Startseite Exploring the effects of culture conditions on Yapsin (YPS) gene expression in Nakaseomyces glabratus
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Exploring the effects of culture conditions on Yapsin (YPS) gene expression in Nakaseomyces glabratus

  • Aneta Bednarek , Agnieszka Kabut , Maria Rapala-Kozik und Dorota Satala EMAIL logo
Veröffentlicht/Copyright: 26. November 2024
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Open Life Sciences
Aus der Zeitschrift Open Life Sciences Band 19 Heft 1

Abstract

Nakaseomyces glabratus, previously known as Candida glabrata, has the great potential to cause systemic fungal infections despite its similarity to baker’s yeast. Its pathogenicity is attributed to the production of numerous virulence factors, among which the YPS genes (YPS1–YPS11) encoding aspartyl proteases have yet to be sufficiently characterized, and limited studies suggest their involvement in cellular homeostasis. The study’s novelty is an investigation of the role of YPS in N. glabratus’s ability to adapt to different host environments. For this purpose, we isolated RNA from N. glabratus cells grown in both host niche-mimicking culture media, such as artificial saliva (AS) and vagina-simulating media (VS), as well as standard yeast media (RPMI 1640 and YPDA). We then performed quantitative real-time PCR to evaluate YPS gene expression at different growth phases. At the early logarithmic phase, we observed a general increase in the expression levels of YPS genes; however, at the stationary phase, high expression levels were maintained for YPS7 in RPMI 1640 and YPDA media and YPS6 in RPMI 1640 and AS media. In addition, although the VS medium does not promote the proliferation of N. glabratus, the yeast can survive in an acidic environment, and the significantly overexpressed gene is YPS7. These findings underscore the significant modulation of N. glabratus YPS gene expression in response to external environmental conditions. This research provides insights into the molecular basis of N. glabratus pathogenicity and highlights new potential targets for antifungal therapy.

Graphical abstract

Keywords: Nakaseomyces glabratus ; YPS gene expression; fungal pathogenicity; protease regulation; host niche adaptation

1 Introduction

Nakaseomyces glabratus – previously identified as Candida glabrata – exhibits high infectious potential despite its close phylogenetic relationship with baker’s yeast. It is the second most common pathogen, following Candida albicans, and is responsible for many mucosal and systemic candidiasis cases, particularly among immunocompromised individuals [1,2]. In recent decades, the increasing incidence of N. glabratus infections and its resistance to fluconazole has posed a significant challenge for medical management [3,4,5,6].

Fungal pathogens use a wide range of molecules, enabling them to invade deep into host tissues, evade defense mechanisms and immune surveillance, and spread to distant niches in the host, where they begin colonization [7,8,9]. This repertoire of molecules includes proteins that are expressed on the cell surface and secreted outside the cell [10,11,12,13,14]. In the case of the primary fungal pathogen C. albicans, it has been shown that one such group of moleclues attributed to pathogenic potential is proteases, specifically the secreted aspartyl proteases family (Sap), which has at least ten identified members [15,16]. These proteases play critical roles in the infection process, including nutrient acquisition through the degradation of host molecules, facilitating adhesion and tissue invasion by disrupting host cell membranes, and evading host immune defenses by degrading host cells and immune molecules [17,18,19,20,21,22,23,24,25,26,27,28]. Interestingly, N. glabratus is a unique species that does not produce the typical candidal extracellular aspartyl proteases belonging to the Sap family. Instead, it displays on its cell surface a poorly characterized group of proteases from a family known as yapsin (Yps) [22,29]. The N. glabratus genome contains at least 11 genes encoding Yps, most of which are likely covalently attached to the cell wall via glycosylphosphatidylinositol anchors located at the C-terminus of the proteins [30].

In the case of C. albicans, SAP expression is modulated by various environmental factors, including pH changes, and by interactions with the host, e.g., adhesion to vaginal epithelial cells or interactions with serum components. These results suggest that C. albicans can fine-tune its virulence factors through sophisticated mechanisms in response to specific host niches [26,31,32,33,34,35,36]. The data on changes in N. glabratus YPS expression is limited to a few reports that demonstrated that upon internalization by neutrophils, the fungus overexpressed YPS1, YPS2, YPS4-6, and YPS8-11, whereas macrophage-associated yeasts overexpress YPS2, YPS4, YPS5, and YPS8-11 [37,38]. Furthermore, Ferrari et al. [39] highlighted the significance of Yps in virulence, indicating that strains of N. glabratus that are resistant to azoles and exhibit mitochondrial dysfunction (BPY41) overexpress genes encoding these proteases.

The primary aim of this study was to investigate the regulatory mechanisms controlling YPS gene expression in N. glabratus under diverse environmental conditions to elucidate how these proteases contribute to the pathogen’s adaptation and survival within different host niches. By examining YPS gene expression not only in standard yeast culture media (RPMI 1640 and YPDA) but also in host-mimicking environments such as artificial saliva (AS) and vagina-simulating media (VS), we sought to identify specific proteases that respond to variations in pH and nutrient availability. The results of this study are intended to deepen our understanding of the adaptive strategies employed by N. glabratus and to highlight potential targets for therapeutic intervention and diagnostics in fungal infections.

2 Materials and methods

2.1 Yeast strains and culture conditions

Cells of the N. glabratus strain CBS138 (ATCC® 2001™) purchased from the American Type Culture Collection (Manassas, VA, USA) were cultured in yeast peptone dextrose (YPD) medium (1% yeast extract, 2% soy peptone, and 2% glucose, pH 6.0; Sigma, St. Louis, MO, USA) for 16 h at 30°C with shaking at 170 rpm. To measure the optical density (OD), 20 µl of the culture was inoculated into 20 ml of different growth media and cultured for approximately 25 h at 37°C and 170 rpm. Then, OD at 600 nm was measured every hour using a Synergy H1 microplate reader (BioTek Instruments, Winooski, VT, USA); however, in cases where the measured OD exceeded 1, samples were diluted 10-fold to ensure accurate measurements and avoid signal saturation. This measurement allowed us to track the exponential growth phase and assess potential growth inhibition in different media, providing crucial data on how varying conditions impact the proliferation of N. glabratus. Based on the observed logarithmic growth of cells over time, the values of the coefficient-specific growth rate (µ max) were calculated using the formula μ max  =  (ln ODmax – ln ODmin)/Δt log [40]. The media used in the experiments is the Roswell Park Memorial Institute (RPMI 1640) defined media (PAA Laboratories GmbH, Pasching, Austria), YPDA media – YPD buffered media with a reduced content of animal-derived peptone (0.1% yeast extract, 0.2% animal peptone, and 2% glucose, pH 7.0) supplemented with 10 mM NaH2PO4, and media mimicking the vaginal microenvironment (VS, pH 4.2), prepared according to the procedure of Moosa et al. [41], and a media consisting of chemically defined AS (pH 7.0), prepared according to the procedure described in the work of Wong and Sissons [42]. Cells intended for RNA isolation were collected at two points of growth – the early logarithmic phase (4 h) and the stationary phase (18 h). Exceptionally, in the case of the VS medium, 50 times more cells were used for inoculation, which, according to the OD measurement, was approximately 7.5 × 108 cells per 20 ml of medium. In this medium, the material for RNA isolation was collected after 18 h.

2.2 Cell viability

Cell integrity was examined using Sytox™ Green nucleic acid stain (Thermo Fisher Scientific, Waltham, MA, USA). For this purpose, 1 × 105 N. glabratus cells cultured in VS and YPD media for 18 h were placed in the wells of a glass-like microplate (CellVis, Mountain View, CA, USA). After adding the dye, they were imaged using an Olympus IX73 microscope (Olympus, Tokyo, Japan). In addition, cell metabolic activity was measured using an assay based on the quantitation of ATP present in the culture. To each well of a 384-well polypropylene microplate (Greiner, Kremsmünster, Austria), 104 N. glabratus cells cultured in YPD or VS media were added to a final volume of 25 µl of PBS. Then, starting the bioluminescence reaction, 50 µl of the BacTiter-Glo™ reagent (Promega, Madison, WI, USA) was added to each well according to the manufacturer’s instructions. After 15 min of incubation at room temperature, the luminescence level was measured using a Synergy H1 microplate reader (BioTek Instruments). To determine the CFUs (colony-forming units), N. glabratus colonies were counted after the same number of cells were seeded onto agar plates and incubated overnight at 37°C.

2.3 Isolation and purification of RNA

After overnight culture of N. glabratus grown in the YPD medium, the cells were transferred with appropriate media and cultured at 37°C with shaking at 170 rpm. After the specified times (4 h or 18 h), the cells were centrifuged for 6 min at 2,500 × g, followed by washing three times with PBS. The cells were centrifuged at 5,000 × g, the filtrate was removed, and the pellet was frozen in liquid nitrogen. Once thawed, the cells were transferred to a tube containing 0.4 ml of glass beads (25–600 μm, Sigma Aldrich, St. Louis, MO, USA) and 0.8 ml of Tri Reagent (Sigma Aldrich). The suspension was then shaken using a FastPrep Precellys Evolution (Bertin Technology, Montigny-le-Bretonneu, France) for 2 cycles at 6 rpm for 45 s with a 2-min break on ice between cycles. In the next step, 160 µl of chloroform was added to the lysate, vortexed for 15 s, and incubated at 4°C for 30 min. After incubation, the suspension was centrifuged at 10,000 × g at 4°C for 15 min. The filtrate (phase with nucleic acids) was transferred to a new tube, and isopropanol was added to a volume equal to the mixture, and the mixture was incubated overnight at −20°C. The next day, the mixture was centrifuged at 10,000 × g for 15 min at 4°C, the filtrate was removed, and the pellet was resuspended in 70% ethanol, incubated for 1 min, vortexed, and then centrifuged under the same conditions. This step was repeated until the pellet was thoroughly dried and resuspended in RNase-free water. The whole pellet was incubated at 56°C for 5 min. RNA purity was verified using a NanoDrop spectrophotometer (Thermo Fisher Scientific), with A260/A280 ratios between 1.8 and 2.0 considered indicative of high purity. Additionally, RNA integrity was confirmed electrophoretically on a 1.5% agarose gel stained with ethidium bromide using the RiboRuler High Range RNA Ladder (Thermo Scientific) (Figure S1 in supplementary material), ensuring the absence of degradation prior to downstream qPCR analyses. These steps were critical to guarantee the accuracy and reproducibility of gene expression results obtained in subsequent experiments.

2.4 Real-time PCR (qPCR)

The level of YPS1–11 transcripts was determined by real-time PCR (qPCR). For this purpose, information from isolated RNA was transcribed into cDNA via reverse transcription. In the first step of this reaction, 2 µg of total RNA was resuspended in RNase-free water supplemented with 0.5 g of oligo(dT)18 primer (Genomed, Warszawa, Poland), heated at 70°C for 5 min, and then cooled to 4°C. In the second step, a reaction mixture containing 200 U of MLV reverse transcriptase (Moloney murine leukemia virus reverse transcriptase; Promega, Madison, WI, USA) was added to the sample, and the PCR was run in a C1000 Touch Thermal Cycler (Bio-Rad, Hercules, CA, USA) for 1 h at 42°C and 10 min at 70°C. For qPCR, 4 times-diluted cDNA was used and applied in triplicate (2 µl per well) to a MicroAmp Fast 96-well reaction plate (Thermo Fisher Scientific), followed by the addition of 8 µl of the reaction mixture, which was prepared according to instructions of the SYBR™ qRT‒PCR Kit (A&A Biotechnology, Gdynia, Poland), which provides high sensitivity for detecting gene expression changes. In addition, a negative control for each gene was performed, in which 2 µl of RNase-free water was added to the well of the plate instead of the cDNA matrix. The reaction was carried out on a QuantStudio™ 3 Real-Time PCR System (Thermo Fisher Scientific) under the following conditions: initial denaturation at 95°C for 5 min and 40 cycles of denaturation at 95°C for 15 s, primer annealing at 58°C for 15 s, and extension at 72°C for 20 s for genes YPS1–10; for YPS11, the only difference was the primer annealing temperature of 56°C. The relative quantification of YPS genes was performed using ACT1, commonly used as a housekeeping gene [43,44]. The primers for each gene were obtained from Genomed (Warszawa, Poland), and their sequences were obtained from the work of Kaur et al. [37]. Melting curve analysis was performed to evaluate the quality of the qPCR results, and relative gene expression levels were analyzed using the ∆∆Cq method [45], where the cell culture in the YPD medium for 4 and 18 h, respectively, was used as the reference growing conditions. The experiments were performed in triplicate with two biological replicates.

3 Results

In this study, three primary media commonly used for culturing S. cerevisiae and Candida spp. cells were employed: YPD (pH 6.0), RPMI 1640 (pH 7.4), and YPD-buffered medium with a reduced content of animal-derived peptone (YPDA, pH 7.0). The YPD medium comprises yeast extract, peptone, and dextrose, where the yeast extract contains essential vitamins and micronutrients, peptone is a source of amino acids and peptides, and dextrose acts as a carbon source. This composition optimizes the growth and proliferation of Candida spp. Conversely, RPMI 1640 is primarily used in studies investigating Candida susceptibility to antibiotics and biofilm formation [46]. The YPDA medium, distinguished by its reduced nitrogen content, predominantly induces the production of proteases [47]; however, at 37°C, it also promotes the generation of filamentous forms of Candida spp. Although N. glabratus cannot produce filamentous cells, which are commonly considered the most virulent form of other Candida species, significant changes in the proteome composition have been demonstrated to occur on the surface of the yeast depending on the culture medium used [48], highlighting the validity of using different types of media in our study. Two types of media with varying compositions and pH levels were used to simulate different potential sites of infection – AS (pH 7.0) to mimic the oral cavity [42] and VS (pH 4.2) to represent the vaginal microenvironment [41].

In the initial phase of our research, we conducted OD measurements to quantify the growth rate (μ max) of N. glabratus cultures (Figure 1). These measurements indicate that N. glabratus exhibits variable growth rates in response to different media compositions and environmental factors. In RPMI 1640 and YPDA media, the growth rate of N. glabratus was reduced compared to YPD (μ max = 0.281, 0.395, and 0.496, respectively), as evidenced by a slower progression through the exponential phase. Despite this, the overall sigmoidal growth pattern was preserved. These findings suggest that while the nutrient composition and pH modulate growth dynamics, N. glabratus can adapt and maintain proliferation across diverse environments. In AS media, we showed delayed growth initiation (μ max = 0.195) but eventually reached OD levels comparable to those of YPD media, indicating that although this medium may have limitations in supporting immediate growth, it ultimately sustains yeast proliferation to a similar degree. We recorded the lowest OD values in the VS medium, indicating an unfavorable environment for yeast growth or a potential inhibitory effect on N. glabratus proliferation. These results were unexpected, given that previous studies identified N. glabratus as one of the main pathogens isolated in cases of vaginal infection [49,50]. Therefore, we decided to conduct further analyses. Based on the CFU assay, microbial metabolic activity assay, and SYTOX Green staining revealing dead cells, we showed that although media-simulating vaginal conditions do not promote yeast cell proliferation, N. glabratus can survive in such environments (Figure 2). Thus, we decided not to exclude this medium from further analyses, raising the question of whether proteases play key roles in yeast survival under low-pH culture conditions.

Figure 1 Analysis of N. glabratus growth in different culture media. (a) Growth curves of N. glabratus based on OD measurements taken hourly over 25 h. Values are presented as the mean ± SD from a representative experiment conducted in triplicate. (b) Growth parameters of N. glabratus, calculated from the OD data.
Figure 1

Analysis of N. glabratus growth in different culture media. (a) Growth curves of N. glabratus based on OD measurements taken hourly over 25 h. Values are presented as the mean ± SD from a representative experiment conducted in triplicate. (b) Growth parameters of N. glabratus, calculated from the OD data.

Figure 2 Survival of N. glabratus cells in the VS medium. N. glabratus cells (1 × 107) were cultured for 18 h in the VS medium at 37°C, and then (a) CFU assays were performed in which 100 cells per plate were seeded based on OD measurements, corresponding to 100% CFU in the graph; (b) cell viability was assessed based on the amount of ATP present in 1 × 104 cells per well of the microplate; and (c) cells were stained with SYTOX Green and imaged on an Olympus IX73 microscope as an overlay of bright field and FITC (BF/FITC). An equal number of N. glabratus cells cultured for 18 h in a YPD medium was used as a control for each analysis.
Figure 2

Survival of N. glabratus cells in the VS medium. N. glabratus cells (1 × 107) were cultured for 18 h in the VS medium at 37°C, and then (a) CFU assays were performed in which 100 cells per plate were seeded based on OD measurements, corresponding to 100% CFU in the graph; (b) cell viability was assessed based on the amount of ATP present in 1 × 104 cells per well of the microplate; and (c) cells were stained with SYTOX Green and imaged on an Olympus IX73 microscope as an overlay of bright field and FITC (BF/FITC). An equal number of N. glabratus cells cultured for 18 h in a YPD medium was used as a control for each analysis.

In recent years, several advanced techniques for gene expression analysis have emerged, the most popular of which are RNA sequencing (RNA-seq) and microarrays. These methods enable high-throughput analyses determining the levels of thousands of genes per sample, which requires advanced bioinformatics analysis [51,52]. A significant advantage of RNA-seq is the ability to identify known and new transcriptomes [51], while microarrays, widely used in clinical studies, are limited in identifying predefined genes for which it is necessary to design appropriate probes [51,53]. Since the choice of the method is closely related to the study’s aim, and in our case, it was to investigate changes in the expression of a specific group of genes, we decided to perform analyses using the real-time PCR method. Due to its high sensitivity, which enables the detection of low-abundance transcripts, rapid measurements, accurate results, and relatively easy analysis, this method remains irreplaceable in basic research. Our analyses were performed on RNA isolated from different culture conditions in two growth phases – the early logarithmic phase (4 h) and the stationary phase (18 h), using cells cultured for analogous times in a YPD medium as a control. Using media with different compositions and pH values ranging from 4.2 to 7.4 provided insights into the regulatory mechanisms involved under different environmental stimuli (Figure 3). As shown, culturing for 4 h in RPMI 1640 and YPDA media leads to an increase in the expression of several YPS genes, namely YPS4, YPS6, and YPS9-11. Remarkably, the YPS7 transcript level significantly increased by more than 30-fold in the RPMI 1640 medium and 15-fold in the YPDA medium after 18 h of culture. Furthermore, pronounced upregulation of YPS6 (more than 20-fold) was observed in the RPMI 1640 medium, which coincided with a decrease in the expression of YPS1 and YPS5. In turn, analysis of changes in gene expression after culturing in media that mimic the host niche revealed an increase of more than 20-fold in the expression of YPS6 and YPS8–YPS11 after 4 h in the AS medium. Extending the culture period under these conditions resulted in elevated YPS6 and YPS11 transcript levels; however, the increase did not exceed five-fold. Simultaneously, decreased expression of YPS1–5 and YPS9 was observed. In the case of the VS medium, which has a pH of 4.2, YPS7 plays a predominant role, with a recorded increase in expression exceeding 35-fold. The only gene that exhibited a significant reduction in expression under these conditions was YPS5. Interestingly, a three-fold increase in YPS1 expression was observed, in contrast with reduced transcript levels after 18 h in other media. The YPS3, YPS4, and YPS6 genes are insensitive to acidic environments.

Figure 3 Changes in the expression of N. glabratus genes encoding YPS in response to changing culture conditions. Bars represent fungal gene expression levels in N. glabratus cells cultured in standard media (4 h and 18 h in RPMI 1640 and YPDA) or (b) in media mimicking host niches (4 h and 18 h of culture in the AS medium and 18 h in the VS medium). Gene expression levels were calculated by normalizing expression to that of ATC1 and determined using the 2−ΔΔCT method. The results were normalized to the YPD medium, in which the expression of individual YPS genes was set to 1 (as indicated by the dashed line in the graph). The bars indicate representative results of two independent experiments as the mean ± SD. The statistical significance of the reference was determined by one-way ANOVA with Dunnett’s multiple comparison test using GraphPad Prism software and is marked with *p  <  0.05, **p  <  0.01, ***p  <  0.001, ****p  <  0.0001.
Figure 3

Changes in the expression of N. glabratus genes encoding YPS in response to changing culture conditions. Bars represent fungal gene expression levels in N. glabratus cells cultured in standard media (4 h and 18 h in RPMI 1640 and YPDA) or (b) in media mimicking host niches (4 h and 18 h of culture in the AS medium and 18 h in the VS medium). Gene expression levels were calculated by normalizing expression to that of ATC1 and determined using the 2−ΔΔCT method. The results were normalized to the YPD medium, in which the expression of individual YPS genes was set to 1 (as indicated by the dashed line in the graph). The bars indicate representative results of two independent experiments as the mean ± SD. The statistical significance of the reference was determined by one-way ANOVA with Dunnett’s multiple comparison test using GraphPad Prism software and is marked with *p  <  0.05, **p  <  0.01, ***p  <  0.001, ****p  <  0.0001.

4 Discussion

The mechanisms of adaptation and virulence of N. glabratus, including its resistance to antifungal drugs and ability to survive in the host, underscore its significance in clinical settings and the necessity for ongoing research into its pathogenicity, which remains insufficiently understood [54,55,56,57]. Surprisingly, despite the widely described role of Saps in the pathogenesis of C. albicans [15,17,22,58–61] and its potential as components of anti-Candida vaccines [62–68], the functions of Yps are poorly understood. To date, N. glabratus proteases have not been isolated or characterized, indicating a gap in our understanding of the virulence strategies of this organism.

YPS1–11 are distributed across three different chromosomes. YPS1 is located on chromosome M, YPS7 is located on chromosome A, and YPS2 and a cluster unique to N. glabratus, including eight genes – YPS3–6 and YPS8–11 – are located on chromosome E [37]. To date, the main role of Yps has been their involvement in maintaining cellular homeostasis, including the cell wall structure and composition, vacuole integrity, pH and glucose homeostasis, secretome regulation, and stress resistance [37,69–71]. Interestingly, Yps are also essential for brain tissue colonization and biofilm formation on abiotic surfaces [69]. Miyazaki et al. [72] demonstrated the key role of YPS1 in cell growth and cell wall integrity, especially under thermal stress conditions. Furthermore, the expression of N. glabratus YPS1 under its native promoter was sufficient to rectify the cell wall defects observed in the S. cerevisiae YPS1 mutant, suggesting that YPS1 plays a role in maintaining glucan homeostasis [73]. Using mutants with deletions of one or more YPS-encoding genes, Yps1 was identified as an essential protein for survival under low pH conditions and menadione-induced oxidative stress [30,74]. This requirement is attributed to its impact on the ATPase activity of the plasma membrane proton pump Pma1 and the NADH:quinone oxidoreductase activity of the flavodoxin-like protein Pst2, which in turn leads to increased production of reactive oxygen species [30,74]. Consistent with these reports, in our analyses for the VS medium at pH 4.2, we also observed an increase in YPS1 expression; however, under these conditions, the most significant increase in YPS7 expression was observed. Interestingly, Cortés-Acosta et al. [75] demonstrated the genetic diversity of YPS genes in clinical N. glabratus strains. Despite the high conservation of the YPS1 and YPS7 genes across these strains, their regulatory regions exhibited significant polymorphisms characterized by diverse arrays of transcription factor-binding sites (TFBSs). A detailed analysis of eight clinical strains cultured under various environmental conditions – nitrogen and carbon starvation, cell wall stress, osmotic stress, acid stress, and thermotolerance – revealed substantial differences in the expression of YPS1 and YPS7, ranging from underexpression to overexpression, among the strains tested [75]. Moreover, studies using mutant strains of N. glabratus with deletions in genes encoding YPS, particularly YPS1 and YPS7, underscore their crucial role in pathogenesis, including colonization, dissemination, and maintenance within the kidneys, liver, and spleen, in a murine model of systemic infection [69].

Although our research revealed high variability in the expression of YPS genes in the cluster, especially YPS6, the current literature exhibited a noticeable gap regarding their potential function. A cluster-deleted mutant study showed that all eight genes were overexpressed upon contact with the murine macrophage line J774A.1, with YPS3 and YPS6 also overexpressed in the culture medium itself [37]. Deleting the YPS cluster alone did not induce phenotypic changes in disseminated infection models or macrophage-based assays. However, strains lacking YPS1 or both YPS1 and YPS7 exhibited an apparent additive phenotype when the YPS cluster was deleted [37]. This evidence implies that the primary role of the YPS cluster is to interact with the host, and its functions may coincide with those of other YPS genes, especially YPS1 [37]. These findings are supported by experiments conducted using the THP-1 line, in which the disruption of eight genes in the YPS cluster adversely affected the intracellular growth and viability of YPS7 and YPS1 mutants, respectively [69].

In our analyses, both under conditions mimicking the host environment and prolonged cultivation in standard media, the increased expression of YPS6 was notable. Unfortunately, conclusions about its potential function based on similarities are difficult because, according to the Candida Genome Database, the protein structurally shares only 24% sequence homology with the Sap5 protein of C. albicans. Furthermore, the Yps6 protein lacks the RGD/KGD amino acid sequences identified as integrin-binding fragments in Sap5 [76]. Moreover, other proteins encoded within the same cluster exhibit structural similarities to Candida parapsilosis Sapp1 and Candida tropicalis Sapt, with sequence homology ranging from 30 to 34% (based on data in the Candida Genome Database). In a study of C. parapsilosis, the enzyme Sapp1 was associated with the cell wall, suggesting that its functionality may be similar to that of the enzymes Sap9 and Sap10 in C. albicans [77,78]. To date, these enzymes have been suggested to play a role in modulating the host inflammatory response. Namely, macrophages exposed to strains lacking SAPP1–SAPP3 secrete lower levels of interleukins IL-1β and IL-6 than those exposed to wild-type strains [79]. Moreover, they induce the influx of neutrophils by modulating the production of chemokines [79]. From the perspective of N. glabratus, which shows a particular ability to survive in human macrophages, it is worth noting that Sapp1 and Sapp2 can inhibit phagosome–lysosome fusion, promoting the yeast survival in human immune cells. This may indicate similar functions of N. glabratus proteases and C. parapsilosis [79]. In the context of Sapt, recent discoveries have revealed the proteolytic effect of this proteases on C-type lectins, likely disrupting the activation of the lectin complement pathway [80].

Proteases from many microorganisms are used in various industries, such as pharmaceuticals, biotechnology, meat, dairy, and bakery production [81–83]. Although our analyses provide preliminary results to understand the regulation of YPS genes and their role in pathogenesis, they may find applications in the biotechnology industry. Using proteases as potential biomarkers of infection will enable early detection of the pathogen and rapid, targeted medical intervention. Due to the uniqueness of the YPS family, identifying proteases expression may be especially interesting in the case of mixed infections, which are particularly difficult to treat. Moreover, our results may find application in the pharmaceutical industry, indicating the direction of designing new drugs and therapies based on inhibition of the function of these enzymes.

5 Conclusion

In conclusion, this study provides novel insights into the dynamic regulation of YPS gene expression in N. glabratus under varying environmental conditions, particularly in host-simulating media. Our research highlights the critical roles of YPS6 and YPS7 in fungal adaptation to acidic and nutrient-limited environments, suggesting that these proteases may be key factors in the pathogen’s survival and virulence. Future studies should focus on understanding the direct functions of individual YPS proteases in disrupting host homeostasis. For this purpose, it would be necessary to isolate and purify native proteins and investigate their involvement in the evasion of the host immune response and tissue damage. Then, extending these studies to in vivo models will significantly deepen the understanding of N. glabratus pathogenic mechanisms and open new avenues for therapeutic interventions targeting YPS proteases.

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  1. Funding information: This work was financially supported by the National Science Center, Poland (grant number 2020/39/D/NZ6/00854 awarded to D.S.).

  2. Author contributions: Conceptualization, D.S. and M.R.-K.; visualization, A.B. and D.S.; investigation, A.K., A.B., and D.S.; validation, A.K., A.B., and D.S.; writing – original draft preparation, A.B. and D.S.; writing – review and editing, A.B., D.S., and M.R.-K.; project administration, D.S.; funding acquisition, D.S. All authors have read and agreed to the published version of the manuscript.

  3. Conflict of interest: Authors state no conflicts of interest.

  4. Data availability statement: The datasets generated and analyzed during the current study are available in the Cracow Open Research Data Repository, https://doi.org/10.57903/UJ/7NK5VH.

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Received: 2024-06-06
Revised: 2024-09-24
Accepted: 2024-10-07
Published Online: 2024-11-26

© 2024 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  64. Evaluation of the role of some non-enzymatic antioxidants among Iraqi patients with non-alcoholic fatty liver disease
  65. The role of Phafin proteins in cell signaling pathways and diseases
  66. Ten-year anemia as initial manifestation of Castleman disease in the abdominal cavity: A case report
  67. Coexistence of hereditary spherocytosis with SPTB P.Trp1150 gene variant and Gilbert syndrome: A case report and literature review
  68. Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells
  69. Exploratory evaluation supported by experimental and modeling approaches of Inula viscosa root extract as a potent corrosion inhibitor for mild steel in a 1 M HCl solution
  70. Imaging manifestations of ductal adenoma of the breast: A case report
  71. Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects
  72. Isomangiferin promotes the migration and osteogenic differentiation of rat bone marrow mesenchymal stem cells
  73. Prognostic value and microenvironmental crosstalk of exosome-related signatures in human epidermal growth factor receptor 2 positive breast cancer
  74. Circular RNAs as potential biomarkers for male severe sepsis
  75. Knockdown of Stanniocalcin-1 inhibits growth and glycolysis in oral squamous cell carcinoma cells
  76. The expression and biological role of complement C1s in esophageal squamous cell carcinoma
  77. A novel GNAS mutation in pseudohypoparathyroidism type 1a with articular flexion deformity: A case report
  78. Predictive value of serum magnesium levels for prognosis in patients with non-small cell lung cancer undergoing EGFR-TKI therapy
  79. HSPB1 alleviates acute-on-chronic liver failure via the P53/Bax pathway
  80. IgG4-related disease complicated by PLA2R-associated membranous nephropathy: A case report
  81. Baculovirus-mediated endostatin and angiostatin activation of autophagy through the AMPK/AKT/mTOR pathway inhibits angiogenesis in hepatocellular carcinoma
  82. Metformin mitigates osteoarthritis progression by modulating the PI3K/AKT/mTOR signaling pathway and enhancing chondrocyte autophagy
  83. Evaluation of the activity of antimicrobial peptides against bacterial vaginosis
  84. Atypical presentation of γ/δ mycosis fungoides with an unusual phenotype and SOCS1 mutation
  85. Analysis of the microecological mechanism of diabetic kidney disease based on the theory of “gut–kidney axis”: A systematic review
  86. Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism
  87. Refractory hypertension complicated with Turner syndrome: A case report
  88. Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma
  89. Association of low attenuation area scores with pulmonary function and clinical prognosis in patients with chronic obstructive pulmonary disease
  90. Long non-coding RNAs in bone formation: Key regulators and therapeutic prospects
  91. The deubiquitinating enzyme USP35 regulates the stability of NRF2 protein
  92. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential diagnostic markers for rebleeding in patients with esophagogastric variceal bleeding
  93. G protein-coupled receptor 1 participating in the mechanism of mediating gestational diabetes mellitus by phosphorylating the AKT pathway
  94. LL37-mtDNA regulates viability, apoptosis, inflammation, and autophagy in lipopolysaccharide-treated RLE-6TN cells by targeting Hsp90aa1
  95. The analgesic effect of paeoniflorin: A focused review
  96. Chemical composition’s effect on Solanum nigrum Linn.’s antioxidant capacity and erythrocyte protection: Bioactive components and molecular docking analysis
  97. Knockdown of HCK promotes HREC cell viability and inner blood–retinal barrier integrity by regulating the AMPK signaling pathway
  98. The role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes
  99. Laryngeal non-Hodgkin lymphoma: Report of four cases and review of the literature
  100. Clinical value of macrogenome next-generation sequencing on infections
  101. Overview of dendritic cells and related pathways in autoimmune uveitis
  102. TAK-242 alleviates diabetic cardiomyopathy via inhibiting pyroptosis and TLR4/CaMKII/NLRP3 pathway
  103. Hypomethylation in promoters of PGC-1α involved in exercise-driven skeletal muscular alterations in old age
  104. Profile and antimicrobial susceptibility patterns of bacteria isolated from effluents of Kolladiba and Debark hospitals
  105. The expression and clinical significance of syncytin-1 in serum exosomes of hepatocellular carcinoma patients
  106. A histomorphometric study to evaluate the therapeutic effects of biosynthesized silver nanoparticles on the kidneys infected with Plasmodium chabaudi
  107. PGRMC1 and PAQR4 are promising molecular targets for a rare subtype of ovarian cancer
  108. Analysis of MDA, SOD, TAOC, MNCV, SNCV, and TSS scores in patients with diabetes peripheral neuropathy
  109. SLIT3 deficiency promotes non-small cell lung cancer progression by modulating UBE2C/WNT signaling
  110. The relationship between TMCO1 and CALR in the pathological characteristics of prostate cancer and its effect on the metastasis of prostate cancer cells
  111. Heterogeneous nuclear ribonucleoprotein K is a potential target for enhancing the chemosensitivity of nasopharyngeal carcinoma
  112. PHB2 alleviates retinal pigment epithelium cell fibrosis by suppressing the AGE–RAGE pathway
  113. Anti-γ-aminobutyric acid-B receptor autoimmune encephalitis with syncope as the initial symptom: Case report and literature review
  114. Comparative analysis of chloroplast genome of Lonicera japonica cv. Damaohua
  115. Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK–Nrf2–HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cells
  116. Electroacupuncture on GB acupoints improves osteoporosis via the estradiol–PI3K–Akt signaling pathway
  117. Renalase protects against podocyte injury by inhibiting oxidative stress and apoptosis in diabetic nephropathy
  118. Review: Dicranostigma leptopodum: A peculiar plant of Papaveraceae
  119. Combination effect of flavonoids attenuates lung cancer cell proliferation by inhibiting the STAT3 and FAK signaling pathway
  120. Renal microangiopathy and immune complex glomerulonephritis induced by anti-tumour agents: A case report
  121. Correlation analysis of AVPR1a and AVPR2 with abnormal water and sodium and potassium metabolism in rats
  122. Gastrointestinal health anti-diarrheal mixture relieves spleen deficiency-induced diarrhea through regulating gut microbiota
  123. Myriad factors and pathways influencing tumor radiotherapy resistance
  124. Exploring the effects of culture conditions on Yapsin (YPS) gene expression in Nakaseomyces glabratus
  125. Screening of prognostic core genes based on cell–cell interaction in the peripheral blood of patients with sepsis
  126. Coagulation factor II thrombin receptor as a promising biomarker in breast cancer management
  127. Ileocecal mucinous carcinoma misdiagnosed as incarcerated hernia: A case report
  128. Methyltransferase like 13 promotes malignant behaviors of bladder cancer cells through targeting PI3K/ATK signaling pathway
  129. The debate between electricity and heat, efficacy and safety of irreversible electroporation and radiofrequency ablation in the treatment of liver cancer: A meta-analysis
  130. ZAG promotes colorectal cancer cell proliferation and epithelial–mesenchymal transition by promoting lipid synthesis
  131. Baicalein inhibits NLRP3 inflammasome activation and mitigates placental inflammation and oxidative stress in gestational diabetes mellitus
  132. Impact of SWCNT-conjugated senna leaf extract on breast cancer cells: A potential apoptotic therapeutic strategy
  133. MFAP5 inhibits the malignant progression of endometrial cancer cells in vitro
  134. Major ozonated autohemotherapy promoted functional recovery following spinal cord injury in adult rats via the inhibition of oxidative stress and inflammation
  135. Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons
  136. Differential expression of phosphoinositide 3-kinase/protein kinase B and Toll-like receptor/nuclear factor kappa B signaling pathways in experimental obesity Wistar rat model
  137. The therapeutic potential of targeting Oncostatin M and the interleukin-6 family in retinal diseases: A comprehensive review
  138. BA inhibits LPS-stimulated inflammatory response and apoptosis in human middle ear epithelial cells by regulating the Nf-Kb/Iκbα axis
  139. Role of circRMRP and circRPL27 in chronic obstructive pulmonary disease
  140. Investigating the role of hyperexpressed HCN1 in inducing myocardial infarction through activation of the NF-κB signaling pathway
  141. Characterization of phenolic compounds and evaluation of anti-diabetic potential in Cannabis sativa L. seeds: In vivo, in vitro, and in silico studies
  142. Quantitative immunohistochemistry analysis of breast Ki67 based on artificial intelligence
  143. Ecology and Environmental Science
  144. Screening of different growth conditions of Bacillus subtilis isolated from membrane-less microbial fuel cell toward antimicrobial activity profiling
  145. Degradation of a mixture of 13 polycyclic aromatic hydrocarbons by commercial effective microorganisms
  146. Evaluation of the impact of two citrus plants on the variation of Panonychus citri (Acari: Tetranychidae) and beneficial phytoseiid mites
  147. Prediction of present and future distribution areas of Juniperus drupacea Labill and determination of ethnobotany properties in Antalya Province, Türkiye
  148. Population genetics of Todarodes pacificus (Cephalopoda: Ommastrephidae) in the northwest Pacific Ocean via GBS sequencing
  149. A comparative analysis of dendrometric, macromorphological, and micromorphological characteristics of Pistacia atlantica subsp. atlantica and Pistacia terebinthus in the middle Atlas region of Morocco
  150. Macrofungal sporocarp community in the lichen Scots pine forests
  151. Assessing the proximate compositions of indigenous forage species in Yemen’s pastoral rangelands
  152. Food Science
  153. Gut microbiota changes associated with low-carbohydrate diet intervention for obesity
  154. Reexamination of Aspergillus cristatus phylogeny in dark tea: Characteristics of the mitochondrial genome
  155. Differences in the flavonoid composition of the leaves, fruits, and branches of mulberry are distinguished based on a plant metabolomics approach
  156. Investigating the impact of wet rendering (solventless method) on PUFA-rich oil from catfish (Clarias magur) viscera
  157. Non-linear associations between cardiovascular metabolic indices and metabolic-associated fatty liver disease: A cross-sectional study in the US population (2017–2020)
  158. Knockdown of USP7 alleviates atherosclerosis in ApoE-deficient mice by regulating EZH2 expression
  159. Utility of dairy microbiome as a tool for authentication and traceability
  160. Agriculture
  161. Enhancing faba bean (Vicia faba L.) productivity through establishing the area-specific fertilizer rate recommendation in southwest Ethiopia
  162. Impact of novel herbicide based on synthetic auxins and ALS inhibitor on weed control
  163. Perspectives of pteridophytes microbiome for bioremediation in agricultural applications
  164. Fertilizer application parameters for drip-irrigated peanut based on the fertilizer effect function established from a “3414” field trial
  165. Improving the productivity and profitability of maize (Zea mays L.) using optimum blended inorganic fertilization
  166. Application of leaf multispectral analyzer in comparison to hyperspectral device to assess the diversity of spectral reflectance indices in wheat genotypes
  167. Animal Sciences
  168. Knockdown of ANP32E inhibits colorectal cancer cell growth and glycolysis by regulating the AKT/mTOR pathway
  169. Development of a detection chip for major pathogenic drug-resistant genes and drug targets in bovine respiratory system diseases
  170. Exploration of the genetic influence of MYOT and MB genes on the plumage coloration of Muscovy ducks
  171. Transcriptome analysis of adipose tissue in grazing cattle: Identifying key regulators of fat metabolism
  172. Comparison of nutritional value of the wild and cultivated spiny loaches at three growth stages
  173. Transcriptomic analysis of liver immune response in Chinese spiny frog (Quasipaa spinosa) infected with Proteus mirabilis
  174. Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis
  175. Plant Sciences
  176. Effect of long-term in-row branch covering on soil microorganisms in pear orchards
  177. Photosynthetic physiological characteristics, growth performance, and element concentrations reveal the calcicole–calcifuge behaviors of three Camellia species
  178. Transcriptome analysis reveals the mechanism of NaHCO3 promoting tobacco leaf maturation
  179. Bioinformatics, expression analysis, and functional verification of allene oxide synthase gene HvnAOS1 and HvnAOS2 in qingke
  180. Water, nitrogen, and phosphorus coupling improves gray jujube fruit quality and yield
  181. Improving grape fruit quality through soil conditioner: Insights from RNA-seq analysis of Cabernet Sauvignon roots
  182. Role of Embinin in the reabsorption of nucleus pulposus in lumbar disc herniation: Promotion of nucleus pulposus neovascularization and apoptosis of nucleus pulposus cells
  183. Revealing the effects of amino acid, organic acid, and phytohormones on the germination of tomato seeds under salinity stress
  184. Combined effects of nitrogen fertilizer and biochar on the growth, yield, and quality of pepper
  185. Comprehensive phytochemical and toxicological analysis of Chenopodium ambrosioides (L.) fractions
  186. Impact of “3414” fertilization on the yield and quality of greenhouse tomatoes
  187. Exploring the coupling mode of water and fertilizer for improving growth, fruit quality, and yield of the pear in the arid region
  188. Metagenomic analysis of endophytic bacteria in seed potato (Solanum tuberosum)
  189. Antibacterial, antifungal, and phytochemical properties of Salsola kali ethanolic extract
  190. Exploring the hepatoprotective properties of citronellol: In vitro and in silico studies on ethanol-induced damage in HepG2 cells
  191. Enhanced osmotic dehydration of watermelon rind using honey–sucrose solutions: A study on pre-treatment efficacy and mass transfer kinetics
  192. Effects of exogenous 2,4-epibrassinolide on photosynthetic traits of 53 cowpea varieties under NaCl stress
  193. Comparative transcriptome analysis of maize (Zea mays L.) seedlings in response to copper stress
  194. An optimization method for measuring the stomata in cassava (Manihot esculenta Crantz) under multiple abiotic stresses
  195. Fosinopril inhibits Ang II-induced VSMC proliferation, phenotype transformation, migration, and oxidative stress through the TGF-β1/Smad signaling pathway
  196. Antioxidant and antimicrobial activities of Salsola imbricata methanolic extract and its phytochemical characterization
  197. Bioengineering and Biotechnology
  198. Absorbable calcium and phosphorus bioactive membranes promote bone marrow mesenchymal stem cells osteogenic differentiation for bone regeneration
  199. New advances in protein engineering for industrial applications: Key takeaways
  200. An overview of the production and use of Bacillus thuringiensis toxin
  201. Research progress of nanoparticles in diagnosis and treatment of hepatocellular carcinoma
  202. Bioelectrochemical biosensors for water quality assessment and wastewater monitoring
  203. PEI/MMNs@LNA-542 nanoparticles alleviate ICU-acquired weakness through targeted autophagy inhibition and mitochondrial protection
  204. Unleashing of cytotoxic effects of thymoquinone-bovine serum albumin nanoparticles on A549 lung cancer cells
  205. Erratum
  206. Erratum to “Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM”
  207. Erratum to “Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation”
  208. Retraction
  209. Retraction to “MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB”
  210. Retraction to “A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis”
  211. Special Issue on Advances in Neurodegenerative Disease Research and Treatment
  212. Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson’s disease
  213. Special Issue on Multi-omics
  214. Inflammasome complex genes with clinical relevance suggest potential as therapeutic targets for anti-tumor drugs in clear cell renal cell carcinoma
  215. Gastroesophageal varices in primary biliary cholangitis with anti-centromere antibody positivity: Early onset?
https://doi.org/10.1515/biol-2022-0995
Schlagwörter für diesen Artikel
Nakaseomyces glabratus; YPS gene expression; fungal pathogenicity; protease regulation; host niche adaptation
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Biomedical Sciences
  2. Constitutive and evoked release of ATP in adult mouse olfactory epithelium
  3. LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior
  4. PEGylated porcine–human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications
  5. Research progress on ocular complications caused by type 2 diabetes mellitus and the function of tears and blepharons
  6. The role and mechanism of esketamine in preventing and treating remifentanil-induced hyperalgesia based on the NMDA receptor–CaMKII pathway
  7. Brucella infection combined with Nocardia infection: A case report and literature review
  8. Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance
  9. Ang-1, Ang-2, and Tie2 are diagnostic biomarkers for Henoch-Schönlein purpura and pediatric-onset systemic lupus erythematous
  10. PTTG1 induces pancreatic cancer cell proliferation and promotes aerobic glycolysis by regulating c-myc
  11. Role of serum B-cell-activating factor and interleukin-17 as biomarkers in the classification of interstitial pneumonia with autoimmune features
  12. Effectiveness and safety of a mumps containing vaccine in preventing laboratory-confirmed mumps cases from 2002 to 2017: A meta-analysis
  13. Low levels of sex hormone-binding globulin predict an increased breast cancer risk and its underlying molecular mechanisms
  14. A case of Trousseau syndrome: Screening, detection and complication
  15. Application of the integrated airway humidification device enhances the humidification effect of the rabbit tracheotomy model
  16. Preparation of Cu2+/TA/HAP composite coating with anti-bacterial and osteogenic potential on 3D-printed porous Ti alloy scaffolds for orthopedic applications
  17. Aquaporin-8 promotes human dermal fibroblasts to counteract hydrogen peroxide-induced oxidative damage: A novel target for management of skin aging
  18. Current research and evidence gaps on placental development in iron deficiency anemia
  19. Single-nucleotide polymorphism rs2910829 in PDE4D is related to stroke susceptibility in Chinese populations: The results of a meta-analysis
  20. Pheochromocytoma-induced myocardial infarction: A case report
  21. Kaempferol regulates apoptosis and migration of neural stem cells to attenuate cerebral infarction by O‐GlcNAcylation of β-catenin
  22. Sirtuin 5 regulates acute myeloid leukemia cell viability and apoptosis by succinylation modification of glycine decarboxylase
  23. Apigenin 7-glucoside impedes hypoxia-induced malignant phenotypes of cervical cancer cells in a p16-dependent manner
  24. KAT2A changes the function of endometrial stromal cells via regulating the succinylation of ENO1
  25. Current state of research on copper complexes in the treatment of breast cancer
  26. Exploring antioxidant strategies in the pathogenesis of ALS
  27. Helicobacter pylori causes gastric dysbacteriosis in chronic gastritis patients
  28. IL-33/soluble ST2 axis is associated with radiation-induced cardiac injury
  29. The predictive value of serum NLR, SII, and OPNI for lymph node metastasis in breast cancer patients with internal mammary lymph nodes after thoracoscopic surgery
  30. Carrying SNP rs17506395 (T > G) in TP63 gene and CCR5Δ32 mutation associated with the occurrence of breast cancer in Burkina Faso
  31. P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy
  32. Probiotics for inflammatory bowel disease: Is there sufficient evidence?
  33. Identification of KDM4C as a gene conferring drug resistance in multiple myeloma
  34. Microbial perspective on the skin–gut axis and atopic dermatitis
  35. Thymosin α1 combined with XELOX improves immune function and reduces serum tumor markers in colorectal cancer patients after radical surgery
  36. Highly specific vaginal microbiome signature for gynecological cancers
  37. Sample size estimation for AQP4-IgG seropositive optic neuritis: Retinal damage detection by optical coherence tomography
  38. The effects of SDF-1 combined application with VEGF on femoral distraction osteogenesis in rats
  39. Fabrication and characterization of gold nanoparticles using alginate: In vitro and in vivo assessment of its administration effects with swimming exercise on diabetic rats
  40. Mitigating digestive disorders: Action mechanisms of Mediterranean herbal active compounds
  41. Distribution of CYP2D6 and CYP2C19 gene polymorphisms in Han and Uygur populations with breast cancer in Xinjiang, China
  42. VSP-2 attenuates secretion of inflammatory cytokines induced by LPS in BV2 cells by mediating the PPARγ/NF-κB signaling pathway
  43. Factors influencing spontaneous hypothermia after emergency trauma and the construction of a predictive model
  44. Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
  45. Application of metagenomic next-generation sequencing technology in the etiological diagnosis of peritoneal dialysis-associated peritonitis
  46. Clinical diagnosis, prevention, and treatment of neurodyspepsia syndrome using intelligent medicine
  47. Case report: Successful bronchoscopic interventional treatment of endobronchial leiomyomas
  48. Preliminary investigation into the genetic etiology of short stature in children through whole exon sequencing of the core family
  49. Cystic adenomyoma of the uterus: Case report and literature review
  50. Mesoporous silica nanoparticles as a drug delivery mechanism
  51. Dynamic changes in autophagy activity in different degrees of pulmonary fibrosis in mice
  52. Vitamin D deficiency and inflammatory markers in type 2 diabetes: Big data insights
  53. Lactate-induced IGF1R protein lactylation promotes proliferation and metabolic reprogramming of lung cancer cells
  54. Meta-analysis on the efficacy of allogeneic hematopoietic stem cell transplantation to treat malignant lymphoma
  55. Mitochondrial DNA drives neuroinflammation through the cGAS-IFN signaling pathway in the spinal cord of neuropathic pain mice
  56. Application value of artificial intelligence algorithm-based magnetic resonance multi-sequence imaging in staging diagnosis of cervical cancer
  57. Embedded monitoring system and teaching of artificial intelligence online drug component recognition
  58. Investigation into the association of FNDC1 and ADAMTS12 gene expression with plumage coloration in Muscovy ducks
  59. Yak meat content in feed and its impact on the growth of rats
  60. A rare case of Richter transformation with breast involvement: A case report and literature review
  61. First report of Nocardia wallacei infection in an immunocompetent patient in Zhejiang province
  62. Rhodococcus equi and Brucella pulmonary mass in immunocompetent: A case report and literature review
  63. Downregulation of RIP3 ameliorates the left ventricular mechanics and function after myocardial infarction via modulating NF-κB/NLRP3 pathway
  64. Evaluation of the role of some non-enzymatic antioxidants among Iraqi patients with non-alcoholic fatty liver disease
  65. The role of Phafin proteins in cell signaling pathways and diseases
  66. Ten-year anemia as initial manifestation of Castleman disease in the abdominal cavity: A case report
  67. Coexistence of hereditary spherocytosis with SPTB P.Trp1150 gene variant and Gilbert syndrome: A case report and literature review
  68. Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells
  69. Exploratory evaluation supported by experimental and modeling approaches of Inula viscosa root extract as a potent corrosion inhibitor for mild steel in a 1 M HCl solution
  70. Imaging manifestations of ductal adenoma of the breast: A case report
  71. Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects
  72. Isomangiferin promotes the migration and osteogenic differentiation of rat bone marrow mesenchymal stem cells
  73. Prognostic value and microenvironmental crosstalk of exosome-related signatures in human epidermal growth factor receptor 2 positive breast cancer
  74. Circular RNAs as potential biomarkers for male severe sepsis
  75. Knockdown of Stanniocalcin-1 inhibits growth and glycolysis in oral squamous cell carcinoma cells
  76. The expression and biological role of complement C1s in esophageal squamous cell carcinoma
  77. A novel GNAS mutation in pseudohypoparathyroidism type 1a with articular flexion deformity: A case report
  78. Predictive value of serum magnesium levels for prognosis in patients with non-small cell lung cancer undergoing EGFR-TKI therapy
  79. HSPB1 alleviates acute-on-chronic liver failure via the P53/Bax pathway
  80. IgG4-related disease complicated by PLA2R-associated membranous nephropathy: A case report
  81. Baculovirus-mediated endostatin and angiostatin activation of autophagy through the AMPK/AKT/mTOR pathway inhibits angiogenesis in hepatocellular carcinoma
  82. Metformin mitigates osteoarthritis progression by modulating the PI3K/AKT/mTOR signaling pathway and enhancing chondrocyte autophagy
  83. Evaluation of the activity of antimicrobial peptides against bacterial vaginosis
  84. Atypical presentation of γ/δ mycosis fungoides with an unusual phenotype and SOCS1 mutation
  85. Analysis of the microecological mechanism of diabetic kidney disease based on the theory of “gut–kidney axis”: A systematic review
  86. Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism
  87. Refractory hypertension complicated with Turner syndrome: A case report
  88. Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma
  89. Association of low attenuation area scores with pulmonary function and clinical prognosis in patients with chronic obstructive pulmonary disease
  90. Long non-coding RNAs in bone formation: Key regulators and therapeutic prospects
  91. The deubiquitinating enzyme USP35 regulates the stability of NRF2 protein
  92. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential diagnostic markers for rebleeding in patients with esophagogastric variceal bleeding
  93. G protein-coupled receptor 1 participating in the mechanism of mediating gestational diabetes mellitus by phosphorylating the AKT pathway
  94. LL37-mtDNA regulates viability, apoptosis, inflammation, and autophagy in lipopolysaccharide-treated RLE-6TN cells by targeting Hsp90aa1
  95. The analgesic effect of paeoniflorin: A focused review
  96. Chemical composition’s effect on Solanum nigrum Linn.’s antioxidant capacity and erythrocyte protection: Bioactive components and molecular docking analysis
  97. Knockdown of HCK promotes HREC cell viability and inner blood–retinal barrier integrity by regulating the AMPK signaling pathway
  98. The role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes
  99. Laryngeal non-Hodgkin lymphoma: Report of four cases and review of the literature
  100. Clinical value of macrogenome next-generation sequencing on infections
  101. Overview of dendritic cells and related pathways in autoimmune uveitis
  102. TAK-242 alleviates diabetic cardiomyopathy via inhibiting pyroptosis and TLR4/CaMKII/NLRP3 pathway
  103. Hypomethylation in promoters of PGC-1α involved in exercise-driven skeletal muscular alterations in old age
  104. Profile and antimicrobial susceptibility patterns of bacteria isolated from effluents of Kolladiba and Debark hospitals
  105. The expression and clinical significance of syncytin-1 in serum exosomes of hepatocellular carcinoma patients
  106. A histomorphometric study to evaluate the therapeutic effects of biosynthesized silver nanoparticles on the kidneys infected with Plasmodium chabaudi
  107. PGRMC1 and PAQR4 are promising molecular targets for a rare subtype of ovarian cancer
  108. Analysis of MDA, SOD, TAOC, MNCV, SNCV, and TSS scores in patients with diabetes peripheral neuropathy
  109. SLIT3 deficiency promotes non-small cell lung cancer progression by modulating UBE2C/WNT signaling
  110. The relationship between TMCO1 and CALR in the pathological characteristics of prostate cancer and its effect on the metastasis of prostate cancer cells
  111. Heterogeneous nuclear ribonucleoprotein K is a potential target for enhancing the chemosensitivity of nasopharyngeal carcinoma
  112. PHB2 alleviates retinal pigment epithelium cell fibrosis by suppressing the AGE–RAGE pathway
  113. Anti-γ-aminobutyric acid-B receptor autoimmune encephalitis with syncope as the initial symptom: Case report and literature review
  114. Comparative analysis of chloroplast genome of Lonicera japonica cv. Damaohua
  115. Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK–Nrf2–HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cells
  116. Electroacupuncture on GB acupoints improves osteoporosis via the estradiol–PI3K–Akt signaling pathway
  117. Renalase protects against podocyte injury by inhibiting oxidative stress and apoptosis in diabetic nephropathy
  118. Review: Dicranostigma leptopodum: A peculiar plant of Papaveraceae
  119. Combination effect of flavonoids attenuates lung cancer cell proliferation by inhibiting the STAT3 and FAK signaling pathway
  120. Renal microangiopathy and immune complex glomerulonephritis induced by anti-tumour agents: A case report
  121. Correlation analysis of AVPR1a and AVPR2 with abnormal water and sodium and potassium metabolism in rats
  122. Gastrointestinal health anti-diarrheal mixture relieves spleen deficiency-induced diarrhea through regulating gut microbiota
  123. Myriad factors and pathways influencing tumor radiotherapy resistance
  124. Exploring the effects of culture conditions on Yapsin (YPS) gene expression in Nakaseomyces glabratus
  125. Screening of prognostic core genes based on cell–cell interaction in the peripheral blood of patients with sepsis
  126. Coagulation factor II thrombin receptor as a promising biomarker in breast cancer management
  127. Ileocecal mucinous carcinoma misdiagnosed as incarcerated hernia: A case report
  128. Methyltransferase like 13 promotes malignant behaviors of bladder cancer cells through targeting PI3K/ATK signaling pathway
  129. The debate between electricity and heat, efficacy and safety of irreversible electroporation and radiofrequency ablation in the treatment of liver cancer: A meta-analysis
  130. ZAG promotes colorectal cancer cell proliferation and epithelial–mesenchymal transition by promoting lipid synthesis
  131. Baicalein inhibits NLRP3 inflammasome activation and mitigates placental inflammation and oxidative stress in gestational diabetes mellitus
  132. Impact of SWCNT-conjugated senna leaf extract on breast cancer cells: A potential apoptotic therapeutic strategy
  133. MFAP5 inhibits the malignant progression of endometrial cancer cells in vitro
  134. Major ozonated autohemotherapy promoted functional recovery following spinal cord injury in adult rats via the inhibition of oxidative stress and inflammation
  135. Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons
  136. Differential expression of phosphoinositide 3-kinase/protein kinase B and Toll-like receptor/nuclear factor kappa B signaling pathways in experimental obesity Wistar rat model
  137. The therapeutic potential of targeting Oncostatin M and the interleukin-6 family in retinal diseases: A comprehensive review
  138. BA inhibits LPS-stimulated inflammatory response and apoptosis in human middle ear epithelial cells by regulating the Nf-Kb/Iκbα axis
  139. Role of circRMRP and circRPL27 in chronic obstructive pulmonary disease
  140. Investigating the role of hyperexpressed HCN1 in inducing myocardial infarction through activation of the NF-κB signaling pathway
  141. Characterization of phenolic compounds and evaluation of anti-diabetic potential in Cannabis sativa L. seeds: In vivo, in vitro, and in silico studies
  142. Quantitative immunohistochemistry analysis of breast Ki67 based on artificial intelligence
  143. Ecology and Environmental Science
  144. Screening of different growth conditions of Bacillus subtilis isolated from membrane-less microbial fuel cell toward antimicrobial activity profiling
  145. Degradation of a mixture of 13 polycyclic aromatic hydrocarbons by commercial effective microorganisms
  146. Evaluation of the impact of two citrus plants on the variation of Panonychus citri (Acari: Tetranychidae) and beneficial phytoseiid mites
  147. Prediction of present and future distribution areas of Juniperus drupacea Labill and determination of ethnobotany properties in Antalya Province, Türkiye
  148. Population genetics of Todarodes pacificus (Cephalopoda: Ommastrephidae) in the northwest Pacific Ocean via GBS sequencing
  149. A comparative analysis of dendrometric, macromorphological, and micromorphological characteristics of Pistacia atlantica subsp. atlantica and Pistacia terebinthus in the middle Atlas region of Morocco
  150. Macrofungal sporocarp community in the lichen Scots pine forests
  151. Assessing the proximate compositions of indigenous forage species in Yemen’s pastoral rangelands
  152. Food Science
  153. Gut microbiota changes associated with low-carbohydrate diet intervention for obesity
  154. Reexamination of Aspergillus cristatus phylogeny in dark tea: Characteristics of the mitochondrial genome
  155. Differences in the flavonoid composition of the leaves, fruits, and branches of mulberry are distinguished based on a plant metabolomics approach
  156. Investigating the impact of wet rendering (solventless method) on PUFA-rich oil from catfish (Clarias magur) viscera
  157. Non-linear associations between cardiovascular metabolic indices and metabolic-associated fatty liver disease: A cross-sectional study in the US population (2017–2020)
  158. Knockdown of USP7 alleviates atherosclerosis in ApoE-deficient mice by regulating EZH2 expression
  159. Utility of dairy microbiome as a tool for authentication and traceability
  160. Agriculture
  161. Enhancing faba bean (Vicia faba L.) productivity through establishing the area-specific fertilizer rate recommendation in southwest Ethiopia
  162. Impact of novel herbicide based on synthetic auxins and ALS inhibitor on weed control
  163. Perspectives of pteridophytes microbiome for bioremediation in agricultural applications
  164. Fertilizer application parameters for drip-irrigated peanut based on the fertilizer effect function established from a “3414” field trial
  165. Improving the productivity and profitability of maize (Zea mays L.) using optimum blended inorganic fertilization
  166. Application of leaf multispectral analyzer in comparison to hyperspectral device to assess the diversity of spectral reflectance indices in wheat genotypes
  167. Animal Sciences
  168. Knockdown of ANP32E inhibits colorectal cancer cell growth and glycolysis by regulating the AKT/mTOR pathway
  169. Development of a detection chip for major pathogenic drug-resistant genes and drug targets in bovine respiratory system diseases
  170. Exploration of the genetic influence of MYOT and MB genes on the plumage coloration of Muscovy ducks
  171. Transcriptome analysis of adipose tissue in grazing cattle: Identifying key regulators of fat metabolism
  172. Comparison of nutritional value of the wild and cultivated spiny loaches at three growth stages
  173. Transcriptomic analysis of liver immune response in Chinese spiny frog (Quasipaa spinosa) infected with Proteus mirabilis
  174. Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis
  175. Plant Sciences
  176. Effect of long-term in-row branch covering on soil microorganisms in pear orchards
  177. Photosynthetic physiological characteristics, growth performance, and element concentrations reveal the calcicole–calcifuge behaviors of three Camellia species
  178. Transcriptome analysis reveals the mechanism of NaHCO3 promoting tobacco leaf maturation
  179. Bioinformatics, expression analysis, and functional verification of allene oxide synthase gene HvnAOS1 and HvnAOS2 in qingke
  180. Water, nitrogen, and phosphorus coupling improves gray jujube fruit quality and yield
  181. Improving grape fruit quality through soil conditioner: Insights from RNA-seq analysis of Cabernet Sauvignon roots
  182. Role of Embinin in the reabsorption of nucleus pulposus in lumbar disc herniation: Promotion of nucleus pulposus neovascularization and apoptosis of nucleus pulposus cells
  183. Revealing the effects of amino acid, organic acid, and phytohormones on the germination of tomato seeds under salinity stress
  184. Combined effects of nitrogen fertilizer and biochar on the growth, yield, and quality of pepper
  185. Comprehensive phytochemical and toxicological analysis of Chenopodium ambrosioides (L.) fractions
  186. Impact of “3414” fertilization on the yield and quality of greenhouse tomatoes
  187. Exploring the coupling mode of water and fertilizer for improving growth, fruit quality, and yield of the pear in the arid region
  188. Metagenomic analysis of endophytic bacteria in seed potato (Solanum tuberosum)
  189. Antibacterial, antifungal, and phytochemical properties of Salsola kali ethanolic extract
  190. Exploring the hepatoprotective properties of citronellol: In vitro and in silico studies on ethanol-induced damage in HepG2 cells
  191. Enhanced osmotic dehydration of watermelon rind using honey–sucrose solutions: A study on pre-treatment efficacy and mass transfer kinetics
  192. Effects of exogenous 2,4-epibrassinolide on photosynthetic traits of 53 cowpea varieties under NaCl stress
  193. Comparative transcriptome analysis of maize (Zea mays L.) seedlings in response to copper stress
  194. An optimization method for measuring the stomata in cassava (Manihot esculenta Crantz) under multiple abiotic stresses
  195. Fosinopril inhibits Ang II-induced VSMC proliferation, phenotype transformation, migration, and oxidative stress through the TGF-β1/Smad signaling pathway
  196. Antioxidant and antimicrobial activities of Salsola imbricata methanolic extract and its phytochemical characterization
  197. Bioengineering and Biotechnology
  198. Absorbable calcium and phosphorus bioactive membranes promote bone marrow mesenchymal stem cells osteogenic differentiation for bone regeneration
  199. New advances in protein engineering for industrial applications: Key takeaways
  200. An overview of the production and use of Bacillus thuringiensis toxin
  201. Research progress of nanoparticles in diagnosis and treatment of hepatocellular carcinoma
  202. Bioelectrochemical biosensors for water quality assessment and wastewater monitoring
  203. PEI/MMNs@LNA-542 nanoparticles alleviate ICU-acquired weakness through targeted autophagy inhibition and mitochondrial protection
  204. Unleashing of cytotoxic effects of thymoquinone-bovine serum albumin nanoparticles on A549 lung cancer cells
  205. Erratum
  206. Erratum to “Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM”
  207. Erratum to “Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation”
  208. Retraction
  209. Retraction to “MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB”
  210. Retraction to “A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis”
  211. Special Issue on Advances in Neurodegenerative Disease Research and Treatment
  212. Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson’s disease
  213. Special Issue on Multi-omics
  214. Inflammasome complex genes with clinical relevance suggest potential as therapeutic targets for anti-tumor drugs in clear cell renal cell carcinoma
  215. Gastroesophageal varices in primary biliary cholangitis with anti-centromere antibody positivity: Early onset?
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Heruntergeladen am 22.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/biol-2022-0995/html
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