Browse publications by year: 2025

A Comprehensive Review of Challenges in Oral Drug Delivery Systems and Recent Advancements in Innovative Design Strategies

Loke YH, Jayakrishnan A, Mod Razif MRF, Yee KM, Kee PE, Goh BH, et al.

Curr Pharm Des, 2025;31(5):360-376.
PMID: 39390835 DOI: 10.2174/0113816128338560240923073357

The oral route of drug administration is often preferred by patients and healthcare providers due to its convenience, ease of use, non-invasiveness, and patient acceptance. However, traditional oral dosage forms have several limitations, including low bioavailability, limited drug loading capacity, and stability and storage issues, particularly with solutions and suspensions. Over the years, researchers have dedicated considerable effort to developing novel oral drug delivery systems to overcome these limitations. This review discusses various challenges associated with oral drug delivery systems, including biological, pharmaceutical, and physicochemical barriers. It also explores common delivery approaches, such as gastroretentive drug delivery, small intestine drug delivery, and colon-targeting drug delivery systems. Additionally, numerous strategies aimed at improving oral drug delivery efficiency are reviewed, including solid dispersion, absorption enhancers, lipidbased formulations, nanoparticles, polymer-based nanocarriers, liposomal formulations, microencapsulation, and micellar formulations. Furthermore, innovative approaches like orally disintegrating tablets (ODT), orally disintegrating films (ODF), layered tablets, micro particulates, self-nano emulsifying formulations (SNEF), and controlled release dosage forms are explored for their potential in enhancing oral drug delivery efficiency and promoting patients' compliance. Overall, this review highlights significant progress in addressing challenges in the pharmaceutical industry and clinical settings, offering novel approaches for the development of effective oral drug delivery systems.

MeSH terms: Administration, Oral; Pharmaceutical Preparations/administration & dosage; Pharmaceutical Preparations/chemistry; Humans; Drug Design; Drug Delivery Systems*
Evaluation of heavy metal pollution and ecological risk of surface sediments in a tropical mountainous River-Estuary-Shelf Continuum system: A case study of the Selangor River, Malaysia

Wang A, Bong CW, Tao S, Ye X, Liu B, Liang H, et al.

Mar Environ Res, 2025 Feb 13;205:107017.
PMID: 39961275 DOI: 10.1016/j.marenvres.2025.107017

As human activities continue to increase, the global production of pollutants has increased significantly, with the majority of pollutants being transported to the ocean via rivers, resulting in intensified pollution in estuaries and coastal areas. To maintain a healthy marine ecological environment, it is necessary to consider rivers, estuaries, and coastal seas as integrated systems and implement pollution management based on the concept of land-ocean integration. In this study, heavy metal elements in the surface sediments of Selangor River-Estuary-Coastal Shelf Continuum were collected and analysed to assess their pollution levels and potential ecological risks. The results show that the heavy metal content is high in the downstream and estuarine regions, with a general decreasing trend observed from nearshore to offshore in the coastal shelf area. The heavy metal pollution assessment indicates that the surface sediments of the Selangor River-Estuary-Coastal Shelf continuum were contaminated, with the most severe pollution occurring downstream and within the estuary. The pollution levels gradually decrease after exiting the estuary. The ecological risk associated with heavy metal pollution in rivers, estuaries, and southeastern coastal areas was classified as moderate to serious, whereas other areas exhibited only slight ecological risks. Specifically, As causes serious pollution in the river and estuary, with moderate-to-serious pollution in the coastal shelf area and moderate-to-serious ecological risks, mainly originating from mining within the river basin. Pb causes moderate pollution in the river, estuary, and coastal areas, with slight ecological risks due to mining within the river basin and inputs from nearby rivers, ports, and industrial activities. Other heavy metals cause minor pollution and pose minimal ecological risks.
Does drug repurposing bridge the gaps in management of Parkinson's disease? Unravelling the facts and fallacies

Bashir B, Vishwas S, Gupta G, Paudel KR, Dureja H, Kumar P, et al.

Ageing Res Rev, 2025 Feb 15;105:102693.
PMID: 39961372 DOI: 10.1016/j.arr.2025.102693

Repurposing the existing drugs for the management of both common and rare diseases is increasingly appealing due to challenges such as high attrition rates, the economy, and the slow pace of discovering new drugs. Drug repurposing involves the utilization of existing medications to treat diseases for which they were not originally intended. Despite encountering scientific and economic challenges, the pharmaceutical industry is intrigued by the potential to uncover new indications for medications. Medication repurposing is applicable across different stages of drug development, with the greatest potential observed when the drug has undergone prior safety testing. In this review, strategies for repurposing drugs for Parkinson's disease (PD) are outlined, a neurodegenerative disorder predominantly impacting dopaminergic neurons in the substantia nigra pars compacta region. PD is a debilitating neurodegenerative condition marked by an amalgam of motor and non-motor symptoms. Despite the availability of certain symptomatic treatments, particularly targeting motor symptoms, there remains a lack of established drugs capable of modifying the clinical course of PD, leading to its unchecked progression. Although standard drug discovery initiatives focusing on treatments that relieve diseases have yielded valuable understanding into the underlying mechanisms of PD, none of the numerous promising candidates identified in preclinical studies have successfully transitioned into clinically effective medications. Due to the substantial expenses associated with drug discovery endeavors, it is understandable that there has been a notable shift towards drug reprofiling strategies. Assessing the efficacy of an existing medication offers the additional advantage of circumventing the requirement for preclinical safety assessments and formulation enhancements, consequently streamlining the process and reducing both the duration of time and financial investments involved in bringing a treatment to clinical fruition. Furthermore, repurposed drugs may benefit from lower rates of failure, presenting an additional potential advantage. Various strategies for repurposing drugs are available to researchers in the field of PD. Some of these strategies have demonstrated effectiveness in identifying appropriate drugs for clinical trials, thereby providing validation for such strategies. This review provides an overview of the diverse strategies employed for drug reprofiling from approaches that place emphasis on single-gene transcriptional investigations to comprehensive epidemiological correlation analysis. Additionally, instances of previous or current research endeavors employing each strategy have been discussed. For the strategies that have not been yet implemented in PD research, their strategic efficacy is demonstrated using examples involving other disorders. In this review, we assess the safety and efficacy potential of prominent candidates repurposed as potential treatments for modifying the course of PD undergoing advanced clinical trials.
Unlocking new frontiers in healthcare: The impact of nano-optical biosensors on personalized medical diagnostics

Taha BA, Addie AJ, Chahal S, Haider AJ, Rustagi S, Arsad N, et al.

J Biotechnol, 2025 Feb 15;400:29-47.
PMID: 39961549 DOI: 10.1016/j.jbiotec.2025.02.005

Nano-optical biosensors have emerged as transformative tools in healthcare and clinical research, offering rapid, portable, and specific diagnostic solutions. This review critically analyzes the recent advancements, translational challenges, and sustainable approaches in nano-optical biosensor implementation for biomedical applications. We explore the integration of innovative nanomaterials, microelectronics, and molecular biology techniques that have significantly enhanced biosensor sensitivity and specificity, enabling detection of biomarkers ranging from cancer indicators to cardiovascular markers. The potential of nanoplasmonic and silicon photonic biosensors in overcoming current limitations is discussed, alongside the promising integration of artificial intelligence and Internet of Things technologies for improved data analytics and clinical validation. We address key challenges, including size constraints, energy efficiency, and integration with existing technologies, and propose sustainable strategies for eco-friendly materials, energy-efficient designs, and circular economy approaches. The review also examines emerging trends such as multiplexed sensing platforms, wearable biosensors, and their applications in personalized medicine. By critically assessing these developments, we provide insights into the prospects of nano-optical biosensors and their potential to revolutionize point-of-care diagnostics and personalized healthcare, while emphasizing the need for interdisciplinary collaboration to overcome remaining obstacles in translating these technologies from laboratory research to real-world clinical applications.
Fulltext Association of nocturnal oxygen saturation with coronary artery calcification: cross-sectional evidence from the population-based SESSA study among Japanese men

Mondal R, Takashima N, Torii S, Harada A, Mohd Azahar N, Moniruzzaman M, et al.

BMJ Open, 2025 Feb 17;15(2):e082584.
PMID: 39961724 DOI: 10.1136/bmjopen-2023-082584

OBJECTIVE: We investigated the associations of nocturnal oxygen saturation (SpO2) with prevalence of coronary artery calcification (CAC) and its level of burden, and whether the associations differ by obesity and mediate through diabetes mellitus (DM), dyslipidaemia and hypertension.
DESIGN: Observational study.
SETTING: Kusatsu, Shiga.
PARTICIPANTS: We analysed data from 510 Japanese men (aged 46-76 years) with no history of myocardial infarction.
PRIMARY AND SECONDARY OUTCOMES: Mean SpO2, minimum SpO2 and oxygen desaturation index (ODI) were measured using overnight pulse oximetry (primary exposures), while CAC was assessed using CT. Prevalence of CAC (>0) and its burden (CAC 0, >0-100, >100-400 and>400) were evaluated as outcomes. Body mass index≥25.0 kg/m2 defined as obesity.
RESULTS: Mean±SD age was 66.7±7.2 years. The prevalence of CAC was 64.7% (CAC scores>0-100, 31.4%; >100-400, 20.0% and>400, 13.3%). In multivariable binary logistic regression, the OR and 95% CI for the prevalence of CAC were 1.25 (1.02 to 1.53) per 1-SD decrement in mean SpO2 and 1.25 (1.01 to 1.55) per 1-SD increment in ODI. The associations lost their significance while further adjusted for DM and dyslipidaemia. Similar trends were observed for the level of CAC burden in multivariable ordinal logistic regression. Obesity did not show significant interaction with SpO2 on CAC. In mediation analysis, the OR (95% CI) for natural indirect effect; percentage mediated through dyslipidaemia in association of 1-SD decrement in mean SpO2 with prevalence of CAC were 1.06 (1.01 to 1.10); 25.4%. These estimates for mediation through DM and dyslipidaemia for 1-SD increment in ODI in the associations were 1.07 (1.01 to 1.12); 29.6% and 1.04 (1.00 to 1.08); 17.5%, respectively.
CONCLUSIONS: Lower mean SpO2 and higher ODI are associated with CAC among Japanese men, independent of age, lifestyle factors and obesity. The associations became non-significant after adjusting for diabetes and dyslipidaemia, but were mediated through these factors.

MeSH terms: Aged; Cross-Sectional Studies; Diabetes Mellitus/epidemiology; Humans; Hypertension/epidemiology; Japan/epidemiology; Male; Middle Aged; Obesity/complications; Obesity/epidemiology; Oximetry; Risk Factors; Prevalence; Logistic Models; Dyslipidemias/epidemiology
Clinical implication of regional osteopenia in complex regional pain syndrome: a retrospective comparative study

Kim J, Rho H, Yoo Y, Cha J, Park S, Kim H, et al.

Reg Anesth Pain Med, 2025 Feb 17.
PMID: 39961729 DOI: 10.1136/rapm-2024-106111

BACKGROUND: Despite the significant role of impaired bone metabolism in complex regional pain syndrome (CRPS), the clinical implications of osteopenia remain a focal point of investigation. We examined the prevalence and risk factors of affected limb osteopenia in CRPS and its association with the response to sympathetic blockade.
METHODS: 167 patients with CRPS who underwent CT of their affected limbs were retrospectively reviewed. After conducting univariable analyses where regional osteopenia determined by CT was dependent and other clinical factors were independent variables, the first multivariable analysis assessed risk predictors associated with regional osteopenia in CRPS. Next, after conducting univariable analyses where sympathetic block response was dependent and others, including regional osteopenia, were independent variables, the second multivariable model predicted factors associated with the response to sympathetic blockades, followed by receiver operating characteristic curve analysis.
RESULTS: Among 116 patients, regional osteopenia was identified in 72.2% early (<1 year) and 52.5% persistent CRPS. In the first multivariable analysis adjusted for age, sex, body mass index (BMI), and other variables with p values<0.1 from initial univariable analyses, older age (OR 1.06; 95% CI 1.02 to 1.10) and positive three-phase bone scintigraphy (TPBS) (OR 3.94; 95% CI 1.46 to 10.66) were significantly associated with regional osteopenia. In the second multivariable model adjusted for age, sex, BMI, and other variables with p values<0.1 from univariable analyses, early phase (OR 5.49; 95% CI 1.44 to 20.88), regional osteopenia (OR 5.11; 95% CI 1.49 to 17.53), and positive TPBS (OR 6.30; 95% CI 2.21 to 17.93) were significantly associated with positive responses to sympathetic blockade in CRPS, showing excellent performance characteristics with a predicted probability>0.358 (sensitivity 0.86; specificity 0.76).
CONCLUSION: Regional osteopenia in the affected limb can anticipate positive responses to sympathetic blockade when combined with TPBS in early CRPS.
Complete genome sequence analysis of the novel bacteriophage PA-1 infecting phytopathogenic Pantoea ananatis in Malaysia

Singh PSS, Toh WK, Lim BH, Wong HL, Loh PC

Arch Virol, 2025 Feb 17;170(3):60.
PMID: 39961917 DOI: 10.1007/s00705-025-06239-z

A novel bacteriophage, PA-1, was isolated using Pantoea ananatis, a bacterium that is responsible for rice leaf blight worldwide, as the host. PA-1 has a linear genome of 46,332 bp with a GC content of 50.55%. It contains 83 protein-encoding genes, and no tRNA-encoding genes were detected. The genome is densely organized, with an average CDS size of 516 bp, and 92.38% of the genome consists of protein-coding regions. Whole-genome sequencing and phylogenetic and morphological analysis showed that PA-1 is a novel phage that is phylogenetically distinct, suggesting that it may represent a new genus within the class Caudoviricetes..

MeSH terms: Base Composition*; Malaysia; Phylogeny*; Open Reading Frames; Genome, Viral*; Sequence Analysis, DNA
Acute-on-chronic liver failure (ACLF): the 'Kyoto Consensus'-steps from Asia

Choudhury A, Kulkarni AV, Arora V, Soin AS, Dokmeci AK, Chowdhury A, et al.

Hepatol Int, 2025 Feb 17.
PMID: 39961976 DOI: 10.1007/s12072-024-10773-4

Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the 'Golden Therapeutic Window', the 'transplant window', and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The 'Kyoto APASL Consensus' presented below carries the final recommendations along with the relevant background information and areas requiring future studies.
Fulltext Research on rechargeable agricultural wireless sensor network based on ZigBee immune routing repair algorithm

Tang R, Wu Y, Tan J, Guan B, Aridas NK, Talip MSA

Sci Rep, 2025 Feb 17;15(1):5756.
PMID: 39962080 DOI: 10.1038/s41598-025-89710-w

WSN (wireless sensor network) plays a very important role in the agricultural environment monitoring. Although solar energy and other power supply methods are used to solve the node energy problem, the monitoring equipment works outdoors for a long time, which is easily affected by the environment. The supply is unstable to cause abnormalities in some nodes. So this study proposes a ZIRRA algorithm (ZigBee immune routing repair algorithm) for the rechargeable agricultural WSN. It simulates the working mechanism of the immune system and designs modules such as identification, processing, cloning and storage, which can provide a better repair strategy for abnormal nodes. Then it compares the quality of the backup nodes and replaces the backup nodes with poor quality, so that the optimal paths are maintained between source nodes and middle relay nodes, which increases the optimization ability of the algorithm. The experimental results show that the ZIRRA algorithm shows significant advantages in routing node repair mechanism. Compared with the LFRA, AR-TORA and ICCO algorithms, the average routing energy consumption of the ZIRRA algorithm reduced 35.33%, 58.37% and 45.15% , the data transmission delay reduced by 23.72%, 36.74% and 16.28%, and the average node survival time extended 25.08%, 33.55% and 13.88%. In addition, the maximum communication time and network throughput of the ZIRRA algorithm increased 44.49% and 13.03% at the scale of 1000 to 2000 nodes. These quantitative results show that the ZIRRA algorithm can improve the energy efficiency, transmission reliability and stability. The ZIRRA algorithm draws on the working principle of the immune system and repairs abnormal nodes through identification, processing, cloning and storage modules. Unlike the traditional node repair algorithms, the ZIRRA algorithm has higher efficiency and accuracy in identifying and processing abnormal nodes through the improved clone tracking algorithm. It uses an improved clone tracking algorithm in the learning module, improves the cloning and mutation mechanisms, and generates the optimal antibodies for repairing abnormal nodes. It also integrates an adaptive energy management strategy to cope with fluctuations in energy levels by prioritizing the transmission of critical data and reducing the frequency of non-essential communications, which improves the network stability and data transmission reliability.
Fulltext Fe3O4@SiO2/Schiff-base/Zn (II) nanocomposite functioning as a versatile antimicrobial agent against bacterial and fungal pathogens

Azadi S, Amani AM, Jangjou A, Vaez A, Zareshahrabadi Z, Zare A, et al.

Sci Rep, 2025 Feb 17;15(1):5694.
PMID: 39962153 DOI: 10.1038/s41598-025-86518-6

Antimicrobial resistance (AMR) presents a critical global health issue, necessitating novel therapeutic strategies to manage bacterial and fungal infections. This study explores the development and evaluation of multifunctional Fe3O₄@SiO₂/Schiff-base/Zn (II) magnetic nanocomposite (MNC) with enhanced antimicrobial properties. The synthesized MNC combines the magnetic characteristics of Fe₃O₄ magnetic nanoparticles (MNPs) with the antimicrobial properties of Schiff-base ligand functionalized with Zn (II) ions. The preparation involved the coprecipitation of Fe₃O₄, coating with SiO₂ via a modified Stöber method, and subsequent functionalization with Schiff-base/Zn (II) complex. Comprehensive characterization using FT-IR, XRD, SEM, TEM, DLS, EDX, VSM, and TGA confirmed successful synthesis, structural integrity, and superparamagnetic behavior of the MNPs and MNC. The antifungal and antibacterial activities were assessed against six Candida species and four bacterial strains using broth microdilution methods. The Fe₃O₄@SiO₂/Schiff-base/Zn (II) MNC exhibited significant inhibitory effects, with MIC values of 8-64 µg/mL for Candida species and 64-512 µg/mL for bacteria, demonstrating potent antimicrobial efficacy. The MTT assay indicated biocompatibility across various concentrations, except for slight cytotoxicity at 256 µg/mL after five days. To our knowledge, this is the first report integrating Zn (II) Schiff-base ligands into magnetic nanoparticles to achieve a versatile platform for both antimicrobial and biofilm inhibition applications.

MeSH terms: Anti-Infective Agents/pharmacology; Anti-Infective Agents/chemistry; Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/chemistry; Antifungal Agents/pharmacology; Antifungal Agents/chemistry; Candida/drug effects; Humans; Microbial Sensitivity Tests*; Magnetite Nanoparticles/chemistry
Linker Ratio-Dependent Physicochemical Properties of ZIF-8 Encapsulated Mini Protein 20 Mimicking Uricase

Abdul Aziz SFN, Salleh AB, Normi YM, Ahmad SAA

Chembiochem, 2025 Feb 17.
PMID: 39962945 DOI: 10.1002/cbic.202400832

Despite a growing interest in zeolitic imidazolate framework-8 (ZIF-8), notably for their potential as a host for various bio- and molecules, including peptides, the critical factors affecting their physicochemical properties and encapsulation efficiency are relatively unknown, limiting their widespread use. Herein, mini protein 20 (mp20), biomolecule mimicking uricase was used as a model to be hosted within ZIF-8 (mp20@ZIF-8) biocomposites. ZIF-8 were synthesized over a range of molar ratio of Zn to 2-methylimidazole(2-HmIm). By systematically exploring the impacts of various linker ratios, we found that a Zn to 2-HmIm ratio of 1:4 offers the highest encapsulation efficiency and thermal stability, making it particularly suitable for applications where these properties are critical. The 1:8 ratio, on the other hand, makes biocomposites with the most crystallized and a well-balanced combination of particle size and surface area, which are advantageous for applications requiring high structural integrity and surface interaction. This approach not only advances our understanding of protein encapsulation in MOFs but also provides new insights into how the linker-to-metal ratio can be optimized for different applications.
The Cause of Pyloric Stenosis of Infancy (PS): The Harald Ernberg Connection

Rogers IM

Acta Paediatr, 2025 Feb 18.
PMID: 39963043 DOI: 10.1111/apa.70033
Fulltext Interruption of mitochondrial symbiosis is associated with the development of osteoporosis

Zhang H, Zhao R, Wang X, Qi Y, Sandai D, Wang W, et al.

Front Endocrinol (Lausanne), 2025;16:1488489.
PMID: 39963284 DOI: 10.3389/fendo.2025.1488489

Mitochondria maintain bacterial traits because of their endosymbiotic origins, yet the host cell recognizes them as non-threatening since the organelles are compartmentalized. Nevertheless, the controlled release of mitochondrial components into the cytoplasm can initiate cell death, activate innate immunity, and provoke inflammation. This selective interruption of endosymbiosis as early as 2 billion years ago allowed mitochondria to become intracellular signaling hubs. Recent studies have found that the interruption of mitochondrial symbiosis may be closely related to the occurrence of various diseases, especially osteoporosis (OP). OP is a systemic bone disease characterized by reduced bone mass, impaired bone microstructure, elevated bone fragility, and susceptibility to fracture. The interruption of intra-mitochondrial symbiosis affects the energy metabolism of bone cells, leads to the imbalance of bone formation and bone absorption, and promotes the occurrence of osteoporosis. In this paper, we reviewed the mechanism of mitochondrial intersymbiosis interruption in OP, discussed the relationship between mitochondrial intersymbiosis interruption and bone marrow mesenchymal stem cells, osteoblasts and osteoclasts, as well as the inheritance and adaptation in the evolutionary process, and prospected the future research direction to provide new ideas for clinical treatment.

MeSH terms: Animals; Humans; Osteoblasts/metabolism; Osteoclasts/metabolism; Symbiosis*
Fulltext Biallelic NDUFA13 variants lead to a neurodevelopmental phenotype with gradual neurological impairment

Kaiyrzhanov R, Thompson K, Efthymiou S, Mukushev A, Zharylkassyn A, Prasad C, et al.

Brain Commun, 2025;7(1):fcae453.
PMID: 39963288 DOI: 10.1093/braincomms/fcae453

Biallelic variants in NADH (nicotinamide adenine dinucleotide (NAD) + hydrogen (H))-ubiquinone oxidoreductase 1 alpha subcomplex 13 have been linked to mitochondrial complex I deficiency, nuclear type 28, based on three affected individuals from two families. With only two families reported, the clinical and molecular spectrum of NADH-ubiquinone oxidoreductase 1 alpha subcomplex 13-related diseases remains unclear. We report 10 additional affected individuals from nine independent families, identifying four missense variants (including recurrent c.170G > A) and three ultra-rare or novel predicted loss-of-function biallelic variants. Updated clinical-radiological data from previously reported families and a literature review compiling clinical features of all reported patients with isolated complex I deficiency caused by 43 genes encoding complex I subunits and assembly factors are also provided. Our cohort (mean age 7.8 ± 5.4 years; range 2.5-18) predominantly presented a moderate-to-severe neurodevelopmental syndrome with oculomotor abnormalities (84%), spasticity/hypertonia (83%), hypotonia (69%), cerebellar ataxia (66%), movement disorders (58%) and epilepsy (46%). Neuroimaging revealed bilateral symmetric T2 hyperintense substantia nigra lesions (91.6%) and optic nerve atrophy (66.6%). Protein modeling suggests missense variants destabilize a critical junction between the hydrophilic and membrane arms of complex I. Fibroblasts from two patients showed reduced complex I activity and compensatory complex IV activity increase. This study characterizes NADH-ubiquinone oxidoreductase 1 alpha subcomplex 13-related disease in 13 individuals, highlighting genotype-phenotype correlations.
Fulltext A rare case of dual left anterior descending artery type 4 in inferior myocardial infarction patient: a case report

Isa WYHW, Yusof Z, Aziz MFA, Othman MK, Suliman A

Eur Heart J Case Rep, 2025 Feb;9(2):ytaf032.
PMID: 39963306 DOI: 10.1093/ehjcr/ytaf032

BACKGROUND: This case highlights a type 4 dual left anterior descending coronary artery anomaly, identified incidentally during coronary angiography.
CASE SUMMARY: A 51-year-old male patient presented with acute myocardial infarction, which was successfully treated with thrombolysis and percutaneous coronary intervention. Angiography revealed an anomalous origin of the left anterior descending artery (LAD) from the right coronary artery. Stenting was performed on the right coronary artery and the right posterior descending artery branch.
DISCUSSION: Type 4 dual LAD is a rare coronary anomaly with potential clinical risks, including sudden cardiac death due to its course between major arteries. Variations in the structure of coronary arteries can present challenges for interventional cardiologists when conducting percutaneous coronary interventions. Accurate coronary anatomy assessment via angiography and computed tomography coronary angiography is crucial for successful percutaneous coronary intervention and surgical planning. Although uncommon, the dual LAD type 4 anomaly is a significant coronary artery variation that interventional cardiologists must consider due to its impact on prognosis and long-term treatment strategies.
Fulltext Quality Control of Fetal Wharton's Jelly Mesenchymal Stem Cells-Derived Small Extracellular Vesicles

Krishnan I, Ng CY, Kee LT, Ng MH, Law JX, Thangarajah T, et al.

Int J Nanomedicine, 2025;20:1807-1820.
PMID: 39963415 DOI: 10.2147/IJN.S497586

BACKGROUND: Quality control (QC) is an important element in ensuring drug substances' safety, efficacy, and quality. The dosing regimen for sEVs can be in the form of protein concentration or the number of particles based on the results of a series of quality controls applied as in-process control.
METHODS: Wharton's Jelly Mesenchymal Stem Cells (WJMSCs) were isolated from four independent umbilical cord samples and were characterized following the International Society for Cellular Therapy (ISCT) guidelines. Small extracellular vesicles (sEVs) were isolated separately from these four WJMSCs samples using the Tangential Flow Filtration (TFF) method and were characterized per Minimal Information for Studies of Extracellular Vesicles (MISEV2018) guidelines. Each isolated and concentrated sEV preparation was standardized and its purity was determined by the ratio of the number of particles to protein concentration.
RESULTS: All the WJMSCs samples passed the Mesenchymal Stem Cells (MSCs) characterization QC tests. Qualitatively, EVs-positive markers (CD63 and TSG101) and intact bilipid membrane vesicles were detected in all the sEV preparations. Quantitatively, the protein and particle concentrations revealed that all the sEV preparations were "impure" with < 1.5 × 109 particles/µg protein. Albumin was co-isolated in all the sEV preparations.
CONCLUSION: In short, all characterized and standardized individual and pooled sEV preparations were deemed "impure" due to albumin co-isolation using the TFF method. For therapeutic development, it is essential to report protein and particle concentrations in EV preparations based on these QC results.

MeSH terms: Cells, Cultured; Humans; Quality Control*
Fulltext Antioxidant and Anti-Inflammatory Potential of Cymbopogon nardus Ethanol Extract on 3T3-L1 Cells

Rohmawaty E, Wiraswati HL, Zahra TA, Amalina SN, Ramadhanti J, Rosdianto AM, et al.

J Inflamm Res, 2025;18:2125-2136.
PMID: 39963686 DOI: 10.2147/JIR.S506189

PURPOSE: Cymbopogon nardus (L). Rendle has traditionally been recognized for its medicinal properties. Recent studies have suggested that its bioactive constituents possess antioxidant and anti-inflammatory properties. However, there is limited scientific evidence of its cellular effects. Given that the pathogenesis of many diseases involves oxidative stress and inflammation, this study aimed to evaluate the potential antioxidant and anti-inflammatory effects of the plant extracts in 3T3-L1 cells.
METHODS: Phytochemical screening of C. nardus extracts was performed to identify bioactive compounds. Antioxidant activity of the extract was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide dismutase (SOD) assays. Toxicity was evaluated using the MTT assay. Additionally, the effects of the extract on the gene expression of hypoxia-inducible factor 1α (HIF-1α) in menadione-induced 3T3-L1 cells, as well as interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced 3T3-L1 cells, were investigated.
RESULTS: Phytochemical screening revealed the presence of phenolics, tannins, alkaloids, and flavonoids in the ethanolic extracts. The extract demonstrated antioxidant activity, with IC50 values of 178.06 ppm for DPPH and 220 ppm for SOD. It did not affect the viability of 3T3-L1 cells at concentrations of up to 500 ppm. At 100 ppm, the extract increased cell viability (p<0.05) and reduced HIF-1α expression in the menadione-treated cells (p<0.05). Additionally, it decreased the expression of IL-6 and COX-2 in LPS-induced cells (p<0.05).
CONCLUSION: The ethanol extract of C. nardus demonstrated promising potential as an antioxidant and anti-inflammatory agent in 3T3-L1 cells. Further analysis is recommended to confirm the potential.
Comparative Analysis of phaC1 and phaC2 Genes Encoding Polyhydroxyalkanoate Synthase in Cupriavidus malaysiensis USMAA1020T

Shafie NAH, Azami NA, Lau NS, Anis SNS, Abdullah AA

J Basic Microbiol, 2025 Feb 18.
PMID: 39963786 DOI: 10.1002/jobm.70008

Two polyhydroxyalkanoate synthase genes, phaC1 and phaC2, were identified in three strains of Cupriavidus malaysiensis (C. malaysiensis): C. malaysiensis USMAA1020T, C. malaysiensis USMAHM13, and C. malaysiensis USMAA2-4. Interestingly, the genome of C. malaysiensis USMAA1020T revealed the presence of the polyhydroxyalkanoate granule-associated protein (phaF), which was not present in C. malaysiensis USMAHM13 and C. malaysiensis USMAA2-4. A Maximum Likelihood phylogenetic analysis shows that the phaC genes were classified into Class I synthases. The phaC1 and phaC2 genes in the three C. malaysiensis strains formed a separate, distinct cluster. To further examine the function of phaC, both phaC genes were cloned from C. malaysiensis USMAA1020T and individually expressed in Cupriavidus necator (C. necator) PHB-4, which serves as a benchmark of functionality for other strains. Using γ-butyrolactone as the sole carbon source, the poly(3-hydroxybutyrate-co-4-hydroxybutyrate) contains up to 83.00 mol% 4-hydroxybutyrate (4HB) and 26.50% PHA content. However, the transformant C. necator PHB-4 with phaC2 produced only 2.30% PHA content and no 4HB monomer. The phaC2 transformant produces up to 100 mol% 3HB monomer and 41.90% PHA content, while the phaC1 transformant produces only 25.80% PHA content when using oleic acid as the sole carbon source. When provided with a mixed substrate of oleic acid and 1-pentanol, the transconjugants accumulated up to 20% PHA content but produced a low 3HV content of only 4%-5%. These findings significantly contribute to the scientific literature by improving the understanding of the genetic and biochemical diversity of the two PHA synthases, phaC1 and phaC2, in Cupriavidus species.
Estimates of Suicide Trends Among Males in the Association of Southeast Asian Nations (ASEAN) From Year 2000 to 2019 Using WHO GHE Data

Siau CS, Chong ASS, Fariduddin MN, Marzo RR, Aslamiah S, Wee LH, et al.

Asia Pac J Public Health, 2025 Feb 18.
PMID: 39963810 DOI: 10.1177/10105395251318912

This study aimed to analyze the estimated suicide trends among males in the Association of Southeast Asian Nations (ASEAN) countries from year 2000 to 2019 and their relationship with unemployment rates. Age-standardized suicide rate and unemployment data of 10 ASEAN countries (Brunei, Cambodia, Indonesia, Lao People's Democratic Republic, Malaysia, Myanmar, the Philippines, Singapore, Thailand, Vietnam) were analyzed using Joinpoint regression. Results showed that ASEAN countries (except the Philippines and Myanmar) recorded an increase or a plateau in the decline of age-standardized suicide rates in males during the second half of the 2010s. This was in contrast with global trends for males, which has been steadily decreasing. Unemployment was significantly associated with suicide rates. Our study found generally increasing or plateauing suicide trends in ASEAN countries between years 2013 and 2017. However, limitations in data quality highlight the importance of improved suicide surveillance to effectively support prevention efforts.
Influencing hair regrowth with EGCG by targeting glycogen synthase kinase-3β activity: a molecular dynamics study

Moqaddasi HR, Singh A, Mukherjee S, Rezai F, Gupta A, Srivastava S, et al.

J Recept Signal Transduct Res, 2025 Feb 18.
PMID: 39964119 DOI: 10.1080/10799893.2025.2465240

Hair follicle growth process through several well-organized stages with specific input by several signaling pathways including Wnt/β-catenin and Sonic Hedgehog with GSK3β in this process. As such, this research focus on investigating the efficacy of molecules that are able to inhibit GSK3β action in inducing hair regrowth. Applying computational techniques, three compounds NMN, Resveratrol and EGCG were analyzed for their GSK3β inhibition. It was established that EGCG has the highest values of molecular docking scores and, in the case of the stability criteria such as RMSD and RMSF, presented the most stable dynamic simulation. EGCG has shown considerable TEMPORAL STABILITY with GSK3β in the complex, because over a period of 200 nanoseconds the molecules remained bound through hydrogen bonds and hydrophobic contacts. As confirmed by PCA, the largest conformational changes in GSK3β suggest significant inhibitory interaction. Out of all the studied compounds, EGCG turns out to be the most potent GSK3β inhibitor for hair regrowth purposes. The result obtained from the molecular dynamics simulation indicates that EGCG might exert a favorable impact to extract signaling pathways related with hair follicle cycling which is a significant objective. These outcome sets the phase for further experimental testing to discover the potential of EGCG in the treatment of alopecia.

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