Pub Date : 2024-05-03Epub Date: 2024-03-08DOI: 10.4274/balkanmedj.galenos.2024.2023-11-90
Mustafa Kemal Demir, Önder Ertem, Deniz Kılıç, Okan Akıncı, Özge Ecertaştan, Deniz Konya, Türker Kılıç
Functional or non-secretory ectopic pituitary neuroendocrine tumors (PitNET) can form around the sella turcica during the development of the adenohypophysis by differentiating and detaching from the pharyngeal roof. These tumors usually appear in the sphenoid sinus, clivus, cavernous sinus, infundibulum, and suprasellar cistern. Ectopic PitNETs typically display the characteristic magnetic resonance imaging findings of pituitary adenomas. However, preoperative diagnosis of PitNETs is usually challenging because of the variety of clinical and imaging presentations, locations, and sizes. Ectopic suprasellar PitNETs resemble mass lesions in the pituitary stalk. Ectopic cavernous sinus of PitNETs are typically microadenomas in the medial wall. Ectopic sphenoclival tumors are characterized by more aggressive tumor activity than the other ectopic PitNETs. Although ectopic PitNETs are exceedingly rare, they should be considered as a differential diagnosis for masses around the sella turcica. Treatment of the disease should be individualized and may include medical care, surgical resection, gamma-knife radiosurgery, and radiotherapy.
{"title":"Ectopic Pituitary Neuroendocrine Tumors/Adenomas Around the Sella Turcica","authors":"Mustafa Kemal Demir, Önder Ertem, Deniz Kılıç, Okan Akıncı, Özge Ecertaştan, Deniz Konya, Türker Kılıç","doi":"10.4274/balkanmedj.galenos.2024.2023-11-90","DOIUrl":"10.4274/balkanmedj.galenos.2024.2023-11-90","url":null,"abstract":"<p><p>Functional or non-secretory ectopic pituitary neuroendocrine tumors (PitNET) can form around the sella turcica during the development of the adenohypophysis by differentiating and detaching from the pharyngeal roof. These tumors usually appear in the sphenoid sinus, clivus, cavernous sinus, infundibulum, and suprasellar cistern. Ectopic PitNETs typically display the characteristic magnetic resonance imaging findings of pituitary adenomas. However, preoperative diagnosis of PitNETs is usually challenging because of the variety of clinical and imaging presentations, locations, and sizes. Ectopic suprasellar PitNETs resemble mass lesions in the pituitary stalk. Ectopic cavernous sinus of PitNETs are typically microadenomas in the medial wall. Ectopic sphenoclival tumors are characterized by more aggressive tumor activity than the other ectopic PitNETs. Although ectopic PitNETs are exceedingly rare, they should be considered as a differential diagnosis for masses around the sella turcica. Treatment of the disease should be individualized and may include medical care, surgical resection, gamma-knife radiosurgery, and radiotherapy.</p>","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":"167-173"},"PeriodicalIF":1.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03Epub Date: 2024-03-18DOI: 10.4274/balkanmedj.galenos.2024.2024-1-64
Angelina Borizanova, Elena Kinova, Plamen Getsov, Assen Goudev
{"title":"Giant Left Atrium in an Octogenarian with a Complex Etiology","authors":"Angelina Borizanova, Elena Kinova, Plamen Getsov, Assen Goudev","doi":"10.4274/balkanmedj.galenos.2024.2024-1-64","DOIUrl":"10.4274/balkanmedj.galenos.2024.2024-1-64","url":null,"abstract":"","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":"226-227"},"PeriodicalIF":1.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.4274/balkanmedj.galenos.2024.2024.060324
Ufuk Usta, Ebru Taştekin
{"title":"Present and Future of Artificial Intelligence in Pathology.","authors":"Ufuk Usta, Ebru Taştekin","doi":"10.4274/balkanmedj.galenos.2024.2024.060324","DOIUrl":"10.4274/balkanmedj.galenos.2024.2024.060324","url":null,"abstract":"","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":"41 3","pages":"157-158"},"PeriodicalIF":1.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Psoriasis is a chronic inflammatory skin disease that has no cure. While the specific cause of psoriasis is unknown, interactions between immune cells and inflammatory cytokines are believed to be important in its pathogenesis. Thymic stromal lymphopoietin (TSLP) is a cytokine produced by epithelial cells that profoundly affects dendritic cells (DCs) and is involved in allergy and inflammatory diseases. In some studies, its expression is higher in the skin of psoriasis patients, whereas it is increased in treated psoriasis patients when compared with untreated patients in others.
Aims: To investigate the role of TSLP in the pathogenesis of psoriasis.
Study design: In vitro and in vivo study.
Methods: To investigate the effect of TSLP on psoriasis in vivo, a mouse psoriasis model and shRNA targeting TSLP to reduce its expression were used. Mouse primary bone marrow dendritic cells (BMDCs) were cultured in vitro and used to investigate the signaling pathways activated by TSLP. Results: We found that reducing TSLP expression in psoriasis skin alleviated disease severity. TSLP activated the Janus kinase (JAK)/SYK pathway in psoriatic skin. In vitro studies with BMDCs demonstrated that TSLP increased DC maturation through the JAK/SYK pathway and activated DCs-secreted cytokines that stimulated CD4+ T cells to develop into T helper 17 (Th17) cells by activating STAT3 signaling. The JAK/SYK pathway inhibitor reduced the effect of TSLP on activating BMDCs and promoting Th17 differentiation by CD4+ T cells.
Conclusion: These findings indicated that TSLP exerted its immune-modulating effect in psoriasis through the JAK/SYK pathway.
{"title":"Thymic Stromal Lymphopoietin Activates Mouse Dendritic Cells Through the JAK/SYK Pathway in Promoting Th17 Response in Psoriasis.","authors":"Cuihao Song, Jie Sun, Zhenkai Zhao, Xu Zhang, Xiangyu Ding, Xiaoqiang Liang, Jia Bai, Liyuan Xing, Lingling Gong, Chengxin Li, Biwen Lin","doi":"10.4274/balkanmedj.galenos.2024.2024-1-96","DOIUrl":"10.4274/balkanmedj.galenos.2024.2024-1-96","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is a chronic inflammatory skin disease that has no cure. While the specific cause of psoriasis is unknown, interactions between immune cells and inflammatory cytokines are believed to be important in its pathogenesis. Thymic stromal lymphopoietin (TSLP) is a cytokine produced by epithelial cells that profoundly affects dendritic cells (DCs) and is involved in allergy and inflammatory diseases. In some studies, its expression is higher in the skin of psoriasis patients, whereas it is increased in treated psoriasis patients when compared with untreated patients in others.</p><p><strong>Aims: </strong>To investigate the role of TSLP in the pathogenesis of psoriasis.</p><p><strong>Study design: </strong>In vitro and in vivo study.</p><p><strong>Methods: </strong>To investigate the effect of TSLP on psoriasis in vivo, a mouse psoriasis model and shRNA targeting TSLP to reduce its expression were used. Mouse primary bone marrow dendritic cells (BMDCs) were cultured in vitro and used to investigate the signaling pathways activated by TSLP. Results: We found that reducing TSLP expression in psoriasis skin alleviated disease severity. TSLP activated the Janus kinase (JAK)/SYK pathway in psoriatic skin. In vitro studies with BMDCs demonstrated that TSLP increased DC maturation through the JAK/SYK pathway and activated DCs-secreted cytokines that stimulated CD4<sup>+</sup> T cells to develop into T helper 17 (Th17) cells by activating STAT3 signaling. The JAK/SYK pathway inhibitor reduced the effect of TSLP on activating BMDCs and promoting Th17 differentiation by CD4<sup>+</sup> T cells.</p><p><strong>Conclusion: </strong>These findings indicated that TSLP exerted its immune-modulating effect in psoriasis through the JAK/SYK pathway.</p>","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":"41 3","pages":"174-185"},"PeriodicalIF":1.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03Epub Date: 2024-01-29DOI: 10.4274/balkanmedj.galenos.2024.2023-11-133
Petros V. Vlastarakos, Alexandros Delides, Giorgos Sideris, Sotirios Tsiodras
{"title":"Spot Diagnosis for Suspected COVID-19 Cases: Is there a Place for a Traditional Weapon in Modern Combat?","authors":"Petros V. Vlastarakos, Alexandros Delides, Giorgos Sideris, Sotirios Tsiodras","doi":"10.4274/balkanmedj.galenos.2024.2023-11-133","DOIUrl":"10.4274/balkanmedj.galenos.2024.2023-11-133","url":null,"abstract":"","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":"228-229"},"PeriodicalIF":1.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139569774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.4274/balkanmedj.galenos.2024.2024-2-110
LéShon Peart, Mustafa Tekin
The Caribbean region has a diverse population of about 40 million people, spread over 13 sovereign states. This review aims to describe the existing studies on hereditary hearing loss (HL) in the Caribbean population. We systematically reviewed scientific articles on HL prevalence, genetic causes, technology use, and environmental effects in Caribbean nations and the Caribbean diaspora in the United States. Key findings show that HL rates, with diverse genetic variables, vary across Puerto Rico, Cuba, and the Dominican Republic. Local resources and technology have been used to diagnose HL, particularly in rural areas. Environmental factors tend to affect HL prevalence in various regions. This literature review of Caribbean-focused studies helps guide future research and healthcare strategies, particularly concerning genetic drift caused by migration to the United States. Understanding these factors can help diagnose and treat HL in America's diverse population.
{"title":"Genetic Landscape of Hearing Loss in the Caribbean: A Narrative Review.","authors":"LéShon Peart, Mustafa Tekin","doi":"10.4274/balkanmedj.galenos.2024.2024-2-110","DOIUrl":"10.4274/balkanmedj.galenos.2024.2024-2-110","url":null,"abstract":"<p><p>The Caribbean region has a diverse population of about 40 million people, spread over 13 sovereign states. This review aims to describe the existing studies on hereditary hearing loss (HL) in the Caribbean population. We systematically reviewed scientific articles on HL prevalence, genetic causes, technology use, and environmental effects in Caribbean nations and the Caribbean diaspora in the United States. Key findings show that HL rates, with diverse genetic variables, vary across Puerto Rico, Cuba, and the Dominican Republic. Local resources and technology have been used to diagnose HL, particularly in rural areas. Environmental factors tend to affect HL prevalence in various regions. This literature review of Caribbean-focused studies helps guide future research and healthcare strategies, particularly concerning genetic drift caused by migration to the United States. Understanding these factors can help diagnose and treat HL in America's diverse population.</p>","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":"41 3","pages":"161-166"},"PeriodicalIF":1.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The level of tumor-infiltrating lymphocytes (TILs) in human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (BC) is positively correlated with pathological complete response.
Aims: To investigate the relationship between ultrasound (US) and magnetic resonance imaging (MRI) features and the level of CD8-positive TILs (CD8+-TILs) in patients with HER2-positive BC.
Study design: Retrospective cohort study.
Methods: This retrospective study included 155 consecutive women with HER2-positive BC. Patients were divided into two groups: CD8+-TILlow (< 35%) and CD8+-TILhigh (≥ 35%) groups. US and MRI features were evaluated using the BI-RADS lexicon, and the apparent diffusion coefficient (ADC) value was calculated using RadiAnt software. Univariate and multivariate analyses revealed the optimal US and MRI features for predicting CD8+-TIL levels. Receiver operating characteristic analysis and the Delong test were used to compare the diagnostic performance of US and MRI features. Furthermore, implementing a nomogram will increase clinical utility.
Results: Univariate analysis of US features showed significant differences in shape, orientation, and posterior echo between the two groups; however, there were no significant differences in margins, internal echo, and microcalcification. Multifactorial analysis revealed that shape, orientation, and posterior echo were independent risk factors, with odds ratios of 11.62, 2.70, and 0.16, respectively. In terms of MRI features, ADC was an independent predictor of CD8+-TIL levels. These three US features and the ADC performed well, with area under the curve (AUC) values of 0.802 and 0.705, respectively. The combination of US and ADC values had higher predictive efficacy (AUC = 0.888) than either US or ADC alone (p = 0.009, US_ADC vs. US; p < 0.001, US_ADC vs. ADC).
Conclusion: US features (shape, orientation, and posterior echo) and ADC value may be a valuable tool for estimating CD8+-TIL levels in HER2-positive BC. The nomogram may help clinicians in making decisions.
背景:目的:研究HER2阳性乳腺癌(BC)患者的超声(US)和磁共振成像(MRI)特征与CD8阳性TILs(CD8+-TILs)水平之间的关系:研究设计:回顾性队列研究:这项回顾性研究包括155名HER2阳性BC女性患者。患者分为两组:CD8+-TIL低(< 35%)组和CD8+-TIL高(≥ 35%)组。使用 BI-RADS 词典评估 US 和 MRI 特征,并使用 RadiAnt 软件计算表观弥散系数(ADC)值。单变量和多变量分析显示了预测 CD8+-TIL 水平的最佳 US 和 MRI 特征。接收者操作特征分析和德隆检验用于比较 US 和 MRI 特征的诊断性能。此外,采用提名图将提高临床实用性:US特征的单变量分析显示,两组患者在形状、方向和后方回声方面存在显著差异;但在边缘、内部回声和微钙化方面没有显著差异。多因素分析显示,形状、方向和后方回声是独立的风险因素,几率比分别为 11.62、2.70 和 0.16。就磁共振成像特征而言,ADC是CD8+-TIL水平的独立预测因子。这三个 US 特征和 ADC 表现良好,曲线下面积 (AUC) 值分别为 0.802 和 0.705。与单独使用 US 或 ADC 相比,US 和 ADC 值的组合具有更高的预测效力(AUC = 0.888)(p = 0.009,US_ADC vs. US;p < 0.001,US_ADC vs. ADC):结论:US特征(形状、方向和后方回声)和ADC值可能是估计HER2阳性BC中CD8+-TIL水平的重要工具。该提名图可帮助临床医生做出决策。
{"title":"Radiological Features for Predicting the Status of CD8-Positive Lymphocytes in HER2 Positive Breast Cancer.","authors":"Yuhong Fan, Xiaoguang Li, Peng Zhong, Hong Guo, Dong Han, Wuguo Tian, Jingqin Fang","doi":"10.4274/balkanmedj.galenos.2024.2024-2-64","DOIUrl":"10.4274/balkanmedj.galenos.2024.2024-2-64","url":null,"abstract":"<p><strong>Background: </strong>The level of tumor-infiltrating lymphocytes (TILs) in human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (BC) is positively correlated with pathological complete response.</p><p><strong>Aims: </strong>To investigate the relationship between ultrasound (US) and magnetic resonance imaging (MRI) features and the level of CD8-positive TILs (CD8<sup>+</sup>-TILs) in patients with HER2-positive BC.</p><p><strong>Study design: </strong>Retrospective cohort study.</p><p><strong>Methods: </strong>This retrospective study included 155 consecutive women with HER2-positive BC. Patients were divided into two groups: CD8<sup>+</sup>-TIL<sub>low</sub> (< 35%) and CD8<sup>+</sup>-TIL<sub>high</sub> (≥ 35%) groups. US and MRI features were evaluated using the BI-RADS lexicon, and the apparent diffusion coefficient (ADC) value was calculated using RadiAnt software. Univariate and multivariate analyses revealed the optimal US and MRI features for predicting CD8<sup>+</sup>-TIL levels. Receiver operating characteristic analysis and the Delong test were used to compare the diagnostic performance of US and MRI features. Furthermore, implementing a nomogram will increase clinical utility.</p><p><strong>Results: </strong>Univariate analysis of US features showed significant differences in shape, orientation, and posterior echo between the two groups; however, there were no significant differences in margins, internal echo, and microcalcification. Multifactorial analysis revealed that shape, orientation, and posterior echo were independent risk factors, with odds ratios of 11.62, 2.70, and 0.16, respectively. In terms of MRI features, ADC was an independent predictor of CD8<sup>+</sup>-TIL levels. These three US features and the ADC performed well, with area under the curve (AUC) values of 0.802 and 0.705, respectively. The combination of US and ADC values had higher predictive efficacy (AUC = 0.888) than either US or ADC alone (<i>p</i> = 0.009, US_ADC vs. US; <i>p</i> < 0.001, US_ADC vs. ADC).</p><p><strong>Conclusion: </strong>US features (shape, orientation, and posterior echo) and ADC value may be a valuable tool for estimating CD8<sup>+</sup>-TIL levels in HER2-positive BC. The nomogram may help clinicians in making decisions.</p>","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":"41 3","pages":"213-221"},"PeriodicalIF":1.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03Epub Date: 2024-03-18DOI: 10.4274/balkanmedj.galenos.2024.2024-1-81
Vitorino Modesto Dos Santos, Lister Arruda Modesto Dos Santos
{"title":"Emphysematous Urinary Tract Infections in Diabetics","authors":"Vitorino Modesto Dos Santos, Lister Arruda Modesto Dos Santos","doi":"10.4274/balkanmedj.galenos.2024.2024-1-81","DOIUrl":"10.4274/balkanmedj.galenos.2024.2024-1-81","url":null,"abstract":"","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":"230-231"},"PeriodicalIF":1.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.4274/balkanmedj.galenos.2024.2024-1-60
Seda Yakut, Tuğçe Atcalı, Cüneyt Çaglayan, Aykut Ulucan, Fatih Mehmet Kandemir, Adem Kara, Turgut Anuk
Background: Paclitaxel (PAX) is a widely used chemotherapy drug for various cancer types but often induces significant toxicity in multiple organ systems. Silymarin (SIL), a natural flavonoid, has shown therapeutic potential due to its multiple benefits.
Aims: To evaluate the therapeutic efficacy of SIL in mitigating liver and kidney damage induced by PAX in rats, focusing on oxidative stress, inflammation, and apoptosis pathways.
Study design: Experimental animal model.
Methods: The study included 28 male Wistar rats aged 12-14 weeks weighing 270-300 g. The rats were divided into four groups: control, SIL, PAX, and PAX + SIL, with seven in each group. The rats received intraperitoneal (i.p.) injections at a dose of 2 mg per kilogram of body weight of PAX for 5 successive days, followed by oral gavage with 200 mg/kg body mass of SIL for 10 uninterrupted days. We examined the effect of SIL on specific serum biochemical parameters using an autoanalyzer and rat-specific kits. The spectrophotometric methods was used to investigate oxidative stress indicators in kidney and liver tissues. Aquaporin-2 (AQP-2), B-cell lymphoma-2 (Bcl-2), cysteine aspartate-specific protease-3 (caspase-3), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), and streptavidin-biotin staining were used to assess immunoreactivity in PAX-induced liver and kidney injury models.
Results: SIL treatment significantly reduced serum levels of alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and C-reactive protein, indicating its effectiveness in treating PAX-induced liver and kidney injury. SIL treatment significantly reduced oxidative stress by increasing essential antioxidant parameters, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione. It also reduced malondialdehyde levels in liver and kidney tissues of SIL-PAX groups (p < 0.05). SIL administration reduced NF-κB, caspase-3, and IL-6 expression while increasing Bcl-2 and AQP2 levels in liver and kidney tissues of rats treated with SIL and PAX (p < 0.05).
Conclusion: Our findings indicate the potential of SIL to alleviate PAX-induced liver and kidney damage in rats by reducing oxidative stress, inflammation, and apoptotic processes.
{"title":"Therapeutic Potential of Silymarin in Mitigating Paclitaxel-Induced Hepatotoxicity and Nephrotoxicity: Insights into Oxidative Stress, Inflammation, and Apoptosis in Rats.","authors":"Seda Yakut, Tuğçe Atcalı, Cüneyt Çaglayan, Aykut Ulucan, Fatih Mehmet Kandemir, Adem Kara, Turgut Anuk","doi":"10.4274/balkanmedj.galenos.2024.2024-1-60","DOIUrl":"10.4274/balkanmedj.galenos.2024.2024-1-60","url":null,"abstract":"<p><strong>Background: </strong>Paclitaxel (PAX) is a widely used chemotherapy drug for various cancer types but often induces significant toxicity in multiple organ systems. Silymarin (SIL), a natural flavonoid, has shown therapeutic potential due to its multiple benefits.</p><p><strong>Aims: </strong>To evaluate the therapeutic efficacy of SIL in mitigating liver and kidney damage induced by PAX in rats, focusing on oxidative stress, inflammation, and apoptosis pathways.</p><p><strong>Study design: </strong>Experimental animal model.</p><p><strong>Methods: </strong>The study included 28 male Wistar rats aged 12-14 weeks weighing 270-300 g. The rats were divided into four groups: control, SIL, PAX, and PAX + SIL, with seven in each group. The rats received intraperitoneal (i.p.) injections at a dose of 2 mg per kilogram of body weight of PAX for 5 successive days, followed by oral gavage with 200 mg/kg body mass of SIL for 10 uninterrupted days. We examined the effect of SIL on specific serum biochemical parameters using an autoanalyzer and rat-specific kits. The spectrophotometric methods was used to investigate oxidative stress indicators in kidney and liver tissues. Aquaporin-2 (AQP-2), B-cell lymphoma-2 (Bcl-2), cysteine aspartate-specific protease-3 (caspase-3), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), and streptavidin-biotin staining were used to assess immunoreactivity in PAX-induced liver and kidney injury models.</p><p><strong>Results: </strong>SIL treatment significantly reduced serum levels of alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and C-reactive protein, indicating its effectiveness in treating PAX-induced liver and kidney injury. SIL treatment significantly reduced oxidative stress by increasing essential antioxidant parameters, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione. It also reduced malondialdehyde levels in liver and kidney tissues of SIL-PAX groups (<i>p</i> < 0.05). SIL administration reduced NF-κB, caspase-3, and IL-6 expression while increasing Bcl-2 and AQP2 levels in liver and kidney tissues of rats treated with SIL and PAX (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>Our findings indicate the potential of SIL to alleviate PAX-induced liver and kidney damage in rats by reducing oxidative stress, inflammation, and apoptotic processes.</p>","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":"41 3","pages":"193-205"},"PeriodicalIF":1.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03Epub Date: 2024-03-11DOI: 10.4274/balkanmedj.galenos.2024.2024-1-73
Bilge Eren Yamasan, Selçuk Korkmaz
<p><strong>Background: </strong>The coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has urgently necessitated effective therapeutic solutions, with a focus on rapidly identifying and classifying potential small-molecule drugs. Given traditional methods’ labor-intensive and time-consuming nature, deep learning has emerged as an essential tool for efficiently processing and extracting insights from complex biological data.</p><p><strong>Aims: </strong>To utilize deep learning techniques, particularly deep neural networks (DNN) enhanced with the synthetic minority oversampling technique (SMOTE), to enhance the classification of binding activities in anti-SARS-CoV-2 molecules across various bioassays.</p><p><strong>Methods: </strong>We used 11 bioassay datasets covering various SARS-CoV-2 interactions and inhibitory mechanisms. These assays ranged from spike-ACE2 protein-protein interaction to ACE2 enzymatic activity and 3CL enzymatic activity. To address the prevalent class imbalance in these datasets, the SMOTE technique was employed to generate new samples for the minority class. In our model-building approach, we divided the dataset into 80% training and 20% test sets, reserving 10% of the training set for validation. Our approach involved employing a DNN that integrates ReLU and sigmoid activation functions, incorporates batch normalization, and uses Adam optimization. The hyperparameters and architecture of the DNN were optimized through various tests on layers, minibatch sizes, epoch sizes, and learning rates. A 40% dropout rate was incorporated to mitigate overfitting. For model evaluation, we computed performance metrics, such as balanced accuracy (BACC), precision, recall, F1 score, Matthews’ correlation coefficient (MCC), and area under the curve (AUC).</p><p><strong>Results: </strong>The performance of the DNN across 11 bioassay test sets revealed varying outcomes, significantly influenced by the ratios of active-to-inactive compounds. Assays, such as AlphaLISA and CoV-PPE, demonstrated robust performance across various metrics, including BACC, precision, recall, and AUC, when configured with more balanced ratios (1:3 and 1:1, respectively). This suggests the effective identification of active compounds in both cases. In contrast, assays with higher imbalance ratios, such as 3CL (1:38) and cytopathic effect (1:15), demonstrated higher recall but lower precision, highlighting challenges in accurately identifying active compounds among numerous inactive compounds. However, even in these challenging settings, the model achieved favorable BACC and recall scores. Overall, the DNN model generally performed well, as indicated by the BACC, MCC, and AUC values, especially when considering the degree of dataset imbalance in each assay.</p><p><strong>Conclusion: </strong>This study demonstrates the significant impact of deep learning, particularly DNN models enhanced with SMOTE, i
{"title":"Binding Activity Classification of Anti-SARS-CoV-2 Molecules using Deep Learning Across Multiple Assays","authors":"Bilge Eren Yamasan, Selçuk Korkmaz","doi":"10.4274/balkanmedj.galenos.2024.2024-1-73","DOIUrl":"10.4274/balkanmedj.galenos.2024.2024-1-73","url":null,"abstract":"<p><strong>Background: </strong>The coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has urgently necessitated effective therapeutic solutions, with a focus on rapidly identifying and classifying potential small-molecule drugs. Given traditional methods’ labor-intensive and time-consuming nature, deep learning has emerged as an essential tool for efficiently processing and extracting insights from complex biological data.</p><p><strong>Aims: </strong>To utilize deep learning techniques, particularly deep neural networks (DNN) enhanced with the synthetic minority oversampling technique (SMOTE), to enhance the classification of binding activities in anti-SARS-CoV-2 molecules across various bioassays.</p><p><strong>Methods: </strong>We used 11 bioassay datasets covering various SARS-CoV-2 interactions and inhibitory mechanisms. These assays ranged from spike-ACE2 protein-protein interaction to ACE2 enzymatic activity and 3CL enzymatic activity. To address the prevalent class imbalance in these datasets, the SMOTE technique was employed to generate new samples for the minority class. In our model-building approach, we divided the dataset into 80% training and 20% test sets, reserving 10% of the training set for validation. Our approach involved employing a DNN that integrates ReLU and sigmoid activation functions, incorporates batch normalization, and uses Adam optimization. The hyperparameters and architecture of the DNN were optimized through various tests on layers, minibatch sizes, epoch sizes, and learning rates. A 40% dropout rate was incorporated to mitigate overfitting. For model evaluation, we computed performance metrics, such as balanced accuracy (BACC), precision, recall, F1 score, Matthews’ correlation coefficient (MCC), and area under the curve (AUC).</p><p><strong>Results: </strong>The performance of the DNN across 11 bioassay test sets revealed varying outcomes, significantly influenced by the ratios of active-to-inactive compounds. Assays, such as AlphaLISA and CoV-PPE, demonstrated robust performance across various metrics, including BACC, precision, recall, and AUC, when configured with more balanced ratios (1:3 and 1:1, respectively). This suggests the effective identification of active compounds in both cases. In contrast, assays with higher imbalance ratios, such as 3CL (1:38) and cytopathic effect (1:15), demonstrated higher recall but lower precision, highlighting challenges in accurately identifying active compounds among numerous inactive compounds. However, even in these challenging settings, the model achieved favorable BACC and recall scores. Overall, the DNN model generally performed well, as indicated by the BACC, MCC, and AUC values, especially when considering the degree of dataset imbalance in each assay.</p><p><strong>Conclusion: </strong>This study demonstrates the significant impact of deep learning, particularly DNN models enhanced with SMOTE, i","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":"186-192"},"PeriodicalIF":1.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}