Biomolecules & biomedicine最新文献

{"title":"Interocular symmetry in dynamic retinal vessel analysis among healthy adults.","authors":"Michael Mendes Wefelnberg, Freerk T Baumann, Henning Guthoff, Damir Zubac","doi":"10.17305/bb.2026.14216","DOIUrl":"https://doi.org/10.17305/bb.2026.14216","url":null,"abstract":"<p><p>Dynamic retinal vessel analysis is a non-invasive approach for assessing retinal microvascular endothelial function, yet the extent to which eye selection, interocular variability, and systemic physiological factors influence dynamic retinal vessel analyzer (DRVA)-derived biomarkers remains insufficiently defined. This prospective methodological study aimed to evaluate the interocular symmetry and absolute and relative reliability of arterial flicker-induced dilation (aFID), venular flicker-induced dilation (vFID), and arteriolar constriction (aCON), and to determine whether these parameters are moderated by eye dominance, peak oxygen uptake (V̇O₂ peak), or intraocular pressure (IOP) in healthy individuals. Twenty apparently healthy adults completed two laboratory visits. During the first visit, aerobic capacity was assessed by cardiopulmonary exercise testing until volitional exhaustion. During the second visit, IOP, resting blood pressure, eye dominance, and retinal vascular endothelial function were assessed using DRVA in both eyes in randomized order. Interocular differences were examined using paired comparisons, Bland-Altman analysis, reliability statistics, and linear mixed-effects models accounting for bilateral measurements within participants. No significant differences were observed between the left and right eyes for aFID, vFID, or aCON. Bland-Altman analysis showed no systematic interocular bias across DRVA-derived parameters, although the limits of agreement were widest for aFID, indicating greater interocular variability. Relative reliability was highest for vFID, followed by aCON, whereas aFID showed only fair agreement. Similarly, absolute reliability analyses identified vFID as the most stable biomarker, with the lowest coefficient of variation, while aFID demonstrated the greatest variability. Linear mixed-effects models showed no significant moderating effects of eye dominance, V̇O₂ peak, or IOP on aFID, vFID, or aCON. These findings suggest that retinal vascular endothelial responses measured by DRVA are not systematically influenced by eye dominance or selected systemic physiological factors in healthy young adults. However, given the observed interocular variability, particularly for aFID, assessment of both eyes should be considered in clinical and research settings to improve measurement precision and reproducibility.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uric acid-to-albumin ratio is associated with metabolic syndrome in a large adult cohort.","authors":"Nagihan Akkaş","doi":"10.17305/bb.2026.14193","DOIUrl":"https://doi.org/10.17305/bb.2026.14193","url":null,"abstract":"<p><p>Serum uric acid has been linked to metabolic syndrome (MetS), although the relationship has been inconsistent. The uric acid-to-albumin ratio (UAR) has emerged as a novel composite biomarker that indicates the balance between systemic prooxidant burden and antioxidant capacity. This study aimed to evaluate the independent association between UAR and MetS in a large, real-world adult cohort. This cross-sectional study utilized retrospectively collected data from 4,596 adults (mean age: 38.78 ± 9.78 years; 64.6% female). MetS was defined according to the modified National Cholesterol Education Program - Adult Treatment Panel III (NCEP-ATP III) framework, excluding waist circumference due to significant missing data. Consequently, MetS classification was based on the remaining four criteria: triglycerides, HDL cholesterol, blood pressure, and fasting plasma glucose. UAR was calculated as uric acid (mg/dL) divided by albumin (g/L) and was dichotomized by the cohort median (low vs. high UAR). The prevalence of MetS was 7.0% (n = 320). Participants diagnosed with MetS were older and predominantly male compared to those without the condition (45.23 ± 9.93 vs. 38.29 ± 9.60 years; 61.2% vs. 33.4%, respectively; both p < 0.001). High UAR was more prevalent in the MetS group (70.9% vs. 44.6%, p < 0.001). Multivariable analysis revealed that age (OR 1.06, 95% CI 1.05-1.07), sex (female vs. male OR 0.43, 95% CI 0.33-0.56), and UAR group (OR 1.89, 95% CI 1.43-2.49) were independently associated with MetS (all p < 0.001). These findings indicate that UAR is significantly associated with MetS and adverse metabolic features, suggesting a relationship with cardiometabolic risk and reflecting an underlying metabolic imbalance.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA sequencing of intestinal Behçet's disease identifies putative pathogenic programs and potential therapeutic targets.","authors":"Chengzhen Lyu, Kun He, Shuai Li, Ziqi Guo, Xiaxiao Yan, Rou Tang, Yanan Shi, Jianyekai Tuerheng, Weiyang Zheng, Lingjuan Jiang, Yi Hu, Dong Wu","doi":"10.17305/bb.2026.14124","DOIUrl":"https://doi.org/10.17305/bb.2026.14124","url":null,"abstract":"<p><p>Intestinal Behçet's disease is a rare, refractory subtype of systemic vasculitis, characterized by deep ileocecal ulcers and extensive clinical overlap with Crohn's disease, while the cellular and molecular mechanisms underlying its pathogenesis remain poorly characterized. This study aimed to delineate the single-cell transcriptomic landscape of intestinal Behçet's disease, characterize its putative disease-associated transcriptomic signatures, and identify potential candidates for differential diagnosis and targeted treatment. We performed single-cell RNA sequencing on paired inflamed and histologically normal terminal ileum biopsy specimens from 4 patients with active intestinal Behçet's disease, and integrated our dataset with a public single-cell dataset from 12 Crohn's disease patients and 6 healthy controls for systematic bioinformatic analysis. We thereby constructed the first single-cell transcriptomic atlas of human intestinal Behçet's disease, profiling 98,119 high-quality cells to identify 3 major cell lineages, 20 distinct cell populations, and 41 functionally defined cell subtypes. Our analysis indicated that intestinal Behçet's disease may be characterized by robust stromal compartment activation, extracellular matrix remodeling, and potentially distinct epithelial antimicrobial signatures, which showed notable differences from the prominent epithelial barrier dysfunction and interferon-driven immune activation observed in Crohn's disease in this parallel intra-disease comparison framework. We further identified predicted pathogenic crosstalk between endothelial cells and neutrophils, which may be mediated by collagen/laminin-CD44 axes. Our findings thereby characterize the potential pathogenic features of intestinal Behçet's disease, and provide hypothesis-generating clues for the clinical management of this rare disorder.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and electrocardiographic predictors of perfusion impairment in symptomatic bradycardia requiring permanent pacemaker implantation.","authors":"Rauf Avcı, Muhammed Rıdvan Ersoysal, Görkem Kuş, Sever Yılmaz, Göksel Cagırcı, Şakir Arslan, Akif Durak, Ayşegül Ülgen Kunak, Ayşe Karaduru Avcı","doi":"10.17305/bb.2026.14123","DOIUrl":"https://doi.org/10.17305/bb.2026.14123","url":null,"abstract":"<p><p>Symptomatic bradycardia can lead to systemic hypoperfusion and hemodynamic instability, particularly in patients with advanced conduction system disease. This study aimed to identify factors associated with perfusion impairment in patients experiencing persistent symptomatic bradycardia who required permanent pacemaker implantation. In this single-center retrospective observational study, 299 patients who underwent pacemaker implantation between December 2021 and June 2025 were screened, resulting in the inclusion of 166 patients with persistent symptomatic bradycardia. Patients were stratified based on the presence of perfusion impairment, defined using specific clinical, biochemical, and organ-specific criteria. We analyzed clinical, laboratory, electrocardiographic, and echocardiographic parameters obtained prior to pacing. Perfusion impairment was identified in 70 patients, who were older and exhibited lower heart rates and blood pressures, elevated lactate levels, a higher incidence of renal dysfunction, and increased inflammatory markers. Multivariable analysis revealed that age (odds ratio [OR] 1.097; p = 0.001), heart rate (OR 0.910; p = 0.022), and high-grade atrioventricular (AV) block (OR 7.546; p = 0.002) were independently associated with perfusion impairment. Receiver operating characteristic (ROC) analysis demonstrated moderate discrimination for age and heart rate, while the multivariable model displayed improved discrimination. Our findings indicate that advanced age, lower baseline heart rate, and high-grade AV block are correlated with perfusion impairment in patients with persistent symptomatic bradycardia requiring pacemaker implantation. Early identification of this high-risk subgroup may facilitate timely monitoring and intervention.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modified albumin-bilirubin grade predicts overall and progression-free survival in metastatic gastric cancer.","authors":"Fatih Sargın, Zeynep Gok Sargin, Ayse Karaduru Avci, Feyza Cetin Cansiz, Ismail Beypinar, Muslih Urun, Yusuf Ilhan, Selman Celebi","doi":"10.17305/bb.2026.14188","DOIUrl":"https://doi.org/10.17305/bb.2026.14188","url":null,"abstract":"<p><p>Gastric cancer (GC) ranks among the most prevalent and lethal cancers worldwide. The albumin-bilirubin (ALBI) score was initially developed to assess liver function in patients with hepatocellular carcinoma. Its modified version, the modified ALBI (mALBI) score, may offer prognostic insights for other malignancies. This study aims to evaluate the prognostic significance of mALBI grade in patients with metastatic GC. Between August 2021 and June 2025, a total of 93 patients with metastatic GC were included in this retrospective multicenter cohort study. mALBI scores were calculated based on serum albumin and total bilirubin concentrations. Patients were classified according to the original mALBI grading system into Grade 1, Grade 2a, Grade 2b, and Grade 3. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method, while independent prognostic factors were analyzed via Cox regression. Kaplan-Meier analysis indicated significant differences in OS (χ² = 44.156, p < 0.001) and PFS (χ² = 22.142, p < 0.001) across the four mALBI grades. Utilizing established mALBI grade thresholds and prior binary grouping methods in GC, patients were further divided into low mALBI (Grades 1 and 2a) and high mALBI (Grades 2b and 3) groups. Those with high mALBI grades exhibited significantly worse median OS compared to patients with low mALBI grades (271 vs. 561 days, p = 0.002), as well as significantly shorter median PFS (199 vs. 423 days, p < 0.001). In multivariate analysis, mALBI grade remained independently associated with both OS (p < 0.001) and PFS (p = 0.001). Patients with lower mALBI grades demonstrated considerably better survival outcomes than those with higher grades. Due to its straightforward calculation from routine laboratory tests, mALBI grade may serve as a valuable prognostic marker for survival stratification in metastatic GC. Nonetheless, prospective validation in larger and more diverse cohorts is necessary before its integration into standard clinical practice. Furthermore, additional studies should explore whether interventions aimed at enhancing nutritional status and liver function can positively impact outcomes in high-risk patients.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum gelsolin as a biomarker for differentiating familial Mediterranean fever from juvenile idiopathic arthritis in children.","authors":"Esra Dişçi, Amra Adrovic Yıldız, Saime Özbek Şebin, Kamber Kaşali","doi":"10.17305/bb.2026.13983","DOIUrl":"https://doi.org/10.17305/bb.2026.13983","url":null,"abstract":"<p><p>Gelsolin (Gsn), an actin-binding protein implicated in cytoskeletal remodeling and the regulation of inflammation, has emerged as a potential biomarker for immune-mediated and inflammatory diseases. This prospective case-control study aimed to evaluate serum Gsn levels in children diagnosed with juvenile idiopathic arthritis (JIA) and familial Mediterranean fever (FMF) and to assess its potential utility in differentiating between these two pediatric rheumatic disorders. The study involved 90 children aged 2-18 years: 30 with JIA, 30 with FMF, and 30 age-matched healthy controls. Serum Gsn concentrations were quantified using enzyme-linked immunosorbent assay (ELISA), and both clinical and laboratory parameters were analyzed. Mean serum Gsn levels were highest in the FMF group (28.8 ± 2.5), followed by the JIA group (25.7 ± 2.8) and healthy controls (23.9 ± 2.7), with significant differences observed among the groups (p < 0.001). Gsn levels were significantly elevated in children with FMF compared to those with JIA, and receiver operating characteristic (ROC) analysis demonstrated strong discriminatory performance, with an area under the curve (AUC) of 0.82. Logistic regression analysis identified serum Gsn, aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) as independent predictors for distinguishing FMF from JIA. Each unit increase in Gsn was associated with increased odds of an FMF diagnosis (odds ratio [OR]: 2.89, 95% confidence interval [CI]: 1.58-5.29, p = 0.001). These findings suggest that serum Gsn may serve as a valuable biomarker in pediatric inflammatory rheumatic diseases, particularly in differentiating FMF from JIA. Further large-scale prospective studies are necessary to validate its diagnostic effectiveness.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic syndrome and incident thyroid cancer risk in adults: A systematic review and meta-analysis.","authors":"Zhengwen He, Jing Zhou, Xianxiang Lu","doi":"10.17305/bb.2026.13977","DOIUrl":"https://doi.org/10.17305/bb.2026.13977","url":null,"abstract":"<p><p>The global incidence of thyroid cancer (TC) has increased, with metabolic syndrome (MetS) identified as a potential modifiable risk factor. However, epidemiological evidence regarding this association remains inconsistent. We conducted a meta-analysis to quantify the relationship between MetS and the risk of incident TC in adult populations. We searched PubMed, Embase, and Web of Science for longitudinal observational studies assessing MetS in relation to incident TC. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models to account for heterogeneity. Our analysis included six cohort studies comprising seven independent datasets and a total of 15,730,432 participants, among whom 83,351 incident TC cases were identified during follow-up periods ranging from 2.7 to 12.0 years. The results indicated that MetS was associated with a significantly increased risk of TC (RR = 1.26, 95% CI 1.10-1.46; p < 0.001), exhibiting substantial heterogeneity (I² = 91%). This association was consistent across prospective and retrospective cohorts, varying sample sizes, follow-up durations, and different strata of TC incidence (all p for subgroup differences > 0.05).  Moreover, sex-specific analyses revealed comparable associations in both men and women. Studies with higher methodological quality (Newcastle-Ottawa Scale score = 9) demonstrated a diminished yet still significant association compared to those with scores of 7-8 (RR = 1.15 vs. 1.80; p for subgroup difference < 0.001). In conclusion, MetS is associated with a moderately increased risk of TC in adults. However, due to the observational nature of the included studies and the potential for residual confounding, these findings should be interpreted as an association rather than definitive evidence of a causal relationship.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pretreatment neutrophil percentage-to-albumin ratio for prognostic assessment in locally advanced nasopharyngeal carcinoma.","authors":"Yanming Hu, Luting Chen, Jie Ling, Sujuan Zhang, Yuhua Feng, Tao Hou, Yangchun Xie","doi":"10.17305/bb.2026.14023","DOIUrl":"https://doi.org/10.17305/bb.2026.14023","url":null,"abstract":"<p><p>Prognosis in locally advanced nasopharyngeal carcinoma (NPC) is influenced not only by tumor burden but also by systemic inflammatory and nutritional status. This study aimed to evaluate the prognostic value of the pretreatment neutrophil percentage-to-albumin ratio (NPAR) in locally advanced NPC and to determine whether its incorporation could enhance risk stratification beyond conventional staging variables. In this retrospective single-center cohort study, we analyzed 804 patients with stage II-IVa NPC who were treated with definitive radiotherapy, with or without concurrent chemotherapy. These patients were randomly assigned to a training cohort (n = 603) and a validation cohort (n = 201). The pretreatment NPAR was calculated from blood samples collected within one week prior to treatment initiation. Associations with overall survival (OS) and progression-free survival (PFS) were primarily assessed using restricted cubic spline Cox models, supplemented by secondary cutoff-based analyses. A prognostic nomogram was developed and internally validated through bootstrap resampling. Higher pretreatment NPAR was consistently associated with adverse outcomes in OS (adjusted hazard ratio [HR] 1.77, 95% confidence interval [CI] 0.97-3.23; p = 0.062) and PFS (adjusted HR 1.74, 95% CI 0.96-3.15; p = 0.066), although these associations did not achieve conventional statistical significance in fully adjusted models. The nomogram incorporating both clinicopathological variables and NPAR demonstrated superior discrimination compared to tumor-node-metastasis staging alone, with optimism-corrected C-indices of 0.625 for OS and 0.617 for PFS. In comparative analyses, NPAR and the neutrophil-to-lymphocyte ratio exhibited similar prognostic performance. In conclusion, pretreatment NPAR is associated with adverse outcomes in locally advanced NPC and may modestly enhance model-based risk stratification. However, its clinical utility should be interpreted with caution and requires external validation.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147789972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asthma and increased carotid intima-media thickness: A systematic review and meta-analysis.","authors":"Mohammed Haroun, Mohamed Ellebedy, Abduraheem F A Farah, Waleed K K Khalid, Mazin M A Abdelmutalab, Omer H T Mohmmed, Aymen Abdalla, Sagad O O Mohamed","doi":"10.17305/bb.2026.14164","DOIUrl":"https://doi.org/10.17305/bb.2026.14164","url":null,"abstract":"<p><p>Asthma has been associated with early vascular changes that elevate the risk of atherosclerosis and cardiovascular diseases. Carotid intima-media thickness (CIMT) serves as a non-invasive marker for subclinical atherosclerosis and cardiovascular risk. However, existing literature presents conflicting results regarding CIMT measurements in asthmatic patients. This study aims to evaluate whether CIMT is elevated in asthma patients compared to healthy controls and to explore potential modifiers. We conducted a systematic review following PRISMA guidelines, performing a literature search across PubMed, Web of Science, ScienceDirect, and the WHO VHL. We calculated pooled standardized mean differences (SMD) with 95% confidence intervals (CI) to assess the differences in CIMT values. Heterogeneity was evaluated using the I² statistic, and subgroup analyses and meta-regression were utilized to identify sources of heterogeneity. Our review included a total of 10 studies. The analysis indicated significantly higher CIMT values in asthma patients compared to healthy controls, with a pooled SMD of 0.65 (95% CI: 0.19 to 1.12, p = 0.005). A limited number of studies addressed various factors, such as disease severity and the use of inhaled corticosteroids, which may influence CIMT measurements. Notably, asthmatic patients, particularly children and adolescents, exhibited higher CIMT values compared to healthy controls, suggesting a potential association with subclinical atherosclerosis in this demographic. However, these findings should be interpreted with caution due to the observational nature of the included studies and the risk of residual confounding. Further longitudinal research is necessary to elucidate the effects of disease characteristics and treatment on vascular health.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quinuclidin-3-one-based quaternary ammonium compounds as potent antibacterials against <i>Staphylococcus aureus </i>and <i>Listeria monocytogenes</i>.","authors":"Antonio Sabljić, Doris Čarija, Karolina Begić, Renata Odžak, Rozelindra Čož-Rakovac, Josip Tomaš, Matilda Šprung","doi":"10.17305/bb.2026.14037","DOIUrl":"https://doi.org/10.17305/bb.2026.14037","url":null,"abstract":"<p><p>Bacterial resistance and the cytotoxicity of conventional quaternary ammonium compounds (QACs) highlight the necessity for safer and more effective membrane-active antibacterials. This study aimed to synthesize a homologous series of quinuclidin-3-one-based QACs (QO-C12, QO-C14, and QO-C16) and to elucidate their structure-activity relationships through comprehensive antibacterial, antibiofilm, cytotoxicity, embryotoxicity, mechanistic, and physicochemical analyses. The compounds were evaluated against clinically relevant pathogens using broth microdilution, growth and time-kill assays, biofilm inhibition testing, membrane permeabilization analysis, cytotoxicity testing in human retinal pigment epithelial (RPE1) and human embryonic kidney (HEK293) cells, zebrafish embryotoxicity assessments, and critical micelle concentration (CMC) measurements. Antibacterial potency was found to increase with alkyl chain length, with QO-C16 exhibiting the highest activity, including minimum inhibitory concentrations (MICs) of 8 µM against Staphylococcus aureus (including methicillin-resistant strains) and 4 µM against Listeria monocytogenes. In Dulbecco's modified Eagle medium (DMEM), MIC values were up to 32-fold lower than those observed in broth media, indicating a significant medium-dependent effect. QO-C14 and QO-C16 demonstrated robust antibiofilm activity, while QO-C16 produced the fastest bactericidal and membrane-disruptive effects. The critical micelle concentration decreased with increasing chain length, aligning with enhanced hydrophobicity and membrane affinity. Compared to commercial QACs, the novel compounds exhibited lower cytotoxicity in human cell lines; however, zebrafish embryotoxicity did increase with chain length. Overall, quinuclidin-3-one represents a promising scaffold for the development of QACs, with QO-C16 identified as the lead compound for further optimization toward selective antibacterial agents.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147789989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}