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In recent years, Malaysia has seen a surge in stem cell therapy for various medical conditions. However, the regulation of stem cell research and therapy in Malaysia faces several challenges such as the emergence of unregulated clinics and a lack of specific legislation. Some urgent measures, including enactment of specific laws, strengthened monitoring, as well as increased public awareness and education, are crucial. Therefore, stem cell therapy regulation requires concerted efforts by the policymakers, regulator bodies and healthcare professionals. This commentary discusses the current guidelines and challenges in Malaysian stem cell therapy regulation and proposes some future recommendations that could pave the way for responsible progress of stem cell research and therapy globally. [ABSTRACT FROM AUTHOR]

Abstract MYB proteins are highly conserved DNA-binding domains (DBD) and mutations in MYB oncoproteins have been reported to cause aberrant and augmented cancer progression. Identification of MYB molecular biomarkers predictive of cancer progression can be used for improving cancer management. To address this, a biomarker discovery pipeline was employed in investigating deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) in predicting damaging and potential alterations on the properties of proteins. The nsSNP of the MYB family; MYB, MYBL1, and MYBL2 was extracted from the NCBI database. Five in silico tools (PROVEAN, SIFT, PolyPhen-2, SNPs&GO and PhD-SNP) were utilized to investigate the outcomes of nsSNPs. A total of 45 nsSNPs were predicted as high-risk and damaging, and were subjected to PMut and I-Mutant 2.0 for protein stability analysis. This resulted in 32 nsSNPs with decreased stability with a DDG score lower than − 0.5, indicating damaging effect. G111S, N183S, G122S, and S178C located within the helix-turn-helix (HTH) domain were predicted to be conserved, further posttranslational modifications and 3-D protein analysis indicated these nsSNPs to shift DNA-binding specificity of the protein thus altering the protein function. Findings from this study would help in the field of pharmacogenomic and cancer therapy towards better intervention and management of cancer.

The TBX1 gene plays a critical role in the development of 22q11.2 deletion syndrome (22q11.2DS), a complex genetic disorder associated with various phenotypic manifestations. In this study, we performed in-silico analysis to identify potentially deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) within the TBX1 gene and evaluate their functional and structural impact on 22q11.2DS. A comprehensive analysis pipeline involving multiple computational tools was employed to predict the pathogenicity of nsSNPs. This study assessed protein stability and explored potential alterations in protein-protein interactions. The results revealed the rs751339103(C>A), rs780800634(G>A), rs1936727304(T>C), rs1223320618(G>A), rs1248532217(T>C), rs1294927055 (C>T), rs1331240435 (A>G, rs1601289406 (A>C), rs1936726164 (G>A), and rs911796187(G>A) with a high-risk potential for affecting protein function and stability. These nsSNPs were further analyzed for their impact on post-translational modifications and structural characteristics, indicating their potential disruption of molecular pathways associated with TBX1 and its interacting partners. These findings provide a foundation for further experimental studies and elucidation of potential therapeutic targets and personalized treatment approaches for individuals affected by 22q11.2DS. [ABSTRACT FROM AUTHOR]

Dysregulation of fibroblast growth factors is linked to the pathogenesis of bladder cancer. The role of FGF1 and FGF3 is evident in bladder cancer; however, the role of FGF4 is vague. Despite being reported that FGF4 interacts with FGF1 and FGF3 in MAPK pathways, its pathogenesis and mechanism of action are yet to be elucidated. Therefore, this study aimed to elucidate pathogenic nsSNPs and their role in the prognosis of bladder cancer by employing in-silico analysis. The nsSNPs of FGF4 were retrieved from the NCBI database. Different in silico tools, PROVEAN, SIFT, PolyPhen-2, SNPs&GO, and PhD-SNP, were used for predicting the pathogenicity of the nsSNPs. Twenty-seven nsSNPs were identified as “damaging”, and further stability analysis using I-Mutant 2.0 and MUPro indicated 22 nsSNPs to cause decreased stability (DDG scores < −0.5). Conservation analysis predicted that Q97K, G106V, N164S, and N167S were highly conserved and exposed. Biophysical characterisation indicated these nsSNPs were not tolerated, and protein-protein interaction analysis showed their involvement in the GFR-MAPK signalling pathway. Furthermore, Kaplan Meier bioinformatics analyses indicated that the FGF4 gene deregulation affected the overall survival rate of patients with bladder cancer, leading to prognostic significance. Thus, based on these analyses, our study suggests that the reported nsSNPs of FGF4 may serve as potential targets for diagnoses and therapeutic interventions focusing on bladder cancer.

Cardiovascular disease (CVD) remains the leading cause of death globally, with unhealthy lifestyles today greatly increasing the risk. Over the decades, scientific investigation has been carried out on reactive oxygen species (ROS) and their resultant oxidative stress based on their changes made on biological targets such as lipids, proteins, and DNA. Since the existing clinical studies with antioxidants failed to provide relevant findings on CVD prediction, the focus has shifted towards recognition of oxidised targets as biomarkers to predict prognosis and response to accurate treatment. The identification of redox markers could help clinicians in providing risk stratification for CVD events beyond the traditional prognostic and diagnostic targets. This review will focus on how oxidant-related parameters can be applied as biomarkers for CVD based on recent clinical evidence.

Competing Interests: Conflict of interest: All authors declare no conflict of interest.

Ventricular septal defect (VSD) is the most common form of cardiac malformations accounting approximately 20% of all congenital heart defects. SMAD7 is an inhibitory protein that antagonizes the signalling of TGF-β family member and has been found in the development and function of mouse heart models. This study aims to screen and identify the polymorphisms of SMAD7 exonic regions in Malay population with VSD. Peripheral blood samples were collected and extracted from 30 clinically diagnosed VSD patients. PCR amplification was performed using 12 sets of designed primers encompassing seven exons of SMAD7 . Re-sequencing was conducted to characterize the polymorphisms of SMAD7 . Observed polymorphisms were then genotyped in 30 healthy individuals using both re-sequencing and allele-specific PCR techniques. A total of 10 variants were identified in the patient population located in the upstream (rs7236774), exonic (rs368427729, rs145686330, rs3764482, rs3809922, rs780863704 and rs3809923), intronic (rs3736242) and 3'UTR regions (rs375444823 and rs16950113). No significant difference of genotype and allele frequency was observed among these SNPs. Two synonymous variants (rs3809922 and rs3809923) were found in complete linkage disequilibrium (r 2 =1.0) with each other indicate a strong correlation of these SNPs. The identification of these SNPs provides a new perspective of the VSD causation.

Aim: To identify genes associated with gastric precancerous lesions in Helicobacter pylori (H. pylori)-susceptible ethnic Malays., Methods: Twenty-three Malay subjects with H. pylori infection and gastric precancerous lesions identified during endoscopy were included as "cases". Thirty-seven Malay subjects who were H. pylori negative and had no precancerous lesions were included as "controls". Venous blood was collected for genotyping with Affymetrix 50K Xba1 kit. Genotypes with call rates < 90% for autosomal single nucleotide polymorphisms (SNPs) were excluded. For each precancerous lesion, associated SNPs were identified from Manhattan plots, and only SNPs with a χ² P value < 0.05 and Hardy Weinberg Equilibrium P value > 0.5 was considered as significant markers., Results: Of the 23 H. pylori-positive subjects recruited, one sample was excluded from further analysis due to a low genotyping call rate. Of the 22 H. pylori-positive samples, atrophic gastritis only was present in 50.0%, complete intestinal metaplasia was present in 18.25%, both incomplete intestinal metaplasia and dysplasia was present in 22.7%, and dysplasia only was present in 9.1%. SNPs rs9315542 (UFM1 gene), rs6878265 (THBS4 gene), rs1042194 (CYP2C19 gene) and rs10505799 (MGST1 gene) were significantly associated with atrophic gastritis, complete intestinal metaplasia, incomplete metaplasia with foci of dysplasia and dysplasia, respectively. Allele frequencies in "cases" vs "controls" for rs9315542, rs6878265, rs1042194 and rs10505799 were 0.4 vs 0.06, 0.6 vs 0.01, 0.6 vs 0.01 and 0.5 vs 0.02, respectively., Conclusion: Genetic variants possibly related to gastric precancerous lesions in ethnic Malays susceptible to H. pylori infection were identified for testing in subsequent trials.

Background/aims: Using genome-wide case-control association approach, the current study aimed to determine whether genetic polymorphism(s) is/are associated with H. pylori infection among ethnic Malays from the north-eastern region of Peninsular Malaysia, a region with an exceptionally low prevalence for H. pylori infection and gastric cancer., Methodology: Twenty-three Malay subjects positive for H. pylori confirmed with urease test and histology were enrolled as "cases" and 37 subjects negative for H. pylori were "controls". Both groups were matched for age and environmental risks. Extracted DNA samples (QIAGEN, Germany) from the venous blood of study subjects were genotyped using the Human Mapping 50k xbal array (Affymetrix, USA). High throughput downstream analyses were then used to determine the significant SNP(s) associated with H. pylori infection., Results: Out of 20,361 SNPs filtered using the genotype association test, the top 1% (203) significant SNPs were selected for functional enrichment analysis. Of the 15 "enriched" SNPs, the rs10502974 which was located within the intronic region of Deleted in Colorectal Cancer (DCC) gene was the SNP most significantly associated with H. pylori infection (p=0.00549)., Conclusions: Ethnic Malays is genetically susceptible to H. pylori infection and is possibly mediated through a genetic variation in the DCC gene.