Maged Mostafa Mahmoud

Antimicrobial activities of chicken β-defensin (4 and 10) peptides against pathogenic bacteria and fungi.

Host Defense Peptides (HDPs) are small cationic peptides found in several organisms. They play a vital role in innate immunity response and immunomodulatory stimulation. This investigation was designed to study the antimicrobial activities of β-defensin peptide-4 (sAvBD-4) and 10 (sAvBD-4) derived from chickens against pathogenic organisms including bacteria and fungi. Ten bacterial strains and three fungal species were used in investigation. The results showed that the sAvBD-10 displayed a higher bactericidal potency against all the tested bacterial strains than that of sAvBD-4. The exhibited bactericidal activity was significant against almost the different bacterial strains at different peptide concentrations except for that of Pseudomonas aeruginosa (P. aeruginosa) and Streptococcus bovis (Str. bovis) strains where a moderate effect was noted. Both peptides were effective in the inactivation of fungal species tested yielding a killing rate of up to 95%. The results revealed that the synthetic peptides were resistant to salt at a concentration of 50 mM NaCl. However, they lost antimicrobial potency when applied in the presence of high salt concentrations. Based on blood hemolysis studies, a little hemolytic effect was showed in the case of both peptides even when applied at high concentrations. The data obtained from this study indicated that synthetic avian peptides exhibit strong antibacterial and antifungal activity. In conclusion, future work and research should be tailored to a better understanding of the mechanisms of action of those peptides and their potential use in the pharmaceutical industry to help reduce the incidence and impact of infectious agent and be marketed as a naturally occurring antibiotic.

An overview on the correlation of neurological disorders with cardiovascular disease

Neurological disorders (NDs) are one of the leading causes of death especially in the developed countries. Among those NDs, Alzheimer’s disease (AD) and Parkinson disease (PD) are heading the table. There have been several reports in the scientific literatures which suggest the linkage between cardiovascular disorders (CVDs) and NDs. In the present communication, we have tried to compile NDs (AD and PD) association with CVDs reported in the literature. Based on the available scientific literature, we believe that further comprehensive study needs to be done to elucidate the molecular linking points associated with the above mentioned disorders.

New haplotypes of the ATP synthase subunit 6 gene of mitochondrial DNA are associated with acute lymphoblastic leukemia in Saudi Arabia.

BACKGROUND Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children and represents approximately 25% of cancer diagnoses among those younger than 15 years of age. AIM AND OBJECTIVES This study investigated substitutions in the ATP synthase subunit 6 gene of mitochondrial DNA (mtDNA) as a potential diagnostic biomarker for early detection and diagnosis of acute lymphoblastic leukemia. Based on mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, approximately 465 bp of the ATP synthase subunit 6 gene were amplified and sequenced. RESULTS The sequencing revealed thirty-one mutations at 14 locations in ATP synthase subunit 6 of mtDNA in the ALL subjects. All were identified as single nucleotide polymorphisms (SNPs) with a homoplasmic pattern. The mutations were distributed between males and females. Novel haplotypes were identified in this investigation: haplotype (G) was recorded in 34% in diagnosed subjects; the second haplotype was (C) with frequency of 13% in ALL subjects. Neither of these were observed in control samples. CONCLUSIONS These haplotypes were identified for the first time in acute lymphoblastic leukemia patients. Five mutations able to change amino acid synthesis for the ATP synthase subunit 6 were associated with acute lymphoblastic leukemia. This investigation could be used to provide an overview of incidence frequency of acute lyphoblastic leukemia (ALL) in Saudi patients based on molecular events.

Biocidal activity of chicken defensin-9 against microbial pathogens

In this study we identified the expression patterns of β-defensin-9 in chickens from Saudi Arabia, evaluated the antimicrobial activities of synthetic chicken β-defensin-9 (sAvBD-9) against pathogenic bacteria and fungi, and investigated the mode of action of sAvBD-9 on bacterial cells. The AvBD-9 gene of Saudi chickens encodes a polypeptide of 67 amino acids, which is highly similar to the polypeptide in duck, quail, and goose (97%, 86%, and 87%, respectively) and shares a low sequence similarity with the mammalian defensins. AvBD-9 is expressed in various organs and tissues of Saudi chickens and inhibits the growth of both Gram-negative and Gram-positive bacteria, as well as showing activity against unicellular and multicellular fungi (Aspergillus flavus, A. niger, and Candida albicans). sAvBD-9 completely inhibited the growth of both Gram-positive and Gram-negative bacterial strains as well as Candida albicans. The haemolytic effects of sAvBD-9 were limited. Morphological analysis by TEM revealed that sAvBD-9 induces shortening and swelling of Staphylococcus aureus and Shigella sonni cells, opens holes and deep craters in their envelopes, and leads to the release of their cytoplasmic content. Our data shed light on the potential applications of sAvBD-9 in the pharmaceutical industry.

Prospects of IL-2 in Cancer Immunotherapy

IL-2 is a powerful immune growth factor and it plays important role in sustaining T cell response. The potential of IL-2 in expanding T cells without loss of functionality has led to its early use in cancer immunotherapy. IL-2 has been reported to induce complete and durable regressions in cancer patients but immune related adverse effects have been reported (irAE). The present review discusses the prospects of IL-2 in immunotherapy for cancer.

A Novel Four-Way Complex Variant Translocation Involving Chromosome 46,XY,t(4;9;19;22)(q25:q34;p13.3;q11.2) in a Chronic Myeloid Leukemia Patient

Philadelphia (Ph) chromosome (9;22)(q34;q11) is well established in more than 90% of chronic myeloid leukemia (CML) patients, and the remaining 5–8% of CML patients show variant and complex translocations, with the involvement of third, fourth, or fifth chromosome other than 9;22. However, in very rare cases, the fourth chromosome is involved. Here, we found a novel case of four-way Ph+ chromosome translocation involving 46,XY,t(4;9;19;22)(q25:q34;p13.3;q11.2) with CML in the chronic phase. Complete blood cell count of the CML patient was carried out to obtain total leukocytes count, hemoglobin, and platelets. Fluorescence in situ hybridization technique was used for the identification of BCR–ABL fusion gene, and cytogenetic test for the confirmation of Ph (9;22)(q34;q11) and the mechanism of variant translocation in the bone marrow. The patient is successfully treated with a dose of 400 mg/day imatinib mesylate (Gleevec). We observed a significant decrease in white blood cell count of 11.7 × 109/L after 48-month follow-up. Patient started feeling better generally. There was a reduction in the swelling of the body, fatigue, and anxiety.

Novel Mutations in the Displacement Loop of Mitochondrial DNA are Associated with Acute Lymphoblastic Leukemia: A Genetic Sequencing Study

BACKGROUND Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children and represents approximately 25% of cancer diagnoses among those younger than 15 years of age. MATERIALS AND METHODS This study investigated alterations in the displacement loop (d-loop) region of mitochondrial DNA (mtDNA) as a risk factor and diagnostic biomarker for early detection and diagnosis of acute lymphoblastic leukemia. Using mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, the first 450 bp of the d-loop region were amplified and successfully sequenced. RESULTS This revealed 132 mutations at 25 positions in this region, with a mean of 6 alterations per subject. The d-loop alterations in mtDNA in subjects were all identified as single nucleotide polymorphisms in a homoplasmic distribution pattern. Mutant alleles were observed in all subjects with individual frequency rates of up to 95%. Thirteen mutant alleles in the d-loop region of mtDNA occurred with a high frequency. Novel alleles and locations were also identified in the d-loop of mtDNA as follows: 89 G insertions (40%), 95 G insertions (13%), 182 C/T substitutions (5%), 308 C insertions (19%), and 311 C insertions (80%). The findings of this study need to be replicated to be confirmed. CONCLUSIONS Further investigation of the relationship between mutations in mitochondrial d-loop genes and incidence of acute lymphoblastic leukemia is recommended.

Studies on immunological and degranulation properties of a galectin-1 purified from goat (Capra hircus) heart

Galectins are mammalian lectins characterized by affinity for β-galactosides and the presence of a conserved carbohydrate recognition domain (CRD). Galectins play crucial role in the causation and progression of deadly human diseases like cancer, neurodegenerative disorders and cardiovascular disorders. Available literature reports relevant roles of galectins in innate as well as adaptive immune responses, along with the modulation of acute inflammatory response. In the current study, we purified the goat heart galectin-1 (GHG-1) and carried out its extensive immunological studies. Immunodiffusion studies revealed that anti-GHG-1 antibodies recognize the GHG-1 more readily as compared to the other galectins, suggesting its preferred utilization in various recognition studies. Antigenic cross-reactivity between galectins isolated from different tissues and species suggest their evolutionary preserved fundamental biological roles. A gradual increase in the lysozyme release was evident when the neutrophils were treated with various neutrophil activating agents. The findings of the present study confirm the increase in lysozyme production under the presence of various neutrophil activators, and thus add new information on GHG-1 induced degranulation.

Implications of prognostic variables in the assessment of autoimmunity in hepatitis C patients receiving interferon therapy

Systematic administration of interferon-alpha (INF-alpha) is considered as the backbone of HCV therapy since 1991. Interferon (IFN) therapy can cause vasculitis, glomerulonephritis, cryoglobulinemia and certain other autoimmune diseases such as sialoadentitis, lichen planus and thyroiditis. Related to the factors of interferons, extensively studied gland is thyroid gland. A strong association was observed between thyroid disease and HCV patient when they were exposed to IFN therapy. Vitamin D, malondialdehyde (MDA), thyroid hormones and auto antibodies were biochemically assessed from the venous blood of seventy five HCV patients and fifty healthy controls. The results of all parameters were analyzed by independent sample t-test. The results of the study demonstrated a clear picture that the levels of vitamin D decreased as compared to control but increases in case of MDA. The levels of antibody titer represent that thyroglobulin-antibody (TGAb) thyroid peroxidase-antibody (TPOAb) as well as thyroid stimulating hormone receptor-antibody (TSHRAb) were raised in the patients suffering from HCV with thyroid dysfunction as compared to control. Similarly, the levels of thyroid hormones were also elevated in the HCV patients. Antibodies generated against thyroidal enzymes leads to impaired function of these enzymes thus causing decreased synthesis of thyroid hormones. As exogenous INF triggers the release of cytokines that mediate the recruitment of immune cells with increased production of inflammatory markers lead to production of lytic granules which have direct toxic action on thyroid cells and ultimately increased lipid peroxidation of thyrocytes. The results of the present study clearly demonstrated that the decreased levels of vitamin D in HCV patients receiving IFN therapy were responsible to induce autoimmunity against thyroid gland and adjutant therapy may be helpful to alleviate the possible thyroid disorders.