation status of phospho PAK1 in glioma tissues and established the role of PAK1 in proliferation of glioblatoma cell lines under γ-irradiation.This study provides molecular evidence signifying the role of PAK1 and its activation status in the progression of Gliomas to more aggressive phenotypes.


Asunto(s)
Neoplasias Encefálicas/enzimología , Glioma/enzimología , Quinasas p21 Activadas/metabolismo , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Proliferación Celular/fisiología , Femenino , Glioma/genética , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
12.
Can J Physiol Pharmacol ; 99(6): 676-684, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33108742

RESUMEN

Diabetes mellitus is associated with an increased risk of cardiac complications; this study aimed to investigate effect of sitagliptin (SITA) alone or combined with γ-irradiation on diabetes-associated cardiac injury. Rats were treated with SITA (100 mg/kg per day; p.o.) for 2 weeks followed by a single dose of whole-body γ-irradiation (3 Gy). Solitary administration of SITA or combined treatment with γ-irradiation succeeded to ameliorate the increase in serum levels of glucose, total cholesterol, triglycerides, creatine kinase-MB, and malondialdehyde, coupled by increased insulin and reduced glutathione levels. Their cardioprotective potential was confirmed through attenuating the apoptotic signaling by mitigating Bcl-2-associated X protein, caspase-3, and apoptosis-inducing factor expression, while augmenting the anti-apoptotic factors, B cell lymphoma-2 (Bcl-2), and heat shock protein 70 (HSP-70) in left ventricular tissue homogenates. These findings were supported histopathologically. In conclusion, treatment with SITA alone or combined with γ-irradiation may prove beneficial in diabetes-accompanied cardiac insult. This could be due to the crosstalk between the antioxidant, anti-apoptotic, and restoration of body's defense capacities.


Asunto(s)
Fosfato de Sitagliptina , Animales , Antioxidantes , Apoptosis/efectos de los fármacos , Rayos gamma , Glutatión/metabolismo , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas
13.
Acta Med Okayama ; 75(2): 169-175, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33953424

RESUMEN

The forced swim test (FST) induces immobility in mice. Low-dose (high-dose-rate) X-irradiation inhibits FSTinduced immobility in mice due to its antioxidative function. We evaluated the effects of low-dose γ-irradiation at a low-dose-rate on the FST-induced depletion of antioxidants in mouse organs. Mice received whole-body low-dose-rate (0.6 or 3.0 mGy/h) of low-dose γ-irradiation for 1 week, followed by daily FSTs (5 days). The immobility rate on day 2 compared to day 1 was significantly lower in the 3.0 mGy/h irradiated mice than in sham irradiated mice. The FST significantly decreased the catalase (CAT) activity and total glutathione (t-GSH) content in the brain and kidney, respectively. The superoxide dismutase (SOD) activity and t-GSH content in the liver of the 3.0 mGy/h irradiated mice were significantly lower than those of the non-FST-treated mice. The CAT activity in the lungs of mice exposed to 3.0 mGy/h γ-irradiation was higher than that of non-FST treated mice and mice treated with FST. However, no significant differences were observed in the levels of these antioxidant markers between the sham and irradiated groups except for the CAT activity in lungs. These findings suggest that the effects of low-dose-rate and low-dose γ-irradiation on FST are highly organ-dependent.


Asunto(s)
Inmovilización , Estrés Oxidativo/efectos de la radiación , Natación , Animales , Antioxidantes/metabolismo , Relación Dosis-Respuesta en la Radiación , Rayos gamma , Ratones , Rayos X
14.
Molecules ; 26(15)2021 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-34361544

RESUMEN

In this work the analysis on the stabilization activities of some natural antioxidants (rosemary extract, capsaicin, quercetin or oleanolic acid) is presented. A similar contribution of an inorganic structure-polyhedral oligomeric silsesquioxane (POSS) nanoparticles-is also evaluated. The stabilization effects on the oxidation protection were investigated for several formulations based on ethylene-propylene-diene-terpolymer (EPDM). The samples were examined in pristine state or after γ-irradiation, when the accelerated degradation scission of polymer macromolecules followed by the mitigation of oxidation. Three evaluation procedures: chemiluminescence, FTIR spectroscopy and thermal analysis were applied for the characterization of stability efficiency. The delaying effect of oxidative aging in EPDM matrix is illustrated by the values of activation energy, which are correlated with the type and concentration of embedded compounds. The durability of studied EPDM formulations is discussed for the assessment of material life. The improved behavior of structured hybrids useful for the optimization application regimes is essentially based on the antioxidant properties of polyphenolic components in the cases of natural antioxidants or on the penetration of free radical intermediates into the free volumes of POSS.

15.
Molecules ; 26(19)2021 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-34641396

RESUMEN

New Pb(II), Mn(II), Hg(II), and Zn(II) complexes, derived from 4-(4-chlorophenyl)-1-(2-(phenylamino)acetyl)thiosemicarbazone, were synthesized. The compounds with general formulas, [Pb(H2L)2(OAc)2]ETOH.H2O, [Mn(H2L)(HL)]Cl, [Hg2(H2L)(OH)SO4], and [Zn(H2L)(HL)]Cl, were characterized by physicochemical and theoretical studies. X-ray diffraction studies showed a decrease in the crystalline size of compounds that were exposed to gamma irradiation (γ-irradiation). Thermal studies of the synthesized complexes showed thermal stability of the Mn(II) and Pb(II) complexes after γ-irradiation compared to those before γ-irradiation, while no changes in the Zn(II) and Hg(II) complexes were observed. The optimized geometric structures of the ligand and metal complexes are discussed regarding density functional theory calculations (DFT). The antimicrobial activities of the ligand and metal complexes against several bacterial and fungal stains were screened before and after irradiation. The Hg(II) complex has shown excellent antibacterial activity before and after γ-irradiation. In vitro cytotoxicity screening of the ligand and the Mn(II) and Zn(II) complexes before and after γ-irradiation disclosed that both the ligand and Mn(II) complex exhibited higher activity against human liver (Hep-G2) than Zn(II). Molecular docking was performed on the active site of MK-2 and showed good results.


Asunto(s)
Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Complejos de Coordinación/farmacología , Hongos/efectos de los fármacos , Compuestos Organometálicos/farmacología , Radiación Ionizante , Tiosemicarbazonas/química , Bacterias/efectos de la radiación , Teoría Funcional de la Densidad , Hongos/efectos de la radiación , Humanos , Ligandos , Simulación del Acoplamiento Molecular
16.
Bull Exp Biol Med ; 171(1): 164-171, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34050418

RESUMEN

Dibasic acids (DBA) with benzene rings having substituents and connected by a sulfurcontaining bridge exhibited radioprotective effectiveness when administered in non-toxic concentrations to laboratory mice 1 h before γ-irradiation in a lethal dose of 8 Gy. The correlation of protonophore activity on bilayer lipid membranes with radioprotective (in mice) and uncoupling activity (in mitochondria) indicates a molecular protonophore uncoupling radioprotective mechanism of DBA action on mitochondria, which manifests in temporary partial inhibition of energy production. The effectiveness of DBA depends on the position and the degree of dissociation of OH-groups and increased in the presence of a sulfur-containing bridge and substituents in the series Br->Cl->NO2->COOCH3->COOH-. The higher radioprotective effect was observed for more effective uncouplers of the processes of oxidative phosphorylation and respiration of mitochondria, DBA1 preparations with OH-groups in the 2nd position of the benzene rings (80-100%), than for DBA2 with OH- in the 4th position (40-60%). The radioprotective effect of DBA was related to their antioxidant activity during and after irradiation to a lesser extent than with their uncoupling efficiency. At the cellular level, the radioprotective mechanism of DBA is related to temporary hypoxia and inhibition of metabolism leading to inhibition of generation of ROS, radicals, and LPO products.


Asunto(s)
Protectores contra Radiación , Animales , Antioxidantes/farmacología , Rayos gamma , Ratones , Protectores contra Radiación/farmacología , Azufre
17.
Exp Dermatol ; 29(6): 562-569, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32298492

RESUMEN

Melanoma is a deadly type of skin cancer that is particularly difficult to treat owing to its resistance to radiation therapy. Here, we attempted to determine the key proteins responsible for melanoma radioresistance, with the aim of improving disease response to radiation therapy. Two melanoma cell lines, SK-Mel5 and SK-Mel28, with different radiosensitivities were analysed via RNA-Seq (Quant-Seq) and target proteins with higher abundance in the more radioresistant cell line, SK-Mel28, identified. Among these proteins, integrin αvß3, a well-known molecule in cell adhesion, was selected for analysis. Treatment of SK-Mel28 cells with cilengitide, an integrin αvß3 inhibitor, as well as γ-irradiation resulted in more significant cell death than γ-irradiation alone. In addition, Akt, a downstream signal transducer of integrin αvß3, showed high basic activation in SK-Mel28 and was significantly decreased upon co-treatment with cilengitide and γ-irradiation. MK-2206, an Akt inhibitor, exerted similar effects on the SK-Mel28 cell line following γ-irradiation. Our results collectively demonstrate that the integrin αvß3-Akt signalling pathway contributes to radioresistance in SK-Mel28 cells, which may be manipulated to improve therapeutic options for melanoma.


Asunto(s)
Integrina alfaVbeta3/metabolismo , Melanoma/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Tolerancia a Radiación , Neoplasias Cutáneas/metabolismo , Línea Celular Tumoral , Supervivencia Celular , Rayos gamma , Compuestos Heterocíclicos con 3 Anillos/farmacología , Humanos , Integrina alfaVbeta3/antagonistas & inhibidores , Melanoma/radioterapia , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Transducción de Señal , Neoplasias Cutáneas/radioterapia , Venenos de Serpiente/farmacología
18.
Mol Biol Rep ; 47(3): 1883-1893, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32016634

RESUMEN

Hepatocellular carcinoma (HCC) is a tough opponent. HCC contributes to 14.8% of all cancer mortality in Egypt. There are many choices for management of HCC; however tumor relapse has been reported in animal and clinical studies. This study was conducted to investigate the impact of low dose γ-irradiation (LDR) and combretastatin A-4 disodium phosphate (CA-4DP) on HCC recurrence. HCC was induced in male Wistar albino rats by oral administration of N-nitrosodiethylamine (NDEA) for 17 weeks. We evaluated the expression of the endothelial cell marker (CD31) by immunostaining. Expression of Rho Associated Coiled-Coil Containing Protein Kinase 1(ROCK1) and Vascular endothelial growth factor (VEGF) expression was assessed by real-time PCR after (6, 24 and 48 h). Our results showed that expression of CD31 and gene expression of ROCK1 and VEGF was significantly repressed at all-time intervals by combination therapy ofLDR and CA-4DP as compared with untreated NDEA/HCC group and NDEA/HCC groups treated with either LDR or CA-4DP alone, (P < 0.05). Our study demonstrated the additive effect of LDR in combination with CA-4DP in suppression of HCC.


Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Estilbenos/administración & dosificación , Factor A de Crecimiento Endotelial Vascular/genética , Quinasas Asociadas a rho/genética , Animales , Antineoplásicos Fitogénicos/farmacología , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Quimioradioterapia , Terapia Combinada , Dietilnitrosamina/efectos adversos , Regulación hacia Abajo , Egipto , Rayos gamma , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Ratas , Ratas Wistar , Estilbenos/farmacología , Resultado del Tratamiento , Ensayos Antitumor por Modelo de Xenoinjerto
19.
J Biochem Mol Toxicol ; 34(11): e22565, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32645248

RESUMEN

The current study evaluated the potential ameliorative and protective impacts of l-carnitine (L-CAR) against γ-irradiation (RAD)-induced oxidative stress and apoptosis in mice testes. Male Swiss mice were allocated into four groups (n = 7). Group 1 served as a control that received saline intraperitoneally (IP). Group 2 received L-CAR (10 mg/kg bw/day; IP in saline) for 17 days. Group 3 received saline for 17 days and on day 7 exposed to RAD at a dose of 0.1 Gy per day for consecutive 10 days. Group 4 (L-CAR + RAD), received L-CAR same as in group 2 and on day 7 exposed to RAD for consecutive 10 days. Testicular antioxidants (malondialdehyde, MDA; γ-glutamyl-cysteine synthetase, gGCS; and catalase) were altered by γ-irradiation. Preadministration of L-CAR protected γ-irradiated mice from altered changes induced by γ-irradiation. γ-Irradiation affected the mRNA expression of pro-apoptotic, apoptotic, and anti-apoptotic genes (c-jun, c-fos, Bcl-xl, caspase-3, and BAX). All altered genes were ameliorated by prior l-carnitine administration to γ-irradiated mice. Testicular cells showed deformities and edema with congestion in seminiferous tubules and strong immunoreactivity for caspase-9 and a decrease in immunoreactivity of Bcl-2 in histological and immunohistochemical examination. Prior administration of L-CAR to γ-irradiated mice protected this group from reported changes in caspase-9 and Bcl-2 immunostaining. In conclusion, the current study provides evidence for the protective and ameliorative impacts of L-CAR against γ-irradiation-induced testicular oxidative stress and apoptosis at biochemical, molecular, and cellular levels.


Asunto(s)
Apoptosis/efectos de la radiación , Carnitina/farmacología , Rayos gamma , Estrés Oxidativo/efectos de la radiación , Testículo/efectos de la radiación , Animales , Apoptosis/efectos de los fármacos , Biomarcadores/sangre , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Testículo/efectos de los fármacos , Testículo/metabolismo , Testículo/patología , Proteína X Asociada a bcl-2/metabolismo , Proteína bcl-X/metabolismo
20.
Biotechnol Appl Biochem ; 67(3): 343-353, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31846537

RESUMEN

R-2-(4-hydroxyphenoxy)propionicacid (HPOPA) is a valuable intermediate for the synthesis of enantiomerically pure aryloxyphenoxypropionic acid herbicides. In this work, to improve the HPOPA biosynthesis by Beauveria bassiana ZJB16002 from the substrate R-2-phenoxypropionic acid (POPA), the original HPOPA producer B. bassiana ZJB16002 was subjected to physical mutagenesis with 137 Cs-γ irradiation and chemical mutagen N-methyl-N'-nitro-N-nitrasoguanidine (NTG) induced mutagenesis. The effects of different treatment doses of the mutagens on the lethal rate and positive mutation rate were investigated, and the results showed that the optimal 137 Cs-γirradiation dose and NTG concentration was 850 Gy and 500 µg/mL, respectively. Under these conditions, a mutant strain CCN-7 with the highest HPOPA production capacity was obtained through two rounds of 137 Cs-γ irradiation treatment followed by one round of NTG mutagenesis. At the substrate (POPA) concentration of 50 g/L, HPOPA titer of CCN-7 reached 36.88 g/L, which was 9.73-fold higher than the parental strain. The morphology of the wild-type and mutant strain was compared and the results might provide helpful information in exploration of the correlation of morphology and biochemical features of B. bassiana.


Asunto(s)
Beauveria/genética , Beauveria/metabolismo , Propionatos/metabolismo , Beauveria/química , Estructura Molecular , Éteres Fenílicos/química , Éteres Fenílicos/metabolismo , Propionatos/química , Estereoisomerismo
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