Milk protein composition has significant effect on the milk quality and nutrient value. Various cattle breeds show distinct milk protein polymorphisms as a result of single nucleotide polymorphism, insertion and deletion of nucleotides, and post-translational modification. The milk casein proteins comprise of one third of the total milk protein content and various variants predominate in different cattle populations. The A1 and A2 alleles of β- casein variants have shown some difference in their effect on human health. A single amino acid difference at 67th position (proline in A2 and histidine in A1) has shown profound effects on their physicochemical and functional properties as well as their effects on human health. The 7-amino acid peptide BCM-7 is produced upon enzymatic cleavage of A1 variant and it is a µ-opioid receptor agonist. The BCM-7 is found to have adverse health effects on the gastrointestinal, cardiovascular, endocrine, and nervous systems. The present review discusses in detail about the A1 and A2 bovine milk and their effects on human health, and how BCM-7 plays role in causing diseases of various organ systems. Future studies should be designed to provide clear guidance on the preferential use of A2 milk and to evaluate any potential consequences of gradually eliminating the A1 β- casein variant from cattle populations through selective breeding. This review presents a comprehensive mechanistic overview of β-casomorphin-7 (BCM-7), with particular emphasis on its interaction with μ-opioid receptors and associated systemic effects. It also discusses methods for the identification of A1 and A2 milk, compares their impacts on human health, and examines the biological effects of BCM-7 across multiple organ systems, including the gastrointestinal, cardiovascular, neurological, and endocrine systems. Furthermore, the review integrates evidence from animal, in vitro, and human studies, alongside considerations of casein genetic variants and dairy breeding strategies. The present review article will guide the researchers for a better research strategy to unravel the details of A1 vs. A2 milk consumption in a long run.
Human body odor occurs when the microflora of the skin degrades the odorless fatty acid produced by the apocrine glands into volatile odor molecules. This study aimed to evaluate the antibacterial activity of methanolic leaf extract of Psidium guajava against odor-producing axillary microflora, including Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, and Corynebacterium xerosis, using the agar well diffusion method for susceptibility testing and the broth microdilution method to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The study showed that all tested bacteria were sensitive to the leaf extract. S. epidermidis exhibited a higher MIC 0.68 mg/mL compared to S. aureus 0.22 mg/mL, whereas the remaining bacteria demonstrated an MIC of 2.05 mg/mL. The MBC for S. aureus was 6.17 mg/mL, while the other bacterial species showed a uniform MBC of 2.05 mg/mL. These findings suggest that guava leaf extract may serve as a potential alternative antibacterial agent for incorporation into cosmetic products, potentially replacing synthetic compounds.
Alizarin (1,2-dihydroxy-9,10-anthraquinone) is a naturally occurring anthraquinone derivative characterized by three conjugated aromatic rings and two central ketone groups. Many studies have also reported the potential of alizarin as an antitumor, anticancer, anti-inflammatory, and antibacterial. This study employs molecular docking simulations to evaluate the potential of alizarin as a natural immunomodulatory agent by assessing its interactions with key immune-related receptor proteins. The receptor proteins used are SYK (PDB ID: 6V0V), SRC (PDB ID: 2BDF), PIK3CG (PDB ID: 7JWE), and ARG1 (PDB ID: 3E6K). Molecular docking was performed using PyRx v.0.8 software, while molecular dynamics validation was conducted using CABS-flex. The results showed that alizarin compounds have drug-like properties with a bioavailability score of 0.55 and comply with the Lipinski Rule of Five. The results of the docking experiments demonstrated that each receptor has the capacity to bind with the compound, as indicated by the binding affinity values found in each complex. Of the four receptor-ligand complexes, alizarin-PIK3CG had the highest binding affinity (1.49 × 10-7 M), followed by alizarin-SRC (2.49 × 10-7 M), alizarin-ARG1 (2.21 × 10-6 M), and alizarin-SYK (1.02 × 10-5 M). Molecular dynamics validation using CABS-flex showed that all receptors had an RMSF value <3 Å, indicating structural stability and low solubility in the body. ADMET data confirmed that alizarin compounds are non-toxic and water-soluble. These findings suggest that alizarin exhibits promising immunomodulatory potential, particularly through its interaction with PIK3CG. Further in vitro and in vivo studies are warranted to validate its efficacy and therapeutic applicability.
SLE, or systemic lupus erythematosus in children, is a very severe long-term autoimmune disease where the body's own tissues are attacked by the immune system, and can lead to lupus nephritis, cardiovascular problems, and neurological complications. The study aims to determine the changes in gene expression of TNIP1, CSK and BANK1 in children with SLE and to compare them with healthy controls, thereby contributing to the understanding of lupus pathogenesis. The total number of samples is 75 serum samples, of which 50 were collected from children attending hospitals who had clinical signs of lupus. In addition, 25 samples were collected from healthy children. The samples were kept in TRIzol to preserve the mRNA. The mRNA was transcribed into cDNA for the determination of gene expression. The results showed that the distribution of SLE in females (66%) was higher than the distribution of SLE in males (34%). The gene expression of TNIP1 and CSK was significantly decreased in SLE children compared to healthy children. At the same time, our work demonstrated that gene expression of the BANK1 gene was significant increased compared to that of healthy children. In conclusion, the gene expression of TNIP1, CSK, and BANK1 differs in SLE children compared to healthy children, which may assist researchers and clinicians in using these genes as potential biomarkers of SLE detection. The findings are useful for understanding the molecular aspects of the disease and may in the future contribute to improved diagnostic and treatment approaches targeting these genes.
This study aimed to identify genetic variants associated with blood disorders in the Orang Asli and Malay populations by analyzing previously sequenced whole genomes thereby shedding light on the genetic burden within these groups. We focused on 14 key genes: BMP2, CD164, CYBRD1, EPAS1, EPO, HAMP, HBB, HFE, MTHFR, SH2B3, SLC40A1, TF, TMPRSS6, and VHL, chosen for their roles in hematopoiesis, iron metabolism, erythropoiesis, and oxygen homeostasis which are essential factors in blood disorders. We developed a bioinformatics pipeline to mine whole-genome sequences and map variants to public databases, identifying pathogenic SNPs linked to blood disorder risks. We predicted the functional impact of these SNPs using SIFT and PolyPhen-2. Of the 4,535-blood disorder-related nsSNPs identified, 45 were found in the Orang Asli and Malay populations. We further analyzed these variants for functional impact, conservation, and stability using HOPE, MutPred2, and I-Mutant, with Jalview for stability evaluation. Among the identified variants, rs235768 (BMP2), rs1799945 (HFE), rs1801133 (MTHFR), rs41298977 (TF), and rs190329416 (TMPRSS6), were classified as pathogenic. Compared with global population data, we observed significantly higher allele frequencies of rs1799945 and rs1801133 in both populations, indicating a population-specific risk for iron overload and folate metabolism disorders. These mutations impact protein interfaces and allosteric sites, influencing cell proliferation, iron transport, and homeostasis. In conclusion, the five identified variants are significant pathogenic factors that increase the risk of blood disorders in the Orang Asli and Malay populations. Further research is necessary to clarify their roles and implications.
The emergence of methicillin-resistant Staphylococcus aureus (MRSA) contributes to increased morbidity and mortality. Vancomycin is a last-resort antibiotic for the treatment of MRSA infections and its extensive use may lead to an increased occurrence of vancomycin-resistant S. aureus (VRSA). Detection of the vanA gene can be used to understand the mechanism of vancomycin resistance in S. aureus and to provide epidemiological data for preventing the spread of resistant strains. This study aimed to determine antibiotic resistance patterns and detect the presence of the vanA gene in S. aureus clinical isolates obtained from patients at Gunung Jati Hospital, Cirebon, Indonesia. A total of twenty S. aureus isolates were identified, and antibiotic susceptibility testing was performed using the Vitek‑2 Compact system. Detection of the vanA gene was carried out by polymerase chain reaction analysis. The Vitek-2 Compact analysis showed that 9 isolates (45%) were identified as MRSA, 2 isolates (10%) as VRSA, 1 isolate (5%) showed characteristics of both MRSA and VRSA, and 8 isolates (40%) were methicillin-sensitive S. aureus (MSSA). Differences in electrophoresis banding patterns were observed among VRSA, MRSA, and MSSA isolates. However, the vanA gene was not detected in any of the S. aureus clinical isolates from Gunung Jati Hospital. Although the vanA gene responsible for vancomycin resistance was not detected, the clinical isolates demonstrated resistance to multiple antibiotics. Therefore, increased vigilance in antibiotic use is necessary. Implementation of antibiotic stewardship strategies, including the use of sensitive antibiotics, may help reduce the risk of disease severity due to infection.
The medicinal properties of Clinacanthus nutans are mostly ascribed to its abundance of bioactive compounds. Therefore, the establishment of C. nutans callus culture is anticipated to play an integral part in the sustainable mass production of these beneficial compounds. The study used Murashige and Skoog (MS) medium added with the hormones of Naphthalene Acetic Acid (NAA), 6-Benzylaminopurine (BAP), or wood vinegar (WV) in single and combination methods. The types of explants applied for this callus induction were nodes and leaf explants. The resulting callus was then further multiplied on MS medium with 0.5 mg/L NAA. Within 7 weeks, measurements on the total phenolic content (TPC), total flavonoid content (TFC), and antioxidant capacity were conducted, and the results were subjected to correlation analysis. The MS + 0.5 mg/L NAA (93.11%) was the most effective medium for inducing callus in C. nutans from nodal explants. The callus extract TPC, TFC, DPPH, and FRAP analyses values were determined at the highest in week 7, given 185.98 mg GAE/g extract, 9.75 mg QE/g extract, 55.72 %, and 32.20 g FeSO4/g DW in C. nutans callus, respectively. The positive correlation between TPC and TFC with the antioxidant activities was documented.
Water kefir is a traditional fermented beverage that comprises a microbially diverse community enriched in lactic acid bacteria (LAB). Previous studies have examined the predominant species recovered from each sample. However, functional strain-level variation among multiple LAB isolates within a single kefir grain source remains insufficiently explored. This study aimed to isolate and characterise Lactobacillus species from Malaysian water kefir grains and evaluate their antioxidant activity and probiotic potential. Bacterial isolates were initially characterized through colony morphology, Gram staining, and catalase testing. Antioxidant activity was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays. Isolates demonstrating high levels of antioxidant activity were evaluated for probiotic characteristics, including acid and bile salt tolerance, adhesion to intestinal epithelial cells, and antibiotic susceptibility. Molecular identification was performed through 16S rRNA gene sequencing. Among fifteen isolates, isolates 2 and 5 exhibited significantly higher antioxidant activities (p < 0.05) with ABTS radical scavenging activities of 72.70 ± 3.38% and 77.74 ± 3.27%, and DPPH radical scavenging activities of 41.62 ± 1.18% and 48.07 ± 5.18%, respectively. Probiotic characterization demonstrated that isolate 2 exhibited higher bile tolerance and adhesion capacity with a 93.57 ± 1.31% survival rate under bile salt stress and 88.8 ± 6.3% adhesion rate to HT-29 cells. Molecular identification identified both isolates as Lacticaseibacillus paracasei, a species widely associated with probiotic functionality. Taken together, these findings highlight isolate 2 as a promising probiotic candidate with antioxidant potential, warranting further investigation to validate its functional efficacy and safety.
The African catfish (Clarias gariepinus) is a widely preferred species utilized in Malaysian aquaculture due to its adaptability and resilience to various environmental conditions. However, economic strains have led some fish breeders to use lower-quality feed that raises concerns about the halal integrity of the fish. This study aimed to investigate the presence of porcine DNA in African catfish sold at local markets, ensuring they meet halal standards for Muslim consumers. In this study, we extracted DNA from different tissues, flesh, stomach, and fins, to determine which offered the highest concentration. Notably, the fin showed the highest yield at 241.33 ng/µL. We used real-time polymerase chain reaction (RT-PCR) for porcine DNA detection because of its specificity and sensitivity. Out of 18 catfish samples tested, five showed positive for porcine DNA, indicating possible contamination linked to pig-derived feed. Interestingly, these samples had distinct characteristics, such as a yellowish hue and an unusual odor. This research underscores the need for strict DNA extraction protocols to ensure quality and compliance with halal standards, highlighting the importance of regulatory measures in aquaculture to protect Muslim consumers and support halal food markets globally.
Plectranthus amboinicus (Lour.) is a spice and medicinal vegetable with tenacious vitality, easy to grow, and able to thrive even in the shade, making it widely cultivated in Vietnam. This study aimed to evaluate the agronomic characteristics of 80 samples of Plectranthus amboinicus (Lour.) from 8 provinces, based on a morphological assessment of stem height, root length, and leaves, combined with molecular biology methods to determine genetic relationships using the Internal Transcribed Spacer (ITS) gene region sequencing. The results of the morphological characteristics of the plant samples showed variations in stem height, leaf length, leaf width, and root length; however, flowers and fruits showed little variation among samples. Samples collected from An Giang and Hau Giang provinces were relatively larger than those from other provinces. Phylogenetic analysis demonstrated a close genetic relatedness among Plectranthus amboinicus (Lour.) genotypes from the eight provinces, while exhibiting a genetic distance of 0.2970 from the control species, Mentha arvensis, an exotic species. Therefore, there were differences in the morphological characteristics of Plectranthus amboinicus (Lour.) among the samples. The amplified sequence of the ITS gene region of the experimental samples was approximately 600 bp in size, and sequencing results showed high similarity to to published Plectranthus amboinicus (Lour.) reference sequences.
Prostate cancer remains a major global health concern, highlighting the need for continuous investigation of bioactive compounds with potential relevance to its management. This study presents a computational assessment of andrographolide through an integrated approach combining Absorption, Distribution, Metabolism, and Excretion (ADME) prediction, network analysis, molecular docking, and molecular dynamics (MD) simulation. ADME profiling indicated that andrographolide meets drug-likeness parameters, including Lipinski’s Rule of Five. Network analysis of prostate cancer-associated genes using the STRING database revealed a cluster of six nodes, from which three key targets, androgen receptor (AR), CYP17A1, and SRD5A2, were selected for docking analysis. Docking results suggested favorable interactions between andrographolide and these targets. Furthermore, MD simulations of the androgen receptor complex, with metribolone as a reference ligand, demonstrated stable binding patterns and comparable binding energies (-49.95 and -50.94 kcal/mol, respectively). While further experimental validation is required, these computational findings provide preliminary insights into the possible role of andrographolide in prostate cancer research.
Mutations within the receptor‑binding domain (RBD) of SARS‑CoV‑2 present significant challenges to the development of vaccines and antibody‑based therapies. These alterations enable the virus to evade neutralizing antibodies produced by vaccination and also therapeutic antibodies currently in use. Research has further demonstrated that the RBD plays a critical role in mediating interactions with host cells and can alternate between two conformational states, referred to as “up” and “down.” In light of these challenges and the urgent need for effective countermeasures against emerging variants, the characterization and design of novel antibody formats are essential. This study aims to examine how RBD mutations and epitope classification can inform the advancement of antibody therapeutics, particularly in the context of ongoing viral evolution. Based on the data analysis, key mutations such as E484 and N501, together with the conserved epitope sequence 469STEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYR509, are proposed as promising targets for the development of antibody‑based therapies and vaccine strategies.
Asthenozoospermia is a form of male infertility characterised by a marked reduction in sperm motility. This condition necessitates the use of Assisted Reproductive Technology techniques to achieve successful conception. These techniques require the preparation of semen samples enriched with active and motile sperm. Various preparation methods have been proposed, including density gradient centrifugation (DGC) and swim-up techniques. DGC is more preferred for poor-quality samples. This study aimed to improve the efficacy of the DGC technique using theophylline as an enhancement factor to increase the yield of active motile sperm. Briefly, semen samples from normozoospermic individuals (n=60) and asthenozoospermic individuals (n=80) were collected and analysed using the conventional sperm analysis. Each sample was divided into three equal aliquots, which were exposed to the conventional density gradient centrifugation, incubation with theophylline and to a combination of both treatments. The results showed that theophylline addition improved the yield of active motile sperm, particularly in samples from asthenozoospermic individuals. Overall, the study suggests that theophylline may serve as an effective enhancement factor for isolating and concentrating active motile sperms in semen samples obtained asthenozoospermic males.
Streptococcus pneumoniae is a significant human pathogen globally, associated with various pneumococcal infections, implicated in conditions such as pneumonia, meningitis, otitis media and sepsis. The pathogen employs numerous virulence factors, such as capsular polysaccaharide (CPS), choline binding protein (CBP), lipoproteins and pneumolysin, to engage with and evade host immune response. Recent studies have emphasised the significance of extracellular membrane vesicles (EMVs) in pathogenesis and immunity, making them potential targets for innovative treatment and vaccination approaches. This review provides a comprehensive overview of EMVs derived from S. pneumoniae and delves into their immunogenic potential as a promising novel vaccine candidate against pneumococcal infections. This review describes the mechanisms of EMVs biogenesis, their various immunogenic properties and their capability to influence host immune responses. This review synthesises findings of the past 10 years (2014-2024) regarding S. pneumoniae EMVs, emphasising their biogenesis, composition, immunogenic properties and roles in host-pathogen interactions. Besides, this review also elaborates on EMV-based vaccines and the challenges associated with their advancement. The research underscores the diverse functions of EMVs derived from S. pneumoniae in pathogenesis, encompassing biofilm formation, immunological evasion and host cell damage. EMVs exhibit strong immunogenic characteristics capable of provoking both innate and adaptive immune responses. Pre-clinical studies have indicated EMVs as a broad-spectrum vaccination candidate, overcoming the constraints of existing serotype-specific vaccines. Nonetheless, challenges such as variations in EMVs’ composition, safety issues and production scalability persist as considerable barriers. EMVs are promising strategies in the global control of pneumococcal infections because of their ability to elicit cross-serotype immunity, yet further study is required to solve safety and manufacturing issues.
Turbinado sugar is often placed as healthier, natural white sugar alternative, based on the minimal processing and maintenance of trace molasses content. The scientific rationale behind such assertions is critically evaluated in this review, by taking into account the nutritional, metabolic, environmental, and ethical aspects of turbinado sugar production and utilization. Available evidence suggests that turbinado sugar and white sugar are very comparable in caloric content and glycemic load, and there are no notable health benefits. Further, most purported health benefits of turbinado sugar are marketing and publicly led misconceptions and not scientifically backed. The environmental issues of water usage, soil loss, and carbon emissions are also relevant to turbinado sugar, and sustainability is place-specific farming and processing procedures. Ethical considerations of exploitation of labor and greenwashing in labeling further muddy the waters. The review is urging enhanced nutrition literacy, more transparent food labelling regulation, and evidence-based nutritional recommendations. Finally, replacing refined sugar with turbinado sugar does not dismiss health risks but rather decreasing total added sugar consumption and promoting whole-food-based dieting as the most ideal method of public health promotion.
Muscle, the largest tissue in geese, is crucial for developing goose fatty liver. Investigating the influence of Insulin-like Growth Factor Binding Protein 2 (IGFBP2) on muscle during fatty liver development is crucial for understanding its regulatory mechanisms. In this study, twenty-four 70-day-old male Landes geese were divided into two groups: an overfeeding group and a control group (n = 12 each). Pectoral muscle samples were collected at 82 and 94 days of age. Additionally, twenty-four 10-day-old geese were divided into a glucose injection group and a saline control group (n = 12 each), with pectoral muscle samples collected 2 hours post-injection at 17 days of age. Goose primary myocytes were treated with glucose (0, 25, 50, and 100 mmol/L) or insulin (0, 5, 10, and 20 nmol/L) and transfected with an IGFBP2 overexpression vector or an empty vector. Results demonstrated that overfeeding, glucose injection, 50 and 200 mmol/L glucose treatment, and 10 and 20 nmol/L insulin treatment significantly inhibited the expression of IGFBP2 in both muscle and cell samples (P < 0.05). Overexpression of IGFBP2 increased the expression of LOC106030908, FGB, and LOC106040417, while inhibiting PLPP4, PTGS2, IL6, and LOC106041919 (P < 0.05). Notably, gene expression showed an inverse pattern in the muscles of overfed geese. Additionally, glucose and insulin upregulated LOC106041919 and LOC106040417 while downregulating LOC106030908 in goose myocytes (P < 0.05). These results suggest that glucose and insulin modulate inflammation and glycolipid metabolism genes in goose muscle via IGFBP2 during fatty liver development, providing new molecular insights.
Secondhand smoke (SHS) exposure injures renal tissue and may accelerate chronic kidney disease, highlighting the need for accessible nephroprotective strategies such as Peperomia pellucida (PP). We conducted a true experimental, post-test–only study in male Wistar rats (n = 21; 8–12 weeks; 180–220 g) randomized to three groups (n = 7 each): normal control, SHS, and SHS plus PP. PP extract (400 mg/kg/day, oral gavage) was administered for five weeks; SHS exposure (one cigarette/rat/day, whole-body chamber) was delivered for four weeks. At endpoint, kidneys were processed for hematoxylin–eosin staining, and histopathology was scored semiquantitatively across endothelial, glomerular, tubular, and interstitial compartments. Two-way ANOVA with Tukey’s post hoc test (α = 0.05) evaluated group differences. Overall effects were significant for all compartments (p < 0.0001). SHS produced the highest injury burden, indicating diffuse renal damage with a tubulointerstitial predominance. Co-treatment with PP significantly reduced lesion scores versus SHS alone across all compartments (p < 0.05), although values did not fully normalize to the control group, indicating partial structural preservation rather than complete rescue. These results demonstrate that PP confers measurable nephroprotection against SHS-induced renal injury in vivo, most notably attenuating tubulointerstitial lesions. Future work incorporating mechanistic biomarkers, dose–response optimization, and pharmacokinetic profiling is warranted to define the mode of action and enhance translational potential.
Endophytic fungi are known to produce bioactive compounds similar to those of their host plants, making them promising sources of novel antimicrobial agents. The use of endophytic fungi offers several advantages, including reduced dependence on rare plants, sustainable production, lower environmental impact, and rapid metabolite yield. This study aimed to evaluate the antibacterial activity of the endophytic fungus Lasiodiplodia pseudotheobromae IBRL OS-64 against selected aquaculture-related pathogenic bacteria. The antibacterial activity of the ethyl acetate extract of L. pseudotheobromae IBRL OS-64 was assessed against four Vibrio species, namely Vibrio parahaemolyticus ATCC 17802, V. alginolyticus CCB-PB317, V. owensii CCB-PG2, and V. azureus CCB-ST2H16, using disc diffusion and broth microdilution assays. The extract exhibited notable antibacterial activity, with inhibition zone diameters ranging from 9.2 ± 0.4 to 12.4 ± 0.4 mm. Minimum inhibitory concentration (MIC) values ranged from 500 to 1000 µg/mL, while minimum bactericidal concentration (MBC) values ranged from 500 to 4000 µg/mL. Time-kill analysis demonstrated that the extract exerted bactericidal effects at higher concentrations, with bacterial reduction influenced by both extract concentration and exposure duration. Scanning electron microscopy revealed severe structural damage to treated bacterial cells, including membrane disruption, cavity formation, cell crumpling, and lysis. These findings suggest that the ethyl acetate extract of L. pseudotheobromae IBRL OS-64 has potential as an alternative antibacterial agent for controlling bacterial infections in aquaculture products.
Rickettsial infections are neglected and underdiagnosed in Malaysia. The epidemiological data and the exact burden of rickettsial infection in Malaysia are limited. The conventional serology method is usually used to diagnose the infection. However, the method is laborious and requires reference serum and antigens. Moreover, it can only detect a limited number of rickettsia species and strains. Hence, molecular genotyping is the method of choice for studying the genetic diversity of rickettsia as it can detect the causative agents at the genomic level. This study aimed to identify and characterize rickettsia species among adults presented to Teluk Intan Hospital, Perak, Malaysia, by polymerase chain reaction and DNA sequencing. A total of 141 Malaysian adult blood samples that fulfil the inclusion and exclusion criteria were recruited. These samples were subjected to PCR for scrub typhus (Orientia tsutsugamushi) by detecting the presence of 56-kDa type-specific antigen (TSA) gene and other rickettsiae by detecting the presence of 17-kDa. Only one sample was detected positive for scrub typhus, and sequence-verified to have a closet match with Orientia tustsugamushi strain UT302, which was originally isolated from Thailand. The number of positive cases was lower than anticipated, this was most likely due to the consequences of the global COVID-19 pandemic since December 2019, which coincide with the period of sample recruitment. The restriction control movement implemented by the Malaysian government and the Hospital being gazetted as a COVID-19 hospital has greatly affected the patient recruitment for this study.
Cervical cancer is one of the leading causes of cancer-related mortality in women worldwide. Persistent infection with Human Papillomavirus (HPPV) is recognized as the predominant etiological factor, primarily through the expression of the viral oncoproteins E6 and E7. These proteins disrupt key cell cycle regulatory pathways, promote uncontrolled cellular proliferation, and drive the malignant transformation. Although various therapeutic approaches, including surgery, chemotherapy, and radiotherapy, have been developed to reduce cervical cancer mortality, the limitations of conventional treatments, including toxicity, recurrence, and reduced efficacy in advanced-stage disease, underscore the urgent need for more effective and targeted strategies. In this context, the E6 and E7 oncoproteins have emerged as highly promising therapeutic targets, not only because of their indispensable roles in HPV-mediated oncogenesis but also due to their strong immunogenic properties. Consequently, substantial efforts have been directed toward developing E6/E7-based therapeutic vaccines. Multiple vaccine platforms, including DNA and protein-based vaccines, have demonstrated favorable safety profiles and the capacity to induce robust immune responses. Furthermore, preclinical and clinical studies suggest their potential to generate antitumor activity while offering prophylactic benefits in certain settings. Despite these advances, several challenges continue to limit the clinical translation and therapeutic efficacy of E6/E7-targeted vaccines. One major barrier is the tumor microenvironment (TME), which suppresses host antitumor immunity and attenuates vaccine-induced immune responses. In addition, intratumoral heterogeneity may facilitate immune escape mechanisms, allowing malignant cells to evade immune surveillance and persist, despite treatment. Therefore, future directions for E6/E7-based vaccine development should focus on overcoming these barriers through combination strategies with other immunotherapeutic modalities, particularly immune checkpoint inhibitors (ICIs), as well as the incorporation of more potent adjuvants, multi-epitope vaccine design, and precision medicine approaches. Collectively, these advances may enhance therapeutic efficacy and pave the way for more personalized and durable treatment options for patients with cervical cancer.
