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Search Results (2,012)

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14 pages, 2578 KB  
Article
IL-17 Cytokines Induce IκBζ in Dermal Fibroblasts to Promote Pro-Inflammatory Gene Expression in Psoriasis
by Lejla Svraka, Anna Skarnvad Andersen, Toke Touborg, Thomas Emmanuel, Udayaraja GK, Haja N. Kadarmideen, Trine Bertelsen, Christian Vestergaard and Claus Johansen
Int. J. Mol. Sci. 2026, 27(3), 1297; https://doi.org/10.3390/ijms27031297 (registering DOI) - 28 Jan 2026
Abstract
IκBζ (NFKBIZ) has been implicated as a key co-transcription factor in psoriasis pathogenesis. While its role in keratinocytes is well established, the involvement in dermal fibroblasts, another critical skin cell type, remains underexplored. This study characterizes cytokine-induced NFKBIZ regulation in human [...] Read more.
IκBζ (NFKBIZ) has been implicated as a key co-transcription factor in psoriasis pathogenesis. While its role in keratinocytes is well established, the involvement in dermal fibroblasts, another critical skin cell type, remains underexplored. This study characterizes cytokine-induced NFKBIZ regulation in human dermal fibroblasts in vitro and integrates spatial transcriptomics to determine NFKBIZ expression patterns in psoriatic skin biopsies. Primary dermal fibroblasts were stimulated with IL-17A, IL-17F, and TNF. Signaling pathways and gene regulation were examined using chemical inhibitors, siRNA knockdown, qPCR, and Western blotting. Additionally, spatial transcriptomics (CosMx™) assessed NFKBIZ expression in paired lesional and non-lesional psoriatic skin biopsies. Results showed significant upregulation of IκBζ expression in dermal fibroblasts following stimulation with both IL-17A and IL-17F. The NF-κB signaling pathway was identified as the primary regulator of NFKBIZ induction. NFKBIZ knockdown significantly reduced cytokine-induced expression of inflammatory mediators (CXCL8, CCL20, CCL2), confirming its regulatory role. Spatial transcriptomics further confirmed NFKBIZ expression in dermal fibroblasts in vivo, particularly in lesional psoriatic skin. This study establishes IκBζ as a critical modulator of inflammatory responses in dermal fibroblasts, expanding its recognized role beyond keratinocytes and immune cells, and highlights IκBζ inhibition as a potential therapeutic strategy. Full article
(This article belongs to the Special Issue Molecular Perspective in Autoimmune Diseases)
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15 pages, 1576 KB  
Article
Establishment of a Dynamic Ear Inflammation Model in Rats for Acne Vulgaris and Evaluation of Adjuvanted Inactivated Cutibacterium acnes-Based Vaccines Efficacy
by Tiannan Lu, Jie Yang, Dongsheng Yang, Yaxin Du, Ling Chen, Jing Guo and Zejun Wang
Vaccines 2026, 14(2), 124; https://doi.org/10.3390/vaccines14020124 - 27 Jan 2026
Abstract
Background/Objectives: Acne vulgaris is a chronic inflammatory skin disorder characterized by sebaceous gland hyperactivity, follicular hyperkeratinization, proliferation of Cutibacterium acnes (C. acnes), and subsequent inflammation. The development of effective therapeutics necessitates reliable preclinical models that accurately replicate key pathological aspects of [...] Read more.
Background/Objectives: Acne vulgaris is a chronic inflammatory skin disorder characterized by sebaceous gland hyperactivity, follicular hyperkeratinization, proliferation of Cutibacterium acnes (C. acnes), and subsequent inflammation. The development of effective therapeutics necessitates reliable preclinical models that accurately replicate key pathological aspects of the human disease. Methods: In this study, we established an inflammatory acne model in Wistar rats via the intradermal injection of live C. acnes into the ear pinnae and thoroughly characterized its temporal dynamics of the induced inflammation. Utilizing this model, we evaluated the protective efficacy of a whole-cell inactivated C. acnes vaccine (HI-C. acnes) formulated with adjuvants WS03 or MA107b. Results: Inflammation peaked between days 1 and 3 post-infection, manifesting as pronounced erythema, ear swelling, increased ear thickness, elevated bacterial load, and significant upregulation of pro-inflammatory cytokines (IL-6, IL-1β, and MCP-1). Histopathological examination revealed extensive neutrophil infiltration and microabscess formation, while immunohistochemistry confirmed localized overexpression of TNF-α, IL-1β, and CXCL1 within the lesional tissue. Inflammatory manifestations gradually subsided by day 5 and were fully resolved by day 7, which coincided with complete bacteria clearance and normalization of pro-inflammatory cytokine levels. Vaccinated rats developed significantly higher C. acnes-specific IgG titers and, upon challenge, exhibited markedly reduced ear swelling, diminished bacterial burden, and suppressed expression of key inflammatory mediators compared to control groups, indicating that vaccine-induced protection is associated with humoral immunity. Conclusions: Collectively, our standardized and quantifiable rat ear inflammation model provides a robust platform for mechanistic investigations and preclinical assessment of novel anti-acne vaccines and therapeutic agents. Full article
(This article belongs to the Special Issue Vaccines and Immunotherapy for Inflammatory Disease)
16 pages, 2619 KB  
Article
Multiparametric Ultrasound Features of the Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma: A Single-Center Case Series
by Monica Latia, Stefania Bunceanu, Andreea Bena, Octavian Constantin Neagoe and Dana Stoian
Diagnostics 2026, 16(2), 346; https://doi.org/10.3390/diagnostics16020346 - 21 Jan 2026
Viewed by 282
Abstract
Background/Objectives: The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is a rare and aggressive subtype characterized by diffuse gland involvement and early cervical lymph node metastasis. Preoperative differentiation from classic papillary thyroid carcinoma and autoimmune thyroid disease remains challenging on B-mode ultrasound. [...] Read more.
Background/Objectives: The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is a rare and aggressive subtype characterized by diffuse gland involvement and early cervical lymph node metastasis. Preoperative differentiation from classic papillary thyroid carcinoma and autoimmune thyroid disease remains challenging on B-mode ultrasound. This study aimed to describe the multiparametric ultrasound features of DSV-PTC in a single-center case series and highlight practical imaging insights. Methods: We retrospectively reviewed seven consecutive patients with histologically confirmed DSV-PTC evaluated at a single center between 2013 and 2025. All patients underwent standardized B-mode ultrasound, color Doppler, and two-dimensional shear-wave elastography prior to surgery. Clinical, autoimmune, cytological, surgical, pathological, and follow-up data were analyzed descriptively. Results: The cohort included five females and two males (mean age 28 years). Autoimmune thyroid disease was present in three patients. High-risk ultrasound features were identified in all cases, with microcalcifications in six patients and a diffuse “snowstorm” appearance in five. Elastography demonstrated increased stiffness in six out of seven lesions (Emean 28–173 kPa; Emax 31–300 kPa). Cervical lymph node metastases were confirmed in all patients. In two cases, elastography aided identification of focal malignant involvement within diffusely altered thyroid parenchyma. All patients underwent total thyroidectomy with central neck dissection; lateral neck dissection and radioiodine therapy were performed selectively. No distant metastases were detected. Conclusions: In this case series, DSV-PTC showed a characteristic multiparametric ultrasound pattern combining high-risk B-mode features with frequently increased tissue stiffness. Elastography provided complementary information, particularly in the presence of autoimmune thyroid disease, by helping localize focal malignant involvement within diffusely altered parenchyma. Full article
(This article belongs to the Special Issue Thyroid Cancer: Types, Symptoms, Diagnosis and Management)
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11 pages, 3491 KB  
Case Report
Clinicopathological Spectrum of EBV-Related Primary Splenic Tumors Identified by Splenectomy: A Case Series
by Minju Kim, Byeong Gwan Noh, Myunghee Yoon, Hyung Il Seo, Myeong Hun Oh, Young Mok Park, Suk Kim, Seung Baek Hong and Kyung Un Choi
Diagnostics 2026, 16(2), 333; https://doi.org/10.3390/diagnostics16020333 - 20 Jan 2026
Viewed by 167
Abstract
Background: Epstein–Barr virus (EBV)-related primary splenic tumors are exceptionally rare and encompass a heterogeneous group of entities, including inflammatory pseudotumor (IPT), IPT-like follicular dendritic cell (FDC) tumors or sarcomas, and EBV-positive diffuse large B-cell lymphoma (DLBCL). Because clinical presentation and imaging findings are [...] Read more.
Background: Epstein–Barr virus (EBV)-related primary splenic tumors are exceptionally rare and encompass a heterogeneous group of entities, including inflammatory pseudotumor (IPT), IPT-like follicular dendritic cell (FDC) tumors or sarcomas, and EBV-positive diffuse large B-cell lymphoma (DLBCL). Because clinical presentation and imaging findings are often nonspecific, establishing a definitive diagnosis remains challenging and frequently necessitates splenectomy for histopathologic confirmation. Methods: We retrospectively reviewed patients who underwent laparoscopic splenectomy for suspected primary splenic lesions at a single tertiary institution between June 2014 and August 2025. Among 67 patients, five consecutive patients were pathologically confirmed as EBV-related primary splenic tumors. Clinical characteristics, imaging features, histopathologic and immunophenotypic findings, EBV in situ hybridization results, treatment, and follow-up outcomes were analyzed. Results: This case series comprised four spindle cell–predominant EBV-related tumors (IPT or IPT-like FDC tumors/sarcomas) and one EBV-positive DLBCL. All patients presented with splenic masses that could not be definitively characterized by preoperative imaging alone and therefore required splenectomy. EBV in situ hybridization was positive in tumor cells in all cases. Patients with non-lymphomatous tumors achieved durable disease control following splenectomy alone, with disease-free survival of up to five years. In contrast, the patient with EBV-positive DLBCL required postoperative systemic immunochemotherapy. Conclusions: EBV-related primary splenic tumors represent a diagnostically challenging and clinically diverse disease spectrum. This case series highlights the pivotal role of splenectomy in establishing definitive diagnosis and guiding subsequent management, particularly for isolated splenic lesions with indeterminate imaging findings. Full article
(This article belongs to the Special Issue Diagnosis and Prognosis of Abdominal Diseases)
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14 pages, 1330 KB  
Article
Development and Internal Validation of a Bailout Risk Score in PCI with Drug-Coated Balloons
by Luigi Alberto Iossa, Marco Ferrone, Luigi Salemme, Elena Laganà, Armando Pucciarelli, Michele Franzese, Giuseppe Ciliberti, Sebastiano Verdoliva, Giulia Sgherzi, Grigore Popusoi, Angelo Cioppa, Tullio Tesorio and Giuseppe Di Gioia
J. Clin. Med. 2026, 15(2), 813; https://doi.org/10.3390/jcm15020813 - 19 Jan 2026
Viewed by 129
Abstract
Background/Objectives: Bail-out stenting remains a procedural challenge for percutaneous coronary intervention (PCI) performed with drug-coated balloons (DCBs). No dedicated bedside tool is currently available to predict this event. We aimed to develop and internally validate a bedside Bail-Out Risk Score. Methods: [...] Read more.
Background/Objectives: Bail-out stenting remains a procedural challenge for percutaneous coronary intervention (PCI) performed with drug-coated balloons (DCBs). No dedicated bedside tool is currently available to predict this event. We aimed to develop and internally validate a bedside Bail-Out Risk Score. Methods: We analyzed patients treated with DCBs between 2021 and 2025. Predictors of bailout stenting were identified through univariate analysis, and variables with p < 0.10 were entered into a multivariable logistic regression model. Regression coefficients were then transformed into integer points using the Sullivan method. Model performance was evaluated by AUC-ROC, calibration, and bootstrap internal validation (B = 1000). Results: A total of 352 patients (399 de novo lesions) were treated with DCB-only PCI. Bail-out stenting occurred in 14.5% of lesions (58/399). Independent predictors of bail-out stenting were prior CABG (OR 4.29, p = 0.002), proximal lesion location (OR 2.99, p = 0.003), and diffuse disease (OR 2.18, p = 0.018). Prior PCI (OR 0.44, p = 0.009) and lipid-lowering therapy (OR 0.42, p = 0.029) were protective, while LAD involvement showed a non-significant trend (OR 1.57, p = 0.137). The model demonstrated moderate discrimination (AUC = 0.734; optimism-corrected AUC = 0.704) and excellent calibration (intercept = 0.000, slope = 1.000). The final score (range −4 to +8) stratified lesions into low (≤−1), intermediate (0–3), and high (≥3) risk groups, with progressively higher predicted probabilities (≤9%, 13–37%, and ≥49%). Conclusions: The Bail-Out Risk Score provides a practical and reliable bedside tool to estimate procedural risk during stentless PCI. Full article
(This article belongs to the Section Cardiology)
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17 pages, 5297 KB  
Article
Liver Safety Assessment of an Indonesian Hexavalent Vaccine Candidate Through Histopathology and ALT/AST Evaluation in Rats and Rabbits
by Elisa D. Pratiwi, Tiza W. Mawaddah, Arif R. Sadjuri, Dimas T. Nugroho, Arip Hidayat, Astria N. Nidom, Zakiyyan I. Ayyuba, Eka S. Wahyuningsih, Kuncoro P. Santoso, Hani Plumeriastuti, Soeharsono, Setyarina Indrasari, Reviany V. Nidom, Acep R. Wijayadikusumah and Chairul A. Nidom
Vaccines 2026, 14(1), 94; https://doi.org/10.3390/vaccines14010094 - 19 Jan 2026
Viewed by 190
Abstract
Background: Administering several separate childhood vaccines can reduce adherence to immunization schedules due to missed appointments and the burden of repeated injections. A hexavalent formulation targeting diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type B, and poliovirus offers a practical approach to improve [...] Read more.
Background: Administering several separate childhood vaccines can reduce adherence to immunization schedules due to missed appointments and the burden of repeated injections. A hexavalent formulation targeting diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type B, and poliovirus offers a practical approach to improve compliance and streamline immunization. Methods: Toxicity testing was performed in Wistar rats and New Zealand White rabbits (60 rats and 30 rabbits). Animals were distributed into three groups: hexavalent vaccine + low-dose sIPV, hexavalent vaccine + high-dose sIPV, and control. Each animal received a 0.5 mL intramuscular injection at weeks 0, 4, 8, and 12. Clinical observations were conducted throughout the study. Serum samples were collected one day before each injection and at the endpoint, while liver tissue was collected at the endpoint. ALT and AST concentrations were analyzed using an automated analyzer, and hepatic morphology was evaluated microscopically. Results: No abnormal clinical signs related to vaccination were observed. ALT concentrations showed no significant differences (p > 0.05). AST differences (p < 0.05) were detected between the high-dose group and the control on day 27 in female rabbits and on day 83 in female rats; however, all values remained within normal physiological limits. Histopathological examination revealed no irreversible hepatic lesions, including hydropic degeneration, portal inflammation, focal necrosis, or connective tissue proliferation, and no significant differences were noted (p > 0.05). Conclusions: Repeated administration of the hexavalent vaccine candidate at low and high doses produced no toxicological effects in animal models, supporting its safety for further clinical development. Full article
(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)
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19 pages, 2268 KB  
Article
The Efficacy of Multicomponent Preparation for Detoxification of Mycotoxins in the Presence of AFB1 and OTA Added to Broiler Feed
by Jelena Nedeljković Trailović, Branko Petrujkić, Saša Trailović, Dragoljub Jovanović, Milutin Đorđević, Darko Stefanović, Nataša Tolimir, Darko Marinković and Stamen Radulović
Poultry 2026, 5(1), 9; https://doi.org/10.3390/poultry5010009 - 19 Jan 2026
Viewed by 111
Abstract
The experimental study was performed to determine the efficacy of a mycotoxin detoxification agent (MS) at a concentration of 0.2% in reducing the toxicity of aflatoxin B1 (AFB1) and ochratoxin A (OTA), alone or in combination, and to examine its effect on performance, [...] Read more.
The experimental study was performed to determine the efficacy of a mycotoxin detoxification agent (MS) at a concentration of 0.2% in reducing the toxicity of aflatoxin B1 (AFB1) and ochratoxin A (OTA), alone or in combination, and to examine its effect on performance, pathohistological (PH) changes, and residues of these toxins in the tissues of broiler chicks. A total of 88 broilers were divided into eight equal groups: group C, the control group (fed a commercial diet without any additives); group MS, which received the mycotoxin detoxification agent (MS) (supplemented with 0.2%); group E I (0.2 mg AFB1/kg of diet); group E II (0.2 mg AFB1/kg of diet + MS 0.2%); group E III (1.5 mg OTA/kg of diet); group E IV (1.5 mg OTA/kg of diet + 0.2% MS); group E V (combination of 0.2 mg AFB1/kg, 1.5 mg OTA/kg of diet); and group E VI (combination of 0.2 mg AFB1/kg, 1.5 mg OTA toxin + 0.2% MS). Results show that feed containing AFB1 and OTA, individually or in combination, negatively affects health, production results, and PH changes in tissues, as well as the presence of mycotoxin residues in the liver and breast muscles of poultry. The addition of a new multicomponent preparation for the detoxification of MS mycotoxins in feed with AFB1 and OTA individually and in combination had a positive effect on TM (BW), growth (BWG), consumption and FCR conversion coefficient, and microscopic lesions in organs. The concentration of OTA residues in the liver and chest muscles was significantly lower in chickens fed a diet with the addition of 0.2% MS of the mycotoxin detoxification preparation. Full article
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18 pages, 1540 KB  
Article
Overestimation of the Apparent Diffusion Coefficient in Diffusion-Weighted Imaging Due to Residual Fat Signal and Out-of-Phase Conditions
by Maher Dhanani, Dominika Skwierawska, Tristan Anselm Kuder, Sabine Ohlmeyer, Michael Uder, Sebastian Bickelhaupt and Frederik Bernd Laun
Tomography 2026, 12(1), 11; https://doi.org/10.3390/tomography12010011 - 16 Jan 2026
Viewed by 197
Abstract
Background/Objectives: Diffusion-weighted imaging (DWI) is a magnetic resonance technique used to map the apparent diffusion coefficient (ADC) of water in human tissue. ADC assessment plays a central role in clinical diagnostics, as malignant tissues typically exhibit [...] Read more.
Background/Objectives: Diffusion-weighted imaging (DWI) is a magnetic resonance technique used to map the apparent diffusion coefficient (ADC) of water in human tissue. ADC assessment plays a central role in clinical diagnostics, as malignant tissues typically exhibit reduced water mobility and, thus, lower ADC values. Accurately measuring the ADC requires effective fat suppression to prevent contamination from the residual fat signal, which is commonly believed to cause ADC underestimation. This study aimed to demonstrate that ADC overestimation may occur as well. Methods: Our theoretical analysis shows that out-of-phase conditions between fat and water signals lead to ADC overestimations. We performed demonstration experiments on fat–water phantoms and the breasts of 10 healthy female volunteers. In particular, we considered three out-of-phase conditions: First and second, short-time inversion recovery (STIR) fat suppression with incorrect inversion time and incorrect flip angle, respectively. Third, phase differences due to spectral fat saturation. The ADC values were assessed in regions of interest (ROIs) that included both water and residual fat signals. Results: In the phantoms and the volunteer data, ROIs containing both fat and water signals consistently exhibited lower ADC values under in-phase conditions and higher ADC values under out-of-phase conditions. Conclusions: We demonstrated that out-of-phase conditions can result in ADC overestimation in the presence of residual fat signals, potentially resulting in false-negative classifications where malignant lesions are misinterpreted as benign due to an elevated ADC. Out-of-phase fat and water signals might also reduce lesion conspicuity in high b-value images, potentially masking clinically relevant findings. Full article
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19 pages, 1071 KB  
Review
Behçet-like Syndromes: A Comprehensive Review
by Gaia Mancuso, Igor Salvadè, Adam Ogna, Brenno Balestra and Helmut Beltraminelli
Dermatopathology 2026, 13(1), 7; https://doi.org/10.3390/dermatopathology13010007 - 16 Jan 2026
Viewed by 250
Abstract
Background: Behçet-like syndrome (BLS) refers to the presence of Behçet’s disease (BD) features occurring in association with distinct clinical–pathological conditions such as inborn errors of immunity, myeloproliferative disorders, infections, or drug exposure. BLS may differ clinically from BD and is increasingly recognized as [...] Read more.
Background: Behçet-like syndrome (BLS) refers to the presence of Behçet’s disease (BD) features occurring in association with distinct clinical–pathological conditions such as inborn errors of immunity, myeloproliferative disorders, infections, or drug exposure. BLS may differ clinically from BD and is increasingly recognized as a separate entity. Distinguishing BLS from primary BD is essential for appropriate management, and studying BLS may provide insights into BD pathogenesis. Objectives: To summarize clinical features, treatments, and genetic abnormalities reported in BLS, we reviewed all published cases up to January 2024. Methods: A systematic search of PubMed, Scopus, and Embase was performed using the terms “Behçet-like syndrome”, “Behçet-like disease”, and “Pseudo-Behçet disease”. We included English-language reports of patients > 12 years old with a defined underlying etiology and Behçet-like manifestations, defined by ≥2 ICBD criteria and/or gastrointestinal involvement, mucosal ulcers, thrombosis, or non-recurrent disease. Epidemiological, clinical, laboratory, histological, and treatment data were extracted and analyzed descriptively. Results: Of 679 publications, 53 met inclusion criteria, comprising 100 patients with BLS. The median age was 44 years (IQR 22–52), with a female predominance (1:2). Fifty-three percent were from non-European countries. A genetic disorder was identified in 70% of cases, while HLA-B51 was present in 10%. Frequent manifestations included skin lesions (68%), fever (56%), intestinal involvement (43%), and joint symptoms (43%). Treatments included glucocorticoids (65%), conventional DMARDs (32%), and biologics (22%), mainly anti-TNF agents. Antiviral/antibiotic therapy was used in 9% and chemotherapy in 15%. Two patients with trisomy-8 MDS underwent allogeneic stem cell transplantation. Conclusions: Diverse conditions—including monogenic diseases, immune defects, myeloproliferative disorders, infections, and drug-related reactions—can produce Behçet-like features. Our findings highlight differences in clinical expression and treatment response across BLS etiologies. Recognizing BLS is essential for appropriate management and may contribute to a deeper understanding of BD pathogenesis and future targeted therapies. Full article
(This article belongs to the Section Clinico-Pathological Correlation in Dermatopathology)
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16 pages, 3840 KB  
Article
Resin Infiltration for Anterior Teeth Affected by Molar Incisor Hypomineralization in Children and Adolescents: A Clinical Study of Color Masking, Sensitivity, and Aesthetic Perception: A Prospective Single-Arm Interventional Clinical Study
by María Dolores Casaña-Ruiz, Mª Ángeles Vello-Ribes and Montserrat Catalá-Pizarro
Children 2026, 13(1), 131; https://doi.org/10.3390/children13010131 - 15 Jan 2026
Viewed by 192
Abstract
Background/objective: To evaluate the effectiveness of resin infiltration in managing anterior molar incisor hypomineralization (MIH) defects, focusing on color improvement, lesion size reduction, sensitivity outcomes and patient aesthetic perception. Enamel defects in MIH result from a combination of environmental, systemic, and genetic factors, [...] Read more.
Background/objective: To evaluate the effectiveness of resin infiltration in managing anterior molar incisor hypomineralization (MIH) defects, focusing on color improvement, lesion size reduction, sensitivity outcomes and patient aesthetic perception. Enamel defects in MIH result from a combination of environmental, systemic, and genetic factors, indicating a multifactorial etiology. These defects, particularly in anterior teeth, pose significant aesthetic and emotional challenges due to their high visibility. This study provides one of the few prospective clinical evaluations of resin infiltration for anterior MIH lesions, assessing not only objective clinical outcomes but also patients’ aesthetic perception. It further introduces a patient-centered approach by comparing aesthetic evaluations made by children and dental professionals over time. Methods: A total of 109 MIH-affected anterior teeth were treated using Icon® resin infiltration (DMG, Hamburg, Germany) in this registered prospective clinical study (ClinicalTrials.gov: NCT05597956). Participants were classified as children (6–12 years) and adolescents (13–17 years) according to standard pediatric age definitions. Of these, 101 teeth were available for evaluation at the 6-month follow-up due to patient loss to follow-up. The evaluation included photographic follow-up, measurement of lesion size and color, and assessment of sensitivity. During follow-up visits, patients rated the appearance of their lesions using the FDI scale. Results: Before treatment, spectrophotometric analysis showed that lesions exhibited a reddish hue (mean a* = 2.12), were distinctly yellowish (mean b* = 23.20), and clearly differed from surrounding enamel (ΔE = 8.62). The brightness level (L* = 69.81) indicated medium-high luminosity. Lesion size was reduced by an average of 4.5 percentage points. Significant increases in L values and reductions in a* and b* components were observed, with clinically perceptible ΔE changes. Sensitivity improved in 36.6% of patients, who reported a 1–2 point decrease on the SCASS. Moreover, patients’ aesthetic perception significantly improved after Icon® infiltration resin. Conclusions: Resin infiltration produced noticeable improvements in color, reduced lesion size and sensitivity, and enhanced aesthetic perception, making it a valuable treatment option for managing MIH-affected anterior teeth in children. Full article
(This article belongs to the Section Pediatric Dentistry & Oral Medicine)
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29 pages, 10725 KB  
Article
Temporal and Spatial Patterns of Glial Activation After Unilateral Cortical Injury in Rats
by Karen Kalhøj Rich, Simone Hjæresen, Marlene Storm Andersen, Louise Bjørnager Hansen, Ali Salh Mohammad, Nilukshi Gopinathan, Tobias Christian Mogensen, Åsa Fex Svenningsen and Mengliang Zhang
Life 2026, 16(1), 142; https://doi.org/10.3390/life16010142 - 15 Jan 2026
Viewed by 278
Abstract
Traumatic brain injury (TBI) often leads to long-lasting motor deficits, but the underlying cellular mechanisms still remain poorly understood. In this study, we examined glial and neuronal responses after focal cortical aspiration injury of the right hindlimb sensorimotor cortex in adult male rats. [...] Read more.
Traumatic brain injury (TBI) often leads to long-lasting motor deficits, but the underlying cellular mechanisms still remain poorly understood. In this study, we examined glial and neuronal responses after focal cortical aspiration injury of the right hindlimb sensorimotor cortex in adult male rats. This is a model we have previously shown induces persistent gait asymmetry and postural deficits. Immunohistochemical analysis of activated microglia/macrophages (CD11b, IBA-1), astrocytes (GFAP), and neurons (NeuN) was performed bilaterally in the peri-lesional cortex at 3, 7, 14, 21, and 28 days post-injury (n = 3–6 per time point). The injury induced an early, sharply localized increase in CD11b-positive myeloid cells in the injured hemisphere, suggesting an activation of both resident microglia and infiltrating monocyte-derived cell. This was followed by a more sustained IBA-1-positive microglial activation that gradually extended contralaterally. Astrocytic activation showed a delayed but prolonged profile, rising ipsilaterally within the first week, peaking around two weeks, and becoming bilaterally elevated by four weeks. Sham-operated animals showed only basal glial immunoreactivity without signs of hypertrophy or reactive morphology at any time point. NeuN immunoreactivity remained stable across timepoints, suggesting preservation of neuronal soma labeling without evidence of overt secondary neuronal loss. These findings reveal a staged and spatially distinct glial response to focal cortical injury, with early myeloid activation, prolonged microglial reactivity, and delayed bilateral astrogliosis. Together, these findings are consistent with the possibility that persistent motor deficits after focal TBI arise from both primary tissue loss within the lesion core and peri-lesional glial remodeling, highlighting glial–neuronal interactions as a potential therapeutic target. Full article
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21 pages, 4769 KB  
Article
Porphyromonas gingivalis Vesicles Control Osteoclast–Macrophage Lineage Fate
by Elizabeth Leon, Shin Nakamura, Satoru Shindo, Maria Rita Pastore, Tomoki Kumagai, Alireza Heidari, Elaheh Dalir Abdolahinia, Tomoya Ueda, Takumi Memida, Ana Duran-Pinedo, Jorge Frias-Lopez, Xiaozhe Han, Xin Chen, Shengyuan Huang, Guoqin Cao, Sunniva Ruiz, Jan Potempa and Toshihisa Kawai
Int. J. Mol. Sci. 2026, 27(2), 831; https://doi.org/10.3390/ijms27020831 - 14 Jan 2026
Viewed by 195
Abstract
Porphyromonas gingivalis (Pg), a keystone pathogen of chronic periodontitis, releases outer membrane vesicles (OMVs) that act as nanoscale vehicles to disseminate virulence factors within periodontal tissues and systemically beyond the oral cavity. Although Pg-OMVs are increasingly recognized as critical mediators [...] Read more.
Porphyromonas gingivalis (Pg), a keystone pathogen of chronic periodontitis, releases outer membrane vesicles (OMVs) that act as nanoscale vehicles to disseminate virulence factors within periodontal tissues and systemically beyond the oral cavity. Although Pg-OMVs are increasingly recognized as critical mediators of host–pathogen interactions, their effects on the differentiation and function of monocyte–macrophage/osteoclast lineage cells remain unclear. Here, we examined the impact of Pg-OMVs on the differentiation of RAW264.7 monocyte/macrophage-like cells into osteoclasts (OC) and/or macrophages (MΦ) in the presence of receptor activator of nuclear factor-κB ligand (RANKL). OMVs were isolated from Pg W83 and applied to RANKL-primed RAW264.7 cells using three distinct stimulation schedules: (1) simultaneous treatment with Pg-OMVs and RANKL at Day 0; (2) RANKL priming at Day 0 followed by Pg-OMV stimulation at Day 1; and (3) RANKL priming at Day 0 followed by Pg-OMV stimulation at Day 3. In all schedules, cells were cultured for 7 days from the initial RANKL exposure. Remarkably, simultaneous exposure to Pg-OMVs and RANKL (Schedule 1) markedly suppressed osteoclastogenesis (OC-genesis) while promoting M1 macrophage polarization. In contrast, delayed Pg-OMV stimulation of RANKL-primed cells (Schedules 2 and 3) significantly enhanced OC-genesis while reducing M1 polarization. These schedule-dependent effects were consistent with altered expression of osteoclastogenic markers, including dc-stamp, oc-stamp, nfatc1, and acp5. Importantly, a monoclonal antibody against OC-STAMP counteracted the Pg-OMV-induced upregulation of OC-genesis in Schedules 2 and 3. Furthermore, levels of Pg-OMV phagocytosis were inversely correlated with osteoclast formation. Finally, co-stimulation with RANKL and Pg-OMVs (Schedule 1) enhanced macrophage migratory capacity, whereas delayed stimulation with Pg-OMVs (Schedules 2 and 3) did not. Collectively, these findings indicate that Pg-OMVs exert stage-specific effects on the OC/MΦ lineage: stimulation at early stages of RANKL priming suppresses OC-genesis and promotes M1 polarization, whereas stimulation at later stages enhances OC-genesis without inducing M1 differentiation. Thus, Pg-OMVs may critically influence the fate of the OC/MΦ unit in periodontal lesions, contributing to disease progression and tissue destruction. Full article
(This article belongs to the Special Issue Molecular Biology of Periodontal Disease and Periodontal Pathogens)
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17 pages, 1662 KB  
Systematic Review
Laser-Based Photobiomodulation in Postoperative Tissue Healing in Oral and Maxillofacial Surgery: Systematic Review of RCTs
by Iwona Niedzielska, Grzegorz Dawiec, Rafał Wiench, Małgorzata Pihut, Dariusz Skaba and Josep Arnabat-Dominguez
J. Clin. Med. 2026, 15(2), 613; https://doi.org/10.3390/jcm15020613 - 12 Jan 2026
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Abstract
Background: Postoperative bone healing can be impaired by systemic factors and surgical trauma, leading to delayed recovery. Photobiomodulation therapy (PBMT) has been proposed as a non-invasive method to enhance osteogenesis, but variability in protocols and outcomes limits its clinical use. Aim: [...] Read more.
Background: Postoperative bone healing can be impaired by systemic factors and surgical trauma, leading to delayed recovery. Photobiomodulation therapy (PBMT) has been proposed as a non-invasive method to enhance osteogenesis, but variability in protocols and outcomes limits its clinical use. Aim: To systematically review and synthesize evidence from randomized controlled trials (RCTs) evaluating PBMT’s effectiveness in promoting postoperative osteogenesis. Methods: A systematic search of PubMed, Embase, Scopus, and Cochrane Library was conducted following the PRISMA 2020 guidelines. Only RCTs comparing PBMT with sham treatment or standard care were included. Data on laser parameters, surgical indications, and outcomes such as bone regeneration, healing time, and implant stability were extracted. The risk of bias of the included randomized studies was evaluated using the Cochrane Risk of Bias 2 (RoB version 2) tool. Results: Twelve RCTs were included. PBMT consistently improved early soft tissue healing and reduced postoperative inflammation and edema. Some studies showed accelerated bone maturation, especially in grafted sockets and distraction osteogenesis, while others reported no significant long-term effects on implant stability or chronic lesion healing. Heterogeneity in laser parameters limited comparability. Conclusions: PBMT is a safe adjunct that reliably enhances early postoperative healing and may promote bone remodeling in selected cases. Standardized protocols and larger, high-quality RCTs are needed to confirm long-term benefits and optimize treatment parameters. Full article
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
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14 pages, 1446 KB  
Systematic Review
Biomarkers for Predicting Malignant Transformation of Premalignant Lesions of the Larynx: A Systematic Review
by Juan P. Rodrigo, Reydson Alcides de Lima-Souza, Fernando López, Göran Stenman, Abbas Agaymy, Miquel Quer, Vinidh Paleri, Ilmo Leivo, Alfons Nadal, Nina Zidar, Fernanda V. Mariano, Henrik Hellquist, Nina Gale and Alfio Ferlito
Diagnostics 2026, 16(2), 236; https://doi.org/10.3390/diagnostics16020236 - 12 Jan 2026
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Abstract
Background/Objectives: Premalignant laryngeal lesions carry a variable risk of malignant transformation to squamous cell carcinoma. Identifying reliable biomarkers that predict malignant transformation could improve patient management and surveillance strategies. The objective of this work is to perform a systematic review of the [...] Read more.
Background/Objectives: Premalignant laryngeal lesions carry a variable risk of malignant transformation to squamous cell carcinoma. Identifying reliable biomarkers that predict malignant transformation could improve patient management and surveillance strategies. The objective of this work is to perform a systematic review of the literature on biomarkers that predict malignant transformation of premalignant laryngeal lesions. Methods: We conducted a systematic review following PRISMA 2020 guidelines. The PubMed, Scopus and Embase databases, and Google Scholar were searched for studies published between January 2011 and November 2025. Studies investigating biomarkers that predict malignant transformation of histopathologically confirmed premalignant laryngeal lesions were included. Risk of bias was assessed using the ROBINS-I tool. Results: From 166 initially identified records, 11 studies met the inclusion criteria, including 730 patients. These studies investigated diverse biomarker categories such as protein markers (cortactin, FAK, NANOG, SOX2, CSPG4), immune markers (tumor-infiltrating lymphocytes, immune gene signatures), microRNAs (miR-183-5p, miR-155-5p, miR-106b-3p), and genetic markers (chromosomal instability, PIK3CA amplification and mutations, FGFR3 mutations). Five studies provided adequate follow-up data on transformation outcomes. Most studies showed a moderate to serious risk of bias primarily due to limited confounder control and incomplete reporting. Conclusions: While several promising biomarker candidates have been identified, the evidence base remains limited due to small sample sizes, heterogeneous methodologies, and inadequate follow-up data. Cortactin/FAK protein expression and immune signatures are the most promising but require validation in larger, well-designed prospective cohorts. Full article
(This article belongs to the Special Issue Clinical Diagnosis of Otorhinolaryngology)
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15 pages, 6566 KB  
Case Report
Fatal H5N1 Highly Pathogenic Avian Influenza with Retrograde Neuroinvasion in a Free-Ranging Leopard Cat (Prionailurus bengalensis) During a Wild Bird Outbreak in South Korea
by So-Hee Gwon, Sang-Ik Park, Hyesung Jeong, Daehun Kim, Yaemoon Son, Min-a Lee, Kwanghee Lee, Young-Jae Si, Hyun-Jun Cho, Suwoong Lee, Hyeon Jeong Moon, Gun Lee, Jaewoo Choi, Chung-Do Lee, Jun-Gyu Park and Yeong-Bin Baek
Animals 2026, 16(2), 200; https://doi.org/10.3390/ani16020200 - 9 Jan 2026
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Abstract
Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses spread efficiently via migratory wild birds and increasingly infect mammals. The leopard cat (Prionailurus bengalensis) is an endangered mesopredator in South Korea that frequents wetland–forest ecotones and overlaps with wild waterbirds, placing [...] Read more.
Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses spread efficiently via migratory wild birds and increasingly infect mammals. The leopard cat (Prionailurus bengalensis) is an endangered mesopredator in South Korea that frequents wetland–forest ecotones and overlaps with wild waterbirds, placing it at risk of exposure. We describe a fatal HPAI H5N1 infection in a free-ranging leopard cat detected through national wildlife surveillance during a period of widespread H5N1 activity in wild birds along the East Asian–Australasian Flyway. The animal showed acute neurological and respiratory signs and died shortly after rescue. H5 viral RNA was detected by RT-qPCR in all examined tissues, with the highest load in the brain, and infectious virus was isolated from the brain, bronchoalveolar lavage fluid, and nasal swab. Pathology revealed acute serofibrinous pneumonia, severe nonsuppurative meningoencephalitis, necrotizing vasculitis with thrombosis, and necrotizing enteritis with secondary mesenteritis. Immunohistochemistry demonstrated abundant viral antigen in nasal and olfactory epithelium, olfactory bulb, neurons, endothelial cells, and bronchial and bronchiolar epithelium, supporting combined olfactory and hematogenous dissemination. This clinicopathological description expands the spectrum of HPAI-associated lesions in felids and underscores the value of wild carnivores as bioindicators of avian influenza spillover in a One Health context. Full article
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