Background. The aim of the study was to analyse the effect of caffeic acid phenethyl ester (CAPE) on fluoxetine-induced hepatotoxicity in rats.Materials and Methods. Group I served as control. Group II received CAPE intraperitoneally. Group III received fluoxetine per orally. Group IV received fluoxetine and CAPE. The total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), and liver enzymes including paraoxonase-1 (PON-1), aspartate transaminase, and alanine transaminase levels were measured. Liver tissues were processed histopathologically for evaluation of liver injury and to validate the serum enzyme levels.Results. An increase in TOS and OSI and a decrease in TAC and PON-1 levels in serum and liver tissues of Group III were observed compared to Groups I and II. After treatment with CAPE, the level of TOS and OSI decreased while TAC and PON-1 increased in serum and liver in Group IV. Histopathological examination of the liver revealed hepatic injury after fluoxetine treatment and reduction of injury with CAPE treatment.Conclusion. Our results suggested that CAPE treatment provided protection against fluoxetine toxicity. Following CAPE treatment with fluoxetine-induced hepatotoxicity, TOS and OSI levels decreased, whereas PON-1 and TAC increased in the serum and liver.

Objectives: To determine the premalignancy and malignancy prevalence in patients diagnosed with endometrial polyps and to investigate factors affecting premalignancy and malignancy. Methods: In our retrospective study, patients who were diagnosed with endometrial polyp with endometrial samples and who underwent polypectomy by hysteroscopy or hysterectomy within one year were included. Results: Premalignant / malignant histopathological results were detected in 7 (2.8%) patients. There were no statistically significant differences in histopathological results and endometrial sampling indications between premenopausal and postmenopausal patients. Hysterectomy in patients with premalignant/ malignant results and hysteroscopy in patients with benign results were found to be significantly different. There was not a statistically significant difference between patients with benign results and those with premalignant/malignant results in menopausal status, symptoms, status of hormone replacement therapy and endometrial polyp size. Conclusion: The possibility of premalignant/ malignant results in patients diagnosed with endometrial polyps should be kept in mind. The menopausal status, symptoms, sizes of endometrial polyps and whether or not the patient is on hormone replacement therapy should be considered while making the management plan. However, these should not be the decisive factors on their own. Keywords: Endometrial polyp; premalignancy; malignancy; hysteroscopy; hysterectomy; endometrial sampling.

Purpose of Review: Malignant pleural mesothelioma (MPM) remains a rare but highly aggressive malignancy with limited treatment options and poor prognosis. For nearly twenty years, platinum–pemetrexed chemotherapy has persisted as the unchanged standard treatment; although recent progress in immunotherapy has modestly disrupted this therapeutic plateau, survival outcomes remain disappointingly limited. This review aims to provide a comprehensive overview of the epigenetic landscape of MPM, focusing particularly on the oncogenic and therapeutic implications of enhancer of zeste homolog 2 (EZH2), and to discuss its potential as a target for novel therapeutic strategies and combination regimens. Recent Findings: Epigenetic dysregulation has emerged as a central driver of mesothelioma pathogenesis. EZH2, the catalytic component of the polycomb repressive complex 2 (PRC2), mediates histone H3K27 trimethylation, silencing tumor suppressor genes and promoting malignant transformation. In addition to its canonical role, EZH2 has non-canonical oncogenic effects that modulate transcription, apoptosis, DNA repair, and immune evasion. High EZH2 expression correlates with BAP1 loss, which enhances chromatin remodeling defects and disease aggressiveness. Preclinical and early clinical data demonstrate that EZH2 inhibitors—including tazemetostat, valemetostat, GSK126, EPZ011989, tulmimetostat, and novel PROTAC-based degraders such as MS1943—can suppress tumor progression, modulate the tumor immune microenvironment, and restore therapeutic sensitivity. Furthermore, combination approaches integrating EZH2 inhibition with chemotherapy or immune checkpoint blockade show synergistic potential in overcoming resistance. Summary: EZH2 represents a pivotal epigenetic regulator and a promising therapeutic target in MPM. Further understanding the dual canonical and non-canonical roles of EZH2 in tumor biology will be key to optimizing targeted and combinatorial treatment strategies. Future research should focus on translating EZH2 inhibition into clinical benefit, identifying predictive biomarkers of response, and exploring rational combinations with chemotherapy, targeted drugs, or immunotherapy to improve survival outcomes in mesothelioma patients.

Amaç Yara iyileşmesi cerrahide yüksek morbiditeye neden olabilen ciddi bir problemdir. Yara iyileşmesini hızlandırmak, nekrozu veya iskemiyi önlemek için değişik farmakolojik ajanlar çalışılmış ve halen yaygın olarak çalışılmaya devam etmektedir. Yara iyileşmesinde klinik pratikte topikal dekspantenolün geniş kulanım alanları mevcuttur. Topikal dekspantenol hem yara bakımında hem de dermatolojik hastalıkların tedavisinde kullanılmaktadır. Bu çalışmamızda, ratlarda oluşturulan deneysel yara modelinde lokal sildenafil sitrat ve topikal dekspantenol uygulamalarının etkilerinin karşılaştırılması amaçlanmıştır. Gereç ve Yöntem Çalışmada 200–250 gram arasında değişen 30 Adet Wistar Albino dişi rat kullanıldı. Hayvanlar üç gruba ayrıldı. Deney hayvanlarının anestezisini takiben sırt orta kesimlerine 2 cm uzunluğunda tam kat kalınlıkta deri defekti oluşturuldu. Yara pansumanında tüm hayvanların yaraları steril % 0.9 NaCl solüsyonu ile yıkandıktan sonra kontrol grubu olduğu gibi bırakılırken, irigasyon sonrası 2. gruba %5’lik dekspantenol krem, 3. gruba % 10’luk sildenafil krem uygulandı. Ratlarda yara boyutları 3., 5., 7., 10., 14. ve 21. günlerde ölçülerek kaydedildi ve 21. gün tüm ratların sırt kısımlarından insizyon hattını içerecek şekilde tam kat deri çıkarılarak histolojik incelemeye alındı. Bulgular Tüm gruplara genel olarak bakıldığında günlere göre yara boyutlarındaki küçülme ve histopatolojik bulgular açısından istatiksel olarak anlamlı fark saptanmadı. Sonuç Sildenafil sitratın yara boyutunda önemli bir azalmaya yol açtığı için yara iyileşmesi için topikal bir krem olarak kullanılabileceğine inanıyoruz.

IgA nephropathy (IgAN) has diverse clinical presentations and responses to treatment. For systemic corticosteroids in particular, randomised controlled trials have reported conflicting effects, highlighting the need for individualised treatment strategies. In this retrospective cohort study, we derived and validated a causal machine learning (ML) framework to estimate individualised corticosteroid treatment effects in IgAN. Eight international cohorts, including the VALIGA, CureGN, and NURTuRE-CKD repositories, comprising 1022 patients, were analysed (derivation, n = 464; validation, n = 558). We integrated baseline clinical data, histopathological classification scores (MEST-C), and deep learning-based histomorphological biomarkers (pathomics) from digitised kidney biopsies. The framework estimated the effect of systemic corticosteroids on the composite endpoint of a ≥50% decline in estimated glomerular filtration rate or kidney failure within five years of biopsy. Across the overall study population, systemic corticosteroid therapy was not associated with a significant improvement in the composite outcome (p = 0·27). However, the causal ML framework revealed substantial treatment heterogeneity, identifying patients with high predicted benefit who achieved longer progression-free survival with corticosteroids (0·43 years, 95% CI 0·18-0·73, p < 0·01), while no benefit was observed in those with low predicted benefit (-0·005 years, 95% CI -0·3 to 0·22, p > 0·05). An individualised framework-guided treatment assignment was estimated to reduce systemic corticosteroid use by 60·7%. Pathomics facilitated the identification of interstitial inflammation and tubulitis as key features of corticosteroid response. This study demonstrates that a causal ML framework integrating clinical, histopathological, and pathomics predictors can individualise treatment assignments for systemic corticosteroids in IgAN. This approach provides a blueprint for precision therapy in IgAN, supporting AI-enhanced clinical decision-making in the era of emerging targeted treatments. German Research Foundation; European Research Council; German Federal Ministry of Education and Research; German Innovation Fund of the Federal Joint Committee; Clinician Scientist Program of the Faculty of Medicine RWTH Aachen University.