Clinical Biochemistry

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    STATINS INHIBITS GROWTH AND METASTASIS OF MELANOMA THROUGH MIR-126/MMP-9
    (An-Najah National University, 2024-11-03) Nasser, Rasha
    Background: Melanoma is the deadliest type of skin cancer, with morbidity and mortality rates increasing globally. Melanoma has an elevated metastatic potential, leading to limited response to the available treatments in addition to poor prognosis. The transcription factor (NF-κB) for nuclear factor kappa B has been up-regulated in melanoma cases. Simvastatin has anticancer properties that can act as a repurposed drug for treating melanoma. Recognizing the signaling pathway and the anti-tumor properties of simvastatin is essential in discovering new kinds of tumors that might be intended by simvastatin. MicroRNA-126 is a significant microRNA family member; recent studies demonstrate its role in cancer as a new tumor suppressor gene because it can stop cancer cells from growing, migrating, and invading by suppressing important oncogenes like matrix metallopeptidase 9 (MMP9). Here, we inspected how simvastatin can affect melanoma growth, tumor cell migration, and angiogenesis. Mechanically, Simvastatin blocks the transcription factor NF-κB, which up-regulates MIR-126 and, therefore, down-regulates the expression of MMP9 as an oncogene of melanoma cancer responsible for cell proliferation, migration, and angiogenesis. Aims: Eliminating melanoma from our lives is our objective. The only way to accomplish this is through study, and it is pretty bold and huge. We propose that, rather than finding a new drug, it would be better to use an existing one to prevent growth and metastasis so that we can investigate the impact of statin drug on melanoma growth and metastasis using an innovative approach. This goal is supported by our unique research technique, which describes how we use the newest ideas to advance the discovery of a new treatment for melanoma. Methods: we use Simvastatin to block the transcription factor NF-κB, which then regulates the expression of MIR-126. Therefore, this micro-RNA inhibits the expression of MMP9 as an oncogene of melanoma cancer, responsible for cell proliferation, migration, angiogenesis, and metastasis. Results: The results of the study demonstrate that simvastatin, via inhibiting the transcription factor NFκB; can influence the growth and spread of melanoma cancer at even low concentrations (5µM). In conclusion: Through downregulation of the transcription factor NFκB, which restores the production of miR-126 that targets the MMP-9 mRNA, simvastatin possesses anti-proliferative characteristics that limit the growth and metastasis of the B16F10 melanoma cell line dependent on dosage and time approach.
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    CD44 EXPRESSION LEVELS AS A BIOMARKER FOR THE EARLY DETECTION OF VARIOUS CANCERS IN BIOLOGICAL SAMPLES: A CASE- CONTROL STUDY
    (An-Najah National University, 2025-02-06) Bsharat, Samah
    BACKGROUND: Cancer stem cells (CSCs) contribute to tumor progression, metastasis, and therapy resistance, with CD44 playing a key role in CSC function. As a transmembrane glycoprotein, CD44 interacts with ligands like hyaluronic acid, regulating adhesion, migration, and signaling pathways (Ras-MAPK/ERK). Its alternative splicing and modifications enhance functional diversity, promoting chemoresistance and metastasis. Elevated CD44 expression in aggressive cancers, including breast and colorectal malignancies, highlights its potential as a diagnostic biomarker and therapeutic target. Given its role in tumor progression, this study aims to evaluate soluble CD44 as a biomarker for the early detection and differentiation of breast and colorectal cancer. By analyzing its expression levels in blood and urine across different cancer stages and types, this research seeks to establish CD44’s diagnostic value and potential contribution to precision medicine in oncology. METHODS: This case-control study (2023–2024) examined CD44 expression as a biomarker for breast cancer (BC) and colorectal cancer (CRC) at three hospitals in Nablus, including 40 BC patients, 23 CRC patients, and 70 healthy controls. Blood and urine samples were analyzed for CD44 gene and soluble forms, with exosomal RNA quantified via real-time PCR (normalized to GAPDH) and soluble CD44 levels measured using ELISA. Statistical analyses (two-way ANOVA, t-tests, p ≤ 0.05) confirmed significant differences, ensuring accuracy through standardized protocols. RESULTS: The research indicates a very strong statistically significant elevation in CD44 expression in breast cancer patients when compared to healthy controls (p < 0.0001) in both fold change (gene expression) and soluble CD44 (sCD44) serum and urine concentrations. Similarly, a moderate statistically significant elevation (p < 0.01) in CD44 gene expression form and soluble form for CRC patients compared to healthy controls. Furthermore, there is a strong statistically significant difference in CD44 expression between patients with breast cancer and those with colorectal cancer (p < 0.001). CONCLUSIONS: The study identified significantly elevated sCD44 levels in serum and urine of breast and colorectal cancer patients, supporting its potential as a cancer biomarker. In contrast, αFP showed minimal diagnostic value, with negligible serum changes and absence in urine, reinforcing its association with liver-related cancers.
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    ASSOCIATION BETWEEN SERUM FOLATE LEVELS AND DEPRESSION AMONG ADULT FEMALE STUDENTS AT AN-NAJAH NATIONAL UNIVERSITY IN NABLUS, PALESTINE: A CROSS-SECTIONAL STUDY
    (An-Najah National University, 2024-07-29) Elewi, Saja
    Background: Depression is considered a major public health concern worldwide. Depression is a prevalent issue among university students compared to the general population. Folate is a B complex group water-soluble vitamin that naturally occurs in food and is essential to the brain for producing norepinephrine, dopamine, and serotonin. Previous studies have indicated that levels of folate are crucial in the development and progression of depression. However, the research findings have been inconclusive when it comes to variations in folate levels among people with depression compared to those without the condition. Objective: This study aimed to assess the relationship between serum folate levels and depression among adult female students at An-Najah National University in Nablus, Palestine. Method: This study was conducted with a cross-sectional observational design. A questionnaire was distributed from 15th September 2023 until 20th October 2023 to participating female students from An-Najah National University. Depressive symptoms were assessed using the DASS-21 scale. The questionnaire also collected the social and demographic characteristics of the female students and several questions related to the factors that affect folate levels in the blood. The internal reliability of the DASS-21 questionnaire was tested using Cronbach's alpha. In addition, venous blood samples were collected within the same period in the scientific research laboratory at An-Najah University after overnight fasting, and serum folate levels were measured. The number of female students participating was 180, and their ages varied from 18 to 30 years old. Results: The mean of serum folate levels was 4.82 ng/ml (SD=3.38). The prevalence of depression among them was 16.7%, 47.2%, 14.4% 12.2%, and 9.4% for extremely severe, severe, moderate, mild, and normal depression, respectively. Levels of serum folate were significantly lower in patients with extremely severe and severe depression, the mean was (3.13 and 3.30 ng/ml) respectively. Additionally, there was a significant moderate inverse correlation between the levels of serum folate and depression severity (r=-0.537, P-value<0.001). Conclusion: Our findings showed that there is a connection between the levels of serum folate and depression among female Palestinian students. Folate serum levels may serve as indicators to evaluate the effectiveness of depression treatment. Measuring folate levels can assist physicians in effectively managing depression. In this regard, folate appears to play a more crucial role in the improvement outcomes of mood disorders and should be assessed more attentively. Keywords: Serum folate, depression, lifestyle, diet, clinical characteristics, An-Najah National University, Palestine.
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    ASSOCIATION BETWEEN VITAMIN D-BINDING PROTEIN AND VITAMIN D3 ‎LEVEL IN HEMODIALYSIS PATIENTS
    (An-Najah National University, 2024-03-07) Hamadneh, Ayat
    Background: Vitamin D deficiency is a common problem among patients with end-stage renal failure who undergo dialysis, which requires extensive research and interventions due to its widespread repercussions in the body. Understanding the physiology of vitamin D, as well as identifying factors contributing to its deficiency, has been the focus of research. In addition, vitamin D binding protein (VDBP) and its potential role in influencing vitamin D levels have been explored, with the hope of finding therapeutic interventionsObjectives: For the time being, there is a limited research about the relationship between VDBP and other vital signs, especially among dialysis patients in Palestine. This study aimed to treat this gap by investigating the relationship between VDBP and vitamin D levels in dialysis patients. Methodology: A prospective study, conducted among hemodialysis patients‎ at Al-Najah hospital, Nablus, Palestine, over 10 ‎months. The patients were treated with different doses of ‎Alfacalcidol and ‎Cholecalciferol for a total of 17 weeks. VDBP measured by specific sandwich utilizing enzyme-linked ‎immunosorbent assay (ELIZA) technique by R&D used polyclonal ‎rabbit ‏anti-VDBP antibodies, vitamin D is also measured by ELIZA technique, both of them defined before and after course of tretment. Results: The results indicated that after a course of vitamin D treatment, VDBP levels decreased significantly while vitamin D levels increased significantly, with no correlation between them. These results were consistent with previous research that showed no significant relationship between VDBP and vitamin D levels in different population groups.Demographic variables such as age and gender did not show a conclusive association with VDBP levels among dialysis patients, which is in contrast to results from other studies. In addition, there was no significant relationship between VDBP levels and the results of other laboratory tests such as albumin, calcium, phosphorus, and parathyroid hormone (PTH). Conclusion: Overall, this study underscores the importance of vitamin D treatment in dialysis patients and ‎highlights the need for further research to fully understand the role of VDBP in vitamin D ‎metabolism and its implications for clinical management. ‎ Keywords: Vitamin D, Vitamin D binding protein, End stage renal disease, Hemodialysis patients
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    TELMISARTAN INHIBITS MELANOMA GROWTH AND METASTASIS THROUGH LRP1 SUPPRESSION
    (An-Najah National University, 2024-03-11) Saymeh,Danah
    Background: Melanoma is the most common type of skin cancer worldwide, which hasa poor prognosis becauseof its high metastatic rate and aggressive nature. Wild-type p53, which has been activated in response to cellular stressors such as oncogene activity, is commonly expressed in melanoma. It has been discovered that TP53 regulates the development of tumors mediated by the multifunctional scavenger protein LRP1 (CD91), which has been connected to the advancement of melanoma.Telmisartan, an antihypertensive medication, possesses anticancer properties that effectively treat melanoma. Moreover, Mir 107 is a crucial tumor suppressor factor that can inhibit the LRP1 oncogene. Aims: Thisstudy aims to determine the effect of angiotensin receptor blocker telmisartan on melanoma growth and metastasis to evaluate it as a potential therapy option for patients with metastatic melanoma who wish to achieve a high survival rate. Methods:An experimental study was carried out at the An-Najah Laboratory for Cancer and Stem Cell Research in Nablus. The B16F10 melanoma cell lineswere seeded in 12 well plates and treated with indicated concentrations of telmisartan to assess cell viability and migration.This study was conducted both in vitro and in vivo using C57BL6 mice to determine telmisartan's impact on tumor growth. To study the effect of LRP1 on melanoma cell proliferation, we utilized lentivirus to overexpress LRP1 and siRNA to knock down LRP1 in B16F10 cells. We also used lentivirus to express tumor suppressor miR107. The expressions of LRP1 (OE) LRP1(KD), and miR107 were verified by qPCR. Results:The study showed that telmisartan inhibits the proliferation and migration of B16F10 cells both in vitro and in vivo.Additionally, the research revealed thattelmisartan restores P53 by phosphorylation, which upregulates the expression of tumor suppressor miR107 and then leadsto downregulating LRP1 expression, inhibiting melanoma growth and metastasis.