Browse publications by year: 2025

  1. Kandasamy V, Simic V, Bacanin N, Pamucar D
    Neural Netw, 2025 Jan;181:106822.
    PMID: 39490023 DOI: 10.1016/j.neunet.2024.106822
    Radiologists utilize pictures from X-rays, magnetic resonance imaging, or computed tomography scans to diagnose bone cancer. Manual methods are labor-intensive and may need specialized knowledge. As a result, creating an automated process for distinguishing between malignant and healthy bone is essential. Bones that have cancer have a different texture than bones in unaffected areas. Diagnosing hematological illnesses relies on correct labeling and categorizing nucleated cells in the bone marrow. However, timely diagnosis and treatment are hampered by pathologists' need to identify specimens, which can be sensitive and time-consuming manually. Humanity's ability to evaluate and identify these more complicated illnesses has significantly been bolstered by the development of artificial intelligence, particularly machine, and deep learning. Conversely, much research and development is needed to enhance cancer cell identification-and lower false alarm rates. We built a deep learning model for morphological analysis to solve this problem. This paper introduces a novel deep convolutional neural network architecture in which hybrid multi-objective and category-based optimization algorithms are used to optimize the hyperparameters adaptively. Using the processed cell pictures as input, the proposed model is then trained with an optimized attention-based multi-scale convolutional neural network to identify the kind of cancer cells in the bone marrow. Extensive experiments are run on publicly available datasets, with the results being measured and evaluated using a wide range of performance indicators. In contrast to deep learning models that have already been trained, the total accuracy of 99.7% was determined to be superior.
    MeSH terms: Algorithms; Bone Marrow/pathology; Bone Neoplasms/diagnosis; Bone Neoplasms/pathology; Humans; Image Processing, Computer-Assisted/methods; Neural Networks (Computer)*
  2. Cheong JY, Koay JSC, Gopal SR, Velayutham TS, Gan WC
    Nanoscale Adv, 2025 Jan 28;7(3):819-829.
    PMID: 39691558 DOI: 10.1039/d4na00820k
    Incorporating carbon-based fillers into triboelectric nanogenerators, TENGs, is a compelling strategy to enhance the power output. However, the lack of systematic studies comparing various carbon fillers and their impact on tribopositive contact layers necessitates further research. To address these concerns, various carbon fillers (including buckminsterfullerene (C60), graphene oxide (GO), reduced graphene oxide (rGO), multi-wall carbon nanotube (MWCNT), and super activated carbon (SAC)) with distinct structural and electrical properties are mixed with polyvinyl alcohol, PVA, to form PVA-carbon composites and used as tribopositive layers in the contact-separation of TENGs. The results show that PVA-SAC provides the largest enhancements to the electrical outputs of the TENG. At the optimal loading of 1 wt%, PVA-SAC composites yielded a peak power density of 12.8 W m-2, a substantial 220% enhancement compared to pristine PVA. The mechanism governing the enhancement is determined by analysing the changes in electrical and structural characteristics caused by the addition of various carbon fillers. Dielectric measurements indicated that enhanced dielectric properties did not significantly contribute to the observed increase in the triboelectric performance. Instead, Raman and FTIR analyses revealed a correlation between the PVA-carbon interactions and an increase in the D/G ratio of carbon fillers, accompanied by a reduction in hydrogen-bonded -OH groups within PVA. This suggests that the interaction between the π electrons of sp2 hybridized carbon atoms and the oxygen lone pairs in PVA inhibits hydrogen bond formation, leading to an increase in free -OH groups. Consequently, these free -OH groups enhanced the electron-donating capability and improved the tribopositive behaviour of the PVA-carbon composites. Our results proved that filler-matrix interactions are paramount in engineering high-performance TENGs by controlling the electron affinity of the triboelectric layers.
  3. Abdul-Aziz MH, Diehl A, Liu X, Cheng V, Corley A, Gilder E, et al.
    Antimicrob Agents Chemother, 2025 Feb 13;69(2):e0143524.
    PMID: 39692515 DOI: 10.1128/aac.01435-24
    This study aimed to describe the population pharmacokinetics of caspofungin in critically ill patients receiving extracorporeal membrane oxygenation (ECMO) and to identify dosing regimens with a high likelihood of achieving effective exposures. Serial blood samples were collected over a single-dosing interval during ECMO. Total plasma concentrations were measured by a validated chromatographic assay. A population pharmacokinetic model was built and Monte Carlo dosing simulations were performed using Monolix. The probability of target attainment (PTA) and fractional target attainment (FTA) rates were simulated for various caspofungin dosing regimens against Candida albicans, Candida glabrata, and Candida parapsilosis. In all, 64 plasma concentration-time points were obtained from 8 critically ill patients receiving ECMO. Plasma concentration-time data for caspofungin were best described by a one-compartment model with first-order elimination. Lean body weight was identified as a significant covariate of volume of distribution. The typical volume of distribution and clearance of caspofungin in this cohort were 8.13 L and 0.55 L/h, respectively. The licensed caspofungin dosing regimen (a loading dose of 70 mg on day 1 followed by a maintenance dose of either 50 mg/day or 70 mg/day) demonstrated optimal PTA rates (≥90%) against C. albicans with an MIC of ≤0.064 mg/L, C. glabrata with an MIC of ≤0.125 mg/L, and C. parapsilosis with an MIC of ≤0.064 mg/L. The FTA analysis suggested that the licensed dosing regimen is only optimal (≥95%) against Candida glabrata, regardless of lean body weight. A higher-than-standard empirical dosing regimen (e.g., a loading dose of 100 mg on day 1, followed by a maintenance dose of 100 mg daily) is likely advantageous for critically ill patients receiving ECMO.
    MeSH terms: Adult; Aged; Candida albicans/drug effects; Candidiasis/drug therapy; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method; Critical Illness*; Echinocandins/pharmacokinetics; Echinocandins/therapeutic use; Lipopeptides/pharmacokinetics
  4. Geng LN, Erlandson KM, Hornig M, Letts R, Selvaggi C, Ashktorab H, et al.
    JAMA, 2025 Feb 25;333(8):694-700.
    PMID: 39693079 DOI: 10.1001/jama.2024.24184
    IMPORTANCE: Classification of persons with long COVID (LC) or post-COVID-19 condition must encompass the complexity and heterogeneity of the condition. Iterative refinement of the classification index for research is needed to incorporate newly available data as the field rapidly evolves.

    OBJECTIVE: To update the 2023 research index for adults with LC using additional participant data from the Researching COVID to Enhance Recovery (RECOVER-Adult) study and an expanded symptom list based on input from patient communities.

    DESIGN, SETTING, AND PARTICIPANTS: Prospective, observational cohort study including adults 18 years or older with or without known prior SARS-CoV-2 infection who were enrolled at 83 sites in the US and Puerto Rico. Included participants had at least 1 study visit taking place 4.5 months after first SARS-CoV-2 infection or later, and not within 30 days of a reinfection. The study visits took place between October 2021 and March 2024.

    EXPOSURE: SARS-CoV-2 infection.

    MAIN OUTCOMES AND MEASURES: Presence of LC and participant-reported symptoms.

    RESULTS: A total of 13 647 participants (11 743 with known SARS-CoV-2 infection and 1904 without known prior SARS-CoV-2 infection; median age, 45 years [IQR, 34-69 years]; and 73% were female) were included. Using the least absolute shrinkage and selection operator analysis regression approach from the 2023 model, symptoms contributing to the updated 2024 index included postexertional malaise, fatigue, brain fog, dizziness, palpitations, change in smell or taste, thirst, chronic cough, chest pain, shortness of breath, and sleep apnea. For the 2024 LC research index, the optimal threshold to identify participants with highly symptomatic LC was a score of 11 or greater. The 2024 index classified 20% of participants with known prior SARS-CoV-2 infection and 4% of those without known prior SARS-CoV-2 infection as having likely LC (vs 21% and 5%, respectively, using the 2023 index) and 39% of participants with known prior SARS-CoV-2 infection as having possible LC, which is a new category for the 2024 model. Cluster analysis identified 5 LC subtypes that tracked quality-of-life measures.

    CONCLUSIONS AND RELEVANCE: The 2024 LC research index for adults builds on the 2023 index with additional data and symptoms to help researchers classify symptomatic LC and its symptom subtypes. Continued future refinement of the index will be needed as the understanding of LC evolves.

    MeSH terms: Adult; Aged; Fatigue/etiology; Female; Humans; Male; Middle Aged; Prospective Studies; Symptom Assessment
  5. Gill H, Raghupathy R, Hou HA, Cheng-Hong Tsai X, Tantiworawit A, Ooi MG, et al.
    Blood Adv, 2025 Feb 25;9(4):862-876.
    PMID: 39693517 DOI: 10.1182/bloodadvances.2024014999
    The Acute Promyelocytic Leukemia (APL) Asian Consortium analyzed a contemporaneous cohort of newly diagnosed patients with APL treated with and without frontline arsenic trioxide (ATO) in 6 centers. The objectives were to define the impact of ATO on early deaths and relapses and its optimal positioning in the overall treatment strategy. In a 21.5-year period, 324 males and 323 females at a median age of 45.5 years (range, 18.1-91.8; low/intermediate risk, n = 448; high risk, n = 199) were treated. Regimens included frontline all-trans retinoic acid (ATRA)/chemotherapy and maintenance with/without ATO (n = 436), ATRA/IV-ATO/chemotherapy (ATRA/IV-ATO; n = 61), and ATRA/oral-ATO/ascorbic acid with ATO maintenance (oral-AAA; n = 150). The ATRA/chemotherapy group had significantly more frequent early deaths within 60 days (8.3% vs 3.3%; P = .05), inferior 60-day survival (91.7% vs 98.4%/96%; P < .001), inferior 5-year relapse-free survival (RFS; 76.9% vs 92.8%/97.8%; P < .001), and inferior 5-year overall survival (OS; 84.6% vs 91.4%/92.3%; P = .03) than ATO-containing groups (ATRA/IV-ATO and oral-AAA). The addition of oral-ATO maintenance partly mitigated the inferior 5-year RFS resulting from the omission of ATO during induction (ATRA/chemotherapy/non-ATO maintenance vs ATRA/chemotherapy/ATO maintenance vs ATRA/IV-ATO vs oral-AAA, 71.1% vs 87.9% vs 92.8% vs 97.8%; P < .001). The favorable survival impacts of ATO were observed in all risk groups. In conclusion, ATO decreased early deaths, improved 60-day survival, and resulted in significantly superior RFS and OS. This trial was registered at www.clinicaltrials.gov as #NCT04251754.
    MeSH terms: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents/therapeutic use; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Arsenicals/therapeutic use; Female; Humans; Male; Middle Aged; Oxides/administration & dosage; Oxides/therapeutic use; Tretinoin/administration & dosage; Tretinoin/therapeutic use; Treatment Outcome; Young Adult
  6. Zhao X, Di J, Luo D, Verma R, Verma SK, Verma S, et al.
    Bioorg Chem, 2025 Jan;154:108035.
    PMID: 39693926 DOI: 10.1016/j.bioorg.2024.108035
    Research on thiazole derivatives has been a popular topic in medicine and one of the most active fields in heterocyclic chemistry. Pharmacological and industrial researchers have been studying thiazole-containing derivatives in great detail because they have a lot of biological uses. These compounds are one of the best examples of a five-membered heterocyclic compound that has a lot of potential and has had a lot of success in recent decades. Investigating viable hybrid designs utilizing thiazole is critical for the development of new anti-tuberculosis medications. This article offers a thorough overview of the latest advancements in thiazole-containing hybrids, offering potential therapeutic applications as anti-TB drugs. We also discussed the structure-activity correlations (SAR) of the powerful thiazole moiety and its several functional groups, along with a few potential molecular targets.
    MeSH terms: Dose-Response Relationship, Drug; Humans; Microbial Sensitivity Tests*; Structure-Activity Relationship; Molecular Structure
  7. Bahari N, Hashim N, Abdan K, Akim AM, Maringgal B, Al-Shdifat L
    Chemosphere, 2025 Feb;370:143961.
    PMID: 39694281 DOI: 10.1016/j.chemosphere.2024.143961
    This study investigated the green synthesis of silver nanoparticles (Ag-NPs) and zinc oxide nanoparticles (ZnO-NPs) using an aqueous extract of stingless bee honey (SBH) as a reducing and stabilising agent. The rich compositions of SBH containing flavonoids, phenolics, organic acids, sugars, and enzymes makes the SBH extract an ideal biocompatible precursor for the NPs synthesis. Physicochemical characterisation of the synthesised NPs was performed using UV-Vis spectroscopy, FESEM, TEM, XRD, and FTIR spectroscopy. The results revealed that the Ag-NPs and ZnO-NPs exhibited polydispersity, with size ranges between 25-50 nm and 15-30 nm, respectively. A majority of the NPs possessed a spherical morphology. Furthermore, the study evaluated the antimicrobial activity of the SBH-based NPs against gram-positive (Staphylococcus aureus, ATCC 43300) and gram-negative (Escherichia coli, ATCC 25922) bacteria. The findings demonstrated significantly higher antimicrobial efficacy of the Ag-NPs with a zone of inhibition (ZOI) of 16.91 mm against S. aureus, and 17.43 mm against E. coli compared to the ZnO-NPs which having a ZOI of 13.05 mm and 14.01 mm, respectively. Notably, cytotoxicity assays revealed no adverse effects of the synthesised NPs on normal mouse fibroblast (3T3) and human lung fibroblast (MRC5) cells up to 100 μg/ml of concentration. These findings suggest the potential of SBH-based Ag-NPs and ZnO-NPs as safe and effective antibacterial agents for various applications, including pharmaceuticals, cosmetics, ointments, and lotions.
    MeSH terms: Animals; Anti-Infective Agents/pharmacology; Anti-Infective Agents/toxicity; Anti-Infective Agents/chemistry; Bees; Microbial Sensitivity Tests*; Mice; Green Chemistry Technology*
  8. Yazid NA, Tan KY, Khor SM, Lee HV
    Int J Biol Macromol, 2025 Feb;291:138876.
    PMID: 39694355 DOI: 10.1016/j.ijbiomac.2024.138876
    This study aimed to develop a sustainable and bio-based nano-additive (sodium caseinate/cellulose nanofibers (SC/CNF) complex) to modulate liquid-based oil-in-water (O/W) colloid interfaces, which function as a fat control agent to slow lipid digestion. Edible protein (SC) was grafted onto CNF through facile electrostatic attraction, which reduces solvent and chemical usage for greener process. The physicochemical properties of SC/CNF showed that adding SC increased the interfacial bonding between CNF particles, resulting in higher interfacial pressure by forming dense and compact layers of SC/CNF. This characteristic improves the mechanical strength and colloidal stability of SC/CNF during water-oil stabilization. Further preparation of O/W Pickering emulsions stabilized by SC/CNF complexes was conducted using different parameters (such as SC concentration, dosage of SC/CNF, and O/W ratio) to investigate profile of free fatty acid (FFA) released during lipid digestion via simulated in vitro gastrointestinal tract (GIT) model. The results showed that the optimized emulsion stabilized by the SC/CNF complex rendered a lower value of free fatty acids (FFA) after undergoing in vitro simulated digestion. The lowest FFA release (31.18 %) was achieved under the following conditions: 1 % w/v (SC concentration), 1 % w/w (dosage of SC/CNF), and 20/80 (O/W) ratio. Low FFA release within the digestive system indicated that the nano-emulsions effectively regulated lipid digestion. The changes in physicochemical characteristics in terms of colloidal stability (particle size, microstructure, and surface charge) of the stabilized emulsions corresponding to the FFA released were studied during each digestion phase (including mouth, stomach, and small intestine). This study revealed that the SC/CNF complex is a promising nano-biomaterial that can function as a bio-functional food additive, particle stabilizer, and fat digestion controller. The unique characteristics of SC/CNF complexes in stabilizing oil-water emulsions present a potential interfacial mechanism for modulating lipid bioavailability. The innovation approach allows for the demand for green-label products, promote development of healthier food options, and the pursuit of sustainable food solutions.
    MeSH terms: Digestion; Fatty Acids, Nonesterified/chemistry; Lipids/chemistry; Lipid Metabolism
  9. Singh H, Kamal YT, Pandohee J, Mishra AK, Biswas A, Mohanto S, et al.
    Exp Gerontol, 2025 Jan;199:112660.
    PMID: 39694450 DOI: 10.1016/j.exger.2024.112660
    Skin aging, often called as premature skin aging, is the hastened deterioration of the skin resulting from multiple factors, including UV radiation, environmental contaminants, inadequate nutrition, stress, etc. Dietary phytochemicals, present in fruits, vegetables, and other plant-derived meals, have gained interest due to their efficiency to eradicate free radicals and lowering the release of inflammatory mediators which accounts for premature skin aging. Several dietary phytochemicals, i.e., carotenoids, polyphenols, flavonoids, terpenes, alkaloids, phytosterols, etc., exhibited potential anti-oxidant, anti-inflammatory, suppression of UV damage, and promote collagen synthesis. In addition, dietary phytochemicals include sulfur, present in various foods safeguard the skin against oxidative stress and inflammation. Thus, this article delves into the comprehension of various dietary phytochemicals investigated to alleviate the premature skin aging. The article further highlights specific phytochemicals and their sources, bioavailability, mechanisms, etc., in the context of safeguarding the skin against oxidative stress and inflammation. The present manuscript is a systematic comprehension of the available literature on dietary phytochemicals and skin aging in various database, i.e., PubMed, ScienceDirect, Google Scholar using the keywords, i.e., "dietary phytochemicals", "nutraceuticals", "skin aging" etc., via Boolean operator, i.e., "AND". The dietary guidelines presented in the manuscript is a unique summarization for a broad reader to understand the inclusion of various functional foods, nutrients, supplements, etc., to prevent premature skin aging. Thus, the utilization of dietary phytochemicals has shown a promising avenue in preventing skin aging, however, the future perspectives and challenges of such phytochemicals should be comprehended via clinical investigations.
    MeSH terms: Animals; Humans; Skin/drug effects; Skin/metabolism; Dietary Supplements; Aging, Premature/prevention & control
  10. Paramasivan T, Md Amin R, Zhao S, Wang T, Roseli N, Li D, et al.
    Environ Sci Pollut Res Int, 2025 Jan;32(2):587-602.
    PMID: 39695036 DOI: 10.1007/s11356-024-35711-7
    Estuarine fronts are formed due to sharp density discontinuities resulting from the convergence of different water masses. This study, conducted in May and August of 2022 during the southwest monsoon season, focuses on assessing the role of estuarine fronts at Kuala Terengganu estuary in the accumulation of microplastics in surface seawater. The Terengganu River basin area covers approximately 4600 km2 and consists of two main tributaries that drain into the Kuala Terengganu estuary. Microplastic samples were collected from three areas, the plume, front, and shelf, utilizing two methods: manta net (> 350 µm) and bucket-water sampling (> 20 µm). Results indicate that the estuarine front consistently exhibited higher microplastic concentrations than the plume and shelf regions throughout the study period, with bucket-water sampling contributing significantly to the abundance. Specifically, peak concentrations occurred during the ebb tide at the frontal region in both months, reaching 5761.703 particles m-3 and 12,687.437 particles m-3, respectively. The microplastics, predominantly transparent fibers smaller than 1000 µm, mostly showed signs of oxidative and mechanical weathering through SEM-EDS analysis, providing insights into their fate in estuarine surface waters. FTIR spectroscopy revealed polypropylene, polyethylene, and polyamide as the dominant polymers. These findings establish a baseline for microplastic abundance at the estuarine front of the Kuala Terengganu estuary and may inform future strategies for mitigating and recovering microplastic contamination in aquatic environments.
    MeSH terms: Environmental Monitoring*; Seawater/chemistry; Rivers/chemistry; Estuaries*
  11. Guo D, Sun J, Feng S
    J Sports Med Phys Fitness, 2025 Jan;65(1):132-139.
    PMID: 39287582 DOI: 10.23736/S0022-4707.24.16206-8
    BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), linked to sedentary lifestyles and metabolic dysfunction, is highly prevalent. Exercise is an established intervention, but the relative efficacy of different exercise modalities remains unclear. The aim of this study was to compare the effects of moderate-intensity continuous aerobic training and High-Intensity Interval Training (HIIT) on physical fitness, biochemical parameters, and liver function in NAFLD patients.

    METHODS: Sixty NAFLD patients (32 males, 28 females; age: 49.7±8.7 years; BMI: 31.1±3.3 kg/m2) were randomized into HIIT, aerobic training, and control cohorts. The HIIT cohort performed 4-minute high-intensity intervals at 85-95% of peak heart rate, interspersed with 3-minute active recovery at 60-70% of peak heart rate for 30-40 minutes per session. The aerobic training cohort performed continuous exercise at 60-70% of peak heart rate for 45-60 minutes per session. Both intervention cohorts underwent 12 weeks of supervised training, thrice weekly. Before and after the intervention, assessments included cardiorespiratory fitness, muscular strength, flexibility, lipid profile, liver enzymes, inflammatory markers, insulin sensitivity, and oxidative stress markers.

    RESULTS: Compared to controls, both exercise cohorts showed significant improvements in cardiorespiratory fitness, muscular strength, and flexibility. However, HIIT elicited superior enhancements in cardiorespiratory fitness and muscular strength. Biochemically, both exercise cohorts exhibited reductions in triglycerides, low-density lipoprotein (LDL) cholesterol, liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST]), inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6]), insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR]), and oxidative stress markers (malondialdehyde [MDA], protein carbonyl). Notably, HIIT yielded more substantial improvements in these parameters.

    CONCLUSIONS: HIIT and traditional aerobic training are effective in improving physical fitness and ameliorating biochemical indicators in NAFLD patients. Notably, HIIT appears to be more advantageous in enhancing cardiorespiratory fitness, muscular strength, and metabolic, inflammatory, and oxidative stress profiles, suggesting its potential as a time-efficient and effective exercise modality for managing NAFLD.

    MeSH terms: Adult; Alanine Transaminase/blood; C-Reactive Protein/metabolism; Exercise Therapy/methods; Female; Heart Rate/physiology; Humans; Insulin Resistance; Lipids/blood; Male; Middle Aged; Physical Fitness/physiology; Biomarkers/blood; Exercise/physiology; Oxidative Stress; Muscle Strength/physiology; Cardiorespiratory Fitness/physiology; High-Intensity Interval Training*
  12. Wood B, Robinson E, McCoy D, Baker P, Sacks G
    Matern Child Nutr, 2025 Jan;21(1):e13721.
    PMID: 39344750 DOI: 10.1111/mcn.13721
    The International Code of Marketing of Breast-milk Substitutes and subsequent resolutions (the Code) was adopted to address increases in mortality and morbidity resulting from the practices of the breast-milk substitute (BMS) industry. The lack of success in ensuring company compliance with the Code has prompted advocates to consider engaging with investors to shape the governance of BMS companies. To support these efforts, this paper aimed to identify prominent investors in the global BMS industry and explore their Code-related policies and practices. Using multiple methods and data sources, we developed a novel approach to identify and rank investors in the world's leading publicly listed BMS companies. We also examined the policies and voting behaviour of a sample of investors using publicly accessible materials from 2020 to 2022. We found that a small number of large investors, led by BlackRock and Vanguard, hold a substantial share in the global BMS industry. Of the top-10 ranked investors, only Norway's Government Pension Fund (NBIM) reported policy information relating specifically to BMS marketing. Most of these large investors also opposed the sample of public health-related shareholder proposals analysed. In addition, we identified several investors that have reported engaging with BMS companies on Code-related issues, including NBIM, Pictet, and UBS, along with several potential investor targets for future advocacy efforts, including some North American public pension funds. The inclusion of Code-related issues as part of broader policies, disclosures and regulations related to environmental, social and governance oriented investment warrants increased attention.
    MeSH terms: Humans; Investments; Global Health; Marketing/methods; Milk Substitutes*
  13. Nabila FH, Islam R, Yamin L, Yoshirou K, Wakabayashi R, Kamiya N, et al.
    ACS Biomater Sci Eng, 2025 Jan 13;11(1):402-414.
    PMID: 39686755 DOI: 10.1021/acsbiomaterials.4c02000
    Transdermal insulin delivery is a promising method for diabetes management, providing the potential for controlled, sustained release and prolonged insulin effectiveness. However, the large molecular weight of insulin hinders its passive absorption through the stratum corneum (SC) of the skin, and high doses of insulin are required, which limits the commercial viability. We developed ethosome (ET) and trans-ethosome (TET) nanovesicle formulations containing a biocompatible lipid-based ionic liquid, [EDMPC][Lin], dissolved in 35% ethanol. TET formulations were obtained by adding isopropyl myristate (IPM), Tween-80, or Span-20 as surfactants to ET formulations. Dynamic light scattering, ζ-potential, transmission electron microscopy, and confocal laser scanning microscopy studies revealed that the nanovesicles had a stable particle size. The formulations remained stable at 4 °C for more than 3 months. ET and TET formulations containing IPM (TET1) significantly (p < 0.0001) enhanced the transdermal penetration of FITC-tagged insulin (FITC-Ins) in both mouse and pig skin, compared with that of the control FITC-Ins solution and other TET formulations, by altering the molecular structure of the SC layer. These nanovesicles were found to be biocompatible and nonirritants (cell viability >80%) in the in vitro and in vivo studies on three-dimensional (3D) artificial human skin and a diabetic mouse model, respectively. The ET and TET1 formulations were applied to the skin of diabetic mice at an insulin dosage of 30 IU/kg. The nanovesicle formulations significantly reduced blood glucose levels (BGLs) compared with the initial high BGL value (>150 mg/dL). The nanovesicle-treated mice maintained low BGLs for over 15 h, as opposed to only 2 h in the injection group. The ET and TET1 formulations reduced the BGLs by 62 and 34%, respectively, of the initial value. These ET and TET1 formulations have a high potential for use in commercial transdermal insulin patches, enhancing comfort and adherence in diabetes treatment.
    MeSH terms: Administration, Cutaneous*; Animals; Diabetes Mellitus, Experimental/drug therapy; Humans; Hypoglycemic Agents/administration & dosage; Hypoglycemic Agents/pharmacokinetics; Hypoglycemic Agents/therapeutic use; Hypoglycemic Agents/chemistry; Male; Skin/drug effects; Skin/metabolism; Skin Absorption/drug effects; Swine; Drug Delivery Systems; Mice; Nanoparticles/chemistry
  14. Binti Adnan NAA, Kalam N, Lim Zi Jiunn G, Komarasamy TV, Balasubramaniam VRMT
    Am J Trop Med Hyg, 2025 Mar 05;112(3):481-490.
    PMID: 39689362 DOI: 10.4269/ajtmh.23-0819
    Chikungunya virus (CHIKV), prevalent in tropical regions, is known for causing frequent outbreaks, particularly in Central Africa, South America, and Southeast Asia. It is an arbovirus transmitted by the Aedes (Ae.) aegypti and Ae. albopictus mosquitoes. Infections lead to severe joint and muscle pain, which can linger and significantly impair an individual's health, quality of life, and economic stability. Recent climatic changes and the globalization of travel have facilitated the worldwide spread of these mosquitoes. Currently, no U.S. Food and Drug Administration (FDA) approved drug is available for treating CHIKV infection. Recently, the FDA approved a live, attenuated vaccine called Ixchiq. However, this vaccine has been linked to side effects, leading the FDA to mandate additional post-marketing studies to assess the risk of severe adverse reactions similar to the virus. An emerging strategy in drug development focuses on targeting host factors that the virus exploits rather than the viral proteins themselves. This review explores the interactions between CHIKV and host factors that could be potential therapeutic targets. Despite progress in understanding the life cycle of CHIKV, the immune system's role in combating the virus still needs to be fully understood. Investigating treatments that enhance the host's immune response may offer new paths to combating CHIKV.
    MeSH terms: Aedes/virology; Animals; Humans; Viral Vaccines/immunology; Host-Pathogen Interactions; Mosquito Vectors/virology
  15. Cai Z, Zhou S, Zhang T, Du Q, Tu M, Wu Z, et al.
    Food Chem, 2025 Mar 15;468:142447.
    PMID: 39689487 DOI: 10.1016/j.foodchem.2024.142447
    Lactiplantibacillus plantarum NUC08, a novel probiotic strain, has demonstrated potential for synergistic fermentation with starter cultures. This study investigates its functional properties in fermented milk and examines how mulberry fruit extract (MFE), rich in bioactive compounds, may influence its fermentation performance. MFE significantly boosted LAB growth, improved texture and rheological properties, and enhanced antioxidant capacity in the probiotic yogurt. GC-MS analysis revealed that MFE enriched the flavor profile by increasing key flavor-related metabolites, contributing to superior sensory qualities. Furthermore, the combination of L. plantarum NUC08 and MFE led to distinct shifts in metabolic pathways, as shown by LC-MS analysis, amplifying the regulatory effects on antioxidant activity. These findings demonstrate the synergy between MFE and L. plantarum NUC08, where MFE enhances the growth and functionality of L. plantarum NUC08, improving the yogurt's physicochemical properties, antioxidant capacity, and flavor, with potential for functional dairy product development.
    MeSH terms: Animals; Fermentation*; Flavoring Agents/metabolism; Flavoring Agents/chemistry; Humans; Milk/microbiology; Milk/chemistry; Taste; Probiotics*; Lactobacillus plantarum/metabolism; Lactobacillus plantarum/chemistry
  16. Ng KH, Fong CY, Kamarudzaman MFS, Lo WH, Khalid F, Chong LA
    Brain Dev, 2025 Feb;47(1):104308.
    PMID: 39675180 DOI: 10.1016/j.braindev.2024.104308
    OBJECTIVES: Children with cerebral palsy (CP) can experience a substantial amount of pain. Effective pain management hinges on precise and prompt assessment. We designed a mobile-based application NeuroPAIN app to monitor pain among children with CP. NeuroPAIN app allowed parents to record pain symptoms, pain duration, and rate the perceived pain their child was facing. We evaluated the usefulness of NeuroPAIN app in pain recognition and monitoring among Malaysian parents of children with bilateral CP.

    METHOD: Prospective cohort study of all parents of children with bilateral non-ambulant CP who owned Android devices. NeuroPAIN app was installed in all participants. At 3-month follow-up, data of the NeuroPAIN app was analyzed and participants were given a feedback questionnaire to complete.

    RESULTS: Total of 60 parents participated in the study (child's median age 7 years, interquartile range 4-8.75 years). The vast majority (95 %) of parents reported pain in their children. Children with assisted tube feeding was associated with reported increased pain frequency. Majority (77 %) felt it was easy to navigate the NeuroPAIN app. Two-thirds regularly tracked their child's pain using the app over a 2-month period. Parents of children with prolonged periods of pain ≥25 s were associated with reduced app usage.

    CONCLUSION: Majority of Malaysian children with bilateral CP often experience pain particularly among those with assisted tube feeding highlighting the importance for clinicians to be vigilant in monitoring pain among these children. Prolonged pain periods among children with CP may lead to parental fatigue in monitoring pain through the NeuoPAIN app.

    MeSH terms: Child; Child, Preschool; Female; Humans; Malaysia; Male; Pain/diagnosis; Pain Measurement/methods; Parents; Prospective Studies; Surveys and Questionnaires; Mobile Applications*
  17. Iqbal MA, Younis MW, Maqbool M, Goh HH, Kurniawan TA, Amjad M, et al.
    Int J Biol Macromol, 2025 Feb;288:138775.
    PMID: 39675599 DOI: 10.1016/j.ijbiomac.2024.138775
    In this study, we present a groundbreaking approach utilizing metal-free, visible light-mediated organic photoredox catalyzed atom transfer radical polymerization (O-ATRP) to synthesize cellulose-based stimuli-responsive polymers. Our method resulted in the successful synthesis of innovative metal-free poly(N-tertiary-butylacrylamide)-graft-hydroxypropyl cellulose (PNTBAM-g-HPC) polymers with exceptional control over molecular weight and narrow dispersity index (Đ) and explored their applications in organo-photocatalytic reactions. This approach addresses the limitations of traditional atom transfer radical polymerization method, which suffer from metal contamination and toxicity related problems. O-ATRP and organic photoredox catalysts have been sought to address these difficult challenges. In this study, we synthesized organic compound; 2,4,5,6-tetrakis(diphenylamino)isophthalonitrile (4DPIPN), which served as an organic photoredox catalyst, enabling the synthesis and application study of PNTBAM-g-HPC polymers via organic photoredox catalysis. Furthermore, by employing 4DPIPN, three different types of PNTBAM-g-HPC polymers were synthesized. Through thorough characterization techniques including FTIR, NMR, UV/Visible spectroscopy, TGA, and GPC analysis, we confirmed the successful synthesis of photocatalyst and three different types of PNTBAM-g-HPC polymers under O-ATRP conditions. By adjusting the molar ratios of PNTBAM side chains, we fine-tuned the LCST of HTA-20 polymers to 37.3 °C, demonstrating their thermoresponsive behavior. This synthetic approach shows great potential for applications in biosensors, pharmaceuticals, biomedical engineering, and drug delivery systems.
    MeSH terms: Acrylamides/chemistry; Catalysis; Light; Oxidation-Reduction*; Polymers/chemical synthesis; Polymers/chemistry; Temperature; Photochemical Processes; Polymerization*
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