Folia Biologica最新文献_第10页

T-lymphopoiesis is Severely Compromised in Ubiquitin-Green Fluorescent Protein Transgenic Mice. 泛素绿色荧光蛋白转基因小鼠t淋巴功能严重受损

IF 1.1 4区医学

Folia Biologica Pub Date : 2020-01-01 DOI: 10.14712/fb2020066020047

K Faltusová, M Báječný, T Heizer, P Páral, E Nečas

{"title":"T-lymphopoiesis is Severely Compromised in Ubiquitin-Green Fluorescent Protein Transgenic Mice.","authors":"K Faltusová, M Báječný, T Heizer, P Páral, E Nečas","doi":"10.14712/fb2020066020047","DOIUrl":"10.14712/fb2020066020047","url":null,"abstract":"Tagging cells of experimental organisms with genetic markers is commonly used in biomedical research. Insertion of artificial gene constructs can be highly beneficial for research as long as this tagging is functionally neutral and does not alter the tissue function. The transgenic UBC-GFP mouse has been recently found to be questionable in this respect, due to a latent stem cell defect compromising its lymphopoiesis and significantly influencing the results of competitive transplantation assays. In this study, we show that the stem cell defect present in UBC-GFP mice negatively affects T-lymphopoiesis significantly more than B-lymphopoiesis. The production of granulocytes is not negatively affected. The defect in T-lymphopoiesis causes a low total number of white blood cells in the peripheral blood of UBC-GFP mice which, together with the lower lymphoid/myeloid ratio in nucleated blood cells, is the only abnormal phenotype in untreated UBCGFP mice to have been found to date. The defective lymphopoiesis in UBC-GFP mice can be repaired by transplantation of congenic wild-type bone marrow cells, which then compensate for the insufficient production of T cells. Interestingly, the wild-type branch of haematopoiesis in chimaeric UBC-GFP/wild-type mice was more active in lymphopoiesis, and particularly towards production of T cells, compared to the lymphopoiesis in normal wild-type donors.","PeriodicalId":12281,"journal":{"name":"Folia Biologica","volume":"66 2","pages":"47-59"},"PeriodicalIF":1.1,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38315015","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}

引用次数: 0

Changes of Hippocampal Noradrenergic Capacity in Stress Condition. 应激状态下海马去甲肾上腺素能能力的变化。

IF 1.1 4区医学

Folia Biologica Pub Date : 2020-01-01 DOI: 10.14712/fb2020066020081

L Gavrilović, N Popović, V Stojiljković, S Pejić, A Todorović, I Pavlović, S B Pajović

引用次数: 0

Comprehensive Analysis of PTEN in Primary Cutaneous Melanoma. 原发性皮肤黑色素瘤中PTEN的综合分析。

IF 1.1 4区医学

Folia Biologica Pub Date : 2020-01-01 DOI: 10.14712/fb2020066010007

K Němejcová, P Dundr, R Jakša, M Bártů, I Stružinská, J Hojný, N Hájková, O Kodet

{"title":"Comprehensive Analysis of PTEN in Primary Cutaneous Melanoma.","authors":"K Němejcová, P Dundr, R Jakša, M Bártů, I Stružinská, J Hojný, N Hájková, O Kodet","doi":"10.14712/fb2020066010007","DOIUrl":"10.14712/fb2020066010007","url":null,"abstract":"Phosphatase and tensin homologue (PTEN) is a tumour suppressor gene implicated in tumorigenesis of melanoma, with distinct cytoplasmic and nuclear functions. Cytoplasmic PTEN negatively regulates the PI3K/AKT/mTOR signalling pathway, while nuclear PTEN works as a tumour suppressor. Clinical data suggest that the loss of PTEN function in melanoma is associated with aggressive tumour behaviour. We performed a comprehensive analysis of PTEN in 112 primary cutaneous melanomas including immunohistochemical (IHC), fluorescent in situ hybridization (FISH), next-generation sequencing (NGS), and epigenetic analysis. The goal of our study was to: (a) correlate PTEN expression with selected clinico-pathological variables, and assess its prognostic significance; (b) correlate molecular aberrations with PTEN expression to consider the utility of immunohistochemical analysis of PTEN protein expression for screening PTEN genetic alterations; (c) review the literature and evaluate the PTEN expression level in melanoma with respect to possible therapeutic targeting. Our results showed that PTEN molecular alterations were present in 4/20 (20 %) cases with a loss of expression, 3/11 (27 %) cases with clonal-like expression, and 1/81 (1 %) cases with positive PTEN expression. No PTEN promoter methylation was found in any of the cases. Even though the value of our observation is limited by the low number of cases fully evaluated by IHC (112 cases), FISH (19 cases) and NGS (30 cases), our data suggest that IHC is not an appropriate method for the screening of PTEN genetic alterations. Our survival analysis suggests that patients with positive cytoplasmic PTEN expression show better disease-free survival (P < 0.05).","PeriodicalId":12281,"journal":{"name":"Folia Biologica","volume":"66 1","pages":"7-16"},"PeriodicalIF":1.1,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38021794","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}

引用次数: 0

Hereditary Haemorrhagic Telangiectasia (HHT) Marked by ACVRL1C1120T Variant Displays Hypopigmented Naevi and Frequent Bleeding Episodes if CYP2C9 Co-Mutated: Clinical Notes & Rationale of Patient Registry. ACVRL1C1120T变异标记的遗传性出血性毛细血管扩张症(HHT)，如果CYP2C9共突变，则显示Naevi色素降低和频繁出血:临床记录和患者登记的基本原理

IF 1.1 4区医学

Folia Biologica Pub Date : 2020-01-01 DOI: 10.14712/fb2020066010001

L Minarik, K Vargova, N Dusilkova, V Kulvait, A Jonasova, O Kodet, T Stopka

{"title":"Hereditary Haemorrhagic Telangiectasia (HHT) Marked by ACVRL1C1120T Variant Displays Hypopigmented Naevi and Frequent Bleeding Episodes if CYP2C9 Co-Mutated: Clinical Notes & Rationale of Patient Registry.","authors":"L Minarik, K Vargova, N Dusilkova, V Kulvait, A Jonasova, O Kodet, T Stopka","doi":"10.14712/fb2020066010001","DOIUrl":"10.14712/fb2020066010001","url":null,"abstract":"Hereditary haemorrhagic telangiectasia (HHT) exhibits considerable phenotypic heterogeneity. Therefore, precise mutation screening and evaluation of patient risk must be determined in every HHT family. We present an HHT-2 case with an initial life-threatening bleeding episode that led to identification of a relatively large HHT family. Exome sequencing of the family members determined HHT-associated ACVRL1C1120T variant resulting in Arg374Trp substitution at the Ser/Thr-kinase domain region. The affected members display typical epistaxis symptomatology from early childhood resulting in sideropoenia. In addition, the HHT patients also displayed dermatology findings such as facial teleangiectasias and trunk/limb white spots representing post-inflammatory hypopigmentation. Interestingly, co-segregating with modifying cytochrome P450 (CYP2C) variant in the HHT patients led to NSAID intolerance marked by increased frequency of bleeding episodes. No arterial-venous malformation of the visceral organs and brain or association with cancer were observed. The heterogeneity of clinical presentation and the role of other variants support the need of regular patient monitoring and development of a nation-wide patient registry.","PeriodicalId":12281,"journal":{"name":"Folia Biologica","volume":"66 1","pages":"1-6"},"PeriodicalIF":1.1,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38021847","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}

引用次数: 0

PD-1, PD-L1 and PD-L2 Expression in Mantle Cell Lymphoma and Healthy Population. PD-1、PD-L1和PD-L2在套细胞淋巴瘤和健康人群中的表达。

IF 1.1 4区医学

Folia Biologica Pub Date : 2020-01-01 DOI: 10.14712/fb2020066040117

J Karolova, M Radek, K Helman, M Spacek, M Trneny, P Klener

{"title":"PD-1, PD-L1 and PD-L2 Expression in Mantle Cell Lymphoma and Healthy Population.","authors":"J Karolova, M Radek, K Helman, M Spacek, M Trneny, P Klener","doi":"10.14712/fb2020066040117","DOIUrl":"10.14712/fb2020066040117","url":null,"abstract":"Cell surface expression of PD-1, PD-L1 and PD-L2 immune checkpoints on B and T cells obtained from patients with mantle cell lymphoma shows ambiguous results across many studies and creates obstacles for the implementation of immune checkpoint inhibitors into the therapy of mantle cell lymphoma. Using multiparameter flow cytometry we analysed surface expression of PD-1, PD-L1 and PD-L2 molecules on B and T cells of 31 newly diagnosed mantle cell lymphomas and compared it with the results of 26 newly diagnosed chronic lymphocytic leukaemias and 20 healthy volunteers. To gain insight into the age-dependent changes of surface expression of these immune checkpoints, flow cytometric subanalysis of 30 healthy volunteers of 25-93 years of age was conducted. Overall, we demonstrated weak surface expression of PD-1, PD-L1 and PD-L2 on B and T cells of mantle cell lymphoma patients (< 10 % when compared to healthy individuals). A significant age-dependent increase in the expression of PD-1 and its ligand PD-L2 was observed in healthy volunteers. Our results suggest that neither PD-1 nor its ligands represent relevant druggable targets for the therapy of mantle cell lymphoma. The observed age-dependent changes in healthy population could impact efficiency of immune checkpoint inhibitors and could be at least partly connected with increased incidence of cancer with age.","PeriodicalId":12281,"journal":{"name":"Folia Biologica","volume":"66 4","pages":"117-122"},"PeriodicalIF":1.1,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25499406","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}

引用次数: 0

Genetic Markers at ANRIL, FTO and 2q36.3 Locus in Czech Patients Undergoing Coronary Artery Bypass Graft Surgery. 捷克冠状动脉搭桥术患者ANRIL、FTO和2q36.3位点的遗传标记

IF 1.1 4区医学

Folia Biologica Pub Date : 2020-01-01 DOI: 10.14712/fb2020066040148

P Kacer, J Pirk, V Lanska, J A Hubacek, V Adamek, T Cervinkova, J Belohoubek, O Auzky, V Adamkova

{"title":"Genetic Markers at ANRIL, FTO and 2q36.3 Locus in Czech Patients Undergoing Coronary Artery Bypass Graft Surgery.","authors":"P Kacer, J Pirk, V Lanska, J A Hubacek, V Adamek, T Cervinkova, J Belohoubek, O Auzky, V Adamkova","doi":"10.14712/fb2020066040148","DOIUrl":"10.14712/fb2020066040148","url":null,"abstract":"Coronary artery bypass graft (CABG) surgery is one of the most commonly performed operations worldwide. We compared genotype frequencies of three major cardiovascular disease (CVD)-associated genetic markers (ANRIL, FTO and 2q36.3 locus) between 753 patients who underwent CABG at the Institute for Clinical and Experimental Medicine (Prague, Czech Republic) and 2,559 controls from the Czech post-MONICA study. Subjects with at least one major A allele in the rs10757274 polymorphism (ANRIL) were more prevalent in patients after CABG than in the controls (81.7 % vs 72.7 %; OR [95 % CI] 1.67 [1.35-2.05]; P < 0.0001). In contrast, variants within the FTO gene (OR 0.87; 95 % CI, 0.70-1. 09 in a TT vs. GG comparison, P = 0.24) and 2q36.3 locus (OR 1.16; 95% CI, 0.98-1.37 in a +A vs. CC comparison, P = 0.08) were not significantly associated with CVD in our study. Variants were not associated with anthropometric, biochemical, or clinical characteristics within the patient group. Our study suggests that patients with CABG are more commonly carriers of some but not all CVD-associated alleles.","PeriodicalId":12281,"journal":{"name":"Folia Biologica","volume":"66 4","pages":"148-153"},"PeriodicalIF":1.1,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25500876","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}

引用次数: 0

Protumorogenic Potential of Pancreatic Adenocarcinoma-Derived Extracellular Vesicles. 胰腺腺癌来源的细胞外囊泡的致癌潜能。

IF 1.1 4区医学

Folia Biologica Pub Date : 2020-01-01 DOI: 10.14712/fb2020066030104

M Baj-Krzyworzeka, B Mytar, K Weglarczyk, R Szatanek, J Kijowski, M Siedlar

{"title":"Protumorogenic Potential of Pancreatic Adenocarcinoma-Derived Extracellular Vesicles.","authors":"M Baj-Krzyworzeka, B Mytar, K Weglarczyk, R Szatanek, J Kijowski, M Siedlar","doi":"10.14712/fb2020066030104","DOIUrl":"10.14712/fb2020066030104","url":null,"abstract":"Cancer development is a highly complicated process in which tumour growth depends on the development of its vascularization system. To support their own growth, tumour cells significantly modify their microenvironment. One of such modifications inflicted by tumours is stimulation of endothelial cell migration and proliferation. There is accumulating evidence that extracellular vesicles (EVs) secreted by tumour cells (tumour-derived EVs, TEVs) may be regarded as \"messengers\" with the potential for affecting the biological activities of target cells. Interaction of TEVs with different cell types occurs in an auto- and paracrine manner and may lead to changes in the function of the latter, e.g., promoting motility, proliferation, etc. This study analysed the proangiogenic activity of EVs derived from human pancreatic adenocarcinoma cell line (HPC-4, TEVHPC) in vitro and their effect in vivo on Matrigel matrix vascularization in severe combined immunodeficient (SCID) mice. TEVHPC enhanced proliferation of HPC-4 cells and induced their motility. Moreover, TEVHPC stimulated human umbilical vein endothelial cell (HUVEC) proliferation and migration in vitro. Additionally, TEVHPC influenced secretion of proangiogenic factors (IL-8, VEGF) by HUVEC cells and supported Matrigel matrix haemoglobinization in vivo. These data show that TEVs may support tumour propagation in an autocrine manner and may support vascularization of the tumour. The presented data are in line with the theory that tumour cells themselves are able to modulate the microenvironment via TEVs to maximize their growth potential.","PeriodicalId":12281,"journal":{"name":"Folia Biologica","volume":"66 3","pages":"104-110"},"PeriodicalIF":1.1,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38499105","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}

引用次数: 0

BMP Inhibition in the Presence of LIF Differentiates Murine Embryonic Stem Cells to Early Neural Stem Cells. LIF对BMP的抑制使小鼠胚胎干细胞向早期神经干细胞分化。

IF 1.1 4区医学

Folia Biologica Pub Date : 2020-01-01 DOI: 10.14712/fb2020066050155

R V Pisal, J Mokry

{"title":"BMP Inhibition in the Presence of LIF Differentiates Murine Embryonic Stem Cells to Early Neural Stem Cells.","authors":"R V Pisal, J Mokry","doi":"10.14712/fb2020066050155","DOIUrl":"10.14712/fb2020066050155","url":null,"abstract":"Early mouse neural stem cells (NSCs) first appear in embryonic day E5.5 and express pluripotency markers Oct4, Sox2, Nanog and early neural marker Sox1. Early NSCs are a good model for understanding the role of various pathways that control initial neural commitment. However, a protocol for differentiation of mouse embryonic stem cells (ESCs) into early NSCs by adherent monolayer culture has not yet been established. Hence, in this study, we identified the combination of growth factors and small molecules that differentiated mouse ESCs into early NSCs and supported their proliferation. Leukaemia inhibitory factor (LIF) was the first factor to be tested and it was found that ESCs can differentiate into early neurogenic lineage in the presence of LIF. However, we found that the induction is weaker in the presence of LIF as compared to cells differentiated in its absence. GSK-3 inhibitor, along with BMP and TGF-β pathway inhibitor (dual SMAD inhibition), are commonly used to sequentially direct ESCs towards NSCs. However, when we used this combination, mouse ESCs failed to differentiate into early NSCs. We observed that by adding Wnt inhibitor to the combination of GSK-3 inhibitor, BMP inhibitor, TGF-β inhibitor and LIF, it was possible to differentiate ESCs into early NSCs. qRT-PCR analysis of early NSCs illustrated that they expressed key pluripotency genes Oct4 and Nanog, albeit at levels lower than non-differentiated ESCs, along with early neural markers Sox1 and Pax6.","PeriodicalId":12281,"journal":{"name":"Folia Biologica","volume":"66 5-6","pages":"155-160"},"PeriodicalIF":1.1,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39062935","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}

引用次数: 0

Anti-CD38 Therapy with Daratumumab for Relapsed/Refractory CD20-Negative Diffuse Large B-Cell Lymphoma. 抗cd38治疗复发/难治性cd20阴性弥漫性大b细胞淋巴瘤

IF 1.1 4区医学

Folia Biologica Pub Date : 2020-01-01 DOI: 10.14712/fb2020066010017

P Vockova, M Svaton, J Karolova, E Pokorna, M Vokurka, P Klener

{"title":"Anti-CD38 Therapy with Daratumumab for Relapsed/Refractory CD20-Negative Diffuse Large B-Cell Lymphoma.","authors":"P Vockova, M Svaton, J Karolova, E Pokorna, M Vokurka, P Klener","doi":"10.14712/fb2020066010017","DOIUrl":"10.14712/fb2020066010017","url":null,"abstract":"Diffuse large B-cell lymphoma (DLBCL) is the most common and one of the most aggressive subtypes of non-Hodgkin's lymphomas. Front-line therapy consists of chemotherapy in combination with anti-CD20 monoclonal antibody rituximab. Relapses after rituximab-based regimen have poor prognosis and call for new treatment options. Immunohistochemistry analysis of relapsed DLBCL often reveal CD20-negative lymphoma, which limits repeated use of rituximab in combination with salvage chemotherapy. CD38 is a surface antigen that binds to CD38, CD31/PECAM-1 and hyaluronic acid. CD38 is an important mediator of signal transmission from the microenvironment into the cell. Anti-CD38 monoclonal antibody daratumumab has been approved for the treatment of multiple myeloma. Expression of CD38 on the surface of DLBCL is highly variable (compared to strong expression on myeloma cells), but can be easily assessed by flow cytometry or immunohistochemistry. A patient-derived xenograft (PDX) model of CD20-negative, CD38-positive DLBCL derived from a patient with rituximab-refractory DLBCL was used for in vivo experiments. We demonstrated that daratumumab suppressed growth of subcutaneous PDX tumours significantly more effectively than rituximab. Analysis of tumours obtained from mice treated with daratumumab revealed down-regulation of surface CD38, suggesting endocytosis of CD38-daratumumab complexes. The results suggest a potential clinical use of daratumumab in combination with salvage chemotherapy in patients with relapses of CD20-negative DLBCL. In addition, daratumumab might potentially serve as a suitable antibody moiety for derivation of antibodydrug conjugates for the targeted delivery of toxic payloads to the lymphoma cells.","PeriodicalId":12281,"journal":{"name":"Folia Biologica","volume":"66 1","pages":"17-23"},"PeriodicalIF":1.1,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38021795","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}

引用次数: 0

The Action of Benzene, Resveratrol and Their Combination on Ovarian Cell Hormone Release. 苯、白藜芦醇及其组合对卵巢细胞激素释放的作用。

IF 1.1 4区医学

Folia Biologica Pub Date : 2020-01-01 DOI: 10.14712/fb2020066020067

A Sirotkin, A Kádasi, A Balaží, J Kotwica, S Alwasel, A H Harrath

引用次数: 0