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BioRxiv : the Preprint Server For... Nov 2023UV light is a potent mutagen that induces bulky DNA damage in the form of cyclobutane pyrimidine dimers (CPDs). In eukaryotic cells, photodamage and other bulky lesions...
UV light is a potent mutagen that induces bulky DNA damage in the form of cyclobutane pyrimidine dimers (CPDs). In eukaryotic cells, photodamage and other bulky lesions occurring in nuclear genomes (nucDNAs) can be repaired through nucleotide excision repair (NER), where dual incisions on both sides of a damaged site precede the removal of a single-stranded oligonucleotide containing the damage. Mitochondrial genomes (mtDNAs) are also susceptible to damage from UV light, but current views hold that the only way to eliminate bulky DNA damage in mtDNAs is through mtDNA degradation. Damage-containing oligonucleotides excised during NER can be captured with anti-damage antibodies and sequenced (XR-seq) to produce high resolution maps of active repair locations following UV exposure. We analyzed previously published datasets from , and to identify reads originating from the mtDNA (and plastid genome in ). In and , the mtDNA-mapping reads have unique length distributions compared to the nuclear-mapping reads. The dominant fragment size was 26 nt in and 28 nt in with distinct secondary peaks occurring in 2-nt () or 4-nt () intervals. These reads also show a nonrandom distribution of di-pyrimidines (the substrate for CPD formation) with TT enrichment at positions 7-8 of the reads. Therefore, UV damage to mtDNA appears to result in production of DNA fragments of characteristic lengths and positions relative to the damaged location. We hypothesize that these fragments may reflect the outcome of a previously uncharacterized mechanism of NER-like repair in mitochondria or a programmed mtDNA degradation pathway.
PubMed: 37986892
DOI: 10.1101/2023.11.07.566130 -
Critical Reviews in Food Science and... Feb 2024Foodborne illnesses occur due to the contamination of fresh, frozen, or processed food products by some pathogens. Among several pathogens responsible for the illnesses,... (Review)
Review
Foodborne illnesses occur due to the contamination of fresh, frozen, or processed food products by some pathogens. Among several pathogens responsible for the illnesses, is one of the lethal bacteria that endangers public health. Several preexisting and novel technologies, especially non-thermal technologies are being studied for their antimicrobial effects, particularly toward . Some noteworthy emerging technologies include ultraviolet (UV) or light-emitting diode (LED), pulsed light, cold plasma, and ozonation. These technologies are gaining popularity since no heat is employed and undesirable deterioration of food quality, especially texture, and taste is devoided. This review aims to summarize the most recent advances in non-thermal processing technologies and their effect on inactivating in food products and on sanitizing packaging materials. These technologies use varying mechanisms, such as photoinactivation, photosensitization, disruption of bacterial membrane and cytoplasm, etc. This review can help food processing industries select the appropriate processing techniques for optimal benefits, in which the structural integrity of food can be preserved while simultaneously destroying present in foods. To eliminate spp., different technologies possess varying mechanisms such as rupturing the cell wall, formation of pyrimidine dimers in the DNA through photochemical effect, excitation of endogenous porphyrins by photosensitizers, generating reactive species, causing leakage of cellular contents and oxidizing proteins and lipids. These technologies provide an alternative to heat-based sterilization technologies and further development is still required to minimize the drawbacks associated with some technologies.
PubMed: 38380625
DOI: 10.1080/10408398.2024.2316295 -
Molecules (Basel, Switzerland) Jul 2023Diosmin is used to relieve chronic venous disease (CVD) symptoms. This study aimed to investigate the anti-inflammatory and antioxidant effects of...
Diosmin is used to relieve chronic venous disease (CVD) symptoms. This study aimed to investigate the anti-inflammatory and antioxidant effects of diosmetin-3--β-d-glucuronide, the major metabolite of diosmin, using human skin explants. The explants were exposed to substance P (inflammation model) or UVB irradiation (oxidative model) and to five diosmetin-3--β-d-glucuronide concentrations. Inflammation was evaluated through interleukin-8 (IL-8) secretion measurements and capillary dilation observation, and oxidation was evaluated by measuring the hydrogen peroxide levels and observing cyclobutane pyrimidine dimers (CPDs). In substance-P-exposed explants, diosmetin-3--β-d-glucuronide induced a significant decrease in IL-8 secretions, with a maximal effect at 2700 pg/mL (-49.6%), and it reduced the proportion of dilated capillaries and the mean luminal cross-sectional area ( < 0.0001 at all tested concentrations), indicating a vasoconstrictive effect. In UVB-irradiated fragments, diosmetin-3--β-d-glucuronide induced a significant decrease in hydrogen peroxide production and in the number of CPD-positive cells, reaching a maximal effect at the concentration of 2700 pg/mL (-48.6% and -52.0%, respectively). Diosmetin-3--β-d-glucuronide induced anti-inflammatory and antioxidant responses, with the maximal effect being reached at 2700 pg/mL and corresponding to the peak plasma concentration estimated after the oral intake of 600 mg of diosmin, the daily dose usually recommended for the treatment of CVD. These ex vivo findings suggest a protective role of diosmetin-3--β-d-glucuronide against inflammatory and oxidative stress affecting the vascular system in CVD pathophysiology.
Topics: Humans; Antioxidants; Glucuronides; Diosmin; Hydrogen Peroxide; Interleukin-8; Anti-Inflammatory Agents; Inflammation; Cardiovascular Diseases
PubMed: 37513462
DOI: 10.3390/molecules28145591 -
International Journal of Molecular... Dec 2023Chronic exposure to ultraviolet (UV) radiation is known to induce the formation of DNA photo-adducts, including cyclobutane pyrimidine dimers (CPDs) and Dewar valence...
Chronic exposure to ultraviolet (UV) radiation is known to induce the formation of DNA photo-adducts, including cyclobutane pyrimidine dimers (CPDs) and Dewar valence derivatives (DVs). While CPDs usually occur at higher frequency than DVs, recent studies have shown that the latter display superior selectivity and significant stability in interaction with the human DNA/topoisomerase 1 complex (TOP1). With the aim to deeply investigate the mechanism of interaction of DVs with TOP1, we report here four all-atom molecular dynamic simulations spanning one microsecond. These simulations are focused on the stability and conformational changes of two DNA/TOP1-DV complexes in solution, the data being compared with the biomimetic thymine dimer counterparts. Results from root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) analyses unequivocally confirmed increased stability of the DNA/TOP1-DV complexes throughout the simulation duration. Detailed interaction analyses, uncovering the presence of salt bridges, hydrogen bonds, water-mediated interactions, and hydrophobic interactions, as well as pinpointing the non-covalent interactions within the complexes, enabled the identification of specific TOP1 residues involved in the interactions over time and suggested a potential TOP1 inhibition mechanism in action.
Topics: Humans; Molecular Dynamics Simulation; DNA Topoisomerases, Type I; Biomimetics; DNA Adducts; Data Interpretation, Statistical; Pyrimidine Dimers
PubMed: 38203410
DOI: 10.3390/ijms25010234 -
Structure-specific DNA endonuclease T7 endonuclease I cleaves DNA containing UV-induced DNA lesions.Journal of Biochemistry Jul 2024The T7 gene 3 product, T7 endonuclease I, acts on various substrates with DNA structures, including Holliday junctions, heteroduplex DNAs and single-mismatch DNAs....
The T7 gene 3 product, T7 endonuclease I, acts on various substrates with DNA structures, including Holliday junctions, heteroduplex DNAs and single-mismatch DNAs. Genetic analyses have suggested the occurrence of DNA recombination, replication and repair in Escherichia coli. In this study, T7 endonuclease I digested UV-irradiated covalently closed circular plasmid DNA into linear and nicked plasmid DNA, suggesting that the enzyme generates single- and double-strand breaks (SSB and DSB). To further investigate the biochemical functions of T7 endonuclease I, we have analysed endonuclease activity in UV-induced DNA substrates containing a single lesion, cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts (6-4PP). Interestingly, the leading cleavage site for CPD by T7 endonuclease I is at the second and fifth phosphodiester bonds that are 5' to the lesion of CPD on the lesion strand. However, in the case of 6-4PP, the cleavage pattern on the lesion strand resembled that of CPD, and T7 endonuclease I could also cleave the second phosphodiester bond that is 5' to the adenine-adenine residues opposite the lesion, indicating that the enzyme produces DSB in DNA containing 6-4PP. These findings suggest that T7endonuclease I accomplished successful UV damage repair by SSB in CPD and DSB in 6-4PP.
Topics: Ultraviolet Rays; DNA Damage; Deoxyribonuclease I; DNA; Escherichia coli; Bacteriophage T7; Pyrimidine Dimers; DNA Repair
PubMed: 38426948
DOI: 10.1093/jb/mvae024 -
Scientific Reports Apr 2024Mutations in PINK1 and Parkin cause early-onset Parkinson's Disease (PD). PINK1 is a kinase which functions as a mitochondrial damage sensor and initiates mitochondrial...
Mutations in PINK1 and Parkin cause early-onset Parkinson's Disease (PD). PINK1 is a kinase which functions as a mitochondrial damage sensor and initiates mitochondrial quality control by accumulating on the damaged organelle. There, it phosphorylates ubiquitin, which in turn recruits and activates Parkin, an E3 ubiquitin ligase. Ubiquitylation of mitochondrial proteins leads to the autophagic degradation of the damaged organelle. Pharmacological modulation of PINK1 constitutes an appealing avenue to study its physiological function and develop therapeutics. In this study, we used a thermal shift assay with insect PINK1 to identify small molecules that inhibit ATP hydrolysis and ubiquitin phosphorylation. PRT062607, an SYK inhibitor, is the most potent inhibitor in our screen and inhibits both insect and human PINK1, with an IC in the 0.5-3 µM range in HeLa cells and dopaminergic neurons. The crystal structures of insect PINK1 bound to PRT062607 or CYC116 reveal how the compounds interact with the ATP-binding pocket. PRT062607 notably engages with the catalytic aspartate and causes a destabilization of insert-2 at the autophosphorylation dimer interface. While PRT062607 is not selective for PINK1, it provides a scaffold for the development of more selective and potent inhibitors of PINK1 that could be used as chemical probes.
Topics: Humans; Protein Kinases; HeLa Cells; Ubiquitin-Protein Ligases; Phosphorylation; Ubiquitin; Adenosine Triphosphate; Cyclohexylamines; Pyrimidines
PubMed: 38565869
DOI: 10.1038/s41598-024-58285-3 -
Genetics May 2024UV light is a potent mutagen that induces bulky DNA damage in the form of cyclobutane pyrimidine dimers (CPDs). Photodamage and other bulky lesions occurring in nuclear...
UV light is a potent mutagen that induces bulky DNA damage in the form of cyclobutane pyrimidine dimers (CPDs). Photodamage and other bulky lesions occurring in nuclear genomes can be repaired through nucleotide excision repair (NER), where incisions on both sides of a damaged site precede the removal of a single-stranded oligonucleotide containing the damage. Mitochondrial genomes (mtDNAs) are also susceptible to damage from UV light, but current evidence suggests that the only way to eliminate bulky mtDNA damage is through mtDNA degradation. Damage-containing oligonucleotides excised during NER can be captured with anti-damage antibodies and sequenced (XR-seq) to produce high resolution maps of active repair locations following UV exposure. We analyzed previously published datasets from Arabidopsis thaliana, Saccharomyces cerevisiae, and Drosophila melanogaster to identify reads originating from the mtDNA (and plastid genome in A. thaliana). In A. thaliana and S. cerevisiae, the mtDNA-mapping reads have unique length distributions compared to the nuclear-mapping reads. The dominant fragment size was 26 nt in S. cerevisiae and 28 nt in A. thaliana with distinct secondary peaks occurring in regular intervals. These reads also show a nonrandom distribution of di-pyrimidines (the substrate for CPD formation) with TT enrichment at positions 7-8 of the reads. Therefore, UV damage to mtDNA appears to result in production of DNA fragments of characteristic lengths and positions relative to the damaged location. The mechanisms producing these fragments are unclear, but we hypothesize that they result from a previously uncharacterized DNA degradation pathway or repair mechanism in mitochondria.
PubMed: 38722894
DOI: 10.1093/genetics/iyae070 -
Journal of Cosmetic Dermatology Mar 2024UV skin exposure is an important matter of public health, as the worldwide rising prevalence of skin cancers indicates. However, a wide majority of commercially...
BACKGROUND
UV skin exposure is an important matter of public health, as the worldwide rising prevalence of skin cancers indicates. However, a wide majority of commercially available sunscreens are responsible for ocean ecosystem damages such as coral reef degradation and phytoplankton mortality.
AIMS
To answer the urge for new eco-friendly UV filters, we studied the use of lecithin-based multilamellar liposomes (MLLs) of controlled size and elasticity as a bio-sourced and biodegradable alternative to classic sunscreens. These parameters control allows different skin layers targeting.
METHODS
The performance of two different MLLs compositions and a commercially available SPF50+ water-resistant liposomal sunscreen was compared on skin explants. SC-MLLs target the stratum corneum and Epi-MLLs the whole epidermis. Preparations were applied prior to skin irradiation. Their efficiencies were evaluated histologically (hematoxylin and eosin staining plus cyclobutane pyrimidine dimer [CPD] immunostaining) and by skin barrier quality assessment (trans-epithelial electrical resistance). Adhesiveness to the skin was also investigated.
RESULTS
Altogether, ex vivo results indicate MLLs offer a solar protection as effective as a SPF50+ water-resistant liposomal sunscreen but with a better skin adhesiveness and an improved skin barrier function.
CONCLUSION
Lecithin-based MLLs of controlled physicochemical parameters can be used as a new eco-friendly and water-resistant agent for solar protection. The stratum corneum targeted action of SC-MLLs appears to be more interesting, as SC-MLLs exhibit an overall better performance than Epi-MLLs at a lower cost. The skin barrier improvement showcased could be of interest to people suffering from dry skin or skin barrier impairment related disease.
Topics: Humans; Sunscreening Agents; Liposomes; Lecithins; Water; Ecosystem; Ultraviolet Rays; Skin
PubMed: 37947116
DOI: 10.1111/jocd.16072 -
Journal of Drugs in Dermatology : JDD May 2024This study aimed to investigate the ultraviolet (UV) protection/repair benefits of a patented Amino Acid Complex (AAComplex).
OBJECTIVE
This study aimed to investigate the ultraviolet (UV) protection/repair benefits of a patented Amino Acid Complex (AAComplex).
METHODS
I) AAComplex was incubated with dermal fibroblasts, with/without UVA, and collagen I was measured with a GlasBoxPlus device. II) A lotion, with/without AAComplex (1%) was applied topically to skin explants, following UVA irradiation, and quantified for health-related biomarkers (TNFalpha, histamine, and MMP-1). III) A broad spectrum sunscreen with SPF 46 and a skincare serum containing AAComplex (2%) were assessed using epidermal equivalents, in the presence of UV irradiation, for effects on IL-1alpha, thymine dimers, Ki-67, filaggrin and Nrf2.
RESULTS
I) Collagen I synthesis in dermal fibroblasts was significantly decreased after UVA compared to without UV. The presence of AAComplex prevented this decrease. II) UVA irradiation of skin explants increased histamine, TNFα, and MMP-1. Hydrocortisone aceponate cream significantly decreases all 3 biomarkers. AAComplex contained lotion also significantly decreased all 3 biomarkers, the no AAComplex control lotion only reduced histamine. III) With the regimen of sunscreen + AAComplex contained skincare serum, the significant reduction in IL-1alpha was observed along with a complete recovery of Ki-67 and stimulation of filaggrin and Nrf2T. No thymine dimer positive cell was observed indicating the most positive skin impact from the regiment. Conclusion: This research using different human skin models demonstrated that AAComplex can provide protection and damage repair caused by UV, at the ingredient level also when formulated in a serum or lotion formula. Skin may be best protected from UV damage when the regimen is used. J Drugs Dermatol. 2024;23(5):366-375. doi:10.36849/JDD.7916.
Topics: Humans; Filaggrin Proteins; Ultraviolet Rays; Fibroblasts; Matrix Metalloproteinase 1; Tumor Necrosis Factor-alpha; Skin; Sunscreening Agents; Amino Acids; Interleukin-1alpha; Histamine; Skin Cream; Biomarkers; Collagen Type I; Intermediate Filament Proteins; Ki-67 Antigen; Pyrimidine Dimers; Cells, Cultured; NF-E2-Related Factor 2
PubMed: 38709706
DOI: 10.36849/JDD.7916 -
Food & Function Sep 2023ζ-Carotene is a key intermediate in the carotenoid pathway, but owing to its low content and difficulties in isolation, its application is restricted. In this study,...
ζ-Carotene is a key intermediate in the carotenoid pathway, but owing to its low content and difficulties in isolation, its application is restricted. In this study, three genes (, , and ) in the carotenoid pathway of Antarctic moss were identified, recombined, and expressed in () BL21(DE3). The expression product was identified as one of the ζ-carotenes by UV absorbance spectrum, thin layer chromatography (TLC), and super-high-performance liquid chromatography-mass spectrum (UPLC-MS), and was called a ζ-carotene-like compound (CLC). Excessive exposure to ultraviolet B (UVB) irradiation is one of the main risk factors for skin photodamage. The purpose of this study was to investigate the preventive and therapeutic effects of CLC on UVB-induced skin photodamage in mice. In this paper, through histological examinations (hematoxylin-eosin, HE; Masson and TdT-mediated dUTP Nick-End Labeling, Tunel), biochemical index detection (reactive oxygen species, ROS; inflammatory factors; cyclobutyl pyrimidine dimers, CPDs and hyaluronic acid, HA), quantitative real time polymerase chain reaction (qRT-PCR), immunohistochemistry and intestinal content flora, , it is concluded that CLC has the potential to enhance skin antioxidant capacity by activating the nuclear transcription factor/antioxidant reaction element (Nrf2/ARE) pathway and also reduce skin inflammation and aging by inhibiting the mitogen-activated protein kinase (MAPK) pathway. Moreover, the regulation of intestinal flora may potentially mitigate skin damage induced by UVB radiation. This research not only developed a green and sustainable platform for the efficient synthesis of CLC but also laid a foundation for its application in functional food and medicine for skin resistance against UVB damage.
Topics: Animals; Mice; zeta Carotene; Antioxidants; Chromatography, Liquid; Escherichia coli; Gastrointestinal Microbiome; Tandem Mass Spectrometry; Inflammation; Carotenoids
PubMed: 37606633
DOI: 10.1039/d3fo02502k