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Objective: Staphylococcus aureus has become an important pathogen in hospitals worldwide. Despite its differentiation into human and animal lineages, common methods are used for genotyping. While these methods are useful, they are based on the stable genome, and hence, are insensitive to host-specific subtyping. The objectives of this study were to investigate the repeat-domain of the Clumping-Factor A gene (clfA-R) as an objective and adaptation-sensitive approach. Methodology: We have used 113 isolates for susceptibility testing and genotyping by polymerase chain reaction amplification of the clfA-R regions. Of these, 105 were from King Fahad Specialist Hospital, Buraidah and eight were published sequences used as references. Isolates were further confirmed as S. aureus by the commercial Kits. Amplicon sizes were measured and the number of the 18-bp-repeating-units in each isolate was determined against that of methicillin-resistant S. aureus COL (MRSA) sequence. Results: Results showed that all 42 nasal screening isolates (100%) and all but six isolates from clinical specimens were MRSA with 37% of the former and 50% of the latter isolates showing community-acquired-MRSA susceptibility patterns. clfA-R analysis grouped 113 isolates into 14 repeat-genotypes. The two dominant types, D and X, represented the long- and short clfA-R types found in humans and animals, respectively. Linezolid, rifampicin, and vancomycin were the drugs of choice. Conclusions: clfA-R was useful in rapid genotyping and implied host-specific phenotypic properties of the ClfA. It has been recommended that the approach used in regional laboratories for uniform strain-profiling. Future work will show more insights into the gene content and origins of clones. [ABSTRACT FROM AUTHOR]

Natural Killer T (NKT) cells play an important role in host’s anti-tumour immune response. Glycosphingolipids (GSLs) isolated from Sphingomonas paucimobilis have the ability to stimulate NKT cells. In this study, the activity of free GSLs or GSLs-incorporated liposomes (glycosphingosomes) was investigated against dimethyl-α-benzanthracene (DMBA)-induced tumours in mice. The anti-tumour immunity of GSLs- or glycosphingosomes-loaded bone marrow-derived dendritic cells (BMDCs) was investigated in tumour-bearing mice. The Immunotherapeutic potential of co-administration of liposomal doxorubicin (Lip-Dox) and GSLs or glycosphingosomes was assessed by measuring cytokine levels and VEGF in the tumour tissues. Pretreatment with glycosphingosomes significantly delayed the frequency of tumour formation. Immunotherapy with glycosphingosomes-loaded BMDCs increased serum IFN-γ level and survival rate in mice. The effect of immunotherapy was dependent on effector functions of NK cells because the depletion of NK cells abolished the effects of immunotherapy. There was reduced tumour growth with low expression of VEGF in the group of mice treated with glycosphingosomes and Lip-Dox combination. Moreover, the splenocytes secreted higher levels of IFN-γ, IL-12 and lower TGF-β level. The results of this study indicate that glycosphingosomes can induce better antitumour immunity and may be considered a novel formulation in antitumour therapy. [ABSTRACT FROM AUTHOR]

Cancer cells have an unusual regulation of hydrogen ion dynamics that are driven by poor vascularity perfusion, regional hypoxia, and increased glycolysis. All these forces synergize/orchestrate together to create extracellular acidity and intracellular alkalinity. Precisely, they lead to extracellular pH (pHe) values as low as 6.2 and intracellular pH values as high as 8. This unique pH gradient (∆pHi to ∆pHe) across the cell membrane increases as the tumor progresses, and is markedly displaced from the electrochemical equilibrium of protons. These unusual pH dynamics influence cancer cell biology, including proliferation, metastasis, and metabolic adaptation. Warburg metabolism with increased glycolysis, even in the presence of Oxygen with the subsequent reduction in Krebs' cycle, is a common feature of most cancers. This metabolic reprogramming confers evolutionary advantages to cancer cells by enhancing their resistance to hypoxia, to chemotherapy or radiotherapy, allowing rapid production of biological building blocks that support cellular proliferation, and shielding against damaging mitochondrial free radicals. In this article, we highlight the interconnected roles of dysregulated pH dynamics in cancer initiation, progression, adaptation, and in determining the programming and re-programming of tumor cell metabolism. [ABSTRACT FROM AUTHOR]

Objective: Staphylococcus aureus has become an important pathogen in hospitals worldwide. Despite its differentiation into human and animal lineages, common methods are used for genotyping. While these methods are useful, they are based on the stable genome, and hence, are insensitive to host-specific subtyping. The objectives of this study were to investigate the repeat-domain of the Clumping-Factor A gene ( clfA- R) as an objective and adaptation-sensitive approach., Methodology: We have used 113 isolates for susceptibility testing and genotyping by polymerase chain reaction amplification of the clfA- R regions. Of these, 105 were from King Fahad Specialist Hospital, Buraidah and eight were published sequences used as references. Isolates were further confirmed as S. aureus by the commercial Kits. Amplicon sizes were measured and the number of the 18-bp-repeating-units in each isolate was determined against that of methicillin-resistant S. aureus COL (MRSA) sequence., Results: Results showed that all 42 nasal screening isolates (100%) and all but six isolates from clinical specimens were MRSA with 37% of the former and 50% of the latter isolates showing community-acquired-MRSA susceptibility patterns. clfA -R analysis grouped 113 isolates into 14 repeat-genotypes. The two dominant types, D and X, represented the long- and short clfA -R types found in humans and animals, respectively. Linezolid, rifampicin, and vancomycin were the drugs of choice., Conclusions: clfA -R was useful in rapid genotyping and implied host-specific phenotypic properties of the ClfA . It has been recommended that the approach used in regional laboratories for uniform strain-profiling. Future work will show more insights into the gene content and origins of clones ., (Copyright: © International Journal of Health Sciences.)