Non-classical monocytes frequency and serum vitamin D3 levels are linked to diabetic foot ulcer associated with peripheral artery disease.

AIMS/INTRODUCTION: Peripheral artery disease (PAD) serves as a risk factor for diabetic foot ulcers (DFUs). PAD pathology involves atherosclerosis and impaired immunity. Non-classical monocytes are believed to have an anti-inflammatory role. 1,25-Dihydroxy vitamin D (vitamin D3 ) is claimed to have immune-modulating and lipid-regulating roles. Vitamin D receptor is expressed on monocytes. We aimed to investigate if circulating non-classical monocytes and vitamin D3 were implicated in DFUs associated with PAD. MATERIALS AND METHODS: There were two groups of DFU patients: group 1 (n = 40) included patients with first-degree DFUs not associated with PAD, and group 2 (n = 50) included patients with DFU with PAD. The monocyte phenotypes were detected using flow cytometry. Vitamin D3 was assessed by enzyme-linked immunosorbent assay. RESULTS: DFU patients with PAD showed a significant reduction in the frequency of non-classical monocytes and vitamin D3 levels, when compared with DFU patients without PAD. The percentage of non-classical monocytes positively correlated with vitamin D3 level (r = 0.4, P < 0.01) and high-density lipoprotein (r = 0.5, P < 0.001), whereas it was negatively correlated with cholesterol (r = -0.5, P < 0.001). Vitamin D3 was negatively correlated with triglyceride/high-density lipoprotein (r = -0.4, P < 0.01). Regression analysis showed that a high vitamin D3 serum level was a protective factor against PAD occurrence. CONCLUSIONS: Non-classical monocytes frequency and vitamin D3 levels were significantly reduced in DFU patients with PAD. Non-classical monocytes frequency was associated with vitamin D3 in DFUs patients, and both parameters were linked to lipid profile. Vitamin D3 upregulation was a risk-reducing factor for PAD occurrence.

Toxoplasmosis and cytomegalovirus infection and their role in Egyptian autistic children.

Autism is a neurodevelopmental disorder with a significantly increased incidence rate across the world over the past few years. Toxoplasmosis and cytomegalovirus (CMV) infection are globally prevalent and have been associated with diverse neurological and psychiatric disorders. A few studies have demonstrated the role of toxoplasmosis and CMV as potential etiological factors for autism. Accordingly, this study was performed to estimate the relationship between toxoplasmosis and CMV infection in children with autism as well as to assess their impact on the Childhood Autism Rating Scale (CARS) score. A total of 45 autistic children (6 girls, 39 boys) and 45 (21 girls, 24 boys) healthy control children were enrolled in our study. Their blood samples were collected and tested for the presence of Toxoplasma and CMV (IgG and IgM) antibodies and DNA by ELISA and real-time PCR (RT-PCR), respectively. Toxoplasmosis was detected in 11 (24.4%) autistic children through the ELISA [10 (22.2%) IgG + /IgM - and 1 (2.2%) IgG + /IgM +]; however, RT-PCR assay recorded only 1 positive case (2.2%), while it was detected in 10 (22.2%) control children through ELISA [9 (20%) IgG + /IgM - and 1 (2.2%) IgG + /IgM +] and 1 (2.2%) by RT-PCR. On the other hand, CMV infection was detected in all autistic children with 44 (97.8%) testing positive by ELISA [24 (53.3%) IgG + /IgM - , 18 (40%) IgG + /IgM + and 2 (4.4%) IgG - /IgM +] and 25 (55.6%) testing positive by RT-PCR assay. In addition, ELISA assay recorded 43 (95.6%) [19 (42.2%) IgG + /IgM + and 22 (48.9%) IgG + /IgM - and 2 (4.4%) IgG-/IgM +] and RT-PCR recorded 21 (46.7%) positive samples in control children with CMV. No significant difference was noted between autistic and control children for the overall prevalence of Toxoplasma or/and CMV infection. Similarly, the CARS score indicated a non-significant difference with Toxoplasma or/and CMV infection. Our data does not show an association between autism and toxoplasmosis or/and CMV infection. Nevertheless, considering that autistic children are at a high risk of contracting these infections, further studies with a larger sample size are recommended.

Impact of miR-155 rs767649 Polymorphism on Rheumatoid Arthritis Activity in Egyptian Patients.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory condition that impacts not only the musculoskeletal system but also various other systems in the body, including the cutaneous, ocular, respiratory, cardiovascular, and circulatory systems. MicroRNAs (miRNAs) are a class of naturally occurring and highly conserved transcripts that primarily function in the regulation of gene expression. They accomplish this by facilitating the degradation of messenger RNA (mRNA) or by repressing mRNA translation. miRNAs are well-known regulators of a variety of cellular processes. Therefore, we aimed to detect the impact of miR-155 rs767649 polymorphism on RA activity. METHODS: This case-control study included 66 Egyptian patients with RA who visited Al-Zhraa University Hospital, Internal Medicine Department, Cairo, Egypt, and 50 apparently healthy control subjects matched for age and sex. The participants were subjected to full clinical evaluation, including assessments of the disease activity score (DAS), erythrocyte sedimentation rate (ESR), liver and kidney function, anti-cyclic citrullinated peptide antibody (anti-CCP), and miR-155 polymorphism using real-time polymerase chain reaction (PCR). RESULTS: In the RA group, the majority (98.5%) were female, with a mean age of 43 years, while in the control group, 94% were female, with a mean age of 43.4 years. Comparison of laboratory parameters indicated significantly lower hemoglobin levels, higher ESR, and higher serum creatinine and anti-CCP levels in the RA group than in the control group. The RA group had a significantly higher frequency of TT genotypes and significantly lower frequencies of TA and TT genotypes than the control group. Considering the TT genotype and T allele as references, TA, AA, and TA/AA genotypes in the dominant model; AA in the recessive model; and A allele were significantly associated with protective effects against RA development (p<0.05, odds ratio<1). CONCLUSION: rs767649, the functional variant of miR-155, plays an important role in susceptibility to the increased risk of RA, suggesting that miR-155 can be used as a therapeutic target for the treatment of Egyptian patients with RA.

Cytotoxic T Cell Expression of Leukocyte-Associated Immunoglobulin-Like Receptor-1 (LAIR-1) in Viral Hepatitis C-Mediated Hepatocellular Carcinoma.

Virus-related hepatocellular carcinoma (HCC) pathogenesis involves liver inflammation, therefore, despite successful treatment, hepatitis C virus (HCV) may progress to HCC from initiated liver cirrhosis. Cytotoxic T cells (Tcs) are known to be involved in HCV-related cirrhotic complications and HCC pathogenesis. The inhibitory checkpoint leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is expressed on Tcs. Therefore, we aimed to determine whether the Tc expression level of LAIR-1 is associated with HCC progression and to evaluate LAIR-1 expression as a noninvasive biomarker for HCC progression in the context of liver cirrhosis related to HCV genotype 4 (G4) in Egyptian patients' peripheral venous blood liquid biopsy. A total of 64 patients with HCC and 37 patients with liver cirrhosis were enrolled in this case-controlled study, and their LAIR-1 expression on Tc related to the progression of liver cirrhosis was examined and compared to that of the apparently healthy control group (n = 20). LAIR-1 expression was analyzed using flow cytometry. Results: The HCC group had significantly higher LAIR-1 expression on Tc and percentage of Tc positive for LAIR-1 (LAIR-1+Tc%) than the HCV G4-related liver cirrhosis group. LAIR-1+Tc% was correlated with the HCC surrogate tumor marker AFP (r = 0.367, p = 0.001) and insulin resistance and inflammation prognostic ratios/indices. A receiver operating characteristic (ROC) curve revealed that adding LAIR-1+Tc% to AFP can distinguish HCC transformation in the Egyptian patients' cohort. Upregulated LAIR-1 expression on Tc could be a potential screening noninvasive molecular marker for chronic inflammatory HCV G4 related liver cirrhosis. Moreover, LAIR-1 expression on Tc may be one of the players involved in the progression of liver cirrhosis to HCC.

Ligand-based design and synthesis of N'-Benzylidene-3,4-dimethoxybenzohydrazide derivatives as potential antimicrobial agents; evaluation by in vitro, in vivo, and in silico approaches with SAR studies.

Herein, a series of N'-benzylidene-3,4-dimethoxybenzohydrazide derivatives were designed and synthesised to target the multidrug efflux pump (MATE). The antibacterial activities were screened against S. aureus, Acinetobacter, S. typhi, E. coli, and P. aeruginosa, whereas their antifungal activities were screened against C. albicans. Compounds 4a, 4h, and 4i showed the most promising antibacterial and antifungal activities. Moreover, compounds 4h and 4i being the broader and superior members regarding their antimicrobial effects were selected to be further evaluated via in vivo testing using biochemical analysis and liver/kidney histological examination. Additionally, molecular docking was carried out to attain further deep insights into the synthesised compounds' binding modes. Also, ADMET studies were performed to investigate the physicochemical/pharmacokinetics features and toxicity parameters of the synthesised derivatives. Finally, a structure-antimicrobial activity relationship study was established to facilitate further structural modifications in the future. HighlightsA series of new N'-benzylidene-3,4-dimethoxybenzohydrazide derivatives were designed and synthesised targeting the multidrug efflux pump (MATE) guided by the pharmacophoric features of the co-crystallized native inhibitor of the target protein.The newly synthesised compounds were assessed through in vitro, in vivo, and in silico approaches.Using the agar well diffusion assay, the antibacterial activities of the synthesised compounds were screened against S. aureus, Acinetobacter, S. typhi, E. coli, and P. aeruginosa, whereas, their antifungal activities were screened against C. albicans.The minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of the synthesised compounds were investigated on variable microbial species.Compounds (4h and 4i) -as the broader and superior members regarding their antimicrobial effects- were further evaluated via in vivo testing using bio-chemical analysis and liver/kidney histological examination.A molecular docking study and ADMET in silico studies were performed.A structure-antimicrobial activity relationship study was established to facilitate further structural modifications in the future.