Experimental and molecular pathology最新文献

{"title":"Predictive molecular pathology after prolonged fixation: A study on tissue from anatomical body donors","authors":"Anja Böckers ,&nbsp;Leon Schurr ,&nbsp;Michael Schön ,&nbsp;Tatjana Scholl ,&nbsp;Tobias M. Böckers ,&nbsp;Konrad Steinestel ,&nbsp;Annette Arndt","doi":"10.1016/j.yexmp.2024.104899","DOIUrl":"https://doi.org/10.1016/j.yexmp.2024.104899","url":null,"abstract":"<div><p>Histopathological assessment of tissue samples after prolonged formalin fixation has been described previously, but currently there is only limited knowledge regarding the feasibility of molecular pathology on such tissue. In this pilot study, we tested routine molecular pathology methods (DNA isolation, DNA pyrosequencing/next-generation sequencing, DNA methylation analysis, RT-PCR, clonality analysis and fluorescence <em>in situ</em> hybridization) on tissue samples from 11 tumor entities as well as non-neoplastic brain tissue from 43 body donors during the gross anatomy course at Ulm University (winter semester 2019/20 and 2020/21). The mean <em>post mortem</em> interval until fixation was 2.5 ± 1.6 days (range, 1–6 days). Fixation was performed with aqueous formaldehyde solution (formalin, 1.5–2%). The mean storage time of body donors was 12.8 ± 5.6 months (range, 7–25 months).</p><p>While most diagnostic methods were successful, samples showed significant variability in DNA quality and evaluability. DNA pyrosequencing as well as next-generation sequencing was successful in all investigated samples. Methylation analyses were partially not successful in some extend due to limited intact DNA yield for these analyses.</p><p>Taken together, the use of prolonged formalin-fixed tissue samples from body donors offers new avenues in research and education, as these samples could be used for morpho-molecular studies and the establishment of biobanks, especially for tissue types that cannot be preserved and studied <em>in vivo</em>. Pathological ward rounds, sample collection, and histopathological and molecular workup have been integrated in the gross anatomy course in Ulm as an integral part of the curriculum, linking anatomy and pathology and providing medical students early insight into the broad field of (molecular) pathology.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000182/pdfft?md5=bb189ec2d7fff443ed3e16b2e3573e45&pid=1-s2.0-S0014480024000182-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140951181","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":"Sodium acetate prevents testicular damage in Wistar rats subjected to testicular ischaemia/reperfusion injury","authors":"Elizabeth Enohnyket Besong ,&nbsp;Roland Eghoghosoa Akhigbe","doi":"10.1016/j.yexmp.2024.104901","DOIUrl":"10.1016/j.yexmp.2024.104901","url":null,"abstract":"<div><h3>Aims</h3><p>The aim of this study was to investigate the potential antioxidant, anti-inflammatory, and sperm function-preserving properties of sodium acetate (ACE), a histone deacetylase (HDAC) inhibitor, in a rat model of testicular torsion/detorsion (T/D).</p></div><div><h3>Main methods</h3><p>Littermate Wistar rats of identical weight were subjected to sham surgery or testicular T/D by rotating the left testis at 720° around its axis along the spermatic cord clockwise and fixing it in this position for two and a half hours. 1 h before detorsion, T/D + ACE-treated rats were treated with ACE (200 mg/kg/day, per os) while T/D rats were vehicle-treated by administering 0.5 mL of distilled water. After 72 h, animals were euthanized, and the left testes were harvested for bio-molecular and histological analysis.</p></div><div><h3>Key findings</h3><p>Acetate administration attenuated T/D-induced rises in serum and testicular HDAC and testicular xanthine oxidase, uric acid, MDA, GSSG, MPO, TNF-α, IL-1β, IL-6, NF<em>k</em>B, HIF-1α, and VCAM-1. In addition, acetate treatment alleviated T/D-induced decline in sperm quality (count, motility, viability, and normal morphology) and testicular 3β-HSD, 17β-HSD, testosterone, GSH, GSH/GSSG, SOD, catalase, GPx, GST, Nrf2, and HO-1. Furthermore, acetate prevented T/D-distorted testicular histoarchitecture and spermatogenic germ cell loss.</p></div><div><h3>Significance</h3><p>Sodium acetate during the post-ischaemic phase of testicular T/D may be beneficial in preventing I/R injury and maintaining fertility.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000200/pdfft?md5=68d7bb828f4aff637382e74ba009abbd&pid=1-s2.0-S0014480024000200-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944458","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":"Urinary soluble CD163 is a putative non-invasive biomarker for primary sclerosing cholangitis","authors":"Tanja Elger ,&nbsp;Tanja Fererberger ,&nbsp;Muriel Huss ,&nbsp;Stefanie Sommersberger ,&nbsp;Patricia Mester ,&nbsp;Petra Stoeckert ,&nbsp;Stefan Gunawan ,&nbsp;Gerhard Liebisch ,&nbsp;Johanna Loibl ,&nbsp;Arne Kandulski ,&nbsp;Martina Müller ,&nbsp;Christa Buechler ,&nbsp;Hauke Christian Tews","doi":"10.1016/j.yexmp.2024.104900","DOIUrl":"https://doi.org/10.1016/j.yexmp.2024.104900","url":null,"abstract":"<div><p>Soluble CD163 (sCD163) is a selective marker of macrophages whose circulating levels have been found to be induced in patients with active inflammatory bowel disease (IBD). Urinary proteins are emerging as non-invasive diagnostic biomarkers, and here, sCD163 levels were measured in the urine of 18 controls and 63 patients with IBD by enzyme-linked immunosorbent assay. Urinary sCD163 levels did, however, not differentiate IBD patients from controls. Analysis of sCD163 in the serum of 51 of these patients did not show higher levels in IBD. Primary sclerosing cholangitis (PSC) is often associated with IBD, and sCD163 was higher in the urine of the 21 patients and in the serum of the 13 patients with PSC compared to patients with IBD. Of clinical relevance, urinary sCD163 levels were higher in PSC patients compared to those with other chronic liver diseases (<em>n</em> = 16), while serum sCD163 levels were comparable between the two groups. Serum sCD163 of IBD and PSC patients positively correlated with serum C-reactive protein. Serum creatinine and glomerular filtration rate, surrogate markers for renal function, did not significantly correlate with urinary or serum sCD163 levels in IBD or PSC patients. Moreover, urinary sCD163 was not related to fecal calprotectin levels whereas serum sCD163 of IBD patients showed a positive trend. PSC associated with IBD and PSC without underlying IBD had similar levels of urinary sCD163 while serum sCD163 tended to be higher in the latter group. In PSC patients, urinary sCD163 did not correlate with serum aminotransferase levels, gamma glutamyl transferase, alkaline phosphatase, bilirubin or the Model for End Stage Liver Disease score. Ursodeoxycholic acid was prescribed to our PSC patients and fecal levels of ursodeoxycholic acid and its conjugated forms were increased in PSC compared to IBD patients. Otherwise, fecal bile acid levels of IBD and PSC patients were almost identical, and were not correlated with urinary and serum sCD163 in PSC. In summary, our study identified urinary sCD163 as a potential biomarker for PSC.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000194/pdfft?md5=d883e6bafe0b03b8ca1f75d081a17a7b&pid=1-s2.0-S0014480024000194-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140901281","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":"Fate control engagement augments NK cell responses in LV/hu-IL-12 transduced sarcoma","authors":"Mary Jo Rademacher ,&nbsp;Mary L. Faber ,&nbsp;Kathleen M. Bone ,&nbsp;Jeffrey A. Medin ,&nbsp;Nathan J. Schloemer","doi":"10.1016/j.yexmp.2024.104898","DOIUrl":"https://doi.org/10.1016/j.yexmp.2024.104898","url":null,"abstract":"<div><h3>Introduction</h3><p>NK cells are an untapped resource for cancer therapy. Sarcomas transduced with lentiviruses to express human IL-12 are only cleared in mice bearing mature human NK cells. However, systemic inflammation limits IL-12 utilization. Fate control a.k.a. “suicide mechanisms” regulate unchecked systemic inflammation caused by cellular immunotherapies. Despite increasing utilization, there remains limited data on immune consequences or tumor-directed effects of fate control.</p></div><div><h3>Objectives</h3><p>We sought to engage the mutant thymidylate kinase (mTMPK) metabolic fate control system to regulate systemic inflammation and assess the impact on NK cell effector functions.</p></div><div><h3>Methods</h3><p>Primary human sarcoma short-passage samples and cell lines were transduced with LV/hu-IL-12_mTMPK engineering expression of IL-12 and an AZT-associated fate control enzyme. We assessed transduced sarcoma responses to AZT engagement and subsequent modulation of NK cell functions as measured by inflammatory cytokine production and cytotoxicity.</p></div><div><h3>Results</h3><p>AZT administration to transduced (LV/hu-IL-12_mTMPK) short-passage primary human sarcomas and human Ewing sarcoma, osteosarcoma, and rhabdomyosarcoma cell lines, abrogated the robust expression of human IL-12. Fate control activation elicited a specific dose-dependent cytotoxic effect measured by metabolic activity (WST-1) and cell death (Incucyte). NK effector functions of IFN-γ and cytotoxic granule release were significantly augmented despite IL-12 abrogation. This correlated with preferentially induced expression of NK cell activation ligands.</p></div><div><h3>Conclusions</h3><p>mTMPK fate control engagement terminates transduced sarcoma IL-12 production and triggers cell death, but also augments an NK cell-mediated response coinciding with metabolic stress activating surface ligand induction. Fate control engagement could offer a novel immune activation method for NK cell-mediated cancer clearance.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000170/pdfft?md5=5c6bcb3072ad12079605419d64782842&pid=1-s2.0-S0014480024000170-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140901282","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":"Analysis of anti-tumor effect and mechanism of GLS1 inhibitor CB-839 in colorectal cancer using a stroma-abundant tumor model","authors":"Ryo Miyamoto ,&nbsp;Hidehiko Takigawa ,&nbsp;Ryo Yuge ,&nbsp;Daisuke Shimizu ,&nbsp;Misa Ariyoshi ,&nbsp;Rina Otani ,&nbsp;Akiyoshi Tsuboi ,&nbsp;Hidenori Tanaka ,&nbsp;Ken Yamashita ,&nbsp;Yuichi Hiyama ,&nbsp;Yuji Urabe ,&nbsp;Akira Ishikawa ,&nbsp;Kazuhiro Sentani ,&nbsp;Shiro Oka","doi":"10.1016/j.yexmp.2024.104896","DOIUrl":"https://doi.org/10.1016/j.yexmp.2024.104896","url":null,"abstract":"<div><h3>Background</h3><p>Glutaminase 1 (GLS1), a key enzyme in glutamine metabolism in cancer cells, acts as a tumor promoter and could be a potential therapeutic target. CB-839, a GLS1-specific inhibitor, was developed recently. Herein, we aimed to elucidate the anti-tumor effects and mechanism of action of CB-839 in colorectal cancer (CRC).</p></div><div><h3>Methods</h3><p>Using the UCSC Xena public database, we evaluated GLS1 expression in various cancers. Immunostaining for GLS1 was performed on 154 surgically resected human CRC specimens. Subsequently, we examined the GLS1 mRNA expression levels in eight CRC cell lines and evaluated the association between GLS1 expression and CB-839 efficacy. To create a reproducible CRC model with abundant stroma and an allogeneic immune response, we co-transplanted CT26 and stem cells into BALB/c mice and treated them with CB-839. Finally, RNA sequencing of mouse tumors was performed.</p></div><div><h3>Results</h3><p>Database analysis showed higher GLS1 expression in CRC tissues than in normal colon tissues. Clinical samples from 114 of the 154 patients with CRC showed positive GLS1 expression. GLS1 expression in clinical CRC tissues correlated with vascular invasion. CB-839 treatment inhibited cancer cell proliferation depending on GLS1 expression <em>in vitro</em> and inhibited tumor growth and metastasis in the CRC mouse model. RNA sequencing revealed that CB-839 treatment inhibited stromal activation, tumor growth, migration, and angiogenesis. These findings were validated through <em>in vitro</em> and <em>in vivo</em> experiments and clinical specimen analysis.</p></div><div><h3>Conclusions</h3><p>GLS1 expression in CRC plays important roles in tumor progression. CB-839 has inhibitory effects on cancer proliferation and the tumor microenvironment.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000157/pdfft?md5=c70522300a81b554d3378dc2df9fd694&pid=1-s2.0-S0014480024000157-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825769","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":"Circulating perturbation of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is associated to cardiac remodeling and NLRP3 inflammasome in cardiovascular patients with insulin resistance risk","authors":"Elena Vianello ,&nbsp;Federico Ambrogi ,&nbsp;Marta Kalousová ,&nbsp;Julietta Badalyan ,&nbsp;Elena Dozio ,&nbsp;Lorenza Tacchini ,&nbsp;Gerd Schmitz ,&nbsp;Tomáš Zima ,&nbsp;Gregory J. Tsongalis ,&nbsp;Massimiliano M. Corsi-Romanelli","doi":"10.1016/j.yexmp.2024.104895","DOIUrl":"https://doi.org/10.1016/j.yexmp.2024.104895","url":null,"abstract":"<div><p>Lipidome perturbation occurring during meta-inflammation is associated to left ventricle (LV) remodeling though the activation of the NLRP3 inflammasome, a key regulator of chronic inflammation in obesity-related disorders. Little is known about phosphatidylcholine (PC) and phosphatidylethanolamine (PE) as DAMP-induced NLRP3 inflammasome. Our study is aimed to evaluate if a systemic reduction of PC/PE molar ratio can affect NLRP3 plasma levels in cardiovascular disease (CVD) patients with insulin resistance (IR) risk.</p><p>Forty patients from IRCCS Policlinico San Donato were enrolled, and their blood samples were drawn before heart surgery. LV geometry measurements were evaluated by echocardiography and clinical data associated to IR risk were collected. PC and PE were quantified by ESI-MS/MS. Circulating NLRP3 was quantified by an ELISA assay.</p><p>Our results have shown that CVD patients with IR risk presented systemic lipid impairment of PC and PE species and their ratio in plasma was inversely associated to NLRP3 levels. Interestingly, CVD patients with IR risk presented LV changes directly associated to increased levels of NLRP3 and a decrease in PC/PE ratio in plasma, highlighting the systemic effect of meta-inflammation in cardiac response. In summary, PC and PE can be considered bioactive mediators associated to both the NLRP3 and LV changes in CVD patients with IR risk.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000145/pdfft?md5=b8fcafb846b5887387b776d9ad27b626&pid=1-s2.0-S0014480024000145-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825770","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":"Effects of toll-like receptor agonists and SARS-CoV-2 antigens on interferon (IFN) expression by peripheral blood CD3+ T cells from COVID-19 patients","authors":"Samaneh Abdolmohammadi-Vahid ,&nbsp;Behzad Baradaran ,&nbsp;Armin Sadeghi ,&nbsp;Gilina Bezemer ,&nbsp;Fatemeh Kiaee ,&nbsp;Ian M. Adcock ,&nbsp;Gert Folkerts ,&nbsp;Johan Garssen ,&nbsp;Esmaeil Mortaz","doi":"10.1016/j.yexmp.2024.104897","DOIUrl":"https://doi.org/10.1016/j.yexmp.2024.104897","url":null,"abstract":"<div><h3>Background</h3><p>Signaling by toll-like receptors (TLRs) initiates important immune responses against viral infection. The role of TLRs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not well elucidated. Thus, we investigated the interaction of TLRs agonists and SARS-COV-2 antigens with immune cells in vitro.</p></div><div><h3>Material &amp; methods</h3><p>30 coronavirus disease 2019 (COVID-19) patients (15 severe and 15 moderate) and 10 age and sex-matched healthy control (HC) were enrolled. Peripheral blood mononuclear cells (PBMCs) were isolated and activated with TLR3, 7, 8, and 9 agonists, the spike protein (SP) of SARS-CoV-2, and the receptor binding domain (RBD) of SP. Frequencies of CD3⁺IFN-β⁺ T cells, and CD3⁺IFN-γ⁺ T cells were evaluated by flow cytometry. Interferon (IFN)-β gene expression was assessed by qRT-PCR.</p></div><div><h3>Results</h3><p>The frequency of CD3⁺IFN-β⁺ T cells was higher in PBMCs from moderate (<em>p</em> &lt; 0.0001) and severe (<em>p</em> = 0.009) patients at baseline in comparison with HCs. The highest increase in the frequency of CD3⁺IFN-β⁺ T cells in cell from moderate patients was induced by TLR8 agonist and SP (<em>p</em> &lt; 0.0001 for both) when compared to HC, while, the highest increase of the frequency of CD3⁺IFN-β⁺ T cells in sample of severe patients was seen with TLR8 and TLR7 agonists (both <em>p</em> = 0.002). The frequency of CD3⁺IFN-γ⁺ T cells was significantly increased upon stimulation with TLR agonists in cell from patients with moderate and severe COVID-19, compared with HC (all <em>p</em> &lt; 0.01), except with TLR7 and TLR8 agonists. The TLR8 agonist did not significantly increase the frequency of CD3⁺IFN-γ⁺ T cells in PBMCs of severe patients, but did so in cells from patients with moderate disease (<em>p</em> = 0.01). Moreover, IFN-β gene expression was significantly upregulated in CD3⁺T cells from moderate (<em>p</em> &lt; 0.0001) and severe (<em>p</em> = 0.002) COVID-19 patients, compared to HC after stimulation with the TLR8 agonist, while, stimulation of T cells with SP, significantly up-regulated IFN-β mRNA expression in cells from patients with moderate (<em>p</em> = 0.0003), but not severe disease.</p></div><div><h3>Conclusion</h3><p>Stimulation of PBMCs from COVID-19 patients, especially patients with moderate disease, with TLR8 agonist and SP increased the frequency of IFN-β-producing T cells and IFN-β gene expression.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000169/pdfft?md5=3fd93203ce33e5c1984c989354a244d5&pid=1-s2.0-S0014480024000169-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140816940","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":"Decreased proteasome function increases oxidative stress in the early stage of pressure ulcer development","authors":"Eri Murata ,&nbsp;Takuma Yoshida ,&nbsp;Utano Tomaru ,&nbsp;Saaki Yamamoto ,&nbsp;Aya Fukui-Miyazaki ,&nbsp;Akihiro Ishizu ,&nbsp;Masanori Kasahara","doi":"10.1016/j.yexmp.2024.104891","DOIUrl":"10.1016/j.yexmp.2024.104891","url":null,"abstract":"<div><p>The aging process in the elderly results in heightened skin fragility associated with various disorders, including pressure ulcers (PUs). Despite the high incidence of PUs in the elderly population, there is a limited body of research specifically examining the impact of aging on the development of pressure ulcers. Therefore, investigating age-related physiological abnormalities is essential to elucidate the pathogenesis of PUs. Ischemia-reperfusion (I/R) injury and the subsequent oxidative stress caused by reactive oxygen species (ROS) play essential roles in the early stage of PUs. In this study, we used a mouse model of proteasomal dysfunction with an age-related phenotype to examine the role of proteasome activity in cutaneous I/R injury <em>in vivo</em>. Decreased proteasome function did not affect the expression of inflammatory cytokines and adhesion molecules in the I/R area in transgenic mice; however, proteasome inhibition increased oxidative stress that was not attenuated by activation of the oxidative stress response mediated by NF-E2-related factor 2 (Nrf2). In dermal fibroblasts (FCs) subjected to hypoxia-reoxygenation (H/R), proteasome inhibition induced oxidative stress and ROS production, and Nrf2 activation did not adequately upregulate antioxidant enzyme expression, possibly leading to antioxidant/oxidant imbalance. The free radical scavenger edaravone had protective effects against I/R injury <em>in vivo</em> and decreased oxidative stress in FCs treated with a proteasome inhibitor and subjected to H/R <em>in vitro</em>. The results suggest that the age-related decline in proteasome activity promotes cutaneous I/R injury-induced oxidative stress, and free radical scavengers may exert protective effects by preventing oxidative stress in the early stage of PUs.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000108/pdfft?md5=f1f9ec6172e98a6e919439d4fa27ed6c&pid=1-s2.0-S0014480024000108-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093744","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":"TBX15 and SDHB expression changes in colorectal cancer serve as potential prognostic biomarkers","authors":"Melika Golozar ,&nbsp;Ali Valipour Motlagh ,&nbsp;Mohammad Mahdevar ,&nbsp;Maryam Peymani ,&nbsp;Kolsoum InanlooRahatloo ,&nbsp;Kamran Ghaedi","doi":"10.1016/j.yexmp.2024.104890","DOIUrl":"10.1016/j.yexmp.2024.104890","url":null,"abstract":"<div><p>Alterations in the expression of certain genes could be associated with both patient mortality rates and drug resistance. This study aimed to identify genes in colorectal cancer (CRC) that potentially serve as hub genes influencing patient survival rates. RNA-Seq data were downloaded from the cancer genome atlas database, and differential expression analysis was performed between tumors and healthy controls. Through the utilization of univariate and multivariate Cox regression analyses, in combination with the MCODE clustering module, the genes whose expression changes were related to survival rate and the hub genes related to them were identified. The mortality risk model was computed using the hub genes. CRC samples and the RT-qPCR method were utilized to confirm the outcomes. PharmacoGx data were employed to link the expression of potential genes to medication resistance and sensitivity. The results revealed the discovery of seven hub genes, which emerged as independent prognostic markers. These included <em>HOXC6</em>, <em>HOXC13</em>, <em>HOXC8</em>, and <em>TBX15</em>, which were associated with poor prognosis and overexpression, as well as <em>SDHB</em>, <em>COX5A</em>, and <em>UQCRC1</em>, linked to favorable prognosis and downregulation. Applying the risk model developed with the mentioned genes revealed a markedly higher incidence of deceased patients in the high-risk group compared to the low-risk group. RT-qPCR results indicated a decrease in <em>SDHB</em> expression and an elevation in <em>TBX15</em> levels in cancer samples relative to adjacent healthy tissue. Also, PharmacoGx data indicated that the expression level of <em>SDHB</em> was correlated with drug sensitivity to Crizotinib and Dovitinib. Our findings highlight the potential association between alterations in the expression of genes such as <em>HOXC6</em>, <em>HOXC13</em>, <em>HOXC8</em>, <em>TBX15</em>, <em>SDHB</em>, <em>COX5A</em>, and <em>UQCRC1</em> and increased mortality rates in CRC patients. As revealed by the PPI network, these genes exhibited the most connections with other genes linked to survival.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480024000091/pdfft?md5=81cba468dad9389365dfdf0369be2e8e&pid=1-s2.0-S0014480024000091-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912433","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":"Molecular and cellular pruritus mechanisms in the host skin","authors":"Li Li ,&nbsp;Zhi-en Li ,&nbsp;Yun-li Mo ,&nbsp;Wan-yao Li ,&nbsp;Hui-jing Li ,&nbsp;Guang-hai Yan ,&nbsp;Xiang-zheng Qin ,&nbsp;Li-hua Piao","doi":"10.1016/j.yexmp.2024.104889","DOIUrl":"10.1016/j.yexmp.2024.104889","url":null,"abstract":"<div><p>Pruritus, also known as itching, is a complex sensation that involves the activation of specific physiological and cellular receptors. The skin is innervated with sensory nerves as well as some receptors for various sensations, and its immune system has prominent neurological connections. Sensory neurons have a considerable impact on the sensation of itching. However, immune cells also play a role in this process, as they release pruritogens. Disruption of the dermal barrier activates an immune response, initiating a series of chemical, physical, and cellular reactions. These reactions involve various cell types, including keratinocytes, as well as immune cells involved in innate and adaptive immunity. Collective activation of these immune responses confers protection against potential pathogens. Thus, understanding the molecular and cellular mechanisms that contribute to pruritus in host skin is crucial for the advancement of effective treatment approaches. This review provides a comprehensive analysis of the present knowledge concerning the molecular and cellular mechanisms underlying itching signaling in the skin. Additionally, this review explored the integration of these mechanisms with the broader context of itch mediators and the expression of their receptors in the skin.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S001448002400008X/pdfft?md5=a2beb07942952267e359459ae10328ef&pid=1-s2.0-S001448002400008X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691587","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}