Zinc (Zn) and copper (Cu) have been shown to have the potential to improve glucose metabolism through interactions with cytokines and signaling events with multiple genes. miRNA-375 and the Calpin-10 gene are potential genetic biomarkers for the early prediction of diabetic nephropathy (DN). 128 healthy controls and 129 type 2 diabetic (T2DM) participants were matched for age and sex. Three subgroups were identified from the T2DM group: 39 patients had microalbuminuria, 41 had macroalbuminuria, and 49 patients had renal problems. Circulating miR-375 expression levels were measured via qPCR. Calpain-10 SNP 19 (rs3842570) genotyping was assessed with allele-specific PCR in all the included participants. Spectrophotometry was used to measure the concentrations of serum copper, zinc, and magnesium, while ELISA was used to measure the levels of TGF-β and IL-17. There was significant up-regulation in the expression of miR-375 and serum levels of TGF-β, IL-17, Cu, and the Cu/Zn ratio, whereas, in contrast to the control group, the Zn and Mg levels were lower in the T2DM group. The DN groups had significantly lower miR-375, TGF-β, IL-17, Mg, and Zn levels compared with the T2DM without nephropathy group. Furthermore, between TGF-β, IL-17, and miRNA-375, there were notable correlations. Calpain-10 SNP 19 genotype 22 and allele 2 were linked to a higher incidence of T2DM and DN. Significant TGF-β, Cu, Cu/Zn ratio, HbAc1, and creatinine levels, but insignificant miRNA-375 levels, were associated with genotype 22 of Calpain-10 SNP 19. interactions between the Calpain-10 SNP 19 genotype 22 and IL-17, TGF-β, mineral levels, and miRNA-375 might contribute to the aetiology of DN and T2DM and may have clinical implications for diagnosis and management.

Background: The adipokine chemerin retinoic acid receptor responder protein 2 (RARRES2) has been associated with insulin resistance, type II diabetes mellitus (T2DM), obesity, and metabolic syndrome (MetS). The impact of RARRES2 rs17173608 gene polymorphism on MetS and chemerin levels is not completely elucidated. This study included 100 patients with MetS and 68 healthy subjects (non-MetS group). The RARRES2 rs17173608 gene variant was analyzed by tetra amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR). Circulating chemerin levels were determined by ELISA. Serum urea, creatinine, fasting blood glucose, glycated hemoglobin, and traditional lipid profile were measured by colorimetric methods. The estimated glomerular filtration rate (eGFR) and non-traditional lipid parameters were calculated. Results: Serum chemerin levels were significantly higher in MetS than in non-MetS subjects, type II diabetics (T2DM) than non-diabetics, and overweight compared to lean subjects, but it did not differ significantly between patients with and without hypertension. Strikingly, newly diagnosed diabetic patients had significantly higher serum chermerin levels. Correlation and multiple linear regression analysis showed that serum chemerin levels and non-traditional lipid parameters were correlated significantly with the clinical criteria of MetS. Genotyping and allelic frequency distribution of RARRES2 rs17173608 gene polymorphism showed its significant association with MetS. The TT genotype of RARRES2 rs17173608 SNP was more distributed in T2DM in comparison with non-diabetics, and it was associated significantly with higher serum chemerin and higher glycated hemoglobin levels. RARRES2 rs17173608 GG genotype and G allele frequency were less distributed in T2DM patients than in non-diabetic patients. Conclusions: The RARRES2 rs17173608 SNP might have an impact on chemerin levels and lipid parameters. The GG genotype and G allele may have a protective role towards the risk of T2DM but not for MetS. Serum chemerin and non-traditional lipid profile are significantly associated with MetS.

Background: Lung cancer (LC) is one of the leading causes of death worldwide. Programmed cell death receptor 1 (PD-1) interacts with its ligand (PDL-1) on T cells inhibiting its functioning which may affect the patient's immunological response. Aim: Investigate if there is a link between smoking and tissue expression of PDL-1 and vitamin D receptor (VDR) in lung cancer patients. In addition, the relation of vitamin D with smoking and these biochemical markers. Methods: PDL-1 and VDR expressions were evaluated by real-time PCR in 54 lung cancer biopsy samples and 36 controls to prove this hypothesis. Vitamin D levels in the blood were measured using an ELISA. Results: Expressions of PDL-1 were significantly upregulated in LC patients than in controls. The highest expression was in stage II and in squamous cell carcinoma followed by small cell carcinoma then adenocarcinoma. However, VDR expressions and vitamin D levels in serum were significantly downregulating in LC patients than in controls. There was a positive correlation between PDL-1expression and duration of smoking but not smoking index. Also, there is an inverse correlation between duration of smoking, smoking index, and VDR. Conclusion: Expression of PDL-1 in LC was significantly upregulated and correlated with staging. Interestingly, our current study for the first time explained the role of duration of smoking on PDL-1 and VDR in the pathogenesis of LC. As PDL-1 expression increased with duration of smoking whereas VDR decreased, this novel findings may provide a possible link between the cumulative effect of smoking and the level of expressions of these biomarkers.

Background: Abnormal plasma levels of free amino acids may predict the severity in patients with drug resistant epilepsy (PRE), having probability to affect their therapeutic approach. Objectives:We aimed to illuminate the effect of plasma free amino acids (PFAAs) profiles on the etiology of patients with PRE and their contribution on the frequencies of epileptic fits. Patients and Methods:We collected clinical and metabolomic data of 90 subjects; 45 of them were PRE patients, and other 45 age and sex matched healthy controls. Quantitative measurements of PFAAs profiles using SykamAutomatic Amino Acid Analyzer S433, in addition to fasting blood sugar, liver function tests, kidney function tests and lipid profile also, were determined. Results: The plasma levels of glutamate, glycine and Gamma amino butyric acid(GABA) plasma levels were significantly increased in PRE group compared to controls (p˂0.0001),their plasma levels also showed significant increase with increased frequency of epileptic fits. Plasma leucine, phenylalanine, aspartate ,ornithine, citrulline, serine and alanine levels (p˂0.0001) were significantly increased in PRE group in relation to healthy controls. Interestingly, on the other hand, histidine, isoleucine, lysine, threonine and the amino acid derivative taurine levels were significantly decreased in PRE patients compared to healthy controls. Conclusion:Few biomarkers of PRE are available to find the severity and rate of progressionof PRE. The present study showed that altered plasma amino acids and their derivatives may be candidate markers for PRE, help explaining its pathogenesis, and for further researches concerning normalization of the disturbed amino acid/s or its derivative/s (GABA and taurine) in managing PRE patients.