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  • 1
    Online Resource
    Online Resource
    MiR-182-5p and miR-375-3p Have Higher Performance Than PSA in Discriminating Prostate Cancer from Benign Prostate Hyperplasia
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 9 ( 2021-04-25), p. 2068-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 9 ( 2021-04-25), p. 2068-
    Abstract: Prostate cancer (PCa) is the most commonly diagnosed neoplasm among men. Since it often resembles benign prostate hyperplasia (BPH), biomarkers with a higher differential value than PSA are required. Epigenetic biomarkers in liquid biopsies, especially miRNA, could address this challenge. The absolute expression of miR-375-3p, miR-182-5p, miR-21-5p, and miR-148a-3p were quantified in blood plasma and seminal plasma of 65 PCa and 58 BPH patients by digital droplet PCR. The sensitivity and specificity of these microRNAs were determined using ROC curve analysis. The higher expression of miR-182-5p and miR-375-3p in the blood plasma of PCa patients was statistically significant as compared to BPH (p = 0.0363 and 0.0226, respectively). Their combination achieved a specificity of 90.2% for predicting positive or negative biopsy results, while PSA cut-off of 4 µg/L performed with only 1.7% specificity. In seminal plasma, miR-375-3p, miR-182-5p, and miR-21-5p showed a statistically significantly higher expression in PCa patients with PSA 〉 10 µg/L compared to ones with PSA ≤10 µg/L. MiR-182-5p and miR-375-3p in blood plasma show higher performance than PSA in discriminating PCa from BPH. Seminal plasma requires further investigation as it represents an obvious source for PCa biomarker identification.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13092068
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 2
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    Online Resource
    Transmembranous and enchondral osteogenesis in transplants of rat limb buds cultivated in serum‐ and protein‐free culture medium
    Wiley ; 2022
    In:  Anatomia, Histologia, Embryologia Vol. 51, No. 5 ( 2022-09), p. 592-601
    Details
    In: Anatomia, Histologia, Embryologia, Wiley, Vol. 51, No. 5 ( 2022-09), p. 592-601
    Abstract: Cartilage differentiates in rat limb buds cultivated in a chemically defined protein‐free medium in the same manner as in the richer serum‐supplemented medium. We aimed to investigate the remaining differentiation potential of pre‐cultivated limb buds by subsequent transplantation in vivo. Rat front (FLBs) and hind‐limb buds (HLBs) were isolated from Fischer rat dams at the 14th gestation day (GD 14) and cultivated at the air‐liquid interface in Eagle's Minimum Essential Medium (MEM) alone; with 5 μM of 5‐azacytidine (5azaC) or with rat serum (1:1). Overall growth was measured seven times during the culture by an ocular micrometre. After 14 days, explants were transplanted under the kidney capsule of adult males. Growth of limb buds was significantly lower in all limb buds cultivated in MEM than in those cultivated with serum. In MEM with 5azaC, growth of LBs was significantly lower only on day 3 of culture. Afterwards, it was higher throughout the culture period, although a statistically significant difference was assessed only for HLBs. In transplants, mixed structures developed with the differentiated transmembranous bone, cartilage with enchondral ossification, bone‐marrow, sebaceous gland, and hair that have never been found in vitro. Nerves differentiated only in transplants precultivated in the serum‐supplemented medium. We conclude that pre‐cultivation of LBs in a chemically defined protein‐free medium does not restrict osteogenesis and formation of epidermal appendages but is restrictive for neural tissue. These results are important for understanding limb development and regenerative medicine strategies.
    Type of Medium: Online Resource
    ISSN: 0340-2096 , 1439-0264
    URL: Issue
    URL: Article
    DOI: 10.1111/ahe.v51.5
    DOI: 10.1111/ahe.12835
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2019889-9
    SSG: 22
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  • 3
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    Online Resource
    Influence of hyperthermal regimes on experimental teratoma development in vitro
    Wiley ; 2018
    In:  International Journal of Experimental Pathology Vol. 99, No. 3 ( 2018-06), p. 131-144
    Details
    In: International Journal of Experimental Pathology, Wiley, Vol. 99, No. 3 ( 2018-06), p. 131-144
    Abstract: We screened for the impact of hyperthermal regimes varying in the cumulative equivalent minutes at 43°C (CEM43°C) and media composition on tumour development using an original teratoma in vitro model. Rat embryos (three germ layers) were microsurgically isolated and cultivated at the air‐liquid interface. During a two week period, ectodermal, mesodermal and endodermal derivatives developed within trilaminar teratomas. Controls were grown at 37°C. Overall growth was measured, and teratoma survival and differentiation were histologically assessed. Cell proliferation was stereologically quantified by the volume density of Proliferating Cell Nuclear Antigen. Hyperthermia of 42°C, applied for 15 minutes after plating (CEM43°C 3.75 minutes), diminished cell proliferation ( P  ˂ .0001) and enhanced differentiation of both myotubes ( P  ˂ .01) and cylindrical epithelium ( P  ˂ .05). Hyperthermia of 43°C applied each day for 30 minutes during the first week (CEM43°C 210 minutes) impaired overall growth ( P  ˂ .01) and diminished cell proliferation ( P  ˂ .0001). Long‐term hyperthermia of 40.5°C applied for two weeks (CEM43°C 630 minutes) significantly impaired survival ( P  ˂ .005). Long‐term hyperthermia of 40.5°C applied from the second day when differentiation of tissues begins (CEM43°C 585 minutes) impaired survival ( P  ˂ .0001), overall growth ( P  ˂ .01) and cartilage differentiation ( P  ˂ .05). No teratomas survived extreme regimes: 43°C for 24 hours (CEM43°C 1440 minutes), hyperthermia in the scant serum‐free medium (CEM43°C 630 minutes) or treatment with an anti‐HSP70 antibody before long‐term hyperthermia 40.5°C from the second day (CEM43°C 585 minutes). This in vitro research provided novel insights into the impact of hyperthermia on the development of experimental teratomas from their undifferentiated sources and are thus of potential interest for future therapeutic strategies in corresponding in vivo models.
    Type of Medium: Online Resource
    ISSN: 0959-9673 , 1365-2613
    URL: Issue
    URL: Article
    DOI: 10.1111/iep.2018.99.issue-3
    DOI: 10.1111/iep.12273
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2010007-3
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  • 4
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    Online Resource
    LIN28 Family in Testis: Control of Cell Renewal, Maturation, Fertility and Aging
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 13 ( 2022-06-29), p. 7245-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 13 ( 2022-06-29), p. 7245-
    Abstract: Male reproductive development starts early in the embryogenesis with somatic and germ cell differentiation in the testis. The LIN28 family of RNA-binding proteins promoting pluripotency has two members—LIN28A and LIN28B. Their function in the testis has been investigated but many questions about their exact role based on the expression patterns remain unclear. LIN28 expression is detected in the gonocytes and the migrating, mitotically active germ cells of the fetal testis. Postnatal expression of LIN28 A and B showed differential expression, with LIN28A expressed in the undifferentiated spermatogonia and LIN28B in the elongating spermatids and Leydig cells. LIN28 interferes with many signaling pathways, leading to cell proliferation, and it is involved in important testicular physiological processes, such as cell renewal, maturation, fertility, and aging. In addition, aberrant LIN28 expression is associated with testicular cancer and testicular disorders, such as hypogonadotropic hypogonadism and Klinefelter’s syndrome. This comprehensive review encompasses current knowledge of the function of LIN28 paralogs in testis and other tissues and cells because many studies suggest LIN28AB as a promising target for developing novel therapeutic agents.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23137245
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
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    Online Resource
    Teratoma: from spontaneous tumors to the pluripotency/malignancy assay
    Wiley ; 2016
    In:  WIREs Developmental Biology Vol. 5, No. 2 ( 2016-03), p. 186-209
    Details
    In: WIREs Developmental Biology, Wiley, Vol. 5, No. 2 ( 2016-03), p. 186-209
    Abstract: A teratoma is a benign tumor containing a mixture of differentiated tissues and organotypic derivatives of the three germ layers, while a teratocarcinoma also contains embryonal carcinoma cells ( EC cells ). Experimental teratomas and teratocarcinomas have been derived from early mammalian embryos transplanted into the adult animal (ectopic sites). In the rat, the pluripotency of the transplanted epiblast was demonstrated and a quantifiable restriction of developmental potential persisted after subsequent transplantation of chemically defined cultivated postimplantation embryos. The rat is nonpermissive for teratocarcinoma development and rat pluripotent cell lines have been established only recently. Transplantation of mouse embryos, epiblast, or embryonic stem cells ( mESCs ) gave rise to teratocarcinomas. The pluripotency of reprogrammed human cells has been tested by a ‘gold standard’ trilaminar teratoma assay in immunocompromised mice in vivo . Human pluripotent stem cells proposed for use in regenerative medicine such as human embryonic stem cell ( hESC ), human nuclear‐transfer/therapeutic cloning embryonic stem cell ( NT‐ESC ), or human induced pluripotent stem cell ( hiPSC ) lines, once differentiated in vitro to the desired cell type, should be again tested in a long‐term animal teratoma assay to exclude their malignancy. Such an approach led to a recently implemented human therapy with retinal pigmented epithelium. For greater biosafety, the teratoma assay should be standardized and complemented by assessments of mutations/epimutations, RNA /protein expression, and possible immunogenicity of autologous pluripotent cells. Furthermore, the standardized teratoma assay should be directed more to the assessment of EC /malignant cell features than of differentiated tissues, especially after a unique case of human therapy with neural stem cells was found to lead to malignancy. WIREs Dev Biol 2016, 5:186–209. doi: 10.1002/wdev.219 This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration 〉 Methods and Principles Adult Stem Cells, Tissue Renewal, and Regeneration 〉 Stem Cells and Disease Comparative Development and Evolution 〉 Model Systems
    Type of Medium: Online Resource
    ISSN: 1759-7684 , 1759-7692
    URL: Issue
    URL: Article
    DOI: 10.1002/wdev.2016.5.issue-2
    DOI: 10.1002/wdev.219
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2649746-3
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  • 6
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    Online Resource
    Valproate Targets Mammalian Gastrulation Impairing Neural Tissue Differentiation and Development of the Placental Source In Vitro
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 16 ( 2022-08-09), p. 8861-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 16 ( 2022-08-09), p. 8861-
    Abstract: The teratogenic activity of valproate (VPA), an antiepileptic and an inhibitor of histone deacetylase (HDACi), is dose-dependent in humans. Previous results showed that VPA impairs in vitro development and neural differentiation of the gastrulating embryo proper. We aimed to investigate the impact of a lower VPA dose in vitro and whether this effect is retained in transplants in vivo. Rat embryos proper (E9.5) and ectoplacental cones were separately cultivated at the air-liquid interface with or without 1 mM VPA. Embryos were additionally cultivated with HDACi Trichostatin A (TSA), while some cultures were syngeneically transplanted under the kidney capsule for 14 days. Embryos were subjected to routine histology, immunohistochemistry, Western blotting and pyrosequencing. The overall growth of VPA-treated embryos in vitro was significantly impaired. However, no differences in the apoptosis or proliferation index were found. Incidence of the neural tissue was lower in VPA-treated embryos than in controls. TSA also impaired growth and neural differentiation in vitro. VPA-treated embryos and their subsequent transplants expressed a marker of undifferentiated neural cells compared to controls where neural differentiation markers were expressed. VPA increased the acetylation of histones. Our results point to gastrulation as a sensitive period for neurodevelopmental impairment caused by VPA.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23168861
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 7
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    Online Resource
    Reply to comments on the article about structural changes in the rat placenta during the last third of gestation discovered by stereology
    Association of Basic Medical Sciences of FBIH ; 2015
    In:  Bosnian Journal of Basic Medical Sciences Vol. 15, No. 3 ( 2015-08-02)
    Details
    In: Bosnian Journal of Basic Medical Sciences, Association of Basic Medical Sciences of FBIH, Vol. 15, No. 3 ( 2015-08-02)
    Type of Medium: Online Resource
    ISSN: 1840-4812 , 1512-8601
    URL: Article
    DOI: 10.17305/bjbms.2015.667
    Language: Unknown
    Publisher: Association of Basic Medical Sciences of FBIH
    Publication Date: 2015
    detail.hit.zdb_id: 2548947-1
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  • 8
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    Online Resource
    Global DNA methylation and chondrogenesis of rat limb buds in a three-dimensional organ culture system
    Association of Basic Medical Sciences of FBIH ; 2022
    In:  Bosnian Journal of Basic Medical Sciences ( 2022-02-21)
    Details
    In: Bosnian Journal of Basic Medical Sciences, Association of Basic Medical Sciences of FBIH, ( 2022-02-21)
    Abstract: Although DNA methylation epigenetically regulates development, data on global DNA methylation during development of limb buds (LBs) are scarce. We aimed to investigate the global DNA methylation developmental dynamics in rat LBs cultivated in a serum-supplemented (SS) and in chemically defined serum- and protein-free (SF) three-dimensional organ culture. Fischer rat front- and hind-LBs at 13th and 14th gestation days (GD) were cultivated at the air-liquid interface in Eagle's Minimal Essential Medium (MEM) or MEM with 50% rat serum for 14 days, as SF and SS conditions, respectively. The methylation of repetitive DNA sequences (SINE rat ID elements) was assessed by pyrosequencing. Development was evaluated by light microscopy and extracellular matrix glycosaminoglycans staining by Safranin O. Upon isolation, weak Safranin O staining was present only in more developed GD14 front-LBs. Chondrogenesis proceeded well in all cultures towards day 14, except in the SF-cultivated GD13 hind-LBs, where Safranin O staining was almost absent on day 3. That was associated with a higher percentage of DNA methylation than in SF-cultivated GD13 front-LBs on day three. In SF-cultivated front-LBs, a significant methylation increase between the 3rd and 14th day was detected. In SS-cultivated GD13 front-LBs, methylation increased significantly on day three and then decreased. In older GD14 SS-cultivated LBs, there was no increase of DNA methylation, but they were significantly hypomethylated relative to the SS-cultivated GD13 at days 3 and 14. We confirmed that the global DNA methylation increase is associated with less developed limb organ primordia that strive towards differentiation in vitro, which is of importance for regenerative medicine strategies.
    Type of Medium: Online Resource
    ISSN: 1840-4812 , 1512-8601
    URL: Article
    DOI: 10.17305/bjbms.2021.6584
    Language: Unknown
    Publisher: Association of Basic Medical Sciences of FBIH
    Publication Date: 2022
    detail.hit.zdb_id: 2548947-1
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  • 9
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    Online Resource
    Teratoma Growth Retardation by HDACi Treatment of the Tumor Embryonal Source
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 11 ( 2020-11-18), p. 3416-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 11 ( 2020-11-18), p. 3416-
    Abstract: Among testicular germ cell tumors, teratomas may often be very aggressive and therapy-resistant. Our aim was to investigate the impact of histone deacetylase inhibitors (HDACi) on the in vitro growth of experimental mouse teratoma by treating their embryonic source, the embryo-proper, composed only of the three germ layers. The growth of teratomas was measured for seven days, and histopathological analysis, IHC/morphometry quantification, gene enrichment analysis, and qPCR analysis on a selected panel of pluripotency and early differentiation genes followed. For the first time, within teratomas, we histopathologically assessed the undifferentiated component containing cancer stem cell-like cells (CSCLCs) and differentiated components containing numerous lymphocytes. Mitotic indices were higher than apoptotic indices in both components. Both HDACi treatments of the embryos-proper significantly reduced teratoma growth, although this could be related neither to apoptosis nor proliferation. Trichostatin A increased the amount of CSCLCs, and upregulated the mRNA expression of pluripotency/stemness genes as well as differentiation genes, e.g., T and Eomes. Valproate decreased the amount of CSCLCs, and downregulated the expressions of pluripotency/stemness and differentiation genes. In conclusion, both HDACi treatments diminished the inherent tumorigenic growth potential of the tumor embryonal source, although Trichostatin A did not diminish the potentially dangerous expression of cancer-related genes and the amount of CSCLC.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12113416
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 10
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    Online Resource
    miRNA in prostate cancer: challenges toward translation
    Future Medicine Ltd ; 2020
    In:  Epigenomics Vol. 12, No. 6 ( 2020-03), p. 543-558
    Details
    In: Epigenomics, Future Medicine Ltd, Vol. 12, No. 6 ( 2020-03), p. 543-558
    Abstract: Prostate cancer (PCa) represents the most commonly diagnosed neoplasm among men. miRNAs, as biomarkers, could further improve reliability in distinguishing malignant versus nonmalignant, and aggressive versus nonaggressive PCa. However, conflicting data was reported for certain miRNAs, and there was a lack of consistency and reproducibility, which has been attributed to diverse (pre)analytical factors. In order to address current challenges in miRNA clinical research on PCa, a PubMed-based literature search was conducted with the last update in May 2019. After identifying critical variations in designs and protocols that undermined clear-cut evidence acquisition, and reliable translation into clinical practice, we propose guidelines for most critical steps that should be considered in future research of miRNA as biomarkers, especially in PCa.
    Type of Medium: Online Resource
    ISSN: 1750-1911 , 1750-192X
    URL: Article
    DOI: 10.2217/epi-2019-0275
    Language: English
    Publisher: Future Medicine Ltd
    Publication Date: 2020
    SSG: 12
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