International Journal Of Experimental Pathology[JOURNAL]
Sun
200 papers
Extracellular matrix dynamics in cell migration, invasion and tissue morphogenesis.
Yamada KM, Collins JW, Cruz Walma DA … +8 more , Doyle AD, Morales SG, Lu J, Matsumoto K, Nazari SS, Sekiguchi R, Shinsato Y, Wang S
Int J Exp Pathol · 2019 Jun · PMID 31179622 · Full text
This review describes how direct visualization of the dynamic interactions of cells with different extracellular matrix microenvironments can provide novel insights into complex biological processes. Recent studies have...
This review describes how direct visualization of the dynamic interactions of cells with different extracellular matrix microenvironments can provide novel insights into complex biological processes. Recent studies have moved characterization of cell migration and invasion from classical 2D culture systems into 1D and 3D model systems, revealing multiple differences in mechanisms of cell adhesion, migration and signalling-even though cells in 3D can still display prominent focal adhesions. Myosin II restrains cell migration speed in 2D culture but is often essential for effective 3D migration. 3D cell migration modes can switch between lamellipodial, lobopodial and/or amoeboid depending on the local matrix environment. For example, "nuclear piston" migration can be switched off by local proteolysis, and proteolytic invadopodia can be induced by a high density of fibrillar matrix. Particularly, complex remodelling of both extracellular matrix and tissues occurs during morphogenesis. Extracellular matrix supports self-assembly of embryonic tissues, but it must also be locally actively remodelled. For example, surprisingly focal remodelling of the basement membrane occurs during branching morphogenesis-numerous tiny perforations generated by proteolysis and actomyosin contractility produce a microscopically porous, flexible basement membrane meshwork for tissue expansion. Cells extend highly active blebs or protrusions towards the surrounding mesenchyme through these perforations. Concurrently, the entire basement membrane undergoes translocation in a direction opposite to bud expansion. Underlying this slowly moving 2D basement membrane translocation are highly dynamic individual cell movements. We conclude this review by describing a variety of exciting research opportunities for discovering novel insights into cell-matrix interactions.
Short-term exposure to chrysin promotes proliferative responses in the ventral male prostate and female prostate of adult gerbils.
Campos MS, Silva JPA, Lima DS … +5 more , Regasini LO, Marques MR, Biancardi MF, Taboga SR, Santos FCA
Int J Exp Pathol · 2019 Jun · PMID 31131507 · Full text
Chrysin (5,7-dihydroxyflavone) is a bioactive compound found in different fruits, vegetables, honey and propolis. This flavone has been suggested for the treatment of reproductive dysfunction, mainly because of its antio...
Chrysin (5,7-dihydroxyflavone) is a bioactive compound found in different fruits, vegetables, honey and propolis. This flavone has been suggested for the treatment of reproductive dysfunction, mainly because of its antioxidant and hormonal properties. However, the effects of this polyphenol on the prostate are still poorly understood. The purpose of this study was to evaluate the effects of short-term chrysin exposure on the ventral male and female prostates of adult gerbils. To evaluate the androgenic potential of chrysin, gerbils were also exposed to testosterone. Male and female gerbils were exposed to chrysin (50 mg/kg/day, orally) or testosterone cypionate (1 mg/kg/week, subcutaneously) for 3, 7 and 21 days. Prostates were dissected for morphological, stereological and immunohistochemical analyses. Serum levels of testosterone and 17β-estradiol were measured by ELISA. Serum testosterone levels were not increased by chrysin supplementation in males or females. However, only females treated with chrysin for 21 days showed an increase in estradiol levels. Increased androgen receptor immunoreactivity, higher proliferation rates and glandular hyperplasia were observed in male and female prostates for all chrysin treatment times. Additionally, increased oestrogen receptor alpha immunoreactivity was observed in all chrysin-treated females. Although chrysin and testosterone promoted similar morphological changes in the gerbil prostate, chrysin supplementation was less deleterious to prostate health, since it resulted in lower incidence of hyperplasia and an absence of neoplastic foci.
Murine experimental leprosy: Evaluation of immune response by analysis of peritoneal lavage cells and footpad histopathology.
Vilani-Moreno FR, Barbosa ASAA, Sartori BGC … +7 more , Diório SM, Silva SMUR, Rosa PS, de Faria Fernandes Belone A, Soares CT, Lauris JRP, Pedrini SCB
Int J Exp Pathol · 2019 Jun · PMID 31124597 · Full text
This study evaluated the immune response of nude and BALB/c mice inoculated in the footpads (FP) with Mycobacterium leprae after 3, 5 and 8 months. At each timepoint peritoneal cells, peripheral blood, FP and popliteal l...
This study evaluated the immune response of nude and BALB/c mice inoculated in the footpads (FP) with Mycobacterium leprae after 3, 5 and 8 months. At each timepoint peritoneal cells, peripheral blood, FP and popliteal lymph nodes (PLN) were collected. Peritoneal cell cultures were performed to measure the H O , O , NO, IL-2, IL-4, IL-10, IL-12, IFN-γ and TNF levels. Serum levels of anti-PGL-I antibodies were also quantified. The results showed that the infection was progressive in nude mice with bacterial multiplication, development of macroscopic lesions in the FP and presence of bacilli in the PLN at 8 months. In BALB/c mice, the infection reached a plateau of bacillary multiplication at 5 months and regressed at 8 months. Histopathological analysis of FP revealed a mononuclear inflammatory infiltrate with a large number of neutrophils at 5 months, with a higher number in nude mice. At 8 months, the number of neutrophils decreased and the infiltrate was predominantly mononuclear in both mouse strains. There was no H O O , IL-2, IL-4, IL-10 and IFN-γ production in the course of infection in nude mice; however, in BALB/c, O and IL-12 production was higher at 5 months and NO, IFN-γ and TNF production was higher at 8 months when there was a decrease in the number of bacilli. The level of anti-PGL-I antibodies was higher in BALB/c mice. Thus, nude and BALB/c mice can be used as experimental models for the study of various aspects of leprosy.
Co-expression of TLR-9 and MMP-13 is associated with the degree of tumour differentiation in prostate cancer.
Kalantari E, Abolhasani M, Roudi R … +5 more , Farajollahi MM, Farhad S, Madjd Z, Askarian-Amiri S, Mohsenzadegan M
Int J Exp Pathol · 2019 Apr · PMID 31090157 · Full text
In vitro experiments demonstrated that stimulation of Toll-like receptor 9 (TLR-9) by synthetic TLR-9 ligands induces the invasion of TLR-9-expressing prostate cancer cells through matrix metalloproteinase 13 (MMP-13). H...
In vitro experiments demonstrated that stimulation of Toll-like receptor 9 (TLR-9) by synthetic TLR-9 ligands induces the invasion of TLR-9-expressing prostate cancer cells through matrix metalloproteinase 13 (MMP-13). However, the clinical value of TLR-9 and MMP-13 co-expression in the pathophysiology of the prostate is unknown. In the study, we evaluated the expression levels and clinical significance of the TLR-9 and MMP-13 in a series of prostate tissues. One hundred and eighty prostate tissues including prostate cancer (PCa) (n = 137), high-grade prostatic intraepithelial neoplasia (HPIN) (n = 18) and benign prostatic hyperplasia (BPH) (n = 25) were immunostained for the TLR-9 and MMP-13 markers. Subsequently, the correlation between the TLR-9 and MMP-13 staining scores and clinicopathological parameters was obtained. Higher expressions of TLR-9 and MMP-13 were found in PCa and high-grade prostatic intraepithelial neoplasia compared to benign prostatic hyperplasia tissues. Among PCa samples, a positive relationship was revealed between the MMP-13 expression and Gleason score (P < 0.001). There was a significant correlation between TLR-9 expression and regional lymph node involvement (P = 0.04). The expression patterns of TLR-9 and MMP-13 markers demonstrated a reciprocal significant correlation between the two markers in the same series of prostate samples (P < 0.001). Furthermore, the Gleason score of TLR-9 /MMP-13 and TLR-9 /MMP-13 phenotypes showed a significant difference (P = 0.002). Higher expressions of TLR-9 and MMP-13 can confer aggressive behaviour to PCa. Therefore, these markers may be used as a valuable target for tailored therapy of PCa.
The impact of variations in transcription of DICER and AGO2 on exacerbation of childhood B-cell lineage acute lymphoblastic leukaemia.
Piroozian F, Bagheri Varkiyani H, Koolivand M … +4 more , Ansari M, Afsa M, AtashAbParvar A, MalekZadeh K
Int J Exp Pathol · 2019 Jun · PMID 31090156 · Full text
The expression of microRNA in eukaryotic cells is subject to tightly regulated processing. The altered expression of microRNAs in a number of cancers suggests their contribution to disease pathogenesis, where processing...
The expression of microRNA in eukaryotic cells is subject to tightly regulated processing. The altered expression of microRNAs in a number of cancers suggests their contribution to disease pathogenesis, where processing pathways may be involved in disease pathogenesis. In the present study, we evaluated changes in the profile of two main components of microRNA biogenesis, AGO2 and DICER, and assessed their correlation with disease progression in childhood acute lymphoblastic leukaemia (ALL). To achieve this aim, 25 patients afflicted with ALL were included in the study along with 25 healthy subjects as control. The expression level of AGO2 and DICER was evaluated by real-time PCR. The results revealed an increase in the expression of DICER and a decrease in AGO2 in patients. The correlation between the alteration levels of these genes with pathologic events was also studied. This increase or decrease proved to be directly correlated with the progression of the disease particularly in L1 to L2. According to the obtained results, it can be deduced that dysregulation in transcription of DICER and AGO2, involved in the formation of mature microRNAs in cytoplasm of ALL cancer cells, is a part of the pathological molecular mechanism implicated in the exacerbation of this malignancy. Therefore, the genes involved in microRNAs biogenesis that have been studied here could be considered as candidate prognostic markers especially in childhood ALL which will help towards a better understanding of the molecular basis of ALL.
Myelination key factor krox-20 is downregulated in Schwann cells and murine sciatic nerves infected by Mycobacterium leprae.
Casalenovo MB, Rosa PS, de Faria Bertoluci DF … +4 more , Barbosa ASAA, Nascimento DCD, de Souza VNB, Nogueira MRS
Int J Exp Pathol · 2019 Apr · PMID 31090128 · Full text
Schwann cells (SCs) critically maintain the plasticity of the peripheral nervous system. Peripheral nerve injuries and infections stimulate SCs in order to retrieve homeostasis in neural tissues. Previous studies indicat...
Schwann cells (SCs) critically maintain the plasticity of the peripheral nervous system. Peripheral nerve injuries and infections stimulate SCs in order to retrieve homeostasis in neural tissues. Previous studies indicate that Mycobacterium leprae (ML) regulates the expression of key factors related to SC identity, suggesting that alterations in cell phenotype may be involved in the pathogenesis of neural damage in leprosy. To better understand whether ML restricts the plasticity of peripheral nerves, the present study sought to determine the expression of Krox-20, Sox-10, c-Jun and p75NTR in SC culture and mice sciatic nerves, both infected by ML Thai-53 strain. Primary SC cultures were stimulated with two different multiplicities of infection (MOI 100:1; MOI 50:1) and assessed after 7 and 14 days. Sciatic nerves of nude mice (NU-Foxn1 ) infected with ML were evaluated after 6 and 9 months. In vitro results demonstrate downregulation of Krox-20 and Sox-10 along with the increase in p75NTR-immunolabelled cells. Concurrently, sciatic nerves of infected mice showed a significant decrease in Krox-20 and increase in p75NTR. Our results corroborate previous findings on the interference of ML in the expression of factors involved in cell maturation, favouring the maintenance of a non-myelinating phenotype in SCs, with possible implications for the repair of adult peripheral nerves.
Modern approaches for modelling dystonia and Huntington's disease in vitro and in vivo.
Zhunina OA, Yabbarov NG, Orekhov AN … +1 more , Deykin AV
Int J Exp Pathol · 2019 Apr · PMID 31090117 · Full text
Dystonia associated with Huntington's disease, Parkinson's disease or other neurodegenerative diseases substantially affects patients' quality of life and is a major health problem worldwide. The above-mentioned diseases...
Dystonia associated with Huntington's disease, Parkinson's disease or other neurodegenerative diseases substantially affects patients' quality of life and is a major health problem worldwide. The above-mentioned diseases are characterized by neurodegeneration accompanied by motor and cognitive impairment and often have complex aetiology. A frequent feature of these conditions is the abnormal accumulation of protein aggregates within specific neuronal populations in the affected brain regions. Familial neurodegenerative diseases are associated with a number of genetic mutations. Identification of these mutations allowed creation of modern model systems for studying neurodegeneration, either in cultured cells or in model animals. Animal models, especially mouse models, have contributed considerably to improving our understanding of the pathophysiology of neurodegenerative diseases. These models have allowed study of the pathogenic mechanisms and development of new disease-modifying strategies and therapeutic approaches. However, due to the complex nature of these pathologies and the irreversible damage that they cause to the neural tissue, effective therapies against neurodegeneration remain to be elaborated. In this review, we provide an overview of cellular and animal models developed for studying neurodegenerative diseases, including Huntington's disease and dystonia of different origins.
MT1-MMP evaluation in neointimal hyperplasia in the late follow-up after prosthesis implantation.
Bruczko M, Gogiel T, Wolańska M … +3 more , Kowalewski R, Sobolewski K, Romanowicz L
Int J Exp Pathol · 2019 Apr · PMID 31058412 · Full text
Vascular surgical interventions are often burdened with late complications, including thrombosis or restenosis. The latter is generally caused by neointimal hyperplasia. Although extracellular matrix (ECM) remodelling is...
Vascular surgical interventions are often burdened with late complications, including thrombosis or restenosis. The latter is generally caused by neointimal hyperplasia. Although extracellular matrix (ECM) remodelling is an important part of neointima formation, this process is not clearly understood. The aim of the study was to assess the content and activity of membrane-type 1 matrix metalloproteinase in human neointima in the late stages of its development. Matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 were also evaluated. The research was performed on neointima samples collected during secondary vascular interventions from patients with chronic limb ischaemia who developed vascular occlusion at 6-18 months after aorto/ilio-femoral bypass grafting. The control material consisted of segments of femoral arteries collected from organ donors. Western blot and/or ELISA were used for the determination of MT1-MMP and TIMP-2 expression. The activity of MT1-MMP was measured by fluorometric assay and that of MMP-2 by zymography. We demonstrated significantly increased MT1-MMP protein content in neointima when compared to normal arteries. However, the activity of MT1-MMP was significantly lower in neointima than in control samples. The decreased MT1-MMP activity was concomitant with reduced activity of MMP-2. The TIMP-2 protein levels in neointima and normal arteries were not significantly different. The results of our study suggest that the reduced activity of MT1-MMP and consequently MMP-2 in human neointima may play a role in decreased degradation of ECM components and thus promote neointimal overgrowth.
Carboxypeptidase A4 promotes proliferation and stem cell characteristics of hepatocellular carcinoma.
Zhang H, Hao C, Wang H … +2 more , Shang H, Li Z
Int J Exp Pathol · 2019 Apr · PMID 31058377 · Full text
Carboxypeptidase A4 (CPA4), a member of the metallo-carboxypeptidase family, is overexpressed in liver cancer and is associated with cancer progression. The role of CPA4 in hepatocellular carcinoma (HCC) remains unclear....
Carboxypeptidase A4 (CPA4), a member of the metallo-carboxypeptidase family, is overexpressed in liver cancer and is associated with cancer progression. The role of CPA4 in hepatocellular carcinoma (HCC) remains unclear. In this study, we aimed to evaluate the relevance of CPA4 to the proliferation and expression of stem cell characteristics of hepatocellular carcinoma cells. Western blot analysis showed high CPA4 expression in the liver cancer cell line Bel7402 and low expression in HepG2 cells. Knock-down of CPA4 decreased cancer cell proliferation as detected by MTT and clone formation assays. The serum-free culture system revealed that downregulated CPA4 suppressed the sphere formation capacities of tumour cells. However, upregulated CPA4 increased the proliferation and sphere formation capacity. In addition, the protein expression of CD133, ALDH1 and CD44 also increased in cells with upregulated CPA4. In vivo, the overexpression of CPA4 in tumour cells that were subcutaneously injected into nude mice markedly increased the growth of the tumours. These data suggest that CPA4 expression leads to poor prognoses by regulating tumour proliferation and the expression of stem cell characteristics and may therefore serve as a potential therapeutic target of HCC.
Absence of the β1 subunit of AMP-activated protein kinase reduces myofibroblast infiltration of the kidneys in early diabetes.
Choy SW, Fraser SA, Katerelos M … +4 more , Galic S, Kemp BE, Mount PF, Power DA
Int J Exp Pathol · 2019 Apr · PMID 31025787 · Full text
Activation of the heterotrimeric energy-sensing kinase AMP-activated protein kinase (AMPK) has been reported to improve experimental diabetic kidney disease. We examined the effect of type 1 diabetes in wild-type (WT) mi...
Activation of the heterotrimeric energy-sensing kinase AMP-activated protein kinase (AMPK) has been reported to improve experimental diabetic kidney disease. We examined the effect of type 1 diabetes in wild-type (WT) mice and mice lacking the β1 subunit of AMPK (AMPK β1 mice), which have reduced AMPK activity in kidneys and other organs. Diabetes was induced using streptozotocin (STZ) and the animals followed up for 4 weeks. Hyperglycaemia was more severe in diabetic AMPK β1 mice, despite the absence of any difference in serum levels of insulin, adiponectin and leptin. There was no change in AMPK activity in the kidneys of diabetic WT mice by AMPK activity assay, or phosphorylation of either the αT172 activation site on the α catalytic subunit of AMPK or the AMPK-specific phosphosite S79 on acetyl CoA carboxylase 1 (ACC1). Phosphorylation of the inhibitory αS485 site on the α subunit of AMPK was significantly increased in the WT diabetic mice compared to non-diabetic controls. Despite increased plasma glucose levels in the diabetic AMPK β1 mice, there were fewer myofibroblasts in the kidneys compared to diabetic WT mice, as evidenced by reduced α-smooth muscle actin (α-SMA) protein by Western blot, mRNA by qRT-PCR and fewer α-SMA-positive cells by immunohistochemical staining. Albuminuria was also reduced in the AMPK β1 mice. In contrast to previous studies, therefore, myofibroblasts were reduced in the kidneys of AMPK β1 diabetic mice compared to diabetic WT mice, despite increased circulating glucose, suggesting that AMPK can worsen renal fibrosis in type 1 diabetes.
Non-inferiority of microencapsulated mesenchymal stem cells to free cells in cardiac repair after myocardial infarction: A rationale for using paracrine factor(s) instead of cells.
Karpov AA, Puzanov MV, Ivkin DY … +5 more , Krasnova MV, Anikin NA, Docshin PM, Moiseeva OM, Galagudza MM
Int J Exp Pathol · 2019 Apr · PMID 31017330 · Full text
A major translational barrier to the use of stem cell (SC)-based therapy in patients with myocardial infarction (MI) is the lack of a clear understanding of the mechanism(s) underlying the cardioprotective effect of SCs....
A major translational barrier to the use of stem cell (SC)-based therapy in patients with myocardial infarction (MI) is the lack of a clear understanding of the mechanism(s) underlying the cardioprotective effect of SCs. Numerous paracrine factors from SCs may account for reduction in infarct size, but myocardial salvage associated with transdifferentiation of SCs into vascular cells as well as cardiomyocyte-like cells may be involved too. In this study, bone marrow-derived rat mesenchymal SC (MSCs) were microencapsulated in alginate preventing viable cell release while supporting their secretory phenotype. The hypothesis on the key role of paracrine factors from MSCs in their cardioprotective activity was tested by comparison of the effect of encapsulated vs free MSCs in the rat model of MI. Intramyocardial administration of both free and encapsulated MSCs after MI caused reduction in scar size (12.1 ± 6.83 and 14.7 ± 4.26%, respectively, vs 21.7 ± 6.88% in controls, P = 0.015 and P = 0.03 respectively). Scar size was not different in animals treated with free and encapsulated MSC (P = 0.637). These data provide evidence that MSC-derived growth factors and cytokines are crucial for cardioprotection elicited by MSC. Administration of either free or encapsulated MSCs was not arrhythmogenic in non-infarcted rats. The consistency of our data with the results of other studies on the major role of MSC secretome components in cardiac protection further support the theory that the use of live, though encapsulated, cells for MI therapy may be replaced with heart-targeted-sustained delivery of growth factors/cytokines.
Gene cloning to clinical trials-the trials and tribulations of a life with collagen.
Boot-Handford RP
Int J Exp Pathol · 2019 Feb · PMID 30912609 · Full text
This review, based on the BSMB Fell-Muir Lecture I presented in July 2018 at the Matrix Biology Europe Conference in Manchester, gives a personal perspective of my own laboratory's contributions to research into type X c...
This review, based on the BSMB Fell-Muir Lecture I presented in July 2018 at the Matrix Biology Europe Conference in Manchester, gives a personal perspective of my own laboratory's contributions to research into type X collagen, metaphyseal chondrodysplasia type Schmid and potential treatments for this disorder that are currently entering clinical trial. I have tried to set the advances made in the context of the scientific technologies available at the time and how these have changed over the more than three decades of this research.
Investigation of expressions of PDK1, PLK1 and c-Myc in diffuse large B-cell lymphoma.
Feng Y, Lin J, Liu Y … +3 more , Tang Y, Zhou Y, Zhong M
Int J Exp Pathol · 2019 Feb · PMID 30912195 · Full text
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Because the prognosis of DLBCL patients varies considerably, there is an urgent need to identify novel prognostic factors. In this...
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Because the prognosis of DLBCL patients varies considerably, there is an urgent need to identify novel prognostic factors. In this study, we investigated the expression levels of the signalling enzyme 3-phosphoinositide-dependent protein kinase-1 (PDK1), the cell cycle regulatory enzyme Polo-like kinase 1 (PLK1) and the transcription factor (c-Myc) in DLBCL tissues and evaluated their clinical and prognostic significance. PDK1, PLK1 and c-Myc were detected by immunohistochemical staining of paraffin-embedded specimens from 152 DLBCL and 48 lymphadenitis patients. Expression levels were correlated with clinicopathological factors. PDK1, PLK1 and c-Myc were more commonly expressed in DLBCL specimens than in lymphadenitis specimens, and the expression of each protein correlated positively with that of the other two molecules. High PDK1, PLK1 and c-Myc expression, high international prognostic index score, high lactate dehydrogenase levels and late Ann Arbor stage were shown to correlate with shorter overall survival time. A multivariate Cox regression model showed that high expression levels of PLK1 and c-Myc were independent prognostic factors for DLBCL. Our findings indicate that PLK1 and c-Myc expression might be promising predictive biomarkers for DLBCL patients.
Vitronectin deficiency attenuates hepatic fibrosis in a non-alcoholic steatohepatitis-induced mouse model.
Hayashida M, Hashimoto K, Ishikawa T … +1 more , Miyamoto Y
Int J Exp Pathol · 2019 Apr · PMID 30887659 · Full text
Vitronectin (VN), an extracellular matrix protein, is a promising immune biomarker of non-alcoholic steatohepatitis (NASH); however, its precise function remains unclear. This study investigated how VN deficiency contrib...
Vitronectin (VN), an extracellular matrix protein, is a promising immune biomarker of non-alcoholic steatohepatitis (NASH); however, its precise function remains unclear. This study investigated how VN deficiency contributes to the development of NASH. Towards this aim, wild-type (WT) and VN-/- mice were fed with a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for 6 and 10 weeks to induce NASH, and the livers were isolated. In WT mice fed with CDAHFD for 6 and 10 weeks, the expression of Vn mRNA and protein was up-regulated compared with that in mice fed with the MF control diet, indicating that VN is regulated in NASH condition. VN-/- mice showed decreased picrosirius red staining in the liver area and Col1a2 mRNA expression levels, compared with WT mice, indicating that the severity of hepatic fibrosis is attenuated in the CDAHFD-fed VN-/- mice. In addition, VN deficiency did not affect the area of lipid droplets in haematoxylin-eosin staining and the mRNA expression levels of fatty acid synthases, Srebp, Acc and Fas in the CDAHFD-fed mice. Moreover, VN deficiency decreased the inflammation score and the mRNA expression levels of Cd11b and F4/80, macrophage markers, as well as Tnf-α and Il-1β, inflammatory cytokines in the CDAHFD-fed mice. Furthermore, VN deficiency decreased the protein and mRNA expression levels of α-smooth muscle actin in the CDAHFD-fed mice, suggesting that VN deficiency inhibits the activation of hepatic stellate cells (HSCs). Our findings indicate that VN contributes to the development of fibrosis in the NASH model mice via modulation of the inflammatory reaction and activation of HSCs.
KRAS mutations in the parental tumour accelerate in vitro growth of tumoroids established from colorectal adenocarcinoma.
Mousavi N, Truelsen SLB, Hagel G … +7 more , Jorgensen LN, Harling H, Timmermans V, Melchior LC, Thysen AH, Heegaard S, Thastrup J
Int J Exp Pathol · 2019 Feb · PMID 30884019 · Full text
The aim of the present study was to characterize a patient-derived in vitro 3D model (ie tumoroid) established from colorectal adenocarcinoma. This study investigated the growth rate of tumoroids and whether the Kirsten...
The aim of the present study was to characterize a patient-derived in vitro 3D model (ie tumoroid) established from colorectal adenocarcinoma. This study investigated the growth rate of tumoroids and whether the Kirsten rat sarcoma (KRAS) mutations in the parental tumour accelerate this rate. The tumoroids were established from surgical resections of primary and metastatic colorectal adenocarcinoma from 26 patients. The in vitro growth rate of these tumoroids was monitored by automated imaging and recorded as relative growth rate. The KRAS hotspot mutations were investigated on the parental tumours by Ion Torrent next-generation sequencing. The KRAS mutations were detected in 58% of the parental tumours, and a significantly higher growth rate was observed for tumoroids established from the KRAS-mutated tumours compared to wild-type tumours (P < 0.0001). The average relative growth rate (log10) on day 10 was 0.360 ± 0.180 (mean ± SD) for the KRAS-mutated group and 0.098 ± 0.135 (mean ± SD) for the KRAS wild-type group. These results showed that the presence of KRAS mutations in parental tumours is associated with an acceleration of the growth rate of tumoroids. The future perspective for such a model could be the implementation of chemoassays for personalized medicine.
CARLo-7-A plausible biomarker for bladder cancer.
Amir H, Khan MA, Feroz S … +7 more , Bibi N, Nawaz M, Mehmood A, Yousuf A, Khawaja MA, Khadim MT, Tariq A
Int J Exp Pathol · 2019 Feb · PMID 30883984 · Full text
Cancer is defined as undifferentiated and unchecked growth of cells damaging the surrounding tissue. Cancers manifest altered gene expression. Gene expression is regulated by a diverse array of non-protein-coding RNA. Ab...
Cancer is defined as undifferentiated and unchecked growth of cells damaging the surrounding tissue. Cancers manifest altered gene expression. Gene expression is regulated by a diverse array of non-protein-coding RNA. Aberrant expression of long non-coding RNAs (lncRNAs) has been recently found to have functional consequences in cancers. In the current study, we report CARLo-7 as the only bladder cancer-specific lncRNA from the CARLos cluster. The expression of this lncRNA correlates with bladder cancer grade. We propose that CARLo-7 has an oncogenic potential and might be regulator of cell proliferation. Furthermore, by comparison the expression of proto-oncogene MYC, which is the only well-annotated gene close to the cancer - associated linkage disequilibrium blocks of this region, does not show a pronounced change in expression between the low- and high-grade tumours. Our results indicate that CARlo-7 can act as a prognostic marker for bladder cancer.
Role of CD97 small isoform in human cervical carcinoma.
He Y, Xu L, Feng M … +1 more , Wang W
Int J Exp Pathol · 2019 Feb · PMID 30883974 · Full text
Various studies revealed that elevated expression of CD97 in carcinomas is associated with the dedifferentiation, aggressiveness and metastasis of tumour. CD97 is a protein member of the epidermal growth factor seven-tra...
Various studies revealed that elevated expression of CD97 in carcinomas is associated with the dedifferentiation, aggressiveness and metastasis of tumour. CD97 is a protein member of the epidermal growth factor seven-transmembrane (EGF-TM7) family of class II TM7 receptors. Our previous study suggested that the overexpression of CD97 in cervical cancer was correlated with the aggressiveness of the tumour and that CD97 might be an independent poor prognostic factor for cervical cancer patients. Based on these data, we have investigated the role of CD97 small isoform in cervical cancer proliferation, migration and invasion in vitro. Three cervical cancer cell lines were tested and the CD97 small isoform was found to be expressed predominantly in the SiHa cells. The mobile and invasive ability of different cervical cancer cell lines was not correlated positively with total CD97 protein expression but was with the level of the CD97 small isoform. Functional significance was assessed 48 hours after transient knockdown using siRNA targeting CD97 small isoform (CD97/EGF1,2,5) or a scrambled control sequence in cervical cancer cell lines. As a result, decreased ability of migration and invasion was found in CD97 small isoform RNAi cells, which showed, however, no change in cell proliferation. This study shed light on the role of the CD97 small isoform in tumour progression and provides a basis for further studies to determine its function in vivo.
Effects of three-month streptozotocin-induced diabetes in mice on blood platelet reactivity, COX-1 expression and adhesion potential.
Przygodzki T, Kassassir H, Talar M … +2 more , Siewiera K, Watala C
Int J Exp Pathol · 2019 Feb · PMID 30811756 · Full text
Diabetes is associated with an increased risk of cardiovascular disease. This is partially attributed to an altered activation status of blood platelets in this disease. Previously, alterations have been shown in COX-1 a...
Diabetes is associated with an increased risk of cardiovascular disease. This is partially attributed to an altered activation status of blood platelets in this disease. Previously, alterations have been shown in COX-1 and protease activated receptor (PAR)-3 receptor expression in platelets in two animal models of diabetes, there have not been studies which address expression of these proteins in mice with long-term streptozotocin (STZ)-induced diabetes. We have also addressed the effect of diabetes on platelet adhesion under flow conditions. With the use of flow cytometry, we have shown that certain markers of platelet basal activation, such as active form of α β and of CD40L were increased in STZ-induced diabetic mice. Platelets from STZ-induced diabetic mice were also more reactive when stimulated with PAR-4 activating peptide as revealed by higher expression of active form of α β , membrane-bound on vWillebrand Factor and binding of exogenous fluorescein isothyanate-labelled fibrinogen. Expression of COX-1 and production of thromboxane A in platelets of STZ-induced diabetic mice were higher than in control animals. We observed no effect of diabetes on ability of platelets to form stable adhesions with fibrinogen in flow conditions. We conclude that although certain similarities exist between patterns of activation of platelets in animal models of diabetes, the differences should also be taken into account.
Nicotinamide riboside has protective effects in a rat model of mesenteric ischaemia-reperfusion.
Toropova YG, Pechnikova NA, Zelinskaya IA … +7 more , Zhuravsky SG, Kornyushin OV, Gonchar AI, Ivkin DY, Leonova YV, Karev VE, Karabak IA
Int J Exp Pathol · 2018 Dec · PMID 30793416 · Full text
Acute mesenteric ischaemia is a syndrome caused by inadequate blood flow through the mesenteric vessels, resulting in ischaemia and eventual gangrene of the bowel wall. Although relatively rare, it is a potentially life-...
Acute mesenteric ischaemia is a syndrome caused by inadequate blood flow through the mesenteric vessels, resulting in ischaemia and eventual gangrene of the bowel wall. Although relatively rare, it is a potentially life-threatening condition. The maintenance of haemodynamic stability, along with adequate oxygen saturation, and the correction of any electrolyte imbalance, are of the utmost importance. However, nicotinamide adenine dinucleotide (NAD) biosynthesis modulation by precursor introduction can also be a powerful tool for preventing injury. Nicotinamide riboside is a pyridine-nucleoside form of vitamin B3 that functions as a precursor to NAD . The present study investigated nicotinamide riboside's effect on endothelium functional state, microcirculation and intestinal morphology in acute mesenteric ischaemia and reperfusion. Mesenteric ischaemia was simulated after the adaptation period (15 minutes) by occluding the superior mesenteric artery for 60 minutes, followed by a reperfusion period of 30 minutes. The functional state of intestinal microcirculation was evaluated by laser Doppler flowmetry. Endothelial functional activity was studied by using wire myography. Intestinal samples were stained with haematoxylin and eosin for histological analysis. The results revealed that nicotinamide riboside protects the intestinal wall from ischaemia-reperfusion injury, as well as improving the relaxation function of mesenteric vessels. Nicotinamide riboside's protective effect in small intestine ischaemia-reperfusion can be used to reduce ischaemia-reperfusion injury, as well as to preserve intestinal grafts until transplant.
Morphofunctional characteristics of skeletal muscle in rats with cerebral palsy.
Buratti P, Covatti C, Centenaro LA … +2 more , Brancalhão RMC, Torrejais MM
Int J Exp Pathol · 2019 Feb · PMID 30773727 · Full text
Knowledge of skeletal muscle adaptations is important to understand the functional deficits in cerebral palsy (CP). This study aimed to investigate the morphofunctional characteristics of skeletal muscle in a CP animal m...
Knowledge of skeletal muscle adaptations is important to understand the functional deficits in cerebral palsy (CP). This study aimed to investigate the morphofunctional characteristics of skeletal muscle in a CP animal model. Initially, pregnant Wistar rats were injected intraperitoneally with saline or lipopolysaccharide over the last five days of pregnancy. The control group (n = 8) consisted of male pups born to females injected with saline. The CP group (n = 8) consisted of male pups born to females injected with lipopolysaccharide, which were submitted to perinatal anoxia [day of birth, postnatal day 0 (P0)] and sensorimotor restriction (P1-P30). The open-field test was undertaken on P29 and P45. On P48, the animals were weighed, and the plantaris muscle was collected and its weight and length were measured. Transverse sections were stained with haematoxylin-eosin, NADH-TR, Masson's trichrome and non-specific esterase reaction for analysis. and transmission electron microscopy was performed. In the CP group, reductions were observed in mobility time, number of crossings and rearing frequency, body weight, muscle weight and length, and nucleus-to-fibre and capillary-to-fibre ratios. There was a statistically significant increase in the percentage area of the muscle section occupied by collagen; reduction in the area and increase in the number of type I muscle fibres; increase in myofibrillar disorganization and Z-line disorganization and dissolution; and reduction in the area and largest and smallest diameters of neuromuscular junctions. Thus this animal model of CP produced morphofunctional alterations in skeletal muscle, that were associated with evidence of motor deficits as demonstrated by the open-field test.
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