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27 pages, 1010 KiB  
Review
The Multifaceted Role of IL-35 in Periodontal Disease and Beyond: From Genetic Polymorphisms to Biomarker Potential
by Zdravka Pashova-Tasseva, Antoaneta Mlachkova, Kamen Kotsilkov and Hristina Maynalovska
Genes 2025, 16(8), 891; https://doi.org/10.3390/genes16080891 - 28 Jul 2025
Viewed by 352
Abstract
Periodontitis is a prevalent chronic inflammatory disease with complex etiopathogenesis involving microbial dysbiosis, host immune response, environmental factors, and genetic susceptibility. Among the cytokines implicated in periodontal immunoregulation, interleukin-35 (IL-35) has emerged as a novel anti-inflammatory mediator with potential diagnostic and therapeutic relevance. [...] Read more.
Periodontitis is a prevalent chronic inflammatory disease with complex etiopathogenesis involving microbial dysbiosis, host immune response, environmental factors, and genetic susceptibility. Among the cytokines implicated in periodontal immunoregulation, interleukin-35 (IL-35) has emerged as a novel anti-inflammatory mediator with potential diagnostic and therapeutic relevance. This narrative review evaluates the role of IL-35 in periodontal disease by exploring its local and systemic expression, response to non-surgical periodontal therapy (NSPT), and association with clinical disease severity. Additionally, current evidence regarding IL-35 gene polymorphisms and their potential contribution to individual susceptibility and disease progression, as well as their relevance in related systemic conditions, is assessed. A comprehensive review and synthesis of recent clinical and experimental studies were conducted, focusing on IL-35 levels in saliva, serum, and gingival crevicular fluid (GCF) among patients with healthy periodontium, gingivitis, and various stages of periodontitis, both before and after NSPT. Emphasis was placed on longitudinal studies evaluating IL-35 dynamics in correlation with periodontal parameters, as well as genetic association studies investigating IL-12A and EBI3 gene polymorphisms. IL-35 levels were generally found to be higher in healthy individuals and reduced in periodontitis patients, indicating a possible protective role in maintaining periodontal homeostasis. Following NSPT, IL-35 levels significantly increased, corresponding with clinical improvement and reduced inflammatory burden. Genetic studies revealed variable associations between IL-35 polymorphisms and susceptibility to periodontitis and related systemic conditions, although further research is needed for validation. IL-35 appears to function as a modulator of immune resolution in periodontal disease, with potential utility as a non-invasive biomarker for disease activity and therapeutic response. Its upregulation during periodontal healing supports its role in promoting tissue stabilization. The integration of cytokine profiling and genetic screening may enhance personalized risk assessment and targeted interventions in periodontal care. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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11 pages, 778 KiB  
Article
Gut and Other Differences Between Female and Male Veterans—Vive La Différence? Bringing It All Together
by Martin Tobi, Donald Bradley, Fadi Antaki, MaryAnn Rambus, Noreen F. Rossi, James Hatfield, Suzanne Fligiel and Benita McVicker
Gastrointest. Disord. 2025, 7(3), 48; https://doi.org/10.3390/gidisord7030048 - 22 Jul 2025
Viewed by 260
Abstract
Background: The number of women veterans has been rising steadily since the Gulf War and many assume the functions of their male counterparts. Women face unique obstacles in their service, and it is imperative that differences in physiology not be overlooked so [...] Read more.
Background: The number of women veterans has been rising steadily since the Gulf War and many assume the functions of their male counterparts. Women face unique obstacles in their service, and it is imperative that differences in physiology not be overlooked so as to provide better and appropriate care to our women in uniform. Despite this influx and incorporation of female talent, dedicated reports contrasting female and male veterans are rare, outside of specific psychological studies. We therefore attempt to contrast gut constituents, absorption, innate immune system, and nutritional differences to provide a comprehensive account of similarities and differences between female and male veterans, from our single-center perspective, as this has not been carried out previously. Herein, we obtained a detailed roster of commonly used biomedical tests and some novel entities to detect differences between female and male veterans. The objective of this study was to detect differences in the innate immune system and other ancillary test results to seek differences that may impact the health of female and male veterans differently. Methods: To contrast biochemical and sociomedical parameters in female and male veterans, we studied the data collected on 450 female veterans and contrasted them to a group of approximately 1642 males, sequentially from 1995 to 2022, all selected because of above-average risk for CRC. As part of this colorectal cancer (CRC) screening cross-sectional and longitudinal study, we also collected stool, urine, saliva, and serum specimens. We used ELISA testing to detect stool p87 shedding by the Adnab-9 monoclonal and urinary organ-specific antigen using the BAC18.1 monoclonal. We used the FERAD ratio (blood ferritin/fecal p87), a measure of the innate immune system to gauge the activity of the innate immune system (InImS) by dividing the denominator p87 (10% N-linked glycoprotein detected by ELISA) into the ferritin level (the enumerator, a common lab test to assess anemia). FERAD ratios have not been performed elsewhere despite past Adnab-9 commercial availability so we have had to auto-cite our published data where appropriate. Results: Many differences between female and males were detected. The most impressive differences were those of the InImS where males clearly had the higher numbers (54,957 ± 120,095) in contrast to a much lower level in females (28,621 ± 66,869), which was highly significantly different (p < 0.004). Mortality was higher in males than females (49.4% vs. 24.1%; OR 3.08 [2.40–3.94]; p < 0.0001). Stool p87, which is secreted by Paneth cells and may have a protective function, was lower in males (0.044 ± 0.083) but higher in females (0.063 ± 0.116; p < 0.031). Immunohistochemistry of the Paneth cell-fixed p87 antigen was also higher in females (in the descending colon and rectum). In contrast, male ferritin levels were significantly higher (206.3 ± 255.9 vs. 141.1 ± 211.00 ng/mL; p < 0.0006). Females were less likely to be diabetic (29.4 vs. 37.3%; OR 0.7 [0.55–0.90]; p < 0.006). Females were also more likely to use NSAIDs (14.7 vs. 10.7%, OR 1.08 [1.08–2.00]; p < 0.015). Females also had borderline less GI bleeding by fecal immune tests (FITs), with 13.2% as opposed to 18.2% in males (OR 0.68 [0.46–1.01]; p = 0.057), but were less inclined to have available flexible sigmoidoscopy (OR 0.68 [0.53–0.89]; p < 0.004). Females also had more GI symptomatology, a higher rate of smoking, and were significantly younger than their male counterparts. Conclusions: This study shows significant differences with multiple parameters in female and male veterans. Full article
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11 pages, 217 KiB  
Article
Effectiveness of a Salivary Testing System to Screen for Periodontal Disease: A Cross-Sectional Study from the NOSE Study
by Takayuki Kosaka, Shuri Fushida, Masahiro Wada, Tomoya Gonda, Kodai Hatta, Masae Kuboniwa, Arisa Wada, Sumiyo Hashimoto, Hiromi Hatanaka, Makiko Higashi, Takeshi Kikuchi, Keiji Terauchi, Michiko Kido, Yuya Akagi, Kei Kamide, Mai Kabayama and Kazunori Ikebe
J. Clin. Med. 2025, 14(14), 4965; https://doi.org/10.3390/jcm14144965 - 14 Jul 2025
Viewed by 314
Abstract
Background: This study aimed to evaluate the effectiveness of a saliva-based screening method for periodontal disease among community-dwelling older adults in Japan. Methods: A total of 372 study participants (mean age: 73.1 years) with 20 or more remaining teeth were included in [...] Read more.
Background: This study aimed to evaluate the effectiveness of a saliva-based screening method for periodontal disease among community-dwelling older adults in Japan. Methods: A total of 372 study participants (mean age: 73.1 years) with 20 or more remaining teeth were included in the study. Of the six parameters assessed by the Salivary Multi Test (SMT), this study focused on the three parameters related to periodontal disease: occult blood, leukocytes, and proteins. Periodontal tissue examinations were performed based on the Community Periodontal Index (CPI) using partial mouth recording. To evaluate screening accuracy, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each of the three markers: occult blood, leukocytes, and proteins. Receiver operating characteristic (ROC) analysis was performed for each SMT item, and area under the curve (AUC) was calculated. Logistic regression analysis was used to calculate the odds ratios for combinations of SMT markers, with the presence of periodontal pockets and gingival inflammation as the respective outcome variables. Results: Among the individual markers, occult blood showed the highest diagnostic performance for detecting both periodontal pockets and gingival inflammation. The combination of elevated occult blood and leukocyte levels yielded the highest odds ratios for both periodontal pockets and gingival inflammation. Conclusions: While several SMT markers showed associations with periodontal conditions, their utility for screening in older Japanese adults remains to be further validated. Combining markers may help improve diagnostic performance, but additional studies are warranted. Full article
(This article belongs to the Special Issue Approaches and Challenges in Oral Rehabilitation)
11 pages, 1422 KiB  
Article
Towards Precision Nutrition: A Novel Smartphone-Connected Biosensor for Point-of-Care Detection of β-Hydroxybutyrate in Human Blood and Saliva
by Cristina Tortolini, Massimiliano Caprio, Daniele Gianfrilli, Andrea Lenzi and Riccarda Antiochia
Sensors 2025, 25(14), 4336; https://doi.org/10.3390/s25144336 - 11 Jul 2025
Viewed by 380
Abstract
Precision nutrition is an emerging approach that tailors dietary recommendations based on an individual’s unique genetic, metabolic, microbiome, and lifestyle factors. β-hydroxybutyrate (β-HB) is a key ketone body produced during fat metabolism, especially in states of fasting, low-carbohydrate intake, or prolonged exercise. Therefore, [...] Read more.
Precision nutrition is an emerging approach that tailors dietary recommendations based on an individual’s unique genetic, metabolic, microbiome, and lifestyle factors. β-hydroxybutyrate (β-HB) is a key ketone body produced during fat metabolism, especially in states of fasting, low-carbohydrate intake, or prolonged exercise. Therefore, monitoring β-HB levels provides valuable insights into an individual’s metabolic state, making it an essential biomarker for precision and personalized nutrition. A smartphone-connected electrochemical biosensor for single-use, rapid, low-cost, accurate, and selective detection of β-HB in whole blood and saliva at the Point-of-Care (POC) is reported. A graphite screen-printed carbon electrode modified with potassium ferricyanide (Fe(III)GSPE) was used as an electrode platform for the deposition of β-hydroxybutyrate dehydrogenase (HBDH), nicotinamide adenine dinucleotide oxidized form (NAD+), and chitosan nanoparticles (ChitNPs). An outer poly(vinyl) chloride (PVC) diffusion-limiting membrane was used to protect the modified electrode. The biosensor showed a linear range in the clinically relevant range, between 0.4 and 8 mM, with a detection limit (LOD) of 0.1 mM. The biosensor was tested on human blood and saliva samples, and the results were compared to those obtained with a commercial ketone meter, showing excellent agreement. Full article
(This article belongs to the Special Issue Feature Papers in Biomedical Sensors 2025)
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20 pages, 3506 KiB  
Article
AuNP/Magnetic Bead-Enhanced Electrochemical Sensor Toward Dual Saliva Alzheimer’s Biomarkers Detection
by Pengcheng Zhao, Jieyu Wang, Hongju Mao, Lin Zhou, Zhenhua Wu, Yunxing Lu, Teng Sun, Jianan Hui and Guowu Ma
Sensors 2025, 25(13), 4088; https://doi.org/10.3390/s25134088 - 30 Jun 2025
Viewed by 641
Abstract
Alzheimer’s disease (AD) early screening requires non-invasive, high-sensitivity detection of low-abundance biomarkers in complex biofluids like saliva. In this study, we present a miniaturized, silicon-based electrochemical sensor for sequential detection of two AD salivary biomarkers, lactoferrin (Lf) and amyloid β-protein 1-42 (Aβ1-42 [...] Read more.
Alzheimer’s disease (AD) early screening requires non-invasive, high-sensitivity detection of low-abundance biomarkers in complex biofluids like saliva. In this study, we present a miniaturized, silicon-based electrochemical sensor for sequential detection of two AD salivary biomarkers, lactoferrin (Lf) and amyloid β-protein 1-42 (Aβ1-42), on a single reusable electrode. The sensor features a three-electrode system fabricated by sputter-coating a quartz substrate with gold (Au) sensing electrodes, which are further modified with gold nanoparticles (AuNPs) to form 3D dendritic structures that enhance surface area and electron transfer. To improve specificity, immunomagnetic beads (MBs) are employed to selectively capture and isolate target biomarkers from saliva samples. These MB–biomarker complexes are introduced into a polydimethylsiloxane chamber aligned with Au sensing electrodes, where a detachable magnet localizes the complexes onto the electrode surface to amplify redox signals. The AuNPs/MBs sensor achieves detection limits of 2 μg/mL for Lf and 0.1 pg/mL for Aβ1-42, outperforming commercial ELISA kits (37.5 pg/mL for Aβ1-42) and covering physiological salivary concentrations. After the MBs capture the biomarkers, the sensor can output the result within one minute. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) measurements confirm enhanced electron transfer kinetics on AuNP-decorated surfaces, while linear correlations (R2 > 0.95) validate quantitative accuracy across biomarker ranges. The compact and integrated design eliminates reliance on bulky instrumentation and enables user-friendly operation, establishing a promising platform for portable, cost-effective AD screening and monitoring. Full article
(This article belongs to the Section Biomedical Sensors)
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31 pages, 1395 KiB  
Review
Salivary Interleukins as Non-Invasive Biomarkers for Psoriasis: Advances and Challenges in Diagnosis and Monitoring
by Anna Sora, Tony Hangan, Sergiu Ioachim Chirila, Leonard Gurgas, Mihaela Botnarciuc, Lavinia Carmen Daba, Ana Maria Cretu, Ionut Burlacu, Mihaela Zamfirescu, Adina Petcu, Adrian Cosmin Rosca, Ramona Mihaela Stoicescu and Lucian Cristian Petcu
Medicina 2025, 61(7), 1180; https://doi.org/10.3390/medicina61071180 - 29 Jun 2025
Viewed by 616
Abstract
Background and Objectives: Psoriasis is a chronic immune-mediated inflammatory disease requiring reliable diagnostic and monitoring tools. Salivary interleukins have emerged as promising non-invasive biomarkers, reflecting systemic inflammation and offering practical advantages such as ease of collection and improved patient compliance. Materials and [...] Read more.
Background and Objectives: Psoriasis is a chronic immune-mediated inflammatory disease requiring reliable diagnostic and monitoring tools. Salivary interleukins have emerged as promising non-invasive biomarkers, reflecting systemic inflammation and offering practical advantages such as ease of collection and improved patient compliance. Materials and Methods: This review synthesizes the current evidence on key salivary cytokines—IL-1β, IL-6, TNF-α, and IL-17—in relation to psoriasis pathogenesis, diagnosis, and treatment monitoring. It also compares saliva to blood-based diagnostics, emphasizing benefits like cost-effectiveness and suitability for repeated sampling. Methodological challenges, including heterogeneity in collection protocols and limited longitudinal data, are critically examined. Results: Advances in biologic therapies have deepened the understanding of psoriasis immunopathogenesis, highlighting interleukins as central biomarkers. Recent findings identify IL-37 and IL-38 as novel regulatory cytokines with anti-inflammatory roles. While elevated serum TNF-α levels in psoriatic patients are well documented, some inconsistencies persist. Notably, saliva has proven to be a viable alternative diagnostic fluid, supporting large-scale screening and routine clinical monitoring. Conclusions: Salivary interleukins—particularly IL-1β, IL-6, TNF-α, and IL-17—represent valuable, non-invasive biomarkers for early detection, disease severity assessment, and therapeutic response monitoring in psoriasis. Standardizing saliva-based methods and conducting large-scale studies are essential next steps to support their integration into personalized clinical practice. Full article
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21 pages, 1081 KiB  
Article
HPV Knowledge, Vaccination Uptake, and Salivary Diagnostics Among Dental Students in Romania
by Sergiu Baranga, Doina Chioran, Octavia Balean, Ramona Dumitrescu, Roxana Popescu, Daniela Jumanca, Roxana Oancea, Ruxandra Sava-Rosianu, Vanessa Bolchis and Atena Galuscan
Vaccines 2025, 13(6), 658; https://doi.org/10.3390/vaccines13060658 - 19 Jun 2025
Viewed by 648
Abstract
Background: Human papillomavirus (HPV) is a key cause of cervical and oropharyngeal cancers. Despite available vaccines, uptake remains low in Romania due to limited awareness and hesitancy. This study assessed HPV knowledge, vaccination status, and the presence of high-risk strains (16 and 18) [...] Read more.
Background: Human papillomavirus (HPV) is a key cause of cervical and oropharyngeal cancers. Despite available vaccines, uptake remains low in Romania due to limited awareness and hesitancy. This study assessed HPV knowledge, vaccination status, and the presence of high-risk strains (16 and 18) in the saliva of dental students from Victor Babeș University in Timișoara. Methods: A cross-sectional study was conducted between February and March 2024, enrolling 199 dental students. Participants completed a 15-item questionnaire addressing HPV-related knowledge, vaccination status, lifestyle factors, and health history. Saliva samples were collected and analyzed using real-time PCR for the detection of HPV types 16 and 18. Logistic regression analysis was employed to identify predictors of vaccination uptake. Results: Only 10.6% of participants had received the HPV vaccine, although 96.9% acknowledged its safety and efficacy. Awareness was higher among females (88.1%) than males (84.3%), and vaccination rates were significantly greater among students under 25 years old (p = 0.0312). A total of 16.6% reported the presence of papillomas or warts. HPV DNA was detected in 10% of saliva samples. Conclusions: Although awareness of HPV was high, vaccination rates remained low, revealing a gap between knowledge and preventive action. Saliva-based screening shows promise as a non-invasive diagnostic tool, and integrating targeted education and advocacy into dental curricula may enhance public health outcomes in Romania. Full article
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13 pages, 2013 KiB  
Review
miRNA-21 and miRNA-27b Expression in Saliva of Patients with Oral Lichen Planus: A Systematic Review
by Dario Di Stasio, Fausto Fiori, Antonio Romano, Annalisa Palmieri, Laura Mosca, Juan Antonio Ruiz Roca, Pia Lopez-Jornet and Alberta Lucchese
Int. J. Mol. Sci. 2025, 26(12), 5824; https://doi.org/10.3390/ijms26125824 - 18 Jun 2025
Viewed by 369
Abstract
Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa with a recognized risk of malignant transformation. MicroRNAs, particularly miRNA-21 and miRNA-27b, have been implicated in the pathogenesis and progression of various diseases, including OLP. Their altered expression in saliva [...] Read more.
Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa with a recognized risk of malignant transformation. MicroRNAs, particularly miRNA-21 and miRNA-27b, have been implicated in the pathogenesis and progression of various diseases, including OLP. Their altered expression in saliva may provide diagnostic and prognostic insights for this condition. This systematic review examines the expression profiles of miRNA-21 and miRNA-27b in the saliva of OLP patients to assess their potential as biomarkers. The review was conducted in accordance with PRISMA guidelines and was registered in the PROSPERO database. A comprehensive search was conducted in PubMed, Embase, and Scopus using specific keywords. Retrieved titles and abstracts were screened based on predefined eligibility criteria, and relevant studies were analyzed. The initial search identified 71 studies. After screening, 17 abstracts were selected for full-text review. Following evaluation, 11 studies were excluded, resulting in 6 studies being included. Findings indicate a consistent upregulation of miRNA-21 and a downregulation of miRNA-27b in OLP saliva samples. These alterations suggest a potential role in disease pathogenesis and risk assessment. The dysregulation of miRNA-21 and miRNA-27b in OLP underscores their potential as salivary biomarkers for diagnosis and disease monitoring. Moreover, the non-invasive nature of salivary miRNAs offers promising clinical applications, enhancing early detection and personalized management strategies for OLP. Full article
(This article belongs to the Special Issue miRNAs in Cancers: From Molecular Biology to Treatment)
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14 pages, 5828 KiB  
Article
Salivary Metabolite Variation After High-Intensity Rowing Training and Potential Biomarker Screening for Exercise-Induced Muscle Damage
by Yue Yi, Junjie Ding, Baoguo Wang, Yuxian Li, Liming Wang, Shumin Bo, Qiongqiong Ren and Aiqin Luo
Metabolites 2025, 15(6), 405; https://doi.org/10.3390/metabo15060405 - 16 Jun 2025
Viewed by 501
Abstract
Background: Exercise-induced muscle damage (EIMD) is the most common health risk in training. So far, EIMD diagnosis predominantly relies on blood biochemical analysis or medical imaging. EIMD prediction by using saliva shows great prospects in public fitness. Methods: A total of 18 participants [...] Read more.
Background: Exercise-induced muscle damage (EIMD) is the most common health risk in training. So far, EIMD diagnosis predominantly relies on blood biochemical analysis or medical imaging. EIMD prediction by using saliva shows great prospects in public fitness. Methods: A total of 18 participants performed high-intensity rowing training. Blood biochemical indicator and pain analyses indicated EIMD occurrence. Pseudo-targeted metabolomics techniques were utilized to analyze changes in salivary metabolites after exercise. Results: A total of 43 salivary metabolites significantly increased while 31 salivary metabolites significantly decreased after exercise. The upregulated metabolites were related to hormone secretion, antioxidation, and muscle repair. A partial least squares discriminant analysis model was established, and three potential salivary biomarkers for EIMD prediction were screened. The sensitivity and specificity of single biomarkers achieved more than 88.9% and 94.4% in classification of EIMD occurrence, respectively. The accuracy of classification increased to ~100% with multiple metabolites. Conclusion: Salivary metabolites significantly changed after high-intensity rowing training and EIMD occurrence. Some salivary metabolites exhibited similar trends with blood biochemical indicators. Salivary biomarkers have great prospects in EIMD prediction, and better performance was achieved with multiple salivary metabolites. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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13 pages, 1792 KiB  
Article
A High-Sensitivity, Bluetooth-Enabled PCB Biosensor for HER2 and CA15-3 Protein Detection in Saliva: A Rapid, Non-Invasive Approach to Breast Cancer Screening
by Hsiao-Hsuan Wan, Chao-Ching Chiang, Fan Ren, Cheng-Tse Tsai, Yu-Siang Chou, Chun-Wei Chiu, Yu-Te Liao, Dan Neal, Coy D. Heldermon, Mateus G. Rocha and Josephine F. Esquivel-Upshaw
Biosensors 2025, 15(6), 386; https://doi.org/10.3390/bios15060386 - 15 Jun 2025
Viewed by 851
Abstract
Breast cancer is a leading cause of cancer-related mortality worldwide, requiring efficient diagnostic tools for early detection and monitoring. Human epidermal growth factor receptor 2 (HER2) is a key biomarker for breast cancer classification, typically assessed using immunohistochemistry (IHC). However, IHC requires invasive [...] Read more.
Breast cancer is a leading cause of cancer-related mortality worldwide, requiring efficient diagnostic tools for early detection and monitoring. Human epidermal growth factor receptor 2 (HER2) is a key biomarker for breast cancer classification, typically assessed using immunohistochemistry (IHC). However, IHC requires invasive biopsies and time-intensive laboratory procedures. In this study, we present a biosensor integrated with a reusable printed circuit board (PCB) and functionalized glucose test strips designed for rapid and non-invasive HER2 detection in saliva. The biosensor achieved a limit of detection of 10−15 g/mL, 4 to 5 orders of magnitude more sensitive than the enzyme-linked immunosorbent assay (ELISA), with a sensitivity of 95/dec and a response time of 1 s. In addition to HER2, the biosensor also detects cancer antigen 15-3 (CA15-3), another clinically relevant breast cancer biomarker. The CA15-3 test demonstrated an equally low limit of detection, 10−15 g/mL, and a higher sensitivity, 190/dec, further validated using human saliva samples. Clinical validation using 29 saliva samples confirmed our biosensor’s ability to distinguish between healthy, in situ breast cancer, and invasive breast cancer patients. The system, which integrates a Bluetooth Low-Energy (BLE) module, enables remote monitoring, reduces hospital visits, and enhances accessibility for point-of-care and mobile screening applications. This ultra-sensitive, rapid, and portable biosensor can serve as a promising alternative for breast cancer detection and monitoring, particularly in rural and underserved communities. Full article
(This article belongs to the Special Issue Aptamer-Based Biosensors for Point-of-Care Diagnostics)
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19 pages, 3716 KiB  
Article
Ultrafast and Ultrasensitive Simultaneous Molecular Recognition and Quantification of CA12-5, CA72-4, HER1, and AFP in Biological Samples
by Ruxandra-Maria Ilie-Mihai, Raluca-Ioana Stefan-van Staden and Bianca-Maria Tuchiu-Stanca
Chemosensors 2025, 13(6), 210; https://doi.org/10.3390/chemosensors13060210 - 9 Jun 2025
Viewed by 1296
Abstract
Simultaneous molecular recognition and quantification of at least four biomarkers in biological samples may contribute to early and fast diagnosis of illnesses such as cancer. The electrodes able to reliably perform on-site these tests are the stochastic sensors. Therefore, three novel 3D stochastic [...] Read more.
Simultaneous molecular recognition and quantification of at least four biomarkers in biological samples may contribute to early and fast diagnosis of illnesses such as cancer. The electrodes able to reliably perform on-site these tests are the stochastic sensors. Therefore, three novel 3D stochastic sensors employing carbon-based powders (graphite, graphene, nanographene) treated with N-(2-mercapto-1H-benzo[d]imidazole-5-yl) oleamide solution were used for screening tests of whole blood, gastric tumoral tissue, urine, and saliva for molecular recognition and quantification of CA12-5, CA72-4, HER1, and AFP. The best performance was achieved for the sensor based on graphene, when the highest sensitivities were recorded, on wide working concentration ranges of: 8.37 × 10−14–8.37 U mL−1 for CA12-5, 4.00 × 10−11–4.00 × 10−3 U mL−1 for CA72-4, 3.90 × 10−16–3.90 × 10−6 g mL−1 for HER1, and 3.00 × 10−20–3.00 × 10−6 g mL−1 for AFP. The wide linear concentration ranges cover levels of biomarkers found in gastric cancer patients from early to late stages. The recovery values were higher than 98.00 with %, RSD lower than 1.00%. Full article
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13 pages, 813 KiB  
Article
Impact of Symptomatic COVID-19 on the Oral Health of Pediatric Patients in Tbilisi City
by Lia Mania, Ketevan Nanobashvili, Tinatin Manjavidze, Mamuka Benashvili, Nino Bzishvili and Ia Astamadze
Children 2025, 12(6), 725; https://doi.org/10.3390/children12060725 - 31 May 2025
Viewed by 1155
Abstract
Background/Purpose: Coronavirus disease 2019 (COVID-19) has become the cause of a global health crisis during the pandemic. This research aimed to study the impact of symptomatic COVID-19 on children’s oral health indices and salivary microbiome composition during the post-COVID-19 period. Methods: An observational, [...] Read more.
Background/Purpose: Coronavirus disease 2019 (COVID-19) has become the cause of a global health crisis during the pandemic. This research aimed to study the impact of symptomatic COVID-19 on children’s oral health indices and salivary microbiome composition during the post-COVID-19 period. Methods: An observational, cross-sectional study was conducted in Tbilisi (Georgia) among children aged 7–12 years. A total of 421 children included in the study had a history of laboratory-confirmed COVID-19 within one year of exposure. No participants met the criteria for comorbid conditions or for PCC. A stratified simple random selection of schools and among selected clusters was used. The selected children were divided into two groups: the exposed group, who were patients with a history of symptomatic COVID-19, and the control group, who were patients with a history of asymptomatic COVID-19. The data were collected from August 2022 to December 2023. Oral screening, microbiological examination of saliva, and administration of questionnaires were also performed. Logistic regression was used to calculate ORs with 95% confidence intervals. The statistical processing of the data was performed with SPSS 23.0. This study was approved by the Biomedical Research Ethical Council of the University of Georgia (UGREC–04–22/9 March 2022). Results: Statistically significant differences in the means of the oral health indicators between the studied groups were detected (exposed: DMFT + deft = 5.9; MGI = 0.92; S-OHI = 1.9; control: DMFT + deft = 3.8; MGI = 0.56; S-OHI = 1.4). According to the logistic regression, symptomatic COVID-19 had a significant effect on the following oral health indicators: DMFT + deft (OR = 1.26; 95% CI = 1.14–1.39), MGI (OR = 2.31; 95% CI = 1.50–3.55), and S-OHI (OR = 3.43; 95% CI = 2.03–5.76). The effect of symptomatic COVID-19 on the frequency of eradication of the studied microbiome was also significant (OR = 2.12; 95% CI = 1.23–3.63). Conclusions: A close association was established between symptomatic COVID-19 and microbiome changes in the oral saliva of children, as well as between oral health indicators and symptomatic COVID-19. Considering the research results, it is assumed that a symptomatic course of COVID-19 may be an additional risk factor associated with poor oral health in the pediatric population in the post-COVID-19 period. Full article
(This article belongs to the Section Pediatric Dentistry & Oral Medicine)
21 pages, 2588 KiB  
Systematic Review
The Role of Salivary Diagnostic Techniques in Screening for Active Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis
by Radwan Darwish, Maya Tama, Sidra Sharief, Osama Zeidan, Sara Mohammed Ahmed Rady, Kareeza Selby Chacko, Bindhu Nair, Vijayalakshmi S. Bhojaraja and Jeevan K. Shetty
Microorganisms 2025, 13(5), 973; https://doi.org/10.3390/microorganisms13050973 - 24 Apr 2025
Viewed by 999
Abstract
Since the World Health Organization (WHO) issued guidelines for developing a non-sputum test for active tuberculosis (TB) diagnosis that exhibits similar performance characteristics to sputum-based diagnosis, salivary diagnostic techniques have gained prominence as potential screening tools or adjuncts to existing diagnostics. We searched [...] Read more.
Since the World Health Organization (WHO) issued guidelines for developing a non-sputum test for active tuberculosis (TB) diagnosis that exhibits similar performance characteristics to sputum-based diagnosis, salivary diagnostic techniques have gained prominence as potential screening tools or adjuncts to existing diagnostics. We searched online databases for studies that looked at salivary diagnostic techniques. Afterwards, duplicates were removed, titles and abstracts were screened, and full-text studies were assessed for eligibility based on inclusion and exclusion criteria. The studies chosen for final analysis underwent a rigorous quality assessment following a QUADAS-2 template, and data were extracted. The primary outcome assessed the difference in mean levels of interleukins between TB+ patients and TB-controls (Hedges’ g). We then conducted two subgroup analyses: the first segregated the control group into healthy patients, and those with other respiratory diseases (ORD), and the second addressed three different interleukins separately (IL-6, IL-5, IL-17). The secondary outcome involved comparing salivary molecular diagnostic assays to WHO guidelines. This study is registered with PROSPERO, CRD42024536884. A total of 17 studies, out of an initial 1010, were chosen for the final analysis, but one was then excluded for being of poor quality. Our meta-analyses for the primary outcome revealed minimal diagnostic potential for interleukins. Our first subgroup analysis showed that interleukins were incapable of differentiating active TB patients from both healthy controls and ORD patients. Our second subgroup analysis showed that IL-17 was reduced in active TB patients. Assessment of the secondary outcome revealed that most studies relied on a GeneXpert MTB/RIF assay on saliva, but none fulfilled WHO guidelines for a non-sputum test. Individual biomarkers currently lack sufficient discriminatory power to definitively distinguish active tuberculosis from healthy individuals or those with other respiratory diseases (ORD), reinforcing the need for multi-biomarker panels. Interleukins may be alternatively used as markers for prognosis, severity, or treatment response. Our findings also suggest that assays are unable to meet WHO guidelines. Full article
(This article belongs to the Special Issue Prevention, Treatment and Diagnosis of Tuberculosis, 2nd Edition)
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13 pages, 2012 KiB  
Article
The Usefulness of Testosterone in Saliva Tests to Detect Testosterone Deficiency in Men with Advanced Chronic Kidney Disease: A Single-Center Study
by Ksymena Leśniak, Arkadiusz Lubas and Stanisław Niemczyk
J. Clin. Med. 2025, 14(8), 2818; https://doi.org/10.3390/jcm14082818 - 19 Apr 2025
Viewed by 1481
Abstract
Background: Hypogonadism frequently occurs among men with chronic kidney disease (CKD) and is a highly unfavorable prognostic factor. Therefore, a simple and common screening for testosterone deficiency may be important. The measurement of testosterone in saliva appears to be an attractive alternative to [...] Read more.
Background: Hypogonadism frequently occurs among men with chronic kidney disease (CKD) and is a highly unfavorable prognostic factor. Therefore, a simple and common screening for testosterone deficiency may be important. The measurement of testosterone in saliva appears to be an attractive alternative to serum testosterone. This study aimed to assess the usefulness of determining free testosterone concentration in saliva to detect testosterone deficiency in men with advanced CKD, including those on dialysis. Methods: A total of 77 adult, male patients (aged 41–89 years old)—30 with CKD stage G3-G4, 30 on hemodialysis (HD), and 17 on peritoneal dialysis (PD)—were evaluated. The concentration of free testosterone was determined in saliva (SalFT), while the concentration of total testosterone (TT) was determined in blood serum. Serum-free testosterone levels were calculated (cFT). Results: SalFT did not differ from cFT in the CKD (p = 0.547) and PD groups (p = 0.409). In the HD group, SalFT was higher than cFT (p = 0.009). SalFT was positively correlated with cFT (r = 0.435 in the CKD and r = 0.479 in the HD) and TT (r = 0.451 in CKD), but only in the group of patients with SalFT levels below 140 pg/mL and 120 pg/mL, respectively. A cut-off value of SalFT ≤ 60.6 pg/mL showed 73.9% sensitivity and 77.8% specificity for testosterone deficiency recognition. Conclusions: Our study supports the value of SalFT measurement as a non-invasive approach in the diagnosis of testosterone deficiency in men with advanced CKD, as well as patients on hemodialysis. Full article
(This article belongs to the Section Nephrology & Urology)
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24 pages, 1661 KiB  
Review
Innovative Methodologies for the Early Detection of Breast Cancer: A Review Categorized by Target Biological Samples
by Antonella Grasso, Vittorio Altomare, Giulia Fiorini, Alessandro Zompanti, Giorgio Pennazza and Marco Santonico
Biosensors 2025, 15(4), 257; https://doi.org/10.3390/bios15040257 - 17 Apr 2025
Cited by 3 | Viewed by 1101
Abstract
Innovative biosensor technologies are revolutionizing cancer detection by offering non-invasive, sensitive, and rapid diagnostic tools, addressing the limitations of conventional screening. Non-invasive samples like breath, saliva, urine, and sweat, analyzed using advanced technologies like electronic nose systems and AI, show promise for early [...] Read more.
Innovative biosensor technologies are revolutionizing cancer detection by offering non-invasive, sensitive, and rapid diagnostic tools, addressing the limitations of conventional screening. Non-invasive samples like breath, saliva, urine, and sweat, analyzed using advanced technologies like electronic nose systems and AI, show promise for early detection and frequent monitoring, though validation is needed. AI integration enhances data analysis and personalization. While blood-based methods remain the gold standard, combining them with less invasive sample types like saliva or sweat, and using sensitive techniques, is a promising direction. Conventional methods (mammography, MRI, etc.) offer proven efficacy, but are costly and invasive. Innovative methods using biosensors offer reduced infrastructure needs, lower costs, and patient-friendly sampling. However, challenges remain in validation, standardization, and low biomarker concentrations. Integrating both methodologies could create a comprehensive framework, combining reliability with accessibility. Future research should focus on robust biosensor development, standardization, expanding application to other cancers, exploring less-studied samples like sweat, and improving affordability for wider adoption, especially in resource-limited settings. The future lies in integrating diverse approaches for more sensitive, specific, and patient-friendly screening, improving early detection and outcomes. Full article
(This article belongs to the Special Issue Innovative Strategies for Cancer Biosensing)
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