Genetic alterations landscape in paediatric thyroid tumours and/or differentiated thyroid cancer: Systematic review.

Differentiated thyroid cancer (DTC) is a rare disease in the paediatric population (≤ 18 years old. at diagnosis). Increasing incidence is reflected by increases in incidence for papillary thyroid carcinoma (PTC) subtypes. Compared to those of adults, despite aggressive presentation, paediatric DTC has an excellent prognosis. As for adult DTC, European and American guidelines recommend individualised management, based on the differences in clinical presentation and genetic findings. Therefore, we conducted a systematic review to identify the epidemiological landscape of all genetic alterations so far investigated in paediatric populations at diagnosis affected by thyroid tumours and/or DTC that have improved and/or informed preventive and/or curative diagnostic and prognostic clinical conduct globally. Fusions involving the gene RET followed by NTRK, ALK and BRAF, were the most prevalent rearrangements found in paediatric PTC. BRAF V600E was found at lower prevalence in paediatric (especially ≤ 10 years old) than in adults PTC. We identified TERT and RAS mutations at very low prevalence in most countries. DICER1 SNVs, while found at higher prevalence in few countries, they were found in both benign and DTC. Although the precise role of DICER1 is not fully understood, it has been hypothesised that additional genetic alterations, similar to that observed for RAS gene, might be required for the malignant transformation of these nodules. Regarding aggressiveness, fusion oncogenes may have a higher growth impact compared with BRAF V600E. We reported the shortcomings of the systematized research and outlined three key recommendations for global authors to improve and inform precision health approaches, glocally.

Mapping the learning styles of medical students in Brazil.

BACKGROUND: Medical education has evolved based on the application of pedagogical actions that place the student as the protagonist of the learning process through the use of active teaching methodologies. Within this context, higher education teachers should use strategies that focus on the student and his/her context and avoid traditional teaching methods. Specifically in medical schools, there is an even greater challenge since the teaching methods of medical curricula differ from those used in previous schooling. Consequently, students acquire their own style of processing information that is often incompatible with the profile of medical schools. This may be one of the factors responsible for the lack of motivation among undergraduates. OBJECTIVE: The aim of this study was to characterize the learning styles of students enrolled in a Brazilian medical school using the Felder-Soloman Index of Learning Styles (ILS). METHODS: This was a cross-sectional, descriptive, quantitative study that included students from the 1st to the 6th year of a Brazilian medical school. The students participating in this study voluntarily answered 44 questions about learning styles of the Felder-Silverman instrument validated in Brazil. The instrument was divided so that each domain consisted of 11 questions with two response options in which only one could be selected. For each domain, a score (1 point) was assigned to the selected option (a, b) of the question and the learning style category was determined as the difference between these values. For data collection and tabulation, we used the Learning Syle Platform (EdA Platform) developed based on Felder's studies since this system processes information about the dimension analyzed, the preferred style, and the most striking characteristics of each style. RESULTS: The results showed that sensing was the preferred learning style of the students, followed by the sequential and visual styles. It was not possible to determine whether gender or age influences the choice of learning methods because of the homogeneity of the results. CONCLUSIONS: The present data will enable teachers of the institution involved in this study to plan pedagogical actions that improve the students' self-awareness, as well as their teaching-learning skills, by choosing the most adequate active methodologies for the medical education programs considering the individuality of each student and class.

Longitudinal SARS-CoV-2 seroprevalence in Portugal and antibody maintenance 12 months after infection.

During the COVID-19 pandemic, Portugal has experienced three distinct SARS-CoV-2 infection waves. We previously documented the prevalence of SARS-CoV-2 immunity, measured by specific antibodies, in September 2020, 6 months after the initial moderate wave. Here, we show the seroprevalence changes 6 months later, up to the second week of March 2021, shortly following the third wave, which was one of the most severe in the world, and 2 months following the start of the vaccination campaign. A longitudinal epidemiological study was conducted, with a stratified quota sample of the Portuguese population. Serological testing was performed, including ELISA determination of antibody class and titers. The proportion of seropositives, which was 2.2% in September 2020, rose sharply to 17.3% (95% CI: 15.8-18.8%) in March 2021. Importantly, circulating IgG and IgA antibody levels were very stable 6 months after the initial determination and up to a year after initial infection, indicating long-lasting infection immunity against SARS-CoV-2. Moreover, vaccinated people had higher IgG levels from 3 weeks post-vaccination when compared with previously infected people at the same time post-infection.

Analytical aspects of the antinuclear antibody test by HEp-2 indirect immunofluorescence: EFLM report on an international survey.

OBJECTIVES: Detection of antinuclear antibodies (ANA) by indirect immunofluorescence assay using HEp-2 cells (HEp-2 IFA) is used to screen for various autoimmune diseases. HEp-2 IFA suffers from variability, which hampers harmonization. METHODS: A questionnaire was developed to collect information on HEp-2 IFA methodology, computer-assisted diagnosis (CAD) systems, training, inter-observer variability, quality assessment, reagent lot change control, and method verification. The questionnaire was distributed to laboratories by Sciensano (Belgium), national EASI groups (Italy, Croatia, Portugal, Estonia, Greece) and ICAP (worldwide). Answers were obtained by 414 laboratories. The results were analysed in the framework of the recent EFLM/EASI/ICAP ANA recommendations (companion paper). RESULTS: Laboratories used either HEp-2, HEp-2000, or HEp-20-10 cells and most laboratories (80%) applied the same screening dilution for children and adults. The conjugate used varied between laboratories [IgG-specific (in 57% of laboratories) vs. polyvalent]. Sixty-nine percent of CAD users reviewed the automatic nuclear pattern and 53% of CAD users did not fully exploit the fluorescence intensity for quality assurance. Internal quality control was performed by 96% of the laboratories, in 52% of the laboratories only with strongly positive samples. Interobserver variation was controlled by 79% of the laboratories. Limited lot-to-lot evaluation was performed by 68% of the laboratories. Method verification was done by 80% of the respondents. CONCLUSIONS: Even though many laboratories embrace high-quality HEp-2 IFA, substantial differences in how HEp-2 IFA is performed and controlled remain. Acting according to the EFLM/EASI/ICAP ANA recommendations can improve the global performance and quality of HEp-2 IFA and nurture harmonization.

Detection of antinuclear antibodies: recommendations from EFLM, EASI and ICAP.

OBJECTIVES: Antinuclear antibodies (ANA) are important for the diagnosis of various autoimmune diseases. ANA are usually detected by indirect immunofluorescence assay (IFA) using HEp-2 cells (HEp-2 IFA). There are many variables influencing HEp-2 IFA results, such as subjective visual reading, serum screening dilution, substrate manufacturing, microscope components and conjugate. Newer developments on ANA testing that offer novel features adopted by some clinical laboratories include automated computer-assisted diagnosis (CAD) systems and solid phase assays (SPA). METHODS: A group of experts reviewed current literature and established recommendations on methodological aspects of ANA testing. This process was supported by a two round Delphi exercise. International expert groups that participated in this initiative included (i) the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group "Autoimmunity Testing"; (ii) the European Autoimmune Standardization Initiative (EASI); and (iii) the International Consensus on ANA Patterns (ICAP). RESULTS: In total, 35 recommendations/statements related to (i) ANA testing and reporting by HEp-2 IFA; (ii) HEp-2 IFA methodological aspects including substrate/conjugate selection and the application of CAD systems; (iii) quality assurance; (iv) HEp-2 IFA validation/verification approaches and (v) SPA were formulated. Globally, 95% of all submitted scores in the final Delphi round were above 6 (moderately agree, agree or strongly agree) and 85% above 7 (agree and strongly agree), indicating strong international support for the proposed recommendations. CONCLUSIONS: These recommendations are an important step to achieve high quality ANA testing.

Cyclin-dependent Kinases 4/6 Inhibitors in Neuroendocrine Neoplasms: from Bench to Bedside.

PURPOSE OF REVIEW: Cyclin-dependent kinases (CDKs) are key regulators that play an important role in cell division. Palbociclib, ribociclib and abemaciclib showed significant antitumor activity in several malignancies and, recently, also a myeloprotective effect for trilaciclib when added to chemotherapy. The purpose of this review is to highlight the current evidence for CDK4/6 inhibitors in neuroendocrine neoplasms (NENs). RECENT FINDINGS: Preclinical results showed a promising antitumor activity of CDK4/6 inhibitors in neuroendocrine tumors (NETs), but so far, the very few small clinical trials did not show a strong impact on progression free survival (PFS) and objective response in NETs. Meanwhile, the CDK4/6 inhibitor trilaciclib revealed significant effects in reducing chemotherapy-induced myelosuppression in small cell lung cancer (SCLC). Up to date, CDK4/6 inhibitors are still considered investigational in NETs as antitumor agents, whereas trilaciclib can be used in the routine clinical practice in extensive stage SCLC patients for reducing myelotoxicity of standard chemotherapy.

Acceptance of SARS-CoV-2 vaccination among cancer patients in Portugal: attitudes and associated factors.

OBJECTIVE: COVID-19 vaccines have shown efficacy and safety in healthy people. However, cancer patients under active immunosuppressive treatment were not included in the clinical trials conducted to test vaccines' efficacy and safety. This study aimed to evaluate the COVID-19 vaccine acceptance in cancer patients undergoing immunosuppressive therapy. METHODS: A total of 200 adult cancer patients received a questionnaire between March 8 and April 2, 2021, before the beginning of cancer patients' vaccination in Portugal. The questionnaire adapted from previously conducted studies included 11 close-ended items, evaluating variables such as patient sociodemographic and clinical characteristics, and the acceptance and underlying reasons to be or not to be vaccinated. The primary outcome was the intended acceptance of the COVID-19 vaccine in cancer patients. Multiple logistic regression was performed to identify factors associated with intended acceptance. RESULTS: Among the 200 delivered questionnaires, only 169 were included in this study. From those, 142 (84%) patients intended to be vaccinated against COVID-19. Only 27 participants (16%) had not yet decided or were reluctant to COVID-19 vaccination. High school degree (odds ratio (OR) 0.133, 95% confidence interval (C.I.) 0.031-0.579, p = 0.007], rural residence (OR 0.282, 95% C.I. 0.081-0.984, p = 0.047), and reluctance in believing in the vaccine efficacy (OR 0.058, 95% C.I. 0.016-0.204, p < 0.001] were identified predictors factor for COVID-19 vaccine hesitancy. CONCLUSION: Most patients intended to be vaccinated against COVID-19, and specific factors such as education level, rural residence and the belief in vaccine efficacy were related to vaccine acceptance.

Criterion validity of 14-item Health Literacy Scale (HLS-14) questionnaire in Brazilian adults and older people.

The objective of this study was to evaluate the criterion validity of the 14-item Health Literacy Scale (HLS-14) in Brazilian adults and older adults. The cross-sectional study performed in an oral health (OH) prospective cohort was conducted in 2017 in Piracicaba, Brazil. The HLS-14 questionnaire was applied to evaluate Health Literacy (HL) by dimensions: Functional literacy (FunL), Communicative literacy (ComL) and Critical literacy (CriL). An evaluation protocol (EP) was proposed to evaluate the criterion validity of HLS-14 considering HL dimensions (FunL: reading of the drug information leaflets; ComL: reading of the medical prescription and CriL: identification of OH conditions). HL (total) was dichotomized by the median in high (≥35 point) or low (<35 point) HL. Kendall's rank correlation coefficient (p < 0.05) and chi-squared test (p < 0.05) were applied. There was agreement between EP and HLS-14 for FunL (p < 0.01). There was association between high HL, measured through the HLS-14 questionnaire, assessing the reading of the drug information leaflets (p < 0.01) and the need for help to read them (p < 0.01). EP showed association between high HL and being able to read the drug information leaflet (p < 0.01), not needing help to read (p < 0.01), having found in the prescription all the information to take the medicine (p < 0.01) and knowing two or more health and OH information in the educational material (p < 0.01). The HSL-14 questionnaire showed criterion validity to measure FunL, and for some items of ComL and CriL evaluation. HL evaluation in a practical and multidimensional way could have an effect on the communication between health professional and patient, motivation and health outcomes.

The bank robbery analogy as a first approach for understanding basic concepts of synthesis, transport, and mechanism of action of hormones.

Learning endocrine physiology can be challenging. Some physiological concepts are abstract, making the process of learning more difficult for students. The comprehension of basic concepts, such as chemical hormone classification, is essential to understand the differences in synthesis, secretion, transport, and mechanism of action of hormones. To assist the students on this subject, we developed an analogy between the basic concepts of hormone synthesis, transport, and mechanism of action and a bank robbery as a first approach to engage and stimulate their learning process. In the analogy, the students are asked to help identify and characterize two bank robbery crews based on a set of evidence collected by the police. The goal is to identify the general profile of lipid- and water-soluble hormones synthesis, transport, and mechanism of action on target cells. When applying the activity, the students showed a great deal of interest in solving the crime and they seemed to understand the similarities between the analogy and the subject.NEW & NOTEWORTHY Two endocrine bank robbery crews are being searched by the police. As an endocrine system student, you have been summoned to help the police solve the robberies.

Prevalence of SARS-CoV-2 Antibodies after First 6 Months of COVID-19 Pandemic, Portugal.

In September 2020, we tested 13,398 persons in Portugal for antibodies against severe acute respiratory syndrome coronavirus 2 by using a quota sample stratified by age and population density. We found a seroprevalence of 2.2%, 3-4 times larger than the official number of cases at the end of the first wave of the pandemic.

Tumour exosome integrins determine organotropic metastasis.

Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6ß4 and α6ß1 were associated with lung metastasis, while exosomal integrin αvß5 was linked to liver metastasis. Targeting the integrins α6ß4 and αvß5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

Health literacy on oral health practice and condition in an adult and elderly population.

The objective of this study was to investigate the impact of health literacy (HL) on health practices and oral health outcomes in an adult and elderly population in Brazil. A cross-sectional study nested in a cohort study was followed up over a period of four years (2011 and 2015) and assessed individuals between 23 and 69 years old from Piracicaba, São Paulo, Brazil. Data were collected by means of oral examinations (coronal caries, periodontal disease and visible biofilm) and interviews (socioeconomic, demographic, oral health-related quality of life, health practices and HL). The 14-item Health Literacy Scale (HLS) was used for HL data, which was the main explanatory variable. The result of the sum of the HLS-14 questionnaire for each participant was dichotomized into the median (46 points): 'high' and 'low' HL. Binary/multinomial logistic regressions were performed on health practice and oral health outcomes, controlled by age and sex (Model 1) and age, sex and socioeconomic status (Model 2; p < 0.05). The final sample consisted of 137 subjects and 43.8% (n = 60) presented low HL (LHL). LHL was associated with health practices, such as use of public dental services in Model 1 (odds ratio [OR] = 0.34, 95% CI: 0.14-0.87) and use of dental services for emergency in Model 1 (OR = 2.69, 95% CI: 1.29-5.51) and Model 2 (OR = 2.93, 95% CI: 1.17-7.30). Based on age and sex, LHL was associated with use of public dental service and use of emergency dental visits. Based on age, sex and socioeconomic status, LHL was associated with use of emergency dental visits.

Success of in vitro fertilization and its association with the levels of psychophysiological stress before and during the treatment.

Despite the advance of assisted reproduction, high rates of failure in treatment are still observed. Herein, we investigated how the psychophysiological stress profiles of patients can modulate the in vitro fertilization treatment (IVF) outcome. The women who had failure in IVF (n = 13; 65%) had higher baseline salivary cortisol awakening response and anxiety-state during treatment than patients who became pregnant (n = 7; 35%). Patients with major stress levels and religious coping style showed lower social support, which was correlated with higher anxiety. Therefore, we appointed stress modulators that negatively affect IVF and should be improved aiming to increase its success.

Acupuncture as a therapeutic resource for treatment of chronic pain in people with haemophilia.

INTRODUCTION: Chronic pain is common in individuals with severe and moderate haemophilia who did not receive prophylaxis during childhood. OBJECTIVE: To verify the effectiveness of acupuncture in reducing intensity in chronic pain, changes in quality of life, joint function and impact on treatment satisfaction of haemophilia patients. METHODS: Single-blinded randomized clinical trial with 28 participants divided into two groups: Acupuncture (G1) treated with traditional unilateral acupuncture (side of greatest referred pain) and Control (G2) treated with transcutaneous electrical nerve stimulation (TENS), with electrodes on the joint of most intense pain. Both groups had a 20-minute session per week, total of 05 consecutive sessions. Before starting treatment, participants underwent sociodemographic assessment, physical assessment (HJHS), quality of life questionnaire (Haem-a-Qol) and treatment expectation (Likert scale). After the end of the fifth session, Haem-a-Qol, HJHS and degree of satisfaction (Likert) were performed. The assessment of pain intensity using the visual analogue scale (VAS) was performed before the beginning and after the end of all sessions in both groups. Statistical analysis was performed using ANOVA, Bonferroni, t test and chi-square test (P < .05). RESULTS: There was a statistical difference within and between groups G1 and G2 in reduction of VAS. In Haem-a-Qol, the groups showed similarity in quality of life. Both groups had high expectations for treatment. G1 presented a better degree of treatment satisfaction than G2. Total HJHS showed no difference within and between groups. CONCLUSION: Acupuncture was effective in reducing pain intensity in haemophilia patients with chronic joint disease when compared to TENS.

Individual behavioral differences and health of golden-headed lion tamarins (Leontopithecus chrysomelas).

Individual behavioral differences may influence how animals cope with altered environments. Depending on their behavioral traits, individuals may thus vary in how their health is affected by environmental conditions. We investigated the relationship between individual behavior of free-living golden-headed lion tamarins (Leontopithecus chrysomelas) responding to a novel object (to assess exploration-avoidance), and their habitat use and health status (endoparasitism; clinical measures: biometric data, heart rate, respiratory frequency, and temperature; fecal glucocorticoid metabolites). As parasite transmission can be affected by individual variation in social contact and social grooming, we also evaluated whether more sociable individuals show higher endoparasite loads compared with less sociable animals. Four groups living in landscapes with different levels of human disturbance were investigated: two in degraded forest fragments in an agricultural matrix (DFAM-higher disturbance), and two in a cocoa agroforestry system (cabruca-lower disturbance) in the Atlantic forest of South Bahia, Brazil. Using a subjective ratings approach, highly correlated adjective descriptors were combined to produce z-score ratings of one derived variable ("confidence"), which was selected to characterize the tamarins' exploration/avoidance responses during a novel object test. The higher the confidence score, the longer female tamarins spent foraging for prey independent of landscape, and the greater their body mass independent of sex and landscape. Only DFAM individuals showed intestinal parasite infection. Endoparasite loads were positively correlated with the number of grooming partners, suggesting an association between social grooming and transmission (more groomers = more endoparasites). Individual behavior, including in a test situation, may thus have some predictive value for behavior in a free-living context, and for its health consequences.

Factors associated with conducting planning for secondary oral health care services in Brazil.

BACKGROUND: Planning in health services specifically aims to improve the health status of a given population, guaranteeing access with equity and justice, as well as streamlining the response of the health system to the needs perceived by the community. This research aims to identify the factors associated with planning Specialized Dental Clinics (SDCs). METHODS: Secondary data were used from the external evaluation of the database of the first National Program for Access and Quality Improvement of SDCs (NPAQI-SDCs) and the informed Outpatient Information System of the Unified Health System (OIS/UHS), which contains data on the specialized dental procedures performed at SDCs. It consisted of a quantitative study in which Pearson chi-square statistical tests (p < 0.05) and a multivariate logistic regression were applied with odds ratio (OR) estimate. RESULTS: The results indicated that the realization of planning in SDCs was associated with lower coverage of the Oral Health Team of the Familiy Health Strategy in a municipality (OR = 1.4; 95% CI: 1.0-1.9, p = 0.049), additional training for managers (p = 0.038), the practice of self-assessment (OR = 8.2; 95% CI: 5.8-11.6; p = 0.000) and meeting service production targets (OR = 1.9; 95% CI: 1.2-3.2; p = 0.011). CONCLUSION: The results indicate that the work processes of the SDCs, especially with regard to service management, are essential to the proper functioning of the service and the practice of planning is linked to the technical capacity and commitment of service managers.

Presence of antigenotoxic and anticytotoxic effects of the chalcone 1E,4E-1-(4-chlorophenyl)-5-(2,6,6-trimethylcyclohexen-1-yl)penta-1,4-dien-3-one using in vitro and in vivo assays.

Chalcones are chemically defined as α,ß-unsaturated ketones with a 1,3-diphenyl-2-propen-1-one nucleus. These compounds occur naturally in plants and are considered precursors of flavonoids. Given that evaluating genetic toxicology tests is essential in investigating the safe use and chemopreventive potential of different natural and synthetic compounds, this study aimed to assess the genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activity of the chalcone 1E,4E-1-(4-chlorophenyl)-5-(2,6,6-trimethylcyclohexen-1-yl)penta-1,4-dien-3-one (CAB7ß). The CAB7ß was synthesized via Claisen-Schmidt reaction. The Ames test was applied using the co-treatment model as well as a micronucleus assay of mouse bone marrow with co-, pre- and post-treatment models. Our results indicate no genotoxic effect for CAB7ß in any of the tests applied. At all the concentrations used, CAB7ß showed a significant DNA protective effect against the mutagenic action of 4-nitroquinoline-1-oxide and sodium azide according to the Ames test, and against doxorubicin in the co-, pre- and post-treatment models of the micronucleus assay. CAB7ß alone displayed cytotoxic activity in the micronucleus test. At concentrations of 12,5 and 50 µg/plate, CAB7ß showed a moderate cytotoxic profile only in Salmonella typhimurium strain TA98. However, an anticytotoxic effect was observed against S. typhimurium strain TA100 for all the concentrations tested and during co-, pre- and post-treatment in the micronucleus assay. It was concluded that CAB7ß exhibited a slightly cytotoxic effect in S. typhimurium strain TA98 and significant antigenotoxic and anticytotoxic effects in cells of mouse, making it a promising candidate in chemoprevention and possibly in the development of new cancer treatments.

Can body mass index identify cardiac autonomic dysfunction in women who are apparently healthy?

We investigated the extent to which obesity could identify autonomic dysfunction of heart control in a cross-sectional study with 65 women (aged 18-45 years), categorized as eutrophic, overweight or obese. We collected anthropometric measures and measures of heart rate variability (HRV) between March 2015 and March 2017. Low frequency in normalized units (LF(nu)) over 46 was considered a marker of autonomic imbalance and high frequency in normalized units (HF(nu)) below 38 a marker of depressed vagal modulation. Overweight (mean difference MΔHF(nu) = -13.11 [95% confidence interval (CI) of difference, -25.88, -0.34], Hedges's g = 0.65, common language effect size (CL) = 68.1%) and obese (MΔHF(nu) = -21.22 [95% CI, -31.89, -10.55], Hedges's g = 1.17, CL = 79.2%) women presented depressed vagal modulation compared to eutrophic women. Autonomic imbalance increased as body mass index increased (eutrophic-to-overweight MΔLF(nu) = 13.06 [95% CI, 1.65, 24.47], g = 0.65, CL = 67.9%, and overweight-to-obese MΔLF(nu) = 21.07 [95% CI, 10.32, 31.82], g = 1.15, CL 78.9%). The odds ratio for depressed HF(nu) among overweight women was 2.36 (95% CI 0.77, 7.29) and 2.18 among obese women (95% CI 0.79, 5.99), as well as 9.17 (95% CI 2.62, 32.04) and 17.39 for increased LF(nu) (95% CI 2.13, 141.76), respectively. The parasympathetic activity is diminished and autonomic imbalance of the cardiac control increased with increasing BMI categories.

Synthesis of a Small Library of Nature-Inspired Xanthones and Study of Their Antimicrobial Activity.

A series of thirteen xanthones 3-15 was prepared based on substitutional (appendage) diversity reactions. The series was structurally characterized based on their spectral data and HRMS, and the structures of xanthone derivatives 1, 7, and 8 were determined by single-crystal X-ray diffraction. This series, along with an in-house series of aminated xanthones 16-33, was tested for in-vitro antimicrobial activity against seven bacterial (including two multidrug-resistant) strains and five fungal strains. 1-(Dibromomethyl)-3,4-dimethoxy-9H-xanthen-9-one (7) and 1-(dibromomethyl)-3,4,6-trimethoxy-9H-xanthen-9-one (8) exhibited antibacterial activity against all tested strains. In addition, 3,4-dihydroxy-1-methyl-9H-xanthen-9-one (3) revealed a potent inhibitory effect on the growth of dermatophyte clinical strains (T. rubrum FF5, M. canis FF1 and E. floccosum FF9), with a MIC of 16 µg/mL for all the tested strains. Compounds 3 and 26 showed a potent inhibitory effect on two C. albicans virulence factors: germ tube and biofilm formation.

Efficacy, Stability, and Safety Evaluation of New Polyphenolic Xanthones Towards Identification of Bioactive Compounds to Fight Skin Photoaging.

Antioxidants have long been used in the cosmetic industry to prevent skin photoaging, which is mediated by oxidative stress, making the search for new antioxidant compounds highly desirable in this field. Naturally occurring xanthones are polyphenolic compounds that can be found in microorganisms, fungi, lichens, and some higher plants. This class of polyphenols has a privileged scaffold that grants them several biological activities. We have previously identified simple oxygenated xanthones as promising antioxidants and disclosed as hit, 1,2-dihydroxyxanthone (1). Herein, we synthesized and studied the potential of xanthones with different polyoxygenated patterns as skin antiphotoaging ingredients. In the DPPH antioxidant assay, two newly synthesized derivatives showed IC50 values in the same range as ascorbic acid. The synthesized xanthones were discovered to be excellent tyrosinase inhibitors and weak to moderate collagenase and elastase inhibitors but no activity was revealed against hyaluronidase. Their metal-chelating effect (FeCl3 and CuCl2) as well as their stability at different pH values were characterized to understand their potential to be used as future cosmetic active agents. Among the synthesized polyoxygenated xanthones, 1,2-dihydroxyxanthone (1) was reinforced as the most promising, exhibiting a dual ability to protect the skin against UV damage by combining antioxidant/metal-chelating properties with UV-filter capacity and revealed to be more stable in the pH range that is close to the pH of the skin. Lastly, the phototoxicity of 1,2-dihydroxyxanthone (1) was evaluated in a human keratinocyte cell line and no phototoxicity was observed in the concentration range tested.