Rosacea is a common chronic inflammation of sebaceous gland-rich facial skin characterized by severe skin dryness, elevated pH, transepidermal water loss, and decreased hydration levels. Until now, there has been no thorough molecular analysis of permeability barrier alterations in the skin of patients with rosacea. Thus, we aimed to investigate the barrier alterations in papulopustular rosacea samples compared with healthy sebaceous gland-rich skin, using RNA sequencing analysis (n = 8). Pathway analyses by Cytoscape ClueGO revealed 15 significantly enriched pathways related to skin barrier formation. RT-PCR and immunohistochemistry were used to validate the pathway analyses. The results showed significant alterations in barrier components in papulopustular rosacea samples compared with sebaceous gland-rich skin, including the cornified envelope and intercellular lipid lamellae formation, desmosome and tight junction organizations, barrier alarmins, and antimicrobial peptides. Moreover, the barrier damage in papulopustular rosacea was unexpectedly similar to atopic dermatitis; this similarity was confirmed by immunofluorescent staining. In summary, besides the well-known dysregulation of immunological, vascular, and neurological functions, we demonstrated prominent permeability barrier alterations in papulopustular rosacea at the molecular level, which highlight the importance of barrier repair therapies for rosacea.

Keratinocytes provide the first line of defense of the human body against carcinogenic ultraviolet (UV) radiation. Acute and chronic UVB-mediated cellular responses were widely studied. However, little is known about the role of mitochondrial regulation in UVB-induced DNA damage. Here, we show that poly (ADP-ribose) polymerase 1 (PARP1) and ataxia-telangiectasia-mutated (ATM) kinase, two tumor suppressors, are important regulators in mitochondrial alterations induced by UVB. Our study demonstrates that PARP inhibition by ABT-888 upon UVB treatment exacerbated cyclobutane pyrimidine dimers (CPD) accumulation, cell cycle block and cell death and reduced cell proliferation in premalignant skin keratinocytes. Furthermore, in human keratinocytes UVB enhanced oxidative phosphorylation (OXPHOS) and autophagy which were further induced upon PARP inhibition. Immunoblot analysis showed that these cellular responses to PARP inhibition upon UVB irradiation strongly alter the phosphorylation level of ATM, adenosine monophosphate-activated kinase (AMPK), p53, protein kinase B (AKT), and mammalian target of rapamycin (mTOR) proteins. Furthermore, chemical inhibition of ATM led to significant reduction in AMPK, p53, AKT, and mTOR activation suggesting the central role of ATM in the UVB-mediated mitochondrial changes. Our results suggest a possible link between UVB-induced DNA damage and metabolic adaptations of mitochondria and reveal the OXPHOS-regulating role of autophagy which is dependent on key metabolic and DNA damage regulators downstream of PARP1 and ATM.

Breast cancer patients are characterized by the oncobiotic transformation of multiple microbiome communities, including the gut microbiome. Oncobiotic transformation of the gut microbiome impairs the production of antineoplastic bacterial metabolites. The goal of this study was to identify bacterial metabolites with antineoplastic properties. We constructed a 30-member bacterial metabolite library and screened the library compounds for effects on cell proliferation and epithelial-mesenchymal transition. The metabolites were applied to 4T1 murine breast cancer cells in concentrations corresponding to the reference serum concentrations. However, yric acid, glycolic acid, d-mannitol, 2,3-butanediol, and trans-ferulic acid exerted cytostatic effects, and 3-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, and vanillic acid exerted hyperproliferative effects. Furthermore, 3-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, 2,3-butanediol, and hydrocinnamic acid inhibited epithelial-to-mesenchymal (EMT) transition. We identified redox sets among the metabolites (d-mannitol—d-mannose, 1-butanol—butyric acid, ethylene glycol—glycolic acid—oxalic acid), wherein only one partner within the set (d-mannitol, butyric acid, glycolic acid) possessed bioactivity in our system, suggesting that changes to the local redox potential may affect the bacterial secretome. Of the nine bioactive metabolites, 2,3-butanediol was the only compound with both cytostatic and anti-EMT properties.

As a contact sport, wrestling may result in injuries. Based on the severity, they are classified as mild, moderate, severe and critical. All injuries occurring at international competitions are documented in a cloud-based surveillance system. The purpose of this study was to analyze the incidence and characteristics of moderate and severe (including critical) wrestling injuries that occurred during five international Olympic-style wrestling competitions in 2016-2019. Three Wrestling World Championships and two European Wrestling tournaments were organized by the Hungarian Wrestling Federation in 2016-2019. A total of 2483 wrestlers in three Olympic wrestling styles have competed in 3007 matches. Data from all injuries were recorded and analyzed to define rates, locations, types and severity, and to compare with previous reports. A total of 53 wrestlers sustained 55 injuries, which is equivalent to an overall injury incidence rate of 9.1‰ (9.1/1000 athletic exposures). Greco-Roman and Women Wrestling had the same injury incidence rate, while Freestyle had a lower one (9.5‰ versus 8.5‰). The injury proportion by regions and anatomic locations were on head and face 29.1%, spine and trunk 16.4 % and the upper-and-lower extremity injuries equally 27.3%. The most common types of injuries included ligament lesions, joint injuries, skin lacerations, and contusions. Five wrestlers (0.8‰) sustained strangulation or concussion. Wrestling injury rates during United World Wrestling competitions are not high, but when happen they can be serious. Despite relatively low incidence rate of injuries, there is a need for continuous education for medical teams, referees and coaches to avoid wrestling injuries.

The Roma population is typified by a poor and, due to difficulties in ethnicity assessment, poorly documented health status. We aimed to compare the usefulness of self-reporting and observer-reporting in Roma classification for surveys investigating differences between Roma and non-Roma populations. Both self-reporting and observer-reporting of Roma ethnicity were applied in a population-based health interview survey. A questionnaire was completed by 1849 people aged 18–64 years; this questionnaire provided information on 52 indicators (morbidity, functionality, lifestyle, social capital, accidents, healthcare use) indicators. Multivariate logistic regression models controlling for age, sex, education and employment were used to produce indicators for differences between the self-reported Roma (N = 124) and non-Roma (N = 1725) populations, as well as between observer-reported Roma (N = 179) and non-Roma populations (N = 1670). Differences between interviewer-reported and self-reported individuals of Roma ethnicity in statistical inferences were observed for only seven indicators. The self-reporting approach was more sensitive for two indicators, and the observer-reported assessment for five indicators. Based on our results, the self-reported identity can be considered as a useful approach, and the application of observer-reporting cannot considerably increase the usefulness of a survey, because the differences between Roma and non-Roma individuals are much bigger than the differences between indicators produced by self-reported or observer-reported data on individuals of Roma ethnicity.

The application of natural plant extracts in UV-protection is popular and intensively studied. Silymarin (from Silibum marianum), a naturally occurring polyphenol, has recently received attention due to its antioxidant, anti-inflammatory and anti-apoptotic effects. However, its role in the UV-mediated keratinocyte cell response is still controversial. In this study, we investigated the effects of Silibum marianum extracts with different origins and formulations on UVA-exposed HaCaT keratinocytes in vitro. Our results show, that silymarin treatment caused an inverse dose-dependent photosensitivity relationship (at higher doses, a decrease in cell viability and ROS production) after UVA exposure. The attenuation of the UVA-induced ROS generation after silymarin treatment was also observed. Moreover, silymarin pre-treatment increased the cyclobutane pyrimidine dimer photolesions in keratinocytes after UVA exposure. These results indicated the dual role of silymarin in UVA-exposed keratinocytes. It scavenges ROS but still induces phototoxicity. Based on our results dermatological applications of silymarin and related compounds should be considered very carefully.