International Journal Of Experimental Pathology[JOURNAL]
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200 papers
Panx1 knockout promotes preneoplastic aberrant crypt foci development in a chemically induced model of mouse colon carcinogenesis.
Espírito Santo SG, Da Silva TC, Cogliati B … +2 more , Barbisan LF, Romualdo GR
Int J Exp Pathol · 2023 Dec · PMID 37594023 · Full text
Colorectal cancer, which is the third leading cause of cancer-related deaths worldwide, is a multistep disease, featuring preneoplastic aberrant crypt foci (ACF) as the early morphological manifestation. The roles of hem...
Colorectal cancer, which is the third leading cause of cancer-related deaths worldwide, is a multistep disease, featuring preneoplastic aberrant crypt foci (ACF) as the early morphological manifestation. The roles of hemichannel-forming transmembrane Pannexin 1 (Panx1) protein have not been investigated in the context of colon carcinogenesis yet, although it has contrasting roles in other cancer types. Thus, this study was conducted to examine the effects of Panx1 knockout (Panx1 ) on the early events of chemically induced colon carcinogenesis in mouse. Wild type (WT) and Panx1 female C57BL6J mice were submitted to a chemically induced model of colon carcinogenesis by receiving six intraperitoneal administrations of 1,2-dimethylhydrazine (DMH) carcinogen. Animals were euthanized 8 h (week 7) or 30 weeks (week 37) after the last DMH administration in order to evaluate sub-acute colon toxicity outcomes or the burden of ACF, respectively. At week 7, Panx1 genetic ablation increased DMH-induced genotoxicity in peripheral blood cells, malondialdehyde levels in the colon, and apoptosis (cleaved caspase-3) in colonic crypts. Of note, at week 37, Panx1 animals showed an increase in aberrant crypts (AC), ACF mean number, and ACF multiplicity (AC per ACF) by 56%, 57% and 20%, respectively. In essence, our findings indicate that Panx1 genetic ablation promotes preneoplastic ACF development during chemically induced mouse colon carcinogenesis, and a protective role of Panx1 is postulated.
Nek6 knockdown polarized macrophages into a pro-inflammatory phenotype via inhibiting STAT3 expression.
Wu X, Deng KQ, Cai HH … +5 more , Zeng Z, Cao JL, Zhang L, Lu Z, Cheng WL
Int J Exp Pathol · 2023 Oct · PMID 37431082 · Full text
Recently macrophage polarization has emerged as playing an essential role in the oathogenesis of atherosclerosis, which is the most important underlying process in many types of cardiovascular diseases. Although Nek6 has...
Recently macrophage polarization has emerged as playing an essential role in the oathogenesis of atherosclerosis, which is the most important underlying process in many types of cardiovascular diseases. Although Nek6 has been reported to be involved in various cellular processes, the effect of Nek6 on macrophage polarization remains unknown. Macrophages exposed to lipopolysaccharide (LPS) or IL-4 were used to establish an in vitro model for the study of regulation of classically (M1) or alternatively (M2) activated macrophage. Bone marrow-derived macrophages (BMDMs) transfected with short hairpin RNA-targeting Nek6 were then in functional studies. We observed that Nek6 expression was decreased in both peritoneal macrophages (PMs) and BMDMs stimulated by LPS. This effect was seen at both mRNA and protein level. The opposite results were obtained after administration of IL-4. Macrophage-specific Nek6 knockdown significantly exacerbated pro-inflammatory M1 polarized macrophage gene expression in response to LPS challenge, but the anti-inflammatory response gene expression that is related to M2 macrophages was attenuated by Nek6 silencing followed by treatment with IL-4. Mechanistic studies exhibited that Nek6 knockdown inhibited the phosphorylated STAT3 expression that mediated the effect on macrophage polarization regulated by AdshNek6. Moreover, decreased Nek6 expression was also observed in atherosclerotic plaques. Collectively, these evidences suggested that Nek6 acts as a crucial site in macrophage polarization, and that this operates in a STAT3-dependent manner.
mRNA expression profile reveals differentially expressed genes in splenocytes of experimental autoimmune encephalomyelitis model.
Mehmood A, Song S, Du X … +4 more , Yan H, Wang X, Guo L, Li B
Int J Exp Pathol · 2023 Oct · PMID 37427716 · Full text
Experimental autoimmune encephalomyelitis (EAE) is a mouse model that can be used to investigate aetiology, pathogenesis, and treatment approaches for multiple sclerosis (MS). A novel integrated bioinformatics approach w...
Experimental autoimmune encephalomyelitis (EAE) is a mouse model that can be used to investigate aetiology, pathogenesis, and treatment approaches for multiple sclerosis (MS). A novel integrated bioinformatics approach was used to understand the involvement of differentially expressed genes (DEGs) in the spleen of EAE mice through data mining of existing microarray and RNA-seq datasets. We screened differentially expressed mRNAs using mRNA expression profile data of EAE spleens taken from Gene Expression Omnibus (GEO). Functional and pathway enrichment analyses of DEGs were performed by Database for Annotation, Visualization, and Integrated Discovery (DAVID). Subsequently, the DEGs-encoded protein-protein interaction (PPI) network was constructed. The 784 DEGs in GSE99300 A.SW PP-EAE mice spleen mRNA profiles, 859 DEGs in GSE151701 EAE mice spleen mRNA profiles, and 646 DEGs in GSE99300 SJL/J PP-EAE mice spleen mRNA profiles were explored. Functional enrichment of 55 common DEGs among 3 sub-datasets revealed several immune-related terms, such as neutrophil extravasation, leucocyte migration, antimicrobial humoral immune response mediated by an antimicrobial peptide, toll-like receptor 4 bindings, IL-17 signalling pathway, and TGF-beta signalling pathway. In the screening of 10 hub genes, including MPO, ELANE, CTSG, LTF, LCN2, SELP, CAMP, S100A9, ITGA2B, and PRTN3, and in choosing and validating the 5 DEGs, including ANK1, MBOAT2, SLC25A21, SLC43A1, and SOX6, the results showed that SLC43A1 and SOX6 were significantly decreased in EAE mice spleen. Thus this study offers a list of genes expressed in the spleen that might play a key role in the pathogenesis of EAE.
Mechanism of the HIF-1α/VEGF/VEGFR-2 pathway in the proliferation and apoptosis of human haemangioma endothelial cells.
Zhang W, Sun L, Gao H … +1 more , Wang S
Int J Exp Pathol · 2023 Oct · PMID 37381118 · Full text
Haemangiomas (HAs) are prevalent vascular endothelial cell tumours. With respect to the possible involvement of HIF-1α in HAs, we have explored its role in haemangioma endothelial cell (HemEC) proliferation and apoptosis...
Haemangiomas (HAs) are prevalent vascular endothelial cell tumours. With respect to the possible involvement of HIF-1α in HAs, we have explored its role in haemangioma endothelial cell (HemEC) proliferation and apoptosis. shRNA HIF-1α and pcDNA3.1 HIF-α were manipulated into HemECs. HIF-α, VEGF, and VEGFR-2 mRNA and protein levels were assessed by qRT-PCR and Western blotting. Cell proliferation and viability, cell cycle and apoptosis, migration and invasion, and ability to form tubular structures were assessed by colony formation assay, CCK-8, flow cytometry, Transwell assay, and tube formation assay. Cell cycle-related protein levels, and VEGF and VEGFR-2 protein interaction were detected by Western blot and immunoprecipitation assays. An Haemangioma nude mouse model was established by subcutaneous injection of HemECs. Ki67 expression was determined by immunohistochemical staining. HIF-1α silencing suppressed HemEC neoplastic behaviour and promoted apoptosis. HIF-1α facilitated VEGF/VEGFR-2 expression and the VEGF had interacted with VEGFR-2 at protein - protein level. HIF-1α silencing arrested HemECs at G0/G1 phase, diminished Cyclin D1 protein level, and elevated p53 protein level. VEGF overexpression partially abrogated the effects of HIF-1α knockdown on inhibiting HemEC malignant behaviours. Inhibiting HIF-1α in nude mice with HAs repressed tumour growth and Ki67-positive cells. Briefly, HIF-1α regulated HemEC cell cycle through VEGF/VEGFR-2, thus promoting cell proliferation and inhibiting apoptosis.
A prognostic model based on regulatory T-cell-related genes in gastric cancer: Systematic construction and validation.
Tong Q, Ling Y
Int J Exp Pathol · 2023 Oct · PMID 37350375 · Full text
Human gastrointestinal tumours have been shown to contain massive numbers of tumour infiltrating regulatory T cells (Tregs), the presence of which are closely related to tumour immunity. This study was designed to develo...
Human gastrointestinal tumours have been shown to contain massive numbers of tumour infiltrating regulatory T cells (Tregs), the presence of which are closely related to tumour immunity. This study was designed to develop new Treg-related prognostic biomarkers to monitor the prognosis of patients with gastric cancer (GC). Treg-related prognostic genes were screened from Treg-related differentially expressed genes in GC patients by using Cox regression analysis, based on which a prognostic model was constructed. Then, combined with RiskScore, survival curve, survival status assessment and ROC analysis, these genes were used to verify the accuracy of the model, whose independent prognostic ability was also evaluated. Six Treg-related prognostic genes (CHRDL1, APOC3, NPTX1, TREML4, MCEMP1, GH2) in GC were identified, and a 6-gene Treg-related prognostic model was constructed. Survival analysis revealed that patients had a higher survival rate in the low-risk group. Combining clinicopathological features, we performed univariate and multivariate regression analyses, with results establishing that the RiskScore was an independent prognostic factor. Predicted 1-, 3- and 5-year survival rates of GC patients had a good fit with the actual survival rates according to nomogram results. In addition patients in the low-risk group had higher tumour mutational burden (TMB) values. Gene Set Enrichment Analysis (GSEA) demonstrated that genes in the high-risk group were significantly enriched in pathways related to immune inflammation, tumour proliferation and migration. In general, we constructed a 6-gene Treg-associated GC prognostic model with good prediction accuracy, where RiskScore could act as an independent prognostic factor. This model is expected to provide a reference for clinicians to estimate the prognosis of GC patients.
Clinical applications of gene therapy for rare diseases: A review.
Papaioannou I, Owen JS, Yáñez-Muñoz RJ
Int J Exp Pathol · 2023 Aug · PMID 37177842 · Full text
Rare diseases collectively exact a high toll on society due to their sheer number and overall prevalence. Their heterogeneity, diversity, and nature pose daunting clinical challenges for both management and treatment. In...
Rare diseases collectively exact a high toll on society due to their sheer number and overall prevalence. Their heterogeneity, diversity, and nature pose daunting clinical challenges for both management and treatment. In this review, we discuss recent advances in clinical applications of gene therapy for rare diseases, focusing on a variety of viral and non-viral strategies. The use of adeno-associated virus (AAV) vectors is discussed in the context of Luxturna, licenced for the treatment of RPE65 deficiency in the retinal epithelium. Imlygic, a herpes virus vector licenced for the treatment of refractory metastatic melanoma, will be an example of oncolytic vectors developed against rare cancers. Yescarta and Kymriah will showcase the use of retrovirus and lentivirus vectors in the autologous ex vivo production of chimeric antigen receptor T cells (CAR-T), licenced for the treatment of refractory leukaemias and lymphomas. Similar retroviral and lentiviral technology can be applied to autologous haematopoietic stem cells, exemplified by Strimvelis and Zynteglo, licenced treatments for adenosine deaminase-severe combined immunodeficiency (ADA-SCID) and β-thalassaemia respectively. Antisense oligonucleotide technologies will be highlighted through Onpattro and Tegsedi, RNA interference drugs licenced for familial transthyretin (TTR) amyloidosis, and Spinraza, a splice-switching treatment for spinal muscular atrophy (SMA). An initial comparison of the effectiveness of AAV and oligonucleotide therapies in SMA is possible with Zolgensma, an AAV serotype 9 vector, and Spinraza. Through these examples of marketed gene therapies and gene cell therapies, we will discuss the expanding applications of such novel technologies to previously intractable rare diseases.
RUNX1 promotes liver fibrosis progression through regulating TGF-β signalling.
Guo Z, Liu X, Zhao S … +3 more , Sun F, Ren W, Ma M
Int J Exp Pathol · 2023 Aug · PMID 37070207 · Full text
Liver fibrosis is caused by chronic liver injury. There are limited treatments for it, and the pathogenesis is unclear. Therefore, there is an urgent need to explore the pathogenesis of liver fibrosis, and to try to iden...
Liver fibrosis is caused by chronic liver injury. There are limited treatments for it, and the pathogenesis is unclear. Therefore, there is an urgent need to explore the pathogenesis of liver fibrosis, and to try to identify new potential therapeutic targets. For this study we used the carbon tetrachloride abdominal injection induced liver fibrosis animal model in mice. Primary hepatic stellate cell isolation was performed by a density-gradient separation method, and this was followed by immunofluorescence stain analyses. Signal pathway analysis was performed by dual-luciferase reporter assay and western blotting. Our results showed that RUNX1 was upregulated in cirrhotic liver tissues compared with normal liver tissues. Besides, overexpression of RUNX1 caused more severe liver fibrosis lesions than control group under CCl -induced conditions. Moreover, α-SMA expression in the RUNX1 overexpression group was significantly higher than in the control group. Interestingly, we found that RUNX1 could promote the activation of TGF-β/Smads in a dual-luciferase reporter assay. Thus we demonstrated that RUNX1 could be considered as a new regulator of hepatic fibrosis by activating TGF-β/Smads signalling. Based on this, we concluded that RUNX1 may be developed as a new therapeutic target in the treatment of liver fibrosis in the future. In addition, this study also provides a new insight about the aetiology of liver fibrosis.
Abnormal expression and role of MicroRNA-214-3p/SLC8A1 in neonatal Hypoxic-Ischaemic encephalopathy.
Yang L, Zhang L, Zhu J … +4 more , Wang Y, Zou N, Liu Z, Wang Y
Int J Exp Pathol · 2023 Aug · PMID 37032493 · Full text
Neonatal hypoxic-ischaemic encephalopathy (HIE) refers to brain damage caused by intra-uterine distress and asphyxia/hypoxia during the perinatal and neonatal periods. MicroRNA (MiR)-214-3p plays a critical role in cell...
Neonatal hypoxic-ischaemic encephalopathy (HIE) refers to brain damage caused by intra-uterine distress and asphyxia/hypoxia during the perinatal and neonatal periods. MicroRNA (MiR)-214-3p plays a critical role in cell growth and apoptosis. The aim of this study was to investigate the expression and role of miR-214-3p in neonatal HIE development, and to explore the underlying mechanisms. The expression of miR-214-3p was significantly down-regulated, while that of Slc8a1, a direct target of miR-214-3p, was significantly up-regulated, in the brain tissue of neonatal HIE rats. The over-expression of miR-214-3p promoted the proliferation and inhibited the apoptosis of neurones, while its down-regulation had the opposite effect. Our results indicate that miR-214-3p expression was down-regulated in neonatal HIE rats, and the up-regulation of miR-214-3p expression protected against HIE development by inhibiting neuronal apoptosis.
High density of FOXP3 predicts better prognosis in germinal and non-germinal centre diffuse large B-cell lymphoma.
Ahmed AM, Abdel-Hakeem SS, Amine MAF … +2 more , Yassin EH, Badary FAM
Int J Exp Pathol · 2023 Jun · PMID 36974470 · Full text
This study highlights the prognostic impact of FOXP3 and CD68 expression in DLBCL, NOS and in its GCB and non-GCB subtypes. This may help the development of individualized therapy, prognostic prediction and therapy strat...
This study highlights the prognostic impact of FOXP3 and CD68 expression in DLBCL, NOS and in its GCB and non-GCB subtypes. This may help the development of individualized therapy, prognostic prediction and therapy stratification.
Arginine vasopressin deficiency and conivaptan (a V1a-V2 receptor antagonist) treatment reverses liver damage and fibrosis in rats with chronic portocaval anastomosis.
Navarro-Gonzalez YD, Ventura-Juarez J, Muñoz-Ortega MH … +5 more , González-Blas D, Calvillo-Robedo A, Avila-Blanco ME, Valdez-Urias F, Quintanar-Stephano A
Int J Exp Pathol · 2023 Aug · PMID 36964979 · Full text
Arginine vasopressin (AVP) is a naturally occurring hormone synthesized in the hypothalamus. AVP demonstrates pro-fibrotic effects as it stimulates hepatic stellate cells to secrete transforming growth factor-β (TGF-β) a...
Arginine vasopressin (AVP) is a naturally occurring hormone synthesized in the hypothalamus. AVP demonstrates pro-fibrotic effects as it stimulates hepatic stellate cells to secrete transforming growth factor-β (TGF-β) and collagen. Previous work in liver cirrhotic (CCL -induced) hamsters demonstrated that AVP deficiency induced by neurointermediate pituitary lobectomy (NIL) can restore liver function. Therefore, we hypothesized that liver fibrosis would decrease in portocaval anastomosis (PCA) rats, which model chronic liver diseases, when they are treated with the V1a-V2 AVP receptor antagonist conivaptan (CV). In this study, changes in liver histology and gene expression were analysed in five experimental groups: control, PCA, NIL, PCA + NIL and PCA + CV, with NIL surgery or CV treatment administered 8 weeks after PCA surgery. Body weight gain was assessed on a weekly basis, and serum liver function, liver weight and liver glycogen content were assessed following euthanasia. Most PCA-induced phenotypes were reverted to normal levels following AVP-modelled deficiency, though hypoglycemia and ammonium levels remained elevated in the PCA + CV group. Liver histopathological findings showed a significant reversal in collagen content, less fibrosis in the triad and liver septa and increased regenerative nodules. Molecular analyses showed that the expression of fibrogenic genes (TGF-β and collagen type I) decreased in the PCA + CV group. Our findings strongly suggest that chronic NIL or CV treatment can induce a favourable microenvironment to decrease liver fibrosis and support CV as an alternative treatment for liver fibrosis.
Clinicopathological features and immunophenotype of Silva pattern system in endocervical adenocarcinoma.
Zeng C, Wu JK, Lu X
Int J Exp Pathol · 2023 Jun · PMID 36928883 · Full text
The aim of this study was to investigate the correlation between Silva pattern system and clinicopathological features of endocervical adenocarcinoma. Moreover, it was to find molecular markers helpful for Silva classifi...
The aim of this study was to investigate the correlation between Silva pattern system and clinicopathological features of endocervical adenocarcinoma. Moreover, it was to find molecular markers helpful for Silva classification, and thus we also explored the expression levels of invasion, adhesion and proliferation biomarkers in cases of Silva non-invasive and invasive types. The survival based on Silva pattern system was analysed by Kaplan-Meier survival analysis, Log-rank test and a COX risk proportionality model. Sixty samples were chosen to detect the MMP-2, MMP-9, u-PA, E-cadherin, β-catenin, EGF, TGF-α, HDGF, c-Met and RGN expression by immunohistochemistry. Multivariate analysis showed that pattern A/pattern B/pattern C Silva pattern system provided independent risk factors for prognosis. Our results found the levels of MMP-2, MMP-9 and u-PA were significantly higher in endocervical adenocarcinoma with destructive growth than in the nondestructive group. The levels of E-cadherin and β-catenin were significantly lower in endocervical adenocarcinoma with destructive growth than in the nondestructive group. The levels of EGF, TGF-α and HDGF were significantly higher in endocervical adenocarcinoma with destructive growth than in the nondestructive group. Compared with 'non-invasive/invasive Silva pattern', this study suggests 'pattern A/pattern B/pattern C Silva pattern' could be a better criteria for predicting the prognosis. Furthermore, the dual-marker combination of 'MMP-2 and u-PA' and 'E-cadherin and β-catenin' is very important in the diagnosis of Silva pattern classification.
Effect of chronic exposure to fine particulate matter on cardiac tissue of NZBWF1 mice.
Waked D, Rodrigues ACB, Silva TM … +3 more , Yariwake VY, Farhat SCL, Veras MM
Int J Exp Pathol · 2023 Aug · PMID 36918483 · Full text
Epidemiological and toxicological studies have shown that inhalation of particulate matter (PM) is associated with development of cardiovascular diseases. Long-term exposure to PM may increase the risk of cardiovascular...
Epidemiological and toxicological studies have shown that inhalation of particulate matter (PM) is associated with development of cardiovascular diseases. Long-term exposure to PM may increase the risk of cardiovascular events and reduce life expectancy. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, autoimmune in nature, that is characterized by the production of autoantibodies that affects several organs, including the heart. Air pollution - which can be caused by several different factors - may be one of the most important points both at the onset and the natural history of SLE. Therefore this study aims to investigate whether exposure to air pollution promotes increased inflammation and cardiac remodelling in animals predisposed to SLE. Female NZBWF1 mice were exposed to an environmental particle concentrator. Aspects related to cardiac remodelling, inflammation and apoptosis were analysed in the myocardium. Body weight gain, cardiac trophism by heart/body weight ratio, relative area of cardiomyocytes and the fibrotic area of cardiac tissue were evaluated during the exposure period. Animals exposed to PM2.5 showed increased area of cardiomyocytes, and area of fibrosis; in addition, we observed an increase in IL-1 and C3 in the cardiac tissue, demonstrating increased inflammation. We suggest that air pollution is capable of promoting cardiac remodelling and increased inflammation in animals predisposed to SLE.
British Society for Matrix Biology Autumn Meeting 2022: "Matrix in Development".
Int J Exp Pathol · 2023 Apr · PMID 36908099 · Full text
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Wnt signalling in the articular cartilage: A matter of balance.
Gill AK, McCormick PJ, Sochart D … +1 more , Nalesso G
Int J Exp Pathol · 2023 Apr · PMID 36843204 · Full text
Degradation of the articular cartilage is a hallmark of osteoarthritis, a progressive and chronic musculoskeletal condition, affecting millions of people worldwide. The activation of several signalling cascades is altere...
Degradation of the articular cartilage is a hallmark of osteoarthritis, a progressive and chronic musculoskeletal condition, affecting millions of people worldwide. The activation of several signalling cascades is altered during disease development: among them, the Wnt signalling plays a pivotal role in the maintenance of tissue homeostasis. Increasing evidence is showing that its activation needs to be maintained within a certain range to avoid the triggering of degenerative mechanisms. In this review, we summarise our current knowledge about how a balanced activation of the Wnt signalling is maintained in the articular cartilage, with a particular focus on receptor-mediated mechanisms.
miR-144-3p represses hepatocellular carcinoma progression by affecting cell aerobic glycolysis via FOXK1.
Xing B, Shen C, Yang Q … +2 more , Wang Z, Tan W
Int J Exp Pathol · 2023 Jun · PMID 36806218 · Full text
Aerobic glycolysis is a unique mark of cancer cells, which enables therapeutic intervention in cancer. Forkhead box K1 (FOXK1) is a transcription factor that facilitates the progression of multiple cancers including hepa...
Aerobic glycolysis is a unique mark of cancer cells, which enables therapeutic intervention in cancer. Forkhead box K1 (FOXK1) is a transcription factor that facilitates the progression of multiple cancers including hepatocellular carcinoma (HCC). Nevertheless, it is unclear whether or not FOXK1 can affect HCC cell glycolysis. This study attempted to study the effect of FOXK1 on HCC cell glycolysis. Expression of mature miRNAs and mRNAs, as well as clinical data, was downloaded from The Cancer Genome Atlas-Liver hepatocellular carcinoma (TCGA-LIHC) dataset. FOXK1 and miR-144-3p levels were assessed through quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Targeting of the relationship between miR-144-3p and FOXK1 was verified via a dual-luciferase assay. Pathway enrichment analysis of FOXK1 was performed by Gene Set Enrichment Analysis (GSEA). Cell function assays revealed the glycolytic ability, cell viability, migration, invasion, cell cycle, and apoptosis of HCC cells in each treatment group. Bioinformatics analysis suggested that FOXK1 was upregulated in tissues of HCC patients, while the upstream miR-144-3p was downregulated in tumour tissues. Dual-luciferase assay implied a targeting relationship between miR-144-3p and FOXK1. Cellular experiments implied that silencing FOXK1 repressed HCC cell glycolysis, which in turn inhibited the HCC malignant progression. Rescue assay confirmed that miR-144-3p repressed glycolysis in HCC cells by targeting FOXK1, and then repressed HCC malignant progression. miR-144-3p/FOXK1 axis repressed malignant progression of HCC via affecting the aerobic glycolytic process of HCC cells. miR-144-3p and FOXK1 have the potential to become new therapeutic targets for HCC, which provide new insights for HCC treatment.
Arnica montana L. associated with microcurrent accelerates the dermis reorganisation of skin lesions.
Zacarias CA, de Mendonça Florenziano RF, de Andrade TAM … +4 more , de Aro AA, do Amaral MEC, Dos Santos GMT, Esquisatto MAM
Int J Exp Pathol · 2023 Apr · PMID 36752313 · Full text
The aim of this study was to test the effect of electrical stimulation in association with topical Arnica montana gel on organisational changes in the dermis during tissue repair. An experimental rat incisional skin lesi...
The aim of this study was to test the effect of electrical stimulation in association with topical Arnica montana gel on organisational changes in the dermis during tissue repair. An experimental rat incisional skin lesion was used for the study. This involved making an incisional lesion on the dorsum of the animals using a scalpel. Ninety-six animals were used divided into the following groups: control (C), microcurrent (MC); topical treatment with Arnica montana gel (ARN); the ARN + microcurrent (ARN + MC). Treatments were administered daily, and injured tissue samples were collected and processed on Days 2, 6 and 10 for dermis analyses. Myeloperoxidase levels were greater in control than in treatment groups on Days 2 and 6. F4/80 expression was similar among all treatment groups and greater than that in control on Day 2. On Day 6, the expression of vascular endothelial growth factor was higher in the MC group than that in other groups, whereas transforming growth factor-β expression increased in the MC and ARN + MC groups on Day 10. The expression of matrix metalloproteinase-2 was higher in the ARN + MC group when compared with other groups on Day 10. Expression levels of collagen I were increased in the ARN and ARN + MC groups when compared with control and MC groups on Day 6, while expression of collagen III was enhanced in MC, ARN, and ARN + MC groups when compared with the control. The protocol combining microcurrent with topical application of ARN reduces the inflammatory process, increases myofibroblasts proliferation and decreases the presence of macrophages in the dermis during skin repair in rats.
The frequency of dysplastic branching crypts in colorectal polypoid tubular adenomas.
Rubio CA, Vieth M, Lang-Schwarz C
Int J Exp Pathol · 2023 Jun · PMID 36734673 · Full text
Dysplastic crypt branching (DCB) was recently found in ulcerative colitis-associated dysplasia. The aim was to assess the frequency and the branching phenotype of DCB in polypoid colorectal tubular adenomas (TA). A total...
Dysplastic crypt branching (DCB) was recently found in ulcerative colitis-associated dysplasia. The aim was to assess the frequency and the branching phenotype of DCB in polypoid colorectal tubular adenomas (TA). A total of 3956 DCB were found in the 139 TA: 98% were in asymmetric branching (DCAB) and the remaining 2% in symmetric branching (DCSB). A linear correlation was found between DCB frequency and the increasing digital size in TA (p < .05). Using a digital ruler, adenomas were divided into small TA (<5 mm) and larger TA (≥5 mm). The difference between the frequency of DCB in small TA (n = 75) vs. larger TA (n = 64), was significant (p < .05). DCB frequency was not influenced by age, gender or TA localization. In the normal colorectal mucosa (≈2 m ), only occasional CSB is found and no CAB. And yet, multiple DCB (mean 16.7 DCB), mostly DCAB, was found in small TA, occupying <5 mm of the mucosal area. In larger TA, as many as 42.1 DCB (mean), mostly DCAB, occurred in merely 7.8 mm (mean) of the colon mucosa. Thus it is suggested that DCB is a standard histologic element of TA. The natural expansion of the adenomatous tissue in larger TA appears to be follow on from newly produced, mostly DCAB, by DCSB and by the accumulation of their dysplastic offspring's progenies. The findings strongly suggest that DCB is a central microstructure in the histological events unfolding in polypoid colorectal TA.
MIMT1 and LINC01550 are uncharted lncRNAs down-regulated in colorectal cancer.
Vejdandoust F, Moosavi R, Fattahi Dolatabadi N … +2 more , Zamani A, Tabatabaeian H
Int J Exp Pathol · 2023 Jun · PMID 36727289 · Full text
Incomplete knowledge of the molecular basis of colorectal cancer, with subsequent limitations in early diagnosis and effective treatment, has contributed to this form of malignancy becoming the second most common cause o...
Incomplete knowledge of the molecular basis of colorectal cancer, with subsequent limitations in early diagnosis and effective treatment, has contributed to this form of malignancy becoming the second most common cause of cancer-related death worldwide. With the advances in high-throughput profiling techniques and the availability of public data sets such as The Cancer Genome Atlas Program (TCGA), a broad range of coding transcripts have been profiled and their underlying modes of action have been mapped. However, there is still a huge gap in our understanding of noncoding RNA dysregulation. To this end, we used a bioinformatics approach to shortlist and evaluate yet-to be-profiled long noncoding RNAs (lncRNAs) in colorectal cancer. We analysed the TCGA RNA-seq data and followed this by validating the expression patterns using a qPCR technique. Analysing in-house clinical samples, the real-time PCR method revealed that the shortlisted lncRNAs, that is MER1 Repeat Containing Imprinted Transcript 1 (MIMT1) and Non-Protein Coding RNA 1550 (LINC01550), were down-regulated in colorectal cancer tumours compared with the paired adjacent normal tissues. Mechanistically, the in silico results suggest that LINC01550 could form a complex competitive endogenous RNA (ceRNA) network leading to the subsequent regulation of colorectal cancer-related genes, such as CUGBP Elav-Like Family Member (CELF2), Polypyrimidine Tract Binding Protein 1 (PTBP1) and ELAV Like RNA Binding Protein 1 (ELAV1). The findings of this work indicate that MIMT1 and LINC01550 could be novel tumour suppressor genes that can be studied further to assess their roles in regulating the cancer signalling pathway(s).
Synergistic activation of genes promoting invasiveness by dual deprivation in oxygen and nutrients.
Jehanno C, Le Page Y, Flouriot G … +2 more , Le Goff P, Michel D
Int J Exp Pathol · 2023 Apr · PMID 36694990 · Full text
By depriving cancer cells of blood supplies of oxygen and nutrients, anti-angiogenic therapy is aimed at simultaneously asphyxiating and starving the cells. But in spite of its apparent logic, this strategy is generally...
By depriving cancer cells of blood supplies of oxygen and nutrients, anti-angiogenic therapy is aimed at simultaneously asphyxiating and starving the cells. But in spite of its apparent logic, this strategy is generally counterproductive over the long term as the treatment seems to elicit malignancy. Since a defect of blood supply is expected to deprive tumours simultaneously of oxygen and nutrients naturally, we examine here these two deprivations, alone or in combination, on the phenotype and signalling pathways of moderately aggressive MCF7 cancer cells. Each deprivation induces some aspects of the aggressive and migratory phenotypes through activating several pathways, including HIF1-alpha as expected, but also SRF/MRTFA and TCF4/beta-catenin. Strikingly, the dual deprivation has strong cooperative effects on the upregulation of genes increasing the metastatic potential, such as four and a half LIM domains 2 (FHL2) and HIF1A-AS2 lncRNA, which have response elements for both pathways. Using anti-angiogenic agents as monotherapy is therefore questionable as it may give falsely promising short-term tumour regression, but could ultimately exacerbate aggressive phenotypes.
Apoptosis versus necrosis in tubal ectopic pregnancies following Methotrexate.
Gil Y, Zubkov A, Balayla J … +2 more , Cohen A, Levin I
Int J Exp Pathol · 2023 Apr · PMID 36692117 · Full text
Methotrexate administration for the treatment of tubal ectopic pregnancies has been shown to cause tubal mass enlargement. Our hypothesis was that, by administrating Methotrexate, a local necrotic reaction occurs, leadin...
Methotrexate administration for the treatment of tubal ectopic pregnancies has been shown to cause tubal mass enlargement. Our hypothesis was that, by administrating Methotrexate, a local necrotic reaction occurs, leading to hematoma formation and eventually fallopian tube rupture. Salpingectomy specimens were collected, analysed and divided into three equal groups: patients who received Methotrexate but who ultimately failed medical treatment, patients who had a viable ectopic pregnancy and patients with a self-resolving ectopic pregnancy that were operated due to other medical indications. The specimens were dyed using the Cleaved Caspase-3 (Asp175) Rabbit mA. Specimens were divided into three equal groups and analysed. The patients in self-resolving ectopic pregnancy group were older and had more pregnancies. Rates of apoptosis were found to be less than 1% per slide. Necrosis was not evident in any of the pathological specimens. It seems Methotrexate administration does not lead to a significant tubal necrotic reaction. Further studies are required.
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