NMN recruits GSH to enhance GPX4-mediated ferroptosis defense in UV irradiation induced skin injury.

Oxidative stress and lipid peroxidation are major causes of skin injury induced by ultraviolet (UV) irradiation. Ferroptosis is a form of regulated necrosis driven by iron-dependent peroxidation of phospholipids and contributes to kinds of tissue injuries. However, it remains unclear whether the accumulation of lipid peroxides in UV irradiation-induced skin injury could lead to ferroptosis. We generated UV irradiation-induced skin injury mice model to examine the accumulation of the lipid peroxides and iron. Lipid peroxides 4-HNE, the oxidative enzyme COX2, the oxidative DNA damage biomarker 8-OHdG, and the iron level were increased in UV irradiation-induced skin. The accumulation of iron and lipid peroxidation was also observed in UVB-irradiated epidermal keratinocytes without actual ongoing ferroptotic cell death. Ferroptosis was triggered in UV-irradiated keratinocytes stimulated with ferric ammonium citrate (FAC) to mimic the iron overload. Although GPX4 protected UVB-injured keratinocytes against ferroptotic cell death resulted from dysregulation of iron metabolism and the subsequent increase of lipid ROS, keratinocytes enduring constant UVB treatment were markedly sensitized to ferroptosis. Nicotinamide mononucleotide (NMN) which is a direct and potent NAD+ precursor supplement, rescued the imbalanced NAD+/NADH ratio, recruited the production of GSH and promoted resistance to lipid peroxidation in a GPX4-dependent manner. Taken together, our data suggest that NMN recruits GSH to enhance GPX4-mediated ferroptosis defense in UV irradiation-induced skin injury and inhibits oxidative skin damage. NMN or ferroptosis inhibitor might become promising therapeutic approaches for treating oxidative stress-induced skin diseases or disorders.

Thymidine decreases the DNA damage and apoptosis caused by tumor-treating fields in cancer cell lines.

BACKGROUND: Tumor-treating fields (TTFields) is an emerging non-invasive cancer-treatment modality using alternating electric fields with low intensities and an intermediate range of frequency. TTFields affects an extensive range of charged and polarizable cellular factors known to be involved in cell division. However, it causes side-effects, such as DNA damage and apoptosis, in healthy cells. OBJECTIVE: To investigate whether thymidine can have an effect on the DNA damage and apoptosis, we arrested the cell cycle of human glioblastoma cells (U373) at G1/S phase by using thymidine and then exposed these cells to TTFields. METHODS: Cancer cell lines and normal cell (HaCaT) were arrested by thymidine double block method. Cells were seeded into the gap of between the insulated wires. The exposed in alternative electric fields at 120 kHz, 1.2 V/cm. They were counted the cell numbers and analyzed for cancer malignant such as colony formation, Annexin V/PI staining, γH2AX and RT-PCR. RESULTS: The colony-forming ability and DNA damage of the control cells without thymidine treatment were significantly decreased, and the expression levels of BRCA1, PCNA, CDC25C, and MAD2 were distinctly increased. Interestingly, however, cells treated with thymidine did not change the colony formation, apoptosis, DNA damage, or gene expression pattern. CONCLUSIONS: These results demonstrated that thymidine can inhibit the TTFields-caused DNA damage and apoptosis, suggesting that combining TTFields and conventional treatments, such as chemotherapy, may enhance prognosis and decrease side effects compared with those of TTFields or conventional treatments alone.

Perilla frutescens Extracts Enhance DNA Repair Response in UVB Damaged HaCaT Cells.

Physiological processes in skin are associated with exposure to UV light and are essential for skin maintenance and regeneration. Here, we investigated whether the leaf and callus extracts of Perilla frutescens (Perilla), a well-known Asian herb, affect DNA damage response and repair in skin and keratinocytes exposed to Untraviolet B (UVB) light. First, we examined the protective effects of Perilla leaf extracts in UVB damaged mouse skin in vivo. Second, we cultured calluses using plant tissue culture technology, from Perilla leaf explant and then examined the effects of the leaf and callus extracts of Perilla on UVB exposed keratinocytes. HaCaT cells treated with leaf and callus Perilla extracts exhibited antioxidant activities, smaller DNA fragment tails, and enhanced colony formation after UVB exposure. Interestingly, keratinocytes treated with the leaf and callus extracts of Perilla showed G1/S cell cycle arrest, reduced protein levels of cyclin D1, Cyclin Dependent Kinase 6 (CDK6), and γH2AX, and enhanced levels of phosphorylated checkpoint kinase 1 (pCHK1) following UVB exposure. These observations suggest that the leaf and callus extracts of Perilla are candidate nutraceuticals for the prevention of keratinocyte aging.

Focused ultrasound radiosensitizes human cancer cells by enhancement of DNA damage.

PURPOSE: High-intensity focused ultrasound (HIFU/FUS) has expanded as a noninvasive quantifiable option for hyperthermia (HT). HT in a temperature range of 40-47 °C (thermal dose CEM43 ≥ 25) could work as a sensitizer to radiation therapy (RT). Here, we attempted to understand the tumor radiosensitization effect at the cellular level after a combination treatment of FUS+RT. METHODS: An in vitro FUS system was developed to induce HT at frequencies of 1.147 and 1.467 MHz. Human head and neck cancer (FaDU), glioblastoma (T98G), and prostate cancer (PC-3) cells were exposed to FUS in ultrasound-penetrable 96-well plates followed by single-dose X­ray irradiation (10 Gy). Radiosensitizing effects of FUS were investigated by cell metabolic activity (WST­1 assay), apoptosis (annexin V assay, sub-G1 assay), cell cycle phases (propidium iodide staining), and DNA double-strand breaks (γH2A.X assay). RESULTS: The FUS intensities of 213 (1.147 MHz) and 225 W/cm2 (1.467 MHz) induced HT for 30 min at mean temperatures of 45.20 ± 2.29 °C (CEM43 = 436 ± 88) and 45.59 ± 1.65 °C (CEM43 = 447 ± 79), respectively. FUS improves the effect of RT significantly by reducing metabolic activity in T98G cells 48 h (RT: 96.47 ± 8.29%; FUS+RT: 79.38 ± 14.93%; p = 0.012) and in PC-3 cells 72 h (54.20 ± 10.85%; 41.01 ± 11.17%; p = 0.016) after therapy, but not in FaDu cells. Mechanistically, FUS+RT leads to increased apoptosis and enhancement of DNA double-strand breaks compared to RT alone in T98G and PC-3 cells. CONCLUSION: Our in vitro findings demonstrate that FUS has good potential to sensitize glioblastoma and prostate cancer cells to RT by mainly enhancing DNA damage.

Ultraviolet absorbance of Sphagnum magellanicum, S. fallax and S. fuscum extracts with seasonal and species-specific variation.

Bryophytes, including Sphagnum, are common species in alpine and boreal regions especially on mires, where full sunlight exposes the plants to the damaging effects of UV radiation. Sphagnum species containing UV-protecting compounds might offer a biomass source for nature-based sunscreens to replace the synthetic ones. In this study, potential compounds and those linked in cell wall structures were obtained by using methanol and alkali extractions and the UV absorption of these extracts from three common Sphagnum moss species Sphagnum magellanicum, Sphagnum fuscum and Sphagnum fallax collected in spring and autumn from western Finland are described. Absorption spectrum screening (200-900 nm) and luminescent biosensor (Escherichia coli DPD2794) methodology were used to examine and compare the protection against UV radiation. Additionally, the antioxidant potential was evaluated using hydrogen peroxide scavenging (SCAV), oxygen radical absorbance capacity (ORAC) and ferric reducing absorbance capacity (FRAP). Total phenolic content was also determined using the Folin-Ciocalteu method. The results showed that methanol extractable compounds gave higher UV absorption with the used methods. Sphagnum fallax appeared to give the highest absorption in UV-B and UV-A wavelengths. In all assays except the SCAV test, the methanol extracts of Sphagnum samples collected in autumn indicated the highest antioxidant capacity and polyphenol content. Sphagnum fuscum implied the highest antioxidant capacity and phenolic content. There was low antioxidant and UV absorption provided by the alkali extracts of these three species.

The Role of Oxidative Stress and Autophagy in Blue-Light-Induced Damage to the Retinal Pigment Epithelium in Zebrafish In Vitro and In Vivo.

Age-related macular degeneration (AMD) is the progressive degeneration of the retinal pigment epithelium (RPE), retina, and choriocapillaris among elderly individuals and is the leading cause of blindness worldwide. Thus, a better understanding of the underlying mechanisms in retinal tissue activated by blue light exposure is important for developing novel treatment and intervention strategies. In this study, blue-light-emitting diodes with a wavelength of 440 nm were applied to RPE cells at a dose of 3.7 ± 0.75 mW/cm2 for 24 h. ARPE-19 cells were used to investigate the underlying mechanism induced by blue light exposure. A trypan blue exclusion assay was used for the cell viability determination. Flow cytometry was used for apoptosis rate detection and autophagy analysis. An immunofluorescence microscopy analysis was used to investigate cellular oxidative stress and DNA damage using DCFDA fluorescence staining and an anti-γH2AX antibody. Blue light exposure of zebrafish larvae was established to investigate the effect on retinal tissue development in vivo. To further demonstrate the comprehensive effect of blue light on ARPE-19 cells, next-generation sequencing (NGS) was performed for an ingenuity pathway analysis (IPA) to reveal additional related mechanisms. The results showed that blue light exposure caused a decrease in cell proliferation and an increase in apoptosis in ARPE-19 cells in a time-dependent manner. Oxidative stress increased during the early stage of 2 h of exposure and activated DNA damage in ARPE-19 cells after 8 h. Furthermore, autophagy was activated in response to blue light exposure at 24-48 h. The zebrafish larvae model showed the unfavorable effect of blue light in prohibiting retinal tissue development. The RNA-Seq results confirmed that blue light induced cell death and participated in tissue growth inhibition and maturation. The current study reveals the mechanisms by which blue light induces cell death in a time-dependent manner. Moreover, both the in vivo and NGS data uncovered blue light's effect on retinal tissue development, suggesting that exposing children to blue light could be relatively dangerous. These results could benefit the development of preventive strategies utilizing herbal medicine-based treatments for eye diseases or degeneration in the future.

Polyscias filicifolia (Araliaceae) Hairy Roots with Antigenotoxic and Anti-Photogenotoxic Activity.

Hairy root cultures are considered as a valuable source of bioactive phytoconstituents with expanding applicability for their production. In the present study, hairy root cultures of Polyscias filicifolia (Araliaceae), a traditional Southeast Asian medicinal plant, were established. The transformation with Agrobacterium rhizogenes ATCC 15834 allowed to obtain 15 root lines. The K-1 line, demonstrating the highest growth capabilities, was subjected to further investigations. To enhance the biosynthetic potential of hairy roots, methyl jasmonate elicitation approach was applied (MeJA; at different doses and exposure time), with subsequent transfer of elicited roots to control medium. This strategy resulted in chlorogenic acid production up to 1.59 mg/g dry weight. HPLC-PDA-ESI-MS analysis demonstrated variation in extracts composition and allowed to identify different caffeic and ferulic acid derivatives. Next, cytotoxic, antigenotoxic, and anti-photogenotoxic properties of hairy roots extracts were determined. None of the tested extracts were cytotoxic. In addition, they demonstrated significant antigenotoxic activity with the highest protective potential; up to 52% and 49% of inhibition of induction ratio (IR) induced by the 2-aminoanthracene was revealed for extracts derived from hairy roots elicited for 3 days with 50 µM MeJA and roots elicited for 7 days with 100 µM MeJA and then transferred for 30 days to control medium, respectively. These same extracts exhibited the highest anti-photogenotoxic potential, up to 36% of inhibition of chloropromazine-induced genotoxicity.

Mechanism of turnover or persistence of radiation-induced myofibroblast in vitro.

We recently made an important discovery that radiation induces myofibroblasts, which play a role in radiation-related carcinogenesis via tumor microenvironment formation. Here, we investigated the threshold dose and the mechanisms of myofibroblast induction to assess adverse radiation effects on normal cells. Single-dose of healthy human fibroblasts in vitro promotes myofibroblast induction at high doses (≥ 5 Gy). In contrast, repeated low dose of fractionated radiation is at least equivalent to high-dose single radiation regarding myofibroblast induction. ROS play a pivotal role in the process of myofibroblast induction in normal tissue injury. Antioxidants, such as epicatechin and ascorbic acid can prevent myofibroblast induction by scavenging ROS. We further investigated the role of DNA damage responses (DDR) on myofibroblast induction. Blocking the DDR using DNA-PK or AKT inhibitors enhanced cellular sensitivity to radiation and facilitated myofibroblast induction, whereas an ATM inhibitor also enhanced radiation sensitivity but abrogated ROS accumulation and myofibroblast induction. In contrast to standard culture conditions, myofibroblasts remained after low or moderate doses of radiation (below 2.5 Gy) under growth-restricted conditions. In conclusion, the recovery of damaged cells from radiation is essential for myofibroblast clearance, which restores stromal cell dormancy and prevents tumor microenvironment formation. However, residual ROS, by way of sustaining myofibroblast presence, can facilitate tumor microenvironment formation. Targeting ROS using antioxidants is effective in the mitigation of radiation-related adverse effects, such as growth retardation and myofibroblast induction, and helps protect normal tissues.

Curcumin from Jianghuang (Rhizoma Curcumae Longae) protects against exposure to ultraviolet B by antioxidation and attenuating mitochondrion-dependent apoptosis.

OBJECTIVE: To investigate the protective effect of curcumin extracted from Jianghuang (Rhizoma Curcumae Longae) against ultraviolet B (UVB) and the possible mechanism. METHODS: Effects of curcumin were detected in vivo and in vitro. Morphological changes of white guinea pig skin were assessed by hematoxylin and eosin staining. HaCaT cell proliferation was measured by 3-[4,5-dimethylthylthiazol-2-yl]-2,5 diphenyltetrazolium broide (MTT) assays. The cell cycle distribution, apoptotic rate, level of reactive oxygen species (ROS), mitochondrial membrane potential, and intracellullar calcium ion concentration of HaCaT cells were detected by flow cytometry. Antioxidant levels in skin tissues and HaCat cells were measured by biochemical methods. RESULTS: UVB inhibited in vitro cell proliferation by inducing G2/M arrest, increasing ROS, apoptosis, and necrosis, and decreasing B-cell lymphoma-2, and increasing Bax, cytochrome c, and caspase-3 levels. CONCLUSION: Curcumin blocks the effects of UVB by reducing ROS and apoptosis, and reversing UVB-induced changes in the expression of apoptotic proteins. The mitochondrial pathway is involved in curcumin-regulated apoptosis.

Amelioration of sperm count and sperm quality by lycopene supplementation in irradiated mice.

Male mice were exposed to lycopene (LYC; 0.15 and 0.30mg kg-1) and irradiation (0.5, 1 Gy) alone or in combination (0.5 Gy+0.15mg kg-1 LYC; 0.5 Gy+0.30mg kg-1 LYC; 1 Gy+0.15mg kg-1 LYC; 1 Gy+0.30mg kg-1 LYC) for 2 weeks. LYC administration in the drinking water was started 24h or on Day 8 after the first irradiation dose or equivalent time point for groups treated with LYC alone. Sperm count, motility, morphology and DNA damage were determined at the end of the 2-week treatment period. Irradiation deteriorated sperm count and quality. Supplementation with LYC from 24h significantly increased the sperm count compared with irradiation alone. In almost all combined treatment groups, the percentage of abnormal spermatozoa was significantly decreased compared with that after irradiation alone. In some cases, combined treatment reduced levels of DNA damage in gametes. Both doses of LYC administered from Day 8 significantly reduced the percentage of morphologically abnormal spermatozoa compared with that seen after 1 Gy irradiation and reduced DNA damage in all combined treatment groups. In conclusion, LYC supplementation after irradiation can ameliorate the harmful effects of irradiation on gametes. Mitigation of radiation-induced damage in germ cells following LYC administration may be useful for radiological accidents and to protect non-treated tissues in patients with cancer undergoing radiotherapy.

Ultraviolet A light effectively reduces bacteria and viruses including coronavirus.

Antimicrobial-resistant and novel pathogens continue to emerge, outpacing efforts to contain and treat them. Therefore, there is a crucial need for safe and effective therapies. Ultraviolet-A (UVA) phototherapy is FDA-approved for several dermatological diseases but not for internal applications. We investigated UVA effects on human cells in vitro, mouse colonic tissue in vivo, and UVA efficacy against bacteria, yeast, coxsackievirus group B and coronavirus-229E. Several pathogens and virally transfected human cells were exposed to a series of specific UVA exposure regimens. HeLa, alveolar and primary human tracheal epithelial cell viability was assessed after UVA exposure, and 8-Oxo-2'-deoxyguanosine was measured as an oxidative DNA damage marker. Furthermore, wild-type mice were exposed to intracolonic UVA as an in vivo model to assess safety of internal UVA exposure. Controlled UVA exposure yielded significant reductions in Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Clostridioides difficile, Streptococcus pyogenes, Staphylococcus epidermidis, Proteus mirabilis and Candida albicans. UVA-treated coxsackievirus-transfected HeLa cells exhibited significantly increased cell survival compared to controls. UVA-treated coronavirus-229E-transfected tracheal cells exhibited significant coronavirus spike protein reduction, increased mitochondrial antiviral-signaling protein and decreased coronavirus-229E-induced cell death. Specific controlled UVA exposure had no significant effect on growth or 8-Oxo-2'-deoxyguanosine levels in three types of human cells. Single or repeated in vivo intraluminal UVA exposure produced no discernible endoscopic, histologic or dysplastic changes in mice. These findings suggest that, under specific conditions, UVA reduces various pathogens including coronavirus-229E, and may provide a safe and effective treatment for infectious diseases of internal viscera. Clinical studies are warranted to further elucidate the safety and efficacy of UVA in humans.

Cytotoxicity and Mutagenicity of Narrowband UVB to Mammalian Cells.

Phototherapy using narrowband ultraviolet-B (NB-UVB) has been shown to be more effective than conventional broadband UVB (BB-UVB) in treating a variety of skin diseases. To assess the difference in carcinogenic potential between NB-UVB and BB-UVB, we investigated the cytotoxicity via colony formation assay, genotoxicity via sister chromatid exchange (SCE) assay, mutagenicity via hypoxanthine phosphoribosyltransferase (HPRT) mutation assay, as well as cyclobutane pyrimidine dimer (CPD) formation and reactive oxygen species (ROS) generation in Chinese hamster ovary (CHO) and their NER mutant cells. The radiation dose required to reduce survival to 10% (D10 value) demonstrated BB-UVB was 10 times more cytotoxic than NB-UVB, and revealed that NB-UVB also induces DNA damage repaired by nucleotide excision repair. We also found that BB-UVB more efficiently induced SCEs and HPRT mutations per absorbed energy dosage (J/m2) than NB-UVB. However, SCE and HPRT mutation frequencies were observed to rise in noncytotoxic dosages of NB-UVB exposure. BB-UVB and NB-UVB both produced a significant increase in CPD formation and ROS formation (p < 0.05); however, higher dosages were required for NB-UVB. These results suggest that NB-UVB is less cytotoxic and genotoxic than BB-UVB, but can still produce genotoxic effects even at noncytotoxic doses.

Elucidating the time course of the transcriptomic response to photobiomodulation through gene co-expression analysis.

Photobiomodulation (PBM) with low-intensity red to near infrared light elicits neuroprotection in various pre-clinical models and in some clinical contexts, yet the intracellular mechanisms triggered by PBM, and their temporal sequence of modulation, remain unclear. We aimed to address this uncertainty by mapping the temporal transcriptomic response to PBM. Human SH-SY5Y neuroblastoma cells were treated with 670 nm PBM and RNA collected a various time points over 24 h. The transcriptome was screened by RNA microarray, and gene co-expression analysis by hierarchical clustering was coupled with bioinformatics analysis to reveal the molecular systems modulated by PBM and their expression patterns over the time course. The findings suggest that PBM induces distinct early phase (up to 8 h post-PBM) and late phase (24 h post-PBM) intracellular responses. The early intracellular response features enrichment of pathways relating to transcriptional regulation and cellular stress responses, while the late intracellular response demonstrates a physiological shift to enrichment of downstream pathways such as cell death and DNA damage. These findings provide support for the hypothesis that PBM acts as a transient stressful stimulus, activating endogenous stress response pathways that in turn enhance cellular resilience. Further, the study introduces a novel method for retaining the richness of the temporal component when analysing transcriptomic time course data sets.

Eriodictyon angustifolium extract, but not Eriodictyon californicum extract, reduces human hair greying.

OBJECTIVE: Yerba Santa (Eriodictyon angustifolium and Eriodictyon californicum) has been used for many years in traditional medicine. However, the effect of Yerba Santa on melanogenesis has not yet been investigated. We aimed to assess the biological effects of Yerba Santa on hair pigmentation. METHODS: Yerba Santa extracts were assessed for their cytological effects following X-ray irradiation treatment and then tested directly for the prevention of human hair greying. Ultra-performance liquid chromatography (UPLC) was utilized to identify the individual extract components. RESULTS: Eriodictyon angustifolium extract significantly increased melanin synthesis in the melanoma cell line through activation of the WNT/MITF/tyrosinase-signalling pathway. In contrast, E. californicum had no effect on melanin synthesis. E. angustifolium extract also demonstrated a protective effect against the damage induced by X-ray irradiation in human keratinocytes. Application of the extracts to subjects who had grey beards demonstrated a reduced number of grey beard hair per year specifically with the E. angustifolium extract. A significant decrease in grey head hair was also observed after application of E. angustifolium extract. Upregulation of gene expression related to melanin production and WNT signalling was observed after the application of E. angustifolium extract. Sterubin was the most abundant flavonoid detected by UPLC in E. angustifolium extract. In addition, sterubin showed the highest difference in terms of quantity, between E. angustifolium and E. californicum extract. CONCLUSION: Eriodictyon angustifolium extract, which is abundant in sterubin, may be suitable as a potential cosmetic and medical agent for the prevention and improvement of hair greying.

OBJECTIF: Yerba Santa (Eriodictyon angustifolium et Eriodictyon californicum) est utilisé depuis de nombreuses années en médecine traditionnelle. Cependant, l'effet de Yerba Santa sur la mélanogenèse n'a pas encore été étudié. Notre objectif était d'évaluer les effets biologiques de Yerba Santa sur la pigmentation des cheveux. MÉTHODES: Les extraits de Yerba Santa ont été évalués pour leurs effets cytologiques après un traitement d'irradiation aux rayons X, puis testés directement pour la prévention du grisonnement des cheveux humains. La chromatographie liquide ultra-performante (UPLC) a été utilisée pour identifier les composants d'extrait individuels. RÉSULTATS: L'extrait d'E. angustifolium a augmenté de manière significative la synthèse de mélanine dans la lignée cellulaire du mélanome par l'activation de la voie de signalisation WNT/MITF/tyrosinase. En revanche, E. californicum n'a eu aucun effet sur la synthèse de mélanine. L'extrait d'E. angustifolium a également démontré un effet protecteur contre les dommages induits par l'irradiation aux rayons X dans les kératinocytes humains. L'application des extraits à des sujets qui avaient une barbe grise a démontré un nombre réduit de poils gris par an spécifiquement avec l'extrait d'E. angustifolium. Une diminution significative des cheveux gris a également été observée après l'application d'extrait d'E. angustifolium. Une régulation à la hausse de l'expression des gènes liée à la production de mélanine et à la signalisation WNT a été observée après l'application d'extrait d'E. angustifolium. La stérubine était le flavonoïde le plus abondant détecté par UPLC dans l'extrait d'E. angustifolium. De plus, la stérubine a montré la plus grande différence en termes de quantité entre E. angustifolium et E. californicum. CONCLUSION: L'extrait d'E. angustifolium, qui est abondant en stérubine, peut convenir comme agent cosmétique et médical potentiel pour la prévention et l'amélioration du grisonnement des cheveux.

Effects of Vitis vinifera L. leaves extract on UV radiation damage in human keratinocytes (HaCaT).

Vitis vinifera L. water extract from red grapevine leaves contains high levels of polyphenols in quantities similar to those found in red grape and grape seeds. Phenolic compounds are the largest group of natural antioxidants with also an anti-inflammatory activity, widely demonstrated both in vitro and in vivo. Interestingly, their antioxidant effect relies not only on the direct radical scavenging activity but also on their ability in modulating cellular signalling transduction pathways. UV radiation exerts multiple effects on skin cells inducing apoptosis, senescence and carcinogenesis. The aim of this study was to investigate the antioxidant and the DNA protective potentials of Vitis vinifera L. water extract against UV-A and UV-B radiation in HaCaT cells, a human keratinocytes cell line. Comet and É£H2AX assays were used to assess DNA damage in UV irradiated cells pre-treated or not with the extract (100 µg/mL). For UV-B, DNA damage resulted significantly increased at 40 mJ/cm2 dose determining cell cycle arrest and apoptosis. For UV-A, DNA damage was significant at 10 J/cm2 while cell cycle arrest and apoptosis were evident only at 25 J/cm2. The extract (1h of pre-treatment) highlights the antioxidant and scavenger activity on the UV-A, while the maintenance of the apoptosis with both UV-A and UV-B must be interpreted as an anti-mutagenic effect.

Effect of blue light at 410 and 455 nm on Pseudomonas aeruginosa biofilm.

Pseudomonas aeruginosa is an opportunistic pathogen resistant to many antibiotics, able to form biofilm and causes serious nosocomial infections. Among anti-Pseudomonas light-based approaches, the recent antimicrobial Blue Light (aBL) treatment seems very promising. The aim of this study was to evaluate the efficiency of blue light in inhibiting and/or eradicating P. aeruginosa biofilm. Light at 410 nm has been identified as successful in inhibiting biofilm formation not only of the model strain PAO1, but also of CAUTI (catheter-associated urinary tract infection) isolates characterized by their ability to form biofilm. Results of this work on 410 nm light also demonstrated that: i) at the lowest tested radiant exposure (75 J cm-2) prevents matrix formation; ii) higher radiant exposures (225 and 450 J cm-2) light impairs the cellular components of biofilm, adherent and planktonic ones; iii) light eradicates with a good rate young and older biofilms in a light dose dependent manner; iv) it is also efficient in inactivating catalase A, a virulence factor playing an important role in pathogenic mechanisms. Light at 455 nm, even if at a lower extent than 410 nm, showed a certain anti-Pseudomonas activity. Furthermore, light at 410 nm caused detrimental effects on enzyme activity of ß-galactosidase and catalase A, and changes on plasmid DNA conformation and ortho-nitrophenyl-ß-D-galactopyranoside structure. This study supports the potential of blue light for anti-infective and disinfection applications.

Ultraviolet A light induces DNA damage and estrogen-DNA adducts in Fuchs endothelial corneal dystrophy causing females to be more affected.

Fuchs endothelial corneal dystrophy (FECD) is a leading cause of corneal endothelial (CE) degeneration resulting in impaired visual acuity. It is a genetically complex and age-related disorder, with higher incidence in females. In this study, we established a nongenetic FECD animal model based on the physiologic outcome of CE susceptibility to oxidative stress by demonstrating that corneal exposure to ultraviolet A (UVA) recapitulates the morphological and molecular changes of FECD. Targeted irradiation of mouse corneas with UVA induced reactive oxygen species (ROS) production in the aqueous humor, and caused greater CE cell loss, including loss of ZO-1 junctional contacts and corneal edema, in female than male mice, characteristic of late-onset FECD. UVA irradiation caused greater mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) damage in female mice, indicative of the sex-driven differential response of the CE to UVA, thus accounting for more severe phenotype in females. The sex-dependent effect of UVA was driven by the activation of estrogen-metabolizing enzyme CYP1B1 and formation of reactive estrogen metabolites and estrogen-DNA adducts in female but not male mice. Supplementation of N-acetylcysteine (NAC), a scavenger of reactive oxygen species (ROS), diminished the morphological and molecular changes induced by UVA in vivo. This study investigates the molecular mechanisms of environmental factors in FECD pathogenesis and demonstrates a strong link between UVA-induced estrogen metabolism and increased susceptibility of females for FECD development.

Ultra-effective near-infrared Photothermal therapy for the prostate cancer Nursing care through novel intended and surface tailored photo-responsive Ga-Au@MPS nanovesicles.

Surface tailored GaAu loaded mesoporous silica nanoparticles are considered as an important nanomaterial for biomedical applications such as diagnosis and cancer treatment. In this study, we used GaAu loaded mesoporous silica nanoparticles (Ga-Au@mSiO2) for the photothermal treatment of two prostate cancer cell lines. We systematically examined the nanocomposite form by various spectroscopic (UV-Vis, TGA and DTA) and electroscopic techniques (TEM and SEM including the elemental mapping analysis). After careful evaluation of the nanocomposite form, we performed cancer cell growth inhibition properties of the prostate cancer cell lines (DU145 and LNCaP). Also, we performed the photothermal effects of these nanocomposites on cell proliferation and apoptosis using different biochemical staining and flow cytometry. Our in vitro investigational datas are established Ga-Au@mSiO2 effectively exhibited and also with Ga-Au@mSiO2 + NIR the photothermal conversion therapy improved prostate cancer cells abolishing the prostate cancer cells. Interestingly, Ga-Au@mSiO2 + NIR was found to surpass the activity of Ga-Au@mSiO2 in all the cancer cells tested a topnotches. Hence, our current results demonstrated that surface tailored GaAu loaded mesoporous silica nanoparticles significantly inhibited the growth of prostate cancer cell lines and shown prominent antitumor effect in vitro. Thus, our study suggests that Ga-Au@mSiO2 + NIR could be used as impending anticancer candidate for photothermal ablation of prostate cancer cells. Further examinations of the mechanism indicated that anticancer activity was accomplished by inducing apoptosis in cancer cells, which is suggesting that these Ga-Au@mSiO2 + NIR nanocomposite can be used as promising candidates for nursing care cancer therapy.

Protective effects of Cordyceps extract against UVB­induced damage and prediction of application prospects in the topical administration: An experimental validation and network pharmacology study.

ETHNOPHARMACOLOGICAL RELEVANCE: UVB is a high energy source that causes the major risk factor for sunburn and skin tumor. However, photochemical interactions lead to beneficial effects such as synthesis of vitamin D and corticosteroids. Therefore, a reasonable therapeutic regime is advocated to reduce UVB injuries but makes use of synthesizing sunlight metabolite. Many natural compounds improving plant cells resistant to oxidative stress by the harnessing of solar energy may be also used to protect human cells. Although many nature plants have shown photoprotective effects on skin, the mechanisms underlying of the effects are still ambiguous. AIM OF THE STUDY: This study evaluates the protective effects of cultivated Cordyceps against UVB-induced damage in human keratinocytes and identifies the photoprotective mechanisms using a transcriptomic network approach. MATERIALS AND METHODS: Cordyceps extract compositions were investigated by HPLC analysis. Cell survival, reactive oxygen species (ROS) generation, H2O2 content, aquaporin 3 (AQP3) level and DNA damage were determined upon UVB irradiation in the presence of Cordyceps extract. In addition, next-generation sequencing was used to profile transcriptomic alteration of 20 mJ/cm2 UVB and non-UV. Finally, a network pharmacology method was applied to study Cordyceps extract-related natural compounds and their UVB-induced differentially change targets using the Cytoscape 3.7.1 software. RESULTS: Adenosine and mannitol were the major contents in Cordyceps extract. Cordyceps caused a significant diminished in intracellular UVB-induced oxidative stress, including ROS production and intracellular H2O2 content. Besides, AQP3 which mediated intracellular signal transmission and transported H2O2 into cells was significantly increased in the presence of Cordyceps extract against UVB irradiation. In addition, DNA repair effect of Cordyceps extract after UV irradiation was proven to be effective by comet assay. Moreover, KEGG analysis showed steroid hormone biosynthesis, ovarian steroidogenesis, fat digestion and absorption were enriched in top 3 between 20 mJ/cm2 UVB and non-UV. Gene ontology (Go) analysis showed that steroid metabolic process, sterol metabolic process, and cholesterol metabolic process were enriched in top3 biology process. By using network analysis, 125 potential bioactive ingredients in Cordyceps and 201 targets were identified. Finally, signal pathway analyses suggested that the protective effects of Cordyceps compounds against low dose UVB­induced changes might target PPAR signaling pathway, cholesterol metabolism, and ovarian steroidogenesis. CONCLUSION: Cordyceps extract may be an ideal product for external use of skin which could not only avoid UVB-induced adverse effects, but also could application of metabolite products by UVB such us steroid hormone and vitamin D3.

Protection from ionizing radiation-induced genotoxicity and apoptosis in rat bone marrow cells by HESA-A: a new herbal-marine compound.

HESA-A is an herbal-marine compound which improves the quality of life of end-stage cancer patients. The aim of the present study was to evaluate the possible protective effect of HESA-A against IR-induced genotoxicity and apoptosis in rat bone marrow. Rats were given HESA-A orally at doses of 150 and 300 mg/kg body weight for seven consecutive days. On the seventh day, the rats were irradiated with 4 Gy X-rays at 1 h after the last oral administration. The micronucleus assay, reactive oxygen species (ROS) level analysis, hematological analysis and flow cytometry were used to assess radiation antagonistic potential of HESA-A. Administration of 150 and 300 mg/kg of HESA-A to irradiated rats significantly reduced the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) and micronucleated normochromatic erythrocytes (MnNCEs), and also increased PCE/(PCE + NCE) ratio in bone marrow cells. Moreover, pretreatment of irradiated rats with HESA-A (150 and 300 mg/kg) significantly decreased ROS level and apoptosis in bone marrow cells, and also increased white blood cells count in peripheral blood. For the first time in this study, it was observed that HESA-A can have protective effects against radiation-induced genotoxicity and apoptosis in bone marrow cells. Therefore, HESA-A can be considered as a candidate for future studies to reduce the side effects induced by radiotherapy in cancer patients.