BioMed Research International

Objective: The APOE {varepsilon}4 genotype is the known most significant risk factor for sporadic Alzheimer's disease (AD), but the association between the blood levels of its encoded apolipoprotein E4 (ApoE4) and AD is poorly understood. Methods: We developed a chemiluminescent quantitative assay and a colloidal gold lateral chromatography qualitative assay to detect ApoE4 protein in plasma samples and compared the results with conventional genotyping. Results: In 185 samples, the plasma ApoE4 protein levels in non-{varepsilon}4 carriers ({varepsilon}2/{varepsilon}3 and {varepsilon}3/{varepsilon}3) were 0.07 +/- 0.23 and 0.05 +/- 0.17 g /mL, respectively; while the levels in {varepsilon}4 carriers ({varepsilon}2/{varepsilon}4, {varepsilon}3/{varepsilon}4, and {varepsilon}4/{varepsilon}4) were 4.58 +/- 1.96, 4.28 +/- 3.49 and 8.27 +/- 9.04 g/mL, respectively. Using a threshold of 1.1 g /mL, the quantitative method achieved a sensitivity of 100% and a specificity of 99.2%, while the qualitative method showed a concordance rate of 96.2% with genotyping. We also observed that among 133 non-{varepsilon}4 carriers, one had plasma ApoE4 protein levels higher than the threshold, which would require further investigation. Conclusion: Quantitative and qualitative detection of ApoE4 protein provides as rapid and accurate method for identifying APOE {varepsilon}4 genotype carriers, offering valuable insights for Alzheimer's disease risk assessment and early intervention.

Objective. A deep learning (DL) model was used to convert smartphone videos of a complete arch implant cast into 3D scans. The aim of current study was to determine if a custom scan body (SB) with geometric features and coating would outperform regular PEEK stock SB in this DL scenario. The DL-derived scan outcomes were compared with those obtained from a conventional splinted open-tray impression and from photogrammetry. Materials and Methods. A maxillary edentulous model with six implants and multi-unit abutment analogs was scanned using four protocols: conventional splinted open-tray impression (CO), photogrammetry (PG; Icam4D), DL using stock SBs (DLS) and DL using custom SBs (DLC). Each protocol was repeated for 10 times. The DL scans were produced from smartphone videos with a high-fidelity, multi-view 3D construction AI model (Neuralangelo). The custom designed SB incorporated geometric features and was fabricated via 3D printing followed by a spray coating. Accuracy (trueness and precision) was assessed using three measurements: Root Mean Square (RMS), linear deviation, and angular deviation. Results. DLC outperformed DLS in both trueness and precision regarding RMS and linear measurements (p<0.001). CO and PG demonstrated the highest RMS and linear trueness, with no significant difference between them (RMS: p=0.93; linear: p=0.663). PG achieved the best precision across RMS, linear and angular measurements. Conclusion. The optimised SB significantly improves the accuracy of DL-based approach for full-arch implant scan comparing to regular PEEK stock scan bodies. While early stage, neural surface reconstruction has potential as a viable option for full-arch implant rehabilitation.

Background: Children in Central Africa face compounded vulnerabilities, yet no comprehensive review has synthesized evidence on ECC prevalence or risk factors. This study aims to determine the prevalence and identify risk factors associated with early childhood caries (ECC) in the Central Africa Sub-region. Methods: This systematic review and meta-analysis was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under the ID CRD420251019424. A comprehensive literature search was conducted across PubMed, African Journals Online, Scopus, Web of Science, CINAHL, and ProQuest as well as through Google Scholar and other grey literature sources, with no language restrictions. Eligible studies were limited to cross-sectional, cohort, case-control, and clinical trials that reported baseline data on the prevalence and risk factors of ECC in the Central Africa sub-region among children under the age of six. There was no restriction on publication date. Exclusion criteria included letters to the editor, commentaries, studies without accessible full texts, systematic reviews, reviews lacking original data, studies with overlapping data already included, and non-peer-reviewed sources such as books. Study quality was assessed using the Joanna Briggs Institute Critical Appraisal Tool. A random-effects meta-analysis was conducted using Review Manager 5.4.1, and heterogeneity was assessed using the I statistic. Results: Five studies met the eligibility criteria, encompassing 640 participants. Three of the studies were from Cameroon, and one from the Democratic Republic of Congo and the Central African Republic, respectively. One study that did not report the prevalence of ECC and another non-peer-reviewed publication were excluded from the meta-analysis. The prevalence of ECC in the region ranged between 29.4% and 80% with a pooled prevalence of 57% (95% CI: 22 to 92%; I = 98%). Identified risk factors for ECC were related to oral hygiene behaviours, diet and feeding practices, parental/caregiver factors, and access to dental care. Conclusions: ECC is highly prevalent in Central Africa, driven by preventable factors. Urgent region-specific policies and programs are needed to improve preventive services and address data gaps across this under-resourced subregion.

Periodontitis, a chronic inflammatory disease affecting approximately 40% of U.S. adults aged 30 years and older, is characterized by dysbiosis of the dental plaque microbiome. However, although scaling and root planing (SRP) is the cornerstone of periodontal treatment, its effects on the taxonomic composition and functional potential of the dental plaque microbiome remain incompletely understood. In this study, we used whole-metagenome shotgun sequencing to characterize taxonomic composition and functional potential in dental plaque microbiomes collected from 39 patients with Stage II or III generalized periodontitis before and 3-4 months after SRP. Consistent with clinical improvement, periodontal therapy significantly reduced bleeding on probing and plaque index. Whole-metagenome shotgun sequencing identified 3.18 million non-redundant genes and 12,353 microbial species across 78 samples, revealing increased gene and species richness after treatment, along with a significant restructuring of microbial community. Established periodontal pathogens, including Porphyromonas gingivalis and Tannerella forsythia, as well as the emerging pathogen Escherichia coli, decreased following treatment, whereas health-associated early colonizers, including multiple Actinomyces species and Streptococcus cristatus, increased. Functional annotation using the Carbohydrate-Active Enzymes (CAZy) database identified treatment-associated differences in several carbohydrate-active enzymes, including multiple glycosyltransferases, indicating remodeling of the predicted functional potential of the dental plaque microbiome. These findings demonstrate that successful SRP promotes coordinated taxonomic and predicted functional remodeling of the dental plaque microbiome and highlight the value of shotgun metagenomic sequencing for characterizing both taxonomic and functional recovery following periodontal therapy.

Background: Sepsis-associated liver injury (SALI) is commonly assessed using static laboratory values, although liver dysfunction during sepsis is dynamic.Methods: This retrospective cohort study included 162 ICU patients with SALI. Early trajectories of alanine aminotransferase, total bilirubin, and albumin during the first 7 days after ICU admission were identified using group-based multi-trajectory modeling. Landmark analysis and Cox regression were used to evaluate 60-day mortality.Results: Twenty-five patients died within 60 days. Four trajectory classes were identified. Between-class separation was driven mainly by alanine aminotransferase and total bilirubin, whereas albumin showed limited short-term variation. After the landmark time point, Class 3 (HR, 4.374; 95% CI, 1.960-9.759; P <0 .001) and Class 4 (HR, 7.451; 95% CI, 3.649-15.212; P <0 .001) had higher mortality risk than Class 1.Conclusions: Early joint trajectories of liver-related laboratory biomarkers may identify clinically meaningful SALI subphenotypes and support risk stratification in critically ill patients.

Background: Subepithelial connective tissue grafting remains a reference treatment for predictable root coverage. Although short- and medium-term outcomes of tunnel-based procedures are well documented, evidence regarding stability beyond 10 years remains limited. This study evaluated the long-term clinical performance of a minimally invasive tunnel technique combined with subepithelial connective tissue grafting (SCTG) under routine clinical conditions. Methods: This retrospective longitudinal cohort study included 74 patients (57 women and 17 men) contributing 710 gingival recession sites treated between 2009 and 2025. All sites were treated with a tunnel approach and SCTG, with enamel matrix derivative (EMD) used in selected cases. The mean follow-up was 6.0 for 4.0 years, with a maximum observation period of 16 years. The primary outcome was recession depth reduction. Secondary outcomes included complete root coverage (CRC), mean root coverage, and long-term marginal stability. Clinically relevant relapse was defined as a 1 mm increase in recession after initial healing. Results: Mean recession reduction was 2.72 mm. Complete root coverage was achieved at 83.4% of treated sites. At the final available follow-up, no treated site showed a clinically relevant relapse of 1 mm after initial healing, and no site deteriorated beyond its baseline recession level. Treatment effects were observed across anterior and posterior regions. Conclusions: Within the limitations of a retrospective cohort design, tunnel surgery combined with SCTG was associated with high root-coverage predictability and durable marginal soft-tissue stability for observation periods extending to 16 years. These real-world data support phenotype-enhancing, minimally invasive soft-tissue augmentation as a durable therapeutic strategy for localized and multiple gingival recessions. Keywords: gingival recession; tunnel technique; subepithelial connective tissue graft; root coverage; periodontal plastic surgery; long-term stability

Therapy of ischemic stroke is currently limited to pharmacological and/or mechanical recanalization. There are no neuroprotective therapies approved for use during the rehabilitative phase of ischemic stroke, which is characterized by neurodegenerative changes. Thus, the search for neuroprotective compounds capable of preventing neuronal death caused by pathogenetic cascades triggered during hypoxia is an urgent task. In this study, we demonstrate increased culture viability following pre- and post-incubation with salicyl-carnosine (SC) in a model of oxygen glucose deprivation on a primary culture of rat cortical neurons. Its neuroprotective properties were greater than that of acetylsalicylic acid and carnosine, and it was effective in lower concentrations. In addition, SC protected the culture from NMDA-induced excitotoxicity. We also showed the passage of SC into neurons, and the presence of its direct antioxidant activity in a model of paraquat-induced oxidative stress. The neuroprotective effects of SC are associated with a decrease in the level of pro-apoptotic protein Bak and a decrease in the activation of kinase p38, as well as an increase in the activation of kinase ERK1/2. The acquired data suggests that SC is a promising neuroprotective compound, and warrants further investigation in vivo.

The incidence of vascular complications differs among dermal filler formulations. This study aimed to evaluate the embolic risk associated with Neofilera(R), a filler composed of carboxymethyl cellulose and polylactic acid microspheres, following intra-arterial injection. The central auricular arteries of rabbits were injected with Neofilera(R) at volumes of 0.1 mL or 0.2 mL under various conditions: normal saline (control) and Neofilera(R) diluted at ratios of 1:5 (Group 1), 1:10 (Group 2), and 1:15 (Group 3). The presence of transparent emboli was assessed immediately after injection, while tissue necrosis (percentage and area) and histopathological alterations were evaluated on days 1 and 7 post-injection. Relative to controls, Neofilera(R) administered at 0.1 mL dispersed within minutes and did not induce significant tissue necrosis at either observation time point. In contrast, administration of 0.2 mL, even in diluted form, was associated with an increased incidence of vascular occlusion. Overall, these findings indicate that Neofilera(R) presents a lower embolic risk when injected at a volume of 0.1 mL, whereas higher injection volumes may substantially increase the likelihood of embolic complications.

Red blood cell (RBC) disorders arose as an advantageous evolutionary response to malaria infections. In a heterozygous condition, such as in Southeast Asian Ovalocytosis (SAO), hosts are protected against severe malaria. In malaria-endemic regions, RBC disorders are presumed to be highly prevalent. Tanjung Leidong, a moderately endemic area in North Sumatra (API 1.13 in 2024), lacks comprehensive data on RBC disorder prevalence beyond G6PD deficiency. Therefore, this study aims to characterize the RBC disorders in this region as well as to characterize the anemia status in children living in Tanjung Leidong. Schoolers attending D. I. Panjaitan elementary to high school were recruited and screened for malaria by microscopy and G6PD deficiency using the STANDARD G6PD Assay. The DNA of the participants was also extracted to be genotyped for SAO, Hemoglobin E (HbE), and -thalassemia. Exclusively, G6PD-deficient DNA samples were genotyped further to determine variants. The proportion of G6PD deficiency, SAO, HbE, -thalassemia one-gene deletion, and two-gene deletion were 0.90%, 0.90%, 2.40%, 6.26%, and 0.30%, respectively. Anemia prevalence was approximately 14%, and RBC disorders were observed across children with normal to obese BMI. No malaria infections were detected by microscopy. The predominance of asymptomatic RBC disorders highlights that they are protective against malaria infection, although their protective role against malaria could not be directly assessed in this study. Both nutritional and genetic factors are found to contribute to anemia in this cohort. These findings underscore the importance of integrated screening strategies for RBC disorders and anemia in malaria-endemic settings.

Objectives: Collaboration among health care professionals and the services they provide can be strengthen by interprofessional education (IPE). IPE can be implemented at the undergraduate level. Accordingly, the objective of the present study was to evaluate senior students' understanding of the terms interdisciplinarity and multidisciplinarity within the context of IPE. Methods: A retrospective cross-sectional study design was used. Students understanding of interdisciplinarity and multidisciplinarity was assessed through an assessment question completed by three consecutive cohorts of senior undergraduate dental students at the UBC Faculty of Dentistry between 2021/22 and 2023/24 (N = 177). Responses had a maximum of 100 words and were categorized into one of four predetermined themes: concordant knowledge (when both definitions were correct), discordant rhetoric (when both definitions were incorrect), switched ideas (when the definitions were reversed), and altered discourse (when the concepts of discipline and specialty were conflated). Descriptive and inferential statistical analyses were performed using SPSS Version 31. Results: Of the 177 students enrolled, 164 provided responses to the question on multidisciplinarity and interdisciplinarity: 60 students in 2021/22, 51 students in 2022/23, and 53 students in 2023/24; the mean age was 25 years and 88 were female. Of the four predetermined themes, 45.7% of responses reflected concordant knowledge, 15.9% discordant rhetoric, 18.3% switched ideas, and 20.1% altered discourse. The logistic regression analysis showed age associated with a higher probability of providing the correct definitions (adjusted OR = 1.39; 95% CI: 1.06 - 1.83; p = 0.017). Conclusions: Knowledge of interdisciplinary and multidisciplinary appeared to be retained by the majority of students. However, dental education programs, alongside other health professional training programs, should continue to incorporate interprofessional education through both didactic and experiential learning opportunities to equip students with the skills necessary to provide collaborative care in future practice.

Dried blood spot (DBS) sampling is becoming a popular alternative to traditional blood sampling approaches, offering advantages such as convenience of collection, transportation, and storage, as well as lower biohazard risk. N-glycosylation, a major post-translational modification of proteins associated with numerous biological and pathological functions, is one area of interest for DBS analysis. In this study, we utilize a protocol for N-glycosylation profiling of DBS by ultra-high-performance liquid chromatography based on hydrophilic interactions and fluorescence detection (HILIC-UHPLC-FLR). The protocol includes DBS cutting, protein extraction and enzymatic digestion, labeling with 2-aminobenzamide, followed by cleanup and HILIC-UHPLC-FLR measurement. We compare DBS with plasma and demonstrate the stability of DBS N-glycosylation profile when DBS are prepared from fresh blood, frozen whole blood, or a combination of separated frozen blood cells and corresponding frozen plasma. Additionally, we compared DBS N-glycans from pre- and diabetic subjects. Fucosylation, bisection, and galactosylation showed a statistically non-significant increasing trend in diabetes, whereas sialylation showed a statistically non-significant decreasing trend in diabetes. The main advantage of this method is the ability to repurpose samples, which were initially not intended for biomarker N-glycan analysis, such as frozen whole blood. Additionally, DBS N-glycan profiling is the easier, cheapest and the least invasive approach to conventional plasma in pre-diabetes and diabetes patients' diagnostics and monitoring.

Abstract Introduction Chronic kidney disease (CKD) in adult patients with type 2 diabetus mellitus (T2DM) is a serious public health challenge and continues to be a major source of morbidity and mortality in Sub-Saharan Africa (SSA). The burden of CKD among T2DM patients in SSA has been documented in several studies, but the results remain heterogeneous, and there is limited comprehensive data on its overall prevalence and factors associated with the diseases. Therefore, this study aimed to estimate the pooled prevalence of CKD and assess its associated factors among adult patients with T2DM in SSA. Methods This systematic review and meta-analysis was conducted and reported according to PRISMA 2020 guidelines, and the study protocol was registered in PROSPERO (CRD420261411707). A comprehensive search of relevant studies was conducted from PubMed, Google Scholar, Scopus, Cochrane Library, and EMBASE published between January 2000 and December 2025 in SSA. Data were analyzed using Stata version 17. A random-effects model was used to estimate the pooled prevalence of CKD among adults with T2DM patients. Heterogeneity was assessed using Cochranes Q and I{superscript 2} statistics with visual inspection through forest and Galbraith plots. Publication bias was evaluated using a funnel plot and Eggers test. Subgroup and sensitivity analyses were also performed. Results Out of the 3702 study participants from 16 included studies, the estimated pooled prevalence of CKD among adult T2DM patients in SSA was 35.8% (95% CI: 27.1-44.4), indicating significant heterogeneity (I{superscript 2}=97.25%, p<0.001) across the studies. Subgroup analyses on the pooled prevalence of CKD on the basis of different diagnostic criteria were conducted. Modification of diet in renal disease (MDRD) reported a prevalence of 34% (26, 43), the chronic kidney diseases epidemiology collaboration (CKD-EPI) reported a prevalence of 39% (21, 57), and the Cockcroft-Gault (CG) method reported a prevalence of 34% (12, 56). In addition, older age (OR = 2.27, 95% CI: 1.19-4.33) and longer diabetes duration (OR = 1.90, 95% CI: 1.07-3.40) were factors significantly associated with the prevalence of CKD. Conclusion The prevalence of CKD in SSA was high, affecting nearly one in three adults with T2DM patients. In addition, factors such as older age and longer diabetes duration significantly contributed to the association with CKD. To lessen this issue, focused public health actions are strongly advised, such as screening, education, and awareness campaigns. Systematic review registrations PROSPERO (2026: CRD420261411707).

This study compared and evaluated two widely used deep learning-based artificial intelligence (AI) models, U-Net++ and YOLOv11, for quantifying tooth and root exposure on intraoral camera images of the mandibular anterior lingual region. Intraoral images of the mandibular anterior lingual region were collected from 291 patients (mean age, 52.8 years) at a university hospital dental clinic with institutional review board approval (YUMC IRB 2021-07-019-002). A total of 266 eligible images (mean, 5.50 teeth per image; 3.70 teeth with root exposure) were annotated. YOLOv11 and U-Net++ were fine-tuned using five-fold cross-validation with data augmentation. Model performance was evaluated on a held-out test set of 40 images using Dice coefficient, Intersection over Union (IoU), accuracy, mean Average Precision at an IoU threshold of 0.5 (mAP50), Lins concordance correlation coefficient (CCC), and intraclass correlation coefficient (ICC). Confidence intervals were estimated using 10,000 bootstrap iterations. For tooth segmentation, U-Net++ demonstrated superior performance, with high accuracy (0.981), Dice coefficient (0.971), and IoU (0.944). In contrast, for root segmentation, YOLOv11 outperformed U-Net++, achieving higher Dice (0.860 vs. 0.746) and IoU (0.762 vs. 0.631). Notably, YOLOv11 showed stronger agreement with the ground truth for quantifying the exposed root ratio (ERR) (CCC, 0.973; ICC, 0.975). These findings suggest that accurate detection of root exposure is important for assessing periodontal tissue loss and that YOLOv11 is a promising model for root exposure quantification in intraoral images. YOLOv11-based quantification of root exposure may serve as a useful adjunctive AI tool for screening and monitoring periodontal conditions and may support individualized treatment planning.

Background Non-alcoholic fatty liver disease (NAFLD) has become a common metabolic disorder in paediatric age groups and is a major contributor to the burden of health economics. However, there is a lack of comprehensive data on the prevalence of this condition among children. Methods English language literature published from inception until April 2025 was searched from the electronic databases, i.e., PubMed/Medline, Scopus, Embase, and CINAHL. Original data published in any form that reported NAFLD prevalence among children and/or adolescents in India were included. The subgroup analysis of prevalence was done based on the risk category, i.e., average risk group and high risk group (obesity or overweight, metabolic syndrome, etc.). The prevalence estimates were pooled using the random-effects model. Results A total of 11 studies (six in high-risk populations and 5 in the average-risk general population) comprising data from 3512 individuals were found eligible and were included. The overall pooled estimate of NAFLD prevalence among the children and adolescents was 35.4% (95% CI: 19.7% to 52.9%) with very high heterogeneity(I2=99.0%). The pooled prevalence of NAFLD among average/low risk children and adolescents was 10.7% (95%CI: 5.2% to 20.5%) with high heterogeneity across the studies (I2= 96.6%, p=0.001) whereas the pooled prevalence of NAFLD in high risk overweight/obese children and adolescents was found to be 59.7% (95% CI:55.2% to 64.1%) with moderate heterogeneity across the studies (I2=50.90%; H2=2.04; Q (5) = 10.03; p=0.07) Conclusion This systematic review demonstrates that non-alcoholic fatty liver disease (NAFLD) poses a growing health concern among Indian children and adolescents, as 1 out of 3 children/adolescents is suffering from it, with a disproportionately high burden observed in those who are overweight or obese.

Alzheimer s disease (AD) is a critical neurological disorder that causes the brain to shrink and leads to the eventual death of brain cells, adversely affecting a person s ability to function. AD is a fast-growing disease in the United States and was the fifth leading cause of death among Americans 65 years of age or older in 2023. In the United States 6.9 million people aged 65 or older were diagnosed with AD, along with a high rate of undiagnosed patients. Thus, the objective of our study is to develop a real data-driven predictive model to identify a patient with AD based on eight risk factors: Age, Gender, ADAS-Cog13, Entorhinal, Fusiform, Intracranial Volume (ICV), Amyloid-Beta, and Tau Protein, with a high degree of accuracy. The quality of the model was evaluated using well-established and sophisticated statistical measures: the area under the receiver operating characteristic curve, calibration plot, Hosmer-Lemeshow goodness-of-fit test, and K-fold cross-validation. If a patient is given information on the above risk factors, our proposed binary logistic regression model can classify the patient as having AD or not with at least 98% accuracy.

Background: Oral dysbiosis has been associated with oral squamous cell carcinoma (OSCC); however, most microbiome studies rely on 16S ribosomal RNA (rRNA) gene sequencing, limiting species-level taxonomic resolution. Methods: Dental plaque, saliva, and tumor tissue samples from 10 patients with OSCC and dental plaque and saliva samples from 10 healthy controls were analyzed in this exploratory cross-sectional study. DNA was extracted and subjected to shotgun metagenomic sequencing using the Illumina MiSeq platform. Sequence reads were quality filtered with fastp, taxonomically classified using Kraken2 v2.1.3, and species-level abundances were re-estimated with Bracken v2.9 following the removal of human reads and low abundance taxa. Relative abundances were compared using the Mann Whitney U test with the Benjamini Hochberg false discovery rate correction, while the Bray Curtis principal coordinate analysis was used as an exploratory approach to visualize microbial community patterns. Results: Shotgun metagenomic sequencing revealed distinct bacterial community profiles across the oral microenvironment. Dental plaque exhibited the highest taxonomic diversity and relative abundance. The control plaque was enriched in Streptococcus koreensis, Capnocytophaga sp. oral taxon 878, Treponema sp. Marseille Q4132, and Leptotrichia sp. oral taxon 498, whereas the plaque from patients with OSCC showed a higher relative abundance of Pyramidobacter piscolens, Parvimonas parva, and Gemella sanguinis. Salivary samples displayed lower diversity and a more homogeneous composition, predominantly comprising Capnocytophaga endodontalis, Prevotella jejuni, Aggregatibacter aphrophilus, and Gemella sanguinis. The tumor tissue showed relatively higher abundance of Sellimonas catena, Escherichia coli, Solobacterium moorei, and Lacrimispora sp. HJ 01. Conclusions: This exploratory study provides species-level characterization of the oral microbiome across multiple oral microenvironments in OSCC and generates hypotheses for future integrative metagenomic and functional studies investigating the potential contribution of oral bacterial communities to OSCC pathogenesis.

Malaria remains one of the most pressing health problems, especially in Sub-Saharan Africa. Various antimalarial drugs, used to combat this debilitating illness, may directly or indirectly affect blood indices in humans. This study aims to evaluate the toxicological effects of sequential administration of Artemether-lumefantrine and sulfadoxine-pyrimethamine in male Wistar rats. Thirty (30) mature male Albino Wistar rats weighing between 190-280g were randomly divided into five groups comprising six (6) rats each. Group 1 served as control, Group 2 received Artemether-lumefantrine (8 mg/kg/bw) for 3 days, Group 3 received sulfadoxine-pyrimethamine (0.079 mg/kg/bw) for 1 day, Group 4 received a sequential dose of Artemether-Lumefantrine for 3days and sulfadoxine-pyrimethamine for 1 day, while Group 5 received a sequential dose of SP for 1 day and AL for 3 days. Sequential administration of AL and SP resulted in a significant (p < 0.05) elevation of ALT, AST, ALP, serum total and direct bilirubin levels, urea, creatinine, and HDL. There was a significant (pL0.05) decrease in the serum total protein and albumin. Notably, HDL levels increased significantly in the SP [-&gt;] AL group (p < 0.05), while other lipid parameters showed sequence-specific significant changes compared to the control. Sequential administration, particularly the SP [-&gt;] AL sequence, was observed to have more pronounced effects on hepatorenal biomarkers compared to independent administration. These findings are relevant, especially in malaria-endemic regions where unregulated self-medication and drug switching are rampant.

BackgroundChronic obstructive pulmonary disease, primarily caused by exposure to cigarette smoke, is a heterogeneous lung condition characterized by complex metabolic alterations. The metabolic changes associated with smoking status have not been thoroughly investigated. Our study aims to explore the metabolite profile of COPD patients categorised by their smoking habits, including smokers, ex-smokers, and non-smokers. MethodsIn this study, the plasma metabolome of smoking stratified COPD patients were assessed using gas chromatography coupled to mass spectrometry. We applied multivariate and univariate statistical analysis to identify the differentially abundant metabolites. ResultsWe identified 23 altered metabolites in the smokers and 36 in the ex-smokers COPD subgroups. Interestingly, in comparison to the control group, no significant alteration was observed in the plasma of non-smoker COPD patients. Additionally, pathway enrichment analysis revealed top dysregulated metabolic pathways, including biosynthesis of unsaturated fatty acids, galactose metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The receiver operating characteristic curve screened five metabolites, such as tetradecanoic acid, 2,4-di-tert-butylphenol, chloroxylenol, tetradecanal, and 1-dodecene, with the highest diagnostic performance (AUC > 0.8). ConclusionThis study reveals distinct plasma metabolic signatures across COPD subgroups categorized by cigarette smoking history.

BackgroundMetabolic reprogramming is a common occurrence in tumor cells, where enhanced glycolysis promotes cell growth, invasion and migration. NF1 is tumor suppressor gene that downregulates the encoded neurofibromin protein. However, the effects of NF1 on energy metabolism and epithelial-mesenchymal transition (EMT) in glioblastoma multiforme (GBM), as well as the underlying molecular mechanisms, remain unclear. MethodsCRISPR/Cas9 gene editing technology was employed to construct GBM cell lines with NF1 gene mutations. Metabolomics was utilized to examine the impact of NF1 on metabolic remodeling in GBM. The Seahorse XF24 extracellular flux analyzer was used to detect the effect of NF1 knockdown on glycolysis and mitochondrial oxidative phosphorylation in GBM cells. Wound healing assay and Transwell chamber assay were utilized to detect the effect of NF1 on GBM cell invasion. Orthotopic tumor model in nude mice was established to explore the role of NF1 in vivo. In addition, Co-IP, western blotting, and immunofluorescence were used to explore the changes of key enzymes in glycolysis and mitochondrial oxidative phosphorylation and the relationship between NF1 and MFN1. ResultsThe expression of NF1 is decreased in glioma tissues and is significantly correlated with patient prognosis. NF1 knockdown may promote the invasion, migration, and EMT of GBM cells. At the same time, the activation of the AKT/mTOR signaling pathway promotes aerobic glycolysis in GBM cells, promotes mitochondrial division through targeted regulation of MFN1, and inhibits mitochondrial oxidative phosphorylation. NF1 deficiency promotes EMT in GBM cells by enhancing aerobic glycolysis and mitochondrial division. ConclusionNF1 deficiency promotes GBM glycolysis by activating the AKT/mTOR signaling pathway and inhibits the mitochondrial oxidative phosphorylation by regulating MFN1; NF1 deletion promotes GBM EMT by remodeling the pattern of energy metabolism.

Adipose-derived mesenchymal stem cells (gAD-MSCs) are promising candidates for veterinary regenerative medicine, yet the characterization of gAD-MSCs from locally adapted Indonesian goat breeds remains limited. This study aimed to isolate and characterize gAD-MSCs from Peranakan Ettawa (PE) goats using tissue explant culture. Subcutaneous adipose tissue was collected from the base of the tail of healthy PE goats (n=3). Primary cell outgrowth from explants was observed by Day 5, displaying characteristic fibroblast-like, spindle-shaped morphology and strong plastic adherence. Serial passaging to Passage 3 (P3) yielded a morphologically stable, homogeneous cell population. Assessment of cellular metabolic activity via the resazurin assay demonstrated sustained cell viability and a statistically significant increase in metabolic activity between Day 3 and Day 5 (p < 0.05). Furthermore, functional clonogenic capacity, evaluated using the colony-forming unit (CFU) assay, showed continuous temporal expansion of colonies over 14 days, yielding an average of 52.0 + - 4.1 colonies per dish. These findings confirm that expanded gAD-MSCs P3from PE goats maintain characteristic mesenchymal morphology, sustained metabolic activity, and clonogenic capacity. This work provides a baseline cellular profile of PE goat gAD-MSCs, supporting their potential use in veterinary regenerative medicine and tissue engineering.