ISSN  2587-2362  |  E-ISSN  2618-642X
International Journal of Medical Biochemistry - Int J Med Biochem : 6 (3)
Volume: 6  Issue: 3 - 2023
1.Front Matter 2023-3

Pages I - IX

2.The effect of dysnatremia on prognosis and mortality in critically ill patients with COVID-19
Sinem Bayrakçı, Huseyin Gurbuz, Hülya Çiçek
doi: 10.14744/ijmb.2023.58070  Pages 137 - 142
INTRODUCTION: Sodium disorders, the most common electrolyte disorders in hospitalized patients, are common in hospitalized patients with pneumonia. Numerous studies have shown that sodium abnormalities are independent risk factors for mortality, medical intensive care unit (ICU) admission, and prolonged hospital stay. The aim of the study was to investigate the prevalence of dysnatremia and the effect of dysnatremia on prognosis and mortality in critically ill COVID-19 patients.
METHODS: This retrospective study was performed between June 1, 2021, and July 30, 2021, in COVID-19 ICUs. 149 critically ill, laboratory-confirmed COVID-19 patients admitted to the ICU were included in the study. The collected data included demographic data, comorbidities, severity of illness, and laboratory tests (serum C-reactive protein, lymphocyte, ferritin, sodium, chloride, and potassium levels). The prognosis was evaluated in terms of mortality, need for mechanical ventilation, and length of ICU stay.
RESULTS: At ICU admission, hyponatremia was present in 33 (22.1%) patients, whereas hypernatremia was detected in 14 (9.5%) patients. 102 (68.4%) patients had normal sodium levels. The mortality rate for normonatremic, hyponatremic, and hypernatremic patients was 50.0%, 57.7%, and 78.6%, respectively. These results indicated a statistically significantly higher mortality rate in patients with baseline hypernatremia (p=0.05).
DISCUSSION AND CONCLUSION: Among critically ill COVID-19 patients in the ICU, dysnatremia was common at admission and hyponatremia was more common than hypernatremia. Hypernatremia was related to mortality. Admission sodium levels can be a predictor of mortality in COVID-19 patients who are critically ill.

3.The relationship between ischemia-modified albumin/albumin ratio levels and disease severity in COVID-19 patients
Murat Aksit, Merve Zeytinli Aksit, Musab Kazar, Taner Çalışkan, Suheyla Serin Senger, Harun Akar, Gursel Ersan, Nisel Yilmaz, Banu Isbilen Basok, Ayfer Colak
doi: 10.14744/ijmb.2023.74436  Pages 143 - 149
INTRODUCTION: In COVID-19 infection, oxidative stress occurs with the abnormal release of proinflammatory cytokines and the disruption of the balance between oxidants and antioxidants. In our study, we aimed to investigate the relationship between ischemia-modified albumin (IMA), a biomarker of oxidative stress, and the severity of the disease in hospitalized COVID-19 patients.
METHODS: One hundred and twenty-four hospitalized patients with a diagnosis of COVID-19 were included in the study. These patients were divided into critical and non-critical groups. Serum IMA levels were measured by the colorimetric albumin cobalt-binding method. The IMA-albumin ratio (IMAR) was calculated by dividing IMA values by albumin values.
RESULTS: The IMA and IMAR values of the critical COVID-19 group were statistically significantly higher than the non-critical group. In the multivariate analysis, the two variables IMAR and glucose were found to have the most important role in the severity of COVID-19 disease. For IMAR, the area under the ROC curve had a value of 0.725 (95% confidence interval 0.636–0.803).
DISCUSSION AND CONCLUSION: IMA and IMAR levels of the critical group were found to be higher than the non-critical group in COVID patients. We have observed that IMAR levels are associated with the severity of the disease and that IMAR is an independent prognostic risk factor for the disease.

4.Synthesis of novel iron chelating and heme-interacting acridone derivatives to prevent free heme- and ironmediated protein oxidation
Chinmay Pal
doi: 10.14744/ijmb.2023.47450  Pages 150 - 158
INTRODUCTION: Various diseases are associated with the accumulation of oxidized proteins. In certain pathological conditions, the breakdown of hemoproteins, such as hemoglobin, leads to the formation of heme. Heme possesses pro-oxidant properties, which contribute to oxidative stress, inflammation, and protein degradation. Furthermore, the presence of reduced transition-metal ion Fe2+ can lead to protein degradation and the generation of harmful hydroxyl radicals (•OH). It would be beneficial to develop a substance that can counteract these processes by detoxifying free heme, chelating Fe2+, and exhibiting antioxidant activity through the scavenging of •OH, thereby preventing protein oxidation.
METHODS: Two new acridones, 2-chloroacridin-9(10H)-one (a) and 2-fluoroacridin-9(10H)-one (b), have been synthesized. These compounds have the ability to interact with heme and bind to free iron. The effectiveness of their interaction with heme and their iron-binding properties was assessed through optical Soret spectroscopy. To determine the protective effects of these newly synthesized acridones on protein degradation induced by heme and iron, a standard protein called bovine serum albumin was employed. In addition, the in vitro antioxidant activity of the synthesized compounds was evaluated using two different assays: the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and the ferric reducing antioxidant power assay.
RESULTS: The acridones demonstrated exceptional abilities in chelating iron, interacting with heme, and exhibiting antioxidant activity. The specific substitutions of chlorine and fluorine atoms in synthesized acridones, respectively, differentiate them from other acridones in terms of their distinct electronic, steric, and chemical characteristics that influence their interactions with iron and heme molecules. Moreover, these compounds effectively inhibited protein degradation induced by heme and the production of •OH resulting from the Fenton’s reaction involving Fe(II) and hydrogen peroxide (H2O2).

DISCUSSION AND CONCLUSION: From the above observation, it is evident that, acridones have the potential to treat disorders by preventing the oxidation of proteins by free heme, iron, and •OH.

5.Age-adjusted reference intervals for serum ceruloplasmin levels: Insights from a hospital data based study
Fatma Hande Karpuzoğlu, Parvana Mikailova, Meltem Kilercik, Mustafa Serteser
doi: 10.14744/ijmb.2023.86580  Pages 159 - 164
INTRODUCTION: Ceruloplasmin (Cp), a plasma protein that acts as a copper transporter, plays a crucial role in the screening process for Wilson’s disease. Measuring the serum Cp level serves as the initial step in this screening procedure. However, serum Cp reference limits can vary over age, sex, and using of different measurement methods. In reference interval (RIs) studies, the utilization of hospital data is considered an accepted approach, especially in situations where achieving strict standardization is challenging, such as in pediatric age group. Our study aimed to determine the RIs for Cp levels from 1 to 80 years of age using laboratory data, providing valuable guidance for clinicians and researchers in interpreting Cp test results across different age groups.
METHODS: Forty-seven thousand five hundred and fifty-six (47,544) Cp data points were collected between July 2010 and 2020 from Acıbadem Labmed Laboratories. To determine the RIs, both common RIs and sex-specific RIs were calculated using the Bhattacharya indirect method.
RESULTS: The RIs for serum Cp levels in children are as follows: 1–5 years: 23–48.2 mg/L, 5–10 years: 23–38.2 mg/L, and 10–15 years: 20.5–36.3 mg/L, respectively. For women, the RIs for serum Cp levels are as follows: 15–20 years: 19–33.5 mg/dL, 20–40 years: 19.6–36.8 mg/dL, 40–60 years: 20.4–42 mg/dL, and 60–80 years: 23.5–45 mg/dL, respectively. For male, the RIs for serum Cp levels are as follows: 15–20 years: 17.0–31.3 mg/dL, 20–40 years: 17.8–34.5 mg/dL, 40–60 years: 18.6–38.0, and 60–80 years: 23.0–40.5 mg/dL, respectively.
DISCUSSION AND CONCLUSION: This study has demonstrated a significant and independent association between age and gender concerning Cp concentrations. Although our methodology provided only approximate RIs for Cp, our results emphasize the significance of age adjustment when determining RIs. Taking age and gender into account is crucial for accurately establishing appropriate reference ranges for Cp in clinical settings.

6.The use of new generation small-volume blood collection tubes for complete blood count
Ahmet Erkin Bozdemir, Fatma Demet Arslan, Banu Isbılen Basok, Sukran Copur, Nisel Ozkalay Yilmaz, Harun Akar
doi: 10.14744/ijmb.2023.19042  Pages 165 - 172
INTRODUCTION: Newborns and especially patients with malignancy develop frequently iatrogenic anemia based on phlebotomy. The use of blood collection tubes with small-volume may reduce the need for blood transfusion and the associated risks due to frequent phlebotomy. Therefore, we evaluated the reliability and accuracy of the complete blood count (CBC) using new generation small-volume blood collection tubes (SV-BCT) instead of large-volume blood collection tubes (LV-BCT).
METHODS: Venous blood samples were taken from 40 adult in-patients and collected to SV-BCT/LV-BCT pairs of three different brand (Microtainer®MAP-0.5 ml/Vacutainer®-2.0 ml; Becton, Dickinson and Company, USA) ([Microvette®-0.5 mL/S-Monovette®-2.6 ml; Sarstedt Ag and Co. KG, Germany]) ([MiniCollect®Complete-0.5 ml/Vacuette®-2.0 ml; Greiner Bio-One GmbH, Austria]). All tubes contained K2EDTA except Microvette®. Sixteen parameters of CBC were analyzed using a DxH 800 (Beckman Coulter Inc., USA). CBC results in tube pairs were compared in terms of statistical and clinical (bias%) significance.
RESULTS: There were statistically significant differences between the results of SV-BCT and LV-BCT pairs of the same brands for some parameters. However, bias% between tubes for 16 parameters was within the desirable limits, the differences were not clinically significant.
DISCUSSION AND CONCLUSION: Health personnel and phlebotomists can safely prefer SV-BCT which is a new generation and technically useful for CBC, especially in patients requiring frequent phlebotomy. Thus, the volume of blood sampling may be reduced to prevent iatrogenic blood loss.

7.The importance of anemia in predicting the prognosis of hospitalized COVID-19 patients: A retrospective and single-center study
Ayfer Çolak, Mesut Fidan, Tuba Kansu Altan, Mustafa Terzioğlu, Zeynep Altın, Nilüfer Saygili, İnanç Karakoyun, Nisel Yilmaz
doi: 10.14744/ijmb.2023.48568  Pages 173 - 178
INTRODUCTION: In our study, we aimed to evaluate the importance of anemia in predicting prognosis in hospitalized COVID-19 patients.
METHODS: A total of 340 patients, 110 with anemia and 230 without anemia, were included in the study. Biochemical parameters were compared between groups with and without anemia, and between severe and non-severe COVID-19 patient groups. Binary logistic regression analysis was performed to evaluate the impact of anemia on the prognosis of COVID-19 patients.
RESULTS: In patients with anemia, age, length of hospital stay, neutrophil count, serum glucose, urea, creatinine, C-reactive protein (CRP), ferritin, procalcitonin (PCT), high-sensitivity troponin I, activated partial thromboplastin time (aPTT), prothrombin time (PT), and D-dimer levels were significantly higher. Among the severe and non-severe COVID-19 patient groups, while hemoglobin (hb), hematocrit (ht) and serum calcium levels were significantly lower; PT, serum glucose, urea, creatinine, lactate dehydrogenase (LDH), ferritin, CRP, PCT, and D-dimer levels were signif-icantly higher. In evaluating the prognosis of COVID-19 patients; anemia Odds Ratio (OR) 1.996 (95% confidence interval [CI]: 1.153–3.453, p<0.014), age (OR) 0.033 (95% CI: 1.016–1.058, p<0.001), and CRP level (OR) 1.009 (95%Cl: 1.005–1.013, p<0.001) were found to be independent risk factors.
DISCUSSION AND CONCLUSION: Advanced age and high serum CRP levels, as well as the presence of anemia, are important risk factors for hospitalized COVID-19 patients. Clinicians should consider that anemia may also be a risk factor in the prognosis of patients with COVID-19.

8.Expression of miRNAs in prostate cancer cell lines and prostate epithelial cell lines
Eda Balkan, Merve Aykaç, Aslı Kara, Semin Gedikli
doi: 10.14744/ijmb.2023.26878  Pages 179 - 184
INTRODUCTION: Prostate cancer (PCa) is among the most frequently diagnosed cancers and a leading cause of cancer-re-lated deaths in men. Although prostate-specific antigen (PSA) testing has become routine in screening and early detection, PSA has high false-positive rates and poorly correlates with disease stage. Consequently, other diagnostic and prognostic markers for PCa are urgently needed. MicroRNAs (miRNAs) modulate gene expression at the transcriptional level and are known to play key roles in various physiological events. Growing evidence indicates that miRNA dysregulation is involved in the initiation and progression of many diseases, including PCa. Various miRNAs have been associated with PCa pathogenesis, suggesting that miRNA expression profiles have potential utility in the prognosis, diagnosis, and treatment of this disease. miRNA expression levels have been investigated in prostate epithelial cells by PCa cell culture.
METHODS: The present study compared the expression levels of selected prognostic miRNAs targeting that have been implicated in the pathogenesis of PCa. Using cDNA obtained from the C4-2 human PCa and PNT1a normal prostate epithelial cell lines, miRNA expression levels were quantitatively analyzed via melting curve analysis using the miScript SYBR Green kit in a Rotor-Gene Q real-time polymerase chain reaction (PCR) device.
RESULTS: Reverse transcription quantitative PCR analyses have demonstrated miRNA expression levels in the C4-2 PCa cell line and PNT1a prostate epithelial cell line. MiR-125, -145, -200, and -222 were found to be overexpressed in the PCa cell line (p<0.05), while there were no statistically significant differences in miR-32 expression of miR-21, -26, Let-7, -34, or -221 between PCa cells and PNT1a cells (p>0.05).
DISCUSSION AND CONCLUSION: Considering the variation in expression level of miRNAs targeting genes responsible for the etiopathogenesis of PCa. Provides information on the use of miRNAs as prognostic markers in PCa.

9.The changes of oxidative stress markers and vitamin E in patients with diabetes using SGLT2 inhibitors
Banu Buyukaydin, Omer Faruk Ozer, Aclan Ozder, Caner Yildiz
doi: 10.14744/ijmb.2023.20053  Pages 185 - 190
INTRODUCTION: This study aimed to research the diversities of vitamin E and oxidative stress parameters related to sodiumglucose transport protein 2 (SGLT2) inhibitor use by type 2 diabetes mellitus (T2DM) patients.
METHODS: This observational clinical study collected data from 67 T2DM patients (55.7±9.3 years, 46% female). Vitamin E, total oxidant status (TOS), total antioxidant status (TAS), total thiol, native thiol, myeloperoxidase, and catalase levels were evaluated. The TOS/TAS ratio was calculated as the oxidative stress index. Correlations of the parameters to each other and differences based on SGLT2 inhibitor use were recorded.
RESULTS: The mean hemoglobin A1c was 7.1 (5.5–13.1). SGLT2 inhibitors (all combinations) were used by 25 patients (37.3%). The mean level of vitamin E was 6 (3.6–9.8) mg/L. There was a positive correlation between vitamin E and low-density lipoprotein cholesterol (p<0.001). While there was no significant correlation between vitamin E and all included oxidative stress parameters, the level of vitamin E was statistically lower in patients using pioglitazone (p=0.036) and statins (p<0.001). In patients using SGLT2 inhibitors, fasting glucose, triglycerides, alanine aminotransferase, and the spot urine protein/creatinine ratio were significantly lower, and the mean TAS was higher (p<0.05).
DISCUSSION AND CONCLUSION: While no differences were observed in vitamin E and other oxidative parameters related to SGLT2 inhibitor use, the increase in TAS provides motivation for further research investigating the antioxidant properties of these inhibitors.

10.Identifying miRNAs associated with amyotrophic lateral sclerosis and mitochondrial dysfunction through bioinformatics approaches
Gülçin Baykal, Burçin Erkal, Senay Vural Korkut
doi: 10.14744/ijmb.2023.43043  Pages 191 - 205
INTRODUCTION: MicroRNAs (miRNAs) are non-coding RNA molecules that control gene expression by causing messenger RNA to degrade after transcription. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that involves the gradual deterioration and death of motor neurons, resulting in muscle weakness, paralysis, and eventual fatality. A prominent feature of ALS is the presence of mitochondrial dysfunction. The identification of miRNAs associated with mitochondrial dysfunction in ALS through in silico approaches can offer valuable insights into underlying processes and targets for therapeutic interventions.
METHODS: Computational tools and publicly available databases were employed for the purpose of identifying specific miRNAs that could potentially play a role in the onset or progression of mitochondrial dysfunction in ALS.
RESULTS: A review of the literature revealed that the genes SOD1, coiled-coil-helix-coiled-coil-helix domain-contain-ing protein 10, C9orf72, OPTN, valosin-containing protein, TARDBP, TBK1, FUS, and BCL2 are linked to mitochondrial dysfunction and are involved in the etiology of ALS. Enrichment analyses of biological pathways performed with the computational tools Enrichr, g: Profiler, and CROssBAR confirmed that the discovered genes are strongly related to ALS, mitochondrial failure, and differentiation of neurons. Furthermore, miRNA computational predictions were per-formed utilizing the publicly available databases miRTargetLink, miRNet, miRWalk, and TargetScan. To identify common miRNAs, a Venn diagram was used, and 28 miRNAs were selected as a result. For further analysis, a set of 28 miRNAs was subjected to functional and enrichment studies using the computational programs miRNet and TAM, respectively. Results from both computational programs consistently revealed that the miRNAs hsa-miR-125b, hsa-miR-9-5p, and hsa-miR-141-3p were related to ALS.
DISCUSSION AND CONCLUSION: We proved that in silico approaches projected the effects of miR-9, miR-141, and miR-125b targeting the identified genes on ALS, and we demonstrated that the genes involved in mitochondrial dysfunction in ALS are based on the literature.

11.Fibrinogen interference mimicking monoclonal band in serum protein electrophoresis of hemodialysis patient
Eda Boztosun, Ayca Inci, Hamit Yasar Ellidag
doi: 10.14744/ijmb.2023.36693  Pages 206 - 209
Serum protein electrophoresis (SPE) is an important laboratory technique in the diagnosis of multiple myeloma. Analytical interference affects SPE as well as many other laboratory methods. Here, we have presented the fibrinogen interference that mimics the monoclonal band in the SPE in the sample sent in the gel biochemistry tube. A female patient presented to the emergency department with abdominal pain, nausea, and decreased urine output. In patients with high serum creatinine and blood urea nitrogen levels, a complete blood count has been found to be compatible with the presence of pancytopenia. Although an abnormal band similar to the M-spike protein was observed in the β/γ-region on the SPE evaluation, no monoclonal immunoglobulin was found in immunofixation electrophoresis. It was assured that the sample sent for SPE was collected in the correct tube (gel biochemistry tube). It was noted that the patient was receiving hemodialysis treatment while the sample was sent for SPE. It was considered that the specimen of the patient was contaminated with heparin. To test this theory, we added 1 ml of heparin to 5 ml of blood taken from a healthy subject in a gel biochemistry tube. Similarly, we observed that a band formed between the beta-gamma region in the SPE. Interferences are one of the most important causes of laboratory errors. Because they can have clinically important consequences such as misdiagnosis and treatment, laboratory specialists need to recognize these interferences and inform clinicians about them.

12.Cellular and molecular mechanisms that underlies the formation of atherosclerotic plaque and plaque rupture-review
Yiglet Mebrat
doi: 10.14744/ijmb.2023.78309  Pages 210 - 222
Atherosclerosis (AS) is the main risk factor for CVD and manifested by lipid accumulation, extracellular matrix protein deposition, and calcification in the intima and media of the large to medium size arteries promoting arterial stiffness and reduction of elasticity. It is initiated by endothelium activation and, followed by a cascade of events (accumulation of lipids, fibrous elements, and calcification), triggers the vessel narrowing and activation of inflammatory pathways. This review focuses on the different stages of AS development, ranging from endothelial dysfunction to plaque rupture and the role of genetic abnormalities in AS development. In addition, the correlation of monocyte recruitment and atherogenesis, cytokine involvement with the role of phagocytosis in AS, fundamental signaling pathways in multiple stages of AS, and genetics of AS and the molecular mechanisms of plaque rupture and cap formation are covered here to provide a global view of the disease.

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