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Nanotechnology in Endodontics and Prosthodontics: Current Advances and Future Perspectives
(Tehran University of Medical Sciences, 2026) Amini, Parviz; Jafari, Elahe; Abbasi-Asl, Masoumeh; Haghverdi, Fatemeh; Motiei, Mehrnaz
Nanotechnology has emerged as a transformative force in modern dentistry, offering unprecedented advancements in both endodontics and prosthodontics through the manipulation of materials at the nanoscale. This review synthesizes current knowledge on nanotechnology applications in these fields, evaluating their impact on treatment outcomes, material performance, and patient care while critically addressing associated challenges and future research directions. In endodontics, nanoparticles have revolutionized root canal therapy by enhancing disinfection efficacy through superior penetration into dentinal tubules, significantly reducing reinfection risks and improving antimicrobial action. Nanomaterial-enhanced sealers and obturating materials exhibit improved mechanical properties, including increased strength, fracture resistance, and adhesion, thereby extending treatment durability. Furthermore, nanotechnology facilitates pulp tissue regeneration via targeted drug delivery systems and scaffolds that support stem cell differentiation and tissue revitalization. In prosthodontics, nanomaterials have dramatically improved the aesthetic and functional quality of dental restorations by closely mimicking the natural optical and structural properties of teeth while enhancing mechanical strength, wear resistance, and longevity. The integration of nanoparticles into prosthodontic materials has also resulted in superior surface hardness, modulus of elasticity, and reduced polymerization shrinkage, alongside antibacterial properties and controlled therapeutic agent delivery that promote oral health and patient comfort. Despite these promising advancements, significant challenges remain, including concerns regarding long-term biocompatibility, cytotoxicity, systemic toxicity, and environmental impact of nanomaterials. The lack of standardized regulatory frameworks and comprehensive clinical safety data further complicates their widespread clinical adoption. Future research must prioritize rigorous preclinical and clinical investigations to establish robust safety profiles, develop application-specific regulatory guidelines, and advance innovative technologies such as smart stimuli-responsive materials, personalized nanotherapies, and nanorobotic interventions. Sustained interdisciplinary collaboration among researchers, clinicians, and regulatory authorities will be essential to fully harness the transformative potential of nanotechnology in dentistry while ensuring patient safety and improved therapeutic outcomes. © 2026 Tehran University of Medical Sciences. All rights reserved.
Cross-Species Generalization and Comparative Performance Analysis of Deep Neural Network Architectures in Histological Image Classification
(2026) Çelen, Kaan; Oltulu, Fatih; Çağlar, Buse; Buhur, Aylin; Kılıçarslan, Burak; Çolak, Burhan Berk; Yavaşoğlu, Altuğ
Histological image classification plays a critical role in biomedical research and diagnostic processes. Advances in the field of deep learning present significant opportunities for enhancing diagnostic accuracy and developing automated decision support systems. This study aims to comparatively evaluate the out-of-distribution generalization and cross-domain classification performance of different deep neural network encoders. In this study, models were trained on an internal dataset of 4307 hematoxylin and eosin (H&E) stained images of male rat lung, cerebellum, and adipose tissues, obtained under ethical committee approval (Ege University, HADYEK 2026-06). To evaluate genuine generalization, testing was conducted on a separate, diverse external cohort of 600 mixed human-and-animal images. Nine different deep learning architectures-MobileNetV3-S, MobileNetV3-L, DenseNet121, DenseNet201, ConvNeXt-S, ConvNeXt-B, DINOv3 ViT-S, DINOv3 ViT-H+, and the pathology foundation model UNI2-h-were evaluated using frozen feature extraction combined with a linear probe. For performance evaluation, accuracy, sensitivity, specificity, F1 score, Cohen's κ, and ROC-AUC metrics were analyzed along with per-image inference times. While all models achieved near-perfect results during internal cross-validation, their performance diverged significantly on the external dataset, confirming that the observed differences reflect genuine cross-domain generalization capabilities rather than under-fitting. All competitive models demonstrated high performance in classifying adipose and cerebellum tissues, achieving an F1 score of 95% or higher for these tissues. In distinguishing the lung tissue, which has the most diverse structure and is the most difficult to classify, the UNI2-h model emerged as the most successful, achieving an F1 score of 97.4% and a recall of 95.0%. When evaluated in terms of computational efficiency, the MobileNetV3-Small model stood out as having the lowest processing time among all scenarios, demonstrating an inferenc
Zafirlukast Exacerbates Behavioral Seizure Activity and Blood–Brain Barrier Disruption Despite Modestly Reducing Neuronal Injury Markers in a PTZ‑Induced Early Epileptogenesis Mouse Model
(Springer, 2026) Görgülü, Volkan; Tomruk, Cansın Şirin; Ergün, Pelin; Özdil, Berrin; Sancı, Ebru; Buhur, Aylin; Sözmen, Eser Y.; Köse, Timur; Yavaşoğlu, Nefise Ülkü Karabay; Yavaşoğlu, Altay
Epilepsy is one of the most prevalent neurological disorders worldwide, and approximately 25% of patients remain refractory to pharmacological treatment. Blood–brain barrier (BBB) disruption and reactive gliosis are key mechanisms implicated in early epileptogenesis. This study investigated the effects of zafirlukast, a leukotriene receptor antagonist, on BBB permeability, reactive gliosis, and behavioral seizure activity in a pentylenetetrazol (PTZ)-induced early epileptogenesis model in C57BL/6 mice. Zafirlukast was administered twice daily at a dose of 10 mg/kg. Seizure activity was evaluated by behavioral observation in terms of seizure severity, latency, duration, and frequency. BBB permeability was assessed using the Evans Blue assay, and brain tissues were analyzed by biochemical and immunohistochemical methods. The PTZ + ZAFIR group exhibited more severe seizures, characterized by increased seizure frequency and duration, shorter latency, and a higher kindling rate (80% vs. 27%). BBB permeability was also increased, whereas MMP-9 levels remained, suggesting disruption may be linked to direct mechanical effects of recurrent seizures rather than inflammation. Clues suggest that zafirlukast may exert paradoxical effects on two prominent cell types involved in reactive gliosis. While increased GFAP and TGF-β1 expression may reflect enhanced astrocyte activation, changes in IL-1β and Iba1 expression suggest suppression of microglial activation. Notably, pro-inflammatory and oxidative stress markers remained unchanged despite the increase in seizure severity. The observed reduction in neurodegeneration may be attributable to the suppressive effects of zafirlukast on microglial activation and the subsequent reduction in pro-inflammatory cytokine release. These findings indicate a complex role for leukotriene signaling during early epileptogenesis. Further studies using different doses, vehicles, and experimental models are warranted to clarify the effects of zafirlukast on the mechanisms underlying early epileptogenesis. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2026.
Assessing Metabolic and Reproductive Consequences of Prenatal Paracetamol Exposure in Female CD1 Mice
(Wiley, 2026) Entezari, Bita; Bozdağ, Deniz; İnce-Ergüç, Elif; Buhur, Aylin; Tomruk, Cansın Şirin; Sabuncuoğlu, Suna; Yavaşoğlu, Altuğ; Gürer, Orhan Hande
Paracetamol is a widely used analgesic during pregnancy; however, emerging evidence suggests it may act as an endocrine/ metabolism disrupting compound. Using an F1 female CD1 mouse model, this study scrutinized the long-term metabolic and reproductive consequences linked to intrauterine paracetamol exposure. Pregnant dams were administered paracetamol at three dose levels (Cmax/10, Cmax, and Cmax×10) during a critical window of organogenesis (gestational days 7.5–16.5). Offspring were monitored until 17weeks of age to assess growth, glucose homeostasis, lipidomic profiles, and ovarian histology. Prenatal exposure did not significantly affect total body weight but induced a dose-dependent increase in peritoneal adipose tissue mass, particularly in the Cmax×10 group. Metabolic assessments revealed impaired glucose tolerance in the Cmax/10 group and increased insulin sensitivity across all dose groups. Adipose tissue gene expression analysis demonstrated upregulation of adipogenic markers (Pparγ, Lpl, Fasn), while untargeted lipidomics revealed consistent dysregulation of lipid species, including lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs), sphingomyelins (SMs), and triacylglycerols (TGs), indicating altered lipid storage and inflammatory signaling. Histological evaluation showed a marked reduction in total follicle number and increased follicular atresia following paracetamol exposure. Degenerative changes in oocytes and granulosa cells were observed, and multi-oocyte follicles (MOFs) were detected exclusively in the Cmax/10. Collectively, these findings demonstrate that intrauterine paracetamol exposure induces persistent developmental reprogramming in female offspring, characterized by visceral adiposity, disrupted lipid homeostasis, and depletion of the ovarian reserve. Notably, several endpoints exhibited non-monotonic dose–response relationships, underscoring the sensitivity of developing systems to even subtherapeutic paracetamol exposure.
Effects of adjuvant propofol on antitumoral effects of carboplatin in experimental endometrial cancer: possible epigenetic associations
(2026) Gürel, Çevik; Kuşçu, Gökçe Ceren; Buhur, Aylin; Dizakar, Saadet Özen Akarca; Kara, Hale Güler; Özateş, Neslihan Pınar; Yıldırım, Nuri; Günüşen, İlkben
Endometrial cancer (EC) is a gynecological malignancy classified into two biologically distinct subtypes, Type I and Type II EC. The more aggressive Type II EC exhibits a poor response to conventional platinum-based chemotherapy. Propofol, an anesthetic agent in gynecologic surgery, has been reported to exert antitumor effects beyond anesthesia; however, its role as a chemoadjuvant in EC remains insufficiently explored. In this study, we investigated the effects of propofol combined with carboplatin on drug resistance- and metastasis-associated microRNAs and genes using in vitro and in vivo Type II EC model. Propofol treatment significantly reduced cancer cell viability and migratory capacity, while the combination treatment showed greater antimetastatic effects compared with carboplatin alone. In xenograft models, combination therapy resulted in a significant reduction in tumor volume and suggested reduced metastatic involvement in lung and liver tissues. Molecular analyses revealed downregulation of oncogenic microRNAs (miR-21, miR-135a) and upregulation of tumor-suppressive microRNAs (miR-34b, miR-98), accompanied by reduced mTOR, c-Myc, MRP7, and N-cadherin expression and increased PTEN and HMGB1 levels. Collectively, these findings indicate that propofol is associated with greater antitumor effects when combined with carboplatin, accompanied by changes in miRNA-gene expression patterns.
Spatial characterization of the phoenixin receptor in the lacrimal and major salivary glands
(2026) Gürler, Esra Bihter; Elmas, M.A.; Eyüpoğlu, I.P.; Arbak, S.; Çevik Aras, H.
Objective: To identify and characterize the expression of phoenixin receptor GPR173 (G protein-coupled receptor 173) in the rat lacrimal and major salivary glands (parotid, submandibular, and sublingual). GPR173 is associated with hormonal regulation and autoimmunity; however, its expression in exocrine glands has yet to be characterized. Design: Under anesthesia, eight Sprague Dawley rats underwent bilateral dissection of the lacrimal and major salivary glands. GPR173 expression was assessed using Western blotting and immunofluorescence. Immunoreactivity was quantified using ImageJ software and compared using the Friedman test with DunnBonferroni post hoc analysis. Results: GPR173 protein expression was found in all examined exocrine glands. In the major salivary glands, GPR173 was detected in both acinar and ductal cells, while expression was confined to acinar cells in the lacrimal gland. The submandibular and parotid glands showed significantly higher immunoreactivity than the lacrimal gland (p < .01 and p < .05, respectively). Ductal epithelium showed stronger immunopositivity compared to acinar epithelium. GPR173 immunoreactivity was also observed in periductal stromal tissue in major salivary glands. Conclusion: GPR173 expression was observed in both acinar and ductal cells of all major salivary glands, while in the lacrimal gland, it was restricted to the acinar cells. This differential localization suggests tissue-specific relevance.
A rare form of schwannomatosis on the volar surface of the hand and wrist: A case report
(Elsevier, 2024) Kıraç, Müge; Kara, Abbdullah Burak; Bulut, Halil İbrahim; Başdemir, Gülçin; Gümüş, Danyal; Özkan, Korhan
Background: Schwannomas, which are also known as neurilemomas, constitute the most common type of peripheral nerve tumors. These tumors can grow slowly and occur as painless swellings over the course of several years before their diagnosis. The aim of this report is to present a case of a very rare plexiform schwannoma originating from second digital nerve and multiple schwannomas from third and fourth digital nerves and palmar cutaneous branch of median nerve with emphasis given on differential diagnosis and treatment strategy. Case Presentation: A 15-year-old patient presented with soft tissue masses on the volar surface of the hand, initially diagnosed as benign nerve sheath tumors. Surgical excision was performed twice, preserving nerves and tendons. Recurrence occurred, and subsequent biopsy confirmed benign nerve sheath tumors. Microscopic examination revealed multinodular/plexiform schwannoma in the larger lesion and simple schwannomas in others, leading to a diagnosis of multiple schwannomatosis. All surgeries resulted in intact sensory and motor function. Conclusion: Surgical treatment can be curative and effectively employed for concomitant schwannoma tumors. Nevertheless, with careful planning and execution, surgery remains a promising option for patients with concomitant schwannomas. Further research and long-term follow-up studies are needed to fully understand the outcomes and refine the techniques used in these surgical treatments.
Post-transcriptional knockdown of BRCC3 via siRNA-loaded niosomes modulates autophagy and endoplasmic reticulum stress in rotenone-induced Parkinson's Disease model
(2026) Gürel, Çevik; Tut, Ezgi; Kuşçu, Gökçe Ceren; Buhur, Aylin; Germiyan, Özgün Selim; Leila Sabour-Takanlou; Maryam Sabour-Takanlou; Güler, Cem; Yavaşoğlu, Nefise Ülkü Karabay; Oltulu, Fatih; Yavaşoğlu, Altuğ
Parkinson's Disease (PD) is a prevalent neurodegenerative disorder. Recent studies implicate BRCA1-/BRCA2-containing complex 3 (BRCC3) in PD-related mechanisms such as ubiquitin-proteasome system dysfunction. This study aimed to evaluate the therapeutic potential of BRCC3 silencing via systemically administered siRNA-loaded niosomes in a rotenone-induced rat model of PD. Niosomes were synthesised by thin-film hydration, and three BRCC3-targeted siRNA sequences were tested in primary midbrain dopaminergic neurons. The most effective sequence, identified by Real-Time Quantitative PCR (RT-qPCR) and immunofluorescence, was used for in vivo studies. The PD model was induced in adult male rats (n = 24/group) by subcutaneous rotenone administration (2 mg/kg/day) for 35 days. In the in vivo phase of the study, behavioural, biochemical, in vivo imaging (IVIS), histological, and RT-qPCR analyses were performed. IVIS analysis confirmed brain accumulation of niosome-siRNA complexes within 3-5 h. Complementary analyses demonstrated that siRNA treatment significantly enhanced locomotor performance, restored redox homeostasis and dopamine levels, attenuated neuronal loss, upregulated autophagy-related proteins (↑LC3-II, ↑Beclin), suppressed endoplasmic reticulum stress markers (↓GRP78/Bip, ↓CHOP), elevated tyrosine hydroxylase expression, and reduced α-synuclein accumulation. In conclusion, siRNA-mediated suppression of BRCC3 via siRNA-loaded niosomes provides neuroprotection by modulating autophagy, ER stress, and antioxidant pathways, supporting BRCC3 as a promising therapeutic target for PD.
Endocrine and metabolism modulating effects of paracetamol: From in vitro signaling to in vivo metabolic reprogramming in male mice
(Elsevier, 2026) Entezari, Bita; Bozdağ, Deniz; Buhur, Aylin; Sabuncuoğlu, Suna; Yavaşoğlu, Altuğ; Orhan, Hande Gürer
Obesity is a major global health challenge associated with a cluster of comorbidities, including metabolic syndrome and type 2 diabetes, necessitating a deeper understanding of the environmental factors contributing to this epidemic. This study investigated the in vitro adipogenic/lipogenic potential of paracetamol and its in vivo endocrine and metabolic modulating effects following prenatal exposure. Using the 3T3-L1 preadipocyte model, cells were exposed to paracetamol at physiologically relevant concentrations. Results demonstrated that paracetamol promoted lipid accumulation and upregulated G3PDH activity. Furthermore, low concentrations significantly increased the protein expression of key adipogenic regulators (PPARγ, C/EBPα, LPL, and SREBP1), suggesting interference with transcriptional cascades governing adipogenesis and lipogenesis. To assess in vivo effects, pregnant CD1 mice were exposed to paracetamol at three human relevant doses (Cmax/10, Cmax, and Cmax×10). In male F1 offspring, prenatal exposure resulted in increased anogenital distance and a higher incidence of sperm morphological abnormalities, indicating reproductive developmental alterations despite unchanged circulating hormone levels. Metabolically, offspring exhibited dyslipidemia characterized by elevated serum triglycerides and total cholesterol. Although body weight and glucose tolerance remained unaffected, lipidomic profiling of epididymal adipose tissue revealed pronounced remodeling, including the accumulation of neutral lipids and altered membrane phospholipid composition. This was accompanied by the upregulation of the adipogenic genes Pparγ, Lpl, and Fasn in adipose tissue. Collectively, these findings suggest that paracetamol may act as an endocrine modulator and metabolic disruptor when exposed prenatally, inducing latent metabolic dysregulation that may predispose offspring to metabolic syndrome later in life, even in the absence of overt obesity
Automated deep learning detection of orthodontically induced external apical root resorption in maxillary incisors on panoramic radiographs
(2026) Özden, Samet; Kula, Betül; Tankuş, Mahmut
Objectives This study aimed to develop and compare two YOLOv12-based deep learning models—object detection and pose estimation—for the automatic classification of orthodontically induced external apical root resorption (OIEARR) using panoramic radiographs. Materials and methods A total of 624 panoramic radiographs obtained from 312 patients aged 10–18 who underwent at least 12 months of fixed orthodontic treatment were retrospectively analyzed. Each maxillary central and lateral incisor was graded for OIEARR severity on a 4-point scale (Grade 0 to Grade 3) by two experienced orthodontists serving as the ground truth. Two YOLOv12-based models were trained: an object detection (OD) model for regional analysis and a pose estimation (PE) model for anatomical landmark localization. Both models were trained and validated on annotated panoramic images and evaluated using accuracy, precision, recall, specificity, F1-score, confusion matrix, and ROC-AUC. Results The PE model outperformed the OD model across all evaluation metrics, demonstrating superior performance in detecting OIEARR. Specifically, the PE model achieved a weighted F1-score of 0.88, compared to 0.60 for the OD model. It also showed higher accuracy (0.93 vs. 0.78), precision (0.88 vs. 0.64), and recall (0.88 vs. 0.59), confirming its robustness in root resorption classification. Particularly in Grade 1 and Grade 2 resorption categories, the PE model demonstrated markedly superior classification performance (F1=0.85 and 0.88, respectively), while maintaining excellent detection in Grade 3 cases (F1=0.95). Confusion matrix analysis revealed that most misclassifications occurred between neighboring grades. ROC-AUC values for the PE model were consistently high (0.90–0.99), indicating strong discriminative ability across all resorption stages. Conclusions The YOLOv12x PE model offers a reliable and sensitive tool for detecting varying degrees of root resorption on panoramic radiographs. Its fine-grained anatomical localization capabilities provide an advantage for early diagnosis, making it a promising approach for clinical decision support in orthodontics.
CD44 Targeting of Cisplatin-Loaded Hyaluronic Acid-Modified Mesoporous Silica Nanoparticles for Lung Adenocarcinoma: Synthesis, Characterization, In Vitro and In Vivo Evaluation
(2026) Güler, Cem; Gelen, S. Sacide; Şancı, Ebru; Buhur, Aylin; Tıkır, H. Ece; Nalbantsoy, Ayşe; Güner, Adem; Medine, E. İlker; Yavaşoğlu, Altuğ; Odacı, Dilek; Yavaşoğlu, N. Ülkü Karabay
Background/Objectives: Cisplatin (CDDP) is widely used in the treatment of non-small cell lung cancer (NSCLC); however, its clinical efficacy is limited by severe systemic toxicity. Hyaluronic acid (HA) modification enables the targeting of CD44-overexpressing cancer cells, enhances biocompatibility, provides controlled drug release, and prolongs systemic circulation. This study aimed to develop high-molecular-weight hyaluronic acid-modified, cisplatin-loaded mesoporous silica nanoparticles (HA-MSN-CDDP) to selectively target CD44- overexpressing lung adenocarcinoma cells. Methods: HA-MSN-CDDP nanoparticles were synthesized via the sol–gel method and characterized by FTIR, DLS, SEM, and TEM methods. Antitumor efficacy was evaluated using both in vitro and in vivo xenograft lung cancer models in mice. Results: HA modification enabled controlled and sustained release of cisplatin from the HA-MSN-CDDP drug delivery system. Through HA-mediated receptor-dependent endocytosis, the nanoparticles exhibited enhanced cellular uptake and selective cytotoxicity toward CD44-positive cells. HA-MSN-CDDP significantly reduced the cytotoxic, genotoxic, and oxidative stress effects of free cisplatin on healthy cells while markedly enhancing apoptosis in A549-Luc-C8 cells. The system showed excellent hemocompatibility, supporting its potential for intravenous use. In vivo, HA-MSN-CDDP effectively suppressed tumor growth, mitigated lipid peroxidation, and preserved antioxidant enzyme activities (SOD and CAT) in major organs. Histological analyses confirmed reduced cisplatin-induced nephrotoxicity. Conclusions: HA-MSN-CDDP demonstrates strong potential as a targeted chemotherapeutic platform for NSCLC, combining high antitumor efficacy with reduced systemic toxicity
Mitochondrial Dynamics‑Related Gene Regulation by Epigenetic Suppression of GCN5 Exerts Neuroprotective Effects in Rotenone‑Induced Parkinson’s Disease Model
(2026) Kuşçu, Gökçe Ceren; Tut, Ezgi; Gürel, Çevik; Buhur, Aylin; Germiyan, Özgün Selim; Avcı, Çığır Biray; Güler, Cem; Şancı, Ebru; Yavaşoğlu, Nefise Ülkü Karabay; Yavaşoğlu, Altuğ
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuron loss and mitochondrial dysfunction. Recent studies implicate the histone acetyltransferase GCN5 in regulating mitochondrial homeostasis and oxidative stress. This study investigated the therapeutic potential of GCN5 silencing via systemically administered siRNA-loaded niosomes in a rotenone-induced rat model of PD. Niosomes were prepared using the thin-film hydration method, and the most effective siRNA sequence was selected through real time quantitative PCR (RT-qPCR) and immunofluorescence in primary mesencephalic neurons. Adult male rats were divided into four groups (n=24/group), and PD was induced with rotenone (2 mg/kg/day, s.c., for 35 days). Behavioral assessments, biochemical analyses, IVIS imaging, histopathology, immunohistochemistry, and RT-qPCR were conducted. IVIS confirmed brain accumulation of siRNA– niosomes within 3–5 h post-injection. GCN5 siRNA treatment significantly improved locomotor activity (p<0.05), decreased MDA levels (p<0.05), and restored SOD and dopamine levels (p<0.05). Molecular findings showed decreased GCN5 and mitochondrial fission-related gene Drp-1 expression, increased expression of mitophagy and biogenesis markers (↑Parkin, ↑PINK1, ↑Mfn2, ↑PGC-1α), elevated TH expression, and reduced α-synuclein accumulation. Histological analysis revealed preserved midbrain cytoarchitecture and reduced neuronal damage. In conclusion, these findings highlight that epigenetic silencing of GCN5 via siRNA-loaded niosomal delivery provides neuroprotection in PD by modulating the expression of genes involved in mitochondrial dynamics, offering preclinical support for its development as a novel therapeutic strategy.
Retrospective Evaluation of Synovial Chondromatosis with Histopathological and Clinical Features
(2025) Öz, Özden; Sezak, Murat; Doğanavşargil, Başak; Tamsel, İpek; Kaya, Hüseyin; Biçer, Elcil Kaya; Büyüktalancı, Emin; Başdemir, Gülçin
Objective: Synovial chondromatosis (SC) is a rare, benign condition characterized by the formation of nodular cartilage within the synovium of joints, bursae, or tendon sheaths. The condition typically presents as loose body-like nodules, which often exhibit calcification and ossification. SC primarily affects adults and most commonly involves large joints. Histologically, it is defined by synovium-lined cartilaginous nodules displaying varying degrees of peripheral cellularity. Due to overlapping features, SC may be misdiagnosed as a chondroid malignancy, particularly in limited biopsy specimens. Methods: We performed a retrospective review of cases diagnosed as SC in the Department of Pathology at Ege University Faculty of Medicine between 1986 and 2020. Archived materials were analyzed for epidemiological characteristics, clinical presentation, macroscopic and microscopic histopathological features, and imaging findings. Results: A total of 114 cases were identified, with a nearly equal gender distribution (male-to-female ratio: 0.95). The median age was 54±16.7 years (range: 18-86 years). The knee was the most affected site (56.14%, n=64), followed by the ankle (14.03%), hip (12.28%), wrist (9.64%), elbow (5.26%), and shoulder (2.63%). Histopathological reevaluation was performed on 62 cases. No correlation was found between histological features and patient age, gender, lesion location, or recurrence. Conclusion: Most cases involved the knee joint, although rarer sites such as the ankle were also observed. Notably, synovial lining over the nodules was not consistently present. Many nodules exhibited increased cellularity, nuclear pleomorphism, and hyperchromatism-features that can mimic low-grade chondrosarcoma. Histological and cytological features did not correlate with recurrence in our cohort.
Salvia argentea L. extract inhibits the production of NO, and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), alleviates the inflammatory response of LPS-induced macrophages cells, and reduces the CRP level on carrageenan-induced paw edema
(Springer Science and Business Media Deutschland GmbH, 2025) Alhamedi, Almonther; Demiroz Akbulut, Tugce; Baykan, Sura; Gümüştaş, Barış; Sanci, Ebru; Alsakini, Karrar Ali Mohammed Hasan; Nalbantsoy, Ayşe; Yavasoğlu, Altuğ; Karabay Yavasoğlu, N. Ülkü; Buhur, Aylin
Salvia argentea L. (Lamiaceae) is a medicinal plant originating from the Mediterranean region and has been used since ancient times for the treatment of various diseases. This study aimed to determine the phytochemical composition of S. argentea L. ethanol extract and to evaluate its in vitro and in vivo anti-inflammatory activity and its acute oral toxicity. The chemical constituents of the ethanol extract prepared from the aerial parts of the plant were identified using HPLC. The in vitro anti-inflammatory activity of the extract was evaluated in LPS-stimulated murine macrophage RAW 264.7 cells and the human monocytic cell line THP-1 by measuring the levels of nitric oxide (NO), pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). Acute toxicity of the extract was assessed in accordance with OECD guideline no 423. In vivo anti-inflammatory activity was evaluated based on the inhibition of 1% carrageenan-induced paw edema in rats. Serum CRP levels as an inflammatory marker, were measured via ELISA. Histological and immunohistochemical assessments were performed to identify tissue changes in the paw. HPLC profiling revealed that the extract contained rosmarinic acid (11.334 µg/mg dry extract), and salvigenin (2.74 µg/mg of dry extract) as major compounds. The extract significantly inhibited the production of NO, IL-1β, IL-6, and TNF-α without affecting cell viability. In vivo, the extract treatment exhibited a dose-dependent reduction in paw edema and serum CRP levels, along with notable histological improvements. Administration of the extract resulted in dose-dependent decreases of NF-κB expressions in the paw tissues. No signs of acute toxicity were observed (oral LD₅₀ > 2000 mg/kg). These findings suggest that S. argentea L. ethanol extract possesses significant anti-inflammatory potential supporting its possible development as a natural therapeutic agent for inflammatory disorders.
Anatomical Relationship of the Mylohyoid Ridge, Lingual Concavity, and Mandibular Canal: A Retrospective CBCT Study
(Multidisciplinary Digital Publishing Institute (MDPI), 2025) Girit, Melike Nur; Ansen, Gamze; Pence, Kadriye Betul; Yuzbasioglu, Neslihan; Şen, Selva
This study aimed to determine the position of the mylohyoid ridge (MR) and lingual concavity (LC) in the mandible and their relationship with the mandibular canal (MC) and submandibular fossa, to provide anatomical guidance for surgical procedures in this region. Methods: A retrospective analysis was performed on cone beam computed tomography (CBCT) scans from 200 adult patients who had undergone imaging for dental treatment. On cross-sectional images at the level between the first and second molar roots, the following measurements were obtained: LC horizontal depth, LC height, LC depth, MR height, MR depth, and the distances from MR to MC (MR–MC) and LC to MC (LC–MC). Results: Mean values were: LC horizontal depth: 3.72 ± 0.90 mm, LC height: 11.74 ± 2.01 mm, LC depth: 12.54 ± 3.03 mm, MR height: 17.66 ± 2.60 mm, MR depth: 6.87 ± 2.38 mm, MR-MC: 8.30 ± 2.00 mm, and LC-MC: 3.72 ± 0.87 mm. All parameters were symmetrical between the right and left sides of the mandible, with no significant sex differences. The positions of the MR and LC were related to each other, and the position of the MC was related to the positions of the LC and MR. There was no correlation between the horizontal depth of the LC and the position of the MR, LC and MC. Conclusions: The vertical positions of the MR and LC are related to each other and MC. Therefore, it can be used as a landmark in implant surgery.
Artificial intelligence solutions for temporomandibular joint disorders: Contributions and future potential of ChatGPT
(Korean J Orthod, 2025) Kula, Betül; Kula, Ahmet; Bagcier, Fatih; Alyanak, Bülent
Objective: This study aimed to evaluate the reliability and usefulness of information generated by Chat Generative Pre-Trained Transformer (ChatGPT) on temporomandibular joint disorders (TMD). Methods: We asked ChatGPT about the diseases specified in the TMD classification and scored the responses using Likert reliability and usefulness scales, the modified DISCERN (mDISCERN) scale, and the Global Quality Scale (GQS). Results: The highest Likert scores for both reliability and usefulness were for masticatory muscle disorders (mean ± standard deviation [SD]: 6.0 ± 0), and the lowest scores were for inflammatory disorders of the temporomandibular joint (mean ± SD: 4.3 ± 0.6 for reliability, 4.0 ± 0 for usefulness). The median Likert reliability score indicates that the responses are highly reliable. The median Likert usefulness score was 5 (4–6), indicating that the responses were moderately useful. A comparative analysis was performed, and no statistically significant differences were found in any subject for either reliability or usefulness (P = 0.083–1.000). The median mDISCERN score was 4 (3–5) for the two raters. A statistically significant difference was observed in the mean mDISCERN scores between the two raters (P = 0.046). The GQS scores indicated a moderate to high quality (mean ± SD: 3.8 ± 0.8 for rater 1, 4.0 ± 0.5 for rater 2). No statistically significant correlation was found between mDISCERN and GQS scores (r = –0.006, P = 0.980). Conclusions: Although ChatGPT-4 has significant potential, it can be used as an additional source of information regarding TMD for patients and clinicians.
Malaria in Turkey: A comprehensive analysis of diagnosis, treatment, and the impact of COVID-19, ten years after malaria elimination (2012-2023)
(Elsevier Inc., 2025) Şahin, Özgün Ekin; Kalay, Zeynepgül; Sarı, Nagehan Didem; Batırel, Ayşe; Ersöz, Gülden; Tuncer, Ertem Günay; Turunç, Tuba; Gözüküçük, Ramazan; Şimşek Çelener, Funda; Kantürk, Arzu; Süer, Kaya; Özer Balın, Şafak; Sağmak Tartar, Ayşe; Çelebi, Güven; Kuşoğlu, Hülya; Ateş, Selma; Alkan, Sevil; Mıstanoğlu Özatağ, Duru; Berk, Hande; Uzun, Cengiz; Karakoç, Çağla; Erdem, İlknur; Mumcu, Necati; Çölkesen, Fatma; Altunçekiç, Arzu; İnci, Ayşe; Yılmaz Karadağ, Fatma; Türkoğlu Yılmaz, Emine; Arslan, Mustafa; Şahin, Ahmet; Erdoğan, Haluk; Zorbozan, Orçun; Ertabaklar, Hatice; Ertan, Oğuz; Gücer, Lal Sude; Ergönül, Önder
Background: The characteristics, diagnosis, and treatment stages of malaria in Turkey in the last ten years are not known except few case reports. We aimed to describe the details of the diagnosis and treatment practices of malaria cases in various hospitals across Turkey between 2012 and 2023 after the declaration of the elimination of malaria. Methods: We collected the patient data from 30 centers by using Qualtrics Survey Software. The patients were categorized according to the WHO Malaria Severe Disease Symptoms guidelines. Results: We detected 299 malaria cases. Of these patients, 23.7% experienced misdiagnosis, with 77.5% of misdiagnosed cases receiving antibiotics. Among the patients, 9 (3%) had no travel history. Additionally, 28 (9.4%) patients required admission to the intensive care unit (ICU) during hospitalization. There is a significant association between misdiagnosis and subsequent ICU admissions. Additionally, the duration between malaria diagnosis and the initiation of treatment significantly affected ICU admissions. Furthermore, the number of cases with severe malaria (according to WHO criteria) and ICU admissions increased after the COVID-19 period. In multivariate analysis, initial misdiagnosis was found to be associated with ICU admission (OR: 2.8, p < 0.05), while each day's treatment delays post-diagnosis increased ICU admissions (OR: 1.26, p < 0.05). Conclusion: Misdiagnosis is common which delays the treatment and is correlated with higher admissions to ICUs. Post-COVID-19, there was a notable increase in both ICU admissions and cases of severe malaria, suggesting an escalation in disease severity that warrants further investigation. The resurgence of rare malaria cases with no travel history to abroad highlights the necessity of continued vigilance for new malaria cases. Efforts to promptly treat upon diagnosis and improve diagnostic accuracy in Turkey, where malaria is uncommon, are crucial. Enhancing diagnostic methods and treatment strategies remains essential, especially in significant events like COVID-19.
Functional changes in metabolic syndrome
(Metabolic Syndrome: A Comprehensive Update with New Insights, 2025) Gürler, Esra Bihter; Aras, Hülya Çevik; Bostanci, Nagihan
Metabolic Syndrome (MetS) is a condition characterized by the cooccurrence of several cardiovascular risk factors, including insulin resistance, obesity, dyslipidemia, and hypertension. The development of MetS is closely linked to visceral adiposity, which refers to fat accumulation around critical vital organs in the abdominal cavity. Visceral fat is metabolically active and produces adipokines, proteins that regulate energy balance and play a role in inflammation and atherosclerosis. Some adipokines, such as leptin and adiponectin, have beneficial effects on glucose homeostasis and are considered protective against MetS. However, other adipokines, such as visfatin and resistin, contribute to glucose intolerance and have pro-atherogenic properties. Visceral obesity also contributes to the development of MetS through its effects on blood pressure. It activates the sympathetic nervous system, the reninangiotensin-aldosterone system, and insulin resistance, leading to elevated blood pressure. Another critical factor in the development of MetS is the activation of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). LOX-1 is a protein that acts as a receptor for oxidized LDL on the cell surface. Its activation leads to the production of reactive oxygen species, a decrease in nitric oxide, and increased expression of molecules contributing to hypertension and vascular damage. LOX-1 is also involved in the development of other complications associated with MetS, such as nephropathy and left ventricular hypertrophy. The renin-angiotensin-aldosterone system (RAAS) regulates blood volume, electrolyte balance, and vascular resistance. In patients with MetS, the activation of RAAS leads to increased levels of angiotensin II (Ang II) and aldosterone, which have various effects on blood pressure and sodium and water retention. Ang II also contributes to oxidative stress and inflammation in the vasculature. Insulin resistance, a key feature of MetS, disrupts the insulin signaling process in adipose tissue, leading to increased lipolysis and elevated levels of circulating free fatty acids. These fatty acids further worsen insulin resistance and contribute to impaired glucose metabolism.Oxidative stress, characterized by an imbalance between the production of reactive oxygen species and the body's antioxidant defenses, is closely associated with the development of MetS. Hyperlipidemia and hyperglycemia, standard features of MetS, are linked to increased oxidative stress and ROS production. Oxidative stress and the activation of RAAS and LOX-1 contribute to the progression of dyslipidemia, type 2 diabetes, hypertension, and cardiovascular diseases. The oral-gut-liver axis is an emerging concept that suggests a relationship between oral infections, such as periodontitis, and metabolic dysfunction, including MetS and liver diseases. Periodontitis has been associated with chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD) and liver cirrhosis. The translocation of oral bacteria from the mouth to the gut may contribute to gut dysbiosis, increased intestinal permeability, and systemic inflammation, which can worsen liver functions. Overall, the development of MetS involves the interplay of various factors, including visceral obesity, adipokines, LOX-1 activation, insulin resistance, oxidative stress, and the oral-gut-liver axis. Understanding these mechanisms is crucial for preventing and managing MetS and its associated complications. Further research is needed to fully elucidate the roles of individual factors and develop targeted interventions for MetS.
The importance of hematological parameters in the prognosis of patients with severe COVID-19, A single-center retrospective study
(Wolters Kluwer Medknow Publications, 2023) Gözüküçük, Ramazan; Kılıç, Hasan Hüseyin; Uyanık, Bekir Sami; Çakıroğlu, Basri
Background: Inflammation biomarkers known as acute phase reactants (APRs) show significant variations in serum concentrations during inflammation brought on by both viral and noninfectious diseases. The erythrocyte sedimentation rate (ESR), the C-reactive protein (CRP), the lactate dehydrogenase (LDH), the ferritin, the fibrinogen, the procalcitonin, the D-dimer, and the troponin I are all significant APRs. During inflammation, the serum levels of each of these positive APRs rise. The sensitivity and specificity of hematologic parameters and indices are as high as the inflammatory biomarkers mentioned above for monitoring disease severity and treatment response. Aim: We aimed to evaluate the differences in hematological parameters and indices, and to reveal their treatment and prognostic values, especially in deceased patients with COVID-19. Materials and Methods: The hemogram parameters of 169 critical patients with COVID-19 (125 males and 44 females) who received inpatient treatment at horizontal ellipsis . between 1 March 2020 and 31 December 2021 were analyzed retrospectively. The patients were divided into two groups-deceased (77) and surviving (92)-noting demographic data such as age and gender. All analyses were performed using SPSS 25.0. Results: Analyses of the hematological parameters used during the treatment processes revealed statistically significant differences between the two patient groups. White blood cell (WBC), neutrophil, and neutrophil-to-lymphocyte ratio (NLR) values were significantly higher (P = 0.019, P = 0.000 and P = 0.000, respectively) for deceased subjects, while lymphocyte, platelet and plateletcrit (PCT) values were significantly lower (for all values, P = 0.000). Platelet volume (MPV) and platelet distribution width (PDW), as well as MPV/PLT, PDW/PLT, MPV/PCT, and PDW/PCT, levels were significantly higher in deceased subjects (P = 0.000). Particularly in our deceased cases, receiver operating characteristic analyses were performed to reveal the importance of such analyses in prognostic status evaluation in COVID-19 since the hematological parameters are quite different. Cut-off values were determined for each parameter, and sensitivity and specificity ratios were calculated. While the sensitivities of MPV/PLT, PDW/PLT, MPV/PCT, and PDW/PCT indices are over 80%, neutrophil and white blood cell sensitivities were found to be lower (74%, 68.8%, respectively). Conclusion: In addition to NLR, which is an important biomarker, the hematological indices MPV/PLT, PDW/PLT, MPV/PCT, and PDW/PCT can be used to determine the risk of death in patients with severe COVID-19.
Management of microcomplications of diabetes mellitus: Challenges, current trends, and future perspectives in treatment
(MDPI, 2024) Yapışlar, Hande; Gürler, Esra Bihter
Diabetes mellitus is a chronic metabolic disorder characterized by high blood sugar levels, which can lead to severe health issues if not managed effectively. Recent statistics indicate a significant global impact, with 463 million adults diagnosed worldwide and this projected to rise to 700 million by 2045. Type 1 diabetes is an autoimmune disorder where the immune system attacks pancreatic beta cells, reducing insulin production. Type 2 diabetes is primarily due to insulin resistance. Both types of diabetes are linked to severe microvascular and macrovascular complications if unmanaged. Microvascular complications, such as diabetic retinopathy, nephropathy, and neuropathy, result from damage to small blood vessels and can lead to organ and tissue dysfunction. Chronic hyperglycemia plays a central role in the onset of these complications, with prolonged high blood sugar levels causing extensive vascular damage. The emerging treatments and current research focus on various aspects, from insulin resistance to the intricate cellular damage induced by glucose toxicity. Understanding and intervening in these pathways are critical for developing effective treatments and managing diabetes long term. Furthermore, ongoing health initiatives, such as increasing awareness, encouraging early detection, and improving treatments, are in place to manage diabetes globally and mitigate its impact on health and society. These initiatives are a testament to the collective effort to combat this global health challenge.

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