Experimental and molecular pathology最新文献

{"title":"Corrigendum to \"Irisin and neuroinflammation: Challenges and opportunities\" [Experimental and Molecular Pathology 140 (2024) 104941].","authors":"Erika Yolanda Hernández Sandoval, Zulma Dueñas","doi":"10.1016/j.yexmp.2024.104943","DOIUrl":"10.1016/j.yexmp.2024.104943","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":" ","pages":"104943"},"PeriodicalIF":2.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617746","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}

{"title":"Diagnostic criteria and therapeutic implications of rapid-onset demyelinating polyneuropathies","authors":"Wiktoria Rałowska-Gmoch ,&nbsp;Magdalena Koszewicz ,&nbsp;Beata Łabuz-Roszak ,&nbsp;Sławomir Budrewicz ,&nbsp;Edyta Dziadkowiak","doi":"10.1016/j.yexmp.2024.104942","DOIUrl":"10.1016/j.yexmp.2024.104942","url":null,"abstract":"<div><div>Guillain-Barré syndrome (GBS) and acute-onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) are the most common autoimmune polyneuropathies. Their aetiology is unclear. The pathomechanism includes damage mainly to the myelin sheath and, in the long-term process, secondary axonal loss. Both inflammatory polyneuropathies involve different combinations of motor, sensory and autonomic fibres in the peripheral nerves. The differential diagnosis should be based on clinical and neurophysiological features, and laboratory tests. Numerous studies aim to demonstrate the most common errors in the diagnosis of Guillain-Barré syndrome and acute-onset CIDP. Misdiagnosis can result in the wrong treatment. We still do not have reliable markers to help diagnose the disease or to monitor the effectiveness of the therapy.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"140 ","pages":"Article 104942"},"PeriodicalIF":2.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142579061","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}

{"title":"Irisin and neuroinflammation: Challenges and opportunities","authors":"Erika Yolanda Hernández Sandoval,&nbsp;Zulma Janeth Dueñas Gómez","doi":"10.1016/j.yexmp.2024.104941","DOIUrl":"10.1016/j.yexmp.2024.104941","url":null,"abstract":"<div><div>Irisin is a myokine that is cleaved from 5-domain type III fibronectin (<em>FNDC5</em>), and is known for its metabolic functions as it stimulates browning of white adipose tissue; similarly, effects on the central nervous system have been described, specifically in neurodevelopmental and neuroprotection processes. The purpose of this review is to describe recent information on the effects of irisin on neuroinflammation to contribute to the knowledge about the mechanisms by which irisin and exercise could generate benefits for some neurological diseases. The review conducted found several studies describing the effect of irisin on pathways such as STAT3, p38, cAMP/PKA/CREB, as well as effects on GFAP protein expression or apoptosis processes in both <em>in vitro</em> and <em>in vivo</em> models; likewise, these pathways are associated with better BDNF expression. Despite increasing information on this topic, it is still necessary to clarify the mechanisms by which irisin has effects on neuroinflammation and this could represent an opportunity to generate more treatments for diseases such as Alzheimer's, Parkinson's or Diabetes Mellitus.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"140 ","pages":"Article 104941"},"PeriodicalIF":2.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521468","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}

{"title":"Assessing pathogenicity of mismatch repair variants of uncertain significance by molecular tumor analysis","authors":"Anne-Sophie van der Werf't Lam ,&nbsp;Noah C. Helderman ,&nbsp;Arnoud Boot ,&nbsp;Diantha Terlouw ,&nbsp;Hans Morreau ,&nbsp;Hailian Mei ,&nbsp;Rebecca E.E. Esveldt-van Lange ,&nbsp;Inge M.M. Lakeman ,&nbsp;Christi J. van Asperen ,&nbsp;Emmelien Aten ,&nbsp;Nandy Hofland ,&nbsp;Pia A.M. de Koning Gans ,&nbsp;Emily Rayner ,&nbsp;Carli Tops ,&nbsp;Niels de Wind ,&nbsp;Tom van Wezel ,&nbsp;Maartje Nielsen","doi":"10.1016/j.yexmp.2024.104940","DOIUrl":"10.1016/j.yexmp.2024.104940","url":null,"abstract":"<div><div>Functional analyses are the main method to classify mismatch repair (MMR) gene variants of uncertain significance (VUSs). However, the pathogenicity remains unclear for many variants because of conflicting results between clinical, molecular, and functional data. In this study, we evaluated whether whole exome sequencing (WES) could add another layer of evidence to elucidate the pathogenicity of MMR variants with conflicting interpretations. WES was performed on formalin-fixed paraffin-embedded tumor tissue of eight patients with a constitutional MMR VUS (seven families), including eight colorectal and two endometrial carcinomas and one ovarian carcinoma. Cell-free CIMRA assays were performed to assign Odds of Pathogenicity to these VUSs. In four families, seven tumors showed MMR deficiency-associated mutational signatures, supporting the pathogenicity of the VUS. Moreover, somatic (second) MMR hits identified in the WES data were found to explain MMR staining patterns when the MMR staining was discordant with the reported germline MMR gene variant. In conclusion, WES did not significantly reclassify VUS in these cases but clarified some phenotypic aspects such as age of onset and explanations in case of discordant MMR stainings.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"140 ","pages":"Article 104940"},"PeriodicalIF":2.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497717","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}

{"title":"Impaired immunoproteasomal function exacerbates renal ischemia-reperfusion injury","authors":"Yasushi Ishii ,&nbsp;Aya Fukui-Miyazaki ,&nbsp;Sari Iwasaki ,&nbsp;Takahiro Tsuji ,&nbsp;Kiyohiko Hotta ,&nbsp;Hajime Sasaki ,&nbsp;Shimpei Nakagawa ,&nbsp;Takuma Yoshida ,&nbsp;Eri Murata ,&nbsp;Koji Taniguchi ,&nbsp;Nobuo Shinohara ,&nbsp;Akihiro Ishizu ,&nbsp;Masanori Kasahara ,&nbsp;Utano Tomaru","doi":"10.1016/j.yexmp.2024.104939","DOIUrl":"10.1016/j.yexmp.2024.104939","url":null,"abstract":"<div><div>Oxidative stress caused by reactive oxygen species (ROS) is involved in the pathogenesis of renal ischemia-reperfusion injury (I/R injury), a major cause of acute kidney injury and delayed graft function (DGF). DGF is an early transplant complication that worsens graft prognosis and patient survival, but the underlying molecular changes are unclear. The proteasome is a multicatalytic enzyme complex that degrades both normal and damaged proteins, and recent studies have revealed that the immunoproteasome, a specific proteasome isoform whose proteolytic activity enhances the generation of antigenic peptides, plays critical roles in the cellular response against oxidative stress. In this study, we demonstrate the impact of the immunoproteasome in human DGF and in a mouse model of I/R injury. In patients with DGF, the expression of β5i, a specific immunoproteasome subunit, was decreased in vascular endothelial cells. In a mouse model, β5i knockout (KO) exacerbated renal I/R injury. KO mice showed greater inflammation, oxidative stress, and endothelial damage compared with wild-type mice. Impaired immunoproteasomal activity also caused increased cell death, ROS production, and expression of inflammatory factors in mouse renal vascular endothelial cells under conditions of hypoxia and reoxygenation. In conclusion, reduced expression of the immunoproteasomal catalytic subunit β5i exacerbates renal I/R injury in vivo, potentially increasing the risk of DGF. Further research targeting β5i expression in DGF could lead to the development of novel therapeutic strategies and biomarkers.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"140 ","pages":"Article 104939"},"PeriodicalIF":2.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461419","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}

{"title":"Histomorphological scoring of murine colitis models: A practical guide for the evaluation of colitis and colitis-associated cancer","authors":"Marianne Remke ,&nbsp;Tanja Groll ,&nbsp;Thomas Metzler ,&nbsp;Elisabeth Urbauer ,&nbsp;Janine Kövilein ,&nbsp;Theresa Schnalzger ,&nbsp;Jürgen Ruland ,&nbsp;Dirk Haller ,&nbsp;Katja Steiger","doi":"10.1016/j.yexmp.2024.104938","DOIUrl":"10.1016/j.yexmp.2024.104938","url":null,"abstract":"<div><h3>Background and aims</h3><div>Histomorphology is a powerful and cost-efficient tool for evaluating inflammatory and neoplastic conditions. Inflammatory bowel disease (IBD) is a widespread condition with globally rising incidences, and a lot of research is done to better understand the pathogenesis of IBD and to identify potential therapeutic approaches. However, standardized and reproducible scores for the histomorphological evaluation of murine IBD models are lacking. Therefore, we aimed to develop an easy-to-use and reproducible score for standardized assessment of colitis and associated cancer models.</div></div><div><h3>Methods</h3><div>In this study, samples from three different colitis models with and without associated cancer formation were analyzed to develop a universal, robust, and reproducible score for the grading of murine colitis models using the following three parameters: 1. Extent of leucocyte infiltration, 2. Tissue damage, 3. Architectural disruption of the mucosa.</div></div><div><h3>Results</h3><div>A scoring system was established for different kinds of colitis models (genetically induced enterocolitis, genetically induced metabolic injury, and chemically induced colitis-associated cancer) and all stages of the disease, from mild inflammatory changes to severe inflammation with neoplastic changes as the extreme extent of IBD. The scoring scheme is easy to use, can easily be learned, and proves to have a high interrater reliability.</div></div><div><h3>Conclusions</h3><div>We propose a robust histological scoring system for the assessment of murine colitis and colitis-associated cancer models, giving more researchers access to conclusive and reliable histological assessment.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"140 ","pages":"Article 104938"},"PeriodicalIF":2.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442772","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}

{"title":"A weighted and cumulative point system for accurate scoring of intestinal pathology in a piglet model of necrotizing enterocolitis","authors":"Simone Margaard Offersen,&nbsp;Nicole Lind Henriksen,&nbsp;Anders Brunse","doi":"10.1016/j.yexmp.2024.104936","DOIUrl":"10.1016/j.yexmp.2024.104936","url":null,"abstract":"<div><div>Necrotizing enterocolitis (NEC) is a serious condition in premature infants, in which a portion of the intestine undergoes inflammation and necrosis. The preterm pig develops NEC spontaneously, making it a suitable model for exploring novel NEC treatments. We aimed to revise the intestinal scoring system to more accurately describe the diversity of NEC lesions in the preterm piglet model. We included 333 preterm piglets from four experiments, each delivered via cesarean section. The piglets were fed either a gently processed (GP) or harshly processed (HP) milk formula for 96 h before euthanasia. At necropsy, the gastrointestinal tract was assessed with 1) an established 6-grade score and 2) a descriptive approach focusing on the distribution and severity of hyperemia, hemorrhage, pneumatosis intestinalis (intramural gas), and necrosis. Subsequently, the descriptive registrations were converted into a weighted and cumulative point (WCP) score. Compared to the 6-grade score, the WCP score enabled a greater segregation of severity levels, especially among organs with more prominent NEC lesions. IL-1β in small intestinal lesions and both IL-8 and IL-1β in colon lesions correlated positively with the WCP scale. A histopathological grade system (0–8) was established and revealed mucosal pathology in lesion biopsies, which were not recognized macroscopically. Finally, the WCP score showed a higher NEC-promoting effect of the HP formula compared to the GP formula. The descriptive registrations and extended score range of this revised intestinal scoring system enhance the accuracy of describing NEC lesions in preterm pigs. This approach may increase the efficiency of preclinical NEC experiments.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"140 ","pages":"Article 104936"},"PeriodicalIF":2.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375356","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}

{"title":"Piperine and piperine-loaded albumin nanoparticles ameliorate adjuvant-induced arthritis and reduce IL-17 in rats","authors":"Nasser Gholijani ,&nbsp;Negar Azarpira ,&nbsp;Samira-Sadat Abolmaali ,&nbsp;Nader Tanideh ,&nbsp;Mohammad-Hadi Ravanrooy ,&nbsp;Farzane Taki ,&nbsp;Gholamreza Daryabor","doi":"10.1016/j.yexmp.2024.104937","DOIUrl":"10.1016/j.yexmp.2024.104937","url":null,"abstract":"<div><h3>Aim</h3><div>Rheumatoid arthritis (RA) is one of the most common chronic, inflammatory, autoimmune diseases affecting mainly the joints. Piperine (PIP), an alkaloid found in black pepper, has anti-inflammatory properties and its use in drug delivery systems such as nanoparticles might be a treatment for RA. This study aims to evaluate the possible anti-inflammatory and anti-arthritic effects of PIP and its use in albumin nanoparticles as a possible approach for the treatment of Adjuvant-induced arthritis (AIA) rats.</div></div><div><h3>Methods</h3><div>PIP-loaded Bovine Serum Albumin nanoparticles (PIP-BSA NPs) were prepared using a desolvation method. AIA rats were given intraperitoneal injections of either 40 mg PIP or 131 mg PIP-BSA NPs every two days until day 28 when animals were sacrificed. Clinical score, histopathology, X-ray radiography, and serum levels of pro-inflammatory cytokines such as IL-1β, IL-17, and TNF-α were evaluated.</div></div><div><h3>Results</h3><div>PIP and PIP-BSA NPs significantly reduced clinical scores, and alleviated inflammation within the joints. PIP was superior to PIP-BSA NPs for the alleviation of fibrin deposition and periosteal reactions while bone inflammation and erosion were less severe in the case of PIP-BSA NPs. Besides, both of the treatments suppressed serum levels of IL-17 in AIA rats (<em>p</em> = 0.003 and <em>p</em> = 0.02; respectively).</div></div><div><h3>Conclusions</h3><div>PIP and PIP-BSA NPs effectively alleviate the severity of AIA and suppress inflammation. Due to the superiority of PIP in improving fibrin deposition and periosteal reactions and the efficacy of PIP-BSA NPs in suppressing bone inflammation and erosion, their simultaneous use might be investigated.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"140 ","pages":"Article 104937"},"PeriodicalIF":2.8,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356773","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}

{"title":"Facilitating cholangiocarcinoma inhibition by targeting CD47","authors":"Kulthida Vaeteewoottacharn ,&nbsp;Sakda Waraasawapati ,&nbsp;Phattarin Pothipan ,&nbsp;Ryusho Kariya ,&nbsp;Saowaluk Saisomboon ,&nbsp;Supawadee Bunthot ,&nbsp;Chawalit Pairojkul ,&nbsp;Kanlayanee Sawanyawisuth ,&nbsp;Kazuhiko Kuwahara ,&nbsp;Sopit Wongkham ,&nbsp;Seiji Okada","doi":"10.1016/j.yexmp.2024.104935","DOIUrl":"10.1016/j.yexmp.2024.104935","url":null,"abstract":"<div><div>Immune evasion is one of the mechanisms by which cancer cells acquire immunity during cancer development and progression. One of these is the increased expression of cluster of differentiation 47 (CD47), a transmembrane glycoprotein that protects cells from phagocytic elimination. The interaction between CD47 and signal regulatory protein alpha (SIRPα) on macrophages alleviates the phagocytic signal. The present group previously reported high CD47 expression in cholangiocarcinoma (CCA), a major health problem in Thailand and East Asia, and that blocking CD47 using anti-CD47 antibodies promoted the removal of CCA. However, the mechanism through which CD47 inhibition attenuates CCA growth remains unclear. This study explored the clinical significance of targeting CD47 in CCA. Expression levels of CD47 and the macrophage marker CD68 were determined in CCA tissues by immunohistochemistry and correlated with clinical parameters. The role of CD47 in CCA cells was established using CD47-deficient KKU-213A CCA clones <em>in vitro</em> and <em>in vivo</em>. The results showed that CD47 was highly expressed in CCA tissues and significantly correlated with lymph node metastasis (<em>P</em> = 0.038). Moderate-to-dense CD68-positive infiltrating cells in CCA tissues were significantly associated with shorter survival of patients (<em>P</em> = 0.019) and were an independent prognostic factor of CCA patients as determined by the Cox proportional hazard model (hazard ratio, 2.040; 95 % confidence interval, 1.109–3.752; <em>P</em> = 0.022). Three CD47-deficient KKU-213A clones (#19, #23, and #28) were generated. The elimination of CD47 did not affect cell proliferation but increased monocyte-derived macrophage-mediated phagocytosis <em>in vitro</em>. Decreased tumor weights and volumes were observed in mice injected with CD47-deficient CCA clones. This revealed a significant role for CD47 in CCA, with a focus on protecting cancer cells from macrophage phagocytosis.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"140 ","pages":"Article 104935"},"PeriodicalIF":2.8,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142326508","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}

{"title":"Corrigendum to \"Anti-tumor effect of antibody-drug conjugate targeting cell adhesion molecule 1 on GIST cells representing small intestinal GIST\" [Experimental and Molecular Pathology 139 (2024) 104922].","authors":"Makoto Yoshida, Jiayin Yuan, Takako Kihara, Neinei Kimura, Takashi Yamasaki, Mizuka Ohkouchi, Yuka Hashikura, Koji Isozaki, Man Hagiyama, Akihiko Ito, Seiichi Hirota","doi":"10.1016/j.yexmp.2024.104934","DOIUrl":"https://doi.org/10.1016/j.yexmp.2024.104934","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":" ","pages":"104934"},"PeriodicalIF":2.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344367","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}