Characterization of the mechanical properties of the cortex region of human hair fibers by multiparametric atomic force microscopy mapping.

We show the benefit of the use of atomic force microscopy (AFM) in spectroscopy force mode (FV: force volume) for evaluation of the cosmetic active effectiveness in improving the mechanical properties of human hair fibers cortex region. For this, we characterized human hair fibers without and with chemical damage caused by bleaching process. Fiber and resin (embedding material) data were obtained simultaneously in the mapping in order to have the resin data as a reference to ensure a coherent comparison between data from the different fiber groups. Our AFM results, which were evaluated using statistical tests, demonstrated the degradation of fibers after bleaching, corroborating the findings of transmission electron microscopy analysis and the effectiveness of a cosmetic active ingredient in improving the Young's modulus (elastic modulus) (E) of the damaged fibers. We also found a radial decrease in the natural logarithm of Young's modulus ln(E) along the cross-section of the active group fiber, which is compatible with confocal Raman spectroscopy analysis by other authors, demonstrating variation of the active permeation with depth. We note that Young's modulus was also determined by a tensile tester (macro-scale technique), in which it was not possible to obtain statistically significant differences between the groups, evidencing the advantage of the FV-AFM analysis. We also found an increase in ln(E) accompanied by a decrease in maximum adhesion force between tip and sample (negative Pearson correlation coefficient). This result can be explained by the fact that structures composed of hydrophobic components have a higher Young's modulus than structures composed of hydrophilic components.

Linking tumor immune infiltrate and systemic immune mediators to treatment response and prognosis in advanced cervical cancer.

Cervical cancer (CC) poses a significant burden on individuals in developing regions, exhibiting heterogeneous responses to standard chemoradiation therapy, and contributing to substantial mortality rates. Unraveling host immune dynamics holds promise for innovative therapies and discovery of clinically relevant biomarkers. We studied prospectively locally advanced CC patients pre-treatment, stratifying them as responders (R) or non-responders (NR). R patients had increased tumor-infiltrating lymphocytes (TILs), while NR patients showed elevated PD-1 scores, CD8+ and PD-L2+ TILs, and PD-L1 immune reactivity. NR patients exhibited higher systemic soluble mediators correlating with TIL immune markers. R patients demonstrated functional polarization of CD4 T cells (Th1, Th2, Th17, and Treg), while CD8+ T cells and CD68+ macrophages predominated in the NR group. Receiver operating characteristic analysis identified potential CC response predictors, including PD-L1-immunoreactive (IR) area, PD-L2, CD8, FGF-basic, IL-7, IL-8, IL-12p40, IL-15, and TNF-alpha. Dysfunctional TILs and imbalanced immune mediators contribute to therapeutic insufficiency, shedding light on local and systemic immune interplay. Our study informs immunological signatures for treatment prediction and CC prognosis.

Taxonomical and functional analyses of epifaunal polychaetes associated with Mussismilia spp.: the effects of coral growth morphology.

Background: The increasing habitat heterogeneity and complexity shows positive effects over different communities, leading to environmental diversity, access to resources and reducing the effectiveness of predation. In the present study we evaluate the structural and functional patterns of polychaete assemblages of three Mussismilia species with different coral morphology. Mussismilia hispida has a massive growth pattern; M. braziliensis also is a massive coral but forms a crevice in the corallum base; and M. harttii has a meandroid pattern. Methods: Ten individuals of the three Mussismilia species were sampled in two reefs in the Todos-os-Santos Bay, and we analyzed the differences in richness and abundance of polychaete species and the functional diversity metrics: Rao's quadratic entropy, functional dispersion, functional evenness, number of functional groups and functional richness, among Mussismilia species. Results: Two-way ANOVA with permutations showed significant differences for polychaete abundances and richness among Mussismilia species (higher values for M. harttii), but no differences were recorded when compared between the two coral reef areas studied. There was no statistical difference among coral species or between reefs in relation to the functional diversity components influenced by abundance, such as Rao quadratic entropy, functional dispersion, and functional evenness. Some individual polychaete functional traits presented differences among Mussismilia species, and that also helped us to build a picture about the effect of different growth structures over functional aspects of polychaete assemblages. Thus, the taxonomical approach, the analysis of individual functional traits and the functional diversity metrics are fundamental tools to characterize the assemblage of organisms associated with corals.

Flow cytometry as an alternative method to evaluate genotoxicity of natural cosmetic actives.

Alternative in vitro methods are important, as there is a call to ban the use of animals in cosmetics research. AIM: To suggest the expansion of the use of in vitro safety techniques recommended by the OECD guidelines and to propose the use of the automation of the in vitro mammalian micronucleus test method by flow cytometry to assess the genotoxic potential of Centella asiatica, Horse Chestnut, Witch Hazel, Blend, Ecoblend, and Caffeine extracts due to their widespread use in commercial products. METHODS: Flow cytometer analysis was performed using the Accuri™ C6 equipment and analyzed using the FlowJo software. Cytotoxicity tests followed OECD 129 guidelines and Phototoxicity followed OECD/GD 432 guidelines. RESULTS: The results showed that the cytotoxicity assay presented a decrease in cell viability when cells were exposed to Centella asiatica from a concentration of 5.0%, horse chestnut 2.5%, Witch hazel 2.5%, Blend 3.13%, and Caffeine 3%, while Ecoblend at the tested concentrations did not show cytotoxicity. In the phototoxicity test, the samples at the tested concentrations showed a PIF <2 being considered potentially non-phototoxic. Finally, in the genotoxicity automated assay, samples were considered potentially non-genotoxic. CONCLUSION: In vitro methods are of paramount importance for the development of pre-clinical tests and the use of test automation helps to reduce the time for analysis and dissemination of results, being a determining factor for the prospect of new compounds.

Recent Advances in Herbal-Derived Products with Skin Anti-Aging Properties and Cosmetic Applications.

Although aesthetic benefits are a desirable effect of the treatment of skin aging, it is also important in controlling several skin diseases, mainly in aged people. The development of new dermocosmetics has rapidly increased due to consumers' demand for non-invasive products with lower adverse effects than those currently available on the market. Natural compounds of plant origin and herbal-derived formulations have been popularized due to their various safe active products, which act through different mechanisms of action on several signaling pathways for skin aging. Based on this, the aim of the review was to identify the recent advances in herbal-derived product research, including herbal formulations and isolated compounds with skin anti-aging properties. The studies evaluated the biological effects of herbal-derived products in in vitro, ex vivo, and in vivo studies, highlighting the effects that were reported in clinical trials with available pharmacodynamics data that support their protective effects to treat, prevent, or control human skin aging. Thus, it was possible to identify that gallic and ferulic acids and herbal formulations containing Thymus vulgaris, Panax ginseng, Triticum aestivum, or Andrographis paniculata are the most promising natural products for the development of new dermocosmetics with skin anti-aging properties.

Whole-genome sequencing of 1,171 elderly admixed individuals from São Paulo, Brazil.

As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enables identification of ~2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS.

Population genetics of PDE4B (phosphodiesterase-4B) in neglected Native Americans: Implications for cancer pharmacogenetics.

PDE4B (phosphodiesterase-4B) has an important role in cancer and in pharmacology of some disorders, such as inflammatory diseases. Remarkably in Native Americans, PDE4B variants are associated with acute lymphoblastic leukemia (ALL) relapse, as this gene modulates sensitivity of glucocorticoids used in ALL chemotherapy. PDE4B allele rs6683977.G, associated with genomic regions of Native American origin in US-Hispanics (admixed among Native Americans, Europeans, and Africans), increases ALL relapse risk, contributing to an association between Native American ancestry and ALL relapse that disappeared with an extra-phase of chemotherapy. This result insinuates that indigenous populations along the Americas may have high frequencies of rs6683977.G, but this has never been corroborated. We studied ancestry and PDE4B diversity in 951 healthy individuals from nine Latin American populations. In non-admixed Native American populations rs6683977.G has frequencies greater than 90%, is in linkage disequilibrium with other ALL relapse associated and regulatory variants in PDE4B-intron-7, conforming haplotypes showing their highest worldwide frequencies in Native Americans (>0.82). Our findings inform the discussion on the pertinence of an extra-phase of chemotherapy in Native American populations, and exemplifies how knowledge generated in US-Hispanics is relevant for their even more neglected and vulnerable Native American ancestors along the American continent.

Modulation of autophagy by an innovative phytocosmetic preparation (Myrothamnus flabelifolia and Coffea arabica) in human fibroblasts and its effects in a clinical randomized placebo-controlled trial.

BACKGROUND: Autophagy is a natural and evolutionary mechanism that reduces cell toxic components and reutilizes metabolites to provide energy and renew cell function, which is linked to a wide range of age-related diseases, including those that affect the skin. Positive modulation of autophagy is useful to treat skin disorders and new active herbal products are potential candidates as autophagy modulators. AIMS: The present study aimed to evaluate the effects of a phytocosmetic formulation containing Myrothamnus flabellifolia leaf and Coffea arabica seed plant extracts (MflCas) on the ubiquitin-proteasome and autophagy markers in human dermal fibroblasts, and investigate its topical skin effects in a randomized, simple-blind, and placebo-controlled trial. METHODS: Human dermal fibroblasts were used to determine proteasome activity, protein carbonylation, LC3B protein, and lipofuscin production by luminescence and immune-enzymatic assays, and to determinate gene expression of autophagy biomarkers (Atg5, Atg7, EI24, EIF2A, Park2, foxo1, and mTOR) by RT-PCR. A clinical trial was conducted to evaluate the effects of MflCas on the hand, face, and forearms skin features after treatment by 56 days. RESULTS: Topical treatment with MflCas improved several skin features of volunteers, mainly skin aging and pigmentation signals. On the hand skin, MflCas 2% after 56 days of treatment, reduced the spots length (30.8%), skin contrast (42.2%), and increased skin homogeneity (63.2%) and skin lightening effect (1.4%). On the face skin, topical treatment after 56 days reduced the spots length (21.5%), wrinkles area (8.1%), and wrinkles volume (5.6%) with an increment in face skin homogeneity (59.5%). These effects were related to the ability of MflCas to reduce proteasome activity protein carbonylation, and lipofuscin level, increase LC3B production, downregulate Atg7 and mTOR genes, and upregulate Park2 gene expressions. CONCLUSIONS: The phytocosmetic preparation containing Myrothamnus flabellifolia leaf and Coffea arabica seed modulated ubiquitin-proteasome and autophagy process, representing an innovative and safe herbal preparation to improve skin features, mainly acting as skin anti-aging and lightening agent.

Influence of the Mixtures of Vegetable Oil and Vitamin E over the Microstructure and Rheology of Organogels.

Candelilla wax (CW) and 12-hydroxystearic acid (12HSA) are classic solid-fiber-matrix organogelators. Despite the high number of studies using those ingredients in oily systems, there is scarce literature using a mixture of oil and antioxidants. Vitamin E (VE) is an important candidate for its lipophilicity and several applications on pharmaceutical, cosmetics, and food industries. In this work, we investigated the influences of mixtures between vegetable oil (VO) and VE on the microstructures and rheological properties of CW and 12HSA organogels. A weak gel (G''/G' > 0.1) with a shear-thinning behavior was observed for all samples. The presence of VE impacted the gel strength and the phase transition temperatures in a dose-dependent pattern. Larger and denser packed crystals were seen for 12HSA samples, while smaller and more dispersed structures were obtained for CW organogels. The results obtained in this work allowed the correlation of the structural and mechanical properties of the organogels, which plays an important role in the physical-chemical characteristics of these materials.

Vaccinium myrtillus L. extract associated with octocrylene, bisoctrizole, and titanium dioxide: in vitro and in vivo tests to evaluate safety and efficacy.

OBJECTIVE: The harmful effects induced by ultraviolet exposition and the significant increment in skin cancer diagnosis confirm the necessity to develop effective and safe sunscreens. Limited efficacy and cutaneous adverse reactions of traditional formulations drove the incorporation of natural extracts into multifunctional sunscreens. Vaccinium myrtillus L. extract (VME), that contains anthocyanins and flavonoids, is a potential candidate for such systems. METHODS: Considering that, we performed in vitro and in vivo tests to evaluate the sun protection factor (SPF), photostability, and safety of sunscreen samples containing VME. RESULTS: As main results, the SPF was reduced in both in vitro and in vivo evaluation in the presence of VME; nonetheless, the samples were photostable and safe. CONCLUSION: Further investigation is required to better understand the unexpected effects of VME over photoprotection, decreasing the SPF value. As a conclusion, even with interesting findings, we highlight the importance of case-by-case investigations to develop multifunctional bioactive sunscreens.

Prevention of chemically induced hair damage by means of treatment based on proteins and polysaccharides.

BACKGROUND: There is currently a great interest not only in developing products for the protection and recovery of chemically damaged hair, but also in developing effective protocols to investigate the impact of chemical treatments and attest the efficacy of innovative hair care products. Among the most relevant cosmetic treatments for hair are bleaching and coloring, which have been shown to significantly impair mechanical and structural properties. OBJECTIVES: This study aimed to characterize the damage induced by hair bleaching and coloring and to evaluate the protective effects of a hair care treatment based on integral silk proteins (fibroin and sericin) and vegetable-derived polysaccharides from linseed (Linum usitatissimum L.). METHODS: Hair swatches were subjected to different treatment protocols in order to evaluate the protective effect of proposed and benchmark products during bleaching and coloring processes. Tensile tests were performed to assess mechanical properties and improvement in resistance to breakage. Goniophotometric measurements were applied to determine improvement in luster. Hair fiber surface and relief were evaluated by SEM image analysis. RESULTS: Swatches bleached and treated with both evaluated products had a significant increase in resistance and reduced structural damage. Swatches colored and treated with both evaluated products showed reduced structural damage, and a significant increase in resistance and luster after the 1st and 5th washes. CONCLUSIONS: The proposed product was effective in protecting and repairing bleached and colored swatches, improving resistance and luster and reducing structural damage. By applying complementary techniques within a reliable evaluation protocol, it was possible to attest the protective properties of the product under study.

Xylityl Sesquicaprylate Efficacy as an Antiseptic Ingredient for Oral Care Products (Mouthwash): An In Vitro Screening Investigation against Eight Microorganisms.

For dental caries and periodontal diseases initiated by dental plaque (as bacterial communities) and to inhibit the growth of oral pathogenic bacteria, oral care products containing antiseptic active ingredients are highly recommended, nonetheless, side effects of such actives are a concern (teeth discoloration/staining and taste perception, for example). In this context, we challenged xylityl sesquicaprylate, an antiseptic compound from natural resources, as an active ingredient to be used in an alcohol-free mouthwash formulation. The xylityl sesquicaprylate sample was compared to a respective blank mouthwash formulation and one containing triclosan. The in vitro efficacy was screened by the time-kill assay against eight microorganisms. The xylityl sesquicaprylate-containing mouthwash (0.45% w/w) presented a particularly interesting profile of efficacy against Actinomyces viscosus, Fusobacterium nucleatum, Porphyromonas gingivalis, and Tannerella forsythia, with results of greater magnitude to reduce the log10 of those microorganisms in comparison with the triclosan sample.

Propanediol (and) Caprylic Acid (and) Xylitol as a New Single Topical Active Ingredient against Acne: In Vitro and In Vivo Efficacy Assays.

In addition to dermatological complications, acne can affect the quality of life of individuals in numerous ways, such as employment, social habits and body dissatisfaction. According to our expertise, caprylic acid and propanediol would not have a direct action on Cutibacterium acnes. Despite this, we investigated the existence of a synergistic effect among xylitol, caprylic acid and propanediol as a mixture of compounds representing a single topical active ingredient that could benefit the treatment against acne. In vitro and in vivo assays were performed to challenge and to prove the efficacy of propanediol, xylitol and caprylic acid (PXCA) against acne. PXCA had its MIC challenged against C. acnes (formerly Propionibacterium acnes) and Staphylococcus aureus, resulting in concentrations of 0.125% and 0.25%, respectively, and it also developed antimicrobial activity against C. acnes (time-kill test). PXCA was able to reduce the 5-alpha reductase expression in 24% (p < 0.01) in comparison with the testosterone group. By the end of 28 days of treatment, the compound reduced the skin oiliness, porphyrin amount and the quantity of inflammatory lesions in participants. According to the dermatologist evaluation, PXCA improved the skin's general appearance, acne presence and size.

Epidemic Spread of SARS-CoV-2 Lineage B.1.1.7 in Brazil.

The emergence of diverse lineages harboring mutations with functional significance and potentially enhanced transmissibility imposes an increased difficulty on the containment of the SARS-CoV-2 pandemic [...].

Segmented worms (Phylum Annelida): a celebration of twenty years of progress through Zootaxa and call for action on the taxonomic work that remains.

Zootaxa has been the leading journal on invertebrate systematics especially within Annelida. Our current estimates indicate annelids include approximately 20,200 valid species of polychaetes, oligochaetes, leeches, sipunculans and echiurans. We include herein the impact of Zootaxa on the description of new annelid species in the last two decades. Since 2001, there have been over 1,300 new annelid taxa published in about 630 papers. The majority of these are polychaetes (921 new species and 40 new genera) followed by oligochaetes (308 new species and 10 new genera) and leeches (21 new species). The numerous papers dealing with new polychaete species have provided us a clear picture on which polychaete families have had the most taxonomic effort and which authors and countries have been the most prolific of descriptions of new taxa. An estimated additional 10,000+ species remain to be described in the phylum, thus we urge annelid workers to continue their efforts and aid in training a new generation of taxonomists focused on this ecologically important group.

Cervical Cancer Stem-Like Cell Transcriptome Profiles Predict Response to Chemoradiotherapy.

Cervical cancer (CC) represents a major global health issue, particularly impacting women from resource constrained regions worldwide. Treatment refractoriness to standard chemoradiotheraphy has identified cancer stem cells as critical coordinators behind the biological mechanisms of resistance, contributing to CC recurrence. In this work, we evaluated differential gene expression in cervical cancer stem-like cells (CCSC) as biomarkers related to intrinsic chemoradioresistance in CC. A total of 31 patients with locally advanced CC and referred to Mário Penna Institute (Belo Horizonte, Brazil) from August 2017 to May 2018 were recruited for the study. Fluorescence-activated cell sorting was used to enrich CD34+/CD45- CCSC from tumor biopsies. Transcriptome was performed using ultra-low input RNA sequencing and differentially expressed genes (DEGs) using Log2 fold differences and adjusted p-value < 0.05 were determined. The analysis returned 1050 DEGs when comparing the Non-Responder (NR) (n=10) and Responder (R) (n=21) groups to chemoradiotherapy. These included a wide-ranging pattern of underexpressed coding genes in the NR vs. R patients and a panel of lncRNAs and miRNAs with implications for CC tumorigenesis. A panel of biomarkers was selected using the rank-based AUC (Area Under the ROC Curve) and pAUC (partial AUC) measurements for diagnostic sensitivity and specificity. Genes overlapping between the 21 highest AUC and pAUC loci revealed seven genes with a strong capacity for identifying NR vs. R patients (ILF2, RBM22P2, ACO16722.1, AL360175.1 and AC092354.1), of which four also returned significant survival Hazard Ratios. This study identifies DEG signatures that provide potential biomarkers in CC prognosis and treatment outcome, as well as identifies potential alternative targets for cancer therapy.

Ten new species of Phyllodoce Lamarck, 1818 (Phyllodocidae, Annelida) from Brazil.

Herein we provide a taxonomic revision of Phyllodoce species from Brazil, describing 10 new species in addition to two new records, Phyllodoce longipes Kinberg, 1866 and Phyllodoce cf. madeirensis Langerhans, 1880. Phyllodoce sp. A. and Phyllodoce sp. B. are probably new but the number and condition of available specimens do not provide adequate and reliable diagnostic features for a formal description. These species have been collected in diverse marine and estuarine environments from shallow estuarine bottoms to continental shelf and slope sediments and submarine canyons from off southern and southeastern Brazil. A key to the fourteen species of Phyllodoce occurring in Brazil is also given.

Vitamin E-loaded bigels and emulsions: Physicochemical characterization and potential biological application.

Bigels have been studied as topical formulations for its benefits over sensory and drug delivery parameters. However, there is still few evidences about the properties of the combination of organogelators, oily phases and bioactive molecules into rheological and stability behavior. We investigated the use of classical organogelators (candelilla wax and 12-hydroxystearic acid) and oily phases (sunflower and mineral oil) in 5/95 organogel/polymeric hydrogel ratio to compare vitamin E bigels with its corresponding emulsions. The rheological measurements, microstructure, physical and oxidative stability properties and biological behavior were evaluated. The obtained oil-in-water bigels and emulsions showed crystallization pattern at the interface with high thermal and centrifuge-stress stability. Viscoelastic weak gels were obtained with higher thixotropy and consistency of 12-hydroxystearic bigels. The diameter of the inner phase was increased by vitamin E, despite its little influence over physical and oxidative stability of bigels and emulsions. Those findings indicated that sensory attributes may be regulated by the organogel composition.