Anna L. Gray, Nabina Pun, Amanda J. L. Ridley, Douglas P. Dyer
{"title":"Role of extracellular matrix proteoglycans in immune cell recruitment","authors":"Anna L. Gray, Nabina Pun, Amanda J. L. Ridley, Douglas P. Dyer","doi":"10.1111/iep.12428","DOIUrl":"10.1111/iep.12428","url":null,"abstract":"<p>Leucocyte recruitment is a critical component of the immune response and is central to our ability to fight infection. Paradoxically, leucocyte recruitment is also a central component of inflammatory-based diseases such as rheumatoid arthritis, atherosclerosis and cancer. The role of the extracellular matrix, in particular proteoglycans, in this process has been largely overlooked. Proteoglycans consist of protein cores with glycosaminoglycan sugar side chains attached. Proteoglycans have been shown to bind and regulate the function of a number of proteins, for example chemokines, and also play a key structural role in the local tissue environment/niche. Whilst they have been implicated in leucocyte recruitment and inflammatory disease, their mechanistic function has yet to be fully understood, precluding therapeutic targeting. This review summarizes what is currently known about the role of proteoglycans in the different stages of leucocyte recruitment and proposes a number of areas where more research is needed. A better understanding of the mechanistic role of proteoglycans during inflammatory disease will inform the development of next-generation therapeutics.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 2","pages":"34-43"},"PeriodicalIF":3.0,"publicationDate":"2022-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39857078","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":"British Society for Matrix Biology Autumn 2021 Autumn Meeting: \"Extracellular Matrix and Rare Disease\"","authors":"","doi":"10.1111/iep.12421","DOIUrl":"10.1111/iep.12421","url":null,"abstract":"","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 1","pages":"A1-A14"},"PeriodicalIF":3.0,"publicationDate":"2022-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781645/pdf/IEP-103-A1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10597129","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":"Colonoscopy Audit Increases Detection of Sessile Serrated Polyps","authors":"A. Fraser","doi":"10.33696/pathology.2.030","DOIUrl":"https://doi.org/10.33696/pathology.2.030","url":null,"abstract":"Detection and removal of all adenomas at colonoscopy is associated with a reduced interval cancer rate [1,2]. This is consistent with the adenoma-carcinoma sequence for colorectal cancer. The identification of the serrated polyp cancer pathway has emphasized the importance of detection and removal of sessile serrated polyps. Serrated polyps are precursor lesions ac counting for 15% to 30% of colorectal cancers. They are overrepresented as a cause of interval cancers [3]. The detection of serrated polyps has been clearly linked to the risk of colorectal cancer in a prospective record linkage study in Sweden with a similar risk to tubular adenomas (HR of 1·77 (1·34-2·34) for sessile serrated polyps and 1·41 (1·30-1·52) for tubular adenomas) [4].","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"1 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2021-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79510843","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}
A. Scafa, G. Santoro, V. Chiarella, N. Greco, Massimo Corsini, Manolo, Piccirilli
{"title":"Spinal Capillary and Cavernous Haemangiomas in Developmental Age: Our Experience","authors":"A. Scafa, G. Santoro, V. Chiarella, N. Greco, Massimo Corsini, Manolo, Piccirilli","doi":"10.33696/pathology.2.027","DOIUrl":"https://doi.org/10.33696/pathology.2.027","url":null,"abstract":"In 1863, Virchow proposed the first classification of vascular anomalies. He considered these lesions to be tumors (“angiomas”) and classified them into three categories (“simplex”, “cavernosum”, and “racemosum”) according to the microscopic appearance of the diseased vascular channels [2]. It was subsequently stated that angiomas could be either capillary, venous or arterial (with or without fistulae) based on the stage at which vascular morphogenesis was altered [3]. Setting aside Virchow’s hypothesis, Mulliken and Glowacki, in 1982, developed a new, “binary” classification model in which they distinguished true (1) vascular “hemangiomas”, characterized by cellular hyperplasia, from (2) vascular “malformations” which instead demonstrated vessel dysplasia with normal rates of cellular turnover. They also described the different biological behavior of the two “entities” in terms of tendency to spontaneous regression (present in vascular hemangiomas, absent in vascular malformations) [4]. This scheme was later embraced by the “International Society for the Study of Vascular Anomalies” (ISSVA) at the 1996 meeting in Rome [5], “expanded” at the 2014 ISSVA workshop in Melbourne, and last revised in 2018 (the updates were crucial to fully incorporate the genetic and histopathological advances in the knowledge of these lesions) [6,7]. Vascular tumors were divided into benign, borderline/locally aggressive, and malignant, and were also further sub-classified by pattern and location to include syndromic associations, such as PHACE (posterior fossa brain malformations, large facial hemangiomas, anatomical anomalies of the cerebral arteries, aortic coarctation and other cardiac anomalies, eye abnormalities) and LUMBAR (lower body congenital infantile hemangiomas and other skin defects, urogenital anomalies and ulceration, myelopathy, bony deformities, anorectal malformations and arterial anomalies, rectal anomalies) [7].","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"60 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2021-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77962303","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":"Varying Presentations of EBV-associated Clinical Entities with Emphasis on EBV-Associated T- and NK-cell Lymphoproliferative Disorders of Childhood","authors":"Jonathan Y. Keow, N. Sangle","doi":"10.33696/pathology.2.028","DOIUrl":"https://doi.org/10.33696/pathology.2.028","url":null,"abstract":"The Epstein-Barr Virus (EBV) is an endemic human herpesvirus, with 90% of people demonstrating serological evidence of prior exposure to EBV. In most cases, primary infections of EBV generate mild or asymptomatic clinical courses, but may present as infectious mononucleosis if contracted during young adulthood. In a small percentage of cases, EpsteinBarr virus infection may manifest as a noncanonical reaction, yielding a wide variety of clinical manifestations.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"8 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2021-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73235964","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":"Neuroprotective Effects of Khaya Anthotheca (Welw.) C.DC (Meliaceae) Decoction on Neurodegeneration Induced by Estrogen Depletion in Rats","authors":"Zemo Gamo Franklin, Djiogue Séfirin, S. Faustin, P. Anatole, Babiker Ali, Yousif, Awounfack Charline Florence, Djikem Tadah Rudig Nikanor, Njamen Dieudonne","doi":"10.33696/pathology.2.029","DOIUrl":"https://doi.org/10.33696/pathology.2.029","url":null,"abstract":"Background: Recently, we reported estrogen-like and anxiolytic effects of the decoction of Khaya anthotheca in ovariectomized rats. Rationale: The purpose of the present study was to assess the putative neuroprotective properties of the plant in ovariectomized rats. Methods: Thirty female Wistar rats were ovariectomized, while 6 were used as sham. After 14 days of endogenous hormonal decline, animals were randomly divided into six groups (n=6) and administered with distilled water, K. anthotheca decoction (125, 250 and 500 mg/kg doses) or estradiol valerate (1 mg/kg) for 28 days. Phytochemical analysis and antioxidant potential of the decoction were determined. Levels of oxidative stress biomarkers were determined in brain homogenates, while histopathological analysis was performed on brain sections, and expressions of neuroinflammation markers determined. Results: Polyphenols were detected in K. anthotheca, and the ferric reducing antioxidant power (FRAP) assay revealed antioxidant properties (635.50 ± 0.58 mg eq quercetin/g of dried decoction). Treatment with K. anthotheca decoction reduced MDA and increased GSH levels in brain homogenates (p<0.01). As estradiol valerate, the decoction, prevented neurodegeneration observed in cortices and hippocampi of untreated ovariectomized animals. Conclusions: Our results suggested that K. anthotheca is endowed with neuroprotective effects and warrant further studies, including other models of neurodegeneration and dementia.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"3 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2021-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89769227","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}
Bayinsilema Ba, Abudoukelimu Mayila, Yankai Guo, Jie Xu, Shifeng Xing, GuiQiu Cao
{"title":"NLRC5 enhances autophagy via inactivation of AKT/mTOR pathway and ameliorates cardiac hypertrophy","authors":"Bayinsilema Ba, Abudoukelimu Mayila, Yankai Guo, Jie Xu, Shifeng Xing, GuiQiu Cao","doi":"10.1111/iep.12427","DOIUrl":"10.1111/iep.12427","url":null,"abstract":"<p>The aim of this study was to investigate the effect of nucleotide-binding oligomerization domain (NOD)-like receptor family CARD domain containing 5 (NLRC5) in cardiac hypertrophy, and to explore the mechanism implicated in this effect Cardiac hypertrophy was induced in neonatal rat cardiac myocytes using 1 μM of angiotensin II (Ang II) for 12, 24 and 48 h. Overexpression of NLRC5 was induced in H9C2 cells, and the NLRC5 + Ang II–treated cells were exposed to SC9 and 3‑methyladenine (3MA). An immunofluorescence assay was used for α-actinin staining, and quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed for NLRC5, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) determination. Western blot analysis was applied to measure the levels of NLRC5, microtubule-associated protein 1A/1B-light chain 3 type I (LC3I), LC3II, sequestosome 1 (p62), protein kinase B (AKT), phosphorylated Akt (pAKT), mammalian target of rapamycin (mTOR) and phosphorylated mTOR (pmTOR). The level of NLRC5 was significantly decreased after Ang II treatment in cardiomyocytes, but the levels of ANP and BNP were increased. Overexpression of NLRC5 reduced the cell size, downregulated the levels of ANP and BNP, increased LC3II / LC3I, but decreased p62 in Ang II–induced cardiomyocyte hypertrophy. In addition, the results from Western blot showed that overexpression of NLRC5 distinctly decreased the ratios of pAKT/AKT and pmTOR/mTOR in cardiomyocyte hypertrophy. SC79 and 3MA significantly downregulated the ratio of LC3I/LC3II but increased the level of p62 in NLRC5 + Ang II–treated cells. These results provide a possible novel therapeutic strategy for cardiac hypertrophy that might be useful in a clinical setting.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 1","pages":"23-30"},"PeriodicalIF":3.0,"publicationDate":"2021-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781646/pdf/IEP-103-23.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10594531","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}
Claudio Córdova, Carlo Lozano, Belén Rodríguez, Ivanny Marchant, Rodrigo Zúñiga, Paola Ochova, Pablo Olivero, Wilfredo Alejandro González-Arriagada
{"title":"Optogenetic control of cancer cell survival in ChR2-transfected HeLa cells","authors":"Claudio Córdova, Carlo Lozano, Belén Rodríguez, Ivanny Marchant, Rodrigo Zúñiga, Paola Ochova, Pablo Olivero, Wilfredo Alejandro González-Arriagada","doi":"10.1111/iep.12426","DOIUrl":"10.1111/iep.12426","url":null,"abstract":"<p>Optogenetics is a molecular biological technique involving transfection of cells with photosensitive proteins and the subsequent study of their biological effects. The aim of this study was to evaluate the effect of blue light on the survival of HeLa cells, transfected with channelrhodopsin-2 (ChR2). HeLa wild-type cells were transfected with a plasmid that contained the gene for ChR2. Transfection and channel function were evaluated by real-time polymerase chain reaction (RT-PCR), fluorescence imaging using green fluorescent protein (GFP) and flow cytometry for intracellular calcium changes using a Fura Red probe. We developed a platform for optogenetic stimulation for use within the cell culture incubator. Different stimulation procedures using blue light (467 nm) were applied for up to 24 h. Cell survival was determined by flow cytometry using propidium iodide and rhodamine probes. Change in cell survival showed a statistically significant (<i>p</i> < 0.05) inverse association with the frequency and time of application of the light stimulus. This change seemed to be associated with the ChR2 cis-trans-isomerization cycle. Cell death was associated with high concentrations of calcium in the cytoplasm and stimulation intervals less than the period of isomerization. It is possible to transfect HeLa cells with ChR2 and control their survival under blue light stimulation. We suggest that this practice should be considered in the future development of optogenetic systems in biological or biomedical research.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"102 6","pages":"242-248"},"PeriodicalIF":3.0,"publicationDate":"2021-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39744305","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}
Kullasit Chutipongpisit, V. Praveen Parachuru, Lara T. Friedlander, Haizal M. Hussaini, Alison M. Rich
{"title":"Immunohistochemical and immunofluorescence expression profile of lymphatic endothelial cell markers in oral cancer","authors":"Kullasit Chutipongpisit, V. Praveen Parachuru, Lara T. Friedlander, Haizal M. Hussaini, Alison M. Rich","doi":"10.1111/iep.12411","DOIUrl":"10.1111/iep.12411","url":null,"abstract":"<p>Lymphangiogenesis makes an important contribution to the tumour microenvironment (TME), but little is known about this in oral squamous cell carcinoma (OSCC). Archival formalin-fixed paraffin-embedded specimens (28 OSCC, 10 inflamed and 6 normal oral mucosa controls) were processed using immunohistochemistry (IHC) with antibodies against lymphatic markers D2-40 (podoplanin), LYVE-1, VEGFR3 and Prox1. After the endothelial cells had been highlighted by the various markers for lymphatic endothelium, the positive stained cells and vessels were identified and counted in a systematic manner to determine microvessel density. Double-labelling immunofluorescence (DLIF) was used to investigate the specificity of D2-40 and LYVE-1 to lymphatic endothelial cells (LECs) as opposed to blood ECs. There was higher D2-40 and Prox1 lymphatic vessel density (<i>P</i> = .001) in the OSCC group when compared with both control groups. Some malignant keratinocytes expressed lymphatic markers, as did a much smaller number of epithelial cells in the control groups. DLIF showed that no vessels co-expressed D2-40/CD34 or LYVE/CD34. Some D2/40<sup>+</sup> LVs were LYVE<sup>−</sup>. D2-40 was the most specific LEC marker in OSCC tissues. These results establish that the OSCC TME contains significantly more lymphatic vessels expressing D2-40 and Prox1 than the control groups, which may play a role in facilitating lymphatic invasion and metastases.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"102 6","pages":"268-278"},"PeriodicalIF":3.0,"publicationDate":"2021-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39901968","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":"Correlation between aryl hydrocarbon receptor and IL-17+ and Foxp3+ T-cell infiltration in bladder cancer","authors":"Soheila Fattahi, Monireh Karimi, Mahdi Ghatreh-Samani, Fatemeh Taheri, Hedayatollah Shirzad, Faramarz Mohammad Alibeigi, Maryam Anjomshoa, Nader Bagheri","doi":"10.1111/iep.12392","DOIUrl":"10.1111/iep.12392","url":null,"abstract":"<p>Bladder cancer (BC) is one of the most prevalent cancers around the world and, if not treated well, has high morbidity and mortality. Many studies have indicated that there may be various roles for the aryl hydrocarbon receptor (AHR) in the immune system. The aim of this study was to determine the frequency of Foxp3<sup>+</sup> regulatory T (Treg) and T helper 17 cells (Th17) in BC tissue in comparison with controls and determine the relationship between AHR, Foxp3<sup>+</sup> Treg and Th17 cells in BC. A total of 40 patients with BC were enrolled in this study. The control group was selected from non-tumoural parts of bladder tissues from the patients who have undergone cystoscopy. The percentage of regulatory T cells (Foxp3<sup>+</sup>/CD4<sup>+</sup>) and Th17 (IL-17<sup>+</sup>/CD4<sup>+</sup>), as well as AHR<sup>+</sup> cells in BC tissues and controls, were determined by immunohistochemistry. The results of this study showed that the number of Foxp3<sup>+</sup> Treg and Th17 is significantly higher in bladder tumour tissues in comparison with non-tumoural tissues. Also, the percentage of AHR<sup>+</sup> lymphocytes and AHR<sup>+</sup> cells was increased significantly in bladder tumour tissues rather than non-tumoural tissues. This study also found a relation between AHR and Foxp3<sup>+</sup>/CD4<sup>+</sup> T lymphocytes ratio cells in BC. The percentage of Foxp3<sup>+</sup> Tregs and AHR<sup>+</sup> cells were significantly correlated with the grade and stage of BC. An increase in the percentage of Foxp3<sup>+</sup> Treg and Th17 cells may play an important role in tumour immunity; and determining the relationship between AHR and differentiation of Th17/Foxp3<sup>+</sup>Treg in BC can lead to a potential cancer therapeutic possibility.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"102 6","pages":"249-259"},"PeriodicalIF":3.0,"publicationDate":"2021-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39611609","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}