Monika StaniszewskaWarsaw University of Technology · Chair of Drug and Cosmetics Biotechnology
Monika Staniszewska
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Publications (94)
Ultraviolet light has a long track record when it comes to use for deactivating harmful microorganisms. With recent developments in LED technology in terms of generating electromagnetic waves from this specific spectral range, new applications have emerged. In this study, the possibility of constructing an effective miniature UV barrier for deactiv...
Environmental concerns and climate protection are gaining increasing emphasis nowadays. A growing number of industries and scientific fields are involved in this trend. Sustainable electronics is an emerging research strand. Environmentally friendly and biodegradable or biobased raw materials can be used for the development of green flexible electr...
We presented the pharmacodynamic relationship between benzoxaborole concentrations and C. albians blastoconidial population dynamics. Bis(benzoxaborole) analogue (2) and Tavaborole (ref.) showed comparable moderate effects against C. albicans. Benzoxaboroles inhibited the C. albicans growth with metabolic reduction (%R=64). BIC 50 =2 μg/mL is the l...
We present a series of preclinical studies focusing on developing in vitro 2D and 3D models for assessing the immunogenic factors in preventing infectious diseases. Human peripheral blood mononuclear cells (PBMC) and Calu-3 cell lines (bronchial epithelial cells) were used to develop 2D and 3D models. Peptides: Spike-S1-His, nucleocapsid-His and ad...
The challenge of integrating hydroxyapatite nanoparticles (nHAp) with polymers is hindered by the conflict between the hydrophilic and hygroscopic properties of nHAp and the hydrophobic properties of polymers. This conflict particularly affects the materials when calcium phosphates, including nHAp, are used as a filler in composites in thermal proc...
A series of novel sulfone derivatives were synthesized and screened in vitro for their cytotoxicity and antifungal activity with annotated primary mechanism of action (MOA). We prioritized sulfones with high (4-(bromodichloromethylsulfonyl)benzoic acid 4, 4-(difluoromethylsulfonyl)benzoic acid 12), little (3-[4-(bromodichloromethylsulfonyl)phenyl]p...
Screening for effective vaccines requires broad studies on their immunogenicity in vitro and ex vivo . We used a PBMC-based system to assess changes in CD4⁺ T cells, CD8⁺ T cells, and CD19⁺ B cells upon stimulation with different combinations of antigens and adjuvants. We studied the activation mechanism using flow cytometry and two different adeno...
New prophylactic vaccine platforms are imperative to combat respiratory infections. The efficacy of T and B memory cell-mediated protection, generated through the adenoviral vector, was tested to assess the effectiveness of the new adenoviral-based platforms for infectious diseases. A combination of adenovirus AdV1 (adjuvant), armed with costimulat...
Introduction: Malignant mesothelioma is a rare and aggressive form of cancer. Despite improvements in cancer treatment, there are still no curative treatment modalities for advanced stage of the malignancy. The aim of this study was to evaluate the anti-tumor efficacy of a novel combinatorial therapy combining AdV5/3-D24-ICOSL-CD40L, an oncolytic v...
Citation: Latko-Durałek, P.; Rzempołuch, J.; Staniszewska, M.; Rosłoniec, K.; Bil, M.; Kozera, R.; Boczkowska, A. The Antifungal Fibers of Polyamide 12 Containing Silver and Metal Oxides. Materials 2023, 16, 5837. Abstract: The textile market is a vast industry that utilizes antimicrobial polymeric materials, including various types of fabrics, for...
Mast cells (MCs) are the immune cells distributed throughout nearly all tissues, mainly in the skin, near blood vessels and lymph vessels, nerves, lungs, and the intestines. Although MCs are essential to the healthy immune response, their overactivity and pathological states can lead to numerous health hazards. The side effect of mast cell activity...
Simple Summary
Current cancer therapies are insufficient to cure advanced malignancies and cause off-target toxicity. Scientists have focused on developing new, more efficacious, and selective therapies to overcome these issues. This review describes a modern approach based on oncotherapy, a type of cancer treatment that helps the immune system fig...
Our previous research suggests an important regulatory role of CK2-mediated phosphorylation of enzymes involved in the thymidylate biosynthesis cycle, i.e., thymidylate synthase (TS), dihydrofolate reductase (DHFR), and serine hydroxymethyltransferase (SHMT). The aim of this study was to show whether silencing of the CK2α gene affects TS and DHFR e...
In recent years, we have faced more and more new diseases caused by viruses and opportunistic infections. There are still no preclinical models that would improve the evaluation of the proposed therapies and the immune system's response to drugs and infections. That is why the models based on the peripheral blood mononuclear cells (PBMCs) have a gr...
The lack of resistance of plastic objects to various pathogens and their increasing activity in our daily life have made researchers develop polymeric materials with biocidal properties. Hence, this paper describes the thermoplastic composites of Polyamide 12 mixed with 1–5 wt % of the nanoparticles of zinc, copper, and titanium oxides prepared by...
Cancer cells employ various mechanisms to evade and suppress anti-cancer immune responses generating a "cold" immunosuppressive tumour microenvironment. Oncolytic viruses are a promising tool to convert tumour immunosuppression to immunomodulation and improve the efficacy of cancer treatment. Emerging preclinical and clinical findings confirm that...
Malignant mesothelioma is a rare and aggressive cancer that develops in the thin layer surrounding the mesothelium and is mainly caused by asbestos exposure. Despite improvements in patient prognosis with conventional cancer treatments, such as surgery, chemotherapy, and radiotherapy, there are still no curative treatment modalities for advanced di...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has completely disrupted people’s lives. All over the world, many restrictions and precautions have been introduced to reduce the spread of coronavirus disease 2019 (COVID-19). Ultraviolet C (UV-C) radiation is widely used to disinfect rooms, surfaces, and medical tools; howe...
Mast cells (MCs) play important roles in normal immune responses and pathological states. The location of MCs on the boundaries between tissues and the external environment, including gut mucosal surfaces, lungs, skin, and around blood vessels, suggests a multitude of immunological functions. Thus, MCs are pivotal for host defense against different...
Tetrazole and benzodiazepine derivatives attract widespread attention due to their remarkable pharmaceutical potential. 5-(2-bromophenyl)-7-fluoro-1-[3-(5-(4-chlorophenyl)-2H-tetrazol-2-yl)propyl]-1,3-dihydro-2H-1,4-benzodiazepin-2-one (6c) and 5-(2-bromophenyl)-7-fluoro-1-[3-(5-(2-chlorophenyl)-2H-tetrazol-2-yl)propyl]-1,3-dihydro-2H-1,4-benzodiaz...
The role of mast cells in severe COVID-19 disease
Joanna Baran1,2, Paulina Musolf2, Anna Sobiepanek2, Monika Staniszewska1
1 Centre of Advanced Materials and Technologies CEZAMAT, Poleczki 19, 02-822 Warszawa, Polska
2 Faculty of Chemistry, Warsaw University of Technology, Koszykowa 75, 00-662 Warszawa, Polska
While the exact pathway of the COVI...
Our study aimed to characterise the action mode of N-phenacyldibromobenzimidazoles against C. albicans and C. neoformans. Firstly, we selected the non-cytotoxic most active benzimidazoles based on the structure–activity relationships showing that the group of 5,6-dibromobenzimidazole derivatives are less active against C. albicans vs. 4,6-dibromobe...
A newly synthetized series of N-phenacyl derivatives of 2-mercaptobenzoxazole, including analogues of 5-bromo- and 5,7-dibromobenzoxazole, were screened against Candida strains and the action mechanism was evaluated. 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(4-bromophenyl)ethanone (5d), 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(2,3,4-trichloro-phenyl)ethanone (5...
Streszczenie: Mastocyty są jednymi z ważniejszych komórek układu odpornościowego człowieka. W stanach fizjologicznych biorą udział w wielu niezbędnych dla organizmu procesach tj. gojenie się ran, naprawa i remodelowanie tkanki, angiogeneza. Do procesów patologicznych zależnych od mastocytów zaliczane są stany zapalne, alergie, inicjacja i progresja...
Malignant melanoma, an aggressive form of skin cancer, has a low five-year survival rate in patients with advanced disease. Immunotherapy represents a promising approach to improve survival rates among patients at advanced stage. Herein, the aim of the study was to design and produce, by using engineering tools, a novel oncolytic adenovirus AdV-D24...
In our research, we optimized the method of purifying microbiologically produced violacein by KP16 strain Janthinobacterium lividum isolated from water sample in 2016. The basis of the purifyingmethod is the extraction of violacein with organic solvents: MeOH (from bacterial biomass) and EtAc (from culture medium). The extraction procedure was enri...
Simple Summary
Here, we review the current state of knowledge in the field of cancer immunotherapy, focusing on the scientific rationale for the use of oncolytic viruses, checkpoint inhibitors and their combination to combat melanomas. Attention is also given to the immunological aspects of cancer therapy and the shift from conventional therapy tow...
Candida albicans CNB1 plays a role in the response in vitro and in vivo to stress generated by PB-WUT-01, namely 1,3-dimethyl-7-(2-((1-(3-(perbromo-2H-benzo[d][1,2,3]triazol-2-yl)propyl)-1H-1,2,3-triazol-4-yl)methoxy)propyl)-1H-purine-2,6(3H,7H)-dione. The antifungal mechanism involved the calcineurin pathway-regulated genes SAP9-10. Galleria mello...
Background:
The combination effect of 5-fluorouracil (5-FU) with either CX-4945 or a new inhibitor of protein kinase CK2, namely 14B (4,5,6,7-tetrabromo-1-(3-bromopropyl)-2-methyl-1H-benzimidazole), on the viability of MCF-7 and triple-negative MDA-MB-231 breast cancer cell lines was studied.
Methods:
Combination index (CI) values were determine...
The current appearance of the new SARS coronavirus 2 (SARS-CoV-2) and it quickly spreading across the world poses a global health emergency. The serious outbreak position is affecting people worldwide and requires rapid measures to be taken by healthcare systems and governments. Vaccinations represent the most effective strategy to prevent the epid...
The secretory pathway in Candida albicans involves the protein translocation into the lumen of the endoplasmic reticulum and transport to the Golgi complex, where proteins undergo posttranslational modifications, including glycosylation and proteolysis. The Golgi-resident Kex2 protease is involved in such processing and disruption of its encoding g...
Since our study showed that sulfone derivatives' action mode creates a lesser risk of inducing widespread resistance among Candida spp., we continued verifying sulfones’ antifungal activity using the following newly synthesized derivatives: bromodichloromethy-4-hydrazinyl-3-nitrophenyl sulfone (S1), difluoroiodomethyl-4-hydrazinyl-3-nitrophenyl sul...
Candida albicans represents an interesting microorganism to study complex host-pathogen interactions and for the development of effective antifungals. Our goal was to assess the efficacy of 4-chloro-3-nitrophenyldifluoroiodomethyl sulfone (named Sulfone) against the C. albicans infections in the Galleria mellonella host model. We assessed invasiven...
Fungal diseases are severe and carry a very high morbidity as well as up to 60% mortality for patients diagnosed with invasive fungal infection. In this review, the in vitro and in vivo studies provided us with the insight into the role of Candida virulence factors that mediate their success as pathogens, such as: membrane and cell wall (CW) barrie...
The paper addresses the issue of fungal infections in the context of growing resistance to currently available antifungal agents and the development of new antimycotics. Fungal pathogens belonging to the genuses Candida, Aspergillus, Pneumocystis and Cryptococcus account for about 90% of all fungal infections. Candida albicans infections are a glob...
The increase of opportunistic fungal infections raises the need for design and synthesis of new antifungal agents. Taking into account that tetrazole derivatives exhibit antifungal activity, and some of them are in the phase of clinical trials, new tetrazole derivatives bearing pyrrolidine moiety were synthesized in order to present their action mo...
Since candidiasis is so difficult to eradicate with antifungal treatment and existing antimycotics display many limitations, hopefully new sulfone derivatives may overcome these deficiencies. It is pertinent to study new strategies such as sulfone derivatives targeting virulence attributes of C. albicans that diverge from pathogens and host. During...
A series of novel tetrazole derivatives was synthetized using N-alkylation or Michael-type addition reactions, and screened for their fungistatic potential against Candida albicans (the lack of endpoint = 100%). Among them, the selected compounds 2d, 4b, and 6a differing in substituents at the tetrazole ring were non-toxic to Galleria mellonella la...
Three out of 16 newly synthesized 1,3-dimethylxanthine derivatives (proxyphylline analogues) exhibited consistencies between antifungal and anticancer properties. Proxyphylline possessing 1-(10H-phenothiazin-10-yl)propan-2-yl (6) and polybrominated benzimidazole (41) or benzotriazole moiety (42) remained selectively cidal against Candida albicans (...
Introduction: Increasing occurrence of fungal infections raises the need to develop novel antifungal agents. In this context, an inhibition of morphological switch may provide an alternative approach to find compounds with a potential to control the Candida albicans infections. Methods: A series of 17 sulfone and sulfanyl derivatives was synthesize...
Invasive fungal infections are associated with high mortality rates, despite appropriate antifungal therapy. Limited therapeutic options, resistance development and the high mortality of invasive fungal infections brought about more concern triggering the search for new compounds capable of interfering with fungal viability and virulence. In this c...
We investigated the role of KEX2, SAP4-6, EFG1, and CPH1 in the virulence of Candida under a novel compound 2-bromo-2-chloro-2-(4-chlorophenylsulfonyl)-1-phenylethanone (Compound 4). We examined whether the exposure of C. albicans cells to Compound 4, non-cytotoxic to mammalian cells, reduces their adhesion to the human epithelium. We next assessed...
Aim:
The effect of KEX2 mutations on C. albicans virulence and resistance to halogenated methyl sulfones was assessed.
Materials & methods:
The mechanism of action of sulfones was studied using flow cytometry and microscopy. Expression of KEX2 and SAP5 was assessed using quantitative Real-Time-PCR. 2,3-Bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tet...
With the appearance of the antifungal resistance, novel antifungal agents need to be identified. In this context new 2,5-disubstituted tetrazole derivatives containing benzothiazole, benzoxazole or phenylsulfonyl moiety were synthesized by N-alkylation of aryltetrazole with 2-[(3-chloropropyl)sulfanyl]-1,3-benzothiazole or 2-[(3-chloropropyl)sulfan...
Hydrolytic enzymes e.g., Saps and KEX2 are, due to their role in Candida virulence, considered important targets for new synthetic inhibitors. MICTI and MICPI values indicate that disruption of SAP1-3 significantly increases the resistance of Candida mutants to β-ketosulfone (1). Contrariwise, sap123∆ showed sensitive phenotype to halogenated methy...
We investigated the antifungal activity of novel a 2-bromo-2-chloro-2-(4-chlorophenylsulfonyl)-1-phenylethanone (compound 4). The synthesis of compound 4 was commenced from sodium 4-chlorobenzene sulfinate and the final product was obtained by treatment of α-chloro-β-keto-sulfone with sodium hypobromite. The sensitivity of 63 clinical isolates belo...
Candida species are the major opportunistic human pathogens accounting for 70-90% of all invasive fungal infections. Candida spp, especially C. albicans, are able to produce and secrete hydrolytic enzymes, particularly aspartic proteases (Saps). These enzymes production is an evolutionary adaptation of pathogens to utilize nutrients and survive in...
A series of new N-substituted benzimidazole derivatives was synthesized and their antifungal activity against Candida albicans was evaluated. The chemical step included synthesis of appropriate ketones containing benzimidazole ring, reduction of ketones to the racemic alcohols, and acetylation of alcohols to the esters. All benzimidazole derivative...
Purpose:
Eight peptide dendrimers were designed as structural mimics of natural cationic amphiphilic peptides with antifungal activity and evaluated for their anti-Candida potential against the wild type strains and mutants.
Methods:
Dendrimer 14 containing four Trp residues and dodecyl tail and a slightly smaller dendrimer 9 decorated with four...
Secreted aspartic proteases (Saps) are considered as key virulence factors of Candida albicans. Hopefully our outlook will widen the knowledge of SAP7's role in C. albicans pathogenesis. The goal of our study was to investigate SAP7 expression during C. albicans adhesion to intestinal human cells. Another objective was to study the role of SAP8-10...
A rapidly growing resistance of Candida spp. requires a search for bioactive compounds with fungicidal or fungistatic activity. In this context a characteristics and comparison of antifungal properties of 19 sulfone derivatives were conducted. MICs of the Compounds were determined using the M27-A3 protocol following CLSI recommendations. The SAP ex...
The production of hydrolytic enzymes is considered a key virulence determinant of Candida albicans. Aminopeptidase 2 (Ape2) facilitates the penetration of C. albicans into the host tissue, by providing free amino acids to support fungal growth and proliferation. The objective of this study was to estimate the APE2 expression profile in C. albicans...
Series of 4-(5-aryl-2H-tetrazol-2-yl)butan-2-ol, 1-(5-aryl-2H-tetrazol-2-yl)propan-2-ol and their acetates have been screened against Candida albicans. Among the tested compounds, (±)-1-[5-(2-chlorophenyl)-2H-tetrazol-2-yl]propan-2-yl acetate (E5) proved to be the most effective inhibitor of fungal growth and was further evaluated against young (ad...
The influence of halogenated methyl sulfones, i.e. bromodichloromethyl-4-chloro-3-nitrophenyl sulfone (named halogenated methyl sulfone 1), dichloromethyl-4-chloro-3-nitrophenyl sulfone (halogenated methyl sulfone 2), and chlorodibromomethyl-4-hydrazino-3-nitrophenyl sulfone (halogenated methyl sulfone 3), on cell growth inhibition, aspartic protea...
The role of peroxisomes in penicillin G production by industrial strains of Penicillium çhrysogenum is discussed. Penicillin G biosynthesis is a compartmentalized process mainly located in sub-apical productive vacuolated non-growing cells of the mycelium. The cellular localization of the pathway of penicillin G biosynthesis is presented, including...
The different members of the secreted aspartyl proteinase (Sap) family of the human pathogenic yeast Candida albicans are proposed to play different roles during infection and are differentially expressed at various body sites. In recent reports, expression analysis has focused on the genes SAP1-6, while the expression pattern of SAP7-10 was less w...
Candida albicans normally exists as harmless commensal inhabiting mucosal surfaces of healthy individuals. Yet, this opportunistic pathogen in immunocompromised hosts causes superficial or invasive life treating infections with high mortality rate. The incidence of candidiasis appeared to have several predisposing factors such as immunosuppressant...
Candida albicans SAP4 gene encodes secretory aspartyl protease Sap4 which is involved in hyphae formation and virulence. Transcriptional factors Cph1 and Efg1 govern the expression of several C. albicans genes and contribute to morphogenesis. We investigated the expression of SAP4 in C. albicans clinical isolate and mutants lacking Efg1 or/ and Cph...
Fungal virulence factors represent a strategy for the design of new compounds with effective activities against Candida spp. Dichloromethyl-4-chloro-3-nitrophenylsulfone (named Compound 1) and chlorodibromomethyl-4-hydrazino-3-nitrophenylsulfone (Compound 2) versus Candida albicans virulence factors (SAP2 expression and adhesion to Caco-2 cell line...
The emergence of drug-resistant Candida albicans strains necessitates identifying new antimycotics along with studying their modes of action. The influence of a new rationally designed dendrimer D186 containing N,N-dioctyl tail and four tryptophane residues on inhibition of planktonic cells, aspartic protease SAP5 expression and adhesion to epithel...
The arrangement of organelles in the sub-apical productive non-growing vacuolated hyphal cells of the high- and the low-penicillin-pro- ducing strains Penicillium chrysogenum was compared using transmission electron microscopy. In the productive cells of the high-yielding strain the endoplasmic reticulum and the polyribosomes with associated peroxi...
Scanning electron microscope (SEM) observations were used to analyze particular morphologies of Candida albicans clinical isolate (strain 82) and mutants defective in hyphae-promoting genes EFG1 (strain HLC52) and/or CPH1 (strains HLC54 and Can16). Transcription factors Efg1 and Cph1 play role in regulating filamentation and adhesion of C. albicans...
The study evaluated the cell wall carbohydrates fraction in blastoconidia grown in YEPD medium at 30 degrees C and in the conglomerate of true hyphae grown in human serum at 37 degrees C.
The clinical isolate obtained from a child with widespread C. albicans infection was used in the study. The cells were broken with glass beads, centrifuged to har...
Recent progress in medical sciences and therapy resulted in an increased number of immunocompromised individuals. Candida albicans is the leading opportunistic fungal pathogen causing infections in humans, ranging from superficial mucosal lesions to disseminated or bloodstream candidiasis. Superficial candidiasis not always presents a risk to the l...
Candida albicans morphogenesis enables colonization of various niches in host body. Various hyphae-dependent genes have been described. Among them secreted aspartyl proteinases (Saps) play a central role in pathogenesis. Candida albicans SAP4-6 genes encode secretory aspartyl proteinases Sap4-6, which are involved in hyphae formation and virulence....
Candida albicans is an opportunistic pathogen that frequently causes infections ranging from superficial mucosal lesions to disseminated or bloodstream infections. Candida infections are a problem of a growing clinical importance worldwide; therefore virulence factors of this pathogen have been extensively studied. This review focuses on the role a...
Candida albicans is the most common etiological factor of opportunistic human fungal infections. In this review, we focus on the major virulence factors that mediate the pathogenesis of C. albicans. Among these virulence factors, secreted aspartyl proteases, adherence, pleomorphism are the most important features of C. albicans infections. Ability...