Jacek Gulczyński, Rosa H Gouveia, David Sunnucks, Vincenzo Canzonieri, Mateusz Michalski, Gabriella Nesi
Anatomical studies of the brain and successive analyses of this organ were performed in ancient times. Indeed, notes found in the Edwin Smith Papyrus mention that the Egyptians identified the meninges and gyri millennia ago. Their successors examined the content of the skull, examined it and illustrated it in greater detail. Alexandrians (Herophilus and Erasistratus) described the cerebral ventricles and blood circulation and supply to the brain. More accurate depictions emerged during the Renaissance with Leonardo da Vinci (1452-1519), Charles Estienne (1504-1564) and Andreas Vesalius (1514-1564), followed by Thomas Bartholin (1616-1680), Franciscus Sylvius (1614-1672) and later scholars. The present study focuses on neuroanatomy and is devoted to the study of nervous system structures by the eminent pathologist Rudolph Virchow. When reorganizing the procedure and reporting of the post-mortem examination, including a meticulous autopsy of the brain, neuropathology was a discipline yet to be developed. He pioneered a new approach to the autopsy and analysis of its results, aiming to benefit not only the patients but also clinicians and pathologists.
{"title":"How Rudolph Virchow changed the approach to autopsy of the brain.","authors":"Jacek Gulczyński, Rosa H Gouveia, David Sunnucks, Vincenzo Canzonieri, Mateusz Michalski, Gabriella Nesi","doi":"10.5114/fn.2025.154621","DOIUrl":"10.5114/fn.2025.154621","url":null,"abstract":"<p><p>Anatomical studies of the brain and successive analyses of this organ were performed in ancient times. Indeed, notes found in the Edwin Smith Papyrus mention that the Egyptians identified the meninges and gyri millennia ago. Their successors examined the content of the skull, examined it and illustrated it in greater detail. Alexandrians (Herophilus and Erasistratus) described the cerebral ventricles and blood circulation and supply to the brain. More accurate depictions emerged during the Renaissance with Leonardo da Vinci (1452-1519), Charles Estienne (1504-1564) and Andreas Vesalius (1514-1564), followed by Thomas Bartholin (1616-1680), Franciscus Sylvius (1614-1672) and later scholars. The present study focuses on neuroanatomy and is devoted to the study of nervous system structures by the eminent pathologist Rudolph Virchow. When reorganizing the procedure and reporting of the post-mortem examination, including a meticulous autopsy of the brain, neuropathology was a discipline yet to be developed. He pioneered a new approach to the autopsy and analysis of its results, aiming to benefit not only the patients but also clinicians and pathologists.</p>","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":"63 3","pages":"220-226"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145502957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: To determine the expression and clinical significance of maternal serum pregnancy-associated plasma protein A (PAPP-A) in pregnant women with different degrees of preeclampsia at 11-14 weeks of gestation.
Material and methods: The clinical data of 65 pregnant women with preeclampsia admitted to our hospital from January 2020 to October 2022 were retrospectively analysed. Another 45 normal pregnant women who came to our hospital for prenatal examination and delivery during the same period were selected as the healthy control group. The serum contents of PAPP-A, a-fetoprotein (AFP) and free estriol (uE3) in each group were compared. The correlation between PAPP-A and AFP as well as uE3 was analysed by Pearson analysis. The clinical value of serological indexes in diagnosing preeclampsia was analysed using ROC curve.
Results: The levels of PAPP-A and uE3 in pregnant women in the preeclampsia group were lower, while the contents of AFP were higher than these in the healthy control group ( p < 0.01). The pregnant women with severe preeclampsia had lower levels of PAPP-A and uE3 with higher levels of AFP compared to these with mild preeclampsia ( p < 0.001). Pearson correlation analysis showed that serum PAPP-A was negatively correlated with AFP (r = -0.246, p < 0.05) and positively correlated with uE3 (r = 0.398, p < 0.01) in preeclampsia patients. ROC curve analysis demonstrated that the area under the curve (AUC) of PAPP-A, AFP and uE3 to assist in the diagnosis of preeclampsia was 0.740, 0.738 and 0.806, respectively. The AUC of the combination of PAPP-A, AFP and uE3 to assist in the diagnosis was 0.912, with a sensitivity of 90.38% and a specificity of 80.33%. The clinical assisted diagnostic value of combined detection was high.
Conclusions: The serum level of PAPP-A in pregnant women with preeclampsia in the early pregnancy was significantly lower and related to the severity of the disease. The combination of routine detection for AFP and uE3 had a good predictive value for preeclampsia, which was helpful to take relevant interventions to reduce the incidence of preeclampsia as early as possible, and had a positive impact on protecting maternal and infant health.
{"title":"The early predictive value of maternal serum PAPP-A concentration at 11-14 weeks of pregnancy for preeclampsia.","authors":"Qing Wang, Weiping Zhang, Wushan Li, Chunmei Yu","doi":"10.5114/fn.2024.140447","DOIUrl":"10.5114/fn.2024.140447","url":null,"abstract":"<p><strong>Introduction: </strong>To determine the expression and clinical significance of maternal serum pregnancy-associated plasma protein A (PAPP-A) in pregnant women with different degrees of preeclampsia at 11-14 weeks of gestation.</p><p><strong>Material and methods: </strong>The clinical data of 65 pregnant women with preeclampsia admitted to our hospital from January 2020 to October 2022 were retrospectively analysed. Another 45 normal pregnant women who came to our hospital for prenatal examination and delivery during the same period were selected as the healthy control group. The serum contents of PAPP-A, a-fetoprotein (AFP) and free estriol (uE3) in each group were compared. The correlation between PAPP-A and AFP as well as uE3 was analysed by Pearson analysis. The clinical value of serological indexes in diagnosing preeclampsia was analysed using ROC curve.</p><p><strong>Results: </strong>The levels of PAPP-A and uE3 in pregnant women in the preeclampsia group were lower, while the contents of AFP were higher than these in the healthy control group ( p < 0.01). The pregnant women with severe preeclampsia had lower levels of PAPP-A and uE3 with higher levels of AFP compared to these with mild preeclampsia ( p < 0.001). Pearson correlation analysis showed that serum PAPP-A was negatively correlated with AFP (r = -0.246, p < 0.05) and positively correlated with uE3 (r = 0.398, p < 0.01) in preeclampsia patients. ROC curve analysis demonstrated that the area under the curve (AUC) of PAPP-A, AFP and uE3 to assist in the diagnosis of preeclampsia was 0.740, 0.738 and 0.806, respectively. The AUC of the combination of PAPP-A, AFP and uE3 to assist in the diagnosis was 0.912, with a sensitivity of 90.38% and a specificity of 80.33%. The clinical assisted diagnostic value of combined detection was high.</p><p><strong>Conclusions: </strong>The serum level of PAPP-A in pregnant women with preeclampsia in the early pregnancy was significantly lower and related to the severity of the disease. The combination of routine detection for AFP and uE3 had a good predictive value for preeclampsia, which was helpful to take relevant interventions to reduce the incidence of preeclampsia as early as possible, and had a positive impact on protecting maternal and infant health.</p>","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":" ","pages":"176-184"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Essential tremor (ET) is one of the most common neurological conditions and the most common movement disorder. The pathophysiological mechanisms that underlie this entity have not yet been described. However, recent post-mortem brain studies have provided useful insight into the underlying pathology of ET. Two brain areas have been consistently found to present neuropathological alterations in patients with ET: the brainstem, for presence of Lewy bodies or neuronal depletion, and the cerebellum, regarding Purkinje cells' morphology and density. In the present study we aim to review the literature on the main neuropathological findings in ET brains.
本质性震颤(ET)是最常见的神经系统疾病之一,也是最常见的运动障碍。这种疾病的病理生理机制尚未被描述清楚。不过,最近的脑部尸检研究为了解 ET 的基本病理提供了有用的信息。研究一致发现,ET 患者的两个脑区存在神经病理学改变:脑干(路易体或神经元耗竭)和小脑(浦肯野细胞的形态和密度)。本研究旨在回顾有关 ET 大脑主要神经病理学发现的文献。
{"title":"Neuropathological findings in essential tremor.","authors":"Ioannis Mavroudis, Foivos Petridis","doi":"10.5114/fn.2024.140569","DOIUrl":"10.5114/fn.2024.140569","url":null,"abstract":"<p><p>Essential tremor (ET) is one of the most common neurological conditions and the most common movement disorder. The pathophysiological mechanisms that underlie this entity have not yet been described. However, recent post-mortem brain studies have provided useful insight into the underlying pathology of ET. Two brain areas have been consistently found to present neuropathological alterations in patients with ET: the brainstem, for presence of Lewy bodies or neuronal depletion, and the cerebellum, regarding Purkinje cells' morphology and density. In the present study we aim to review the literature on the main neuropathological findings in ET brains.</p>","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":" ","pages":"11-18"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Malignant tumours diagnosed in the central nervous system are among the leading causes of death from cancer. Central nervous system tumours are the 10th most frequent cause of mortality due to cancer. Immunohistochemistry has become an important tool in the diagnosis of brain tumours. Brain tissue and meninges tumours comprise a heterogeneous group with diverse biological behaviour, treatment management, and different prognoses. Although conventional haematoxylin-eosin staining is crucial for diagnosis, diagnostic neuropathology has benefited from the inclusion of immunohistochemistry and recent advances in the field over the past 20 years. GFAP, S100, IDH, OLIG 2, EMA, ATRX, P53 and Ki67 are the most frequently used immunohistochemical markers globally, which we also highlighted in our study.
Material and methods: Ninety-seven cases including primary-metastatic intracranial tumours, operated on in the Neurosurgery Clinic and diagnosed in the Medical Pathology Laboratory between 2018 and 2023 years, were examined retrospectively from the archive. Haematoxylin-eosin slides were re-evaluated under the light microscope by 2 double-blind pathologists and immunohistochemical features and characteristics of tumours were examined. Data were analysed using the program SPSS 22. Differences were accepted as statistically significant at p < 0.05.
Results: According to the analysis of results, 46 (47.4%) of the 97 included patients were female and 51 (52.6%) were male. The most common tumour types were meningioma with 31 (32%) and high-grade neuroglial tumours with 31 (32%). GFAP, OLIG2, ATRX, and P53 values were found to be significantly higher in high-grade neuroglial tumours. While S 100 and EMA values were especially high in meningiomas, a positive correlation was found with IDH value in low-grade neuroglial tumours. The study showed that the median Ki67 value was significantly higher in high-grade neuroglial tumours and metastatic tumours.
Conclusions: Intracranial tumours cause significant morbidity and mortality in patients. Diagnostic, prognostic and predictive biomarkers evaluated in patient biopsy specimens and/or body fluids are important in neuropathological oncology. By regularly updating our biomarkers and following new treatment approaches, we can improve survival with rapid diagnosis and appropriate treatment in central nervous system tumours after surgery.
{"title":"Retrospective analysis and comparison of immunohistochemical features of surgically treated primary-metastatic brain tumours.","authors":"Sule Gokturk, Yasin Göktürk, Nihal Kaya, Arzu Erdem Taşdemir","doi":"10.5114/fn.2025.149487","DOIUrl":"https://doi.org/10.5114/fn.2025.149487","url":null,"abstract":"<p><strong>Introduction: </strong>Malignant tumours diagnosed in the central nervous system are among the leading causes of death from cancer. Central nervous system tumours are the 10th most frequent cause of mortality due to cancer. Immunohistochemistry has become an important tool in the diagnosis of brain tumours. Brain tissue and meninges tumours comprise a heterogeneous group with diverse biological behaviour, treatment management, and different prognoses. Although conventional haematoxylin-eosin staining is crucial for diagnosis, diagnostic neuropathology has benefited from the inclusion of immunohistochemistry and recent advances in the field over the past 20 years. GFAP, S100, IDH, OLIG 2, EMA, ATRX, P53 and Ki67 are the most frequently used immunohistochemical markers globally, which we also highlighted in our study.</p><p><strong>Material and methods: </strong>Ninety-seven cases including primary-metastatic intracranial tumours, operated on in the Neurosurgery Clinic and diagnosed in the Medical Pathology Laboratory between 2018 and 2023 years, were examined retrospectively from the archive. Haematoxylin-eosin slides were re-evaluated under the light microscope by 2 double-blind pathologists and immunohistochemical features and characteristics of tumours were examined. Data were analysed using the program SPSS 22. Differences were accepted as statistically significant at p < 0.05.</p><p><strong>Results: </strong>According to the analysis of results, 46 (47.4%) of the 97 included patients were female and 51 (52.6%) were male. The most common tumour types were meningioma with 31 (32%) and high-grade neuroglial tumours with 31 (32%). GFAP, OLIG2, ATRX, and P53 values were found to be significantly higher in high-grade neuroglial tumours. While S 100 and EMA values were especially high in meningiomas, a positive correlation was found with IDH value in low-grade neuroglial tumours. The study showed that the median Ki67 value was significantly higher in high-grade neuroglial tumours and metastatic tumours.</p><p><strong>Conclusions: </strong>Intracranial tumours cause significant morbidity and mortality in patients. Diagnostic, prognostic and predictive biomarkers evaluated in patient biopsy specimens and/or body fluids are important in neuropathological oncology. By regularly updating our biomarkers and following new treatment approaches, we can improve survival with rapid diagnosis and appropriate treatment in central nervous system tumours after surgery.</p>","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":"63 1","pages":"30-38"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qing Li, Zhenzhen Qu, Zhuofeng Mao, Lijing Jia, Qi Qiao, Yange Zhang, Kaiping Zhou, Liqin Che, Weiping Wang
Introduction: The nucleotide-binding domain leucine-rich repeat-containing family pyrin domain-containing 3 (NLRP3) inflammasome has been implicated in numerous neurological disorders, including epilepsy, through its role in inflammation and pyroptosis. Dihydromyricetin (DHM) has neuroprotective effects in patients with neurological disorders. However, the impact of DHM on the NLRP3 inflammasome pathway in epilepsy and related cognitive impairment is yet to be fully understood. Herein, we evaluated whether DHM can alleviate pilocarpine-induced neuronal injury and learning and memory disorders in the hippocampal body of rats by regulating the NLRP3 inflammasome.
Material and methods: An epileptic rat model was established, and spontaneous recurrent seizure (SRS) frequency and duration were recorded. The function of hippocampal pyramidal neurons was evaluated using Nissl staining. Western blotting, real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays were used to detect changes in NLRP3 inflammatory pathway-related factors in the hippocampus. Cognitive function was verified using the Morris water maze test, hippocampal late-phase long-term potentiation recording and associated synaptic protein expression assessment.
Results: Treatment with DHM after status epilepticus (SE) induction decreases the frequency and length of SRS in rats receiving pilocarpine, suggesting that DHM has the potential to improve long-term potentiation and cognitive deficits after SE induction in rats. Additionally, after inducing SE in rats, DHM raises the expression of synaptic proteins. It may prevent harm to hippocampal pyramidal neurons, and DHM-induced neuroprotection may contribute to the pyroptosis associated with NLRP3 in epileptic rats. DHM guards against harm to hippocampus pyramidal neurons.
Conclusions: We found that DHM plays a role in treating epilepsy and its comorbid cognitive impairment by inhibiting pyroptosis and inflammation.
{"title":"Dihydromyricetin mitigates epilepsy and cognitive impairment via NLRP3 inhibition in rats.","authors":"Qing Li, Zhenzhen Qu, Zhuofeng Mao, Lijing Jia, Qi Qiao, Yange Zhang, Kaiping Zhou, Liqin Che, Weiping Wang","doi":"10.5114/fn.2025.149520","DOIUrl":"https://doi.org/10.5114/fn.2025.149520","url":null,"abstract":"<p><strong>Introduction: </strong>The nucleotide-binding domain leucine-rich repeat-containing family pyrin domain-containing 3 (NLRP3) inflammasome has been implicated in numerous neurological disorders, including epilepsy, through its role in inflammation and pyroptosis. Dihydromyricetin (DHM) has neuroprotective effects in patients with neurological disorders. However, the impact of DHM on the NLRP3 inflammasome pathway in epilepsy and related cognitive impairment is yet to be fully understood. Herein, we evaluated whether DHM can alleviate pilocarpine-induced neuronal injury and learning and memory disorders in the hippocampal body of rats by regulating the NLRP3 inflammasome.</p><p><strong>Material and methods: </strong>An epileptic rat model was established, and spontaneous recurrent seizure (SRS) frequency and duration were recorded. The function of hippocampal pyramidal neurons was evaluated using Nissl staining. Western blotting, real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays were used to detect changes in NLRP3 inflammatory pathway-related factors in the hippocampus. Cognitive function was verified using the Morris water maze test, hippocampal late-phase long-term potentiation recording and associated synaptic protein expression assessment.</p><p><strong>Results: </strong>Treatment with DHM after status epilepticus (SE) induction decreases the frequency and length of SRS in rats receiving pilocarpine, suggesting that DHM has the potential to improve long-term potentiation and cognitive deficits after SE induction in rats. Additionally, after inducing SE in rats, DHM raises the expression of synaptic proteins. It may prevent harm to hippocampal pyramidal neurons, and DHM-induced neuroprotection may contribute to the pyroptosis associated with NLRP3 in epileptic rats. DHM guards against harm to hippocampus pyramidal neurons.</p><p><strong>Conclusions: </strong>We found that DHM plays a role in treating epilepsy and its comorbid cognitive impairment by inhibiting pyroptosis and inflammation.</p>","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":"63 1","pages":"51-66"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Autoimmune diseases (AID) such as multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory neuropathies, and some 100 other conditions, affect 5-10% of the global population, and their incidence is increasing, particularly in women. Among these, myasthenia gravis (MG) is a relatively rare but debilitating disease, which represents a prototype antibody-mediated autoimmune condition with well-studied pathogenesis. MG is a neuromuscular junction disorder marked clinically by fatigable muscle weakness and serologically by the presence of pathogenic autoantibodies. In MG pathological B- and T-cell subtypes are implicated, including memory B and plasma cells. In recent years there has been significant progress in the field of therapy, with several novel drugs introduced targeting major components of the pathogenetic pathway. However, there are still unmet needs in the treatment, especially the lack of a curative, upstream approach in contrast to the existing chronic downstream immunomodulatory actions. A nucleoside analog cladribine was primarily developed for the treatment of chronic leukaemias, in particular hairy cell leukaemia. For these indications, the injectable formulation of the drug was registered in 1997, and it has been manufactured in several countries since then. Later the oral formulation of cladribine (Mavenclad, Merck KGaA) was registered worldwide for use as immune reconstitution therapy (IRT) for relapsing multiple sclerosis. In this setting it has gained a strong position in the group of high-efficacy compounds, exerting long-term impact on the immune system. In a pilot clinical study, we found appreciable efficacy and safety profile of a short course of cladribine in MG. Herein, we present the design of a prospective, multicentre, randomised, controlled trial (RCT) using a parenteral preparation of cladribine in MG, currently ongoing in 6 clinical centres in Poland (EudraCT No. 2020-005762-34). In addition, we discuss the concept of immune reconstitution, which seems applicable for MG treatment.
{"title":"Immune reconstitution for the treatment of myasthenia gravis: the focus on cladribine.","authors":"Konrad Rejdak, Dariusz Baranowski, Paweł Grieb","doi":"10.5114/fn.2025.158395","DOIUrl":"https://doi.org/10.5114/fn.2025.158395","url":null,"abstract":"<p><p>Autoimmune diseases (AID) such as multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory neuropathies, and some 100 other conditions, affect 5-10% of the global population, and their incidence is increasing, particularly in women. Among these, myasthenia gravis (MG) is a relatively rare but debilitating disease, which represents a prototype antibody-mediated autoimmune condition with well-studied pathogenesis. MG is a neuromuscular junction disorder marked clinically by fatigable muscle weakness and serologically by the presence of pathogenic autoantibodies. In MG pathological B- and T-cell subtypes are implicated, including memory B and plasma cells. In recent years there has been significant progress in the field of therapy, with several novel drugs introduced targeting major components of the pathogenetic pathway. However, there are still unmet needs in the treatment, especially the lack of a curative, upstream approach in contrast to the existing chronic downstream immunomodulatory actions. A nucleoside analog cladribine was primarily developed for the treatment of chronic leukaemias, in particular hairy cell leukaemia. For these indications, the injectable formulation of the drug was registered in 1997, and it has been manufactured in several countries since then. Later the oral formulation of cladribine (Mavenclad, Merck KGaA) was registered worldwide for use as immune reconstitution therapy (IRT) for relapsing multiple sclerosis. In this setting it has gained a strong position in the group of high-efficacy compounds, exerting long-term impact on the immune system. In a pilot clinical study, we found appreciable efficacy and safety profile of a short course of cladribine in MG. Herein, we present the design of a prospective, multicentre, randomised, controlled trial (RCT) using a parenteral preparation of cladribine in MG, currently ongoing in 6 clinical centres in Poland (EudraCT No. 2020-005762-34). In addition, we discuss the concept of immune reconstitution, which seems applicable for MG treatment.</p>","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":"63 4","pages":"327-334"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146200684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Beata Dąbrowska-Bouta, Grzegorz Sulkowski, Małgorzata Frontczak-Baniewicz, Dorota Sulejczak, Lidia Strużyńska
Polychlorinated biphenyls (PCBs) and brominated flame retardants (BFRs) are dominant environmental and food contaminants. Tetrabromobisphenol A (TBBPA) is the most widely used BFR in the world to improve the fire safety of laminates in electrical and electronic equipment. Aroclor 1254, one of the PCBs, is widely distributed in the environment due to its extensive use in industrial applications around the world. Both groups of substances are potent toxicants. There is also increasing evidence that they have neurotoxic effects. In this study we tested the pro-inflammatory effects of Aroclor 1254 and TBBPA based on markers of microglial reactivity and levels of pro-inflammatory factors in the brain of immature rats. Aroclor 1254 or TBBPA were administered to the rats by oral gavage for two weeks at a dose of 10 mg/kg b.w. Both light and electron microscopy studies revealed features indicative of microglia activation in brains of exposed rats. Morphological changes were associated with overexpression of pro-inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Analysis of cytokine/chemokine array revealed significant secretion of inflammatory mediators following exposure to both TBBPA and Aroclor 1254, which was stronger in the cerebellum than in the forebrain of exposed immature rats. The results indicate a pro-inflammatory profile of microglia activation as one of the neurotoxic mechanisms of both examined toxicants.
{"title":"Proinflammatory microglial response is a common mechanism of Aroclor 1254- and Tetrabromobisphenol-A-induced neurotoxicity in immature chronically exposed rats","authors":"Beata Dąbrowska-Bouta, Grzegorz Sulkowski, Małgorzata Frontczak-Baniewicz, Dorota Sulejczak, Lidia Strużyńska","doi":"10.5114/fn.2023.133796","DOIUrl":"https://doi.org/10.5114/fn.2023.133796","url":null,"abstract":"Polychlorinated biphenyls (PCBs) and brominated flame retardants (BFRs) are dominant environmental and food contaminants. Tetrabromobisphenol A (TBBPA) is the most widely used BFR in the world to improve the fire safety of laminates in electrical and electronic equipment. Aroclor 1254, one of the PCBs, is widely distributed in the environment due to its extensive use in industrial applications around the world. Both groups of substances are potent toxicants. There is also increasing evidence that they have neurotoxic effects. In this study we tested the pro-inflammatory effects of Aroclor 1254 and TBBPA based on markers of microglial reactivity and levels of pro-inflammatory factors in the brain of immature rats. Aroclor 1254 or TBBPA were administered to the rats by oral gavage for two weeks at a dose of 10 mg/kg b.w. Both light and electron microscopy studies revealed features indicative of microglia activation in brains of exposed rats. Morphological changes were associated with overexpression of pro-inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Analysis of cytokine/chemokine array revealed significant secretion of inflammatory mediators following exposure to both TBBPA and Aroclor 1254, which was stronger in the cerebellum than in the forebrain of exposed immature rats. The results indicate a pro-inflammatory profile of microglia activation as one of the neurotoxic mechanisms of both examined toxicants.","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":"58 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140564772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zuzanna Kuczynska, Pawan Kumar Neglur, Erkan Metin, Michal Liput, Marzena Zychowicz, Valery Zayat, Natalia E. Krześniak, Leonora Buzanska, Marta Kot
Human induced pluripotent stem cells (hiPSCs) are a potential source of somatic cells for cell therapies due to their ability to self-renew and differentiate into various cells of the body. To date, the clinical application of hiPSCs has been limited due to safety issues. The present study aims to standardize the safety procedure of the derivation of GMP-compliant induced pluripotent stem cell (iPSC) lines from human fibroblasts. The hiPSC lines were generated using the nonintegrative Sendai virus method to incorporate Yamanaka reprogramming factors (OCT3/4, SOX2, KLF4 and c-MYC) into cells. A constant temperature was maintained during the cell culture, including all stages of the culture after transduction with Sendai virus. Pluripotency was proved in six independently generated hiPSC lines from adult female (47 years old) and male (57 years old) donors’ derived fibroblasts via alkaline phosphatase live (ALP) staining, qPCR, and immunocytochemistry. The hiPSC lines showed a gradual decrease in the presence of the virus with each subsequent passage, and this reduction was specific to the hiPSC line. The frequency and probability of chromosomal aberrations in hiPSCs were dependent on both the iPSC clone identity and sex of the donor. In summary, the generation of hiPSC for clinical applications requires safety standards application (biosafety protocol, quality control of hiPSC lines, viral and genetic integrity screening) from the first stages of the clonal selection of hiPSC from the same donor.
{"title":"Safety of GMP-compliant iPSC lines generated by Sendai virus transduction is dependent upon clone identity and sex of the donor","authors":"Zuzanna Kuczynska, Pawan Kumar Neglur, Erkan Metin, Michal Liput, Marzena Zychowicz, Valery Zayat, Natalia E. Krześniak, Leonora Buzanska, Marta Kot","doi":"10.5114/fn.2024.134026","DOIUrl":"https://doi.org/10.5114/fn.2024.134026","url":null,"abstract":"Human induced pluripotent stem cells (hiPSCs) are a potential source of somatic cells for cell therapies due to their ability to self-renew and differentiate into various cells of the body. To date, the clinical application of hiPSCs has been limited due to safety issues. The present study aims to standardize the safety procedure of the derivation of GMP-compliant induced pluripotent stem cell (iPSC) lines from human fibroblasts. The hiPSC lines were generated using the nonintegrative Sendai virus method to incorporate Yamanaka reprogramming factors (OCT3/4, SOX2, KLF4 and c-MYC) into cells. A constant temperature was maintained during the cell culture, including all stages of the culture after transduction with Sendai virus. Pluripotency was proved in six independently generated hiPSC lines from adult female (47 years old) and male (57 years old) donors’ derived fibroblasts via alkaline phosphatase live (ALP) staining, qPCR, and immunocytochemistry. The hiPSC lines showed a gradual decrease in the presence of the virus with each subsequent passage, and this reduction was specific to the hiPSC line. The frequency and probability of chromosomal aberrations in hiPSCs were dependent on both the iPSC clone identity and sex of the donor. In summary, the generation of hiPSC for clinical applications requires safety standards application (biosafety protocol, quality control of hiPSC lines, viral and genetic integrity screening) from the first stages of the clonal selection of hiPSC from the same donor.","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":"7 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140564913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Barbara Bobek-Billewicz, Sylwia Heinze, Krzysztof Majchrzak, Patrycja Mazgaj, Anna Hebda
The accurate diagnosis of brain tumour is very important in modern neuro-oncology medicine. Magnetic resonance spectroscopy (MRS) is supposed to be a promising tool for detecting cancerous lesions. However, the interpretation of MRS data is complicated by the fact that not all cancerous lesions exhibit elevated choline (Cho) levels. The main goal of our study was to investigate the lack of Cholesion/Choref elevation in the population of grade II-III gliomas.
89 cases of gliomas grade II and III were used for the retrospective analysis – glioma (astrocytoma or oligodendroglioma) grade II (74 out of 89 cases [83%]) and III (15 out of 89 cases [17%]) underwent conventional MRI extended by MRS before treatment. Histopathological diagnosis was obtained either by biopsy or surgical resection. Gliomas were classified to the group of no-choline elevation when the ratio of choline measured within the tumour (Cholesion) to choline from NABT (Choref) were equal to or lower than 1. Significant differences were observed between ratios of Cholesion/Crlesion calculated for no-choline elevation and glial tumour groups as well as in the NAAlesion/Crlesion ratio between the no-choline elevation group and glial tumour group. With consistent data concerning choline level elevation and slightly lower NAA value, the Cholesion/NAAlesion ratio is significantly higher in the WHO II glial tumour group compared to the no-choline elevation cases (p < 0.000).
In the current study the results demonstrated possibility of lack of choline elevation in patients with grade II-III gliomas, so it is important to remember that the lack of elevated choline levels does not exclude neoplastic lesion.
{"title":"The diagnostic challenge of lack of choline level elevation on 1H-MR spectroscopy in grade II-III gliomas","authors":"Barbara Bobek-Billewicz, Sylwia Heinze, Krzysztof Majchrzak, Patrycja Mazgaj, Anna Hebda","doi":"10.5114/fn.2024.136469","DOIUrl":"https://doi.org/10.5114/fn.2024.136469","url":null,"abstract":"The accurate diagnosis of brain tumour is very important in modern neuro-oncology medicine. Magnetic resonance spectroscopy (MRS) is supposed to be a promising tool for detecting cancerous lesions. However, the interpretation of MRS data is complicated by the fact that not all cancerous lesions exhibit elevated choline (Cho) levels. The main goal of our study was to investigate the lack of Cho<sub>lesion</sub>/Cho<sub>ref</sub> elevation in the population of grade II-III gliomas. <br/><br/> 89 cases of gliomas grade II and III were used for the retrospective analysis – glioma (astrocytoma or oligodendroglioma) grade II (74 out of 89 cases [83%]) and III (15 out of 89 cases [17%]) underwent conventional MRI extended by MRS before treatment. Histopathological diagnosis was obtained either by biopsy or surgical resection. Gliomas were classified to the group of no-choline elevation when the ratio of choline measured within the tumour (Cho<sub>lesion</sub>) to choline from NABT (Cho<sub>ref</sub>) were equal to or lower than 1. Significant differences were observed between ratios of Cho<sub>lesion</sub>/Cr<sub>lesion</sub> calculated for no-choline elevation and glial tumour groups as well as in the NAA<sub>lesion</sub>/Cr<sub>lesion</sub> ratio between the no-choline elevation group and glial tumour group. With consistent data concerning choline level elevation and slightly lower NAA value, the Cho<sub>lesion</sub>/NAA<sub>lesion</sub> ratio is significantly higher in the WHO II glial tumour group compared to the no-choline elevation cases (<i>p</i> < 0.000).<br/><br/> In the current study the results demonstrated possibility of lack of choline elevation in patients with grade II-III gliomas, so it is important to remember that the lack of elevated choline levels does not exclude neoplastic lesion.","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":"34 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140564873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paweł Sobczyk, Michał Sobstyl, Albert Acewicz, Joanna Rosa, Marta Grabiec, Wiesława Grajkowska
Gliosarcoma (GS) is a rare variant of IDH-wildtype glioblastoma. It is classified as grade 4 in the latest WHO CNS classification of both glial and mesenchymal components. Gliosarcoma may arise de novo or secondary from glioblastoma. It occurs in up to 2% of patients diagnosed with glioblastoma. We present a case report of a 51-year-old patient who was initially diagnosed with glioblastoma multiforme, which transformed into secondary gliosarcoma with an osteosarcoma component 16 months after the initial diagnosis. We believe that increasing reporting of secondary gliosarcoma (sGS) will be helpful in understanding, diagnosing and providing more effective treatment for this cancer.
{"title":"Transformation of IDH-wildtype glioblastoma to gliosarcoma with features of osteosarcoma","authors":"Paweł Sobczyk, Michał Sobstyl, Albert Acewicz, Joanna Rosa, Marta Grabiec, Wiesława Grajkowska","doi":"10.5114/fn.2024.136020","DOIUrl":"https://doi.org/10.5114/fn.2024.136020","url":null,"abstract":"Gliosarcoma (GS) is a rare variant of IDH-wildtype glioblastoma. It is classified as grade 4 in the latest WHO CNS classification of both glial and mesenchymal components. Gliosarcoma may arise de novo or secondary from glioblastoma. It occurs in up to 2% of patients diagnosed with glioblastoma. We present a case report of a 51-year-old patient who was initially diagnosed with glioblastoma multiforme, which transformed into secondary gliosarcoma with an osteosarcoma component 16 months after the initial diagnosis. We believe that increasing reporting of secondary gliosarcoma (sGS) will be helpful in understanding, diagnosing and providing more effective treatment for this cancer.","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":"41 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140564784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}