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  • 1
    Online Resource
    Online Resource
    Unravelling the Role of Melanin in Cd and Zn Tolerance and Accumulation of Three Dark Septate Endophytic Species
    MDPI AG ; 2020
    In:  Microorganisms Vol. 8, No. 4 ( 2020-04-08), p. 537-
    Details
    In: Microorganisms, MDPI AG, Vol. 8, No. 4 ( 2020-04-08), p. 537-
    Abstract: Dark septate endophytes (DSEs) are often trace element (TE)-tolerant fungi and are abundant in TE-polluted environments. The production of melanin, a black polymer found in cell walls, was hypothesized by several authors to play a role in the TE tolerance of DSEs. To test this hypothesis, we established a series of experiments using albino strains and melanin inhibitors and examined the responses to Cd and Zn. Six DSEs belonging to genera Cadophora sp., Leptodontidium sp. and Phialophora mustea, were evaluated. The strains mainly produced 1,8-dihydroxynaphthalene (DHN) melanin whereas 3,4-dihydroxyphenylalanin melanin was also synthetized. Cd and Zn decreased melanin synthesis in most of the strains. A reduction in melanin concentration in hyphae through the use of tricyclazole, an inhibitor of DHN-melanin synthesis, did not reduce the tolerance of the strains to Cd and Zn. Similarly, albino mutants of Leptodontidium sp. were not more sensitive to Cd and Zn than the WT strain. Moreover, tricyclazole-treated colonies accumulated less Cd but more Zn compared to untreated colonies. The Cd and Zn contents of Leptodontidium albino strains were variable and similar to that of the WT. The results suggest that melanin production is not an important functional trait that contributes to Cd and Zn tolerance, but might contribute to Cd accumulation.
    Type of Medium: Online Resource
    ISSN: 2076-2607
    URL: Article
    DOI: 10.3390/microorganisms8040537
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2720891-6
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  • 2
    Online Resource
    Online Resource
    Natural Compounds as Target Biomolecules in Cellular Adhesion and Migration: From Biomolecular Stimulation to Label-Free Discovery and Bioactivity-Based Isolation
    MDPI AG ; 2021
    In:  Biomedicines Vol. 9, No. 12 ( 2021-11-26), p. 1781-
    Details
    In: Biomedicines, MDPI AG, Vol. 9, No. 12 ( 2021-11-26), p. 1781-
    Abstract: Plants and fungi can be used for medical applications because of their accumulation of special bioactive metabolites. These substances might be beneficial to human health, exerting also anti-inflammatory and anticancer (antiproliferative) effects. We propose that they are mediated by influencing cellular adhesion and migration via various signaling pathways and by directly inactivating key cell adhesion surface receptor sites. The evidence for this proposition is reviewed (by summarizing the natural metabolites and their effects influencing cellular adhesion and migration), along with the classical measuring techniques used to gain such evidence. We systematize existing knowledge concerning the mechanisms of how natural metabolites affect adhesion and movement, and their role in gene expression as well. We conclude by highlighting the possibilities to screen natural compounds faster and more easily by applying new label-free methods, which also enable a far greater degree of quantification than the conventional methods used hitherto. We have systematically classified recent studies regarding the effects of natural compounds on cellular adhesion and movement, characterizing the active substances according to their organismal origin (plants, animals or fungi). Finally, we also summarize the results of recent studies and experiments on SARS-CoV-2 treatments by natural extracts affecting mainly the adhesion and entry of the virus.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines9121781
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720867-9
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  • 3
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    Online Resource
    In Vivo Efficacy of Amphotericin B against Four Candida auris Clades
    MDPI AG ; 2022
    In:  Journal of Fungi Vol. 8, No. 5 ( 2022-05-11), p. 499-
    Details
    In: Journal of Fungi, MDPI AG, Vol. 8, No. 5 ( 2022-05-11), p. 499-
    Abstract: Candida auris is a multidrug-resistant fungus against which in some clinical situations amphotericin B (AMB) remains the alternative or first line drug. We compared daily 1 mg/kg of AMB efficacy in a neutropenic murine bloodstream infection model against 10 isolates representing four C. auris clades (South Asian n = 2; East Asian n = 2; South African n = 2; South American n = 4; two of which were of environmental origin). Five days of AMB treatment significantly increased the survival rates in mice infected with isolates of the East Asian clade, and 1 isolate each from the South African and South American clades (originated from bloodstream), but not in mice infected with the South Asian and 2 environmental isolates from the South American clades. AMB treatment decreased the fungal burden in mice infected with the 2 isolates each from East Asian and South African, and 1 out of 2 bloodstream isolates from South American clades in the hearts (p 〈 0.01), kidneys (p 〈 0.01) and brain (p 〈 0.05). AMB treatment, regardless of clades, significantly decreased colony forming units in the urine at day 3. However, histopathological examination in AMB-treated mice revealed large aggregates of yeast cells in the kidneys and hearts, and focal lesions in the cerebra and cerebelli, regardless of precise C. auris clade. Our clade-specific data confirm that the efficacy of AMB against C. auris is weak, explaining the therapeutic failures in clinical situations. Our results draw attention to the necessity to maximize the killing at the start of treatment to avoid later complications in the heart and central nervous system.
    Type of Medium: Online Resource
    ISSN: 2309-608X
    URL: Article
    DOI: 10.3390/jof8050499
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2784229-0
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  • 4
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    Online Resource
    The AtCRK5 Protein Kinase Is Required to Maintain the ROS NO Balance Affecting the PIN2-Mediated Root Gravitropic Response in Arabidopsis
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 11 ( 2021-06-01), p. 5979-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 11 ( 2021-06-01), p. 5979-
    Abstract: The Arabidopsis AtCRK5 protein kinase is involved in the establishment of the proper auxin gradient in many developmental processes. Among others, the Atcrk5-1 mutant was reported to exhibit a delayed gravitropic response via compromised PIN2-mediated auxin transport at the root tip. Here, we report that this phenotype correlates with lower superoxide anion (O2•−) and hydrogen peroxide (H2O2) levels but a higher nitric oxide (NO) content in the mutant root tips in comparison to the wild type (AtCol-0). The oxidative stress inducer paraquat (PQ) triggering formation of O2•− (and consequently, H2O2) was able to rescue the gravitropic response of Atcrk5-1 roots. The direct application of H2O2 had the same effect. Under gravistimulation, correct auxin distribution was restored (at least partially) by PQ or H2O2 treatment in the mutant root tips. In agreement, the redistribution of the PIN2 auxin efflux carrier was similar in the gravistimulated PQ-treated mutant and untreated wild type roots. It was also found that PQ-treatment decreased the endogenous NO level at the root tip to normal levels. Furthermore, the mutant phenotype could be reverted by direct manipulation of the endogenous NO level using an NO scavenger (cPTIO). The potential involvement of AtCRK5 protein kinase in the control of auxin-ROS-NO-PIN2-auxin regulatory loop is discussed.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22115979
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
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    Online Resource
    Unpredictable In Vitro Killing Activity of Amphotericin B against Four Candida auris Clades
    MDPI AG ; 2021
    In:  Pathogens Vol. 10, No. 8 ( 2021-08-06), p. 990-
    Details
    In: Pathogens, MDPI AG, Vol. 10, No. 8 ( 2021-08-06), p. 990-
    Abstract: Candida auris is an emerging multiresistant yeast against which amphotericin B (AMB) is still the first therapeutic choice in certain clinical situations (i.e., meningitis, endophthalmitis, and urinary tract infections). As data about the in vitro killing activity of AMB against C. auris clades are lacking, we determined MICs, minimum fungicidal concentrations (MFCs), and killing activity of AMB against 22 isolates representing the 4 major C. auris clades (South Asian n = 6; East Asian n = 4; South African n = 6, and South American n = 6). MIC values were ≤1 mg/L regardless of clades; MFC ranges were, 1–4 mg/L, 2–4 mg/L, 2 mg/L, and 2–8 mg/L for South Asian, East Asian, South African, and South American clades, respectively. AMB showed concentration-, clade-, and isolate-dependent killing activity. AMB was fungicidal at 1 mg/L against two of six, two of four, three of six, and one of six isolates from the South Asian, East Asian, South African, and South American clades, respectively. Widefield fluorescence microscopy showed cell number decreases at 1 mg/L AMB in cases of the South Asian, East Asian, and South African clades. These data draw attention to the weak killing activity of AMB against C. auris regardless of clades, even when MICs are low (≤1 mg/L). Thus, AMB efficacy is unpredictable in treatment of invasive C. auris infections.
    Type of Medium: Online Resource
    ISSN: 2076-0817
    URL: Article
    DOI: 10.3390/pathogens10080990
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2695572-6
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  • 6
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    Online Resource
    Relative Frequency of Paradoxical Growth and Trailing Effect with Caspofungin, Micafungin, Anidulafungin, and the Novel Echinocandin Rezafungin against Candida Species
    MDPI AG ; 2020
    In:  Journal of Fungi Vol. 6, No. 3 ( 2020-08-17), p. 136-
    Details
    In: Journal of Fungi, MDPI AG, Vol. 6, No. 3 ( 2020-08-17), p. 136-
    Abstract: Rezafungin is a next-generation echinocandin that has favorable pharmacokinetic properties. We compared the occurrence of paradoxical growth (PG) and trailing effect (TE) characteristics to echinocadins with rezafungin, caspofungin, micafungin and anidulafungin using 365 clinical Candida isolates belonging to 13 species. MICs were determined by BMD method according to CLSI (M27 Ed4). Disconnected growth (PG plus TE) was most frequent with caspofungin (49.6%), followed by anidulafungin (33.7%), micafungin (25.7%), while it was least frequent with rezafungin (16.9%). PG was relatively common in the case of caspofungin (30.1%) but was rare in the case of rezafungin (3.0%). C. tropicalis, C. albicans, C. orthopsilosis and C. inconspicua exhibited PG most frequently with caspofungin, micafungin or anidulafungin. PG never occurred in the case of C. krusei isolates. Against C. tropicalis and C. albicans, echinocandins frequently showed PG after 24 h followed by TE after 48 h. All four echinocandins exhibited TE for the majority of C. auris and C. dubliniensis isolates. Disconnected growth was common among Candida species and was echinocandin- and species-dependent. In contrast to earlier echinocandins, PG was infrequently found with rezafungin.
    Type of Medium: Online Resource
    ISSN: 2309-608X
    URL: Article
    DOI: 10.3390/jof6030136
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2784229-0
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  • 7
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    Comparison of In Vitro Killing Activity of Rezafungin, Anidulafungin, Caspofungin, and Micafungin against Four Candida auris Clades in RPMI-1640 in the Absence and Presence of Human Serum
    MDPI AG ; 2021
    In:  Microorganisms Vol. 9, No. 4 ( 2021-04-16), p. 863-
    Details
    In: Microorganisms, MDPI AG, Vol. 9, No. 4 ( 2021-04-16), p. 863-
    Abstract: Candida auris is an emerging and frequently multidrug-resistant pathogen against which the echinocandins are the preferred therapeutic option. We compared killing activities of anidulafungin, caspofungin, micafungin, and rezafungin against 13 isolates representing four C. auris clades (South Asian n = 3; East Asian n = 3; South African n = 3; South American n = 4, of which two were of environmental origin). Minimum inhibitory concentration MICs and killing kinetics in RPMI-1640 and RPMI-1640 plus 50% serum (50% serum) were determined. The four echinocandins were never fungicidal and induced large aggregates in RPMI-1640 and, less markedly, in 50% serum. Colony forming unit CFU decreases were found more consistently in 50% serum than in RPMI-1640. Isolates from the East Asian clade were killed at ≥1–≥ 4 mg/L with all echinocandins regardless of media. Anidulafungin and micafungin produced killing at peak drug serum concentration (8 mg/L) against environmental but not clinical isolates from the South American and the South African clades. Micafungin at ≥8 mg/L but not anidulafungin produced CFU decreases against the South Asian clade as well. In 50% serum, rezafungin at ≥1–≥ 8 mg/L produced killing against all four clades. The next generation echinocandin, rezafungin, showed the same or better activity at clinically attainable trough concentration regardless of media, compared with anidulafungin, caspofungin, and micafungin against all four tested C. auris clades.
    Type of Medium: Online Resource
    ISSN: 2076-2607
    URL: Article
    DOI: 10.3390/microorganisms9040863
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720891-6
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  • 8
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    Online Resource
    Distinct Molecular Signatures of Amyloid-Beta and Tau in Alzheimer’s Disease Associated with Down Syndrome
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 14 ( 2023-07-18), p. 11596-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 14 ( 2023-07-18), p. 11596-
    Abstract: Limited comparative data exist on the molecular spectrum of amyloid-beta (Aβ) and tau deposition in individuals with Down syndrome (DS) and sporadic Alzheimer’s disease (sAD). We assessed Aβ and tau deposition severity in the temporal lobe and cerebellum of ten DS and ten sAD cases. Immunohistochemistry was performed using antibodies against eight different Aβ epitopes (6F/3D, Aβ38, Aβ39, Aβ40, Aβ42, Aβ43, pyroglutamate Aβ at third glutamic acid (AβNp3E), phosphorylated- (p-)Aβ at 8th serine (AβpSer8)), and six different pathological tau epitopes (p-Ser202/Thr205, p-Thr231, p-Ser396, Alz50, MC1, GT38). Findings were evaluated semi-quantitatively and quantitatively using digital pathology. DS cases had significantly higher neocortical parenchymal deposition (Aβ38, Aβ42, and AβpSer8), and cerebellar parenchymal deposition (Aβ40, Aβ42, AβNp3E, and AβpSer8) than sAD cases. Furthermore, DS cases had a significantly larger mean plaque size (6F/3D, Aβ42, AβNp3E) in the temporal lobe, and significantly greater deposition of cerebral and cerebellar Aβ42 than sAD cases in the quantitative analysis. Western blotting corroborated these findings. Regarding tau pathology, DS cases had significantly more severe cerebral tau deposition than sAD cases, especially in the white matter (p-Ser202/Thr205, p-Thr231, Alz50, and MC1). Greater total tau deposition in the white matter (p-Ser202/Thr205, p-Thr231, and Alz50) of DS cases was confirmed by quantitative analysis. Our data suggest that the Aβ and tau molecular signatures in DS are distinct from those in sAD.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241411596
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 9
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    Triple-Negative Breast Cancer Histological Subtypes with a Favourable Prognosis
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 22 ( 2021-11-14), p. 5694-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 22 ( 2021-11-14), p. 5694-
    Abstract: Triple-negative breast cancers (TNBC), as a group of tumours, have a worse prognosis than stage-matched non-TNBC and lack the benefits of routinely available targeted therapy. However, TNBC is a heterogeneous group of neoplasms, which includes some special type carcinomas with a relatively indolent course. This review on behalf of the European Working Group for Breast Screening Pathology reviews the literature on the special histological types of BC that are reported to have a triple negative phenotype and indolent behaviour. These include adenoid cystic carcinoma of classical type, low-grade adenosquamous carcinoma, fibromatosis-like metaplastic carcinoma, low-grade mucoepidermoid carcinoma, secretory carcinoma, acinic cell carcinoma, and tall cell carcinoma with reversed polarity. The pathological and known molecular features as well as clinical data including treatment and prognosis of these special TNBC subtypes are summarised and it is concluded that many patients with these rare TNBC pure subtypes are unlikely to benefit from systemic chemotherapy. A consensus statement of the working group relating to the multidisciplinary approach and treatment of these rare tumour types concludes the review.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13225694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 10
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    The Neosartorya fischeri Antifungal Protein 2 (NFAP2): A New Potential Weapon against Multidrug-Resistant Candida auris Biofilms
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 2 ( 2021-01-14), p. 771-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 2 ( 2021-01-14), p. 771-
    Abstract: Candida auris is a potential multidrug-resistant pathogen able to persist on indwelling devices as a biofilm, which serve as a source of catheter-associated infections. Neosartorya fischeri antifungal protein 2 (NFAP2) is a cysteine-rich, cationic protein with potent anti-Candida activity. We studied the in vitro activity of NFAP2 alone and in combination with fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin against C. auris biofilms. The nature of interactions was assessed utilizing the fractional inhibitory concentration index (FICI), a Bliss independence model, and LIVE/DEAD viability assay. NFAP2 exerted synergy with all tested antifungals with FICIs ranging between 0.312–0.5, 0.155–0.5, 0.037–0.375, 0.064–0.375, and 0.064–0.375 for fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin, respectively. These results were confirmed using a Bliss model, where NFAP2 produced 17.54 μM2%, 2.16 μM2%, 33.31 μM2%, 10.72 μM2%, and 111.19 μM2% cumulative synergy log volume in combination with fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin, respectively. In addition, biofilms exposed to echinocandins (32 mg/L) showed significant cell death in the presence of NFAP2 (128 mg/L). Our study shows that NFAP2 displays strong potential as a novel antifungal compound in alternative therapies to combat C. auris biofilms.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22020771
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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