Malaysian Journal of Science (MJS)

The Role of The EphrinB2-EphB4 Bidirectional Signalling on Bone Remodeling: A Review

2025-04-25T00:47:00+08:00

Postmenopausal osteoporosis is a prevalent disease that can lead to serious outcomes such as fractures. Oestrogen deficiency during menopause and postmenopause increases bone turnover, with elevated bone resorption and formation. However, resorption surpasses formation, resulting in bone loss. Identifying intervention targets in bone physiology to restore bone remodeling balance and normal bone mass is the initial aim in developing new effective therapies. Currently, EphrinB2/EphB4, one of the membrane coupling factors between osteoclasts (OCs) and osteoblasts (OBs), is a prominent topic in bone disease research. However, the regulatory mechanisms of EphrinB2-EphB4 bidirectional signalling on OC and OB and its effects remain incompletely understood. This review seeks to clarify the physiological roles and mechanisms of known EphrinB2-EphB4 bidirectional signalling in bone remodeling, providing insights for future studies on modulating this signalling pathway.

Policy Elements Influencing the Sustainability of the Biosimilar Market in Malaysia: A Review

2025-04-25T00:46:28+08:00

Sustaining the market for biosimilars is key to securing the long-term benefits from biosimilar medicines. Policy can influence the achievement of those elements that contribute to the sustainability of biosimilars. Despite being the first country to implement regulatory guidelines for the approval and marketing of biosimilars, the availability and adoption of biosimilars in Malaysia remain suboptimal. This study aims to create the roadmap of policy elements that influence the sustainability of the biosimilar market in Malaysia. The study searched and reviewed articles in PubMed, Google Scholar, National Library of Medicine from 1/1/2003 to 14/04/2024. A total of 3469 results were found, with PubMed contributing 39 records (n=39), Google Scholar contributing 3074 records (n=3074), and the National Library of Medicine contributing 356 records (n=356). The biosimilars policy framework and sustainability measures were adopted from IQVIA Country Scorecards for Biosimilar Sustainability. After eliminating duplicates and applying selection criteria, 20 articles were chosen for review. The selection was justified based on relevance to the five policy domains: regulatory environment and clinical guidelines, awareness and education, incentives, pricing rules and dynamics, and purchasing mechanisms. The 20 selected papers were categorized into five main domains: regulatory environment and clinical guidelines, awareness and education, incentives, pricing rules and dynamics, and purchasing mechanisms. The analysis revealed positive developments in regulatory compliance and clinical guidelines, pricing regulations, and purchasing mechanisms. However, challenges were identified in the areas of awareness and education, pricing rules and dynamics, and incentives. Awareness and education challenges were primarily attributed to limited pharmacist training and physician skepticism regarding biosimilars. Additionally, the absence of strong financial incentives and limited patient education hindered adoption. The "single-winner tendering system" constrained market diversity, restricting competitive pricing. The literature review emphasizes the need for setting up specific prescription targets, promoting competition, and offering incentives to biosimilar manufacturers to increase market appeal. Furthermore, it is critical to enforce strict quality standards for the incorporation of tenders and align the registration requirements with global standards. Education for pharmacists and continuous training for healthcare practitioners are also essential. In Malaysia, these steps are crucial in ensuring the affordability and accessibility of biosimilars. Improving these policy components could help Malaysia create a competitive biosimilar market, increase access to affordable treatments, and eventually raise the standard of healthcare service.

Assessing Diabetes Screening Outcomes in Klang Valley, Malaysia: A Cross-Sectional Study

2025-04-24T22:37:09+08:00

Diabetes mellitus, once primarily affecting the elderly, is now increasingly diagnosed in younger individuals due to poor lifestyle habits. Early detection through health screening is essential for effective management. A government agency that has conducted diabetes screening programs since 2013 launched its third initiative, aiming for an 80% detection rate among screened participants using HbA1c (cutoff ≥ 6.3%), rather than reflecting national diabetes prevalence. This cross-sectional study evaluated the program’s effectiveness in detecting diabetes among Malaysian adults aged 40 to 59 in Klang Valley. A total of 188 participants attended free screenings at registered clinics between September and December 2023. The cohort included 47.35% men and 52.65% women, with 41.5% Malays, 40.4% Chinese, 14.4% Indians, and 3.7% from other ethnic groups. HbA1c levels ≥ 6.3% were found in 27.12% of participants, with the highest prevalence among Indians (33.3%), followed by Malays (29%), Chinese (23.68%), and others (14.28%). Statistical analysis (ANOVA) showed no significant association between HbA1c levels and age, gender, or ethnicity (p = 0.188). The program did not meet its 80% detection target, suggesting that alternative screening approaches, including revised diagnostic criteria or additional risk assessments, may be needed to improve diabetes detection and intervention efforts.

Expression Profile of PmiR-31, Novel npcRNA Of Proteus Mirabilis Under Different Growth Phases and Stress Conditions

2025-07-02T07:42:34+08:00

Proteus mirabilis (P. mirabilis), known for its swarming motility, is a facultatively anaerobic, rod-shaped, Gram-negative bacterium. It forms extended swarmer cells as well as moves in a bull’s-eye formation. Proteus mirabilis significantly causes catheter-associated urinary tract infections through virulence components including flagella, fimbriae, hemolysin, urease, and proteases. Flagella-related motility allows P. mirabilis to infect the urinary system. The flagellum, composed of about 20 proteins, has a body that penetrates the cell wall, a curved hook, and a filament extending several micrometers. Previously, we knocked out PmiR-137, anticipated to modulate flhDC, which involve in the central transcriptional activator for flagellum formation and performed a differential gene expression study. We discovered npcRNA PmiR-31, expected to influence fliZ production via the TargetRNA web tool. We analyzed PmiR-31 expression under various stress and growth phases via northern blot. The PmiR-31 was highly expressed in stress conditions but not in the mutant strain. Since FliZ regulates flagella assembly, npcRNA PmiR-31 may repress fliZ translation, preventing flagella synthesis and promoting biofilm formation to evade the immune system.

Unveiling The Roles of npcRNA Modulating the Molecular Mechanism of Pathogenic Bacteria Causing Urinary Tract Infections (UTIs)

2025-05-06T08:52:36+08:00

Urinary tract infections (UTIs) are among the most prevalent and chronic health problems worldwide, impacting millions of individuals annually and posing a substantial financial burden on healthcare systems. UTIs typically initiate when pathogenic bacteria, originating from the gastrointestinal tract, colonize the urethra or periurethral region. Women are more susceptible to UTIs compared to men because of the differences in female lower urinary tract anatomy and its proximity to reproductive organs. The pathogenic bacteria, which are on the World Health Organization (WHO) priority list and cause both uncomplicated and complicated UTIs, are Escherichia coli (UPEC), Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus aureus. Different therapeutic approaches are necessary to combat UTIs, as seen by the rise in antibiotic resistance in bacteria. Non-protein coding RNAs (npcRNAs) have emerged as promising candidates for regulating genes involved in bacterial pathogenesis and infection, playing a role in modulating gene expression and host-pathogen interactions. By targeting bacterial virulence factors, biofilm formation, and antibiotic resistance mechanisms, npcRNAs provide a novel approach to disrupting infection pathways while minimizing the risk of resistance development.

A Patient with Platelet Transfusion Refractoriness

2025-05-19T12:34:30+08:00

Platelet transfusion refractoriness is a less-than-expected increase in platelet count following platelet transfusions. We report a case of platelet transfusion refractoriness with identification of anti-HLA class I alloantibody. In patients with thrombocytopenia, even when multiple established aetiologies are present, it is essential to recognise platelet transfusion refractoriness and to perform further laboratory investigations, including platelet immunology test. This approach enables identification of additional contributing factors to thrombocytopenia and clarification of the underlying causes of platelet refractoriness, thereby guiding appropriate therapeutic strategies.

A Patient’s Journey with Immunoglobulin Light Chain (Al) Amyloidosis

2025-05-19T12:29:10+08:00

A 64-year-old man presented with progressively worsening difficulty in breathing and was subsequently diagnosed with immunoglobulin light chain (AL) amyloidosis. However, he was keen to seek a second opinion, causing a delay in initiating definitive treatment. His clinical manifestations included heart failure, chronic diarrhoea, symmetric lower extremity peripheral neuropathy, and autonomic neuropathy (postural hypotension). As he was non-transplant eligible and had financial constraints, he was initially treated with conventional chemotherapy [two cycles of cyclophosphamide + thalidomide + dexamethasone, followed by seven cycles of melphalan + prednisolone (MP)]. Throughout his disease course, he experienced chronic diarrhoea and profound oedema of lower limbs. He had to relocate to his son’s residence in Kuala Lumpur to enable frequent and regular hospital visits. He had impaired health-related quality of life (HRQoL); however, he had excellent family support. After nine cycles of conventional chemotherapy, the optimal response was not achieved. Bortezomib was added to MP therapy [bortezomib + melphalan + prednisolone (VMP) regimen]. Following three cycles of VMP, he achieved complete haematologic response (CR), resulting in symptomatic improvement and his eventual return to his hometown. He continued the same treatment regimen to control the disease. His hospital admissions decreased, and his HRQoL improved, although no organ response was noted. Three years later, he developed decompensated cardiac failure and passed away. His overall survival was five years and two months. This case report highlights that achieving CR leads to prolonged overall survival and improved long-term clinical outcomes, including HRQoL.

Bioinformatics Analysis of Potential Biomarkers for Lupus Nephritis

2025-05-11T06:20:35+08:00

Lupus Nephritis (LN) is a complication of Systemic Lupus Erythematosus affecting the kidney. The purpose of this study was to identify signalling pathways and hub genes involved in the pathogenesis of LN. Methods: The mRNA expression profiles of LN were obtained from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) were identified using the online tool GEO2R. Enrichment analysis was conducted in DAVID. The Protein-Protein Interaction network of DEGs was constructed in STRING, and hub genes were identified with Cytoscape. The hub genes were validated using differentially expressed proteins (DEPs) from proteomics data to identify potential biomarkers for LN. Results: A total of 138 DEGs were identified, primarily associated with immune response, neutrophil chemotaxis, and antimicrobial humoral immunity. In KEGG analysis, the NOD-like receptor signalling pathway and the Cytokine-cytokine receptor interaction pathway were mainly involved. Nine hub genes of LN, including Ifit1, Ifit3, Ifih1, Ifi44, Irf7, Irf9, Oasl1, Stat1, and Usp18 were identified. Conclusion: Ifi44 and Stat1 were expressed in both DEGs and DEPs. Ifi44 and Stat1 may be potential biomarkers and therapeutic targets for LN.

Safety Assessment of One Day Treatment of Liquorice Extract in Female Sprague Dawley Rats

2025-05-02T17:29:17+08:00

This study aimed to provide preliminary data on the safe use of liquorice extracts for herbal product consumers. Female Sprague Dawley rats received a single-day treatment with liquorice extract (50–2000 mg/kg) or distilled water (control). Liver and kidney functions were evaluated through blood biochemical analysis, gross, and histological evaluation. This animal study adhered to the OECD Test Guideline 423. Fifteen female SD rats, aged 16 weeks, were randomly assigned to five groups (n = 3). The control group received distilled water, while treatment groups T1, T2, T3, and T4 were administered liquorice extract at doses of 2000, 200, 100, and 50 mg/kg via oral gavage. Body and organ weights (liver, kidney, heart) were measured. Blood samples were collected to assess serum biochemical markers, including alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), creatinine, and urea levels. Data were analysed using Dunnett’s tests, with p < 0.05 denoting statistical significance. No significant changes in body or organ weights occurred across groups. Liquorice extract had no effect on ALT or GGT. Serum creatinine decreased (p < 0.05) at 200 mg/kg, and serum urea decreased at 50 mg/kg compared with controls. A single-day liquorice extract treatment (50–2000 mg/kg) was safe and caused no hepatic or renal toxicity in female SD rats.

A Rare Case of Fibrosing Obliterative Appendicitis in a Young Patient: Case Report

2025-05-11T06:41:06+08:00

Fibrosing obliterative appendicitis is an uncommon inflammatory condition of the appendix that can lead to significant diagnostic challenges, particularly in younger patients. In a patient presenting with abdominal pain at the emergency department, appendicitis must be considered and ruled out. However, due to various causes of abdominal pain, the diagnosis of appendicitis may be challenging. Therefore, thorough history taking and a careful clinical examination are essential for identifying appendicitis and ensuring prompt treatment. This study describes a young patient who presented with a complaint of right lower abdominal pain for the past 4 days. A 14-year-old male presented to the emergency department with right lower abdominal pain, without associated symptoms. He had a similar episode three months earlier and was treated conservatively. Ultrasound suggested mesenteric lymphadenitis. Diagnostic laparoscopy was initially performed, but was then converted to open surgery due to an invisible appendix. The procedure revealed an inflamed, slender appendix adhering to the cecum with enlarged mesenteric lymph nodes. Appendectomy and lymph node excision were performed. Histopathology confirmed fibrosing obliterative appendicitis with reactive lymphadenitis. The patient was discharged after two days in stable condition. This case highlights the diagnostic challenge of chronic appendicitis in paediatric patients. Diagnostic laparoscopy proved valuable in identifying fibrosing obliterative appendicitis, allowing for effective surgical intervention.

Integrated Analysis of Cytoskeleton-Associated lncRNAs and Their Regulatory Networks in Mouse Oocyte Maturation

2025-05-02T17:51:23+08:00

With the increase in maternal age and the impact of environmental stress, the decline in ovarian reserve and oocyte quality has emerged as a primary cause of infertility. Dysfunction of cytoskeletal proteins plays a central role in this process. This study aims to examine the differential expression and regulatory functions of cytoskeleton-associated long non-coding RNAs (lncRNAs) during the development of mouse oocytes at the germinal vesicle (GV) and metaphase II (MII) stages. This study employed bioinformatics analyses and machine learning techniques to analyze publicly accessible data from the Gene Expression Omnibus (GEO) database, which comprised 13 samples of Germinal Vesicle (GV) stage oocytes and 15 samples of Metaphase II (MII) stage oocytes. Differential expression analysis, weighted gene co-expression network analysis (WGCNA), and interaction network construction were performed to screen for lncRNAs closely related to oocyte development. A total of 338 differentially expressed lncRNAs (DE-lncRNAs) with statistical significance were identified, including 136 upregulated and 202 downregulated lncRNAs, indicating their potential roles in the transition from the GV to the MII stage during oocyte development. WGCNA further identified modules strongly correlated with cytoskeletal proteins by integrating these results with the differentially expressed lncRNAs. A total of 47 candidate lncRNAs were shortlisted. Subsequently, LASSO regression and random forest algorithms were applied to identify six key lncRNAs from the candidate set. Combined with miRNA prediction and target gene analysis, a lncRNA-miRNA-mRNA regulatory network was constructed, revealing that these key lncRNAs may indirectly regulate downstream target gene expression through specific miRNAs. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these key lncRNAs are primarily involved in cytoskeletal remodeling, cell proliferation, and differentiation, and may play critical roles in follicle structure formation and oocyte development. This study systematically mapped the regulatory network of lncRNAs during oocyte development and elucidated the lncRNA-miRNA-mRNA interactions. The results emphasize the key roles of lncRNAs in cytoskeletal remodeling and oocyte maturation, providing valuable insights for the diagnosis and treatment of ovarian disorders.

Rare Case of High Voltage Electric Injury Resulting in Bowel Perforation: A Successful Management with Diversion Colostomy

2025-05-11T06:50:09+08:00

Electrical injuries are categorized into low-voltage injuries (<1 kilovolt) and high-voltage injuries (>1 kilovolt). Electrical injuries usually present with an entry wound at the site of contact and an exit wound where the current leaves the body. Bowel perforation caused by an electric current is a rare but serious complication. We report a case of a high-voltage electric burn with entry wounds on both hands and an exit wound on the right foot, complicated by descending colon perforation, which presented late with peritonitis. The patient was successfully treated with a diversion colostomy and subsequent takedown. This case highlights the potential for significant internal injuries, such as bowel perforation, following high-voltage electrical injuries and emphasizes the importance of timely surgical intervention for such complications.

Behavioral and Neuronal Alterations Following Oral Naphthalene Exposure in Rats

2025-05-06T09:15:39+08:00

Naphthalene (NP), a widely used polycyclic aromatic hydrocarbon, is present in various commercial products and environmental pollutants. Despite its established toxicity, its impact on neuronal integrity and behavior remains relatively underexplored. This study investigates oral NP-induced behavioral and neuronal alterations in Sprague Dawley rats. Twenty-five animals were divided into five groups and oral NP was administered at varying doses (200 mg/kg and 400 mg/kg) for 28 days, with post-treatment evaluations up to 42 days. Behavioral assessments using the open field test revealed initial hyperactivity, followed by a progressive decline in locomotion and increased anxiety-related behavior in high-dose groups. Cresyl violet staining of the basolateral amygdala showed significant neurodegeneration, with pyramidal neuronal damage more pronounced in high-dose groups. Statistical analysis was conducted using one-way ANOVA, and post-hoc Duncan's test was applied to confirm a dose-dependent decrease in neuronal viability (p < 0.05). Post-treatment observations indicated partial behavioral recovery but no significant reversal of neuronal damage. The findings suggest that oral NP exposure induces anxiety-associated behavioral changes and neurotoxicity in the amygdala, potentially affecting emotional regulation. Further investigation is required to assess the long-term effects of oral NP exposure on brain function.

Therapeutic Potential of Cannabidiol in Alleviating Cognitive Decline and Hippocampal Damage in a Rat Model of Alzheimer's Disease

2025-04-25T00:44:18+08:00

Alzheimer's disease (AD) is a common neurodegenerative disorder marked by progressive cognitive decline. Due to its effects on cognitive functioning and hippocampal integrity, the combined treatment of D-galactose (D-gal) and Aluminium chloride (AlCl3) in rats is a widely used model for producing AD-like symptoms. Previous studies demonstrated that Cannabidiol (CBD) exhibits neurotherapeutic effects. This study examines the efficacy of CBD in reducing cognitive deficits and brain ultrastructural damage induced by D-gal and AlCl3. Male Wistar rats were treated with D-gal (60 mg/kg body weight/day) and AlCl3 (200 mg/kg body weight/day) for 10 weeks to induce AD-like symptoms, followed by CBD administration at doses of 20, 40, and 80 mg/kg/day. Donepezil (1 mg/kg body weight/day) served as a positive control. Cognitive performance was evaluated using the modified elevated plus maze and T-maze spontaneous alternation tests. Ultrastructural changes in the hippocampus were examined using transmission electron microscopy. Rats exposed to D-gal and AlCl3 exhibited significant cognitive impairments, including deficits in spatial learning and memory, as well as hippocampal ultrastructural damage. The results indicated that D-gal and AlCl3 exposure produced notable cognitive deficits and structural alterations in the hippocampus. Administration of CBD at all doses significantly enhanced cognitive function and reduced pathological changes, providing protective effects comparable to donepezil. These findings support CBD's potential as a neurotherapeutic compound for mitigating cognitive decline and hippocampal damage associated with AD.