Volume 34(1); 2026

The CRL4^Cdt2 E3 ubiquitin ligase: A comprehensive review of its substrates, mechanisms, and roles in genomic stability

Afiqah Aimie Murba, Muhammad Aidil Ibrahim, Sarah Shazwani Zakaria, Nurul Hidayah Adenan, Mohamad Ikhwan Jamaludin, Hideo Nishitani, Mohd Shukuri Mohamad Ali, Mu’adz Ahmad Mazian

APJMBB 34(1): 1-22

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.01

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The CRL4^Cdt2 ubiquitin ligase complex plays a pivotal role in maintaining genomic integrity and regulating the cell cycle, specifically during the S phase. By targeting key proteins such as Cdt1, p21, and Set8 for ubiquitination and degradation, CRL4^Cdt2 ensures proper DNA replication and cell cycle progression. Dysregulation of this complex has been implicated in various cancers, including melanoma, breast cancer, gliomas, and ovarian cancer, where elevated levels of Cdc10-dependent transcript 2 (Cdt2) expression is often associated with poor prognosis and increased tumor aggressiveness. CRL4^Cdt2 role extends beyond cell cycle regulation, as it also participates in the DNA damage response by degrading proteins like XPG, which is essential for nucleotide excision repair. Impaired CRL4^Cdt2 function leads to DNA re-replication, genomic instability, and cancer progression. Recent studies have highlighted the therapeutic potential of targeting CRL4^Cdt2 in cancer treatment, with inhibitors like pevonedistat showing promise in preclinical models. However, challenges remain, including the lack of a three-dimensional structure for Cdt2, which limits our understanding of its substrate recognition and degradation mechanisms. This review revisits the role of CRL4^Cdt2 in regulating its cellular substrates, updated substrates targeted by CRL4^Cdt2, explores its pathological consequences in cancer, and discusses potential therapeutic strategies to target this complex, offering new insights into its function and clinical relevance.

Effects of extracellular vesicles of Clostridium butyricum on migration, PANoptosis, and macrophage polarization in lipopolysaccharide-induced RAW264.7 macrophages

Zhang Qingyu, He Kailun, Mohd Shafiq Aazmi, Mohd Fakharul Zaman Raja Yahya

APJMBB 34(1): 23-34

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.02

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Extracellular vesicles (EVs) are nano-sized membrane-bound vesicles released by cells, playing a crucial role in intercellular communication and exchange between cells and their hosts. EVs from probiotics serve as important carriers, enabling probiotics to interact with host cells and exert their beneficial effects. Clostridium butyricum-derived EVs have been shown to exhibit a high yield, contain minimal toxic substances, and possess the ability to modulate cytokine expression in macrophages. This study aimed to investigate the effects of C. butyricum-derived EVs on cytokine expression, migration, PANoptosis, and polarization in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. EVs were isolated from C. butyricum and characterized using transmission electron microscopy and nanoparticle tracking analysis. Quantitative PCR (q-PCR) was employed to assess cytokine expression in RAW264.7 macrophages, while the transwell assay was used to evaluate their migration capacity. Flow cytometry and q-PCR were further utilized to examine the PANoptosis and polarization of the macrophages. The results demonstrated that C. butyricum-derived EVs could promote the expression of proinflammatory cytokines, such as IL-6, IL-12, and TNF-α (p<0.05), while inhibiting anti-inflammatory cytokines like IL-4 and TGF-β (p<0.05). The EVs also restored the migratory ability of RAW264.7 macrophages. Furthermore, C. butyricum-derived EVs exhibited a protective effect on LPS-stimulated RAW264.7 macrophages by reducing PANoptosis through the inhibition of ZBP1 and iNOS gene expression (p<0.05). Additionally, these EVs induced M1 polarization of the macrophages. This study provides novel insights into the immunoregulatory effects of C. butyricum-derived EVs on macrophages, highlighting their potential therapeutic applications.

Unveiling molecular melanogenesis inhibition of lime
(Citrus aurantifolia (Christm.) Swingle) peel extract

Clarissa Nadya Santoso, Brigitta Amanda Maharani, K. Ariex Widyantara, Adam Hermawan,
Rini Dwiastuti, Agustina Setiawati

APJMBB 34(1): 35-45

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.03

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The overproduction of melanin induces multiple types of hyperpigmentation, including post-inflammatory melanoderma, solar lentigo lesions, and melasma. Consequently, the design of melanogenesis inhibitors as skin-enlightening agents through various molecular mechanisms is urgently needed. Citrus aurantifolia (Christm.) Swingle, or lime, has garnered significant interest as a natural product that contains secondary metabolites to inhibit melanogenesis. Nevertheless, the molecular mechanism of its effect on melanogenesis is not yet fully understood. The lime peel was extracted using 70% ethanol, and the major compounds of the extract were detected by thin-layer chromatography (TLC). The gene target and the top ten target proteins associated with molecular pathways were further investigated based on bioinformatics analysis. Additionally, molecular docking studies were carried out on two specific protein targets to assist in further study.  Finally, in vitro study of tyrosinase (TYR) and carbonic anhydrase 2 (CA2) enzyme inhibition was carried out to confirm the extract's anti-melanogenic effect. There are 10 target genes, including CA2, CYP1B1, CA1, CYP19A1, CA9, ABCB1, CA3, ABCG2, TYR, and ADORA1. An in silico study of hesperidin (HD) and tangeretin (TN) to bind with TYR and CA2 found that the binding affinity was binding energy of -10.01 and -6.85 kcal/mol.  The in vitro study demonstrated that the extract inhibited TYR with an IC₅₀ value of 59.71 ppm, which is in vitro more effective in inhibiting it than kojic acid. Based on these findings, Citrus aurantifolia peel is effective in impeding melanogenesis and can be explored as a plant-based cosmetic.

Extract of Allium sativum L. as a sustainable biopesticide candidate: Phytochemical, toxicity, and molecular characterization

Slamet Isworo, Zahra Yulia Putri

APJMBB 34(1): 46-58

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.04

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The excessive use of synthetic pesticides has raised growing concerns about environmental safety, human health risks, and the emergence of pest resistance. In addressing these issues, this study evaluates the biopesticidal potential of Allium sativum L. (garlic) extract through a multidisciplinary approach involving phytochemical screening, toxicity assessment, and molecular identification. Two hypotheses were proposed: (1) that garlic ethanol extract containing alkaloids, saponins, and steroids would exhibit significant bioactivity against Artemia salina with an LC₅₀ below 100 ppm; and (2) that molecular validation using the chloroplast-encoded matK gene would confirm species identity with ≥ 99% sequence similarity to known A. sativum cultivars. Garlic was extracted via maceration using 70 % ethanol, yielding 19.94% crude extract. Phytochemical tests confirmed the presence of alkaloids, saponins, and steroids. Acute toxicity analysis using the Brine Shrimp Lethality Test (BSLT) yielded an LC₅₀ of 93.54 ppm, classifying the extract as moderately toxic by EPA guidelines. Sequencing of matK gene (854 bp) revealed 99.74% similarity to A. sativum cv. Cang ShanPuKe (GenBank: MK335928.1), supported by a 98% bootstrap in phylogenetic analysis. These findings validate both hypotheses and establish garlic extract as a bioactive, molecularly verified candidate for eco-friendly pest control within sustainable agricultural frameworks.

Expression profiling and clinicopathological correlation of miR-100-5p and miR-141-3p in HPV-mediated cervical carcinogenesis

Nur Sabrina Abd Rashid, Ahmad Aizat Abdul Aziz, Sarina Sulong, Mohd Pazudin Ismail,
Nur Asyilla Che Jalil, Daniel Roza Duski, Nazihah Mohd Yunus

APJMBB 34(1): 59-66

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.05

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Cervical cancer is one of the most prevalent malignancies affecting women worldwide, primarily driven by high-risk human papillomavirus (HPV) infection. Recent findings highlight the critical role of non-coding RNAs, particularly microRNAs (miRNAs), in regulating HPV-mediated oncogenic processes. However, the genotype specific miRNA expression patterns in HPV positive cervical cancer remain underexplored. This study aims to profile miRNA dysregulation in HPV-positive cervical cancer and explore their associations with histopathological parameters. miRNA profiling was performed on paired normal adjacent and cancerous cervical tissues using the NanoString nCounter™ Human V3 miRNA Panel to identify differentially expressed miRNAs (DEMs) followed by Taqman RT-qPCR validation in 50 paired cervical cancer. Expression data were normalized using miR-423-3p and miR-25-3p as endogenous controls, and relative quantification was calculated using the 2^{^−ΔΔCT} method. Statistical analyses were employed to determine their association with clinicopathological data. A total of 62 DEMs were identified, comprising 35 upregulated and 27 downregulated miRNAs (FC ≥ 2.0, p < 0.05, FDR < 0.3). RT-qPCR confirmed downregulation of miR-100-5p (p < 0.0001) and upregulation of miR-141-3p (p = 0.0018) in cancerous tissues. miR-100-5p expression were reduced in squamous cell carcinoma, while miR-141-3p was significantly elevated in early-stage cervical cancer. The distinct expression of these miRNAs across tumour subtypes and stages suggests their involvement in early tumorigenic transformation. In conclusion, differential expression of miR-100-5p and miR-141-3p correlates with tumour histopathological subtype, stage, and HPV genotype highlighting their potential as diagnostic and prognostic biomarkers in HPV-associated cervical cancer.

The effect of vinasse in various trophic conditions on the growth rate and metabolite contents of Euglena sp. with CO₂ aeration

Maya Cindiati, Tia Erfianti, Renata Adaranyssa Egistha Putri, Dedy Kurnianto, Eko Agus Suyono

APJMBB 34(1): 67-82

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.06

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Euglena sp. is capable of accumulating valuable metabolites in its biomass, making it useful across various industries. Due to the high cost of production, this research explores the utilization of cost-effective and readily available carbon sources, such as vinasse. This research aimed to determine the effect of vinasse on Euglena sp. cultivation under various trophic conditions with CO₂ aeration on the growth rate and metabolite contents. The study involved measuring cell density daily using spectrophotometry, while biomass and metabolite contents were measured every three days over an 18-day observation period using standard dry-weight and biochemical assay methods. Cell size and morphology were measured at the beginning and end of cultivation. Data were analyzed using one-way ANOVA followed by Duncan’s multiple-range test. The results indicated that the heterotrophic condition yielded the highest growth rate, biomass, carbohydrates, protein, and paramylon contents. Meanwhile, the positive control exhibited the highest lipid and pigment contents. Aspect ratio value showed that the control treatment produced spindle and elongated-shaped cells, while heterotrophic and mixo-heterotrophic conditions resulted in spherical and spindle-shaped cells. Mixotrophic conditions produced a mix of spherical, spindle, and elongated cells. Our findings suggest that vinasse has potential as an alternative medium for cultivating Euglena sp., offering a cost-effective approach for metabolite production.

Association of DPF3 polymorphisms (rs10129954) with male infertility in the Malaysian population - A preliminary study

Wafa Liyana Mohamad Zainol, Ahmad Aizat Abdul Aziz, Nazihah Mohd Yunus, Sarina Sulong,
Adibah Ibrahim, Aziati Azwari Annuar

APJMBB 34(1): 83-88

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.07

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Male infertility is a multifactorial disorder with genetic abnormalities contributing to 15-30% of cases. Numerous genetic polymorphisms have been investigated to understand their role in male infertility, but few studies show significant associations. The Double PHD Fingers 3 (DPF3) gene is essential for chromatin remodelling and histone-to-protamine transition during spermatogenesis. This study aims to investigate the association between DPF3 (rs10129954) polymorphism and male infertility in Malaysians. This case-control study involved 30 infertile and 30 fertile control males. Genomic DNA was extracted, and genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Associations between genotypes and infertility risk were assessed using Fisher’s Exact Test and odds ratios (ORs) with 95% confidence intervals (CI).  The frequencies of CC, CT, and TT genotypes of DPF3 (rs10129954) polymorphism were 3.3%, 36.7%, and 60.0% in infertile males, and 0%, 23.3%, and 76.7% in fertile controls, respectively. The allele frequencies for C and T were 21.7% and 78.3% in infertile males, compared to 11.7% and 88.3% in fertile control males. No significant differences were observed between the frequencies of DPF3 (rs10129954) genotype and allele in infertile and fertile groups (p>0.05). The T allele was associated with a reduced risk of male infertility (OR: 0.478; 95% CI: 0.176-1.297;  p=0.074), differing from studies in Chicago, Japanese and Han Chinese populations, which linked the T allele to an increased risk. Our findings suggest that the T allele of DPF3 (rs10129954) is not significantly associated with male infertility. Larger studies are needed to confirm this observation.

Production of phytase enzyme by Frateuria sp. UMK-PPS3, a phosphate-solubilising bacterium isolated from paddy rhizosphere

Ainihayati Abdul Rahim, Dibasree Hari Krishnan, Nik Fatin Qharanie Nik Mohd Kamaruzaman

APJMBB 34(1): 89-97

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.08

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Frateuria sp. are known for their plant growth-promoting abilities, particularly in phosphate solubilisation and nutrient cycling within the rhizosphere. Phosphate-solubilising bacteria (PSB) can solubilise organic phosphorus compounds into a form available for plant uptake by producing the phytase enzyme, whose activity is influenced by carbon and nitrogen sources. This study was conducted to identify a previously isolated PSB strain from the paddy rhizosphere and to determine the optimal nutrient condition for phytase production. The PSB strain, labelled as UMK-PPS3, was molecularly identified by 16S rRNA gene analysis. Phytase production was assessed by measuring the amount of inorganic phosphate released from sodium phytate using the molybdate-blue method under different nutrient conditions. To determine the optimal enzyme production, the Pikovskaya medium was prepared with varying carbon sources, including glucose, fructose, and sucrose, while maintaining ammonium sulphate as the nitrogen source. Additionally, the production of phytase enzyme under different nitrogen sources, namely ammonium sulphate, potassium nitrate, and sodium nitrate, while maintaining glucose as a carbon source, was also tested. Molecular identification revealed that isolate UMK-PPS3 shared 99% similarity with Frateuria aurantia based on 16S rRNA gene analysis. The results for phytase production showed that the isolate produced the highest phytase activity in the presence of glucose and ammonium sulphate, with 37.620 ± 0.185 U/mL and 33.542 ± 0.731 U/mL, respectively. These findings highlight that determining optimal nutrient conditions can enhance phytase production and provide essential information for designing biofertilizer formulations that sustain the enzyme activity and phosphorus-solubilising efficiency of Frateuria sp. UMK-PPS3 under soil conditions.

Systematic review on Ganoderma lucidum and its nanoparticles in oral cancer: Cytotoxicity, apoptosis and immunomodulation

Goot Heah Khor, Gabriele Ruth Anisah Froemming, Siti Nurhidayah binti Mohd Azhar, Siti Nursyahirah binti Haizan, Shivkanya Fuloria, Neeraj Kumar Fuloria

APJMBB 34(1): 98-113

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.09

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Oral cancer carries high morbidity and mortality, yet although many studies have tested Ganoderma extracts, the evidence remains scattered. This study reviewed six years of literature on Ganoderma lucidum (GL) and its nanoparticles (GLNP) for evaluating the impacts of cytotoxicity, apoptosis and immunomodulation on oral cancer. A total of 67 studies of Science Direct (20), Web of Science (12), Scopus (30) and PubMed (5) were retrieved from 447 articles from the electronic databases.  Among these 33 studies focused on GLNP, demonstrating significant cytotoxic effects against oral cancer cells. Additionally, 60 studies examined GL’s active compounds, particularly triterpenoids and polysaccharides, which exhibited anticancer and immunomodulatory properties. The quality of the included studies was evaluated using a modified risk assessment framework. The results showed that in-vitro studies demonstrated the highest quality, with 66% (40 articles) rated as good, 16% (10 articles) as fair, and 18% (11 articles) as poor. Followed by in-vivo studies with 53% (27 articles) rated as good, 33% (17 articles) as fair, and 14% (7 articles) as poor. In contrast, clinical trials showed the lowest quality, with only 22% (2 articles) rated as good, 33% (3 articles) as fair, and 45% (4 articles) as poor. The combined evidences indicate that GL and GLNP can induce apoptosis, suppress tumour growth, and boost immune responses. Nanoparticle delivery further enhances these effects by improving bioavailability and targeted delivery. However, well-designed studies are still required to confirm their true therapeutic value and clarify their clinical role as adjunct or alternative options for oral cancer.

Metagenomic insights from NGS into water and soil microbiomes surrounding the Temuan Orang Asli communities of Serendah, Malaysia

Aishath Maumoon, Navindra Kumari Palanisamy, Heo Chong Chin, Jamal Houssaini

APJMBB 34(1): 114-126

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.10

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The Orang Asli has a profound knowledge of the forest and its resources which are shaped by the complex microbial communities present in the soil and water sources around their settlements. However, there is a significant gap in the understanding of the environmental microbiome associated with Orang Asli communities. Investigating the diversity and composition of these microbial communities could provide insights into the intricate relationships between the Orang Asli and their surrounding ecosystems. Environmental samples were collected from sites in triplicate across the village. Water quality was assessed using National Water Quality Standard (NWQS). Genomic DNA was extracted from the 3 water and 3 soil samples using a commercial DNA extraction kit and sent for NGS. Findings found that Proteobacteria, Bacteroidota, Firmicutes, and Actinobacteria were the dominant phyla across all water and soil samples specific phyla were significantly more abundant in soil. Soil microbiomes consistently exhibited higher alpha diversity compared to water microbiomes across various metrics. The soil quality across these sites varies considerably but were low overall. All the water samples fell under Class II, indicating "Good" water quality according to the DOE Water Quality Index. In conclusion, key phyla differed significantly between the two environments, likely due to varying conditions. More detailed studies are needed to fully understand how environmental factors shape these microbial communities and their functions in soil and water ecosystems.

Anti-proliferative activity of bioactive sphingolipids from Leishmania donovani against human cervical cancer cells (HeLa) 

Mriganka Mandal, Jishu Mandal, Krishna Das Saha

APJMBB 34(1): 127-134

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.11

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Leishmanial total membrane lipids and Sphingolipid(s) play an immunomodulatory role in the synovial fluid mononuclear cells of patients with rheumatoid arthritis. Additionally, they exhibit an anti-proliferative effect on various malignant cells, such as B16F10, as well as several acute myeloid leukaemia (AML) cells, including those referenced in K562, U937, and HL-60. Based on our previous experiment, we here represent the anti-proliferative nature of Leishmanial Sphingolipid(s) on Human cervical malignant cell HeLa. Sphingolipid fractions were isolated from attenuated Leishmania donovani by the Bligh and Dyer method, then separated into three fractions by Thin layer Chromatographic method (TLC). Three fractions were named LSL–1, LSL–2, and LSL–3. HeLa cells were treated with three fractions separately. Data were collected following the treatment with sphingolipids, applying a dose- and time-dependent approach. Trypan blue exclusion and MTT assay were performed to study the antiproliferative pattern of HeLa cells. It has been observed that LSL–1 demonstrated greater bioactivity and showed potential for anti-proliferation. We have analysed the morphological characteristics and DNA breakdown of cells after treatment with LSL–1 (60 µg/ml) using phase contrast microscopy and fluorescence microscopy. Sphingolipid (LSL–1) treated cells exhibited morphological changes, including cell shrinkage and membrane blebbing due to the externalisation of phosphatidylserine in the outer leaflet of the membrane. DNA fragmentation was verified by colorimetric assay. Analysis of morphological changes using phage contrast and fluorescence microscopy has shown that an apoptotic body-like structure is formed due to cell shrinkage and the externalisation of phosphatidylserine from the cell membrane. Additionally, DNA fragmentation was observed through Acridine orange/Ethidium Bromide (AO/EtBr) staining. The ELISA assay technique demonstrated histones containing fragmented DNA in a dose-dependent manner. Preliminary investigations have found that Leishmanial sphingolipids possess potent anti-proliferative activity against human cervical cancer cells.

Heavy metal cleanup from contaminated soil by phytoremediation: An update

Palivela Pranay Pritham, Tadikonda Sai Siri, Sudhakar Kancharla, Prachetha Kolli, Gowtham Mandadapu, Manoj Kumar Jena

APJMBB 34(1): 135-143

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.12

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Phytoremediation can be defined as a modern method of removing pollutants from water bodies and soil using plants as a means of remediating the environment for a relatively cheaper price while ensuring environmental safety compared to traditional techniques, particularly for soil and water containing heavy metal pollutants. The approach employs various processes such as phytoextraction where pollutants are sequestered in harvestable plant biomass, phytostabilization where movement of pollutants is inhibited, phytovolatilization which refers to the conversion of pollutants to a volatile form, and phytodegradation where plant tissues that contain the pollutants need to be broken down significantly transforming the tissues. Of these methods, phytoextraction has more commercial applicability, especially in regions with diffused pollution. The efficiency of phytoremediation varies according to the bioavailability of heavy metals, soil characteristics, and availability of selective vegetative cover.  Various aspects of phytoremediation of the heavy metals have been discussed in this article with more focus on the methods of phytoremediation. It is essential to select appropriate plants for different methodologies, such as use of high-biomass plants to limit food chain contamination and use of aromatics for non-edible plant by-products. Besides, this review highlights the significance of phytoremediation as a well-suited solution for cleanup of heavy metal contaminated soil and its contribution to a clean and healthier surrounding.

Identification and in-silico analysis of non-synonymous single nucleotide polymorphism (nsSNPs) in the human GH1 gene

Rita Maliza, Alimuddin Tofrizal, Putra Santoso, Bramadi Arya, Diana Fadhilah

APJMBB 34(1): 144-154

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.13

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Non-synonymous SNPs can affect protein structure and function, including GH1, which regulates growth and metabolism. This study aimed to investigate the functional and structural effects of non-synonymous single nucleotide polymorphisms (nsSNPs) in the GH1 gene, focusing on how these variations might impact protein function and stability, and to explore the GH1 gene network using bioinformatics tools. Bioinformatics techniques were employed to analyze specific GH1 gene nsSNPs, namely rs2001345 (T3A/T3P) and rs151263636 (A39V). Various computational tools, including SIFT, PhD-SNP, PROVEAN, PolyPhen-2, and PANTHER, were used to predict the effects of these nsSNPs on protein function, while the I-Mutant 2.0 server assessed the impact on protein stability. GeneMANIA was utilized to explore the GH1 gene network and its connections to other gene categories. The study found that the rs2001345 variations (T3A/T3P) were predicted to be neutral with no significant impact on protein function, whereas the rs151263636 variant (A39V) was predicted to be disease-causing, likely reducing the function of the GH1 protein. Additionally, the I-Mutant 2.0 server predicted a decrease in protein stability for these nsSNPs. GeneMANIA analysis revealed strong links between the GH1 gene and 20 other gene categories. The study indicates that the GH1 gene variation rs151263636 (A39V) may significantly impact protein function and structural stability. Despite its limitations, the study highlights the value of computational analysis in identifying GH1 gene-related disorders and its potential application in drug discovery and personalized medicine development.

Modulation of methylglyoxal-triggered oxidative damage and apoptosis in human osteoblasts by metformin, berberine, and genistein

Alyaa Al-Khateeb, Suhaila Abd. Muid, Gabriele Ruth Anisah Froemming

APJMBB 34(1): 155-165

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.14

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Bone fragility in diabetes is linked to redox imbalance and advanced glycation end products (AGEs). Methylglyoxal (MGO), a reactive carbonyl compound and precursor of AGEs, complicates the pathogenesis of diabetes mellitus and oxidative stress. Metformin lowers the AGEs level. Genistein and berberine decrease MGO levels and inhibit AGE formation. This study investigates the individual and combinatorial effects of metformin, berberine, and genistein on osteoblast-treated MGO in terms of apoptosis and oxidative stress. Human foetal osteoblast cells (hFOB 1.19) were incubated with MGO for 24 hours and treated with metformin, berberine, genistein, and combinations of these compounds. The cells were assessed for apoptosis, AGE levels, oxidative stress markers, and the polymerization status of actin and tubulin fibers. Incubation with metformin, berberine, or genistein alone showed that these compounds significantly reduced apoptotic cells (26.16%, 31.83%, and 41.83%, respectively) compared to MGO alone(p<0.001). Metformin or berberine individual treatment significantly decreased AGEs compared to MGO alone (p< 0.001 for metformin and p< 0.01 for berberine). Individual treatment resulted in lower reactive oxygen species (ROS), with the alliance of genistein and metformin leading to reduced ROS production in comparison to individual treatment. MGO-induced osteoblast cell death was significantly attenuated by metformin, berberine, and genistein. The results of the current study suggest that genistein, berberine, and metformin may serve as potential therapeutic compounds that contribute to the alleviation of bone-related complications resulting from MGO harmfulness.

Educational note on primer design for in-frame cloning

Wei Chong Gan, Yan Kien Lee, Natalie Yong Xin Wong, Hien Fuh Ng, Yun Fong Ngeow

APJMBB 34(1): 166-168

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.15

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Enhancing antimicrobial compound production in Streptomyces sp. VITGV100 using chitosan and its nanoparticles

Madhuri Mukindrao Moon, John Godwin Christopher

APJMBB 34(1): 169-181

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.16

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Streptomyces, a gram-positive bacterium, is renowned for producing a wide array of secondary metabolites with therapeutic potential. This study evaluates the efficacy of chitosan and chitosan nanoparticles (CNPs) as elicitors to enhance antimicrobial compound production by Streptomyces sp. VITGV100 against selected human pathogens, including Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, and Staphylococcus aureus. Chitosan (100 and 200 µg/ml) and CNPs (20, 50, and 100 mg/ml) were added to the growth medium, while a control group received no elicitor. Minimum Inhibitory Concentration (MIC) results from the microdilution method confirmed that both elicitors significantly enhanced antimicrobial compound synthesis. GC-MS analysis was performed on the extracts, and bioactive compounds were validated via molecular docking with target proteins (PDB IDs: 1KZN, 1GSK, 4RLC, and 4URM). Among the tested concentrations, 100 mg/ml CNPs demonstrated the highest activity, showing 70% inhibition of E. coli at 5 µl/ml, while chitosan at 200 µg/ml showed 55% inhibition against S. aureus at 7 µl/ml. GC-MS profiling of CNP-treated extracts revealed 36 unique peaks compared to 16 in the control. The compound Cholest-5-ene-16,22dione,3,26- dihydroxy-, (3β,25R)- exhibited the strongest binding affinity with 4URM in docking studies, indicating potent antimicrobial potential. The results confirm that CNPs are more effective than chitosan in stimulating secondary metabolite production. Overall, Streptomyces sp. VITGV100 is validated as a potent source of bioactive compounds, and nanoparticle elicitation emerges as a promising strategy for enhancing antimicrobial metabolite biosynthesis for potential therapeutic applications.

Evaluation of antioxidant, antibacterial, and antidiabetic activities in vitro of extracts from Abutilon indicum

Van Mai Do, Le Anh Thu Do, Truong Han Le, Hong Phong Ngo, Chi Linh Tran, Van Hung Mai

APJMBB 34(1): 182-192

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.17

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Plant-derived bioactive compounds play a crucial role in developing natural therapeutic agents. However, limited evidence exists regarding the multifunctional properties of Abutilon indicum (A. indicum). This study aimed to evaluate the in vitro antioxidant, antidiabetic, and antibacterial activities of A. indicum extracts to identify their potential health benefits. The study was carried out by extracting leaves and stems of A. indicum, which were then assessed for antioxidant activity using ABTS, DPPH, NO, RP, FRAP, and TAC assays. Antidiabetic potential was evaluated through α-amylase and α-glucosidase inhibitory assays, while antibacterial activity was determined using the agar well diffusion method against six pathogenic bacteria. The results showed that the leaf extracts of A. indicum exhibited antioxidant activity with IC₅₀ values and in vitro antidiabetic activity with IC₅₀ values, outperforming extracts from roots and stems. For antibacterial activity, leaf extracts strongly inhibited Gram-positive bacteria with MIC values from 250 to 500 µg/mL, while MIC values for Gram-negative bacteria ranged from 1000 to 2000 µg/mL. A. indicum is a promising natural resource for pharmaceutical and health-protective products with antioxidant, antibacterial, and antidiabetic properties. These findings support further exploration for therapeutic applications, although additional in vivo and mechanistic studies are required to validate and extend these results.

Trends in genetics and genomics publications in Malaysia:
A Web of Science bibliometrics review

Amin Abdurrahman Abdul Rashid, Wan Amirul Syazwan Wan Ahmad Munawar, Marjanu Hikmah Elias, Sarina Sulong

APJMBB 34(1): 193-206

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.18

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Genetic research, originating from foundational discoveries in DNA structure and function, has evolved into a pivotal scientific discipline. As sequencing technology becomes increasingly accessible, the field is rapidly entering the 'genomic age,' with Malaysia making significant and distinct contributions through advancements in tropical biodiversity and molecular studies. The rapid accumulation of high-throughput genomic and genetic data highlights the critical need for systematic quantitative analyses to chart scientific output and policy relevance within key geographical regions. In this study, we aimed to analyse the trends in genomic and genetic research related to Malaysia. Records were retrieved from the Web of Science Core Collection using a strategic search approach with terms such as “genetic” and “Malaysia”. The R package, Bibliometrix, and VOSviewer were used to analyse the articles' metadata, including publication trends, contributing institutions, journal sources, authors, and keywords. Thematic analysis was conducted to identify research themes from common words in titles, abstracts, and keywords. A total of 4630 articles published between 1976 and 28 April 2025 were retrieved. The earliest publication was in 1976, and the highest number of publications was recorded in 2022. The thematic analysis revealed that the articles could be categorised into four main research themes: ‘tropical medicine and infectious diseases’, ‘medical genetics and heredity’, ‘biotechnology and agriculture’, and ‘ecology, environment, and preservation’. These findings highlight Malaysia's remarkable advancements in genetic and genomic research, demonstrating the country’s growing expertise in biotechnology and molecular biology. As Malaysia continues to address emerging scientific challenges, it is establishing itself as a key player in applying molecular biology technologies.

Interleukin – 4 (IL-4) gene polymorphism (C-589T) in pregnant women with preeclampsia

Awatif Zabel Bdiwi, Sally Salih Jumaa, Azhar Hamid Rassol, Hayder Hussein Jalood

APJMBB 34(1): 207-213

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.19

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Preeclampsia is a common complication of pregnancy, contributing significantly to maternal mortality worldwide. The C-589T polymorphism in the IL-4 gene is believed to play a role in the impaired immune response associated with gestational hypertension, but this relationship has not been adequately investigated in pregnant women. This study aims to reveal the relationship between IL-4 gene polymorphism (C-589T) and pregnant women with hypertension. The polymorphism (C-589T) in the IL-4 gene is associated with lower blood IL-4 levels in pregnant women with hypertension, which may contribute to an immune dysregulation that increases the risk of preeclampsia. Sequence analysis is used to determine the genotypes and allele frequencies of the IL-4 gene polymorphism. ELISA is used to estimate interleukin-4 in blood serum. The CT genotype is more common in pregnant women with hypertension (30%) compared to the control group (20%). The higher frequency of the TT genotype in pregnant women with hypertension compared to healthy controls may indicate a protective role for the T allele. The present study indicates that the serum IL-4 concentration in pregnant women with hypertension (21.82 ± 3.79 rg/ml) is significantly lower than in the control group (24.03 ± 3.03). The protective trend observed for the T allele and TT genotype warrants further investigation in other studies. Although no strong genetic association was detected, the findings support the hypothesis that immune dysregulation, including lower IL-4 activity, contributes to the development of hypertensive disorders in pregnancy.

Hypoxia-conditioned MSC secretome attenuates CD38 expression and cellular senescence in a diabetic rat brain model

Bhirau Wilaksono, Agung Putra, Chodidjah, Mas Rizky A.A. Syamsunarno, Prasetyowati Subchan, Titiek Sumarawati, Nurul Hidayah, Mohammad Ariq Nazar

APJMBB 34(1): 214-223

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.20

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Diabetes accelerates neurodegeneration, partly through CD38-mediated NAD+depletion and cellular senescence. Secretome hypoxia mesenchymal stem cells (S-HMSCs) secrete anti-inflammatory factors such as IL-10, which may counteract neurodegenerative damage. This study evaluated the effects of S-HMSC therapy on CD38, p16, p21, and SIRT1 expression in the brains of STZ-induced diabetic rats. Male Wistar rats were divided into four groups: SHAM (healthy control), C (diabetic control), P1 (500 µL S-HMSC), and P2 (1000 µL S-HMSC). Diabetes was induced using streptozotocin (65 mg/kg, IP), confirmed by blood glucose >200 mg/dL. S-HMSCs were administered intraperitoneally on days 0, 7, 14, and 21. CD38 expression was assessed using immunohistochemistry (IHC); p16, p21, and SIRT1 were analyzed by qRT-PCR. CD38 expression significantly decreased in P1 (12.72 ± 2.65) and P2 (8.43 ± 1.01) compared to C (19.07 ± 2.70). p16 and p21 expression levels were significantly reduced in P1 and P2 compared to C (P < 0.05). SIRT1 was significantly upregulated in P1 (2.48) but downregulated in P2 (0.67), suggesting a nonlinear dose response. S-HMSC therapy reduces CD38 expression and senescence markers (p16, p21) in the diabetic brain. However, SIRT1 expression exhibits a biphasic dose response. These findings support the potential of S-HMSC therapy for modulating neurodegeneration in diabetes.

Isolation and characterization of non-symbiotic N-fixing bacteria from rhizosphere of Calopogonium mucunoides Desv.

Sri Anggreni Lindawati, Ni Nyoman Sista Jayasanti, I Wayan Suarna, Ni Nyoman Suryani

APJMBB 34(1): 224-233

Article DOI: https://doi.org/10.35118/apjmbb.2026.034.1.21

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Calopogonium mucunoides is a leguminous plant that thrives in low-fertility soils and possesses the ability to fix atmospheric nitrogen. Furthermore, the growth of C. mucunoides is supported by the interactions of rhizospheric bacteria and plant roots. The rhizosphere of C. mucunoides consists of diverse bacteria that are able to provide nutrients like nitrogen and produce plant growth hormones. The nitrogen fixation process in the rhizosphere of C. mucunoides can be carried out by non-symbiotic nitrogen fixing bacteria. This study aimed to isolate non-symbiotic N-fixing bacteria from the rhizosphere of C. mucunoides and evaluate their ability to produce Indole-3-Acetic Acid (IAA) as one of plant growth-promoting bacteria (PGPB) traits. Colony and cell morphology, phenotypic characterisation, IAA assay, 16S rRNA sequencing and phylogenetic analyses were conducted. Nine isolates capable of growth on Ashby’s Mannitol Agar were obtained. All isolates were catalase positive, and had optimal pH and temperature at 7 and 37 ⁰C. Seven of the nine isolates were subjected to 16S rRNA gene analysis and identified as Arthrobacter sp. (isolates K2.1 and K2.2), Ensifer adhaerens (isolate K4), Arthrobacter enclensis (isolate K5), Bacillus sp. (isolate K6), Gordonia namibiensis (isolate K8), and Kocuria sp. (isolate K9). IAA results showed that two isolates, namely K4 and K6 produced significant pink coloration and had similarity with Ensifer adhaerens PZS_S05 (99.78% identity) and Bacillus sp. (100% identity). These results indicated that the isolates from this study possess the potential to act as PGPB.