BioMed Research International

Objective: To critically evaluate the influence of extracellular matrix stiffness on tumor progression, prognosis, and clinical implications in patients with oral squamous cell carcinoma. Design: This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and the protocol was registered in PROSPERO (CRD420251156429). Five databases (PubMed, Scopus, Embase, Web of Science, and OATD) were searched without restrictions on publication year or language. Human studies that evaluated extracellular matrix stiffness in oral squamous cell carcinoma, either as an assessment method or as a prognostic factor, were included; in vitro and animal studies were excluded. Results: Eight human studies involving 436 patients were included. Elastography was the most frequent measurement method, employed in four studies. Mean tumor thickness was reported in three studies and ranged from 3.0 to 4.4 mm. Extracellular matrix stiffness was expressed in various units (e.g., 37.7 gf, 23.5 kPa) and was consistently higher in tumor tissue than in normal mucosa in all studies. Three studies demonstrated a significant positive correlation between stiffness and tumor thickness. One study identified predictive cut-off values for lymph node metastasis and reported that high matrix stiffness was an independent predictor of worse overall survival (HR = 4.022; 95% CI: 1.294-12.495; p = 0.016) and recurrence-free survival (HR = 5.680; 95% CI: 1.146-28.143; p = 0.033). A meta-analysis of five studies (307 patients) showed a significantly higher standardized stiffness in oral squamous cell carcinoma compared with normal oral mucosa (standardized mean difference = 5.28; 95% CI: 2.61-7.94; p < 0.001), with substantial heterogeneity (I2= 98.6%). Conclusions: Extracellular matrix stiffness is elevated in oral squamous cell carcinoma and is associated with greater tumor thickness, lymph node metastasis and, in one study, worse survival. These findings support extracellular matrix stiffness as a potential biomechanical marker, pending further validation in standardized prospective studies.

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.

Kidney stones are a disorder in which urinary solutes precipitate to form crystalline aggregates in the urinary space. The blood urea nitrogen-to-albumin ratio (BAR), a common inflammatory indicator, has an unclear association with kidney stones. Using NHANES 2007-2020 data, we compared baseline characteristics between kidney stone formers and controls and evaluated the BAR-stone relationship via weighted multivariate logistic regression (WMLR), restricted cubic splines (RCS), stratification analyses, and XGBoost, with validation in an independent external cohort. Twenty baseline features, including BAR and age, differed significantly between groups (P < 0.05). In all WMLR models, BAR was positively and nonlinearly associated with kidney stone risk (OR > 1, P < 0.05). Subgroup analyses revealed stable associations in females (OR = 1.10, P < 0.001), low vitamin A intake (OR = 1.10, P < 0.001), high water intake (OR = 1.11, P < 0.001), age < 50 years (OR = 1.14, P < 0.01), and education less than high school (OR = 1.11, P < 0.01). XGBoost identified BAR and water intake as prominent risk factors (AUC = 0.658). External validation confirmed a positive association (Model 1 OR = 1.029, 95% CI 1.016-1.043; Model 2 OR = 1.030, 95% CI 1.016-1.044; Model 3 OR = 1.029, 95% CI 1.015-1.045; all P < 0.001), and RCS confirmed a nonlinear dose-response relationship (nonlinear P = 0.0006). Subgroups aged [&ge;] 60 years, males, and females showed significant associations (ORs = 1.027-1.034). In XGBoost, BAR was the most important predictor (Gain = 0.265). These findings reveal a significant association between BAR and kidney stones, offering theoretical insights for prevention and risk stratification; BAR may serve as a valuable marker in kidney stone management.

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

Background: Chronic kidney disease (CKD) may progress to stage 5 CKD (end-stage renal disease, ESRD), but stage-associated molecular alterations remain incompletely characterized. This study aimed to identify candidate biomarkers associated with CKD and ESRD. Methods: Two discovery datasets comparing CKD or ESRD with healthy controls were analyzed using differential expression analysis and weighted gene co-expression network analysis. Candidate genes were identified by intersecting differentially expressed genes with key co-expression modules, followed by protein-protein interaction network analysis using Degree, Closeness, and Maximal Clique Centrality algorithms. Candidate genes were evaluated in independent GEO validation datasets and further examined by quantitative real-time PCR and western blotting using clinical blood samples. Results: Ten hub genes were identified, among which EPB42, KLF1, and H3F3A were prioritized for further evaluation. EPB42 showed decreased expression in CKD but increased expression in ESRD, indicating an opposite-direction pattern between the two disease states. KLF1 showed no significant difference between healthy controls and CKD but was increased in ESRD, whereas H3F3A was increased in CKD and further increased in ESRD. Functional enrichment analysis highlighted processes related to oxygen transport, mitochondrial function, muscle-associated processes, and inflammation, suggesting possible involvement of hypoxia-associated oxidative injury and ferroptosis-related processes. Conclusions: Integrated transcriptomic and experimental analyses identified EPB42, KLF1, and H3F3A as candidate stage-associated biomarkers in CKD and ESRD. In particular, the opposite-direction expression pattern of EPB42 may provide additional molecular information for distinguishing CKD from ESRD.

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.

Background/Aims: In medical practice, the rising prevalence of infections in kidney transplant recipients (KTRs) is a notable concern. However, understanding the incidence and risk factors associated with infections in KTRs remains limited. This study aims to assess the incidence and factors associated infection among KTRs. Additionally, we also investigate the median time of each infection among KTRs. Methods: A retrospective cohort study was conducted from 1 January 2018- 31 December 2022 at Thailand's tertiary hospital. We performed univariable and multivariable logistic regression analyses to identify potential risk factors related infection and investigated for the incidence and median time of each infection among KTRs. Results: A total of 179 participants were included in this study. Our findings reveal the kidney from living donor was protective factor for infection among KTRs (aOR 0.063, 95% CI 0.005-0.792; p = 0.032). Urinary tract infections (UTIs)showed as the predominant pathogenic manifestation among KTRs (43%). The median time of UTIs, cytomegalovirus (CMV) infection and pneumocystis pneumonia (PCP) were 16, 57 and 94.5 days, respectively. Conclusions: Our study establishes that receiving a kidney from a living donor is a protective factor against post-kidney transplant infections. Particularly urinary tract infections were most common of infection. Monitoring urinary tract infections post-transplantation is recommended. Moreover, awareness of UTI, CMV infection and PCP should be concerned during 2-3 months after transplantation. However, due to a small sample size; we recommend to increase the number of particular participants in further investigations.

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.

Objective Based on the bioinformatics method of multi-database integration, this study systematically analyzes the expression characteristics, clinical pathological correlation, prognostic value, potential molecular mechanisms, and immune infiltration patterns of hepatocyte growth factor receptor (MET) in gastric cancer. Methods The UALCAN and GEPIA databases were employed to examine the differential expression of MET between gastric cancer and normal gastric mucosal tissues, as well as its associations with clinicopathological features. Kaplan-Meier Plotter was utilized to evaluate the impact of MET expression on overall survival (OS) and progression-free survival (PFS). Protein-protein interaction (PPI) network was constructed via LinkedOmics, followed by Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of co-expressed genes. Four algorithms, TIMER, CIBERSORT, EPIC, and MCPcounter, were used to cross evaluate the correlation between MET expression and immune cell infiltration; Further validate the cell type specific expression of MET using the gastric cancer single-cell sequencing queues (GSE134520, GSE167297) built into the TISCH database. Results MET expression was significantly elevated in gastric cancer tissues compared with normal gastric mucosa (P < .05), and its expression level was significantly correlated with tumor grade and TNM stage. Patients with high MET expression exhibited significantly poorer OS and PFS than those with low MET expression (P < .05). The PPI network revealed that MET could interact with 20 key proteins, including EGFR, ERBB2, HGF, STAT3, and GRB2 etc. GO enrichment analysis suggests that differentially expressed genes are significantly enriched in functions such as the ERBB signaling pathway, cadherin binding, and DNA repair complexes; KEGG enrichment analysis showed that MET related genes were significantly enriched in pathways such as homologous recombination, nuclear cytoplasmic transport, mismatch repair, and oxidative phosphorylation. Immune infiltration analysis showed that the negative association between MET and B cells infiltration has cross algorithm robustness, while the association with neutrophils, CD8+ T cells, CD4+ T cells, and macrophages exhibits algorithmic heterogeneity or insignificance; There is no significant correlation between MET and common immune checkpoint molecules such as PD-1, PD-L1, CTLA4, etc. Single cell validation further confirmed that MET is mainly enriched in malignant epithelial cells and endothelial cells, and is almost not expressed in immune cells. Conclusions Multidimensional bioinformatic analyses demonstrate that elevated MET expression serves as an independent risk factor for unfavorable prognosis in gastric cancer. MET may mediate dual drug resistance in gastric cancer via crosstalk with multiple signaling molecules (including EGFR, ERBB2, HGF, STAT3 and GRB2) and dysregulation of the homologous recombination repair pathway. Results from multiple-algorithm immune infiltration analysis, single-cell dataset analysis and immune checkpoint correlation analysis indicate that MET exerts only modest direct regulatory effects on the gastric cancer immune microenvironment. This exploratory study offers systematic bioinformatic evidence supporting MET as a candidate prognostic biomarker and potential therapeutic target for gastric cancer. Further functional experiments and prospective cohort studies are required to validate its molecular mechanisms and clinical utility.

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.

Objectives: To systematically compare the outcomes of zirconia-based versus metal framework veneered implant-supported fixed complete dental prostheses (ISFCDPs). We integrate cost effectiveness analysis comparing monolithic zirconia versus titanium PMMA ISFCDPs to model the 20 year costs and benefits associated with each arm. Data sources: PubMed/MEDLINE, Cochrane CENTRAL, Scopus, ClinicalTrials.gov and WHO ICTRP were searched on March 6 2026 with no date restrictions applied. Study selection: Two arm comparative studies reporting clinical outcomes for both zirconia-based and metal framework veneered ISFCDPs with a minimum of one year follow up after prosthesis delivery. Data extraction and synthesis: Two independent reviewers extracted data and assessed the risk of bias using the Newcastle Ottawa Scale. Narrative synthesis followed SWiM guidelines. A tiered material classification system was employed to handle framework alloy heterogeneity. Meta-analysis was not possible due to heterogeneity in outcomes reported and methodological differences. A Markov cohort model estimated cost-effectiveness from a patient perspective over a 20 year horizon. Deterministic and probabilistic sensitivity analysis (PSA) tested results robustness. Results: Eight retrospective cohort studies (396 patients; 551 prostheses) were included in final analysis. All were classified as Tier 1 due to inconsistent alloy reporting. Prosthesis and implant survival rates were high across both arms but with no statistical difference for any primary outcome. Cost-effectiveness analysis estimated total discounted per-patient costs of {pound}23,295 for titanium-PMMA and {pound}29,170 for monolithic zirconia over 20 years. This results in an ICER of {pound}315,417 per QALY gained. PSA confirmed zirconia as cost-effective in only 0.50% of 10,000 iterations at the {pound}20,000/QALY threshold. Net monetary benefit was consistently negative for zirconia. Conclusions: Both types of ISFCDPs provided high prosthesis and implant survival with no statistically significant difference in primary clinical outcomes, though all evidence was graded at very low certainty. We estimated a per-patient premium of {pound}5,875 for monolithic zirconia over a 20 year horizon with marginal QALY gains (0.019). Adequately powered RCTs with standardised material reporting are needed to strengthen our clinical and economic conclusions. Systematic review registration: OSF: 10.17605/OSFJO/CF796

The Enterobacteriaceae pathogens like E. coli, Shigella, Klebsiella and Salmonella cause a wide range of gastrointestinal and other mucosal infections when the contaminated food and water are consumed. Conventional microbiological methods are time-consuming and laborious process to detect these pathogens. Molecular assays are fast and sensitive to detect the pathogens. But a potential target for the detection is very essential to develop a molecular assay for the rapid detection. In this study, we explored the cpn60 UT region as a potential target for the detection of significant Enterobacteriaceae members like E. coli, Shigella sp, Salmonella, Klebsiella etc. We did the phylogenetic analysis of cpn60 UT region among the Enterobacteriaceae pathogenic groups. This analysis has revealed the presence of 13 clusters and two oligonucleotide regions with highest nucleotide conservation. Targeting these regions we have designed a set of oligonucleotide primer pairs and developed a SYBR green real time PCR assay to detect the Enterobacteriaceae pathogenic members. The degenerate oligonucleotide primers designed amplified a 132 bp UT region of cpn60 gene present in Enterobacteriaceae pathogens. The sensitivity of the assay was initially investigated by 10-fold dilution series of overnight broth culture of E. coli ATCC 10536 and had a detection limit of 101 CFU/mL. The specificity was assessed by comparing the amplification plot of a set of Enterobacteriaceae pathogens and non-Enterobacteriaceae members like Staphylococcus aureus (S. aureus) and Listeria monocytogenes (L. monocytogenes) and found to detect all the Enterobacteriaceae cultures included in the study whereas amplification was not seen in S. aureus and L. monocytogenes.

Esophageal cancer (EC) is characterized by complex transcriptional alterations and therapeutic resistance, posing challenges for traditional computational methods. In this study, we propose a deep learning (DL)-based computational framework to identify important genes and biologically relevant pathways in bulk cell RNA-seq data (GSE234304 and GSE273848), which comprise tumor and non-tumor esophageal tissue samples. A fully connected feedforward neural network was trained for binary classification, and two feature selection strategies were implemented: Neural Network followed by Support Vector Regression (NN+SVR) and Integrated Gradients combined with SVR (IG+SVR). The genes were then ranked according to their weights in SVR deriving the importance scores, and the top 100 genes were subjected to enrichment analysis using Enrichr and Metascape. The proposed DL-based approaches identified a greater number of expressed genes across established esophageal cancer cell lines than LIMMA, SAM, and the t-test did. Specifically, in the GSE234304 dataset, IG + SVR, our best method, identified a total of 9 expressed genes while the best baseline method, LIMMA, identified a total of 3 expressed genes. In terms of GSE273848 dataset, IG + SVR was also the best identifying a total of 11 expressed genes while the best baseline method, t-test, had a total of 7 expressed genes. The key genes identified included CEBPB, SUMO1, RORA, STAT1, GATA, OCT1, RUNX1, and NR3C1, as well as pathways related to nucleoprotein maturation, collagen fibril organization, the immunoglobulin-mediated immune response, immune regulation, and insulin signaling. These results show that combining neural networks and attribution-based regression creates an effective and interpretable framework for selecting genes in esophageal cancer research.

Background/Objectives: Urapidil with propofol is clinically efficient against elevated blood pressure during sedation. However, their physicochemical compatibility and emulsion stability upon continuous infusion remain unclear. This study aimed to evaluate different mixing ratios and diluents, thereby proving the safety limits for their co-administration. Methods: Urapidil solutions prepared with either sodium chloride (NS) or glucose injection (GS), and emulsified with propofol at different ratios (v/v), were stored for 12 h. Physical compatibility was assessed by visual inspection, pH, osmolality, mean droplet diameter (MDD), polydispersity index (PDI), zeta potential, and percentage of fat globules larger than 5 m (PFAT5). Chemical stability was quantified using high-performance liquid chromatography. Results: pH and osmolality stabilized. Urapidil hydrochloride and propofol contents remained pure at > 95%, MDD was < 500 nm, and PDI was < 0.2. Urapidil proportion in NS was significantly negatively correlated with the zeta potential. PFAT5 was > 0.05% after 2-8 h. In contrast, in GS at a 1:2 ratio, PFAT5 remained < 0.05%, which increased slightly in the 1:1 group at 8 h. PFAT5 stabilized in the high-propofol group (10:1) under all conditions. Conclusions: The chemical compatibility of the admixture was acceptable after 12 h of storage. However, physical compatibility was influenced by the mixing ratio, diluent type, and storage time. For clinical Y-site co-administration, a 10:1 mixing ratio or dilution in 5% GS is recommended. Enhanced proportions must be mixed with NS, while continuous infusion time must be < 2 h to mitigate fat embolism risk.

Background Pediatric nephrotic syndrome (NS) significantly increases cardiovascular risk, primarily through activation of the renin-angiotensin-aldosterone system (RAAS) and chronic inflammation. This study aimed to evaluate the relationship between serum aldosterone and interleukin 6 (IL-6) levels with carotid intima-media thickness (CIMT) in children with steroid-sensitive (SSNS) and steroid-resistant NS (SRNS), both before and after combined treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB). Materials and methods A prospective cohort study enrolled 32 children aged 2-18 years with idiopathic NS at Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia (May-June 2024). Participants received lisinopril (ACEI) or valsartan (ARB) for 12 weeks. Serum aldosterone was quantified via liquid chromatography-tandem mass spectrometry, IL-6 via electrochemiluminescence immunoassay, and CIMT via high-resolution B-mode Doppler ultrasound. Data were analyzed using SPSS version 26.0, including Shapiro Wilk normality testing, Pearson/Spearman correlations, and multivariate linear regression (enter method, R2=0.022), with statistical significance set at p<0.05. Results CIMT decreased significantly post-treatment (0.13{+/-}0.04 cm to 0.06{+/-}0.01 cm; p<0.001). Serum aldosterone remained stable (5.15 to 4.0 ng/dL; p=0.933), as did IL-6 (3.5 pg/mL; p=0.156). Univariate analyses revealed weak correlations (aldosterone-CIMT: R2=0.075; IL-6-CIMT: R2=0.215). Multivariate regression (R2=0.022) identified SRNS as positively associated with CIMT change (p=0.047), while aldosterone and IL-6 showed no significant independent effects. Conclusion This study highlights that ACEI and ARB therapy improved CIMT regardless of steroid sensitivity, suggesting vascular benefits may occur through pathways independent of aldosterone and IL-6 modulation.

The Spike protein (S-protein) of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) exhibits important and negative effects on human cells. Accordingly, the adverse effects of COVID-19 mRNA vaccines could be due to the presence of circulating spike and need to be mitigated. One of the biological activities of the Spike protein (and, indirectly, of the Spike-producing vaccines) is the high induction of apoptosis and pro-inflammatory gene expression in different cellular systems. We have recently demonstrated that Aged Garlic Extract (AGE) and its components S-allyl-Cysteine (SAC) and S1-propenyl-I-Cysteine (S1PC) are potent inhibitors of the expression of pro-inflammatory genes induced by treatment of the bronchial epithelial IB3-1 cells with the Spike RNA-based BNT162b2 vaccine. The main purpose of the present study was to determine (a) whether treatment of the IB3-1 bronchial epithelia cells with the BNT162b2 vaccine is associated with activation of the apoptotic pathway and (b) whether AGE, SAC and S1PC have any effect of therapeutic relevance on this experimental model system. We have exposed IB3-1 cells to increasing amounts of the BNT162b2 vaccine and, after 3 days of culture, apoptosis was assessed using the Annex V and the Caspase 3/7 apoptosis assays. The results obtained demonstrated highly significant increase of the percentage of apoptotic cells after treatment of IB3-1 cells with the BNT162b2 vaccine. The percentage of apoptotic cells was found to be significantly reduced in cell populations treated with the BNT162b2 vaccine in the presence of AGE, SAC and S1PC. The main conclusion of the results of our study is that Aged Garlic Extracts, and its components S-allyl-Cysteine and S1-propenyl-l-Cysteine are able to mitigate the pro-apoptotic effects of the Spike-producing BNT162b2 vaccine using the bronchial epithelial IB3-1 cell line as experimental model system. The efficacy of the reversion of BNT162b2 induced apoptosis suggests that AGE, SAC and S1PC should be considered for the development of protocols aimed at counteracting apoptosis induced by the Spike mRNA-based COVID-19 vaccines. This might be of potential clinical relevance, since one of the biological adverse effects of Spike protein (and, indirectly, of the Spike-producing vaccines) is the high induction of apoptosis in different cellular systems.

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.

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.

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.

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.