A new bacteriophage, vB_KpnM_KP1, was identified and characterized, exhibiting a strong lytic effect on Klebsiella pneumoniae. Host range analysis revealed its effectiveness against 77.4% of clinical strains, achieving complete lysis of those associated with urinary tract infections (UTIs). Phage stability tests demonstrated that vB_KpnM_KP1 remained stable at neutral pH and across all tested temperatures. However, inactivation was observed at high ethanol concentrations and extreme pH levels. Transmission electron microscopy (TEM) analysis identified vB_KpnM_KP1 as a Myo-type phage with an icosahedral head and a contractile tail. Moreover, genome annotation of vB_KpnM_KP1 revealed a linear DNA genome of 174,802 bp, containing 307 open reading frames. Functional predictions suggest the presence of genes involved in DNA replication, transcription, morphogenesis, and cell lysis. Phylogenetic analysis classified vB_KpnM_KP1 within the Slopekvirus genus of the Straboviridae family, showing high sequence identity with phages that infect Enterobacter, Escherichia and Klebsiella species. These findings highlight the potential of phage vB_KpnM_KP1 as an alternative treatment for multidrug-resistant K. pneumoniae infections, particularly in UTIs, while offering valuable insights into its stability and genetic composition.

Proteins in aerosols can undergo multiphase reactions when exposed to air pollutants like ozone (O3) and nitrogen dioxide (NO2), posing adverse impacts on the environment and human health. The influence of radiation on the reactions has not been thoroughly studied and the reaction mechanism remains unclear. We coated bovine serum albumin (BSA) in a flow tube and exposed it to different combinations of O3 and NO2 under dark and ultraviolet (UV) radiation conditions. The results showed that O3 could significantly promote the degradation, nitration and oligomerization of BSA, indicating that O3 is the primary driver of the multiphase reactions. We found that UV enhanced protein degradation after exposure to NO2 and O3. Meanwhile, UV also enhanced the nitration and oligomerization of protein by NO2. When exposed to NO2 and O3, the effects of nitration and oligomerization on tyrosine residues of BSA were also investigated. Nitrated tyrosine (NTyr) levels were always higher than those of cross-linked tyrosine (DiTyr), highlighting the dominance of nitration in modification reactions. However, the negative influence of UV radiation on protein nitration and oligomerization of BSA was observed in our exposure experiment. We propose that UV radiation-induced degradation may be an important factor to suppress nitration and oligomerization via the breakage of nitrated and oligomerized protein products. This work provides the dataset and knowledge by laboratory exposure to emphasize the possible role of radiation in the multiphase reactions of proteins in the atmosphere, which will help to gain a better understanding of reaction mechanisms.

Hypersaline environments, including brines and brine inclusions of evaporite crystals, are currently of great interest due to their unique preservation properties for the search for terrestrial and potentially extraterrestrial biosignatures of ancient life. However, much is still unclear about the specific effects that dictate the preservation properties of brines. Here we present the first insights into the preservation of cell envelope fragments in brines, characterizing the relative contributions of brine composition, UV photochemistry, and cellular macromolecules on biosignature preservation. Cell envelopes from the model halophile Halobacterium salinarum were used to simulate dead microbial cellular remains in hypersaline environments based on life as we currently know it. Using different Early Earth and Mars analogue brines, we show that acidic and NaCl-dominated brine compositions are more predisposed to preserving complex biosignatures from UV degradation, but that the composition of the biological material also influences this preservation. Furthermore, a combinatory effect between chaotropicity and photochemistry occurs, with the relative importance of each being brine-specific. These results provide an experimental framework for biosignature detection in hypersaline environments, emphasizing the need for laboratory simulations to evaluate preservation properties of each potential brine environment, on Earth and elsewhere in the solar system.

Cataracts are the leading cause of reversible blindness worldwide, primarily associated with the aggregation of proteins such as γ-crystallins, which are essential for maintaining lens transparency. Among these, human γD-crystallin (HγD) contains four conserved tryptophans, hypothesized to act as a protective mechanism against ultraviolet (UV) radiation. This study investigated the effects of low-dose UV-B radiation on HγD and its variants, in which each tryptophan was replaced by phenylalanine. The substitutions did not significantly affect the protein's secondary or tertiary structure but markedly reduced thermal stability, particularly in the W42F mutant. Aggregation kinetics were accelerated in all variants, with pronounced increases observed in the W130F and W156F mutants. Molecular dynamics simulations revealed that these substitutions disrupt hydrophobic interactions in both the N- and C-terminal domains, promoting instability and enhancing aggregation propensity. UV radiation induced chemical modifications, where Trp42 and Trp130 were the most affected, further driving aggregation. Changes in fluorescence spectra after UV exposure indicated the breakdown of the tryptophan indole ring and the formation of degradation products. These results confirm that tryptophans in HγD serve a crucial protective role against UV-induced damage by preserving structural stability and minimizing aggregation.

The multi-subunit pyruvate dehydrogenase complex (PDC) plays a crucial role in glucose oxidation as it determines whether pyruvate is used for mitochondrial oxidative phosphorylation or is converted to lactate for aerobic glycolysis. PDC contains multiple lipoic acid groups, covalently attached at lysine residues to give lipoyllysine, which are responsible for acyl group transfer and critical to complex activity. We have recently reported that both free lipoic acid, and lipoyllysine in alpha-keto glutarate dehydrogenase, are highly susceptible to singlet oxygen (1O2)-induced oxidation. We therefore hypothesized that PDC activity and structure would be influenced by 1O2 (generated using Rose Bengal and light) via modification of the lipoyllysines and other residues. PDC activity was decreased by photooxidation, with this being dependent on light exposure, O2, the presence of Rose Bengal, and D2O consistent with 1O2-mediated reactions. These changes were modulated by pre-illumination addition of free lipoic acid and lipoamide. Activity loss occurred concurrently with lipoyllysine and sidechain modification (determined by mass spectrometry) and protein aggregation (detected by SDS-PAGE). Peptide mass mapping provided evidence for modification at 42 residues (Met, Trp, His and Tyr; with modification extents of 20-50 %) and each of the lipoyllysine sites (6-20 % modification). Structure modelling indicated the modifications occur across all 4 subunit types, and occur in functional domains or at multimer interfaces, consistent with damage at multiple sites contributing to the overall loss of activity. These data indicate that PDC activity and structure are susceptible to 1O2-induced damage with potential effects on cellular pathways of glucose metabolism.

Pterin (Ptr) is the model compound of aromatic pterins, which are efficient photosensitizers present in human skin and are able to oxidize biomolecules upon UVA irradiation. Photosensitization involves chemical alteration of a biomolecule as a result of the initial absorption of radiation by another chemical species, the photosensitizer. Under anaerobic conditions, Ptr reacts with thymine (T) to form photoadducts (T-Ptr). In this work, we present a method to prepare and purify T-Ptr adducts, using 2'-deoxythymidine 5'-monophosphate (dTMP) and single stranded oligonucleotide 5'-d(TTTTT)-3' (dT5), and investigate their photosensitizing properties. Interestingly, the Ptr moiety, when attached to T, retains its photophysical properties. The adduct dTMP-Ptr, upon excitation, forms singlet and triplet excited states, the latter being capable of transferring energy to dissolved O2 and generating singlet oxygen, with an efficiency similar to Ptr. In air-equilibrated solutions, both dTMP-Ptr and dT5-Ptr adducts can photosensitize the oxidation of tryptophan and 2'-deoxyguanosine 5'-monophosphate, two of the main targets of photosensitization in biological systems, with efficiencies close to that of free Ptr. The mechanisms involved in the oxidation of biomolecules can be either type I (electron transfer) or type II (singlet oxygen).

The discovery of useful synthetic transformations has made light-mediated catalysis, a widely employed method in chemical synthesis. Since the catalyst, light source, and substrate needed to produce a photoredox reaction are the same as those needed for photosensitization, photoredox reactions are perfect for examining biological surroundings. An attempt has been made to cover the development of future-oriented catalysts and the therapeutic use of photosensitization. New applications of photoredox catalytic techniques for investigating intricate biological environments in living cells and protein bioconjugation is also discussed.

Different from reversible agonist-stimulated receptor activation, singlet oxygen oxidation activates permanently G protein-coupled receptor (GPCR) cholecystokinin 1 (CCK1R) in type II photodynamic action, with soluble photosensitizer dyes (sulphonated aluminum phthalocyanine, λmax 675 nm) or genetically encoded protein photosensitizers (KillerRed λmax 585 nm; mini singlet oxygen generator λmax 450 nm), together with a pulse of light (37 mW/cm2, 1-2 minutes). Three lines of evidence shed light on the mechanism of GPCR activated by singlet oxygen (GPCR-ABSO): (1) CCK1R is quantitatively converted from dimer to monomer; (2) Transmembrane domain 3, a pharmacophore for permanent photodynamic CCK1R activation, can be transplanted to non-susceptible M3 acetylcholine receptor; and (3) Larger size of disordered region in intracellular loop 3 correlates with higher sensitivity to photodynamic CCK1R activation. GPCR-ABSO will add to the arsenal of engineered designer GPCR such as receptors activated solely by synthetic ligands and designer receptors exclusively activated by designer drugs, but show some clear advantages: Enhanced selectivity (double selectivity of localized photosensitizer and light illumination), long-lasting activation with no need for repeated drug administration, antagonist-binding site remains intact when needed, ease to apply to multiple GPCR. This type of permanent photodynamic activation may be applied to functional proteins other than GPCR.

This research aimed to explore the changes in two sampling locations (internal and external) of the Longissimus thoracis et lumborum (LTL) beef muscle proteomes subjected to ultraviolet light before dry-aging. It further compared the biological processes and associated proteins at interplay at the external locations of UV pre-treated and control dry-aged samples. Before dry-aging, proteins related to external stimuli were differentially abundant between both locations possibly due to the early post-mortem energy metabolism attempting to compensate for energy deficiencies and stress derived from slaughter and processing. The biochemical status of muscle during chilling and hanging of the carcasses and the impact of the UV pre-treatment may have also influenced the abundance of these proteins before dry-aging. Proteins associated to muscle structure, energy and fatty acids metabolism were differentially abundant between locations after 21 days of dry-aging. These dynamic changes in the meat proteome and related biological processes suggested that both evolved differently between the two sampling locations during dry-aging, and these may underlie the development of dry-aged beef properties. The proteome of the external locations sampled from UV pre-treated beef loins was compared to control counterparts during dry-aging. The results show that aging time appeared to outweigh the effect of UV since the differentially abundant proteins between both groups decreased as dry-aging progressed. These proteins were associated with mRNA stabilization, the matrisome, energy pathways and heat shock proteins (HSPs). Further research is warranted to better understand the role of these proteins in the production of dry-aged beef and their relation to the UV pre-treatment.

Antimicrobial photodynamic therapy is a promising alternative to deal with antimicrobial resistance. However, both the low specificity and low local oxygen molecular concentrations decrease the antimicrobial efficiency limiting its use. An interesting approach to the problem is the use of molecules that can react reversibly with singlet oxygen by the formation of reversible endoperoxides, such as naphthalene, anthracene and pyridone derivatives. Particularly, the use of these molecules with mannosyl derivatives allow the interaction with adhesins presented on pili and fimbriae improving the localization near to bacteria. In this work, we synthesized polymeric nanoparticles able to generate singlet oxygen (under both irradiation and dark conditions) in the vicinity of a center capable of recognizing mannose and oxidize nearby biomolecules. Rose Bengal was used as photosensitizer due to its attractive photophysical properties (vis absorption, high singlet oxygen generation) and biocompatibility. The polymeric nanoparticles were obtained by radical polymerization using polyvinyl alcohol as a template, showing sizes around 300 nm with negative zeta potential by dynamic light scattering. The singlet oxygen generation was monitored following DPBF consumption and showed to be dependent on the amount of pyridone in the feed of polymers. In addition, the release of singlet oxygen was also dependent on pyridone concentration showing a slower rate constant at 40 % pyridone, while for contents of 10 % and 60 % higher rate constants were observed. The specific interaction of glycopolymers with Concanavalin A was demonstrated by successful agglutination assays, but also a low participation of unspecific interactions for polymers without mannosyl derivatives was observed. On the other hand, the oxidation of amino acids of Concanavalin A was monitored by acrylamide gel electrophoresis. Type I and Type II photosensitization were observed with the formation of dimers and fragments with lower molecular weight, while in dark conditions only products with lower molecular weight were observed, result consistent with singlet oxygen released by pyridone endoperoxides.

Human norovirus, a major global cause of gastroenteritis, forms vesicle-cloaked virus clusters (known as viral vesicles), showing increased infectivity and persistence in aquatic environments. We investigated UVB disinfection, a key mechanism of solar disinfection commonly employed in developing countries, targeting murine norovirus vesicles and free murine noroviruses as surrogates for human noroviruses. At low viral concentrations of 109 gene copies per liter, viral infectivity loss as quantified by the integrated cell culture-reverse transcription-quantitative polymerase chain reaction (ICC-RT-qPCR) indicated that vesicles were 1.51 to 1.73 times more resistant to disinfection compared to free viruses. Virus inactivation was primarily due to protein damage as quantified by bicinchoninic acid and Western blot assays, and the damage of virus binding to host cells as quantified by RT-qPCR. Molecular simulations predicted that the oxidation of a tyrosine residue in the viral protein 1 prohibited binding. UVB irradiation of viral/vesicle proteins resulted in 1O2 formation as quantified by time-resolved phosphorescence, and for the first time, endogenous 1O2 was confirmed to contribute to virus inactivation by UVB. Our study recognizes the limitation of UVB disinfection of viral vesicles particularly in solar wastewater treatment and advocates for enhanced disinfection strategies to protect public health.

In the course of 266 nm nanosecond laser flash photolysis of carbazole (CBL) in acetonitrile, we discovered a new transient absorption band centered at 360 nm that has been heretofore unreported despite numerous reports on similar topics. To put some limits on possible transients responsible for this absorption band and thus to solve the mechanism of CBL photolysis, we employed the strategy of selectively blocking the CBL active sites by various modifications in the structure. This strategy was supported by the use of the solvent effect and triplet quenching by molecular oxygen. As a result, the mechanism of carbazole photolysis has been elucidated, part of which was our new discovery that the carbazolyl radical can be formed by the deprotonation of the cation radical. The proposed mechanism has been supported by the reaction with TEMPO, theoretical calculations, and also LC-MS/UV analysis of the stable photoproducts. Given the high impact of CBL-based compounds as one of the key compounds in material science (e.g., OLEDs, TADF, and other light-emitting materials), the understanding of the observed radical-driven processes that occur in the photolysis of carbazole seems to be of great interest.

Use of permanent hair dyes causes unintended oxidative damage during the short time frame of the dyeing process that leads to perceivable changes in the feel, manageability and appearance of hair. Moreover, after hair has been dyed, regular exposure to the sun as a key environmental stressor continues to stimulate additional oxidative damage and to induce newly developed hair colours to fade prematurely or undergo changes in colour quality.

To document the utility of acetyl zingerone methyl ether (MAZ) as a newly designed haircare ingredient to afford extra protection against oxidative damage and safeguard the integrity of hair colour.

We demonstrate that MAZ is compatible chemically with the high alkaline conditions required for the colouring process and from theoretical calculations preferentially binds Fe and Cu ions relative to Ca or Zn ions. In model Fenton reactions MAZ effectively chelated active redox metals (Fe and Cu ions) in the presence of excess Ca+2 ions to inhibit the production of hydroxyl radicals, and in separate studies, MAZ neutralized singlet oxygen with greater efficiency than α-tocopherol by a factor of 2.5. When mixed into permanent dyes prior to hair tress application, MAZ significantly reduced combing forces, and SEM images led to substantial reductions in visual signs of surface damage. In a 28-day clinical study, relative to controls, mixing MAZ into hair dyes prior to application interfered neither with colour development nor with ability to cover grey hair and led to significant improvements in perceived attributes associated with hair's condition immediately following the dyeing process. Over a 28-day maintenance phase, especially between Day 14 and Day 28, continued use of shampoo and conditioner containing MAZ significantly preserved gloss measurements and hair colour in terms of longevity and colour quality as remaining desired and fresh compared to use of control shampoo and conditioner.

This work establishes MAZ as a next-generation hair care ingredient for use in permanent dyes to attenuate oxidative damage and in shampoos and conditioners to promote longevity of hair colour and to maintain overall health and appearance of hair on a daily basis.

Chronic exposure to ultraviolet (UV) light can cause cutaneous damage, resulting in specific pathological changes such as actinic keratosis and dermatitis. Despite actinic dermatosis being well documented in both humans and animals, it has rarely been reported in non-human primates (NHPs). Here, we describe a case of chronic UV light exposure in cynomolgus macaque (Macaca fascicularis). An adult female was presented with a seven-month history of multifocal irregular alopecic, erythematous and hyperkeratotic plaques on the dorsum with itching. Skin biopsies were sampled for histopathological analysis. A biopsy of normal skin from the neck region of an adult macaque was used as a control. Histopathological analysis revealed epidermal changes ranging from moderate to marked hyperplasia associated with hyperkeratosis and mild stratification disorders. Fibrosis was observed in the upper dermis, and multiple areas of elastotic material deposition were confirmed in the mid and deep dermis by Van Gieson special staining. The diagnosis was "solar dermatitis with elastosis". Systemic treatment with nutritional supplements (retinol and omega-3) and firocoxib (5 mg/kg orally once a day for 3 months) did not show any improvement. Concurrently, a topical therapy with aloe gel and a sunscreen spray (SPF50) was added. The lesions did not show further clinical progression. During the period of the study, two other cynomolgus macaques from the same enclosure developed comparable clinical lesions on the dorsum. The authors describe UV-light induced skin damage in a cynomolgus macaque, which remained clinically stable.

Oxidative modifications can disrupt protein folds and functions, and are strongly associated with human aging and diseases. Conventional oxidation pathways typically involve the free diffusion of reactive oxygen species (ROS), which primarily attack the protein surface. Yet, it remains unclear whether and how internal protein folds capable of trapping oxygen (O2) contribute to oxidative damage. Here, we report a hidden pathway of protein damage, which we refer to as O2-confined photooxidation. In this process, O2 is captured in protein cavities and subsequently converted into multiple ROS, primarily mediated by tryptophan residues under blue light irradiation. The generated ROS then attack the protein interior through constrained diffusion, causing protein damage. The effects of this photooxidative reaction appear to be extensive, impacting a wide range of cellular proteins, as supported by whole-cell proteomic analysis. This photooxidative mechanism may represent a latent oxidation pathway in human tissues directly exposed to visible light, such as skin and eyes.

Riboflavin (RF) sensitized photooxidation of pyridoxine HCl (PD) in the pH range of 2.0-12.0 has been carried out under UV and visible irradiation in aerobic and anaerobic conditions. PD follows first-order kinetics in the absence and presence of RF for its photodegradation. The first-order rate constants (k obs) for the photodegradation of PD in the presence of RF (0.05-0.50 × 10-4 M) in aerobic and anaerobic conditions range from 0.046-0.755 and 0.0089-0.755 × 10-2 min-1, respectively. RF acts as a promoter for the photodegradation of PD and the second-order rate constants (k 2) are in the range of 0.026-1.285 and 0.004-0.128 × 10-2 M-1 min-1 in aerobic and anaerobic conditions, respectively. The k 2-pH profile for the photodegradation shows a slanted curve, indicating that with an increase in pH, the rate of photodegradation of PD also increases. Green UV-visible spectrometric and high-performance liquid chromatographic (HPLC) methods have been developed for the simultaneous determination of PD and RF in pure and degraded solutions. These two developed methods are statistically compared and it is found that there is no significant difference between them. We have conducted in silico studies to assess the formation of ground state complexes, molecular interactions, and the binding affinities of RF and PD.

Algae-derived organic matter (ADOM) is a key source of chromophoric dissolved organic matter (CDOM) in natural waters. When exposed to solar irradiation, ADOM undergoes gradual degradation and transformation. The escalating presence of microplastics (MPs) can act as a novel type of environmental photosensitizer, however its impacts on ADOM photodegradation remains largely unexplored. Thus, in this study, ADOM were extracted from four common algal species (Microcystis aeruginosa, Synechococcus sp., Chlorella pyrenoidosa and Scenedesmus obliquus) and exposed to UV irradiation with or without polystyrene (PS) MPs, namely ADOM+PS groups and ADOM groups, respectively. The results indicated that a more rapid degradation of amino acid-like substances (∼38 % vs. ∼22 %) and more ammonia products (1.86 vs. 1.21 mg L-1) were observed in the ADOM+PS groups compared to the ADOM groups after a five-day exposure. This enhanced photodegradation might be attributed to the production of environmentally persistent free radicals and reactive species during the photoaging of PS. Furthermore, PS-derived high electron transfer belt activity of ADOM led to the production of highly aromatic and humified products. These humic-like products could potentially accelerate the degradation of amino acid-like compounds by exciting the generation of excited triplet CDOM. This study underscores the role of MPs as environmental photosensitizers in promoting ADOM degradation and ammonia generation, providing insights on the transformation of ADOM mediated by emerging pollutants and its impact on aquatic carbon and nitrogen cycles.

The large multi-subunit mitochondrial alpha-keto glutarate dehydrogenase (KGDH) complex plays a key, rate-determining, role in the tricarboxylic acid (Krebs) cycle, catalyzing the conversion of alpha-keto glutarate to succinyl-CoA. This complex is both a source and target of oxidants, but the sites of modification and association with structural changes and activity loss are poorly understood. We report here oxidative modifications induced by Rose Bengal (RB) in the presence of O2, a source of singlet oxygen (1O2). A rapid loss of activity was detected, with this being dependent on light exposure, illumination time, and the presence of RB and O2. Activity loss was enhanced by D2O (consistent with 1O2 involvement), but diminished by both pre- and (to a lesser extent) post-illumination addition of lipoic acid and lipoamide. Aggregates containing all three KGDH subunits were detected on photooxidation. LC-MS experiments provided evidence for oxidation at 45 sites, including specific Met, His, Trp, Tyr residues and the lipoyllysine active-site cofactor. Products include mono- and di-oxygenated species, and kynurenine from Trp. Mapping of the modifications to the 3-D structure showed that these are localized to both the inner channel and the external surface, consistent with reactions of free 1O2, however the sites and extent of modification do not correlate with their solvent accessibility. These products are generated concurrently with loss of activity, indicative of strong links between these events. These data provide evidence for the impairment of KGDH activity by 1O2 via the oxidation of specific residues on the protein subunits of the complex.

Histidine (His) photo-oxidation has been widely investigated with several transient and stable products characterized, especially for aerobic conditions. Due to its role and structure, His-side chain can be a key player in the quenching of excited states such as the triplet state of the photosensitizer 3-carboxybenzophenone (3CB*). The capacity of His and its derivatives to quench 3CB* under anaerobic conditions are characterized in the current study by laser flash photolysis, with the resulting oxidation products examined by mass spectrometry to determine the reaction mechanism. The latter include adducts of the 3-carboxybenzophenone ketyl radical (CBH•) to the imidazole ring (Imid-CH2-CBH), His-His dimers, and other products with lower yields. The data obtained with model compounds are compared to those obtained with more complicated systems, including the peptide Exendin-4, and the protein MtHpt1. The data obtained from transient spectroscopy and product analyses indicate that two CB* quenching mechanisms occur: (i) proton-coupled electron transfer (as reported previously) yielding radicals that can recombine to give His-His dimers and CBH-adducts, and (ii) energy transfer yielding 3His* undergoing further reaction leading to formation of Imidazyl-CH2-CBH adduct. The latter, unexpected process only occurs when His and its derivatives have a free α-amino group. This process yielded a novel adduct between the imidazole ring and the CBH• formed by sensitizer reduction.

Photobiomodulation therapy, as an emerging treatment modality, has been widely used in dentistry. However, reports on blue light therapy for oral cancer are scarce. This study investigated the effects of 457 and 475 nm LED irradiation on SCC-25 cells and explored the potential mechanisms underlying the impact of blue light. Both wavelengths were found to inhibit cell viability, induce oxidative stress, and cause cell cycle arrest without leading to cell death. Notably, the inhibitory effect of 457 nm blue light on cell proliferation was more sustained. Transcriptome sequencing was performed to explore the underlying mechanisms, revealing that blue light induced endoplasmic reticulum stress in SCC-25 cells, with 457 nm light showing a more pronounced effect. Moreover, 457 nm blue light upregulated the expression of the aryl hydrocarbon receptor pathway, indicating potential therapeutic prospects for the combined use of blue light and pharmacological agents.

The oxidation of proteins and, in particular, of tryptophan (Trp) residues leads to chemical modifications that can affect the structure and function. The oxidative damage to proteins in photochemical processes is relevant in the skin and eyes and is related to a series of pathologies triggered by exposure to electromagnetic radiation. In this work, we studied the photosensitized formation of N-formylkynurenine (NFKyn) from Trp in different reaction systems. We used two substrates: free Trp and a peptide of nine amino acid residues, with Trp being the only oxidizable residue. Two different photosensitizers were employed: Rose Bengal (RB) and pterin (Ptr). The former is a typical type II photosensitizer [acts by producing singlet oxygen (1O2)]. Ptr is the parent compound of oxidized or aromatic pterins, natural photosensitizers that accumulate in human skin under certain pathological conditions and act mainly through type I mechanisms (generation of radicals). Experimental data were collected in steady photolysis, and the irradiated solutions were analyzed by chromatography (HPLC). Results indicate that the reaction of Trp with 1O2 initiates the process leading to NFKyn, but different competitive pathways take place depending on the photosensitizer and the substrate. In Ptr-photosensitization, a type I mechanism is involved in secondary reactions accelerating the formation of NFKyn when free Trp is the substrate.

Molecular oxygen, O2, has long provided a cornerstone for studies in chemistry, physics, and biology. Although the triplet ground state, O2(X3Σg-), has garnered much attention, the lowest excited electronic state, O2(a1Δg), commonly called singlet oxygen, has attracted appreciable interest, principally because of its unique chemical reactivity in systems ranging from the Earth's atmosphere to biological cells. Because O2(a1Δg) can be produced and deactivated in processes that involve light, the photophysics of O2(a1Δg) are equally important. Moreover, pathways for O2(a1Δg) deactivation that regenerate O2(X3Σg-), which address fundamental principles unto themselves, kinetically compete with the chemical reactions of O2(a1Δg) and, thus, have practical significance. Due to technological advances (e.g., lasers, optical detectors, microscopes), data acquired in the past ∼20 years have increased our understanding of O2(a1Δg) photophysics appreciably and facilitated both spatial and temporal control over the behavior of O2(a1Δg). One goal of this Review is to summarize recent developments that have broad ramifications, focusing on systems in which oxygen forms a contact complex with an organic molecule M (e.g., a liquid solvent). An important concept is the role played by the M+•O2-• charge-transfer state in both the formation and deactivation of O2(a1Δg).

Recent advances in chemical proteomics have focused on developing chemical probes that react with nucleophilic amino acid residues. Although histidine is an attractive candidate due to its importance in enzymatic catalysis, metal binding and protein-protein interaction, its moderate nucleophilicity poses challenges. Its modification is frequently influenced by cysteine and lysine, which results in poor selectivity and narrow proteome coverage. Here we report a singlet oxygen and chemical probe relay labelling method that achieves high selectivity towards histidine. Libraries of small-molecule photosensitizers and chemical probes were screened to optimize histidine labelling, enabling histidine profiling in live cells with around 7,200 unique sites. Using NMR spectroscopy and X-ray crystallography, we characterized the reaction mechanism and the structures of the resulting products. We then applied this method to discover unannotated histidine sites key to enzymatic activity and metal binding in select metalloproteins. This method also revealed the accessibility change of histidine mediated by protein-protein interaction that influences select protein subcellular localization, underscoring its capability in discovering functional histidines.

Light exposure during manufacturing, storage, and administration can lead to the photodegradation of therapeutic proteins. This photodegradation can be promoted by pharmaceutical buffers or impurities. Our laboratory has previously demonstrated that citrate-Fe(III) complexes generate the •CO2- radical anion when photoirradiated under near UV (λ = 320-400 nm) and visible light (λ = 400-800 nm) [Subelzu, N.; Schöneich, C. Mol. Pharmaceutics 2020, 17 (11), 4163-4179; Zhang, Y. Mol. Pharmaceutics 2022, 19 (11), 4026-4042]. Here, we evaluated the impact of citrate-Fe(III) on the photostability and degradation mechanisms of disulfide-containing proteins (bovine serum albumin (BSA) and NISTmAb) under pharmaceutically relevant conditions. We monitored and localized competitive disulfide reduction and protein oxidation by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis depending on the reaction conditions. These competitive pathways were affected by multiple factors, including light dose, Fe(III) concentration, protein concentration, the presence of oxygen, and light intensity.

Monoclonal antibodies (mAbs) are an essential class of therapeutic proteins for the treatment of cancer, autoimmune and rare diseases. During their production, storage, and administration processes, these proteins encounter various stressors such as temperature fluctuations, vibrations, and light exposure, able to induce chemico-physical modifications to their structure. Viral inactivation is a key step in downstream processes, and it is achieved by titration of the mAb at low pH, followed by neutralization. The changes of the pH pose a significant risk of unfolding and subsequent aggregation to proteins, thereby affecting their manufacturing. This study aims to investigate whether a combined exposure to light during the viral inactivation process can further affect the structural integrity of Ipilimumab, a mAb primarily used in the treatment of metastatic melanoma. The biophysical and biochemical characterization of Ipilimumab revealed that pH variation is a considerable risk for its stability with irreversible unfolding at pH 2. The threshold for Ipilimumab denaturation lies between pH 2 and 3 and is correlated with the loss of the protein structural cooperativity, which is the most critical factor determining the protein refolding. Light has demonstrated to exacerbate some local and global effects making pH-induced exposed regions more vulnerable to structural and chemical changes. Therefore, specific precautions to real-life exposure to ambient light during the sterilization process of mAbs should be considered to avoid loss of the therapeutic activity and to increase the yield of production. Our findings underscore the critical role of pH optimization in preserving the structural integrity and therapeutic efficacy of mAbs. Moreover, a detailed conformational study on the structural modifications of Ipilimumab may improve the chemico-physical knowledge of this effective drug and suggest new production strategies for more stable products under some kind of stress conditions.

The development of diverse types of biomaterials has significantly contributed to bringing new biomedical strategies to treat clinical conditions. Applications of these biomaterials can range from mechanical support and protection of injured tissues to joint replacement, tissue implants, and drug delivery systems. Among the strategies commonly used to prepare biomaterials, the use of electromagnetic radiation to initiate crosslinking stands out. The predominance of photo-induced polymerization methods relies on a fast, efficient, and straightforward process that can be easily adjusted to clinical needs. This strategy consists of irradiating the components that form the material with photons in the near ultraviolet-visible wavelength range (i.e., ∼310 to 750 nm) in the presence of a photoactive molecule. Upon photon absorption, photosensitive molecules can generate excited species that initiate photopolymerization through different reaction mechanisms. However, this process could promote undesired side reactions depending on the target zone or treatment type (e.g., oxidative stress and modification of biomolecules such as proteins and lipids). This review explores the basic concepts behind the photopolymerization process of ex situ and in situ biomaterials. Particular emphasis was put on the photosensitization initiated by the most employed photosensitizers and the photoreactions that they mediate in aqueous media. Finally, the undesired oxidation reactions at the bio-interface and potential solutions are presented.

Whey protein isolate (WPI) is mainly composed of β-lactoglobulin (β-LG), α-lactalbumin (α-LA) and bovine serum albumin (BSA). The aim of this study was to compare and analyze the influence of WPI and its three main constituent proteins, as well as proportionally reconstituted WPI (R-WPI) on resveratrol. It was found that the storage stability of resveratrol was protected by WPI, not affected by R-WPI, but reduced by individual whey proteins at 45°C for 30 days. The rank of accelerated degradation of resveratrol by individual whey proteins was BSA > α-LA > β-LG. The antioxidant activity, localization of resveratrol and oxidation of carrier proteins were determined by ABTS, H2O2 assay, synchronous fluorescence, carbonyl and circular dichroism. The non-covalent interactions and disulfide bonds between constituent proteins improved the antioxidant activity of the R-WPI-resveratrol complex, the oxidation stability of the carrier and the solvent shielding effect on resveratrol, which synergistically inhibited the degradation of resveratrol in R-WPI system. The results gave insight into elucidating the interaction mechanism of resveratrol with protein carriers.

There have been significant advances in the formulation and stabilization of proteins in the liquid state over the past years since our previous review. Our mechanistic understanding of protein-excipient interactions has increased, allowing one to develop formulations in a more rational fashion. The field has moved towards more complex and challenging formulations, such as high concentration formulations to allow for subcutaneous administration and co-formulation. While much of the published work has focused on mAbs, the principles appear to apply to any therapeutic protein, although mAbs clearly have some distinctive features. In this review, we first discuss chemical degradation reactions. This is followed by a section on physical instability issues. Then, more specific topics are addressed: instability induced by interactions with interfaces, predictive methods for physical stability and interplay between chemical and physical instability. The final parts are devoted to discussions how all the above impacts (co-)formulation strategies, in particular for high protein concentration solutions.'

Oxidation is one of the most common degradation pathways of biopharmaceutics, potentially leading to altered product stability, pharmacokinetics, reduced biological activity and/or an increased immunogenicity. However, it is often insufficiently assessed in early development stages, leaving potential molecule liabilities undiscovered. Aim of the present work was the development of a high throughput oxidation profiling strategy, applicable throughout various stages of biopharmaceutical development. The study demonstrates that the combination of multiple stress assays, including peroxide-based, visible light, and metal-catalyzed oxidation (MCO), enables a comprehensive understanding of a mAb's oxidation susceptibility. The most effective parameters to evaluate oxidation in a high-throughput screening workflow are aggregation, tryptophan oxidation and changes in the hydrophobicity profile of the Fc and Fab subunit measured via Size Exclusion Chromatography, Intrinsic Tryptophan Fluorescence Emission spectroscopy and Reversed-Phase Chromatography subunit analysis, respectively. This oxidation profiling approach is valuable tool to systematically characterize the oxidation susceptibility under relevant conditions, time effective and with minimal sample consumption.

Despite phototherapy (in the form of photodynamic therapy (PDT)-mediated oxidative stress) being utilized in the management of oral potentially malignant disorders (OPMDs), the evidence of certainty remains unclear. Hence, this systematic review and meta-analysis (PROSPERO # CRD42021218748) is aimed to evaluate the clinical efficacy of PDT-induced oxidative stress in OPMDs METHODS: PubMed, Embase, Web of Science, Scopus, and Cochrane Library databases were searched without restriction of language or year of publication. In addition, gray literature was searched and a manual search was performed. Two independent reviewers screened all the studies, assessing data extraction, risk of bias and certainty of evidence. A narrative synthesis was carried out. For the meta-analysis, random effects were considered to determine the prevalence of a total and a partial remission (PR) of oral potentially malignant disorders (OPMDs). The certainty of evidence was explored using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.

Twenty-three studies were included in the qualitative and quantitative syntheses. A total of 880 patients were included (564 males; 218 females) with an age range between 24 and 89-years-old. The results showed the prevalence of the total and partial remissions respectively for the following OPMLs: actinic cheilitis (AC): 69.9% and 2.4%; oral leukoplakia (OL): 44% and 36.9%; oral verrucous hyperplasia (OVH): 98.5%; oral erythroleukoplakia (OEL): 92.1% and 7.9%. The prevalence of no remission of OL was 18.8%.

PDT demonstrated significant results in clinical remission of OPMDs and most of the eligible studies have shown a total or a partial remission of the included lesions, but at a low or a very low certainty of evidence. Hence, further clinical studies with robust methodology are warranted to offer further validated data. Also, further evidence is required to understand further the mechanism of PDT-induced oxidative stress.

Understanding the competing processes that govern far ultraviolet photodissociation (FUV-PD) of biopolymers such as proteins is a challenge. Here, we report a combined experimental and theoretical investigation of FUV-PD of protonated leucine-enkephalin pentapeptide ([YGGFL + H]+) in the gas-phase. Time-dependent density functional theory (TD-DFT) calculations in combination with experiments and previous results for amino acids and shorter peptides help in rationalizing the evolution of the excited states. The results confirm that fragmentation of [YGGFL + H]+ results mainly from vibrationally excited species in the ground electronic state, populated after internal conversion. We also propose fragmentation mechanisms for specific photo-fragments such as tyrosine side chain loss (with an extra hydrogen) or hydrogen loss. In general, we observe the same mechanisms as for smaller peptides or protonated Tyr and Phe, that are not quenched by the presence of other amino acids. Nevertheless, we also found some differences, as for H loss, in part due to the fact that the charge is solvated by the peptide chain and not only by the COOH terminal group.

Herein, BPC catalyzed visible-light-triggered target-specific late-stage solution phase desulfonylation from tryptophan in oligopeptides is portrayed by overcoming the isolation issue up to octamers. This robust and mild method is highly predictable and chemoselective, tolerating myriad of functional groups in aza-heteroaromatics and peptides. Interestingly, reductive desulfonylation is also amenable to biologically significant reactive histidine and tyrosine side chains, signifying the versatility of the strategy. Additional efficacy of BPC is demonstrated by solution phase phenacyl deprotection from C-terminal in peptides. Furthermore, excellent catalyst loading of 0.5 mol% and recyclability demonstrate the practical utility and applicability of this strategy.

Formation of the protein crosslink di-Tyrosine was studied in PET-bottled pasteurized milk exposed to fluorescent light in a commercial display cabinet. An HPLC method with fluorescence detection was developed and intra-laboratory validated using pure di-Tyrosine synthesized on purpose. Di-Tyrosine was detected after 1-day lightening and increased up to 7 days, reaching around 250 and 320 µg/g protein in whole and partly skimmed milk, respectively. Afterward, a progressive decrease occurred. By transmission electron microscopy with specific immune gold labelling, presence of di-Tyrosine was observed for the first time on the surface of casein micelles of lightened milk. The crosslink formation, however, did not bring to protein aggregation phenomena detectable by laser light scattering measurements. Exposure to light also induced degradation of riboflavin and decrease of yellowness index. Di-Tyrosine proved to be a suitable indicator to evaluate the progress of protein oxidation in pasteurized milk during storage on the market.

The present study compared the impact of two UV light devices: conventional UV lamp and UV-LED on the colour, pH, lipid and protein oxidation of fresh chicken breast meat aerobically stored at 4 °C for 10 days. Lipid oxidation was the most impacted quality attribute in UV lamp treated meat, unlike UV-LED that showed no effect compared to non-treated meat. Slight changes were observed in colour, pH and protein oxidation of chicken samples subjected to UV lamp and UV-LED. To evaluate these changes from a consumer perspective, the different treatment samples were stored at 4 °C for 3 days and colour likeness, odour likeness and overall appearance were assessed by consumer sensory analysis. However, alterations in quality parameters of chicken meat caused by UV light did not decrease overall acceptance in the sensory analysis. UV-LED was the preferred chicken meat by the participants, even compared to non-treated meat.

Over the years, bioinspired mineralization-based approaches have been applied to synthesize multifunctional organic-inorganic nanocomposites. These nanocomposites can address the growing demands of modern biomedical applications. Proteins, serving as vital biological templates, play a pivotal role in the nucleation and growth processes of various organic-inorganic nanocomposites. Protein-mineralized nanomaterials (PMNMs) have attracted significant interest from researchers due to their facile and convenient preparation, strong physiological activity, stability, impressive biocompatibility, and biodegradability. Nevertheless, few comprehensive reviews have expounded on the progress of these nanomaterials in biomedicine. This article systematically reviews the principles and strategies for constructing nanomaterials using protein-directed biomineralization and biomimetic mineralization techniques. Subsequently, we focus on their recent applications in the biomedical field, encompassing areas such as bioimaging, as well as anti-tumor, anti-bacterial, and anti-inflammatory therapies. Furthermore, we discuss the challenges encountered in practical applications of these materials and explore their potential in future applications. This review aspired to catalyze the continued development of these bioinspired nanomaterials in drug development and clinical diagnosis, ultimately contributing to the fields of precision medicine and translational medicine.

Radical prostatectomy is a primary treatment option for localized prostate cancer (PCa), although high rates of recurrence are commonly observed postsurgery. Photodynamic therapy (PDT) has demonstrated efficacy in treating nonmetastatic localized PCa with a low incidence of adverse events. However, its limited efficacy remains a concern. To address these issues, various organic polymeric nanoparticles (OPNPs) loaded with photosensitizers (PSs) that target prostate cancer have been developed. However, further optimization of the OPNP design is necessary to maximize the effectiveness of PDT and improve its clinical applicability. This Review provides an overview of the design, preparation, methodology, and oncological aspects of OPNP-based PDT for the treatment of PCa.

Unfolding in combination with or without acid hydrolysis is crucial for the formation of functional amyloid (fibrillar) or amyloid-like (worm-like) β-lactoglobulin (BLG) aggregates, which can be induced through temperature treatment for several hours at pH 2-4. A preceding conformational destabilization of BLG might affect its aggregation. We investigated ultraviolet (UV) B radiation as conformational perturbing treatment to facilitate temperature-induced protein aggregation. 2-h UVB pretreated BLG (UV-BLG) exhibited an accelerated worm-like aggregation at pH 3.5, while at pH 2 the formation of fibrils was decelerated. The UV-induced conformational destabilization lowered the thermal stability and thus facilitates unfolding during thermal treatment. Thereby, the formation of covalent and non-covalent intermolecular interactions was favored, which promoted assembly of intact proteins resulting in worm-like aggregates. The oxidative degradation of UV-BLG was suggested to alter fibrillation-prone protein regions and thereby impede peptide assembly.

Tissue autofluorescence poses significant challenges for RNA and protein analysis using fluorescence-based techniques. Here, we present a protocol that combines oxidation-mediated autofluorescence reduction with detergent-based tissue permeabilization for whole-mount RNA-fluorescence in situ hybridization (FISH) on mouse embryonic limb buds. We describe the steps for embryo collection, fixation, photochemical bleaching, permeabilization, and RNA-FISH, followed by optical clearing of RNA-FISH and immunofluorescence samples for imaging. The protocol alleviates the need for digital image post-processing to remove autofluorescence and is applicable to other tissues, organs, and vertebrate embryos.

Natural dissolved organic matter (DOM) is one of the Earth's dynamic carbon pools and a key intermediate in the global carbon cycle. Photochemical processes potentially affect DOM composition and activity in surface water. Suspended particulate matter (SPM) is the integral component of slow-moving rivers, and holds the potential for photochemical reactivity. To further investigate the influence of SPM on DOM photochemical transformation, this study conducted experiments comparing samples with and without SPM irradiated under simulated sunlight. Surface water samples from slow-moving urban rivers were collected. DOM optical characteristics and molecular features obtained by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) were investigated. Photolabile DOM was enriched in unsaturated and highly aromatic terrestrial substances. Photoproduced DOM had low aromaticity and was dominated by saturated aliphatics, protein-like substances, and carbohydrates. Study results indicated that the presence of SPM had a nonnegligible impact on the molecular traits of DOM, such as composition, molecular diversity, photolability, and bioavailability during photochemical reactions. In the environment affected by SPM, molecules containing heteroatoms exhibit higher photosensitivity. SPM promotes the photochemical transformation of a wider range of chemical types of photolabile DOM, particularly nitrogen-containing compounds. This study provides an essential insight into the more precise simulation of photochemical reactions of DOM influenced by SPM occurring in natural rivers, contributing to our understanding of the global carbon cycle from new theoretical perspectives.

Adipokinetic hormones (AKHs) regulate important physiological processes in insects. AKHs are short peptides with blocked termini and Trp in position 8. Often, proline occupies position 6. Few post-translational modifications have been found, including hydroxyproline ([Hyp6]) and kynurenine. Our recent data suggest that the Hyp- and Kyn-containing AKHs occur more often than originally thought and we here investigate if they are natural or artifactual.

From crude extracts of the corpora cardiaca (CC) of various insect species, AKHs were analyzed using liquid chromatography coupled to high-resolution mass spectrometry (LC-MS). Synthetic [Hyp6]-AKHs were tested in an in vivo metabolic assay. Freshly dissected Periplaneta americana and Blaberus atropos CCs (with precautions taken against oxidation) were analyzed. B. atropos CC were placed into a depolarizing saline and the released AKHs were measured.

Hyp was detected in several decapeptides from cockroaches. The modified form accompanied the AKH at concentrations below 7%. The [Hyp6]-AKHs of B. atropos were present in fresh CC preparations and were shown to be releasable from the CC ex vivo. Synthetic [Hyp6]-containing peptides tested positively in a hypertrehalosemic bioassay. Hydroxyprolination was also detected for Manto-CC from the termite Kalotermes flavicollis and for Tetsu-AKH of the grasshopper, Tetrix subulata. Oxidized Trp-containing forms of Nicve-AKH were found in species of the burying beetle genus Nicrophorus.

Trp oxidation is known to occur easily during sample handling and is likely the reason for the present findings. For hydroxyprolination, however, the experimental evidence suggests endogenous processes.

Protein modifications such as oligomerization and tyrosine nitration alter the immune response to allergens and may contribute to the increasing prevalence of allergic diseases. In this mini-review, we summarize and discuss relevant findings for the major birch and grass pollen allergens Bet v 1 and Phl p 5 modified with tetranitromethane (laboratory studies), peroxynitrite (physiological processes), and ozone and nitrogen dioxide (environmental conditions). We focus on tyrosine nitration and the formation of protein dimers and higher oligomers via dityrosine cross-linking and the immunological effects studied.

Effective and accessible treatments for Alzheimer's disease (AD) are urgently needed. Soluble Aβ oligomers are identified as neurotoxic species in AD and targeted in antibody-based drug development to mitigate cognitive decline. However, controversy exists concerning their efficacy and safety. In this study, an alternative strategy is proposed to inhibit the formation of Aβ oligomers by selectively oxidizing specific amino acids in the Aβ sequence, thereby preventing its aggregation. Targeted oxidation is achieved using biocompatible and blood-brain barrier-permeable multicomponent nanoscintillators that generate singlet oxygen upon X-ray interaction. Surface-modified scintillators interact selectively with Aβ and, upon X-ray irradiation, inhibit the formation of neurotoxic aggregates both in vitro and in vivo. Feeding transgenic Caenorhabditis elegans expressing human Aβ with the nanoscintillators and subsequent irradiation with soft X-ray reduces Aβ oligomer levels, extends lifespan, and restores memory and behavioral deficits. These findings support the potential of X-ray-based therapy for AD and warrant further development.

Histidine photooxygenation has been the subject of extensive investigation for many years. The intricate nature of histidine distinguishes it from other amino acids, as its side chain readily undergoes changes in charge state and tautomerization in response to pH, and the polarity of the imidazole ring inverts upon oxidation. This complexity gives rise to a diverse range of oxidation products and mechanisms, posing challenges in their interpretation. This review aims to provide a thorough overview of the chemistry involved in histidine photooxygenation, encompassing a comprehensive analysis of resulting products, mechanisms engaged in their formation, and analytical techniques that have contributed to their identification. Additionally, it explores a wide range of applications stemming from this transformation, offering valuable insights into its practical implications in fields such as materials science, biomedical research, and drug development. By bridging the existing gap in literature, this review serves as a resource for understanding the intricacies of histidine photooxygenation and its diverse ramifications.

Advances in optical imaging always look for an increase in sensitivity and resolution among other practicability aspects. Within the same scope, in this work we report a versatile interference contrast imaging technique, with high phase sensitivity and a large field-of-view of several mm2. Sensitivity is increased through the use of a self-imaging non-resonant cavity, which causes photons to probe the sample in multiple rounds before being detected, where the configuration can be transmissive or reflective. Phase profiles can be resolved individually for each round thanks to a specially designed single-photon camera with time-of-flight capabilities and true pixels-off gating. Measurement noise is reduced by novel data processing combining the retrieved sample profiles from multiple rounds. Our protocol is especially useful under extremely low light conditions as required by biological or photo-sensitive samples. Results demonstrate more than a four-fold reduction in phase measurement noise, compared to single round imaging, and values close to the predicted sensitivity in case of the best possible cavity configuration, where all photons are maintained until n rounds. We also find good agreement with the theoretical predictions for low number of rounds, where experimental imperfections would play a minor role. The absence of a laser or cavity lock-in mechanism makes the technique an easy to use inspection tool.

We report the characterization of the penilumamide biosynthetic cluster from Aspergillus flavipes CNL-338. In vitro reconstitution experiments demonstrated that three nonribosomal peptide synthetases are required for constructing the tripeptide and studies with dissected adenylation domains allowed for the first biochemical characterization of a domain that selects a pterin-derived building block.

Excessive ultraviolet (UV) exposure is the primary environmental factor that contributes to skin aging. Orbitides have been considered as important functional components in linseed, and they are complex and multiple. In this study, linseed orbitides (LOs) were divided into oxidized linseed orbitides (OLOs) and reduced linseed orbitides (RLOs) and used to investigate protection against ultraviolet B-induced photoaging in zebrafish. First, the results of the zebrafish embryo acute toxicity test showed that the OLOs had obvious embryo toxicity compared with RLOs. And RLOs had better effect in ultraviolet B-treated zebrafish, which may significantly reduce the reactive oxygen species levels and inhibit the degradation of collagen. Besides, we also found that RLOs could effectively inhibit the oxidation of proteins and lipids and regulate the activity of antioxidant enzymes. Furthermore, neutrophil recruitment to the dorsal and caudal fin regions was observed in UVB-treated zebrafish, and RLOs effectively alleviated this migration. In conclusion, RLOs have strong photoprotective effects and potential to be used as antiphotoaging ingredients.

Systemic lupus erythematosus is a heterogeneous autoimmune disease in which skin involvement is a common manifestation. It is currently thought that the photosensitivity of SLE skin involvement is associated with anti-SSA antibodies. This study aimed to expand the current state of knowledge surrounding the molecular pathophysiology of SLE skin photosensitivity through Serum metabolomics analysis.

The serum metabolites of 23 cases of skin-involved SLE (SI) group, 14 cases of no SI (NSI) group, and 30 cases of healthy controls (HC) were analyzed by using UPLC-MS/MS technology, and subgroup analysis was performed according to the expression of anti-SSA antibodies in SI. MetaboAnalyst 5.0 was used for enrichment analysis and ROC curve construction, identifying serum metabolic markers of skin-involved SLE associated with anti-SSA antibodies.

We identified several metabolites and metabolic pathways associated with SLE photosensitivity. Two metabolites, SM (d18:1/24:0) and gamma-CEHC can distinguish between anti-SSA antibody-positive and negative SI, with AUC of 0.829 and 0.806. These two photosensitization-related substances may be potential markers of skin involvement in SLE associated with anti-SSA antibody.

This study provides new insights into the pathogenesis of SI patients, and provides a new molecular biological basis for the association between anti-SSA antibodies and skin photoallergic manifestations of SLE.