A novel professional-use synergistic peel technology to reduce visible hyperpigmentation on face: Clinical evidence and mechanistic understanding by computational biology and optical biopsy.

Topicals and chemical peels are the standard of care for management of facial hyperpigmentation. However, traditional therapies have come under recent scrutiny, such as topical hydroquinone (HQ) has some regulatory restrictions, and high concentration trichloroacetic acid (TCA) peel pose a risk in patients with skin of colour. The objective of our research was to identify, investigate and elucidate the mechanism of action of a novel TCA- and HQ-free professional-use chemical peel to manage common types of facial hyperpigmentation. Using computational modelling and in vitro assays on tyrosinase, we identified proprietary multi-acid synergistic technology (MAST). After a single application on human skin explants, MAST peel was found to be more effective than a commercial HQ peel in inhibiting melanin (histochemical imaging and gene expression). All participants completed the case study (N = 9) without any adverse events. After administration of the MAST peel by a dermatologist, the scoring and VISIA photography reported improvements in hyperpigmentation, texture and erythema, which could be linked to underlying pathophysiological changes in skin after peeling, visualized by non-invasive optical biopsy of face. Using reflectance confocal microscopy (VivaScope®) and multiphoton tomography (MPTflex™), we observed reduction in melanin, increase in metabolic activity of keratinocytes, and no signs of inflammatory cells after peeling. Subsequent swabbing of the cheek skin found no microbiota dysbiosis resulting from the chemical peel. The strong efficacy with minimum downtime and no adverse events could be linked to the synergistic action of the ingredients in the novel HQ- and TCA-free professional peel technology.

Graphene oxide films as a novel tool for the modulation of myeloid-derived suppressor cell activity in the context of multiple sclerosis.

Despite the pharmacological arsenal approved for Multiple Sclerosis (MS), there are treatment-reluctant patients for whom cell therapy appears as the only therapeutic alternative. Myeloid-derived suppressor cells (MDSCs) are immature cells of the innate immunity able to control the immune response and to promote oligodendroglial differentiation in the MS animal model experimental autoimmune encephalomyelitis (EAE). However, when isolated and cultured for cell therapy purposes, MDSCs lose their beneficial immunomodulatory properties. To prevent this important drawback, culture devices need to be designed so that MDSCs maintain a state of immaturity and immunosuppressive function similar to that exerted in the donor organism. With this aim, we select graphene oxide (GO) as a promising candidate as it has been described as a biocompatible nanomaterial with the capacity to biologically modulate different cell types, yet its immunoactive potential has been poorly explored to date. In this work, we have fabricated GO films with two distintive redox and roughness properties and explore their impact in MDSC culture right after isolation. Our results show that MDSCs isolated from immune organs of EAE mice maintain an immature phenotype and highly immunosuppressive activity on T lymphocytes after being cultured on highly-reduced GO films (rGO200) compared to those grown on conventional glass coverslips. This immunomodulation effect is depleted when MDSCs are exposed to slightly rougher and more oxidized GO substrates (rGO90), in which cells experience a significant reduction in cell size associated with the activation of apoptosis. Taken together, the exposure of MDSCs to GO substrates with different redox state and roughness is presented as a good strategy to control MDSC activity in vitro. The versatility of GO nanomaterials in regards to the impact of their physico-chemical properties in immunomodulation opens the door to their selective therapeutic potential for pathologies where MDSCs need to be enhanced (MS) or inhibited (cancer).

Gut microbiota and inflammatory mediators differentiate IgE mediated and non-IgE mediated cases of cow's milk protein at diagnosis.

OBJECTIVE: Analyze fecal and blood samples at point of diagnosis in IgE mediated cow's milk protein allergy (CMPA) and non-IgE mediated (NIM)-CMPA patients to look for potential new biomarkers. PATIENTS AND METHODS: Fourteen patients with IgE mediated CMPA and 13 with NIM-CMPA were recruited in three hospitals in the north of Spain, and were compared with 25 infants from a control group of the same age range. To characterize intestinal microbiota, 16S rDNA gene and internal transcribed spacer amplicons of bifidobacteria were sequenced with Illumina technology. Fatty acids were analyzed by gas chromatography, meanwhile intestinal inflammation markers were quantified by enzyme-linked immunosorbent assay and a multiplex system. Immunological analysis of blood was performed by flow cytometry. RESULTS: The fecal results obtained in the NIM-CMPA group stand out. Among them, a significant reduction in the abundance of Bifidobacteriaceae and Bifidobacterium sequences with respect to controls was observed. Bifidobacterial species were also different, highlighting the lower abundance of Bifidobacterium breve sequences. Fecal calprotectin levels were found to be significantly elevated in relation to IgE mediated patients. Also, a higher excretion of IL-10 and a lower excretion of IL-1ra and platelet derived growth factor-BB was found in NIM-CMPA patients. CONCLUSIONS: The differential fecal parameters found in NIM-CMPA patients could be useful in the diagnosis of NIM food allergy to CM proteins.

Contrasting plant transcriptome responses between a pierce-sucking and a chewing herbivore go beyond the infestation site.

BACKGROUND: Plants have acquired a repertoire of mechanisms to combat biotic stressors, which may vary depending on the feeding strategies of herbivores and the plant species. Hormonal regulation crucially modulates this malleable defense response. Jasmonic acid (JA) and salicylic acid (SA) stand out as pivotal regulators of defense, while other hormones like abscisic acid (ABA), ethylene (ET), gibberellic acid (GA) or auxin also play a role in modulating plant-pest interactions. The plant defense response has been described to elicit effects in distal tissues, whereby aboveground herbivory can influence belowground response, and vice versa. This impact on distal tissues may be contingent upon the feeding guild, even affecting both the recovery of infested tissues and those that have not suffered active infestation. RESULTS: To study how phytophagous with distinct feeding strategies may differently trigger the plant defense response during and after infestation in both infested and distal tissues, Arabidopsis thaliana L. rosettes were infested separately with the chewing herbivore Pieris brassicae L. and the piercing-sucker Tetranychus urticae Koch. Moderate infestation conditions were selected for both pests, though no quantitative control of damage levels was carried out. Feeding mode did distinctly influence the transcriptomic response of the plant under these conditions. Though overall affected processes were similar under either infestation, their magnitude differed significantly. Plants infested with P. brassicae exhibited a short-term response, involving stress-related genes, JA and ABA regulation and suppressing growth-related genes. In contrast, T. urticae elicited a longer transcriptomic response in plants, albeit with a lower degree of differential expression, in particular influencing SA regulation. These distinct defense responses transcended beyond infestation and through the roots, where hormonal response, flavonoid regulation or cell wall reorganization were differentially affected. CONCLUSION: These outcomes confirm that the existent divergent transcriptomic responses elicited by herbivores employing distinct feeding strategies possess the capacity to extend beyond infestation and even affect tissues that have not been directly infested. This remarks the importance of considering the entire plant's response to localized biotic stresses.

Short-course combination treatment for experimental chronic Chagas disease.

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects millions of people in the Americas and across the world, leading to considerable morbidity and mortality. Current treatment options, benznidazole (BNZ) and nifurtimox, offer limited efficacy and often lead to adverse side effects because of long treatment durations. Better treatment options are therefore urgently required. Here, we describe a pyrrolopyrimidine series, identified through phenotypic screening, that offers an opportunity to improve on current treatments. In vitro cell-based washout assays demonstrate that compounds in the series are incapable of killing all parasites; however, combining these pyrrolopyrimidines with a subefficacious dose of BNZ can clear all parasites in vitro after 5 days. These findings were replicated in a clinically predictive in vivo model of chronic Chagas disease, where 5 days of treatment with the combination was sufficient to prevent parasite relapse. Comprehensive mechanism of action studies, supported by ligand-structure modeling, show that compounds from this pyrrolopyrimidine series inhibit the Qi active site of T. cruzi cytochrome b, part of the cytochrome bc1 complex of the electron transport chain. Knowledge of the molecular target enabled a cascade of assays to be assembled to evaluate selectivity over the human cytochrome b homolog. As a result, a highly selective and efficacious lead compound was identified. The combination of our lead compound with BNZ rapidly clears T. cruzi parasites, both in vitro and in vivo, and shows great potential to overcome key issues associated with currently available treatments.

The Arabidopsis thioredoxin TRXh5regulates the S-nitrosylation pattern of the TIRK receptor being both proteins essential in the modulation of defences to Tetranychus urticae.

The interaction between plants and phytophagous arthropods encompasses a complex network of molecules, signals, and pathways to overcome defences generated by each interacting organism. Although most of the elements and modulators involved in this interplay are still unidentified, plant redox homeostasis and signalling are essential for the establishment of defence responses. Here, focusing on the response of Arabidopsis thaliana to the spider mite Tetranychus urticae, we demonstrate the involvement in plant defence of the thioredoxin TRXh5, a small redox protein whose expression is induced by mite infestation. TRXh5 is localized in the cell membrane system and cytoplasm and is associated with alterations in the content of reactive oxygen and nitrogen species. Protein S-nitrosylation signal in TRXh5 over-expression lines is decreased and alteration in TRXh5 level produces changes in the JA/SA hormonal crosstalk of infested plants. Moreover, TRXh5 interacts and likely regulates the redox state of an uncharacterized receptor-like kinase, named THIOREDOXIN INTERACTING RECEPTOR KINASE (TIRK), also induced by mite herbivory. Feeding bioassays performed withTRXh5 over-expression plants result in lower leaf damage and reduced egg accumulation after T. urticae infestation than in wild-type (WT) plants. In contrast, mites cause a more severe injury in trxh5 mutant lines where a greater number of eggs accumulates. Likewise, analysis of TIRK-gain and -loss-of-function lines demonstrate the defence role of this receptor in Arabidopsis against T. urticae. Altogether, our findings demonstrate the interaction between TRXh5 and TIRK and highlight the importance of TRXh5 and TIRK in the establishment of effective Arabidopsis defences against spider mite herbivory.

Online Reputation for Food Sector Exporters in the B2B Context: The Importance of Sustainability.

Food exporting companies play a fundamental role in the development of international trade. However, the conceptualization and measurement of their online corporate reputation has not been extensively studied in Business to Business markets, unlike in Business to Consumer contexts. The aim of this research is to identify the variables that determine the online reputation of food companies operating in B2B markets, and to analyze their relationship with the volume of food exports. For this purpose, a three-stage quantitative and qualitative study has been developed, based on in-depth interviews with experts from export organizations and managers of Peruvian food exporting companies, the estimation of an Advanced Sentiment Analysis, the construction of a Total Online Reputation Index (TOR), and the development of regression analysis. The study has identified 13 variables that affect the online reputation of food exporting companies and indicates that the presence of sustainability content on their website and the number of pages visited positively affect the volume of food exports. Moreover, the TOR could have a significant explanatory capacity with respect to company exports. These results constitute a reference guide for both companies in the sector and official export agencies, highlighting the critical aspects to promote their exports.

The Benefits of a Multimechanistic Antiaging Skin Technology.

INTRODUCTION: Facial aging is a multifactorial phenomenon due to poor skin hydration, deficient intercellular communication, collagen/elastin breakdown, and oxidative stress. The objective of this study was to assess the efficacy of a multimechanistic antiaging prototype formulation on the appearance of photoaged facial skin after 24 weeks of twice daily use. METHODS: Fifty female subjects 35-65 years of age of all Fitzpatrick skin types with mild to moderate facial photoaging concerns (fine lines, wrinkles, sagging skin, tone and texture) were enrolled in this monadic study. Investigator and subject tolerability assessments were performed along with facial noninvasive corneometry hydration and elasticity measurements. The dermatologist investigator assessed fine lines, wrinkles, skin evenness, radiance, plumping, texture/smoothness, sagging/firming/lifting, and global appearance on a 5-point ordinal scale. RESULTS: Forty-seven of the 50 subjects completed the study with a 19% increase in skin firmness and a 35% increase in skin hydration via bio-instrumentation readings after 24 weeks of study product use. The investigator assessed a 40% improvement in lines, a 23% improvement in wrinkles, a 42% improvement in evenness, a 64% improvement in radiance, a 58% improvement in plumping, a 65% improvement in texture, a 60% improvement in firmness, and a 45% improvement in overall appearance at 24 weeks. CONCLUSION: The serum combination of humectants, peptides, and antioxidants yielded excellent tolerability with visual and mechanistic skin improvement beginning at 1 week with cumulative continuing improvement through 24 weeks of use in terms of hydration, firmness, texture, radiance, and fine lines.

Multi-omic approach to decipher the impact of skincare products with pre/postbiotics on skin microbiome and metabolome.

Introduction: Although pre/pro/postbiotics have become more prevalent in dermatologic and cosmetic fields, the mode of action when topically applied is largely unknown. A multi-omic approach was applied to decipher the impact of the skincare products with pre/postbiotics on skin microbiome and metabolome. Methods: Subjects with dry skin applied a body wash and body lotion with or without pre/postbiotics for 6 weeks. Skin hydration was measured at baseline, 3 and 6 weeks. Skin swabs were collected for 16S rRNA gene sequencing, metagenomics and metabolomics analysis. Results: Skin hydration significantly increased in both groups. The prebiotic group significantly reduced opportunistic pathogens, e.g., Pseudomonas stutzeri and Sphingomonas anadarae, and increased the commensals, e.g., Staphylococcus equorum, Streptococcus mitis, Halomonas desiderata. Bacterial sugar degradation pathways were enriched in the prebiotic group, while fatty acid biosynthesis pathways were reduced in control. The changes on skin metabolome profiles by the products were more prominent. The prebiotic group performed greater modulation on many clinically-relevant metabolites compared to control. Correlation analysis showed H. desiderata and S. mitis positively correlated with skin hydration, P. stutzeri and S. anadarae negatively correlated with the metabolites that are positively associated with skin hydration improvement. Conclusion: This holistic study supported a hypothesis that the pre/postbiotics increased skin hydration through the modulation of skin microbiome, metabolic pathways and metabolome.

Microbial and immune faecal determinants in infants hospitalized with COVID-19 reflect bifidobacterial dysbiosis and immature intestinal immunity.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide, seriously endangering human health. Although SARS-CoV-2 had a lower impact on paediatric population, children with COVID-19 have been reported as suffering from gastrointestinal (GI) symptoms at a higher rate than adults. The aim of this work was to evaluate faeces as a source of potential biomarkers of severity in the paediatric population, with an emphasis on intestinal microbiota and faecal immune mediators, trying to identify possible dysbiosis and immune intestinal dysfunction associated with the risk of hospitalization. This study involved 19 patients with COVID-19 under 24 months of age hospitalized during the pandemic at 6 different hospitals in Spain, and it included a comparable age-matched healthy control group (n = 18). Patients and controls were stratified according to their age in two groups: newborns or young infants (from 0 to 3 months old) and toddlers (infants from 6 to 24 months old). To characterize microbial intestinal communities, sequencing with Illumina technology of total 16S rDNA amplicons and internal transcribed spacer (ITS) amplicons of bifidobacteria were used. Faecal calprotectin (FC) and a range of human cytokines, chemokines, and growth factors were measured in faecal samples using ELISA and a multiplex system. Significant reduction in the abundance of sequences belonging to the phylum Actinobacteria was found in those infants with COVID-19, as well as in the Bifidobacteriaceae family. A different pattern of bifidobacteria was observed in patients, mainly represented by lower percentages of Bifidobacterium breve, as compared with controls. In the group of hospitalized young infants, FC was almost absent compared to age-matched healthy controls. A lower prevalence in faecal excretion of immune factors in these infected patients was also observed. CONCLUSION:  Hospitalized infants with COVID-19 were depleted in some gut bacteria, such as bifidobacteria, in particular Bifidobacterium breve, which is crucial for the proper establishment of a functional intestinal microbiota, and important for the development of a competent immune system. Our results point to a possible immature immune system at intestine level in young infants infected by SARS-CoV2 requiring hospitalization. WHAT IS KNOWN: • Although SARS-CoV-2 had a lower impact on paediatric population, children with COVID-19 have been reported as suffering from gastrointestinal symptoms at a higher rate than adults. • Changes in microbial composition have been described in COVID-19 adult patients, although studies in children are limited. WHAT IS NEW: • The first evidence that hospitalized infants with COVID-19 during the pandemic had a depletion in bifidobacteria, particularly in Bifidobacterium breve, beneficial gut bacteria in infancy that are crucial for the proper establishment of a competent immune system. • In young infants (under 3 months of age) hospitalized with SARS-CoV2 infection, the aberrant bifidobacterial profile appears to overlap with a poor intestinal immune development as seen by calprotectin and the trend of immunological factors excreted in faeces.

Isolation and Quantification of Mandelonitrile from Arabidopsis thaliana Using Gas Chromatography/Mass Spectrometry.

Mandelonitrile is a nitrogen-containing compound, considered an essential secondary metabolite. Chemically, it is a cyanohydrin derivative of benzaldehyde, with relevant functions in different physiological processes including defense against phytophagous arthropods. So far, procedures for detecting mandelonitrile have been effectively applied in cyanogenic plant species such as Prunus spp. Nevertheless, its presence in Arabidopsis thaliana , considered a non-cyanogenic species, has never been determined. Here, we report the development of an accurate protocol for mandelonitrile quantification in A. thaliana within the context of A. thaliana -spider mite interaction. First, mandelonitrile was isolated from Arabidopsis rosettes using methanol; then, it was derivatized by silylation to enhance detection and, finally, it was quantified using gas chromatography-mass spectrometry. The selectivity and sensitivity of this method make it possible to detect low levels of mandelonitrile (LOD 3 ppm) in a plant species considered non-cyanogenic that, therefore, will have little to no cyanogenic compounds, using a small quantity of starting material (≥100 mg).

Structure-Guided Design and Synthesis of a Pyridazinone Series of Trypanosoma cruzi Proteasome Inhibitors.

There is an urgent need for new treatments for Chagas disease, a parasitic infection which mostly impacts South and Central America. We previously reported on the discovery of GSK3494245/DDD01305143, a preclinical candidate for visceral leishmaniasis which acted through inhibition of the Leishmania proteasome. A related analogue, active against Trypanosoma cruzi, showed suboptimal efficacy in an animal model of Chagas disease, so alternative proteasome inhibitors were investigated. Screening a library of phenotypically active analogues against the T. cruzi proteasome identified an active, selective pyridazinone, the development of which is described herein. We obtained a cryo-EM co-structure of proteasome and a key inhibitor and used this to drive optimization of the compounds. Alongside this, optimization of the absorption, distribution, metabolism, and excretion (ADME) properties afforded a suitable compound for mouse efficacy studies. The outcome of these studies is discussed, alongside future plans to further understand the series and its potential to deliver a new treatment for Chagas disease.

Fe-Al binary composite filled dialysis membrane tubes (DMT-HFAO): a modified method for assessment of phosphate desorption from aqueous and soil solutions.

Phosphorus (P) limits plant growth particularly in strongly acidic soils due to P fixation. P availability to a plant is a functional concept of time rather than a measurable quantity. Therefore, a method that can estimate P availability over time is required. This research work was intended to synthesize a nanocomposite material that can monitor soil P desorption kinetics. To this effect, a binary sorbent system filled in a dialysis membrane tube was developed. Accordingly, calcined and amorphous powder samples of Fe-Al binary mixed oxides were synthesized by a gel-evaporation method and characterized by XRD, FTIR, TGA-DTA, SEM-EDX and BET techniques. The performance, as a phosphate sink, of crystalline hydrous ferric aluminum oxide (HFAO) and hydrous amorphous ferric aluminum oxide (HAFAO) each filled in a dialysis membrane tube (DMT) was evaluated. A single hydrated ferric oxide (HFO) suspension filled in dialysis membrane tubes (DMT) designated DMT-HFO was used as a benchmark. For the aqueous system, the sorption capacity of the DMT-HFAO was found to be 260% (mg mg-1 phosphate) whereas the amorphous congener (DMT-HAFAO) was approximately 200% (mg mg-1 phosphate) times that of DMT-HFO during the 24 h equilibration. For the soil solution system, the phosphate desorbed by the DMT-HFAO was about 520% (mg mg-1 phosphate) compared with a single system, DMT-HFO, in 168 h. For the desorption experiment carried out with soil solution, the data fitted fairly well with first order kinetics for both sorbents (R2 = 0.946-0.998), the amount adsorbed by DMT-HFAO being greater than DMT-HFO. The soil data fitted an intra-particle diffusion model fairly well for both sorbents (R2 = 0.98-0.992) with rate constants, kp, following the order: DMT-HFAO > DMT-HAFAO > DMT-HFO. The DMT-HFAO approach also showed better fit to the two component first order model (R2 = 0.994 & 0.997) indicating that the modified method has promising potential for a long-term phosphate desorption kinetics study from soil, the implication of which is important both from agricultural and environmental perspectives. However, correlation of the P adsorbed by this sink method with actual plant P uptake in various soils should be carried out to validate the universality of this technique.

Host adaptation and specialization in Tetranychidae mites.

Composite generalist herbivores are comprised of host-adapted populations that retain the ability to shift hosts. The degree and overlap of mechanisms used by host-adapted generalist and specialist herbivores to overcome the same host plant defenses are largely unknown. Tetranychidae mites are exceptionally suited to address the relationship between host adaptation and specialization in herbivores as this group harbors closely related species with remarkably different host ranges-an extreme generalist the two-spotted spider mite (Tetranychus urticae Koch [Tu]) and the Solanaceous specialist Tetranychus evansi (Te). Here, we used tomato-adapted two-spotted spider mite (Tu-A) and Te populations to compare mechanisms underlying their host adaptation and specialization. We show that both mites attenuate induced tomato defenses, including protease inhibitors (PIs) that target mite cathepsin L digestive proteases. While Te solely relies on transcriptional attenuation of PI induction, Tu and Tu-A have elevated constitutive activity of cathepsin L proteases, making them less susceptible to plant anti-digestive proteins. Tu-A and Te also rely on detoxification of tomato constitutive defenses. Te uses esterase and P450 activities, while Tu-A depends on the activity of all major detoxification enzymatic classes to disarm tomato defensive compounds to a lesser extent. Thus, even though both Tu-A and Te use similar mechanisms to counteract tomato defenses, Te can better cope with them. This finding is congruent with the ecological and evolutionary times required to establish mite adaptation and specialization states, respectively.

Jasmonic acid catabolism in Arabidopsis defence against mites.

Jasmonates are essential modulators of plant defences but the role of JA-derivatives has been scarcely studied, particularly in the plant-pest interplay. To deepen into the JA catabolism and its impact on plant responses to spider mite infestation, we selected the Arabidopsis JAO2 gene as a key element involved in the first step of the JA-catabolic route. JAO2 is responsible for the hydroxylation of JA into 12-OH-JA, contributes to attenuate JA and JA-Ile content and consequently, determines the formation of other JA-catabolites. JAO2 was up-regulated in Arabidopsis by mite infestation. Mites also induced JA-derivative accumulation in plants. In jao2 mutant lines, and in the triple mutant jaoT (jao2-1, jao3-1, jao4-2), mite feeding produced less leaf damage, minor callose deposition and lower mite fecundity rates than in Col-0 plants. The impairment of JA oxidation in jao2 lines not only diminished the 12-OH-JA levels but turned off further sulfation as shown the significant reduction of 12-HSO4-JA form. Thus, JAO2 acts as a negative modulator of defences to spider mites mediated by changes in the generation of JA catabolic molecules, and the consequent production of defensive metabolites such as glucosinolates or camalexin.

Evaluating satisfaction with teaching innovation, its relationship to academic performance and the application of a video-based microlearning.

AIM: To develop and validate a questionnaire to assess satisfaction with teaching innovation, assess the student satisfaction with a video-based microlearning intervention in its video-based modality and to verify its impact on academic performance. DESIGN: A descriptive cross-sectional study was conducted. The study used the COSMIN checklist for studies on measurement instruments. METHODS: One hundred and ten nursing students from Salus Infirmorum University Centre (Andalusia, Spain) participated in the study. The items of the instrument were designed based on a literature review and its validity and stability were analysed. After that, 6 weeks of video-based microlearning intervention were implemented. Then students were asked to fill the satisfaction questionnaire and then took the subject exam. RESULTS: The resulting questionnaire consisted of 5 items with only one dimension. The questionnaire showed good validity and reliability. A direct correlation was observed between satisfaction with the video-based microlearning intervention and the marks of the subject exam.

Treatment of mild-to-moderate facial cutaneous aging using a combination peel containing 6% trichloroacetic acid and 12% lactic acid.

Chemical peeling treats facial cutaneous aging and may avoid risks in patients with sensitive skin, darker skin types, limited finances, or concern for side effects of other resurfacing techniques. Tolerability and improvement of photoaging using a combination peel containing 6% trichloroacetic acid and 12% lactic acid for treatment of mild-to-moderate signs of facial photoaging were assessed. This is a prospective, single-center, single-arm, study of 32 female subjects with mild-to-moderate signs of facial aging and Fitzpatrick Skin Types I-V treated with three monthly treatments of a combination peel containing 6% trichloroacetic acid and 12% lactic acid. After 3 treatments, there were statistically significant improvements in clarity, brightness, redness, pigmentation, fine lines, tactile and visual roughness, and overall appearance scores. Subjective improvements in photoaging parameters varied from 53% (fine lines) to 91% (clarity/brightness). Three treatments with a combination peel containing 6% trichloroacetic acid and 12% lactic acid achieved improvements in signs of facial photoaging. This procedure is safe and effective at treating cutaneous aging for all skin types and a viable option for patients who wish to avoid other resurfacing techniques such as laser resurfacing, microneedling among others.

Central and peripheral myeloid-derived suppressor cell-like cells are closely related to the clinical severity of multiple sclerosis.

Multiple sclerosis (MS) is a highly heterogeneous demyelinating disease of the central nervous system (CNS) that needs for reliable biomarkers to foresee disease severity. Recently, myeloid-derived suppressor cells (MDSCs) have emerged as an immune cell population with an important role in MS. The monocytic-MDSCs (M-MDSCs) share the phenotype with Ly-6Chi-cells in the MS animal model, experimental autoimmune encephalomyelitis (EAE), and have been retrospectively related to the severity of the clinical course in the EAE. However, no data are available about the presence of M-MDSCs in the CNS of MS patients or its relation with the future disease aggressiveness. In this work, we show for the first time cells exhibiting all the bona-fide phenotypical markers of M-MDSCs associated with MS lesions, whose abundance in these areas appears to be directly correlated with longer disease duration in primary progressive MS patients. Moreover, we show that blood immunosuppressive Ly-6Chi-cells are strongly related to the future severity of EAE disease course. We found that a higher abundance of Ly-6Chi-cells at the onset of the EAE clinical course is associated with a milder disease course and less tissue damage. In parallel, we determined that the abundance of M-MDSCs in blood samples from untreated MS patients at their first relapse is inversely correlated with the Expanded Disability Status Scale (EDSS) at baseline and after a 1-year follow-up. In summary, our data point to M-MDSC load as a factor to be considered for future studies focused on the prediction of disease severity in EAE and MS.

Cyanogenesis, a Plant Defence Strategy against Herbivores.

Plants and phytophagous arthropods have coevolved in a long battle for survival. Plants respond to phytophagous feeders by producing a battery of antiherbivore chemical defences, while herbivores try to adapt to their hosts by attenuating the toxic effect of the defence compounds. Cyanogenic glucosides are a widespread group of defence chemicals that come from cyanogenic plants. Among the non-cyanogenic ones, the Brassicaceae family has evolved an alternative cyanogenic pathway to produce cyanohydrin as a way to expand defences. When a plant tissue is disrupted by an herbivore attack, cyanogenic substrates are brought into contact with degrading enzymes that cause the release of toxic hydrogen cyanide and derived carbonyl compounds. In this review, we focus our attention on the plant metabolic pathways linked to cyanogenesis to generate cyanide. It also highlights the role of cyanogenesis as a key defence mechanism of plants to fight against herbivore arthropods, and we discuss the potential of cyanogenesis-derived molecules as alternative strategies for pest control.

The clinical benefit of a multimodal topical approach to treating skin dyspigmentation.

BACKGROUND: The recent removal of hydroquinone from the over-the-counter market has created a need for modern skin lightening formulations. An effective pigment lightening formulation must be non-irritating to prevent skin darkening from post-inflammatory hyperpigmentation, penetration enhanced to reach the epidermal/dermal junction, contain anti-inflammatory ingredients, and address multiple mechanisms of pigment production. OBJECTIVE: The objective of this research was to demonstrate the efficacy of a topical multimodal pigment lightening preparation containing tranexamic acid, niacinamide, and licorice. METHODS: Fifty female subjects 18+ years of all Fitzpatrick skin types with mild to moderate facial dyspigmentation were enrolled. Subjects were provided with the study product for twice daily use on the entire face and an SPF50 sunscreen with evaluations occurring at Week 4, Week 8, Week 12, and Week 16. The investigator used a face map to identify a pigmented target site on the face for dermaspectrophotometer (DSP) measurement. The dermatologist investigator completed a baseline facial efficacy and tolerability assessment. The subjects completed a tolerability assessment. RESULTS: 48/50 subjects completed the study without tolerability issues. The DSP readings demonstrated a statistically significant reduction in target spot pigmentation at Week 16. The investigator assessed a 37% decrease in pigment intensity, a 31% decrease in pigment extent, a 30% decrease in pigment homogeneity, a 45% improvement in brightness, a 42% improvement in clarity, and a 32% improvement in overall facial skin dyspigmentation at Week 16. CONCLUSION: The combination of penetration enhanced tranexamic acid, niacinamide, and licorice was effective in inducing facial pigment lightening.