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  1. Tusimin M, Ahmed SME, Wei Lee K, Siew Mooi C, Md Noor S, Nordin N
    Croat Med J, 2021 Dec 31;62(6):590-597.
    PMID: 34981691
    AIM: To evaluate the effects of gestational diabetes mellitus (GDM) on the quantity and quality of hematopoietic stem cells (HSC).

    METHODS: In this case-control study, HSC were isolated from umbilical cord blood (UCB) procured at delivery from 63 mothers with GDM and 67 healthy mothers. Total nucleated cells (TNC) and CD34+ cells were quantified using BD FACSCalibur flow cytometer. The quantity and quality of stem cells were determined.

    RESULTS: The GDM group had lower total cord blood volume and lower number of nucleated HSC compared with healthy mothers. Regarding stem cell quantity parameters, they had significantly lower UCB volume (P=0.041), TNC count (P=0.022), total viable NC count (P=0.014), and CD34+ percentage (P=0.014). Regarding the quality of stem cells, they had significantly lower viable TNC percentage (P=0.015). The predictors for total TNC count were longer labor duration (adjusted B coefficient [p]: 0.031 [0.046]), greater estimated blood loss (0.089 [0.005]), female neonates (12.322 [0.049]), and higher placenta weight (0.080 [0.033]). The predictors of total viable NC count were greater estimated blood loss (0.092 [0.003]), female neonates (13.16 [0.035]), and greater placenta weight (0.083 [0.026]).

    CONCLUSION: The GDM group had much lower quantity and quality of UCB stem cells. Our results should be taken into consideration when drawing cord blood for unrelated stem cell banking in an obstetric unit to ensure the obtaining of optimal cord blood samples and to avoid unnecessary expenses.

  2. Ng PY, Nafi SNM, Jalil NAC, Kueh YC, Lee YY, Zin AAM
    Croat Med J, 2023 Feb 28;64(1):29-36.
    PMID: 36864816
    AIM: To assess the association of the expression of apolipoprotein B (apoB) and 4-hydroxynonenal (4HNE) with the clinicopathological data of patients with colorectal cancer (CRC).

    METHODS: We obtained 80 CRC histopathological specimens sent to the Pathology Laboratory of Hospital Universiti Sains Malaysia from 2015 to 2019. Data on demographic factors, body mass index (BMI), and clinicopathological characteristics were also collected. Formalin-fixed paraffin-embedded tissues were stained by using an optimized immunohistochemical protocol.

    RESULTS: Patients were mostly older than 50 years, male, Malay, and overweight or obese. A high apoB expression was observed in 87.5% CRC samples (70/80), while a high 4HNE expression was observed in only 17.5% (14/80) of CRCs. The expression of apoB was significantly associated with the sigmoid and rectosigmoid tumor sites (p =0.001) and tumor size 3-5 cm (p =0.005). 4HNE expression was significantly associated with tumor size 3-5 cm (p =0.045). Other variables were not significantly associated with the expression of either marker.

    CONCLUSION: ApoB and 4HNE proteins may play a role in promoting CRC carcinogenesis.

  3. Khair SZNM, Ab Radzak SM, Idris Z, Zin AAM, Ahmad WMAW, Yusoff AAM
    Croat Med J, 2024 Apr 30;65(2):111-121.
    PMID: 38706237
    AIM: To assess the presence of mitochondrial (mt) DNA somatic mutations, determine the relationship between clinicopathological characteristics and mutations, and assess the survival outcomes in Malay patients with primary brain tumors.

    METHODS: The study enrolled 54 patients with primary brain tumors. DNA extracted from paired tissue and blood samples was subjected to Sanger sequencing to identify alterations in the entire mtDNA. The associations between clinicopathological characteristics and mutations were evaluated. Cox-regression multivariate analysis was conducted to identify factors significantly associated with survival, and Kaplan-Meier analysis was used to compare the survival of patients with and without mutations.

    RESULTS: Overall, 29.6% of the patients harbored 19 somatic mutations distributed across 15 loci within the mtDNA. Notably, 36.8% of these mutations were not previously documented in MITOMAP. One newly identified mutation caused a frameshift in the ATPase6 gene, resulting in a premature stop codon. Three mutations were classified as deleterious in the MitImpact2 database. Overall, 1097 mtDNA polymorphisms were identified across 331 different locations. Patients with mutations exhibited significantly shorter survival than patients without mutations.

    CONCLUSIONS: mtDNA mutations negatively affected the survival outcomes of Malaysian patients with primary brain tumors. However, studies with larger samples are needed to confirm the association between mutation burden and survival rates.

  4. Rosdi SNM, Omar S, Ghazali MM, Ghani ARI, Yusoff AAM
    Croat Med J, 2025 Feb 28;66(1):56-61.
    PMID: 40047162
    Chiari malformation type 1 (CM 1) is a rare and complex neurological condition. This congenital condition affects the lower posterior fossa, where the brain connects to the spinal cord. Although the exact cause of CM 1 remains unclear, genetic predisposition plays a considerable role in structural defects of the cerebellum. Here, we report on a 15-year-old female patient with CM 1 who exhibited both nuclear and mitochondrial genetic variants, a combination that has not been previously described. We identified a silent mutation in exon 2 (c. 556 G>A, p. Lys185=) of PAX1 and a DKK1 variant in intron 3 (548-3 t>C) in the nuclear DNA. We also screened the D-loop region of mitochondrial DNA as it exhibits a higher susceptibility to mutations than other mitochondrial DNA regions. Several hotspot variants were revealed, including those in positions 303-309 and 16519 (t>C), as well as some variants that had not been documented in MITOMAP. Our findings highlight the potential role of genetic alterations in D-loop in CM 1.
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