Reports of Biochemistry and Molecular Biology最新文献

Background: Red blood cell distribution (RDW), an index of the size variability of erythrocytes, is significantly associated with coronary stenosis and can strongly predict the mortality risk in coronary artery disease (CAD). The biological mechanisms involved are not fully understood but may include oxidative stress. We sought to investigate the relationship between RDW and markers of oxidative stress in patients with CAD.

Methods: Participants were 112 consecutive patients referred to department of cardiac surgery for evaluation of chest pain. 32 patients had stable CAD, 40 patients had unstable CAD and 40 subjects were diagnosed as non-CAD. The levels of lipid peroxidation (TBARS) were measured in plasma and membrane samples by a fluorometric method. The plasma levels of glutathione (GSH) and total antioxidant capacity (TAC) were determined using spectrophotometric methods.

Results: Lipid peroxidation levels were significantly higher in the erythrocyte membrane of stable CAD patients than non-CAD patients. The levels of TAC were significantly lower in both stable and unstable groups when compared to that of the control group (P< 0.019 and P< 0.001, respectively), but did not differ between stable and unstable CAD. In addition, there was no significant difference in the serum GSH levels among the study groups. Membrane TBARS was directly associated with RDW in three groups of study.

Conclusions: We found an independent association between RDW levels and membrane lipid peroxidation in patients with CAD. This finding suggests that oxidative stress may be a potential underlying biological mechanism for increased RDW in CAD patients.

Background: The number of erythromycin-resistant Streptococcus pneumoniae has significantly increased around the world. The present study aimed to determine the serotype distribution and molecular epidemiology of the erythromycin-resistant Streptococcus pneumoniae (ERSP) isolated from patients with invasive disease.

Methods: A total of 44 Streptococcus pneumoniae isolates were tested for susceptibility to several antimicrobial agents. Additionally, the polymerase chain reaction (PCR) was applied to evaluate ERSP isolates in terms of the presence of erythromycin resistance genes (e.g., ermB and mefA). The isolates were serotyped using the sequential multiplex-PCR method, and molecular epidemiology was assessed through the multilocus sequence typing (MLST) analysis.

Results: The results represented multidrug resistance (MDR) in approximately half of the pneumococcal isolates. Among 22 ERSP isolates, 20 (90.9%) and 12 (56%) ones contained ermB and mefA, respectively. Further, 14 (31.8%), 3 (22.7%), and 19A (18.1%) were the common serotypes among the isolates. No significant correlation was observed between serotypes and erythromycin resistance genes. Furthermore, the MLST results revealed 18 different sequence types (STs), the top ones of which were ST3130 (3 isolates) and ST166 (3 isolates). Population genetic analysis disclosed that CC63 (32%), CC156 (18%), and CC320 (18%) were identified as the predominant clonal complexes.

Conclusions: The ERSP isolates exhibited high genetic diversity. The large frequency of MDR isolates suggests the emergence of high resistant strains, as well as the need to implement vaccination in the immunization schedule of Iran. These accumulating evidences indicate that 13-valent pneumococcal conjugate vaccines provided higher serotype coverage in the ERSP isolates.

Background: Preeclampsia (PE) is a multisystem pregnancy disorder that increases maternal-perinatal morbidity and mortality significantly. MicroRNA-155 (miR-155) overexpression in the sera of pregnant women has been linked to preeclampsia. Researchers discovered that miR-155 acts during pregnancy by down-regulating and reducing the cysteine-rich angiogenic inducer 61 (CYR61), which causes local ischemia as well as oxidative stress.

Methods: The level of miR-155 expression in all serum samples was quantified using real-time polymerase chain reaction (RT-PCR), and serum CYR61 was measured using enzyme-linked immunosorbent assays. Together with the Cyr-61/miR-155 ratio, they were evaluated as biomarkers for PE pathogenesis and severity prediction.

Results: MiR-155 expression, serum CYR61 levels, and Cyr-61/miR-155 ratios were all significantly higher in PE patients compared to the control group. Serum CYR61 levels and the Cyr-61/miR-155 ratio differed significantly between mild and severe PE patients.

Conclusions: MiR-155 expression, serum CYR61 levels, and Cyr-61/miR-155 may serve as biomarkers for PE pathogenesis and severity prediction.

Background: Allergic rhinitis (AR) is an inflammatory disorder of the nasal mucosa, caused by exposure to environmental allergens. It is known that 15-lipoxygenase (15-LOX) is involved in the biosynthetic pathways of anti-inflammatory lipid mediators, including resolvins and protectins.

Methods: In this study, which was performed on 130 AR patients and 130 healthy controls, we aimed to investigate the association of susceptibility to AR with two selected single-nucleotide polymorphisms (SNPs), that is, rs2619112:A>G and rs7217186:C>T, in the intron regions of arachidonic acid 15-LOX (ALOX15) gene, using SNPinfo and Regulome DB tools.

Results: The results showed that the CT genotype of rs7217186: C>T was significantly associated with the increased risk of AR compared to the CC genotype (P= 0.037, OR=1.943, CI: 1.038-0.638). However, there was no strong evidence of the association of rs2619112: A>G with susceptibility to AR (P> 0.05).

Conclusions: The present results indicated that rs7217186 polymorphism of ALOX15 gene might be a potential biomarker for susceptibility to AR.

Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune condition that affects multiple organs significantly impacts morbidity and mortality. The development of SLE is influenced by genetic predisposition and dysregulated immune response. Our objective was to investigate miR-21, IL-10, and PDCD4 expression in SLE patient plasma and analyze their correlations and potential diagnostic and prognostic values.

Methods: The study included 100 healthy subjects, 50 newly diagnosed (ND), and 50 under-treatment (UT) SLE patients. The patients were observed for 24 weeks to track relapses. miR-21 and PDCD4 gene expression levels were measured using real-time RT-PCR, and IL-10 production was measured using ELISA.

Results: miR-21 and IL-10 expression levels were significantly greater in SLE patients than in healthy subjects, with the highest levels observed in ND patients. PDCD4 expression was also significantly greater in SLE patients than in subjects, with the highest levels observed in UT patients. ROC curve analyses and Cox-Mantel Log-rank tests indicated miR-21, PDCD4, and IL-10 as proper diagnostic and prognostic biomarkers for SLE. The study also revealed a significant positive correlation between miR-21 and PDCD4 and IL-10 levels in SLE patients.

Conclusions: The studies suggest that dysregulation of miR-21, PDCD4, and IL-10 in patients with SLE may contribute to disease development and provides new diagnostic and prognostic markers. Additionally, the observed correlation between miR-21, PDCD4, and IL-10 levels in SLE patients signifies a potential interplay between these molecules.

Background: The oxidative balance is a state of equilibrium between oxidants and antioxidants disrupted in various disorders, including BC. This study aimed to assess this equilibrium in breast cancer (BC) patients by looking at the oxidant-to-antioxidant ratio.

Methods: This case-control study comprised 40 women patients with breast cancer and 30 age-matched healthy individuals. The oxidation-reduction colorimetric technique was used to determine serum levels of total oxidant status (TOS) and total antioxidant capacity (TAC). The oxidant-to-antioxidant balance was estimated using the TOS- to- TAC ratio (TOS/TAC).

Results: The mean TOS in healthy individuals was 8.40±2.06 µmol/L, while in BC patients it was 13.31±2.16 µmol/L (P< 0.001). The mean serum level of TAC was 1.43±0.21 mmol/L in healthy individuals and 1.19±0.15 mmol/L in BC patients (P< 0.001). The mean serum TOS/TAC was 6.01±0.32 in the healthy individuals and 11.42±0.41 in the BC patients (P< 0.0001). There were direct correlations between TAC and estrogen receptor (r=0.339, P=0.038). The TOS/TAC level has a sensitivity of 100% and specificity of 83.33%, distinguishing patients with BC from healthy controls (P< 0.001). A significant trend of increasing risk with rising TOS/TAC levels was also seen [OR=3.62, (95 % CI 1.79, 7.35)].

Conclusions: In breast cancer, the serum TOS to TAC ratio can better diagnose oxidative equilibrium than either component alone.

Background: Alzheimer´s disease (AD) is one of the most common forms of dementia, is characterized by memory loss and cognitive impairment that affects more than 30 million people worldwide. The pathogenesis of Alzheimer's disease is primary driven by brain accumulation of the amyloid β peptide generated from the amyloid-β precursor protein (APP) via cleavages by β- and γ-secretase. In this study, we propose an approach by molecular docking to select compounds as γ-secretase inhibitors for decreasing the APP generation.

Methods: We selected potential γ-secretase inhibitors by molecular docking in the potential site between Asp257, Lue268, Asp385, Ile387, Phe388, and Leu432 amino acids in presenilin-1 (PS-1), using a chemical library of over 500,000 compounds.

Results: Eight compounds (AZ1 - AZ8) were selected by molecular docking to develop γ-secretase inhibitors for decreasing the APP generation.

Conclusions: AZ1 - AZ8 compounds could be interacting in the potential site between Asp257, Lue268, Asp385, Ile387, Phe388, and Leu432 amino acids in PS-1. These compounds could specifically interact in the binding pocket in PS-1 to prevent/decrease the APP generation, to develop a new drug against Alzheimer's disease.

Background: The role and regulation mechanisms of the interleukin-6 and 10 (IL6 and IL-10) serum levels and the interaction between CD4+ and CD8+ lymphocytes with SARS-COV-2 IgM and IgG in the context of COVID-19 infection are not fully understood.

Methods: This study was conducted on 45 COVID-19 patients and 45 healthy individuals. The IL-6 and IL-10 promoter methylation, IL-6 and IL-10 gene expression, SARS-COV-2 IgM, and IgG antibodies and CD4+ and CD8+ lymphocytes were studied by qMSP-PCR, Real-time PCR, ELISA, and flow cytometry techniques, respectively.

Results: The male ratio and mean age of critically ill patients' group were significantly higher in compared to controls (P< 0.05). IL-6 gene expression and serum levels were significantly increased in patients compared to controls (P=0.002, 0.001), but IL-6 promoter methylation was not significantly decreased in patients (P=0.835). The IL-10 promoter methylation and expression were not different between cases and controls (0.326, 0.455), but serum IL-10 levels were higher in patients (P< 0.001). The CD4+ and CD8+ lymphocytes decreased (P< 0.001) and mean SARS-COV-2 IgG increased (P=0.002) in the patients compared to controls.

Conclusions: The COVID-19 disease result in severe complications in men and elderly. The serum levels of interleukin-6 and 10 increases in COVID-19 infection, and the gene expression of these two interleukins underlying in this increase. The serum levels of IL-6, IL-10 and SARS-COV-2 IgG as well as CD4+ and CD8+ lymphocyte counts should be investigated to monitor patients and predict the course of disease.

Background: Persistent liver damage contributes to the development of liver fibrosis, marked by an accumulation of extracellular matrix. Macrophages play a pivotal role in this process, with the CCL2-CCR2 and CX3CR1-CX3CL1 axes serving as key regulators of macrophage recruitment, liver infiltration, and differentiation. In this study, utilizing a rat model of carbon tetrachloride (CCL4)-induced liver fibrosis, we aimed to investigate the impact of imatinib and bone marrow-derived mesenchymal stem cells (BM-MSCs) on the expression of these axis.

Methods: Sixteen Sprague-Dawley rats were divided into four groups: healthy, liver fibrosis, imatinib-recipient, and BM-MSC-recipient. Treatment effects were evaluated using histopathology and Sirus-red staining. Quantitative real-time PCR was employed to analyze changes in the expression of the genes CCL2, CCR2, CX3CL1, and CX3CR1.

Results: Histopathological assessments revealed the efficacy of imatinib and BM-MSCs in mitigating liver fibrosis. Our findings demonstrated a significant reduction in CCL2 and CCR2 expression in both imatinib and BM-MSCs treatment groups compared to the liver fibrosis group. Conversely, the gene expression of CX3CL1 and CX3CR1 increased in both therapeutic groups compared to the liver fibrosis groups.

Conclusions: The notable decrease in CCL2-CCR2 genes in both therapeutic groups suggests that BM-MSCs and imatinib may contribute to a decline in inflammatory macrophages within the liver. The lower CCL2-CCR2 expression in imatinib-recipient rats indicates better efficacy in modulating the recruitment of inflammatory macrophages. The elevated expression of CX3CL1 in BM-MSC-recipient rats suggests a greater impact on the polarization of LY6Chigh (inflammatory) to LY6Clow (anti-inflammatory) macrophages, warranting further investigation.

Background: T-cell acute lymphoblastic leukemia (T-ALL) is known as an aggressive malignant disease resulting from the neoplastic alteration of T precursor cells. Although treatment with stringent chemotherapy regimens has achieved an 80% cure rate in children, it has been associated with lower success rates in adult treatment. Silver nanoparticles (Ag-NPs) have a toxic effect on human breast cancer cells, human glioblastoma U251 cells, and chronic myeloid leukemia cells in vitro. This study aimed to investigate the effect of Ag nanostructures (Ag-NSs) on Jurkat cells' viability and apoptosis.

Methods: The Jurkat cell line was acquired. Following the synthesis Ag-NSs and their characterization, they were incubated with Jurkat cells at different doses for 24, 48, and 72 hours to determine the optimal time and dose. Two groups were examined: a control group with Jurkat cells without nanostructure maintained in the same medium as the cells in the treatment group without changing the medium, and a treatment group with cells treated with the Ag nanostructure solution at a dose of 75 µg/ml for 48 hours according to the MTT results. After 48 hours, the cells from the two groups were used for the q RT-PCR of the apoptotic genes (BAX, BCL-2, and CASPASE-3).

Results: According to our results, the rod-shaped silver nanostructures had a size of about 50 nm, increased apoptotic markers, including BAX and CASPASE-3, and induced cell death.

Conclusions: Ag-NSs have anticancer properties and can induce apoptosis of cells; therefore, they may be a potential candidate for the treatment of T-cell acute lymphoblastic leukemia.