Reports of Biochemistry and Molecular Biology最新文献

Background: Congenital heart defects (CHD) are recognized as the most common heart abnormalities amongst newborns and children, and atrial septal defect (ASD) is recognized as one of the most frequent forms of CHD. Prior studies indicated that the methylenetetrahydrofolate reductase (MTHFR) gene contributes to the etiology of CHD. Therefore, we designed a case-control study to assess the possible role of the MTHFR gene, specifically the C677T (rs1801133) and A1298C (rs1801131) polymorphisms within the Iranian ASD population sample.

Methods: A total of 166 subjects (81 children diagnosed with ASD and 85 control participants) were enrolled in this research. Samples genotyped for MTHFR rs1801133 and rs1801131 polymorphisms using the PCR-RFLP and ARMS-PCR approaches.

Results: Our results indicated that rs1801131 variant reduced the risk of ASD in codominant (OR [95%CI]: 0.41[0.21-0.83], P=0.012), dominant (OR[95%CI]: 0.48 [0.25-0.93], p=0.028) and overdominant (OR[95%CI]: 0.44 [0.23-0.81], P=0.009) models. Moreover, rs1801133 variant increased the risk of ASD in codominant (OR[95%CI]: 2.68[1.39-5.16], P = 0.003), dominant (OR [95% CI]: 2.72 [1.43-5.14], P = 0.002), overdominant (OR [95% CI]: 2.50 [1.31-4.78], P = 0.005), and allelic (OR [95% CI]: 2.16 [1.27-3.69], P = 0.004) models.

Conclusions: Our findings suggest that MTHFR rs1801133 and rs1801131 variants may potentially affect the onset of ASD.

Background: Type 2 diabetes mellitus (T2DM) poses a significant public health challenge due to its high prevalence. Diabetic nephropathy (DN) is one of the most severe complications associated with T2DM. Early prediction of DN in patients with T2DM can significantly aid in managing this disease. This study takes an approach by investigating the potential role of melatonin and thyroid hormone levels as predictive biomarkers for the progression of diabetic nephropathy in individuals diagnosed with type 2 diabetes mellitus.

Methods: Our cross-sectional study involved 120 male participants, divided into two groups: 60 patients with T2DM and 60 with DN. The Cobas technique was used to measure serum thyroid hormone levels and quantified melatonin levels using an enzyme-linked immunosorbent assay (ELISA). A receiver utilizing characteristic (ROC) curve analysis to evaluate the predictive value of serum melatonin for DN was performed.

Results: No notable disparities in thyroid function tests were observed between diabetic patients with and without DN. However, the average serum melatonin quantity in patients with DN. (177.25 ± 60.48 pg/mL) was drastically lower in those with T2DM without DN (199.9 ± 55.16 pg/mL). The sensitivity and specificity of melatonin in predicting DN were 78% and 76%, respectively, with an optimal cut-off value of 178 pg/mL.

Conclusions: Serum melatonin levels exhibited a notable reduction. among individuals who were diabetic with DN, suggesting its potential utility as an additional predictive marker for developing DN in patients with T2DM.

Background: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune condition that can lead to long-term complications due to oxidative stress and metabolic dysregulation. Paraoxonase-1 (PON-1), an enzyme associated with high-density lipoprotein (HDL), has dual activities: arylesterase and lactonase. These activities protect lipids from oxidative damage. The functional status of PON-1 in children with T1DM may provide insights into the relationship between oxidative stress and the enzyme's protective role. This study aims to assess the arylesterase and lactonase activities of PON-1 in Iraqi children with T1DM.

Methods: Sixty-seven children with T1DM were enrolled and compared with 57 age-matched healthy controls. The enzymatic activities of arylesterase and lactonase were measured to evaluate PON-1's functional status. The Paraoxonase-1/HDL (PON/HDL) ratio was calculated to assess lipid protection and antioxidant capacity. Oxidative status was assessed by measuring total oxidative status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI).

Results: PON-1 activity analysis showed a significant reduction in arylesterase (2.36 ± 1.17) and lactonase (21.9 ± 7.31) in the patients group compared to controls (arylesterase=4.54 ± 1.84, lactonase =29.51 ± 9.92). TOS and OSI were significantly higher, while TAS was significantly lower in the patients group. Pearson correlation revealed a positive correlation between HDL-C and arylesterase (P = 0.002, r = 0.379), and HDL-C and lactonase (P = 0.040, r = 0.366).

Conclusions: Reduced PON-1 activity is associated with T1DM, suggesting that enhancing PON-1 or reducing oxidative stress may help prevent diabetic complications and improve cardiovascular health.

Background: Fusobacterium nucleatum (F. nucleatum) is known to increase in number under hyperglycemic conditions, as it is thought to utilize glucose as a nutrient source. The process of glucose utilization in bacteria occurs with the assistance of enzymatic proteins such as glucokinase. This study aims to investigate the glucose utilization by F. nucleatum ATCC 25586 by examining its growth in glucose-enriched media and its relationship with protein activity through FTIR analysis.

Methods: F. nucleatum ATCC 25586 was cultured in media enriched with 2%, 1%, 0.75%, 0.5%, and 0.25% glucose. Its growth was measured using a spectrophotometer, and protein activity was assessed with FTIR at 24 and 48 hours of incubation.

Results: The results showed that F. nucleatum could utilize glucose as a nutrient source, indicated by growth and protein activity. The maximum growth of F. nucleatum occurred at a 0.75% glucose concentration at 24 hours. However, the Kruskal-Wallis test showed no significant differences in the growth and protein activity of F. nucleatum across the five glucose concentrations (growth, p =0.271 and protein, p =0.149). Spearman correlation analysis indicated no correlation between the growth and protein activity of F. nucleatum (p=0.323). The protein activity of F. nucleatum remained stable across various growth levels.

Conclusions: It can be concluded that glucose could influence the growth of F. nucleatum, although the growth and protein activity of the bacteria did not differ significantly based on glucose concentration. F. nucleatum grown in various glucose concentrations exhibits stable protein activity.

Background: The green synthesis of nanoparticles through algae-mediated processes offers an eco-friendly, cost-effective, and scalable approach for producing nanomaterials with potential applications in cancer therapy. The present study investigated the algae-mediated green synthesis of dextran-coated titanium oxide nanoparticles (TiO₂NPs) and evaluated their cytotoxic effects against MCF-7 breast cancer cells.

Methods: Chlorella vulgaris was isolated and identified. The polymerase chain reaction (PCR)-amplification of the 18S ribosomal RNA gene was used to confirm the isolate. Dextran from C. vulgaris was used to prepare coated TiO₂NPs), characterized using three techniques. The cytotoxicity of the dextran-coated TiO2NPs was evaluated using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay on MCF7- breast cancer cells at various concentrations (25, 50, and 75%) and exposure times (24, 48, and 72 hours). The bioactive compounds in the algal extract were also identified by gas chromatography-mass spectrometry (GC-MS).

Results: Chlorella vulgaris was successfully isolated as confirmed by the 345-bp PCR-amplified fragment. The characterization of the TiO₂NPs confirmed the successful nanoparticle formation. A cluster of nanocrystalline particles had an average diameter of 71.44 nm. Compositional analysis revealed 15.85% atomic percentage for titanium. The dextran-coated TiO2NPs exhibited an impressive cytotoxicity rate of up to 99% at optimal concentration (25%) and exposure time (48 hours). Additionally, GC-MS analysis identified bioactive compounds in the algal extract, such as fatty acids, which may contribute to the observed anticancer effects.

Conclusions: The study demonstrated the potential of algae-mediated TiO₂NPs in cancer co-therapy, enhancing treatment effectiveness and reducing the side effects of traditional therapies.

Background: Hepatocellular carcinoma (HCC) is one of the lethal malignancies with a poor prognosis due to metastatic complications. Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), have an important role in metastasis. MicroRNA-21 (miR-21) is significantly overexpressed in nearly all types of human cancers, including HCC. Targeting miR-21 pharmacologically could be a promising therapeutic approach for HCC. 3,4-dihydroxyphenylethanol (DHPE), a phenolic phytochemical compound found in olive, has potent antioxidant and anticancer properties. This study aimed to investigate the effect of DHPE on the expression of miR-21 with genes associated with metastasis (MMP-2, MMP-9, TIMP-1, and TIMP-2) and their correlation with miR-21 in HepG2 cells.

Methods: This experimental study had four groups, including a control, and three groups of treatment with different concentrations of DHPE (50, 100, and 150 µM) for 24 hours. The expression levels of genes were determined by RT-qPCR.

Results: The results showed that the treatment of cells with DHPE significantly reduced the expression of miR-21, MMP-2, MMP-9, and TIMP-1 but increased TIMP-2 compared to the control group; additionally, there was a negative correlation between miR-21 and TIMP-2 but a positive correlation between miR-21 with MMP-2, MMP-9, and TIMP-1.

Conclusions: The results showed that DHPE, likely by reducing the expression of miR-21, can increase TIMP-2 and reduce MMP-2, MMP-9, and TIMP-1 gene expression and may play a role in inhibiting cell migration in HepG2 cells.

Background: The important role of SMAD6 and several microRNAs (miRNAs), such as miR-17-5p, miR-26b-5p, and miR-32-5p, has been demonstrated in controlling the proliferation and differentiation of cardiomyocytes (CMs). Hence, this study was designed to assess the role of these regulatory factors in cardiac cell generation from human endometrium-derived mesenchymal stem cells (hEMSCs).

Methods: To induce transdifferentiation into CMs, hEMSCs were treated with a cardiac-inducing medium containing 5-azacytidine and bFGF for 30 days. Immunofluorescence staining and qRT-PCR, respectively, were used to measure the protein levels of SMAD6 and the mRNA expression of SMAD6 and the three miRNAs every six days.

Results: Our findings demonstrated the mesenchymal stem cell properties of hEMSCs and their ability to differentiate into various types of mesenchymal stem cells. The differentiated hEMSCs exhibited morphological features resembling CMs. During the induction period, the number of positive cells for SMAD6 protein and the expression level of miR-26b-5p increased and peaking on days 24 and 30, while the expression levels of miR-17-5p and miR-32-5p decreased. The Pearson correlation coefficients revealed that SMAD6 level is inversely correlated with miR-17-5p and miR-32-5p and directly correlated with miR-26b-5p.

Conclusions: Our results indicate that miR-17-5p, miR-26b-5p, miR-32-5p, and SMAD6 are potentially involved in the molecular signaling pathways of transdifferentiation of hEMSCs to CMs.

Background: Pre-eclampsia (PE) is a severe pregnancy condition with genetic and environmental factors affecting the placental function and vascular changes. Genetic variants in the apelinergic system may influence preeclampsia risk and birth outcomes. Therefore, this study aimed to compare apelin (APLN) rs56204867 and apelin receptor (APLNR) rs11544374 gene polymorphisms and to investigate their association with mothers' body mass index and infant's birth weight among women with preeclampsia and control group in southeast Iran.

Methods: A total of 123 PE patients and 125 age- and gender-matched control subjects were enrolled in the study. The PCR-RFLP method was employed to genotype the APLN rs56204867 and APLNR rs11544374 gene polymorphisms.

Results: There was no significant association between the genotypes of the rs11544374 variant and the PE risk. The incidence of the AG genotype of the rs54204867 variant in the control group was considerably greater than in the PE group. Also, a significant relationship was found between the body mass profile of patients with PE and the APLN rs54204867 gene polymorphism.

Conclusions: It was observed that the APLN rs54204867 gene polymorphism could affect the PE risk. No significant difference was found between the PE group and the control group in terms of the genotypes of the APLNR rs11544374 variant. It was not statistically significant between mothers' BMI and rs11544374 of the APLNR gene, whereas an obvious link was observed between mothers' BMI and rs54204867 of the APLN gene.

Background: Graves' disease (GD) is the most frequent reason for hyperthyroidism, which is brought on by an excess of thyroid hormone and a form of autoimmune thyroid disease (AITD). Patients with GD have higher levels of thyroid receptor antibody (TRAb). The current study, investigates the impact of excessive thyroid hormone production on glucose and cholesterol metabolism in thyroid disorders, particularly focusing on GD.

Methods: This study included 96 subjects (32 GD patients, 32 from non-autoimmune hyperthyroidism and 32 from healthy controls). All samples were obtained from Al-Kadhimiya Teaching Hospital (Baghdad) for the period between September 2023 and January 2024.

Results: The results revealed that mean± SD values of FT3 and FT4 for GD patients were significantly higher (P<0.001) accompanied by a significant decrease in mean±SD values of TSH (P<0.001) when compared to non-autoimmune hyperthyroidism and control groups. Conversely, TC and glucose levels did not show significant variations among GD patients, the non-immune hyperthyroidism and control groups (P > 0.05).

Conclusions: Our findings indicated thyroid function analysis is crucial for the diagnosis and differentiation of GD, TC and glucose levels do not contribute additional discriminatory power.

Background: Timely treatment actions are critical for the early detection of sepsis in patients at high risk of acute kidney injury (AKI). This study aimed to investigate inflammatory biomarkers as potential predictors of AKI in patients with sepsis.

Methods: This prospective observational cohort study included 300 patients who received treatment in the Intensive Care Unit (ICU) of hospitals located in Padang, Indonesia. We obtained blood samples to evaluate inflammatory biomarkers, such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and procalcitonin (PCT). AKI development was predicted using multivariate logistic regression analysis to identify independent inflammatory biomarkers.

Results: IL-6, TNF-α, and PCT levels were markedly elevated in patients who developed AKI compared with those who did not (p < 0.001). The multivariable logistic regression analysis showed that IL-6 (OR = 1.82; 95% CI = 1.25-2.66; p = 0.002) and PCT (OR = 2.45; 95% CI = 1.58-3.80; p < 0.001) can both predict the development of AKI in patients with sepsis. The area under the curve (AUC) for IL-6 was 0.70, whereas the AUC for PCT was 0.81. These findings demonstrate that IL-6 and PCT exhibit strong predictive abilities for the onset of AKI in patients with sepsis. The ideal threshold values for IL-6 and PCT were 12.91 pg/mL and 1.79 ng/mL, respectively.

Conclusions: IL-6 and PCT can serve as inflammatory biomarkers for predicting the occurrence of AKI in patients with sepsis.