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1.
Int Immunopharmacol ; 132: 111985, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38603862

ABSTRACT

BACKGROUND: Bronchial asthma is a severe respiratory condition characterized by airway inflammation, remodeling, and oxidative stress. ß-Glucan (BG) is a polysaccharide found in fungal cell walls with powerful immunomodulatory properties. This study examined and clarified the mechanisms behind BG's ameliorativeactivitiesin an allergic asthma animal model. METHOD: BG was extracted from Chaga mushroom and characterized using FT-IR, UV-visible, zeta potential, and 1H NMR analysis. The mice were divided into five groups, including control, untreated asthmatic, dexamethasone (Dexa)-treated (1 mg/kg), and BG (30 and 100 mg/kg)-treated groups. RESULTS: BG treatment reduced nasal scratching behavior, airway-infiltrating inflammatory cells, and serum levels of IgE significantly. Additionally, BG attenuated oxidative stress biomarkers by lowering malonaldehyde (MDA) concentrations and increasing the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT). Immunohistochemical and flow cytometric analyses have confirmed the suppressive effect of BG on the percentage of airway-infiltrating cytotoxic CD8+ T cells. CONCLUSION: The findings revealed the role of CD8+ T cells in the pathogenesis of asthma and the role of BG as a potential therapeutic agent for asthma management through the suppression of airway inflammation and oxidative stress.


Subject(s)
Asthma , CD8-Positive T-Lymphocytes , Mice, Inbred BALB C , Ovalbumin , Oxidative Stress , beta-Glucans , Animals , Oxidative Stress/drug effects , beta-Glucans/pharmacology , beta-Glucans/therapeutic use , beta-Glucans/chemistry , Asthma/drug therapy , Asthma/immunology , Asthma/chemically induced , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/drug effects , Ovalbumin/immunology , Mice , Disease Models, Animal , Immunoglobulin E/blood , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Lung/pathology , Lung/drug effects , Lung/immunology , Female , Anti-Asthmatic Agents/pharmacology , Anti-Asthmatic Agents/therapeutic use
2.
Medicine (Baltimore) ; 102(20): e33836, 2023 May 19.
Article in English | MEDLINE | ID: mdl-37335685

ABSTRACT

Acute lymphoblastic leukemia (ALL) is a common cancer affecting children worldwide. The development of ALL is driven by several genes, some of which can be targeted for treatment by inhibiting gene fusions. PAX5 is frequently mutated in ALL and is involved in chromosomal rearrangements and translocations. Mutations in PAX5 interact with other genes, such as ETV6 and FOXP1, which influence B-cell development. PAX5/ETV6 has been observed in both B-ALL patients and a mouse model. The interaction between PAX5 and FOXP1 negatively suppresses the Pax5 gene in B-ALL patients. Additionally, ELN and PML genes have been found to fuse with PAX5, leading to adverse effects on B-cell differentiation. ELN-PAX5 interaction results in the decreased expression of LEF1, MB1, and BLNK, while PML-PAX5 is critical in the early stages of leukemia. PAX5 fusion genes prevent the transcription of the PAX5 gene, making it an essential target gene for the study of leukemia progression and the diagnosis of B-ALL.


Subject(s)
PAX5 Transcription Factor , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Animals , Mice , Mutation , Oncogene Proteins, Fusion/genetics , Oncogene Proteins, Fusion/metabolism , PAX5 Transcription Factor/genetics , PAX5 Transcription Factor/metabolism , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Transcription Factors/genetics
3.
Sci Rep ; 13(1): 2749, 2023 02 16.
Article in English | MEDLINE | ID: mdl-36797452

ABSTRACT

Both gallic and citrate are well-established antioxidants that show promise as new selective anti-cancer drugs. Gold nanoparticles (AuNPs) as well can be developed as flexible and nontoxic nano-carriers for anti-cancer drugs. This article evaluating the efficiency and biocompatibility of gallic acid and citrate capping gold nanoparticles to be used as anti-cancer drug. The biosafety and therapeutic efficiency of prepared nano-formulations were tested on Hela and normal BHK cell line. Gold nanospheres coated with citrate and gallate were synthesized via wet chemical reduction method. The prepared nano-formulations, citrate and gallate coated gold nanospheres (Cit-AuNPs and Ga-AuNPs), were characterized with respect to their morphology, FTIR spectra, and physical properties. In addition, to assess their cytotoxicity, cell cycle arrest and flow cytometry to measure biological response were performed. Cit-Au NPs and Ga-Au NPs were shown to significantly reduce the viability of Hela cancer cells. Both G0/G cell cycle arrest and comet assay results showed that genotoxic effect was induced in Hela cells by Cit-Au NPs and Ga-Au NPs. The results of this study showed that Cit-Au NPs and Ga-AuNPs inhibit the growth of metastatic cervical cancer cells, which could have therapeutic implications.


Subject(s)
Antineoplastic Agents , Metal Nanoparticles , Nanospheres , Humans , Citric Acid/chemistry , HeLa Cells , Gold/pharmacology , Gold/chemistry , Metal Nanoparticles/chemistry , Citrates , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry
4.
Anim Biotechnol ; 34(7): 2499-2504, 2023 Dec.
Article in English | MEDLINE | ID: mdl-35855643

ABSTRACT

This study aimed to detect putative genomic loci in candidate genes associated with milk composition in Egyptian Zaraibi goats. A total number of 50 samples were tested to detect polymorphism in exons 15 and 16 of the diacylglycerol acyltransferase 1 (DGAT1) gene. The PCR products were sequenced and aligned. Sequence analysis showed three new genotypes in the studied samples: T1C1 (T12C SNP), T2C2 (T84C), and AG (G219A), then three groups were created: the first group was BB with C1T1 and AG genotypes, the second was DD which contains C2T2 and AG genotypes, and the third was AG with only AG genotype. GLM showed that the DD group with C84T and G219A SNPs had significantly the highest fat percent. Meanwhile, the BB group with C84T and G219A SNPs recorded significantly the highest total solids levels. On the other hand, the AG group which has G219A SNP showed a non-significant effect on milk components. Those new SNPs were submitted to GenBank and approved to be published. Moreover, translation of those sequences showed that the G219A SNP causes a substitution of Glycine to Serine in exon 16 at position 106. This SNP (G106S) was predicted to be tolerated by SIFT with a score of 0.48.


Subject(s)
Milk , Polymorphism, Single Nucleotide , Animals , Polymorphism, Single Nucleotide/genetics , Diacylglycerol O-Acyltransferase/genetics , Goats/genetics , Egypt , Genotype
5.
Mutat Res ; 726(2): 195-9, 2011 Dec 24.
Article in English | MEDLINE | ID: mdl-22001193

ABSTRACT

Human exposure to metals is of increasing concern due to the well-documented toxic and carcinogenic effects of metals and metal compounds, and the rising environmental levels due to industrial processes and pollution. It has been reported that metals can be genotoxic by several modes of action including generation of reactive oxygen species and inhibition of DNA repair. The aim of this study was to evaluate microsatellite instability (MSI) in three microsatellite loci (D6mit3, D9mit2 and D15Mgh1) located within three common fragile sites in the genome of the laboratory rat (6q21, 9q32-9q33 and 15p14) exposed to acute and chronic doses of a metal salt (lead acetate trihydrate) and a metalloid oxide (arsenic trioxide). In the acute and sub-chronic studies with the two compounds, MSI was observed in the three loci as deletions or additions of microsatellite repeats. The percentages of MSI were 36.4% and 42.1% for lead acetate and arsenic trioxide, respectively. Results of the present work indicate that the microsatellites located within fragile sites provide a convenient assay system to detect changes in DNA sequences resulting from exposure to genotoxic agents.


Subject(s)
Chromosome Fragile Sites/drug effects , Microsatellite Instability/drug effects , Mutagens/toxicity , Organometallic Compounds/toxicity , Oxides/toxicity , Animals , Arsenic Trioxide , Arsenicals , Male , Rats
6.
Mutat Res ; 696(2): 160-6, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20100592

ABSTRACT

Cadmium (Cd) is a non-essential element and is a widespread environmental pollutant. Exposure to cadmium can result in cytotoxic, carcinogenic and mutagenic effects. Mutagenesis is an indicative of genetic instability and can be assayed using microsatellites instability. The aim of the present study is to investigate; based on the rat model, the effects of oral acute (single 8.8mg/kg BW, 1/10 LD(50)) and sub-chronic (2.93mg/kg BW, 1/30 LD(50), for 4 weeks) doses of cadmium chloride on microsatellite instability at D6mit3, D9mit2 and D15Mgh1 loci, which are located in three different common fragile sites (6q21, 9q32-q33 and 15p14, respectively), within rat genome. In the acute study, no microsatellite instability (MSI) was observed in all the three tested loci (D6mit3, D9mit2 and D15Mgh1). In the sub-chronic study, the MSI were observed in the three studied loci and was in the form of deletion of 2-3bp or addition of 3-6bp. These finding may indicate the sensitivity of microsatellite sequences located at the fragile sites and the sensitivity of the simple sequence repeats (SSRs) assay for the detection of small variations in DNA sequence. However, additional chronic toxicological trials are needed in order to assess genotoxic effects of chronic exposure to Cd.


Subject(s)
Cadmium/toxicity , Chromosome Fragile Sites/drug effects , Microsatellite Instability , Microsatellite Repeats/drug effects , Mutagens/toxicity , Animals , Rats , Sequence Deletion/drug effects
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