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Planta Medica Jun 2024Antimicrobial photodynamic therapy (aPDT) is an evolving treatment strategy against human pathogenic microbes such as the species, including the emerging pathogen ....
Antimicrobial photodynamic therapy (aPDT) is an evolving treatment strategy against human pathogenic microbes such as the species, including the emerging pathogen . Using a modified EUCAST protocol, the light-enhanced antifungal activity of the natural compound parietin was explored. The photoactivity was evaluated against three separate strains of five yeasts, and its molecular mode of action was analysed via several techniques, i.e., cellular uptake, reactive electrophilic species (RES), and singlet oxygen yield. Under experimental conditions ( = 428 nm, H = 30 J/cm, PI = 30 min), microbial growth was inhibited by more than 90% at parietin concentrations as low as c = 0.156 mg/L (0.55 µM) for and , c = 0.313 mg/L (1.10 µM) for , c = 0.625 mg/L (2.20 µM) for , and c = 1.250 mg/L (4.40 µM) for . Mode-of-action analysis demonstrated fungicidal activity. Parietin targets the cell membrane and induces cell death via ROS-mediated lipid peroxidation after light irradiation. In summary, parietin exhibits light-enhanced fungicidal activity against all species tested (including ) and , covering three of the four critical threats on the WHO's most recent fungal priority list.
Topics: Antifungal Agents; Cryptococcus neoformans; Microbial Sensitivity Tests; Candida auris; Light; Candida; Reactive Oxygen Species; Photochemotherapy; Anthraquinones; Photosensitizing Agents
PubMed: 38843798
DOI: 10.1055/a-2249-9110 -
BMC Genomics Jun 2024The search for new bioactive natural compounds with anticancer activity is still of great importance. Even though their potential for diagnostics and treatment of cancer...
BACKGROUND
The search for new bioactive natural compounds with anticancer activity is still of great importance. Even though their potential for diagnostics and treatment of cancer has already been proved, the availability is still limited. Hypericin, a naphthodianthrone isolated essentially from plant source Hypericum perforatum L. along with other related anthraquinones and bisanthraquinones belongs to this group of compounds. Although it has been proven that hypericin is synthesized by the polyketide pathway in plants, none of the candidate genes coding for key enzymes has been experimentally validated yet. Despite the rare occurrence of anthraquinones in plants, their presence in microorganisms, including endophytic fungi, is quite common. Unlike plants, several biosynthetic genes grouped into clusters (BGCs) in fungal endophytes have already been characterized.
RESULTS
The aim of this work was to predict, identify and characterize the anthraquinone BGCs in de novo assembled and functionally annotated genomes of selected endophytic fungal isolates (Fusarium oxysporum, Plectosphaerella cucumerina, Scedosporium apiospermum, Diaporthe eres, Canariomyces subthermophilus) obtained from different tissues of Hypericum spp. The number of predicted type I polyketide synthase (PKS) BGCs in the studied genomes varied. The non-reducing type I PKS lacking thioesterase domain and adjacent discrete gene encoding protein with product release function were identified only in the genomes of C. subthermophilus and D. eres. A candidate bisanthraquinone BGC was predicted in C. subthermophilus genome and comprised genes coding the enzymes that catalyze formation of the basic anthraquinone skeleton (PKS, metallo-beta-lactamase, decarboxylase, anthrone oxygenase), putative dimerization enzyme (cytochrome P450 monooxygenase), other tailoring enzymes (oxidoreductase, dehydrogenase/reductase), and non-catalytic proteins (fungal transcription factor, transporter protein).
CONCLUSIONS
The results provide an insight into genetic background of anthraquinone biosynthesis in Hypericum-borne endophytes. The predicted bisanthraquinone gene cluster represents a basis for functional validation of the candidate biosynthetic genes in a simple eukaryotic system as a prospective biotechnological alternative for production of hypericin and related bioactive anthraquinones.
Topics: Hypericum; Multigene Family; Polyketides; Endophytes; Anthraquinones; Fungi; Genome, Fungal; Computer Simulation; Polyketide Synthases; Perylene; Anthracenes; Genomics; Phylogeny
PubMed: 38831295
DOI: 10.1186/s12864-024-10475-z -
Future Science OA 2024Leukemia is a malignant clonal illness stem from the mutations of hematopoietic cells. Acute lymphoblastic leukemia is one of the utmost prevalent kinds of leukemia, is...
Leukemia is a malignant clonal illness stem from the mutations of hematopoietic cells. Acute lymphoblastic leukemia is one of the utmost prevalent kinds of leukemia, is brought on by atypical lymphoid progenitor cell division in the bone marrow. A comparative study between, titanium Nanoparticle-loaded doxorubicin or cisplatin and lactoferrin-loaded doxorubicin or cisplatin, on 7,12-dimethylbenz[a]-anthracene (DMBA)-induced leukemia was investigated and confirming the hypothesis that messenger RNA of is a forthcoming signaling pathways in leukemia. A significant alteration in , , , , and genes was observed post DMBA intoxication the aforementioned Nanodrugs modulated these signaling pathways. The carrier-loaded drugs triggered cytotoxicity of cancer cells via enhancing drug efficacy and bio-availability.
PubMed: 38827790
DOI: 10.2144/fsoa-2023-0111 -
ACS Nano Jun 2024Photon upconversion via triplet-triplet annihilation (TTA-UC) provides a pathway to overcoming the thermodynamic efficiency limits in single-junction solar cells by...
Photon upconversion via triplet-triplet annihilation (TTA-UC) provides a pathway to overcoming the thermodynamic efficiency limits in single-junction solar cells by allowing the harvesting of sub-bandgap photons. Here, we use mixed halide perovskite nanocrystals (CsPbX, X = Br/I) as triplet sensitizers, with excitation transfer to 9,10-diphenylanthracene (DPA) and/or 9,10-bis[(triisopropylsilyl)ethynyl]anthracene (TIPS-An) which act as the triplet annihilators. We observe that the upconversion efficiency is five times higher with the combination of both annihilators in a composite system compared to the sum of the individual single-acceptor systems. Our work illustrates the importance of using a composite system of annihilators to enhance TTA upconversion, demonstrated in a perovskite-sensitized system, with promise for a range of potential applications in light-harvesting, biomedical imaging, biosensing, therapeutics, and photocatalysis.
PubMed: 38820532
DOI: 10.1021/acsnano.4c03753 -
Reproductive Toxicology (Elmsford, N.Y.) Aug 2024Zebrafish embryo assays are used by pharmaceutical and chemical companies as new approach methodologies (NAMs) in developmental toxicity screening. Despite an overall...
Zebrafish embryo assays are used by pharmaceutical and chemical companies as new approach methodologies (NAMs) in developmental toxicity screening. Despite an overall high concordance of zebrafish embryo assays with in vivo mammalian studies, false negative and false positive results have been reported. False negative results in risk assessment models are of particular concern for human safety, as developmental anomalies may be missed. Interestingly, for several chemicals and drugs that were reported to be false negative in zebrafish, skeletal findings were noted in the in vivo studies. As the number of skeletal endpoints assessed in zebrafish is very limited compared to the in vivo mammalian studies, the aim of this study was to investigate whether the sensitivity could be increased by including a skeletal staining method. Three staining methods were tested on zebrafish embryos that were exposed to four teratogens that caused skeletal anomalies in rats and/or rabbits and were false negative in zebrafish embryo assays. These methods included a fixed alizarin red-alcian blue staining, a calcein staining, and a live alizarin red staining. The results showed a high variability in staining intensity of larvae exposed to mammalian skeletal teratogens, as well as variability between control larvae originating from the same clutch of zebrafish. Hence, biological variability in (onset of) bone development in zebrafish hampers the detection of (subtle) treatment-related bone effects that are not picked-up by gross morphology. In conclusion, the used skeletal staining methods did not increase the sensitivity of zebrafish embryo developmental toxicity assays.
Topics: Animals; Zebrafish; Teratogens; Embryo, Nonmammalian; Toxicity Tests; Staining and Labeling; Bone and Bones; Embryonic Development; Fluoresceins; Anthraquinones
PubMed: 38815770
DOI: 10.1016/j.reprotox.2024.108615 -
Frontiers in Bioscience (Landmark... Apr 2024The review focuses on the recent knowledge on natural anthraquinones (AQs) of plant origin and their potential for application in an exclusive medicinal curative and... (Review)
Review
The review focuses on the recent knowledge on natural anthraquinones (AQs) of plant origin and their potential for application in an exclusive medicinal curative and palliative method named photodynamic therapy (PDT). Green approach to PDT is associated with photosensitizers (PS) from plants or other natural sources and excitation light in visible spectrum. The investigations of plants are of high research interests due to their unique health supportive properties as herbs and the high percentage availability to obtain compounds with medical value. Up-to-date many naturally occurring compounds with therapeutic properties are known and are still under investigations. Some natural quinones have already been evaluated and clinically approved as anti-tumor agents. Recent scientific interests are beyond their common medical applications but also in directions to their photo-properties as natural PSs. The study presents a systematic searches on the latest knowledge on AQ derivatives that are isolated from the higher plants as photosensitizers for PDT applications. The natural quinones have been recognized with functions of natural dyes since the ancient times. Lately, AQs have been explored due to their biological activity including the photosensitive properties useful for PDT especially towards medical problems with no other alternatives. The existing literature' overview suggests that natural AQs possess characteristics of valuable PSs for PDT. This method is based on an application of a photoactive compound and light arrangement in oxygen media, such that the harmful general cytotoxicity could be avoided. Moreover, the common anticancer and antimicrobial drug resistance has been evaluated with very low occurrence after PDT. Natural AQs have been focused the scientific efforts to further developments because of the high range of natural sources, desirable biocompatibility, low toxicity, minimal side effects and low accident of drug resistance, together with their good photosensitivity and therapeutic capacity. Among the known AQs, only hypericin has been studied in anticancer clinical PDT. Currently, the natural PSs are under intensive research for the future PDT applications for diseases without alternative effective treatments.
Topics: Anthraquinones; Photochemotherapy; Photosensitizing Agents; Humans; Plants
PubMed: 38812303
DOI: 10.31083/j.fbl2905168 -
Journal of Nanobiotechnology May 2024Chemotherapy, as a conventional strategy for tumor therapy, often leads to unsatisfied therapeutic effect due to the multi-drug resistance and the serious side effects....
Chemotherapy, as a conventional strategy for tumor therapy, often leads to unsatisfied therapeutic effect due to the multi-drug resistance and the serious side effects. Herein, we genetically engineered a thermal-responsive murine Ferritin (mHFn) to specifically deliver mitoxantrone (MTO, a chemotherapeutic and photothermal agent) to tumor tissue for the chemotherapy and photothermal combined therapy of colorectal cancer, thanks to the high affinity of mHFn to transferrin receptor that highly expressed on tumor cells. The thermal-sensitive channels on mHFn allowed the effective encapsulation of MTO in vitro and the laser-controlled release of MTO in vivo. Upon irradiation with a 660 nm laser, the raised temperature triggered the opening of the thermal-sensitive channel in mHFn nanocage, resulting in the controlled and rapid release of MTO. Consequently, a significant amount of reactive oxygen species was generated, causing mitochondrial collapse and tumor cell death. The photothermal-sensitive controlled release, low systemic cytotoxicity, and excellent synergistic tumor eradication ability in vivo made mHFn@MTO a promising candidate for chemo-photothermal combination therapy against colorectal cancer.
Topics: Animals; Colorectal Neoplasms; Mice; Ferritins; Photothermal Therapy; Humans; Mitoxantrone; Lasers; Cell Line, Tumor; Reactive Oxygen Species; Mice, Inbred BALB C; Antineoplastic Agents; Mice, Nude; Female
PubMed: 38812019
DOI: 10.1186/s12951-024-02566-6 -
Nature Communications May 2024Photocatalysis through energy transfer has been investigated for the facilitation of [4 + 2] cycloaddition reactions. However, the high reactivity of radical species...
Photocatalysis through energy transfer has been investigated for the facilitation of [4 + 2] cycloaddition reactions. However, the high reactivity of radical species poses a challenging obstacle to achieving enantiocontrol with chiral catalysts, as no enantioselective examples have been reported thus far. Here, we present the development of catalytic asymmetric [4 + 2] dearomative photocycloaddition involving anthracene and its derivatives with alkenylazaarenes. This accomplishment is achieved by utilizing a cooperative photosensitizer and chiral Brønsted acid catalysis platform. Importantly, this process enables the activation of anthracene substrates through energy transfer from triplet DPZ, thereby initiating a precise and stereoselective sequential transformation. The significance of our work is highlighted by the synthesis of a diverse range of pharmaceutical valuable cycloadducts incorporating attractive azaarenes, all obtained with high yields, ees, and drs. The broad substrate scope is further underscored by successful construction of all-carbon quaternary stereocenters and diverse adjacent stereocenters.
PubMed: 38811663
DOI: 10.1038/s41467-024-48982-y -
Acta Cirurgica Brasileira 2024To evaluate the chemotherapeutic activity of temozolomide counter to mammary carcinoma.
PURPOSE
To evaluate the chemotherapeutic activity of temozolomide counter to mammary carcinoma.
METHODS
In-vitro anticancer activity has been conducted on MCF7 cells, and mammary carcinoma has been induced in Wistar rats by introduction of 7, 12-Dimethylbenz(a)anthracene (DMBA), which was sustained for 24 weeks. Histopathology, immunohistochemistry, cell proliferation study and apoptosis assay via TUNEL method was conducted to evaluate an antineoplastic activity of temozolomide in rat breast tissue.
RESULTS
IC50 value of temozolomide in MCF7 cell has been obtained as 103 μM, which demonstrated an initiation of apoptosis. The temozolomide treatment facilitated cell cycle arrest in G2/M and S phase dose dependently. The treatment with temozolomide suggested decrease of the hyperplastic abrasions and renovation of the typical histological features of mammary tissue. Moreover, temozolomide therapy caused the downregulation of epidermal growth factor receptor, extracellular signal-regulated kinase, and metalloproteinase-1 expression and upstream of p53 and caspase-3 proliferation to indicate an initiation of apoptotic events.
CONCLUSIONS
The occurrence of mammary carcinoma has been significantly decreased by activation of apoptotic pathway and abrogation of cellular propagation that allowable for developing a suitable mechanistic pathway of temozolomide in order to facilitate chemotherapeutic approach.
Topics: Temozolomide; Animals; Apoptosis; Female; ErbB Receptors; Rats, Wistar; Antineoplastic Agents, Alkylating; Matrix Metalloproteinase 1; Cell Proliferation; Dacarbazine; Breast Neoplasms; Humans; MCF-7 Cells; Extracellular Signal-Regulated MAP Kinases; Immunohistochemistry; Reproducibility of Results; Rats; Mammary Neoplasms, Experimental
PubMed: 38808816
DOI: 10.1590/acb391624 -
Environmental Science and Pollution... Jun 2024Classical monitoring of air pollution provides information on environmental quality but involves high costs. An alternative to this method is the use of bioindicators....
Classical monitoring of air pollution provides information on environmental quality but involves high costs. An alternative to this method is the use of bioindicators. The purpose of our work was to evaluate atmospheric aerosol pollution by selected polycyclic aromatic hydrocarbons conducted as part of annual active biomonitoring ("moss-bag" technique) with the use of three moss species: Pleurozium schreberi, Sphagnum fallax, and Dicranum polysetum. The gas chromatography-mass spectrometry (GC-MS) was utilized to determine certain 13 polycyclic aromatic hydrocarbons (PAHs). Three seasonal variations in PAH concentrations have been observed as a result of the study. A fire on the toilet paper plant caused an increase of five new compounds: benzo(k)fluoranthene (BkF), benzo(a)pyrene (BaP), indeno(1.2.3)-cd_pyrene (IP), dibenzo(a.h)anthracene (Dah), and benzo(g.h.i)perylene (Bghi) in proximity after 8 months of exposure compared to previous months. The effect of meteorological conditions on the deposition of PAHs (mainly wind direction) in mosses was confirmed by principal component analysis (PCA). Dicranum polysetum moss accumulated on average 26.5% more PAHs than the other species, which allows considering its broader use in active biomonitoring. The "moss-bag" technique demonstrates its feasibility in assessing the source of PAH air pollution in a long-term study. It is recommended to use this biological method as a valuable tool in air quality monitoring.
Topics: Polycyclic Aromatic Hydrocarbons; Biological Monitoring; Bryophyta; Air Pollutants; Environmental Monitoring; Air Pollution; Gas Chromatography-Mass Spectrometry; Seasons
PubMed: 38802616
DOI: 10.1007/s11356-024-33831-8