Potential risk factors for diabetic neuropathy: a case control study

Background  

Diabetes mellitus type II afflicts at least 2 million people in Iran. Neuropathy is one of the most common complications of diabetes and lowers the patient's quality of life. Since neuropathy often leads to ulceration and amputation, we have tried to elucidate the factors that can affect its progression.     

Effects of Influenza Derived Peptide on CD8 T Cell Responses to MHC Class I-Restricted Human Telomerase Reverse Transcriptase (hTERT)-Derived Peptide

International Journal of Peptide Research and Therapeutics - Tumor cells in breast cancer are immunogenic and express proteins that can induce immune responses. One important antigen is human...     

A study of the impact of cytokine gene polymorphism in acute rejection of renal transplant recipients

Acute rejection is a common phenomenon in transplantation. Inflammatory and anti-inflammatory mediators affect the graft microenvironment. Th1 responses cause acute rejection while Th2 immune responses help the survival of the graft. In this study, we evaluated gene polymorphisms of IL-6 G-174C, TGF-β T+869C, IL-4 C-590T, and IFN-γ T+874A cytokines in renal transplant patients. ARMS-PCR method was used to characterize IL-6 G-174C (rs76144090), TGF-β T+869C (rs1800471), and IFN-γ T+874A (rs2430561) polymorphisms and PCR-RFLP, for characterization of IL-4 C-590T (rs2243250) in 100 renal transplant patients. Acute rejection episodes were diagnosed according to the standard criteria. Analysis of the results showed that IL-6-174 GG genotype (P = 0.018, OR = 3.023, 95% CI = 1.183–7.726) and IL-6-174G allele (P = 0.046, OR = 2.114, 95% CI = 1.005–4.447) were more frequent, but IL-6-174GC genotype was less frequent in acute rejection of kidney transplantation in comparison with control group (P = 0.024, OR = 0.302, 95% CI = 0.103–0.883). IFN-γ+874 T allele was associated with a higher risk of acute rejection (P = 0.019, OR = 2.088, 95% CI = 1.124–3.880) while IFN-γ+874 AA genotype was associated with a lower risk of rejection (P = 0.023, OR = 0.318, 95% CI = 0.115–0.875). Frequencies of TGF-β T+869C and IL-4 C-590T were not significantly different (P > 0.05). Consequently, our results show that IL-6 G-174C and IFN-γ T+874A gene polymorphisms have predictive values for acute rejection after renal transplantation in Iranian patients.     

Antibody light chain variable domains and their biophysically improved versions for human immunotherapy

We set out to gain deeper insight into the potential of antibody light chain variable domains (V_Ls) as immunotherapeutics. To this end, we generated a naïve human V_L phage display library and, by using a method previously shown to select for non-aggregating antibody heavy chain variable domains (V_Hs), we isolated a diversity of V_L domains by panning the library against B cell super-antigen protein L. Eight domains representing different germline origins were shown to be non-aggregating at concentrations as high as 450 µM, indicating V_L repertoires are a rich source of non-aggregating domains. In addition, the V_Ls demonstrated high expression yields in E. coli, protein L binding and high reversibility of thermal unfolding. A side-by-side comparison with a set of non-aggregating human V_Hs revealed that the V_Ls had similar overall profiles with respect to melting temperature (T_m), reversibility of thermal unfolding and resistance to gastrointestinal proteases. Successful engineering of a non-canonical disulfide linkage in the core of V_Ls did not compromise the non-aggregation state or protein L binding properties. Furthermore, the introduced disulfide bond significantly increased their T_ms, by 5.5–17.5 °C, and pepsin resistance, although it somewhat reduced expression yields and subtly changed the structure of V_Ls. Human V_Ls and engineered versions may make suitable therapeutics due to their desirable biophysical features. The disulfide linkage-engineered V_Ls may be the preferred therapeutic format because of their higher stability, especially for oral therapy applications that necessitate high resistance to the stomach’s acidic pH and pepsin.