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  • 1
    Online Resource
    Online Resource
    Arginase Inhibition Mitigates Bortezomib-Exacerbated Cardiotoxicity in Multiple Myeloma
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 7 ( 2023-04-06), p. 2191-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 7 ( 2023-04-06), p. 2191-
    Abstract: Background: Multiple myeloma (MM) is associated with increased cardiovascular morbidity and mortality, while MM therapies also result in adverse cardiac effects. Endothelial dysfunction and impaired nitric oxide (NO) pathway is their possible mediator. Objective: Since MM is associated with increased arginase expression, resulting in the consumption of ʟ-arginine, precursor for NO synthesis, our aim was to test if cardiotoxicity mediated by MM and MM therapeutic, bortezomib (a proteasome inhibitor), can be ameliorated by an arginase inhibitor through improved endothelial function. Methods: We used a mouse Vĸ*MYC model of non-light chain MM. Cardiac function was assessed by echocardiography. Results: MM resulted in progressive left ventricular (LV) systolic dysfunction, and bortezomib exacerbated this effect, leading to significant impairment of LV performance. An arginase inhibitor, OAT-1746, protected the heart against bortezomib- or MM-induced toxicity but did not completely prevent the effects of the MM+bortezomib combination. MM was associated with improved endothelial function (assessed as NO production) vs. healthy controls, while bortezomib did not affect it. OAT-1746 improved endothelial function only in healthy mice. NO plasma concentration was increased by OAT-1746 but was not affected by MM or bortezomib. Conclusions: Bortezomib exacerbates MM-mediated LV systolic dysfunction in a mouse model of MM, while an arginase inhibitor partially prevents it. Endothelium does not mediate either these adverse or beneficial effects. This suggests that proteasome inhibitors should be used with caution in patients with advanced myeloma, where the summation of cardiotoxicity could be expected. Therapies aimed at the NO pathway, in particular arginase inhibitors, could offer promise in the prevention/treatment of cardiotoxicity in MM.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15072191
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 2
    Online Resource
    Online Resource
    Systematic Evaluation of Chemically Distinct Tissue Optical Clearing Techniques in Murine Lymph Nodes
    The American Association of Immunologists ; 2020
    In:  The Journal of Immunology Vol. 204, No. 5 ( 2020-03-01), p. 1395-1407
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 5 ( 2020-03-01), p. 1395-1407
    Abstract: Activation of adaptive immunity is a complex process coordinated at multiple levels in both time and the three-dimensional context of reactive lymph nodes (LNs). Although microscopy-based visualization of its spatiotemporal dynamics unravels complexities of developing immune response, such approach is highly limited by light-obstructing nature of tissue components. Recently, tissue optical clearing (TOC) techniques were established to bypass this obstacle and now allow to image and quantify the entire murine organs with cellular resolution. However, the spectrum of TOC is represented by wide variety of chemically distinct methods, each having certain advantages and disadvantages that were unsatisfactorily compared for suitability to LNs clearing. In this study, we have systematically tested 13 typical TOC techniques and assessed their impact on a number of critical factors such as LN transparency, imaging depth, change in size, compatibility with proteinaceous fluorophores, immunostaining, H & E staining, and light-sheet fluorescence microscopy. Based on the detailed data specific to TOC process of murine LNs, we provide a reliable reference for most suitable methods in an application-dependent manner.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.1900847
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2020
    detail.hit.zdb_id: 1475085-5
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  • 3
    Online Resource
    Online Resource
    LED Light Quality Affected Bioactive Compounds, Antioxidant Potential, and Nutritional Value of Red and White Cabbage Microgreens
    MDPI AG ; 2023
    In:  Applied Sciences Vol. 13, No. 9 ( 2023-04-27), p. 5435-
    Details
    In: Applied Sciences, MDPI AG, Vol. 13, No. 9 ( 2023-04-27), p. 5435-
    Abstract: Microgreens are environmentally friendly and have health benefits in addition to their basic nutritional contents. The effect of white (W), white–blue (W + B), and white–red (W + R) light on the bioactive compounds, nutrient composition, and antioxidant potential of red and white cabbage microgreens were investigated using light-emitting diodes (LEDs). The results showed that protein, fat, ash, chlorophylls, and carotenoids were the highest in microgreens under W light, while phenolic compounds were highest in microgreens under W + B light. Supplementation with white light, as well as red or blue light, resulted in higher levels of sugars and total fiber in both white and red microgreens. Twenty-six and thirty-three phenolic compounds were identified in white and red cabbage microgreens, respectively. The identified phenolics belonged to three classes, including phenolic acids, flavonols, and anthocyanins. The antioxidant potential of both cabbage microgreens was determined by four methods (ABTS, DPPH, ORAC, and FRAP). It was found that the highest antioxidant potential was observed in microgreens grown under the W + B light combination. On the other hand, the W + R light combination increased the content of β-sitosterol and campesterol. The results may be helpful in the selection of the type of LED lighting that determines the high nutritional and health-promoting potential of white and red cabbage microgreens.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    URL: Article
    DOI: 10.3390/app13095435
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2704225-X
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  • 4
    Online Resource
    Online Resource
    Targeting arginase-1 exerts antitumor effects in multiple myeloma and mitigates bortezomib-induced cardiotoxicity
    Springer Science and Business Media LLC ; 2022
    In:  Scientific Reports Vol. 12, No. 1 ( 2022-11-16)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-11-16)
    Abstract: Multiple myeloma (MM) remains an incurable malignancy of plasma cells despite constantly evolving therapeutic approaches including various types of immunotherapy. Increased arginase activity has been associated with potent suppression of T-cell immune responses in different types of cancer. Here, we investigated the role of arginase 1 (ARG1) in Vκ*MYC model of MM in mice. ARG1 expression in myeloid cells correlated with tumor progression and was accompanied by a systemic drop in ʟ-arginine levels. In MM-bearing mice antigen-induced proliferation of adoptively transferred T-cells was strongly suppressed and T-cell proliferation was restored by pharmacological arginase inhibition. Progression of Vκ*MYC tumors was significantly delayed in mice with myeloid-specific ARG1 deletion. Arginase inhibition effectively inhibited tumor progression although it failed to augment anti-myeloma effects of bortezomib. However, arginase inhibitor completely prevented development of bortezomib-induced cardiotoxicity in mice. Altogether, these findings indicate that arginase inhibitors could be further tested as a complementary strategy in multiple myeloma to mitigate adverse cardiac events without compromising antitumor efficacy of proteasome inhibitors.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-022-24137-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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  • 5
    Online Resource
    Online Resource
    Potent but transient immunosuppression of T-cells is a general feature of CD71+ erythroid cells
    Springer Science and Business Media LLC ; 2021
    In:  Communications Biology Vol. 4, No. 1 ( 2021-12-10)
    Details
    In: Communications Biology, Springer Science and Business Media LLC, Vol. 4, No. 1 ( 2021-12-10)
    Abstract: CD71 + erythroid cells (CECs) have been recently recognized in both neonates and cancer patients as potent immunoregulatory cells. Here, we show that in mice early-stage CECs expand in anemia, have high levels of arginase 2 (ARG2) and reactive oxygen species (ROS). In the spleens of anemic mice, CECs expansion-induced L -arginine depletion suppresses T-cell responses. In humans with anemia, CECs expand and express ARG1 and ARG2 that suppress T-cells IFN-γ production. Moreover, bone marrow CECs from healthy human donors suppress T-cells proliferation. CECs differentiated from peripheral blood mononuclear cells potently suppress T-cell activation, proliferation, and IFN-γ production in an ARG- and ROS-dependent manner. These effects are the most prominent for early-stage CECs (CD71 high CD235a dim cells). The suppressive properties disappear during erythroid differentiation as more differentiated CECs and mature erythrocytes lack significant immunoregulatory properties. Our studies provide a novel insight into the role of CECs in the immune response regulation.
    Type of Medium: Online Resource
    ISSN: 2399-3642
    URL: Article
    DOI: 10.1038/s42003-021-02914-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2919698-X
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  • 6
    Online Resource
    Online Resource
    Psychological gender, self-esteem, body-esteem, and the use of wellness treatments in women with excessive body weight
    Termedia Sp. z.o.o. ; 2017
    In:  Nutrition, Obesity & Metabolic Surgery Vol. 1 ( 2017), p. 12-17
    Details
    In: Nutrition, Obesity & Metabolic Surgery, Termedia Sp. z.o.o., Vol. 1 ( 2017), p. 12-17
    Type of Medium: Online Resource
    ISSN: 2353-9437
    URL: Article
    DOI: 10.5114/noms.2017.69834
    Language: Unknown
    Publisher: Termedia Sp. z.o.o.
    Publication Date: 2017
    detail.hit.zdb_id: 3031776-9
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  • 7
    Online Resource
    Online Resource
    Toll-like Receptor 2 as a Marker Molecule of Advanced Ovarian Cancer
    MDPI AG ; 2021
    In:  Biomolecules Vol. 11, No. 8 ( 2021-08-13), p. 1205-
    Details
    In: Biomolecules, MDPI AG, Vol. 11, No. 8 ( 2021-08-13), p. 1205-
    Abstract: Ovarian cancer is a global problem that affects women of all ages. Due to the lack of effective screening tests and the usually asymptomatic course of the disease in the early stages, the diagnosis is too late, with the result that less than half of the patients diagnosed with ovarian cancer (OC) survive more than five years after their diagnosis. In this study, we examined the expression of TLR2 in the peripheral blood of 50 previously untreated patients with newly diagnosed OC at various stages of the disease using flow cytometry. The studies aimed at demonstrating the usefulness of TLR2 as a biomarker in the advanced stage of ovarian cancer. In this study, we showed that TLR2 expression levels were significantly higher in women with more advanced OC than in women in the control group. Our research sheds light on the prognostic potential of TLR2 in developing new diagnostic approaches and thus in increasing survival in patients with confirmed ovarian cancer.
    Type of Medium: Online Resource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom11081205
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2701262-1
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  • 8
    Online Resource
    Online Resource
    In Vitro Inhibitory Effects of Viburnum opulus Bark and Flower Extracts on Digestion of Potato Starch and Carbohydrate Hydrolases Activity
    MDPI AG ; 2022
    In:  Molecules Vol. 27, No. 10 ( 2022-05-13), p. 3118-
    Details
    In: Molecules, MDPI AG, Vol. 27, No. 10 ( 2022-05-13), p. 3118-
    Abstract: One of the effective treatments for diabetes is to reduce and delay the absorption of glucose by inhibition of α-amylase and α-glucosidase in the digestive tract. Currently, there is a great interest in natural inhibitors from various part of plants. In the present study, the phenolic compounds composition of V. opulus bark and flower, and their inhibitory effects on in vitro potato starch digestion as well as on α-amylase and α-glucosidase, have been studied. Bark and flower phenolic extracts reduced the amount of glucose released from potato starch during tree-stage simulated digestion, with IC50 value equal to 87.77 µg/mL and 148.87 µg/mL, respectively. Phenolic bark extract showed 34.9% and 38.4% more potent inhibitory activity against α-amylase and α-glucosidase, respectively, but the activity of plant extracts was lower than that of acarbose. Chlorogenic acid (27.26% of total phenolics) and (+)-catechin (30.48% of total phenolics) were the most prominent phenolics in the flower and bark extracts, respectively. Procyanidins may be responsible for the strongest V. opulus bark inhibitory activity against α-amylase, while (+)-catechin relative to α-glucosidase. This preliminary study provides the basis of further examination of the suitability of V. opulus bark compounds as components of nutraceuticals and functional foods with antidiabetic activity.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules27103118
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2008644-1
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  • 9
    Online Resource
    Online Resource
    The Effect of Different Growth Stages of Black Chokeberry Fruits on Phytonutrients, Anti-Lipase Activity, and Antioxidant Capacity
    MDPI AG ; 2022
    In:  Molecules Vol. 27, No. 22 ( 2022-11-19), p. 8031-
    Details
    In: Molecules, MDPI AG, Vol. 27, No. 22 ( 2022-11-19), p. 8031-
    Abstract: The present study investigated the nutrients, biologically-active compounds, as well as antioxidant and anti-lipase activities of chokeberry fruits across four different stages of development, from the unripe green to mature black forms. The highest content of total phenolics (12.30% dry weight (DW)), including proanthocyanidins (6.83% DW), phenolic acids (6.57% DW), flavanols (0.56% DW), flavonols (0.62% DW), and flavanones (0.10% DW), was observed in unripe fruits. The unripe green fruits were also characterized by the highest content of protein (2.02% DW), ash (4.05% DW), total fiber (39.43% DW), and chlorophylls (75.48 mg/100 g DW). Ripe black fruits were the richest source of total carotenoids (8.53 mg/100 g DW), total anthocyanins (2.64 g/100 g DW), and total sugars (33.84% DW). The phenolic compounds of green fruits were dominated by phenolic acids (above 83% of the total content), the semi-mature fruits by both phenolic acids and anthocyanins (90%), while the mature berries were dominated by anthocyanins (64%). Unripe fruits were the most effective inhibitor of pancreatic lipase in triolein emulsion, scavenger of 2,2’-azinobis-(3-ethylbenzothiazolin-6-sulfonic acid) radical cation, and reducer of ferric ion. Biological activities were mainly correlated with total proanthocyanidins and total phenolics. Considering their strong anti-lipase and antioxidant activities, unripe chokeberry fruits may have potential applications in nutraceuticals and functional foods.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules27228031
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2008644-1
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  • 10
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    Online Resource
    Towards higher scientific validity and regulatory acceptance of predictive models for PFAS
    Royal Society of Chemistry (RSC) ; 2023
    In:  Green Chemistry Vol. 25, No. 4 ( 2023), p. 1261-1275
    Details
    In: Green Chemistry, Royal Society of Chemistry (RSC), Vol. 25, No. 4 ( 2023), p. 1261-1275
    Abstract: Per- and polyfluoroalkyl substances (PFAS) are widespread in the environment. Properly developed QSAR/QSPR models can be used to assess the impact of these chemicals on humans and the environment. This work assesses 38 in silico models developed for this group of compounds, which mainly show physicochemical (22), and also toxic (8) and ecotoxic (8) properties. The evaluation of the models was carried out based on the (Q)SAR Model Reporting Format (QMRF), which was found in the QSAR Database (5) or was prepared manually, according to the information contained in scientific publications based on the QMRFEditor-v3.0.0 format (33). We based our evaluations on an individual assessment of each of the OECD principles described in the document and then summing up everything together. During the analysis, we identified 22 models as scientifically valid and could be used in the prediction of new compounds. Twelve of them contained all the information necessary to reproduce the model, and another 10, despite the lack of some information, are still reproducible. The other 16 models do not contain enough information to reproduce them and therefore they are scientifically invalid. The present work allows identifying the remaining gaps, needs, and recommendations that should be considered in further development of predictive models in the PFAS area.
    Type of Medium: Online Resource
    ISSN: 1463-9262 , 1463-9270
    URL: Article
    DOI: 10.1039/D2GC04341F
    Language: English
    Publisher: Royal Society of Chemistry (RSC)
    Publication Date: 2023
    detail.hit.zdb_id: 1485110-6
    detail.hit.zdb_id: 2006274-6
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