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14 pages, 2398 KB  
Article
Inhibition of Porphyromonas gingivalis-Induced Respiratory Inflammation by an Alkaline Extract of Sasa senanensis Leaves
by Asako Takagi, Akira Hasuike, Noriaki Kamio, Ryo Sakai, Yukihiro Karahashi, Kozue Sugimoto, Yurika Nakajima, Misaki Horiuchi, Kazuki Toeda, Hiroshi Sakagami, Shuichi Sato and Kenichi Imai
Pathogens 2026, 15(2), 135; https://doi.org/10.3390/pathogens15020135 (registering DOI) - 26 Jan 2026
Abstract
Periodontal pathogens, including Porphyromonas gingivalis (P. gingivalis), are implicated in respiratory inflammatory conditions, and aspirated oral bacterial components may contribute to airway inflammation. This association has prompted the exploration of innovative therapeutic strategies in addition to conventional oral hygiene practices. We [...] Read more.
Periodontal pathogens, including Porphyromonas gingivalis (P. gingivalis), are implicated in respiratory inflammatory conditions, and aspirated oral bacterial components may contribute to airway inflammation. This association has prompted the exploration of innovative therapeutic strategies in addition to conventional oral hygiene practices. We evaluated the anti-inflammatory efficacy of an alkaline extract of Sasa senanensis leaves (SE) against heat-inactivated P. gingivalis-induced inflammation in respiratory tissues. In human bronchial epithelial cells (BEAS-2B), SE reduced interleukin (IL)-6 and IL-8 mRNA expression and cytokine secretion in a dose-dependent manner. Moreover, SE attenuated nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs), including p38 and c-Jun N-terminal kinase (JNK), indicating broad anti-inflammatory actions. In mice, SE administration decreased early lung cytokine levels and reduced NF-κB activity following intratracheal challenge with heat-inactivated P. gingivalis. Together, these in vitro and in vivo findings indicate that SE suppresses proinflammatory signaling triggered by P. gingivalis components and may serve as a natural adjunct to mitigate bacteria-associated airway inflammatory responses. Full article
(This article belongs to the Section Vaccines and Therapeutic Developments)
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19 pages, 3189 KB  
Article
The Use of Rheological and Tribological Techniques for Texture Assessment of Ambient Yoghurt
by Shuli Hu, Hui Li, Hongliang Li, Hairan Ma, Yajun Fei, Xiuying Wu, Wenbin Zhu, Jianshe Chen and Shuanghong Li
Foods 2026, 15(3), 440; https://doi.org/10.3390/foods15030440 (registering DOI) - 26 Jan 2026
Abstract
Background: Ambient yoghurt, also known as room-temperature yoghurt, has gained increasing attention due to its convenience in distribution and consumption without needing cold storage. To ensure extended shelf life, ambient yoghurt normally undergoes an additional heat treatment during manufacturing, the post-fermentation sterilisation [...] Read more.
Background: Ambient yoghurt, also known as room-temperature yoghurt, has gained increasing attention due to its convenience in distribution and consumption without needing cold storage. To ensure extended shelf life, ambient yoghurt normally undergoes an additional heat treatment during manufacturing, the post-fermentation sterilisation process (typically at 65–85 °C), which may induce the formation of fine particle aggregates and result in undesirable textural attributes, particularly graininess. Assessing textural attributes of such products remains a challenge. Methods: By mimicking the oral behaviour of ambient yoghurt, this study uses rheological as well as tribological techniques for objective assessment of the textural sensations of slipperiness and graininess. Various experimental conditions, including the amount of saliva incorporation, sliding speed, and ball-contact and plate-contact lubrication, were examined, and results were analysed against perceived texture by panellists. Main findings: The results indicate that viscosity changes are closely associated with perceived slipperiness under the tested conditions. The friction coefficient obtained from a plate-contact tribometer shows a positive correlation with the sensation of graininess (Pearson’s r was 0.74, p < 0.05, N = 8). It was also observed that a 20% saliva incorporation showed the closest agreement with sensory perception, although this observation should be interpreted cautiously due to the limited sample size. Implications: Results obtained from this work indicate the feasibility of using rheology and tribology techniques for texture prediction in ambient yoghurt. The findings are exploratory in nature, and further studies with larger sample sets are required to validate the proposed approach. The methodology presented here may serve as a reference framework for investigating texture perception in other dairy systems. Full article
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7 pages, 560 KB  
Brief Report
A Comparative Study of the Use of Half-Dose (7.5 MG) Versus Full-Dose (15 MG) of Tolvaptan in the Treatment of Hyponatremia Caused by the Syndrome of Inappropriate Antidiuresis (SIAD)
by Vincenzo Bassi, Valentina Apuzzi, Ciro Salzano and Olimpia Fattoruso
Therapeutics 2026, 3(1), 4; https://doi.org/10.3390/therapeutics3010004 (registering DOI) - 26 Jan 2026
Abstract
Background: Hyponatremia (serum sodium levels below 135 mEq/L) is the most prevalent electrolyte imbalance, with the syndrome of inappropriate antidiuresis (SIAD) being the most common cause among inpatients. Fluid restriction is the primary treatment for SIAD, yet its efficacy is inconsistent. A novel [...] Read more.
Background: Hyponatremia (serum sodium levels below 135 mEq/L) is the most prevalent electrolyte imbalance, with the syndrome of inappropriate antidiuresis (SIAD) being the most common cause among inpatients. Fluid restriction is the primary treatment for SIAD, yet its efficacy is inconsistent. A novel therapeutic approach involves the use of oral vaptans, such as tolvaptan (TLV), which are non-peptide antagonists of arginine vasopressin receptors. The recommended daily dose of TLV is 15 mg; however, the risk of overcorrection and osmotic demyelination syndrome must be considered. Methods: Consequently, a more cautious approach involving a 7.5 mg dose of TLV was studied in SIAD patients to determine its safety and efficacy compared with a 15 mg dose. Results: The findings of our investigation show that the results obtained from the two doses are highly similar. However, it is important to note that the risk of overcorrection was lower in the 7.5 mg TLV group than in the 15 mg group. Furthermore, a more gradual increase in serum Na was observed in the 7.5 mg group than in the 15 mg group after the most critical first 24 h. Conclusions: TLV therapy can be initiated with a 7.5 mg dose, with serum sodium levels monitored at 12 and 24 h to confirm or adjust the TLV dose as required. Full article
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27 pages, 1794 KB  
Article
Narrow Versus Broad Phenotype Definitions Affect Genetic Analysis of Language More than Other Broad Autism Phenotype Traits
by Mudassir K. Lodi, Judy F. Flax, Christine Gwin, Sherri Wilson, Amber Robinson, Steven Buyske, Linda M. Brzustowicz, Jinchuan Xing and Christopher W. Bartlett
Genes 2026, 17(2), 125; https://doi.org/10.3390/genes17020125 - 25 Jan 2026
Abstract
Background/Objectives: Autism spectrum disorder (ASD) is a heritable neurodevelopmental condition that displays heterogeneity in both presentation and etiology, and often presents with concomitant communication difficulties. The hypothesis behind the New Jersey Language and Autism Genetic Study is that genetic heterogeneity for component phenotypes [...] Read more.
Background/Objectives: Autism spectrum disorder (ASD) is a heritable neurodevelopmental condition that displays heterogeneity in both presentation and etiology, and often presents with concomitant communication difficulties. The hypothesis behind the New Jersey Language and Autism Genetic Study is that genetic heterogeneity for component phenotypes of ASD may be reduced relative to the disorder as a whole. We previously published an initial phase of this study with family recruitment that used very restricted inclusion/exclusion criteria for both autism and language deficits. Here, we present an expanded sample that includes a wider range of phenotypic presentations in the autism and language domains. Methods: Bioinformatics tools focusing on variant prioritization were used to identify candidate risk genes. Results: Our previous findings on 15q and 16q, connecting ASD and oral/written communication, are only relevant to the narrow ASD and language impairment phenotypes, though addition of families did reduce both critical regions. After variant and gene prioritization, we determined a set of ten and six top candidate risk genes with a strong association with language impairment and reading impairment, respectively. The top candidate genes include both genes previously implicated in neurodevelopmental disorders (e.g., ZNF774 and DNAH3) and genes not previously reported but with strong evidence of being involved in neurodevelopmental phenotypes. Conclusions: Our analysis elucidates the genetic architecture and interaction of ASD and language-related phenotypes. In addition, we reported a number of high-confidence candidate genes within the top linkage regions. These genes will provide insights into the genetic etiology of neurodevelopmental disorders. Full article
(This article belongs to the Special Issue Genetic Insights into Neurodevelopmental Disorders)
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16 pages, 2143 KB  
Article
On-Demand Neutral Electrolyzed Water-Containing Hydrogel with Tunable Available Chlorine Concentration Based on Methylcellulose–Agar Composite
by Yuki Nagamatsu, Hiroshi Ikeda and Hiroshi Nagamatsu
Appl. Sci. 2026, 16(3), 1216; https://doi.org/10.3390/app16031216 - 24 Jan 2026
Viewed by 48
Abstract
Neutral electrolyzed water (NW) is widely used in dentistry because of its strong bactericidal activity and high biosafety; however, its clinical application is limited by short retention time in the oral cavity and by the difficulty in maintaining and adjusting the available chlorine [...] Read more.
Neutral electrolyzed water (NW) is widely used in dentistry because of its strong bactericidal activity and high biosafety; however, its clinical application is limited by short retention time in the oral cavity and by the difficulty in maintaining and adjusting the available chlorine concentration (ACC) on-site. This study aimed to develop an on-demand NW-containing hydrogel (NWJ) that allows adjustment of ACC immediately before use while maintaining antimicrobial efficacy and handling properties. A methylcellulose–agar composite gel was prepared as a base gel and mixed with high-concentration NW to obtain prototype NWJs with target ACCs ranging 20–100 mg/L. Physicochemical properties (pH and ACC), time-dependent changes in ACC, bactericidal activity against Streptococcus mutans, and gel spreadability were evaluated. The base gel showed improved resistance to syneresis compared with an agar-only gel. All NWJs maintained a pH of approximately 6–7, exceeding the critical pH for enamel demineralization. Loss of ACC during gel preparation was less than 5%, and gradual ACC reduction was observed. Complete bactericidal activity was achieved at ACCs of 10 mg/L or higher, and gelation did not compromise antibacterial efficacy. These findings demonstrate that the developed NWJ provides a practical platform for clinical application of NW in dentistry. Full article
(This article belongs to the Special Issue New Approaches to Water Treatment: Challenges and Trends, 2nd Edition)
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14 pages, 1111 KB  
Article
Should Super-Selective Intra-Arterial Chemoradiotherapy Be Prioritized over Surgical Resection for Locally Advanced Oral Cavity Cancer?
by Beng Gwan Teh, Wataru Kobayashi, Kosei Kubota, Shinya Kakehata, Norihiko Narita and Yoshihiro Tamura
Cancers 2026, 18(3), 365; https://doi.org/10.3390/cancers18030365 (registering DOI) - 24 Jan 2026
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Abstract
Background/Objectives: Super-selective intra-arterial chemoradiotherapy (SSIACRT) is an alternatively effective treatment for locally advanced oral cavity cancer although no comparative studies on prognosis between SSIACRT and surgical resection with or without post-operative radiotherapy (S+R) have been reported. This study aimed to compare the 5-year [...] Read more.
Background/Objectives: Super-selective intra-arterial chemoradiotherapy (SSIACRT) is an alternatively effective treatment for locally advanced oral cavity cancer although no comparative studies on prognosis between SSIACRT and surgical resection with or without post-operative radiotherapy (S+R) have been reported. This study aimed to compare the 5-year survival rate and Quality of Life (QoL) between S+R and SSIACRT for locally advanced oral cavity cancer. Methods: From a total of 326 patients with stage III and IV oral cavity cancer treated between 2000–2020 at a single institution, 149 patients treated with S+R and SSIACRT were analyzed by using Propensity Score Matching (PSM) method, a pseudo-randomized controlled trial, and the matched cases were retrospectively evaluated. The 5-year survival rate and QoL were evaluated using the Kaplan–Meier method and the University of Washington QoL questionnaire, respectively. Log-rank test and Cox proportional hazards model were used to compare 5-year survival rate and to assess factors affecting survival rates, respectively. Paired t-test was used to compare QoL. Results: To compare the 5-year survival rate and QoL between S+R and SSIACRT, 48 and 15 cases were matched after PSM. The 149 cases were further evaluated for covariates affecting survival rates. The 5-year disease-specific survival rate and 5-year crude survival rate were 52.4% and 44.3% for S+R and 71.3%, and 62.9% for SSIACRT, respectively. There was no statistical difference in survival rates between both treatments, based on Log-rank test analysis. Treatment method was the only independent variable that influenced survival rates. SSIACRT showed better statistical difference in QoL evaluation, specifically in appearance, activity, recreation, swallowing, speech, shoulder, taste, mood, and total score. Conclusions: Propensity score-matched analysis demonstrated survival outcomes that were comparable to, and not inferior to, S+R. However, SSIACRT was associated with superior quality-of-life outcomes compared with S+R, as shown by Cox proportional hazards modeling. These findings suggest that SSIACRT is an effective treatment option and, from a quality-of-life perspective, may be considered a preferable approach in the management of locally advanced oral cavity cancer. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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14 pages, 449 KB  
Article
Profiling of Patients Attending the Initial Dental Consultation at a Dental Clinic in Southern Italy: A Single-Centre Retrospective Cross-Sectional Study
by Domenico De Falco, Barbara Barone, Francesca Iaquinta, Doriana Pedone, Laura Roselli and Massimo Petruzzi
Appl. Sci. 2026, 16(3), 1186; https://doi.org/10.3390/app16031186 - 23 Jan 2026
Viewed by 81
Abstract
In Italy, access to public dental care is limited, and the characteristics of patients seeking hospital-based services are poorly described. A single-centre retrospective cross-sectional study was conducted, including all individuals attending their first appointment at the public Dental Clinic of Bari University Hospital [...] Read more.
In Italy, access to public dental care is limited, and the characteristics of patients seeking hospital-based services are poorly described. A single-centre retrospective cross-sectional study was conducted, including all individuals attending their first appointment at the public Dental Clinic of Bari University Hospital (Southern Italy) between 1 January and 31 December 2023. Demographic and clinical variables, comorbidities, reasons for consultation, and travel distance from residence were retrieved from electronic records and analysed. Among 1361 patients (49% male; mean age 47.8 ± 23.3 years), most attended for oral surgery (35%) or oral pathology (17%), while other specialties accounted for the remaining visits. Many patients presented with multiple systemic conditions, particularly cardiovascular and metabolic diseases; however, a sizeable proportion were young, apparently healthy individuals who did not meet national eligibility criteria for publicly funded dental care. The dental clinic served a wide catchment area, including referrals from other regions. Documentation on education and behavioural risk factors was frequently incomplete. Overall, these findings show that complex oral medicine and oral surgery needs are concentrated in a small number of hospital clinics and support the expansion of Italian public dental services and improvements in routine data collection. Full article
18 pages, 2558 KB  
Article
Standardized Hericium erinaceus Extract Powder Improves Scopolamine-Induced Cognitive Deficits via BDNF-Mediated Neuroplasticity
by Seon-Hyeok Kim, Se Jeong Kim, Eun Ji Ko, Hae Ran Lee, Seong Min Hong, Se Hwan Ryu, Dae Hee Lee, Young Guk Kim, Jeong Yun Yu, Jae Kang Lee, Mi Kyeong Lee and Sun Yeou Kim
Sci. Pharm. 2026, 94(1), 12; https://doi.org/10.3390/scipharm94010012 - 23 Jan 2026
Viewed by 68
Abstract
Alzheimer’s disease and related neurodegenerative disorders are associated with progressive cognitive decline, primarily driven by cholinergic dysfunction and impaired synaptic signaling. Hericium erinaceus, also known as lion’s mane mushroom, has been reported to promote neuronal differentiation and synaptic plasticity. In this study, [...] Read more.
Alzheimer’s disease and related neurodegenerative disorders are associated with progressive cognitive decline, primarily driven by cholinergic dysfunction and impaired synaptic signaling. Hericium erinaceus, also known as lion’s mane mushroom, has been reported to promote neuronal differentiation and synaptic plasticity. In this study, a standardized H. erinaceus extract powder (HEP) was prepared from fruiting bodies and quantified using hericene A as a marker compound. The neuroprotective effects of HEP were then evaluated in both cellular and animal models of scopolamine-induced cognitive dysfunction. Pretreatment of SH-SY5Y human neuroblastoma cells with HEP (5–25 μg/mL) significantly improved cell viability and reduced scopolamine-induced apoptosis, while enhancing the activation of neuroplasticity-related signaling proteins, including brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and extracellular signal-regulated kinase (ERK). In vivo, oral administration of HEP (300 mg/kg) to scopolamine-treated ICR mice markedly improved cognitive performance, increasing the recognition index to 63.8% compared with 41.6% in the scopolamine group, and enhancing spontaneous alternation in the Y-maze test to 59.6%. These cognitive improvements were accompanied by preserved hippocampal neuronal structure and increased BDNF immunoreactivity. Additionally, HEP improved cholinergic function by restoring serum acetylcholine levels and reducing acetylcholinesterase activity. Collectively, these findings suggest that standardized HEP exerts neuroprotective and cognition-enhancing effects via modulation of cholinergic markers and activation of BDNF-mediated neuroplasticity, highlighting its potential as a functional food ingredient or nutraceutical for preventing cognitive decline related to cholinergic dysfunction. Full article
(This article belongs to the Topic Functional Foods and Nutraceuticals in Health and Disease)
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23 pages, 1026 KB  
Article
Anticancer Potential of Thieno[2,3-d]pyrimidine Derivatives in Oral Carcinoma Models
by Ivan Iliev, Aleksandrina Nesheva, Anelia Mavrova, Denitsa Yancheva, Aneliya Kostadinova, Severina Semkova, Albena Momchilova, Iana Tsoneva, Galya Staneva and Biliana Nikolova
Molecules 2026, 31(3), 397; https://doi.org/10.3390/molecules31030397 - 23 Jan 2026
Viewed by 74
Abstract
Oral squamous cell carcinoma (OSCC) remains a major therapeutic challenge due to aggressive progression, high recurrence, and limited selectivity of current treatments. In this study, a series of seven 4-amino-2-substituted tetrahydrobenzothieno[2,3-d]pyrimidines were evaluated for their cytotoxic, antiproliferative, and mechanistic effects against oral cancer [...] Read more.
Oral squamous cell carcinoma (OSCC) remains a major therapeutic challenge due to aggressive progression, high recurrence, and limited selectivity of current treatments. In this study, a series of seven 4-amino-2-substituted tetrahydrobenzothieno[2,3-d]pyrimidines were evaluated for their cytotoxic, antiproliferative, and mechanistic effects against oral cancer cell lines with different metastatic potential (HSC-3 and SCC-9), alongside non-tumorigenic keratinocytes (HaCaTs). Several compounds demonstrated selective anticancer activity, with Compounds 5 and 6 showing the most favorable balance between potency and selectivity. Antiproliferative assays revealed effective inhibition of cancer cell growth, while clonogenic assays confirmed a pronounced reduction in long-term survival, particularly in highly metastatic HSC-3 cells. Mechanistic studies indicated that the anticancer effects are associated with S-phase cell cycle arrest, apoptosis induction, and profound disruption of the actin cytoskeleton. In silico ADME and drug-likeness analyses supported the lead-like properties of the most active derivatives. Overall, these findings identify thienopyrimidine derivatives as promising scaffolds for the development of targeted therapies against OSCC and warrant further optimization and in vivo evaluation. Full article
(This article belongs to the Special Issue The Anticancer Drugs: A New Perspective)
17 pages, 1087 KB  
Article
Bioactivity of Ribes nigrum L. Juice and Waste Extracts: Chemical Composition, Antioxidant, and Antiproliferative Properties
by Milica Trajković, Bojana Miladinović, Dragan Mihailović, Stevo Najman, Milica Milutinović, Milica Randjelović, Miloš Jovanović, Nemanja Kitić, Katarina Šavikin and Dušanka Kitić
Plants 2026, 15(3), 356; https://doi.org/10.3390/plants15030356 - 23 Jan 2026
Viewed by 86
Abstract
This study aimed to assess phytochemical profiles and antioxidant activities of lyophilized black currant fruit juice (BCLJ) and its corresponding waste extract (BCLW) from the Čačanska crna variety, and to evaluate their antiproliferative properties. The main anthocyanins quantified through HPLC-DAD analysis were delphinidin-3- [...] Read more.
This study aimed to assess phytochemical profiles and antioxidant activities of lyophilized black currant fruit juice (BCLJ) and its corresponding waste extract (BCLW) from the Čačanska crna variety, and to evaluate their antiproliferative properties. The main anthocyanins quantified through HPLC-DAD analysis were delphinidin-3-O-rutinoside and cyanidin-3-O-rutinoside, with significantly higher levels in BCLW. Antioxidant activity was examined using the DPPH and β-carotene/linoleic acid methods, with BCLW showing superior effects in both. Antiproliferative potential was evaluated by determining the Ki67 index in renal epithelial cells of rats treated with BCLJ or BCLW. Thirty healthy male rats were randomly assigned to five groups (n = 6) and administered BCLJ or BCLW orally for ten days, receiving 100, 200, and 300 mg/kg b.w. of BCLW (BCLW1, BCLW2, and BCLW3 groups, respectively) or 200 mg of BCLJ. Histopathological and immunohistochemical parameters were assessed in rats’ kidneys. Across all epithelial types (cortical proximal tubules, distal medullary proximal tubules, collecting ducts, and urothelial cells of the renal pelvis), the highest Ki67 indices were observed in control animals, particularly in collecting ducts and cortical proximal tubules. The lowest Ki67 values in cortical proximal tubules occurred in the BCLW2 group (p < 0.05 vs. control). These findings suggest that black currant preparations could be valuable functional ingredients. Full article
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15 pages, 11246 KB  
Article
Antiseptic Mouthwashes After Dental Surgical Procedures: Comparative Antimicrobial and Antibiofilm Efficacy Against Oral Postoperative Pathogens
by Marzena Korbecka-Paczkowska, Magdalena Paczkowska-Walendowska, Aneta A. Ptaszyńska, Jakub Piontek, Judyta Cielecka-Piontek and Tomasz M. Karpiński
Appl. Sci. 2026, 16(3), 1167; https://doi.org/10.3390/app16031167 - 23 Jan 2026
Viewed by 74
Abstract
This in vitro study compared the antimicrobial and antibiofilm efficacy of four commercially available chlorhexidine (CHX)-based mouthwashes, with different nominal CHX concentrations, against clinically relevant postoperative oral pathogens, including Staphylococcus aureus, Streptococcus mutans, Escherichia coli, Pseudomonas aeruginosa, Candida albicans [...] Read more.
This in vitro study compared the antimicrobial and antibiofilm efficacy of four commercially available chlorhexidine (CHX)-based mouthwashes, with different nominal CHX concentrations, against clinically relevant postoperative oral pathogens, including Staphylococcus aureus, Streptococcus mutans, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, and Candida auris. Antimicrobial potency was evaluated using MIC and CEMIC indices, while biofilm thickness reduction was quantified using 3D digital microscopy and custom image analysis software. Among the tested formulations, the excipient-enriched formulation exhibited the lowest MIC values and the most significant reduction in biofilm thickness, particularly against Gram-negative bacteria and Candida species. All mouthwashes achieved CEMIC < 0.1, confirming high theoretical applicability margins; however, CEMIC reflects potential clinical usefulness rather than clinical superiority. The findings demonstrate that the antimicrobial and antibiofilm activity of CHX rinses is formulation-dependent and cannot be predicted solely by CHX concentration. The influence of excipients is discussed as a possible contributing factor, but related mechanisms remain speculative and require direct validation in future studies. This work supports a formulation-driven, evidence-based approach to antiseptic comparison in postoperative dentistry, without assessing clinical wound-healing outcomes. Full article
(This article belongs to the Special Issue Oral Diseases and Clinical Dentistry—2nd Edition)
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16 pages, 1092 KB  
Article
Therapeutic Potential, Predictive Pharmaceutical Modeling, and Metabolic Interactions of the Oxindole Kratom Alkaloids
by Md Harunur Rashid, Matthew J. Williams, Andres Garcia Guerra, Arunporn Itharat, Raimar Loebenberg and Neal M. Davies
J. Phytomed. 2026, 1(1), 2; https://doi.org/10.3390/jphytomed1010002 - 23 Jan 2026
Viewed by 53
Abstract
Kratom (Mitragyna speciosa (Korth.) Havil.) oxindole alkaloids remain underexplored compared to the well-studied indole constituents mitragynine and 7-hydroxymitragynine. Previous research has primarily focused on phytochemical identification and preliminary pharmacology, with limited pharmacokinetic insight. This study pioneers an in silico ADMET modeling analysis of [...] Read more.
Kratom (Mitragyna speciosa (Korth.) Havil.) oxindole alkaloids remain underexplored compared to the well-studied indole constituents mitragynine and 7-hydroxymitragynine. Previous research has primarily focused on phytochemical identification and preliminary pharmacology, with limited pharmacokinetic insight. This study pioneers an in silico ADMET modeling analysis of 27 kratom-derived oxindole alkaloids using ADMET Predictor™ v3.0, delivering the first comprehensive predictions of their physicochemical properties, CYP450/UGT enzyme interactions, transporter affinities, permeability, and pharmacokinetic parameters. Representative compounds such as speciophylline, isomitraphylline, and isospeciophylline displayed notably favorable predicted jejunal permeability and moderate metabolic stability, suggesting promising oral drug-like characteristics. Across the dataset, high CYP3A4 substrate affinity (98% confidence), variable CYP3A4, CYP2D6, CYP2C19 inhibition, strong P-gp substrate potential, and differential BBB penetration probabilities (46–99%) were observed. These findings provide a foundational computational framework to guide future experimental validation and rational drug development of kratom oxindole alkaloids. Full article
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13 pages, 1767 KB  
Article
Nicotine Negatively Affects Its Users’ Health and Psychology in Saudi Arabia: A Cross-Sectional Study
by Jehad A. Aldali
Healthcare 2026, 14(3), 286; https://doi.org/10.3390/healthcare14030286 - 23 Jan 2026
Viewed by 74
Abstract
Background: Recently introduced nicotine pouches (NPs) are smokeless nicotine products. They are held between the lips and gums for 30 min to absorb nicotine into the bloodstream through the oral mucosa. Attractiveness may increase nicotine use, especially among young people and teens. [...] Read more.
Background: Recently introduced nicotine pouches (NPs) are smokeless nicotine products. They are held between the lips and gums for 30 min to absorb nicotine into the bloodstream through the oral mucosa. Attractiveness may increase nicotine use, especially among young people and teens. The objective of this study is to investigate the health issues and psychological effects associated with nicotine pouch use among individuals in Saudi Arabia. Methods: A cross-sectional online survey using Google Forms. It was conducted between 13 February and 4 November 2025, in the Riyadh province of Saudi Arabia, restricted to users of nicotine pouches willing to answer a questionnaire on the occasion of buying them (at regional tobacco stores/supermarkets) or online via WhatsApp or the Telegram platform. Statistical analysis was conducted using SPSS Version 27, with a p < 0.05 indicating significance. Results: The current study included data of 489 participants, with a total of 395 participants using nicotine pouches. The most commonly reported symptoms were difficulty breathing and shortness of breath (both 40.5%), changes in taste or smell (36.7%), headache and stomach ulcers (33.4% each), and rapid or irregular heartbeat (28.4%). Most common psychological symptoms at any severity level (slightly to extremely) were appetite changes (78.7%), difficulty concentrating or focusing (75.4%), difficulty sleeping (74.9%), and increased anxiety or irritability (73.4%). Depression (72.2%), anger management (71.1%), and stress (70.4%) were also common. Regression analyses revealed that educational attainment was a significant predictor of both physical and psychological health outcomes. Conclusions: The findings show the most common physical symptoms were difficulty breathing and shortness of breath, followed by taste or smell changes, headaches, stomach ulcers, and rapid or irregular heartbeat. Appetite changes, concentration issues, sleep disturbances, and anxiety or irritability were common across all severity levels. Depression, anger issues, and stress were common. Full article
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23 pages, 348 KB  
Article
Phytochemical Composition, Biological Activity and Application of Cymbopogon citratus In Vitro Microshoot Cultures in Cosmetic Formulations
by Ewelina Błońska-Sikora, Jakub Wawrzycki, Paulina Lechwar, Katarzyna Gaweł-Bęben, Paulina Żarnowiec, Klaudia Wojtaszek and Małgorzata Wrzosek
Appl. Sci. 2026, 16(3), 1158; https://doi.org/10.3390/app16031158 - 23 Jan 2026
Viewed by 78
Abstract
This study investigated the phytochemical composition and biological activity of Cymbopogon citratus microshoot cultures and evaluated their suitability for incorporation into a cosmetic formulation. Microshoot cultures were established on Murashige and Skoog media supplemented with plant growth regulators and served as a reproducible [...] Read more.
This study investigated the phytochemical composition and biological activity of Cymbopogon citratus microshoot cultures and evaluated their suitability for incorporation into a cosmetic formulation. Microshoot cultures were established on Murashige and Skoog media supplemented with plant growth regulators and served as a reproducible source of biomass. Methanolic and ethanolic extracts were analyzed for total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Chemical composition was characterized using LC-MS/MS analysis, which revealed the presence of phenolic acids and flavonoids, with p-coumaric, caffeic, and ferulic acids being among the most abundant detected constituents. In biological assays, the extracts inhibited murine tyrosinase in a concentration-dependent manner and exhibited antimicrobial activity against selected oral and skin-associated microorganisms, including Streptococcus mutans, Streptococcus pyogenes, and Staphylococcus epidermidis, as well as showing fungistatic and fungicidal effects against Candida albicans. Cytotoxicity analysis performed on HaCaT keratinocytes confirmed biocompatibility within the tested concentration range. To assess formulation suitability, the microshoot extract was incorporated into an oil-in-water (O/W) cream, which maintained stable pH, viscosity, and physical properties while preserving the antioxidant activity of the extract. Overall, these findings indicate that C. citratus microshoot cultures represent a reproducible source of bioactive metabolites with potential application in cosmetic formulations. Full article
23 pages, 1182 KB  
Article
A Systematic Study of the Hepatic–Intestinal First-Pass Effect and Excretion Pathways of Punicalagin Based on UPLC-MS/MS
by Zixin Chen, Zhanying Chang, Pengxia Yao and Xiaoli Gao
Molecules 2026, 31(3), 393; https://doi.org/10.3390/molecules31030393 - 23 Jan 2026
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Abstract
Punicalagin, the major polyphenol in pomegranate peel, shows broad bioactivity but suffers from poor oral bioavailability. Whether hepatic or intestinal first-pass processes dominate this limitation remains unresolved. We developed a quantitative UPLC-MS/MS workflow to dissect punicalagin’s first-pass disposition and elimination in rats. Sprague–Dawley [...] Read more.
Punicalagin, the major polyphenol in pomegranate peel, shows broad bioactivity but suffers from poor oral bioavailability. Whether hepatic or intestinal first-pass processes dominate this limitation remains unresolved. We developed a quantitative UPLC-MS/MS workflow to dissect punicalagin’s first-pass disposition and elimination in rats. Sprague–Dawley rats received punicalagin by intravenous, portal vein, oral, or intraduodenal dosing; plasma exposure was quantified by UPLC-MS/MS and analyzed noncompartmentally. We also profiled urinary and fecal excretion of punicalagin and key metabolites (punicalin, ellagic acid, urolithin C and urolithin A) to define biotransformation and clearance. Punicalagin displayed an absolute oral bioavailability of ~3.49%. First-pass analysis revealed modest hepatic extraction (~13.94%) but near-complete intestinal extraction (95.95%), identifying intestinal first-pass metabolism as the dominant barrier to systemic exposure. Consistently, parent and metabolites were eliminated mainly in feces, whereas urine contained only trace conjugated urolithin A. Collectively, these findings demonstrate that the poor oral bioavailability of punicalagin is driven primarily by extensive intestinal first-pass metabolism rather than hepatic clearance, and that its feces-dominant elimination is compatible with widespread hydrolysis and microbiota-mediated conversion within the gut. This work provides a pharmacokinetic framework to guide strategies aimed at improving oral delivery and systemic exposure of punicalagin. Full article
(This article belongs to the Section Natural Products Chemistry)
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