Abstract Our epidemiologic studies on invasive Group A Streptococci (GAS) infections identified specific HLA class II haplotypes/alleles conferring high-risk or protection from streptococcal toxic shock syndrome with a strong conferred by the DRB1*15/DQB1*06 haplotype. We used HLA-transgenic mice to provide an in vitro and vivo validation for direct role of allelic variation syndrome. When splenocytes expressing protective HLA-DQB1*06 (DQ6) allele were stimulated mixture superantigens...

Hyper- or hypothyroidism can impair testicular function leading to infertility. The present study was designed examine the protective effect of date palm pollen (DPP) extract on thyroid disorder-induced dysfunction. Rats were divided into six groups. Group I normal control. II received oral DPP (150 mg kg(-1)), group III (hyperthyroid group) intraperitoneal injection L-thyroxine (L-T4, 300 μg kg(-1); i.p.), IV L-T4 plus extract, V (hypothyroid propylthiouracil (PTU, 10 i.p.) and VI PTU...

Paraquat (PQ) is one of the most used herbicide worldwide. Its cytotoxicity attributed to reactive radical generation. Resveratrol (Res) and montelukast (MK) have anti‐inflammatory antioxidant properties. The protective effects Res, MK, or their combination against PQ‐induced acute liver injury not been investigated before. Therefore, we explored potential Res and/or MK PQ hepatic toxicity in a mouse model. Mice were randomly assigned five groups: group I served as normal control II received...

Protein kinase A-anchoring proteins (AKAPs) participate in the formation of macromolecular signaling complexes that include protein kinases, ion channels, effector enzymes, and G-protein-coupled receptors. We examined role AKAP79/150 (AKAP5) trafficking β1-adrenergic receptor (β1-AR). shRNA-mediated down-regulation AKAP5 HEK-293 cells inhibited recycling β1-AR. Recycling β1-AR knockdown was rescued by shRNA-resistant AKAP5. However, truncated mutants with deletions domains involved membrane...

G protein-coupled receptor family C group 6 member A (GPRC6A) is activated by testosterone and modulates prostate cancer progression. Most humans have a GPRC6A variant that contains recently evolved KGKY insertion/deletion in the third intracellular loop (ICL3) (designated as GPRC6A^ICL3_KGKY) replaces ancestral KGRKLP sequence (GPRC6A^ICL3_RKLP) present all other species. In vitro assays purport human GPRC6A^ICL3_KGKY retained intracellularly lacks function....

Vitiligo is the most common depigmentation disorder of skin. Oxidative stress implicated as one probable events involved in vitiligo pathogenesis possibly contributing to melanocyte destruction. Evidence indicates that certain genes including those oxidative and melanin synthesis are crucial for development vitiligo. This study evaluates status, role catalase (CAT) catechol-O-Methyltransferase (COMT) gene polymorphisms etiology generalized Egyptians. Total antioxidant capacity (TAC)...

Lately, long noncoding (lnc) RNAs are increasingly appreciated for their involvement in multiple sclerosis (MS). In inflammation and autoimmunity, a role of apoprotein A1 (ApoA1), mediated by sphingosine 1-phosphate receptors (S1PRs), was reported. However, the epigenetic mechanisms regulating these biomolecules MS remains elusive. This case control study investigated ApoA1, kinase 1 2 (SPHK1 & 2), S1PR1 5, interferon-γ (IFN-γ) interleukin 17 (IL17) MS, beside three lncRNA: APOA1-AS,...

Superantigens (SAgs) play an important role in the pathogenesis of severe invasive infections caused by Group A Streptococcus (GAS). We had shown earlier that expression streptococcal cysteine protease SpeB results partial loss immune-stimulating activity native secreted GAS SAgs, namely pyrogenic exotoxins produced globally disseminated M1T1 strain, associated with worldwide. In this study, we examined susceptibility each recombinant SAgs to degradation rSpeB. Whereas SmeZ was degraded...

Striking individual differences in severity of group A streptococcal (GAS) sepsis have been noted, even among patients infected with the same bacterial strain. We had provided evidence that HLA class II allelic variation contributes significantly to systemic disease by modulating host responses superantigens. Inasmuch as bacteria produce additional virulence factors participate pathogenesis this complex disease, we sought identify gene networks GAS sepsis. Accordingly, applied a systems...

Abstract The immunomodulatory properties of peptidoglycan (PGN), a constituent the bacterial cell wall, have been studied extensively but with contrasting results. Recent studies demonstrated that TLR2-mediated inflammatory responses elicited by Gram-positive PGN preparations are in fact result contaminating lipoproteins and lipoteichoic acid can be removed only through sophisticated extraction procedures. Here, we report commercial Staphylococcus aureus or Streptococcus pyogenes...

Host immunogenetic variations strongly influence the severity of group A streptococcus sepsis by modulating responses to streptococcal superantigens (Strep-SAgs). Although HLA-II-DR15/DQ6 alleles protect against severe sepsis, HLA-II-DR14/DR7/DQ5 significantly increase risk for toxic shock syndrome. We found that, regardless individual in TCR-Vβ repertoires, presentation Strep-SAgs protective attenuated proliferative Strep-SAgs, whereas their high-risk augmented it. Importantly, HLA-II...

Recombinant human myelin basic protein (rhMBP) was previously produced in the milk of transgenic cows. Differences molecular recognition either hMBP or rhMBP by surface-immobilized anti-hMBP antibodies were demonstrated. This indicated differences immunological response between and hMBP. Here, activity free controlled release poly(ε-caprolactone) nanoparticles (NPs), as a therapeutic vaccine against multiple sclerosis (MS) demonstrated experimental autoimmune encephalomyelitis (EAE) animal...

The β1-adrenergic receptor (β1-AR) is a target for treatment of major cardiovascular diseases, such as heart failure and hypertension. Recycling agonist-internalized β1-AR dependent on type I PSD-95/DLG/ZO1 (PDZ) in the C-tail protein kinase A (PKA) activity (Gardner, L. A., Naren, A. P., Bahouth, S. W. (2007) J. Biol. Chem. 282, 5085-5099). We explored effects point mutations PDZ PKA recycling its binding to PDZ-binding SAP97. These studies indicated that was inhibited by inhibitors...

Background Vitamin D has been considered a key player in various malignancies including cutaneous cancers. To date, mycosis fungoides (MF) the least studied relation to vitamin D. Furthermore, receptor (VDR) single nucleotide polymorphisms (SNPs) have not tackled before context of MF, despite their incrimination numerous diseases. Aim study assess role MF by measuring its serum level, and studying VDR SNPs (TaqI, BsmI, FokI) different stages MF. Patients Methods 48 patients with 45 healthy...

Abstract Superantigens (SAgs) are microbial toxins that bind to both TCR β-chain variable domains (Vβs) and MHC class II molecules, resulting in the activation of T cells a Vβ-specific manner. It is now well established different isoforms molecules can play significant role immune response bacterial SAgs. In this work, using directed mutational studies conjunction with functional analyses, we provide complete map low-affinity α-chain binding interface SAg streptococcal pyrogenic exotoxin C...

Previous studies have determined that the type-1 PDZ sequence at extreme carboxy-terminus of ß1-adrenergic receptor (ß1-AR) binds SAP97 and AKAP79 to organize a scaffold involved in trafficking ß1-AR. In this study we focused on characterizing domains were recycling resensitization ß1-AR HEK-293 cells. Using knockdown rescue strategy, PDZ-deletion mutants containing PDZ2 rescued Among three PDZs SAP97, displayed highest affinity binding Expression isolated PDZ2, but not other PDZs, inhibited...

Several studies have affirmed the effectiveness of some Bauhinia plants as antihyperglycemic agents.We investigated possible effect vahlii leaves extract in reducing hyperglycemia and reversing signs organ damage associated with diabetes streptozotocin (STZ) rat model.Both polar fraction B. (defatted ethanolic [DEE]) nonpolar (n-hexane extract) were evaluated vitro for α-glucosidase inhibition 2,2-diphenyl-1-picrylhydrazyl radical scavenging potential. DEE was selected further vivo...

Individuals infected with genetically identical group Astreptococcal (GAS) strains develop starkly different dis-ease progression and outcome [1]. We reported that HLAclass II allelic variation contributes to differences in sys-temic disease severity by modulating host responses tostreptococcal superantigens [2]. Inasmuch as the bacteriaproduce additional virulence factors, we sought iden-tify gene networks GAS sep-sis. Accordingly, used two parallel approaches todefine these networks,...

The <i>β</i>₁-adrenergic receptor (<i>β</i>₁-AR) is a major cardiac G protein-coupled receptor, which mediates actions of catecholamines and involved in genesis treatment numerous cardiovascular disorders. In mammalian cells, induce the internalization <i>β</i>₁-AR into endosomes their removal promotes recycling endosomal back to plasma membrane; however, whether these redistributive processes occur terminally differentiated cells unknown....