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Flavanols are extremely relevant for application and study due to the beneficial effect they have for humans when used internally or externally. They are identified in almost all plant cultures, as their metabolic products. Their pronounced benefit for protecting and restoring the skin in case of mechanical damage, radiation, allergens, chemicals and infections has been proven. Due to their natural origin, their dermatological application is also preferred. In such a case, the action of the chemical compounds and the generated skin metabolites have different mechanisms of action with respect to DNA and binding to proteins. The preliminary assessment of skin sensitization is a complex and lengthy task. Depending on the results, it is necessary to have an efficient technological approach for the isolation of flavanols with skin sensitization. Evaluation of the probable skin metabolic activity of cosmetic products containing flavanol (Luteolin) from processed rose wastewater is the aim of the conducted research, as well as prediction of protein and DNA binding of its metabolites by in silico methods (OECD QSAR Toolbox). The parent structure of the compound, as well as some of its generated metabolites, exhibit reactivity, i.e. they have different mechanisms of action in terms of DNA and protein binding.

The positive effect of catechins has been proven with their antimicrobial, antiviral, anti-inflammatory and antioxidant actions for organisms, i.e. have important biological significance. More pharmacological functions have been discovered with catechins in-depth research. Catechins have various uses, such as controlling obesity, scavenging free radicals, delaying aging, inhibiting human pathogenic bacteria without harming the reproduction of beneficial bacteria, etc. The task of the work is to determine the properties (toxic) and environmental fate of catechin by means of in silico metods.

Context. Human zonulin is a protein that regulates the intercellular tight junctions in various tissues and organs of the human body. Hashimoto's thyroiditis (HT) is one of the most common endocrine autoimmune disorder, but the role of increased intestinal permeability in its pathogenesis is still being studied. Objective and design. This pilot cross-sectional study investigates serum zonulin concentration in adults with Hashimoto's thyroiditis and assesses the relationship between zonulin levels, clinical hormonal and immunological characteristics. Subjects and methods. A group of 62 adults with HT participated in this study and were divided into three groups: hypothyroid (n=33) euthyroid (n=25) and hyperthyroid (n=4). Serum zonulin was determined using an ELISA method. Results. Age, gender and BMI were different between groups (hypothyroid and euthyroid ones). Serum zonulin values ranged from 2.6 to 198.0 ng/mL in participants. A direct positive correlation was found between serum zonulin levels and weight and BMI (r = 0.351, p = 0.008 and r = 0.236, p = 0.05, respectively). Conclusions. There is no correlation between zonulin and thyroid hormones or autoantibodies in Hashimoto thyroiditis patients. There is a difference in zonulin levels between the studied groups, but they are not statistically significant. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EV), key players in cell-to-cell communication, may contribute to disease propagation in several neurodegenerative diseases, including Alzheimer's disease (AD), by favoring the dissemination of neurotoxic proteins within the brain. Interestingly, growing evidence supports the role of herpes simplex virus type 1 (HSV-1) infection in the pathogenesis of AD. Here, we investigated whether HSV-1 infection could promote the spread of phosphorylated tau (ptau) among neurons via EV. We analyzed the ptau species that were secreted via EV following HSV-1 infection in neuroblastoma cells and primary neurons, focusing particularly on T205, T181, and T217, the phosphorylation sites mainly associated with AD. Moreover, by overexpressing human tau tagged with GFP (htau GFP ), we found that recipient tau knockout (KO) neurons uptook EV that are loaded with HSV-1-induced phtau GFP . Finally, we exploited an in vivo model of acute infection and assessed that cerebral HSV-1 infection promotes the release of ptau via EV in the brain of infected mice. Overall, our data suggest that, following HSV-1 infection, EV play a role in tau spreading within the brain, thus contributing to neurodegeneration.IMPORTANCEHerpes simplex virus type 1 (HSV-1) infection that reaches the brain has been repeatedly linked with the appearance of the pathognomonic markers of Alzheimer's disease (AD), including accumulation of amyloid beta and hyperphosphorylated tau proteins, and cognitive deficits. AD is a multifactorial neurodegenerative disease representing the most common form of dementia in the elderly, and no cure is currently available, thus prompting additional investigation on potential risk factors and pathological mechanisms. Here, we demonstrate that the virus exploits the extracellular vesicles (EV) to disseminate phosphorylated tau (ptau) among brain cells. Importantly, we provide evidence that the HSV-1-induced EV-bearing ptau can be undertaken by recipient neurons, thus likely contributing to misfolding and aggregation of native tau, as reported for other AD models. Hence, our data highlight a novel mechanism exploited by HSV-1 to propagate tau-related damage in the brain.

Competing Interests: Conflicts of interest M.M. has served on advisory boards and/or as a consultant for Novartis and Pfizer, and has received research funds (grants paid to the institution) from Pfizer. P.R. has received research funds (grants paid to the institution) from Novartis.

Competing Interests: The authors have no conflicts of interest to declare.

Competing Interests: The authors have no conflicts of interest to declare.

In the light of recent retrovirus pandemics, the issue of discovering new and diverse RNA-specific fluorochromes for research and diagnostics became of acute importance. The great majority of nucleic acid-specific probes either do not stain RNA or cannot distinguish between DNA and RNA. The versatility of polymethine dyes makes them suitable as stains for visualization, analysis, and detection of nucleic acids, proteins, and other biomolecules. We synthesized the asymmetric dicationic homodimeric monomethine cyanine dyes 1,1'-(1,3-phenylenebis(methylene))bis(4-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)pyridin-1-ium) bromide (Т1) and 1,1'-(1,3-phenylenebis(methylene))bis(4-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)quinolin-1-ium) bromide (M1) and tested their binding specificity, spectral characteristics, membrane penetration in living and fixed cells, cellular toxicity, and stability of fluorescent emission. Mesenchymal cells have diverse phenotypes and extensive proliferation and differentiation properties. We found dyes T1 and M1 to show high photochemical stability in living mesenchymal stem cells from apical papilla (SCAP) with a strong fluorescent signal when bound to nucleic acids. We found M1 to perform better than control fluorochrome (Hoechst 33342) for in vivo DNA visualization. T1, on the other hand, stains granular cellular structures resembling ribosomes in living cells and after permeabilization of the nuclear membrane stains the nucleoli and not the chromatin in the nucleus. This makes T1 suitable for the visualization of structures rich in RNA in living and fixed cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Beard alopecia areata, or alopecia areata barbae, (BAA) is a subset of alopecia areata, a T-cell mediated inflammatory disease that disrupts the hair follicle cycle leading to early onset of catagen. The aim of this review is to help strengthen clinicians' skills in the evaluation, diagnosis, and management of BAA. We performed a literature review according to the modified PRISMA guidelines, using a combination of relevant key words in electronic databases. According to the data from the 25 articles on BAA reviewed here, BAA mostly affects middle-aged men (mean age 31 years) who typically experience patchy hair loss in the neck region, which spreads to the scalp within 12 months. Similar to AA, BAA is associated with autoimmune diseases such as H. pylori and thyroiditis; however, BAA has no clear genetic pattern of inheritance which is observed in alopecia areata. Common dermoscopic findings in BAA include vellus white hairs and exclamation mark hairs, which may help distinguish it from other pathologies affecting facial hair. In clinical trials, the ALBAS tool offers clinicians an objective metric to evaluate BAA severity. Until recently, topical steroids have been the mainstay therapy; however, topical and oral janus kinase inhibitors are achieving improved results, with up to 75% beard regrowth in an average of 12 months., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 by S. Karger AG, Basel.)

Despite advances in acute care, ischemic stroke remains a major cause of long-term disability. Approaches targeting both neuronal and glial responses are needed to enhance recovery and improve long-term outcome. The complement C3a receptor (C3aR) is a regulator of inflammation with roles in neurodevelopment, neural plasticity, and neurodegeneration. Using mice lacking C3aR (C3aR-/-) and mice overexpressing C3a in the brain, we uncovered 2 opposing effects of C3aR signaling on functional recovery after ischemic stroke: inhibition in the acute phase and facilitation in the later phase. Peri-infarct astrocyte reactivity was increased and density of microglia reduced in C3aR-/- mice; C3a overexpression led to the opposite effects. Pharmacological treatment of wild-type mice with intranasal C3a starting 7 days after stroke accelerated recovery of motor function and attenuated astrocyte reactivity without enhancing microgliosis. C3a treatment stimulated global white matter reorganization, increased peri-infarct structural connectivity, and upregulated Igf1 and Thbs4 in the peri-infarct cortex. Thus, C3a treatment from day 7 after stroke exerts positive effects on astrocytes and neuronal connectivity while avoiding the deleterious consequences of C3aR signaling during the acute phase. Intranasal administration of C3aR agonists within a convenient time window holds translational promise to improve outcome after ischemic stroke.

Competing Interests: Conflicts of interest None disclosed.

Millions of new cancer patients receive chemotherapy each year. In addition to killing cancer cells, chemotherapy is likely to damage rapidly proliferating healthy cells, including the hair follicle keratinocytes. Chemotherapy causes substantial thinning or loss of hair, termed chemotherapy-induced alopecia (CIA), in approximately 65% of patients. CIA is often ranked as one of the most distressing adverse effects of chemotherapy, but interventional options have been limited. To date, only scalp cooling has been cleared by the US Food and Drug Administration (FDA) to prevent CIA. However, several factors, including the high costs not always covered by insurance, preclude its broader use. Here we review the current options for CIA prevention and treatment and discuss new approaches being tested. CIA interventions include scalp cooling systems (both non-portable and portable) and topical agents to prevent hair loss, versus topical and oral minoxidil, photobiomodulation therapy (PBMT), and platelet-rich plasma (PRP) injections, among others, to stimulate hair regrowth after hair loss. Evidence-based studies are needed to develop and validate methods to prevent hair loss and/or accelerate hair regrowth in cancer patients receiving chemotherapy, which could significantly improve cancer patients' quality of life and may help improve compliance and consequently the outcome of cancer treatment.

Background: Lichen planopilaris (LPP) is a primary lymphocytic cicatricial alopecia for which therapy is often ineffective and there is no cure., Objectives: Looking for a new targetable molecule in the treatment of LPP, we sought to verify whether IL-17 expression is increased in scalp biopsies from patients with active scalp lesions of LPP., Methods: Horizontal sections of hematoxylin and eosin-stained slides from 40 scalp biopsies of active LPP were retrospectively collected and stained with the monoclonal antibody against IL-17 (Abcam, Cambridge, MA; ab79056, dilution 1:100). Twenty biopsies from patients with chronic telogen effluvium served as controls because of their morphological resemblance to the normal scalp. Statistical analysis was performed using IBM SPSS Statistics for Windows (IBM Corporation, Armonk, NY)., Results: The main finding was the positive cytoplasmic expression of IL-17 in the perifollicular fibrosis of the affected follicles in LPP which was statistically significant compared with the controls ( P < 0.0001). The labeled cells were identified as fibroblasts based on their spindle shape and fascicular concentric arrangement in tight perifollicular distribution. Although most of the LPP specimens (n = 35; 87.5%) also revealed cytoplasmic IL-17 expression in the lichenoid inflammatory infiltrate, the results were not statistically significant ( P = 0.1351)., Conclusion: Our immunohistochemistry results show that blocking the IL-17 inflammatory pathway may interfere with the progression of the perifollicular fibrosis and inflammation in LPP., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Primary cicatricial alopecia (PCA), also known as scarring alopecia, comprises a diverse group of hair disorders that cause permanent destruction of the pilosebaceous unit, resulting in disappearance of the follicular ostia. Lichen planopilaris (LPP) is a subtype of primary lymphocytic cicatricial alopecia. There is an urgent need to identify novel molecules that successfully target specific pathogenic pathways in LPP to inhibit and reverse disease progression. Recent studies into LPP pathogenesis have discovered that follicular stem cells undergo epithelial-mesenchymal transition (EMT). We sought to identify drugs that target molecules involved in EMT to repurpose these drugs for treatment of LPP. We identified 8 molecules and 15 drugs that target these EMT molecules. Only four of these drugs (pioglitazone, tofacitinib, barcitinib and apremilast) have been reported in individual cases or case series of patients with LPP and controlled studies are missing. We describe each drug and mechanism of action target EMT in detail. Although previous studies have demonstrated the efficacy of EMT inhibitors in anticancer therapy, there are, to our knowledge, no studies using EMT-attenuating drugs for the treatment of LPP. The treatment molecules discussed in this paper provide a new platform for clinical studies and controlled trials in LPP., (© 2022 British Association of Dermatologists.)

Polymeric nanoparticles have been introduced as a delivery vehicle for active compounds in a broad range of medical applications due to their biocompatibility, stability, controlled release of active compounds, and reduced toxicity. The oral route is the most used approach for delivery of biologics to the body. The homeostasis and function of oral cavity tissues are dependent on the activity of stem cells. The present work focuses, for the first time, on the interaction between two types of polymeric nanoparticles, poly (lactic-co-glycolic acid) or PLGA and PLGA/chitosan, and two stem cell populations, oral keratinocyte stem cells (OKSCs) and stem cells from human exfoliated deciduous teeth (SHEDs). The main results show that statistical significance was observed in OKSCs uptake when compared with normal keratinocytes and transit amplifying cells after 24 h of incubation with 5 and 10 µg/mL PLGA/chitosan. The CD117 + SHED subpopulation incorporated more PLGA/chitosan nanoparticles than nonseparated SHED. The uptake for PLGA/chitosan particles was better than for PLGA particles with longer incubation times, yielding better results in both cell types. The present results demonstrate that nanoparticle uptake depends on stem cell type, incubation time, particle concentration, and surface properties.

ABCG2/BCRP is an ABC transporter that plays an important role in tissue protection by exporting endogenous substrates and xenobiotics. ABCG2 is of major interest due to its involvement in multidrug resistance (MDR), and understanding its complex efflux mechanism is essential to preventing MDR and drug-drug interactions (DDI). ABCG2 export is characterized by two major conformational transitions between inward- and outward-facing states, the structures of which have been resolved. Yet, the entire transport cycle has not been characterized to date. Our study bridges the gap between the two extreme conformations by studying connecting pathways. We developed an innovative approach to enhance molecular dynamics simulations, 'kinetically excited targeted molecular dynamics', and successfully simulated the transitions between inward- and outward-facing states in both directions and the transport of the endogenous substrate estrone 3-sulfate. We discovered an additional pocket between the two substrate-binding cavities and found that the presence of the substrate in the first cavity is essential to couple the movements between the nucleotide-binding and transmembrane domains. Our study shed new light on the complex efflux mechanism, and we provided transition pathways that can help to identify novel substrates and inhibitors of ABCG2 and probe new drug candidates for MDR and DDI., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Dandruff is a common scalp condition, which frequently causes psychological distress in those affected. Dandruff is considered to be caused by an interplay of several factors. However, the pathogenesis of dandruff remains under-investigated, especially with respect to the contribution of the hair follicle. As the hair follicle exhibits unique immune-modulatory properties, including the creation of an immunoinhibitory, immune-privileged milieu, we propose a novel hypothesis taking into account the role of the hair follicle. We hypothesize that the changes and imbalance of yeast and bacterial species, along with increasing proinflammatory sebum by-products, leads to the activation of immune response and inflammation. Hair follicle keratinocytes may then detect these changes in scalp microbiota resulting in the recruitment of leukocytes to the inflammation site. These changes in the scalp skin immune-microenvironment may impact hair follicle immune privilege status, which opens new avenues into exploring the role of the hair follicle in dandruff pathogenesis. Also see the video abstract here: https://youtu.be/mEZEznCYtNs., (© 2021 The Authors. BioEssays published by Wiley Periodicals LLC.)