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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 -
Nucleic Acids Research Dec 2023Ultraviolet light generates cyclobutane pyrimidine dimer (CPD) and pyrimidine 6-4 pyrimidone (6-4PP) photoproducts that cause skin malignancies if not repaired by...
Ultraviolet light generates cyclobutane pyrimidine dimer (CPD) and pyrimidine 6-4 pyrimidone (6-4PP) photoproducts that cause skin malignancies if not repaired by nucleotide excision repair (NER). While the faster repair of the more distorting 6-4PPs is attributed mainly to more efficient recognition by XPC, the XPD lesion verification helicase may play a role, as it directly scans the damaged DNA strand. With extensive molecular dynamics simulations of XPD-bound single-strand DNA containing each lesion outside the entry pore of XPD, we elucidate strikingly different verification processes for these two lesions that have very different topologies. The open book-like CPD thymines are sterically blocked from pore entry and preferably entrapped by sensors that are outside the pore; however, the near-perpendicular 6-4PP thymines can enter, accompanied by a displacement of the Arch domain toward the lesion, which is thereby tightly accommodated within the pore. This trapped 6-4PP may inhibit XPD helicase activity to foster lesion verification by locking the Arch to other domains. Furthermore, the movement of the Arch domain, only in the case of 6-4PP, may trigger signaling to the XPG nuclease for subsequent lesion incision by fostering direct contact between the Arch domain and XPG, and thereby facilitating repair of 6-4PP.
Topics: Humans; DNA; DNA Damage; DNA Helicases; DNA Repair; Pyrimidine Dimers; Ultraviolet Rays
PubMed: 37933861
DOI: 10.1093/nar/gkad974 -
Photochemistry and Photobiology 2024Xeroderma pigmentosum (XP) variant cells are deficient in the translesion synthesis (TLS) DNA polymerase Polη (eta). This protein contributes to DNA damage tolerance,...
Xeroderma pigmentosum (XP) variant cells are deficient in the translesion synthesis (TLS) DNA polymerase Polη (eta). This protein contributes to DNA damage tolerance, bypassing unrepaired UV photoproducts and allowing S-phase progression with minimal delay. In the absence of Polη, backup polymerases perform TLS of UV lesions. However, which polymerase plays this role in human cells remains an open question. Here, we investigated the potential role of Polι (iota) in bypassing ultraviolet (UV) induced photoproducts in the absence of Polη, using NER-deficient (XP-C) cells knocked down for Polι and/or Polη genes. Our results indicate that cells lacking either Polι or Polη have increased sensitivity to UVC radiation. The lack of both TLS polymerases led to increased cell death and defects in proliferation and migration. Loss of both polymerases induces a significant replication fork arrest and G1/S-phase blockage, compared to the lack of Polη alone. In conclusion, we propose that Polι acts as a bona fide backup for Polη in the TLS of UV-photoproducts.
Topics: Humans; DNA Polymerase iota; DNA Damage; Translesion DNA Synthesis; DNA Replication; Xeroderma Pigmentosum; Ultraviolet Rays; DNA Repair
PubMed: 37926965
DOI: 10.1111/php.13879 -
Chemical Communications (Cambridge,... Nov 2023Nucleic acids can be damaged by ultraviolet (UV) irradiation, forming structural photolesions such as cyclobutane-pyrimidine-dimers (CPD). In modern organisms,...
Nucleic acids can be damaged by ultraviolet (UV) irradiation, forming structural photolesions such as cyclobutane-pyrimidine-dimers (CPD). In modern organisms, sophisticated enzymes repair CPD lesions in DNA, but to our knowledge, no RNA-specific enzymes exist for CPD repair. Here, we show for the first time that RNA can protect itself from photolesions by an intrinsic UV-induced self-repair mechanism. This mechanism, prior to this study, has exclusively been observed in DNA and is based on charge transfer from CPD-adjacent bases. In a comparative study, we determined the quantum yields of the self-repair of the CPD-containing RNA sequence, GAU = U to GAUU (0.23%), and DNA sequence, d(GAT = T) to d(GATT) (0.44%), upon 285 nm irradiation UV/Vis spectroscopy and HPLC analysis. After several hours of irradiation, a maximum conversion yield of ∼16% for GAU = U and ∼33% for d(GAT = T) was reached. We examined the dynamics of the intermediate charge transfer (CT) state responsible for the self-repair with ultrafast UV pump - IR probe spectroscopy. In the dinucleotides GA and d(GA), we found comparable quantum yields of the CT state of ∼50% and lifetimes on the order of several hundred picoseconds. Charge transfer in RNA strands might lead to reactions currently not considered in RNA photochemistry and may help understanding RNA damage formation and repair in modern organisms and viruses. On the UV-rich surface of the early Earth, these self-stabilizing mechanisms likely affected the selection of the earliest nucleotide sequences from which the first organisms may have developed.
Topics: Pyrimidine Dimers; DNA Repair; RNA; DNA; Ultraviolet Rays; DNA Damage
PubMed: 37899697
DOI: 10.1039/d3cc04013e -
JID Innovations : Skin Science From... Nov 2023Sunscreens have been shown to protect against UVR-induced DNA damage in human skin under laboratory conditions. We presently extended these observations to real-life...
Sunscreens have been shown to protect against UVR-induced DNA damage in human skin under laboratory conditions. We presently extended these observations to real-life conditions in volunteers after their ordinary exposure habits during summer holidays. Volunteers were randomly assigned to a control group and an educated group supplied with a SPF ≥50 sunscreen and receiving instructions for use. A questionnaire was used to determine the extent of exposure. No difference in average solar UVR exposure was found between the two groups. DNA photoprotection was first assessed by, to our knowledge, a previously unreported noninvasive assay on the basis of the quantification of pyrimidine dimers released by DNA repair in urine. Damage was also quantified in the nuclear DNA extracted from the roof of suction blisters collected after recreational exposure. The urinary concentration of photoproducts was significantly higher in the control than in the educated group. The same trend was observed for the level of photoproducts in the DNA from suction blisters. The unambiguous observation of an efficient photoprotection against DNA damage afforded by sunscreen under real-life conditions provides strong support for the efficiency of the sunscreens. In addition, the results validate the use of urinary DNA photoproducts as a noninvasive assay applicable to photoprotection.
PubMed: 37886699
DOI: 10.1016/j.xjidi.2023.100227 -
Physiologia Plantarum 2023The single-stranded DNA/RNA binding protein WHIRLY1 is a major chloroplast nucleoid-associated protein required for the compactness of nucleoids. Most nucleoids in...
The single-stranded DNA/RNA binding protein WHIRLY1 is a major chloroplast nucleoid-associated protein required for the compactness of nucleoids. Most nucleoids in chloroplasts of WHIRLY1-knockdown barley plants are less compact compared to nucleoids in wild-type plants. The reduced compaction leads to an enhanced optical cross-section, which may cause the plastid DNA to be a better target for damaging UV-B radiation. To investigate this hypothesis, primary foliage leaves, chloroplasts, and nuclei from wild-type and WHIRLY1-knockdown plants were exposed to experimental UV-B radiation. Thereafter, total, genomic and plastid DNA were isolated, respectively, and analyzed for the occurrence of cyclobutane pyrimidine dimers (CPDs), which is a parameter for genome stability. The results of this study revealed that WHIRLY1-deficient chloroplasts had strongly enhanced DNA damages, whereas isolated nuclei from the same plant line were not more sensitive than nuclei from the wild-type, indicating that WHIRLY1 has different functions in chloroplasts and nucleus. This supports the hypothesis that the compaction of nucleoids may provide protection against UV-B radiation.
Topics: Pyrimidine Dimers; Plant Proteins; Chloroplasts; Ultraviolet Rays; DNA
PubMed: 37882276
DOI: 10.1111/ppl.14049 -
Zhonghua Gan Zang Bing Za Zhi =... Sep 2023To evaluate the role and molecular mechanism of Nei endonuclease VIII-like protein 3 (NEIL3) in hepatocellular carcinoma (HCC) through The Cancer Genome Atlas database....
To evaluate the role and molecular mechanism of Nei endonuclease VIII-like protein 3 (NEIL3) in hepatocellular carcinoma (HCC) through The Cancer Genome Atlas database. RNA sequencing of HCC samples was the first step in determining the level of gene NEIL3 expression in normal tissues and tumors. Then, NEIL3 was used for the Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes, gene enrichment analysis, immune cell infiltration analysis. The samples were divided into high and low expression groups according to the median expression level of NEIL3 in liver cancer tissues. Logistic regression analysis, Kaplan-Meier analysis, univariate and multivariate Cox regression analysis, and a nomogram prognostic model were used to explore the clinical and prognostic significance of NEIL3 in HCC. Compared with normal samples, NEIL3 was highly expressed in most malignant tumors, including HCC ( < 0.05). High expression of NEIL3 was related to cell cycle, DNA replication, and cell receptor pathways. In addition, the high expression of NEIL3 was significantly positively correlated with T-helper 2 lymphocytes and infiltration levels ( = 0.670, < 0.001). Compared with the NEIL3 low expression group, the NEIL3 high expression group had a higher level of Th2 cell infiltration in tumor tissues ( < 0.001). Logistic regression analysis showed that NEIL3 overexpression was associated with high T stage, high pathological stage, high tissue grade, AFP > 400 μg/L and vascular invasion of HCC. The Kaplan-Meier analysis results showed that overall survival [hazard ratio () = 2.53, < 0.001)], disease-specific survival ( = 2.52, < 0.001), and progression-free interval ( = 1.82, < 0.001) in patients with HCC with high NEIL3 expression were unfavorable. Cox regression analysis results showed that high NEIL3 expression was an independent risk factor for an unfavorable prognosis in HCC patients ( = 0.002). The nomogram and calibration chart further demonstrated that high NEIL3 expression was one of the risk factors for an unfavorable prognosis in HCC patients. Elevated expression of NEIL3 is associated with an unfavorable prognosis and an increased proportion of immune cells in HCC, and it is likely to be used as a potential biomarker for evaluating the prognosis and immune infiltration level.
Topics: Humans; Carcinoma, Hepatocellular; Deoxyribonuclease (Pyrimidine Dimer); Liver Neoplasms; Prognosis
PubMed: 37872095
DOI: 10.3760/cma.j.cn501113-20220108-00009 -
ACS Omega Oct 2023UV1C is an enzymatically active DNA sequence (deoxyribozyme, DNAzyme) that functions as a cyclobutane pyrimidine dimer (CPD) photolyase. UV1C forms parallel guanine...
UV1C is an enzymatically active DNA sequence (deoxyribozyme, DNAzyme) that functions as a cyclobutane pyrimidine dimer (CPD) photolyase. UV1C forms parallel guanine quadruplexes (G-quadruplexes) with a DNA substrate in the presence of 240 mM Na, the structure of which is important for the enzymatic activity. To investigate the repair mechanism of CPD by UV1C, we designed light-induced Fourier transform infrared (FTIR) spectroscopy. Prior to FTIR measurements, circular dichroism (CD) spectroscopy was conducted to determine the Na concentration at which the most G-quadruplexes were formed. We found that UV1C also forms a hybrid G-quadruplex structure at over 500 mM Na. By assuming a concentration equilibrium between G-quadruplexes and Na, 1.3 and 1.8 Na were found to bind to parallel and hybrid G-quadruplexes, respectively. The hybrid G-quadruplex form of UV1C was also suggested to exhibit photolyase activity. Light-induced FTIR spectra recorded upon the photorepair of CPD by UV1C were compared for parallel G-quadruplex-rich and hybrid G-quadruplex-rich samples. Spectral variations were indicative of structural differences in parallel and hybrid G-quadruplexes before and after CPD cleavage. Differences were also observed when compared to the CPD repair spectrum by CPD photolyase. The spectral differences during CPD repair by either protein or DNAzyme suggest the local environment of the substrates, the surrounding protein, or the aqueous solution.
PubMed: 37841180
DOI: 10.1021/acsomega.3c05083 -
International Journal of Molecular... Sep 2023Multiple polyposes are heterogeneous diseases with different underlying molecular backgrounds, sharing a common symptom: the presence of transforming into cancerous...
Multiple polyposes are heterogeneous diseases with different underlying molecular backgrounds, sharing a common symptom: the presence of transforming into cancerous intestinal polyps. Recent reports have indicated biallelic mutations in the gene, which is involved in base excision repair (BER), as predisposing to an elevated risk of colorectal cancer (CRC). We aimed to evaluate the significance of the p.Q82* truncating variant in predisposition to intestinal polyposis by assessing its frequency in polyposis patients. We genotyped 644 Polish patients and 634 control DNA samples using high-resolution melting analysis (HRM) and Sanger sequencing. We found the p.Q82* variant in four polyposis patients; in three, it was homozygous (OR = 6.90, value = 0.202). Moreover, the p.R92C mutation was detected in one patient. We also looked more closely at the disease course in patients carrying mutations. Two homozygous patients also presented other neoplasia. In the family case, we noticed the earlier presence of polyps in the proband and early hepatoblastoma in his brother. We cannot univocally confirm the relationship of p.Q82* with an increased risk of CRC. However, homozygous p.Q82* was more frequent by 10-fold in patients without other mutations identified, which makes gene screening in this group reasonable.
Topics: Male; Humans; Adenomatous Polyposis Coli; Poland; Genetic Predisposition to Disease; Colorectal Neoplasms; Mutation; Deoxyribonuclease (Pyrimidine Dimer)
PubMed: 37834005
DOI: 10.3390/ijms241914548 -
Frontiers in Immunology 2023Chronic metabolic changes relevant to human immunodeficiency virus type 1 (HIV-1) infection and in response to antiretroviral therapy (ART) remain undetermined....
BACKGROUND
Chronic metabolic changes relevant to human immunodeficiency virus type 1 (HIV-1) infection and in response to antiretroviral therapy (ART) remain undetermined. Moreover, links between metabolic dysfunction caused by HIV and immunological inflammation in long-term treated individuals have been poorly studied.
METHODS
Untargeted metabolomics and inflammatory cytokine levels were assessed in 47 HIV-infected individuals including 22 immunological responders (IRs) and 25 non-responders (INRs) before and after ART. The IRs and INRs were matched by age, gender, baseline viral load, and baseline CD4+T cell counts. Another 25 age-matched uninfected healthy individuals were also included as controls.
RESULTS
Among the 770 plasma compounds detected in the current study, significant changes were identified in lipids, nucleotides, and biogenic amino acids between HIV-infected patients and healthy controls. Principal Component Analysis (PCA) and the Random Forest (RF) model suggested that levels of selected metabolites could differentiate HIV-infected patients clearly from healthy controls. However, the metabolite profiles identified in our patients were similar, and only three metabolites, maltotetraose, N, N-dimethyl-5-aminovalerate, and decadienedioic acid (C10:2-DC), were different between IRs and INRs following long-term ART. The pathway enrichment analysis results revealed that disturbances in pyrimidine metabolism, sphingolipid metabolism, and purine metabolism after HIV infection and these changes did not recover to normal levels in healthy controls even with suppressive ART. Correlation analysis of the metabolism-immune network indicated that interleukin (IL)-10, D-dimer, vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and TNF-RII were positively correlated with most of the significantly changed lipid and amino acid metabolites but negatively correlated with metabolites in nucleotide metabolism.
CONCLUSIONS
Significant changes in many metabolites were observed in HIV-infected individuals before and after ART regardless of their immunological recovery status. The disturbed metabolic profiles of lipids and nucleotides in HIV infection did not recover to normal levels even after long-term ART. These changes are correlated with modified cytokines and biomarkers of chronic non-AIDS events, warranting tryout of interventions other than ART.
Topics: Humans; HIV Infections; HIV-1; CD4-Positive T-Lymphocytes; Lipids; Nucleotides
PubMed: 37828979
DOI: 10.3389/fimmu.2023.1254155