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Nutrients Jun 2024, commonly known as , is a photosynthetic filamentous cyanobacterium (blue-green microalga) that has been utilized as a food source since ancient times. More recently,... (Review)
Review
, commonly known as , is a photosynthetic filamentous cyanobacterium (blue-green microalga) that has been utilized as a food source since ancient times. More recently, it has gained significant popularity as a dietary supplement due to its rich content of micro- and macro-nutrients. Of particular interest is a water soluble phycobiliprotein derived from known as phycocyanin C (C-PC), which stands out as the most abundant protein in this cyanobacterium. C-PC is a fluorescent protein, with its chromophore represented by the tetrapyrrole molecule phycocyanobilin B (PCB-B). While C-PC is commonly employed in food for its coloring properties, it also serves as the molecular basis for numerous nutraceutical features associated with . Indeed, the comprehensive C-PC, and to some extent, the isolated PCB-B, has been linked to various health-promoting effects. These benefits encompass conditions triggered by oxidative stress, inflammation, and other pathological conditions. The present review focuses on the bio-pharmacological properties of these molecules, positioning them as promising agents for potential new applications in the expanding nutraceutical market.
Topics: Dietary Supplements; Spirulina; Phycocyanin; Humans; Phycobilins; Phycobiliproteins; Oxidative Stress
PubMed: 38892686
DOI: 10.3390/nu16111752 -
International Journal of Molecular... Jun 2024Nitric oxide (NO) and reactive nitrogen species (RNS) exert profound biological impacts dictated by their chemistry. Understanding their spatial distribution is... (Review)
Review
Nitric oxide (NO) and reactive nitrogen species (RNS) exert profound biological impacts dictated by their chemistry. Understanding their spatial distribution is essential for deciphering their roles in diverse biological processes. This review establishes a framework for the chemical biology of NO and RNS, exploring their dynamic reactions within the context of cancer. Concentration-dependent signaling reveals distinctive processes in cancer, with three levels of NO influencing oncogenic properties. In this context, NO plays a crucial role in cancer cell proliferation, metastasis, chemotherapy resistance, and immune suppression. Increased NOS2 expression correlates with poor survival across different tumors, including breast cancer. Additionally, NOS2 can crosstalk with the proinflammatory enzyme cyclooxygenase-2 (COX-2) to promote cancer progression. NOS2 and COX-2 co-expression establishes a positive feed-forward loop, driving immunosuppression and metastasis in estrogen receptor-negative (ER) breast cancer. Spatial evaluation of NOS2 and COX-2 reveals orthogonal expression, suggesting the unique roles of these niches in the tumor microenvironment (TME). NOS2 and COX2 niche formation requires IFN-γ and cytokine-releasing cells. These niches contribute to poor clinical outcomes, emphasizing their role in cancer progression. Strategies to target these markers include direct inhibition, involving pan-inhibitors and selective inhibitors, as well as indirect approaches targeting their induction or downstream effectors. Compounds from cruciferous vegetables are potential candidates for NOS2 and COX-2 inhibition offering therapeutic applications. Thus, understanding the chemical biology of NO and RNS, their spatial distribution, and their implications in cancer progression provides valuable insights for developing targeted therapies and preventive strategies.
Topics: Humans; Breast Neoplasms; Cyclooxygenase 2; Female; Nitric Oxide Synthase Type II; Disease Progression; Tumor Microenvironment; Animals; Nitric Oxide; Gene Expression Regulation, Neoplastic; Reactive Nitrogen Species
PubMed: 38892290
DOI: 10.3390/ijms25116103 -
International Journal of Molecular... May 2024Astronauts on exploratory missions will be exposed to galactic cosmic rays (GCR), which can induce neuroinflammation and oxidative stress (OS) and may increase the risk...
Astronauts on exploratory missions will be exposed to galactic cosmic rays (GCR), which can induce neuroinflammation and oxidative stress (OS) and may increase the risk of neurodegenerative disease. As key regulators of inflammation and OS in the CNS, microglial cells may be involved in GCR-induced deficits, and therefore could be a target for neuroprotection. This study assessed the effects of exposure to helium (He) and iron (Fe) particles on inflammation and OS in microglia in vitro, to establish a model for testing countermeasure efficacy. Rat microglia were exposed to a single dose of 20 cGy (300 MeV/n) He or 2 Gy Fe (600 MeV/n), while the control cells were not exposed (0 cGy). Immediately following irradiation, fresh media was applied to the cells, and biomarkers of inflammation (cyclooxygenase-2 [COX-2], nitric oxide synthase [iNOS], phosphorylated IκB-α [pIκB-α], tumor necrosis factor-α [TNFα], and nitrite [NO]) and OS (NADPH oxidase [NOX2]) were assessed 24 h later using standard immunochemical techniques. Results showed that radiation did not increase levels of NO or protein levels of COX-2, iNOS, pIκB-α, TNFα, or NOX2 compared to non-irradiated control conditions in microglial cells ( > 0.05). Therefore, microglia in isolation may not be the primary cause of neuroinflammation and OS following exposures to helium or iron GCR particles.
Topics: Animals; Microglia; Cosmic Radiation; Oxidative Stress; Rats; Inflammation; Biomarkers; Nitric Oxide Synthase Type II; Iron; Cyclooxygenase 2; Helium; Tumor Necrosis Factor-alpha; NADPH Oxidase 2
PubMed: 38892109
DOI: 10.3390/ijms25115923 -
International Journal of Molecular... May 2024Utilizing bioinformatics tools, this study expands our understanding of secondary metabolism in , identifying novel genes within polyketide synthase (PKS), non-ribosomal...
Utilizing bioinformatics tools, this study expands our understanding of secondary metabolism in , identifying novel genes within polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS), sesquiterpene cyclase (STC), diterpene cyclase (DTC), and dimethylallyltryptophan synthase (DMATS) families. These findings enrich the genetic framework associated with 's pathogenicity and ecological adaptation, offering insights into uncharted metabolic pathways. Significantly, the discovery of previously unannotated genes provides new molecular targets for developing targeted antifungal strategies, promising to enhance crop protection and advance our understanding of fungal biochemistry. This research not only broadens the scope of known secondary metabolites but also opens avenues for future exploration into 's biosynthetic capabilities, potentially leading to novel antifungal compounds. Our work underscores the importance of integrating bioinformatics and genomics for fungal research, paving the way for sustainable agricultural practices by pinpointing precise molecular interventions against . This study sets a foundation for further investigations into the fungus's secondary metabolism, with implications for biotechnology and crop disease management.
Topics: Botrytis; Secondary Metabolism; Peptide Synthases; Polyketide Synthases; Fungal Proteins; Computational Biology; Multigene Family; Genes, Fungal
PubMed: 38892087
DOI: 10.3390/ijms25115900 -
International Journal of Molecular... May 2024Photosystem II (PSII) functions were investigated in basil ( L.) plants sprayed with 1 mM salicylic acid (SA) under non-stress (NS) or mild drought-stress (MiDS)...
Photosystem II (PSII) functions were investigated in basil ( L.) plants sprayed with 1 mM salicylic acid (SA) under non-stress (NS) or mild drought-stress (MiDS) conditions. Under MiDS, SA-sprayed leaves retained significantly higher (+36%) chlorophyll content compared to NS, SA-sprayed leaves. PSII efficiency in SA-sprayed leaves under NS conditions, evaluated at both low light (LL, 200 μmol photons m s) and high light (HL, 900 μmol photons m s), increased significantly with a parallel significant decrease in the excitation pressure at PSII (1-) and the excess excitation energy (EXC). This enhancement of PSII efficiency under NS conditions was induced by the mechanism of non-photochemical quenching (NPQ) that reduced singlet oxygen (O) production, as indicated by the reduced quantum yield of non-regulated energy loss in PSII (Φ). Under MiDS, the thylakoid structure of water-sprayed leaves appeared slightly dilated, and the efficiency of PSII declined, compared to NS conditions. In contrast, the thylakoid structure of SA-sprayed leaves did not change under MiDS, while PSII functionality was retained, similar to NS plants at HL. This was due to the photoprotective heat dissipation by NPQ, which was sufficient to retain the same percentage of open PSII reaction centers (q), as in NS conditions and HL. We suggest that the redox status of the plastoquinone pool (q) under MiDS and HL initiated the acclimation response to MiDS in SA-sprayed leaves, which retained the same electron transport rate (ETR) with control plants. Foliar spray of SA could be considered as a method to improve PSII efficiency in basil plants under NS conditions, at both LL and HL, while under MiDS and HL conditions, basil plants could retain PSII efficiency similar to control plants.
Topics: Photosystem II Protein Complex; Salicylic Acid; Ocimum basilicum; Droughts; Plant Leaves; Stress, Physiological; Chlorophyll; Photosynthesis; Thylakoids; Light
PubMed: 38891916
DOI: 10.3390/ijms25115728 -
International Journal of Molecular... May 2024The proteasome generates the majority of peptides presented on MHC class I molecules. The cleavage pattern of the proteasome has been shown to be changed via the...
The proteasome generates the majority of peptides presented on MHC class I molecules. The cleavage pattern of the proteasome has been shown to be changed via the proteasome activator (PA)28 alpha beta (PA28αβ). In particular, several immunogenic peptides have been reported to be PA28αβ-dependent. In contrast, we did not observe a major impact of PA28αβ on the generation of different major histocompatibility complex (MHC) classI ligands. PA28αβ-knockout mice infected with the () or virus showed a normal cluster of differentiation (CD) 8 response and viral clearance. However, we observed that the adoptive transfer of wild-type cells into PA28αβ-knockout mice led to graft rejection, but not vice versa. Depletion experiments showed that the observed rejection was mediated by CD8 cytotoxic T cells. These data indicate that PA28αβ might be involved in the development of the CD8 T cell repertoire in the thymus. Taken together, our data suggest that PA28αβ is a crucial factor determining T cell selection and, therefore, impacts graft acceptance.
Topics: Animals; Graft Rejection; Mice; CD8-Positive T-Lymphocytes; Histocompatibility Antigens Class I; Mice, Knockout; Proteasome Endopeptidase Complex; Ligands; Mice, Inbred C57BL; Lymphocytic choriomeningitis virus; Vaccinia virus
PubMed: 38891837
DOI: 10.3390/ijms25115649 -
International Journal of Molecular... May 2024Cellular senescence is closely related to DNA damage, proteasome inactivity, histone loss, epigenetic alterations, and tumorigenesis. The mammalian proteasome activator... (Review)
Review
Cellular senescence is closely related to DNA damage, proteasome inactivity, histone loss, epigenetic alterations, and tumorigenesis. The mammalian proteasome activator PA200 (also referred to as PSME4) or its yeast ortholog Blm10 promotes the acetylation-dependent degradation of the core histones during transcription, DNA repair, and spermatogenesis. According to recent studies, PA200 plays an important role in senescence, probably because of its role in promoting the degradation of the core histones. Loss of PA200 or Blm10 is a major cause of the decrease in proteasome activity during senescence. In this paper, recent research progress on the association of PA200 with cellular senescence is summarized, and the potential of PA200 to serve as a therapeutic target in age-related diseases is discussed.
Topics: Proteasome Endopeptidase Complex; Cellular Senescence; Humans; Animals; Proteolysis; Histones; Saccharomyces cerevisiae Proteins; Nuclear Proteins
PubMed: 38891826
DOI: 10.3390/ijms25115637 -
International Journal of Molecular... May 2024In the cosmetics industry, the extract from L. is fermented using specific starter cultures. These cosmetic ingredients act as preservatives and skin conditioners.... (Comparative Study)
Comparative Study
In the cosmetics industry, the extract from L. is fermented using specific starter cultures. These cosmetic ingredients act as preservatives and skin conditioners. Kombucha is traditionally made by fermenting sweetened tea using symbiotic cultures of bacteria and yeast and is used in cosmetic products. The aim of this study was to evaluate the cosmetic properties of radish leaf and root extract fermented with the SCOBY. Both unfermented water extracts and extracts after 7, 14, and 21 days of fermentation were evaluated. The analysis of secondary plant metabolites by UPLC-MS showed higher values for ferments than for extracts. A similar relationship was noted when examining the antioxidant properties using DPPH and ABTS radicals and the protective effect against HO-induced oxidative stress in fibroblasts and keratinocytes using the fluorogenic dye HDCFDA. The results also showed no cytotoxicity to skin cells using Alamar Blue and Neutral Red tests. The ability of the samples to inhibit IL-1β and COX-2 activity in LPS-treated fibroblasts was also demonstrated using ELISA assays. The influence of extracts and ferments on bacterial strains involved in inflammatory processes of skin diseases was also assessed. Additionally, application tests were carried out, which showed a positive effect of extracts and ferments on TEWL and skin hydration using a TEWAmeter and corneometer probe. The results obtained depended on the concentration used and the fermentation time.
Topics: Plant Extracts; Plant Leaves; Anti-Inflammatory Agents; Raphanus; Fermentation; Anti-Bacterial Agents; Humans; Antioxidants; Plant Roots; Fibroblasts; Kombucha Tea; Cyclooxygenase 2; Interleukin-1beta; Oxidative Stress
PubMed: 38891811
DOI: 10.3390/ijms25115622 -
Cells Jun 2024Over the past few decades, the worldwide incidence of cutaneous melanoma, a malignant neoplasm arising from melanocytes, has been increasing markedly, leading to the...
Over the past few decades, the worldwide incidence of cutaneous melanoma, a malignant neoplasm arising from melanocytes, has been increasing markedly, leading to the highest rate of skin cancer-related deaths. While localized tumors are easily removed by excision surgery, late-stage metastatic melanomas are refractory to treatment and exhibit a poor prognosis. Consequently, unraveling the molecular mechanisms underlying melanoma tumorigenesis and metastasis is crucial for developing novel targeted therapies. We found that the multiple endocrine neoplasia type 1 (MEN1) gene product Menin is required for the transforming growth factor beta (TGFβ) signaling pathway to induce cell growth arrest and apoptosis in vitro and prevent tumorigenesis in vivo in preclinical xenograft models of melanoma. We further identified point mutations in two MEN1 family members affected by melanoma that led to proteasomal degradation of the MEN1 gene product and to a loss of TGFβ signaling. Interestingly, blocking the proteasome degradation pathway using an FDA-approved drug and RNAi targeting could efficiently restore MEN1 expression and TGFβ transcriptional responses. Together, these results provide new potential therapeutic strategies and patient stratification for the treatment of cutaneous melanoma.
Topics: Melanoma; Humans; Transforming Growth Factor beta; Animals; Cell Line, Tumor; Signal Transduction; Mice; Neoplasm Metastasis; Proto-Oncogene Proteins; Apoptosis; Carcinogenesis; Skin Neoplasms; Proteasome Endopeptidase Complex; Cell Proliferation; Gene Expression Regulation, Neoplastic
PubMed: 38891107
DOI: 10.3390/cells13110973 -
Structural basis for an early stage of the photosystem II repair cycle in Chlamydomonas reinhardtii.Nature Communications Jun 2024Photosystem II (PSII) catalyzes water oxidation and plastoquinone reduction by utilizing light energy. It is highly susceptible to photodamage under high-light...
Photosystem II (PSII) catalyzes water oxidation and plastoquinone reduction by utilizing light energy. It is highly susceptible to photodamage under high-light conditions and the damaged PSII needs to be restored through a process known as the PSII repair cycle. The detailed molecular mechanism underlying the PSII repair process remains mostly elusive. Here, we report biochemical and structural features of a PSII-repair intermediate complex, likely arrested at an early stage of the PSII repair process in the green alga Chlamydomonas reinhardtii. The complex contains three protein factors associated with a damaged PSII core, namely Thylakoid Enriched Factor 14 (TEF14), Photosystem II Repair Factor 1 (PRF1), and Photosystem II Repair Factor 2 (PRF2). TEF14, PRF1 and PRF2 may facilitate the release of the manganese-stabilizing protein PsbO, disassembly of peripheral light-harvesting complexes from PSII and blockage of the Q site, respectively. Moreover, an α-tocopherol quinone molecule is located adjacent to the heme group of cytochrome b, potentially fulfilling a photoprotective role by preventing the generation of reactive oxygen species.
Topics: Photosystem II Protein Complex; Chlamydomonas reinhardtii; Thylakoids; Light-Harvesting Protein Complexes; Plant Proteins; Cytochrome b Group; Oxidation-Reduction; Reactive Oxygen Species; Light
PubMed: 38890314
DOI: 10.1038/s41467-024-49532-2