ISSN  2587-2362  |  E-ISSN  2618-642X
International Journal of Medical Biochemistry - Int J Med Biochem : 7 (1)
Volume: 7  Issue: 1 - 2024
1.Front Matter

Pages I - X

2.The relationship between serum vitamin D levels and hematological inflammatory indices in patients with heart failure
Yasemin Ustundag, Canan Demir, Mehmet Demir, Kagan Huysal, Meryem Rumeysa Yesil, Muhammed Said Karaca
doi: 10.14744/ijmb.2023.71501  Pages 1 - 5
INTRODUCTION: Recent studies have suggested that chronic systemic inflammation increases the risk of development and progression of heart failure (HF). Vitamin D may contribute to the pathogenesis of HF by modulating inflammatory pathways. Changes in brain natriuretic peptide (BNP) levels are critical for the diagnosis and assessment of HF severity. We aimed to investigate the association between serum vitamin D levels, BNP, and novel hematological systemic inflammation indices in chronic heart failure (CHF) patients.
METHODS: In this retrospective study, we report data from 187 participants admitted to the outpatient clinic, with 85 CHF and 102 without CHF (control group). Vitamin D, BNP, and complete blood cell samples were analyzed. Novel hematological systemic inflammation indices—the systemic immune-inflammation index (SII; neutrophil × platelet / lymphocyte), the systemic inflammation response index (SIRI; neutrophil count × monocyte/lymphocyte count), the pan-immune-inflammation value (PIV; neutrophil count × platelet count × monocyte count)/lymphocyte count, monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR)—were calculated
RESULTS: Binomial logistic regression showed that only MLR was significantly associated with CHF (P < 0.001). A weak, negative, and statistically significant correlation was found between BNP and vitamin D (r=-0.185, p=0.011) levels. There was a weak negative correlation between vitamin D and PLR (r=-0.196, p=0.007), PIV (r=-0.145, p=0.048), and SIRI (r=-0.156, p=0.033).
DISCUSSION AND CONCLUSION: An independent association between systemic hematological inflammatory indicators and vitamin D with the severity of CHF expressed by elevated BNP levels was revealed.

3.Effect of dapagliflozin on oxidative stress in heart embryonic H9c2 cardiomyocytes
Zeki Doğan, Hafize Uzun
doi: 10.14744/ijmb.2024.49368  Pages 6 - 12
INTRODUCTION: Dapagliflozin is a drug used to treat type 2 diabetes and is also used in certain heart failure and chronic kidney disease conditions. In this study, we investigated the effects of dapagliflozin (DAPA) on malondialdehyde (MDA), lipid hydroperoxide (LOOH), superoxide dismutase (SOD), total thiol (T-SH), and total antioxidant capacity (TAC) as oxidative stress parameters in heart embryonic H9c2 cardiomyocytes.
METHODS: H9c2 cardiomyocyte cells were treated with methotrexate (MTX) (10-0.160 μM) and DAPA (10-0.150 µM). The cell viability and oxidative stress parameters were measured.
RESULTS: MDA and LOOH levels were significantly lower in the control (p<0.001 for both) and DAPA groups (p<0.001; p<0.05, respectively) compared to the MTX groups, while SOD (p<0.001 for both), T-SH (p<0.001; p<0.01, respectively), and TAC (p<0.01; p<0.05, respectively) were significantly higher in the control and DAPA groups compared to the MTX groups. There was no significant difference between the control and DAPA groups in other parameters except for MDA. However, MDA levels were significantly higher in the DAPA group (p<0.05) compared to the control group. The decrease in MDA levels was significantly correlated with the increase in SOD activity (r: -0.814; p: 0.014) in the DAPA treatment group.
DISCUSSION AND CONCLUSION: Cell viability increased, and the levels of MDA and LOOH decreased, while the SOD, T-SH, and TAC levels increased in H9c2 cardiomyocytes induced by oxidative stress. The findings obtained in this study suggest that DAPA may have beneficial effects in cardiomyopathy caused by oxidative stress.

4.EZH2 gene and CA-IX prompt relation: An effective therapeutic target approach for melanoma progression
Ozen Ozensoy Guler, Beyza Ecem Oz Bedir, Emine Terzi
doi: 10.14744/ijmb.2023.19970  Pages 13 - 17
INTRODUCTION: Melanoma is a common type of skin cancer originating from melanocytes. Its standard treatments include surgery, chemotherapy, radiotherapy, and targeted therapy. However, due to limitations in drug treatments, new targets must be identified. One important enzyme in carcinogenesis, CA-IX, creates an acidic and hypoxic niche within tumor cells. Additionally, EZH2, a gene that encodes a histone-lysine N-methyltransferase, is involved in DNA methylation and plays a crucial role in cancer development by modulating epigenetic changes. In this study, our goal is to elucidate the effect of CA-IX inhibition on the EZH2 gene in melanoma.
METHODS: We evaluated the effects of CA-IX inhibition with AZA on EZH2 gene expression levels in the A375 human melanoma cell line. Cell culture, ELISA, and qPCR experiments were conducted. The cytotoxic activities of AZA were assessed using the WST-1 assay. CA-IX protein levels were measured using a Human Carbonic Anhydrase IX ELISA Kit. qPCR was performed using the QuantiNova LNA Probe PCR assay.
RESULTS: An IC50 value was observed at a concentration of 10.7 μM for AZA in the WST-1 assay. Decreased CA-IX protein levels were observed following AZA treatment (p<0.0001). Additionally, EZH2 mRNA levels were significantly reduced when CA-IX protein was inhibited by AZA (p<0.05).
DISCUSSION AND CONCLUSION: Inhibition of CA-IX and the consequent changes in the acidity of the tumor microenvironment may modulate EZH2 levels. CA-IX could be a promising target for the epigenetic treatment of melanoma.

5.The association of serum proprotein convertase furin/PCSK3 concentrations with stable coronary artery disease and coroner artery lesion severity
Fulya Balaban Yücesan, Asim Orem, Cihan Orem, Abdulselam Ilter, Serap Ozer Yaman, Hüseyin Yaman, Buket Akcan, Tugba Mazlum Sen
doi: 10.14744/ijmb.2023.09326  Pages 18 - 25
INTRODUCTION: Furin (Proprotein Convertase Subtilisin/Kexin Type 3, PCSK3) is a proprotein convertase involved in the processing of precursor proteins. Furin substrates play significant roles in the initiation and progression of atherosclerosis, which is the primary cause of coronary artery disease (CAD). This study aimed to investigate the serum furin concentrations in stable CAD patients and their relationship with disease severity.
METHODS: The study included 81 stable CAD patients and 50 subjects without coronary artery lesions. Coronary angiography was performed via the percutaneous femoral artery approach, and the severity of CAD was assessed using the Gensini score. Serum furin concentrations were measured using an enzyme-linked immunosorbent assay.
RESULTS: Serum furin concentrations were significantly higher in CAD patients compared to CAD-negative subjects (p=0.0001). The serum furin levels of mild, moderate, and severe CAD patients were 1.53 ng/mL, 2.01 ng/mL, and 3.03 ng/mL, respectively, which were significantly different from CAD-negative subjects (p=0.018, p=0.002, and p=0.0001, respectively). Furin levels were found to be an independent predictor of CAD and exhibited potential diagnostic value for CAD and severe CAD.
DISCUSSION AND CONCLUSION: The study concluded that serum furin concentrations could be considered a new risk factor for CAD, in addition to well-known biomarkers.

6.Biomarkers of a Football Match-play - Internal load analysis using Technical Soccer Specific Aerobic Field Test (TSAFT90)
Janani Gopalakrishnan, Kaveen Dharanirajan, Zanetta Petra Brewart, Santhi Silambanan, Thiagarajan Alwar, Arumugam Sivaraman
doi: 10.14744/ijmb.2023.48278  Pages 26 - 32
INTRODUCTION: The study measured the magnitude of physiological, immune, endocrine, and muscle damage markers of exercise-induced fatigue using the Technical Soccer Specific Aerobic Field Test (TSAFT90). We examined the effect of fatigue on performance and recovery at 24 hours post-exercise using biochemical indices.
METHODS: Professional football players (n=30) with a mean age of 19.20 years participated in the study during their preseason. To induce fatigue, participants underwent a 90-minute fatigue simulation program, TSAFT90. Venous blood samples were collected at baseline, 0-hour, and 24 hours post-fatigue. Analyzed markers included fatigue metabolites (lactate and uric acid), endocrine response marker (cortisol), muscle damage marker (creatine kinase), immunological markers (leukocytes, lymphocytes, neutrophils, and monocytes), inflammatory marker (CRP), hydration indicator (serum osmolality), and recovery marker (magnesium). Ball velocity and a 7-point Likert scale for muscle soreness were recorded to assess performance and perception of fatigue, respectively.
RESULTS: All biomarkers studied were significantly elevated (p<0.05) at 0 hours post-fatigue. Uric acid, creatine kinase, leukocytes, monocytes, CRP, serum osmolality, and magnesium remained altered at 24 hours. Ball velocity significantly reduced post-fatigue (p=0.04) from 94.67 km/hr to 90.47 km/hr, whereas there was no change in the soreness scale.
DISCUSSION AND CONCLUSION: The failure of the biomarkers to return to baseline levels within 24 hours indicates disrupted homeostasis. Monitoring the internal load with biomarkers aids in formulating strategies that can delay or mitigate fatigue and help achieve optimal performance and recovery, thus reducing the likelihood of injury.

7.Exploratory role of serum FGF-8 as a marker of bone metastasis in tumor progression
Gurpreet Singh Gill, Meenakshi Kaushik, Simmi Kharb, Gitanjali Goyal, Uttam Malik
doi: 10.14744/ijmb.2023.36002  Pages 33 - 40
INTRODUCTION: FGF-8, a member of the FGF family, plays a crucial role in cellular processes and has been implicated in cancer progression. The study aims to comprehend FGF-8's involvement in bone metastasis, emphasizing its potential as a diagnostic marker and focusing on its association with Bone-Alkaline Phosphatase (B-ALP) and other biochemical parameters.
METHODS: The case-control study spans 12 months, involving 60 participants, including 30 with secondary bone metastases and an equal number without metastasis. FGF-8 levels were quantified using ELISA, and B-ALP, serum ALP, and various biochemical parameters were assessed. The study employed standardized procedures to minimize bias, including matching cases and controls, and obtaining ethical approval.
RESULTS: In patients with bone metastasis, serum ALP levels, particularly B-ALP, were significantly higher. The metastatic group exhibited elevated FGF-8 concentrations, showcasing a positive correlation with B-ALP and serum calcium levels. The study successfully differentiated ALP isoenzymes through heat inactivation and L-phenylalanine inhibition. Additionally, serum calcium levels were markedly elevated in the metastatic group.
DISCUSSION AND CONCLUSION: The findings suggest that FGF-8 is a potential diagnostic marker for bone metastasis, particularly in breast and prostate cancers. Elevated FGF-8 levels correlate with increased B-ALP and serum calcium, indicating its role in osteoblastic differentiation in metastasis. The study proposes the utility of ELISA-based kits for FGF-8 in serum as a practical and efficient method for assessing bone tumor progression.

8.Unmeasurable HbA1c result due to hemoglobinopathy
Ayşe Aktas, Belkiz Öngen Ipek, Okan Dikker
doi: 10.14744/ijmb.2023.59480  Pages 41 - 44
The aim of this study was to show the interference caused by hemoglobinopathy in the measurement of hemoglobin A1c (HbA1c). In our case presentation, we reported two patients whose HbA1c values were unmeasurable when using our laboratory's cation exchange chromatography. We detected HbSβ+ and HbSC variants by remeasuring the samples with another chromatography instrument. Measurement of HbA1c is a commonly performed procedure for the diagnosis of diabetes and for the assessment of blood glucose control in patients with diabetes. However, various hemoglobinopathies, chronic kidney disease, and abnormalities in red cell turnover rate may interfere with HbA1c quantification.

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