Combined exposure to UV and PM affect skin oxinflammatory responses and it is prevented by antioxidant mix topical application: Evidences from clinical study.

BACKGROUND: Exposure to environmental stressors like particulate matter (PM) and ultraviolet radiation (UV) induces cutaneous oxidative stress and inflammation and leads to skin barrier dysfunction and premature aging. Metals like iron or copper are abundant in PM and are known to contribute to reactive oxygen species (ROS) production. AIMS: Although it has been suggested that topical antioxidant may be able to help in preventing and/or reducing outdoor skin damage, limited clinical evidence under real-life exposure conditions have been reported. The aim of the present study was to evaluate the ability of a topical serum containing 15% ascorbic acid, 0.5% ferulic acid, and 1% tocopherol (CF Mix) to prevent oxinflammatory skin damage and premature aging induced by PM + UV in a human clinical trial. METHODS: A 4-day single-blinded, clinical study was conducted on the back of 15 females (18-40 years old). During the 4 consecutive days, the back test zones were treated daily with or without the CF Mix, followed by with/without 2 h of PM and 5 min of UV daily exposure. RESULTS: Application of the CF Mix prevented PM + UV-induced skin barrier perturbation (Involucrin and Loricrin), lipid peroxidation (4HNE), inflammatory markers (COX2, NLRP1, and AhR), and MMP9 activation. In addition, CF Mix was able to prevent Type I Collagen loss. CONCLUSION: This is the first human study confirming the multipollutants cutaneous damage and suggesting the utility of a daily antioxidant topical application to prevent pollution induced skin damage.

Cutaneous Redox Senescence.

Our current understanding of skin cell senescence involves the role of environmental stressors (UV, O3, cigarette smoke, particulate matter, etc.), lifestyle (diet, exercise, etc.) as well as genetic factors (metabolic changes, hormonal, etc.). The common mechanism of action of these stressors is the disturbance of cellular redox balance characterized by increased free radicals and reactive oxygen species (ROS), and when these overload the intrinsic antioxidant defense system, it can lead to an oxidative stress cellular condition. The main redox mechanisms that activate cellular senescence in the skin involve (1) the oxidative damage of telomeres causing their shortening; (2) the oxidation of proteomes and DNA damage; (3) an a in lysosomal mass through the increased activity of resident enzymes such as senescence-associated ß-galactosidase (SA-ß-gal) as well as other proteins that are products of lysosomal activity; (4) and the increased expression of SASP, in particular pro-inflammatory cytokines transcriptionally regulated by NF-κB. However, the main targets of ROS on the skin are the proteome (oxi-proteome), followed by telomeres, nucleic acids (DNAs), lipids, proteins, and cytoplasmic organelles. As a result, cell cycle arrest pathways, lipid peroxidation, increased lysosomal content and dysfunctional mitochondria, and SASP synthesis occur. Furthermore, oxidative stress in skin cells increases the activity of p16INK4A and p53 as inhibitors of Rb and CDks, which are important for maintaining the cell cycle. p53 also promotes the inactivation of mTOR-mediated autophagic and apoptotic pathways, leading to senescence. However, these markers alone cannot establish the state of cellular senescence, and multiple analyses are encouraged for confirmation. An updated and more comprehensive approach to investigating skin senescence should include further assays of ox-inflammatory molecular pathways that can consolidate the understanding of cutaneous redox senescence.

Nutlin-3 Loaded Ethosomes and Transethosomes to Prevent UV-Associated Skin Damage.

The skin's protective mechanisms, in some cases, are not able to counteract the destructive effects induced by UV radiations, resulting in dermatological diseases, as well as skin aging. Nutlin-3, a potent drug with antiproliferative activity in keratinocytes, can block UV-induced apoptosis by activation of p53. In the present investigation, ethosomes and transethosomes were designed as delivery systems for nutlin-3, with the aim to protect the skin against UV damage. Vesicle size distribution was evaluated by photon correlation spectroscopy and morphology was investigated by cryogenic transmission electron microscopy, while nutlin-3 entrapment capacity was evaluated by ultrafiltration and HPLC. The in vitro diffusion kinetic of nutlin-3 from ethosomes and transethosomes was studied by Franz cell. Moreover, the efficiency of ethosomes and transethosomes in delivering nutlin-3 and its protective role were evaluated in ex vivo skin explants exposed to UV radiations. The results indicate that ethosomes and transethosomes efficaciously entrapped nutlin-3 (0.3% w/w). The ethosome vesicles were spherical and oligolamellar, with a 224 nm mean diameter, while in transethosome the presence of polysorbate 80 resulted in unilamellar vesicles with a 146 nm mean diameter. The fastest nutlin-3 kinetic was detected in the case of transethosomes, with permeability coefficients 7.4-fold higher, with respect to ethosomes and diffusion values 250-fold higher, with respect to the drug in solution. Ex vivo data suggest a better efficacy of transethosomes to promote nutlin-3 delivery within the skin, with respect to ethosomes. Indeed, nutlin-3 loaded transethosomes could prevent UV effect on cutaneous metalloproteinase activation and cell proliferative response.

Ethosomes for Curcumin and Piperine Cutaneous Delivery to Prevent Environmental-Stressor-Induced Skin Damage.

Diesel particulate matter is one of the most dangerous environmental stressors affecting human health. Many plant-derived compounds with antioxidant and anti-inflammatory properties have been proposed to protect the skin from pollution damage. Curcumin (CUR) has a plethora of pharmacological activities, including anticancer, antimicrobial, anti-inflammatory and antioxidant. However, it has low bioavailability due to its difficult absorption and rapid metabolism and elimination. CUR encapsulation in nanotechnological systems and its combination with biopotentiators such as piperine (PIP) can improve its pharmacokinetics, stability and activity. In this study, ethosomes (ETs) were investigated for CUR and PIP delivery to protect the skin from damage induced by diesel particulate matter. ETs were produced by different strategies and characterized for their size distribution by photon correlation spectroscopy, for their morphology by transmission electron microscopy, and for their drug encapsulation efficiency by high-performance liquid chromatography. Franz cells enabled us to evaluate in vitro the drug diffusion from ETs. The results highlighted that ETs can promote the skin permeation of curcumin. The studies carried out on their antioxidant activity demonstrated an increase in the antioxidant power of CUR using a combination of CUR and PIP separately loaded in ETs, suggesting their possible application for the prevention of skin damage due to exogenous stressors. Ex vivo studies on human skin explants have shown the suitability of drug-loaded ETs to prevent the structural damage to the skin induced by diesel engine exhaust exposure.

Vitamin C compounds mixture prevents skin barrier alterations and inflammatory responses upon real life multi pollutant exposure.

Cutaneous tissues is among the main target of outdoor stressors such as ozone (O3 ), particulate matter (PM), and ultraviolet radiation (UV) all involved in inducing extrinsic skin aging. Only a few reports have studied the multipollutant interaction and its effect on skin damage. In the present work, we intended to evaluate the ability of pollutants such as O3 and PM to further aggravate cutaneous UV damage. In addition, the preventive properties of a cosmeceutical formulation mixture (AOX mix) containing 15% vitamin C (L-ascorbic acid), 1% vitamin E (α-tocopherol) and 0.5% ferulic acid was also investigated. Skin explants obtained from three different subjects were exposed to 200 mJ UV light, 0.25 ppm O3 for 2 h, and 30 min of diesel engine exhaust (DEE), alone or in combination for 4 days (time point D1 and D4). The results showed a clear additive effect of O3 and DEE in combination with UV in terms of keratin 10, Desmocollin and Claudin loss. In addition, the multipollutant exposure significantly induced the inflammatory response measured as NLRP1/ASC co-localization suggesting the activation of the inflammasome machinery. Finally, the loss of Aquaporin3 was also affected by the combined outdoor stressors. Furthermore, daily topical pre-treatment with the AOX Mix significantly prevented the cutaneous changes induced by the multipollutants. In conclusion, this study is among the first to investigate the combined effects of three of the most harmful outdoor stressors on human skin and confirms that daily topical of an antioxidant application may prevent pollution-induced skin damage.

Signature of paraoxonases in the altered redox homeostasis in Alzheimer's disease.

Paraoxonase (PON) enzymes (PON1, PON2 and PON3) exert antioxidant properties through arylesterase, lactonase and paraoxonase activities. Increasing findings suggested their potential involvement, particularly PON1 and PON2, in Alzheimer's disease (AD), a neurodegenerative pathology characterized by early oxidative stress. Specifically, decreased serum PON1-arylesterase and lactonase activities seem to be associated with an increased brain oxidative damage in early AD, leading to hypothesize that PON activity alterations might be an early event in AD. To address this hypothesis, the levels of 4-hydroxynonenal (4-HNE; i.e. a marker of oxidative stress damage) along with the protein expression and enzymatic activity of PON1 and PON2 have been investigated in the brain and serum of young [Postnatal day (PD)8-10, 20-25 and 60-65] asymptomatic 3xTg-AD female mice, one of the most used transgenic models of AD. At PD 8-10, there were no differences in hippocampus and prefrontal cortex (PFC) 4-HNE expression levels between 3xTg-AD mice compared to controls (Non-Tg mice). On the other hand, significant increased levels of 4-HNE were detected in PD 20-30 3xTg-AD mice hippocampus, while a significant reduction was observed in 3xTg-AD group at PD 60-65. In the PFC, 4-HNE levels were significantly reduced in 3xTg-AD mice brain at PD 20-30, while no differences in 4-HNE levels were detected at PD 60-65. No significant differences in arylesterase and lactonase activities were observed in the plasma of 3xTg-AD and Non-Tg mice at the different considered ages. Compared to Non-Tg mice, a reduction of brain arylesterase activity was found in 3xTg-AD female at PD 20-30 and PD 60-65, but it was significant only in the younger group. Finally, a similar trend was observed also for PON1 and PON2 protein levels, with both significantly, and solely, decreased in 3xTg-AD mice brain at PD 20-30. Overall, these findings suggest that the altered oxidative stress homeostasis in the 3xTg-AD female mice may be related to an early reduction in activity and expression of PONs enzymes most likely via a reduced brain arylesterases activity.

A proteomic approach to investigate the role of the MECP2 gene mutation in Rett syndrome redox regulatory pathways.

Mutations in the X-linked methyl-CpG-binding 2 (MECP2) gene lead to Rett Syndrome (RTT; OMIM 312750), a devasting neurodevelopmental disorder. RTT clinical manifestations are complex and with different degrees of severity, going from autistic-like behavior to loss of acquired speech, motor skills and cardiac problems. Furthermore, the correlation between the type of MECP2 mutation and the clinical phenotype is still not fully understood. Contextually, different genotypes can differently affect the patient's phenotype and omics methodologies such as proteomics could be an important tool for a molecular characterization of genotype/phenotype correlation. The aim of our study was focused on evaluating RTT oxidative stress (OS) responses related to specific MECP2 gene mutations by using proteomics and bioinformatics approaches. Primary fibroblasts isolated from patients affected by R133C and R255× mutations were compared to healthy controls (HC). After clustering primary dermal fibroblasts based on their specific MECP2 mutations, fibroblast-derived protein samples were qualitative and quantitative analyzed, using a label free quantification (LFQ) analysis by mass spectrometry (MS), achieving a preliminary correlation for RTT genotype/phenotype. Among the identified proteins involved in redox regulation pathways, NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1) was found to be absent in R255× cells, while it was present in R133C and in HC fibroblasts. Moreover, NQO1 aberrant gene regulation was also confirmed when cells were challenged with 100 µM hydrogen peroxide (H2O2). In conclusion, by employing a multidisciplinary approach encompassing proteomics and bioinformatics analyses, as well as molecular biology assays, the study uncovered phenotypic responses linked to specific MECP2 gene mutations. These findings contribute to a better understanding of the complexity of RTT molecular pathways, confirming the high heterogeneity among the patients.

Comparison of Pollutant Effects on Cutaneous Inflammasomes Activation.

The skin is the outermost layer of the body and, therefore, is exposed to a variety of stressors, such as environmental pollutants, known to cause oxinflammatory reactions involved in the exacerbation of several skin conditions. Today, inflammasomes are recognized as important modulators of the cutaneous inflammatory status in response to air pollutants and ultraviolet (UV) light exposure. In this study, human skin explants were exposed to the best-recognized air pollutants, such as microplastics (MP), cigarette smoke (CS), diesel engine exhaust (DEE), ozone (O3), and UV, for 1 or 4 days, to explore how each pollutant can differently modulate markers of cutaneous oxinflammation. Exposure to environmental pollutants caused an altered oxidative stress response, accompanied by increased DNA damage and signs of premature skin aging. The effect of specific pollutants being able to exert different inflammasomes pathways (NLRP1, NLRP3, NLRP6, and NLRC4) was also investigated in terms of scaffold formation and cell pyroptosis. Among all environmental pollutants, O3, MP, and UV represented the main pollutants affecting cutaneous redox homeostasis; of note, the NLRP1 and NLRP6 inflammasomes were the main ones modulated by these outdoor stressors, suggesting their role as possible molecular targets in preventing skin disorders and the inflammaging events associated with environmental pollutant exposure.

Bone Fracture in Rett Syndrome: Mechanisms and Prevention Strategies.

The present study aimed to evaluate the burden and management of fragility fractures in subjects with Rett syndrome. We searched all relevant medical literature from 1 January 1986 to 30 June 2023 for studies under the search term "Rett syndrome and fracture". The fracture frequency ranges from a minimum of 13.9% to a maximum of 36.1%. The majority of such fractures occur in lower limb bones and are associated with low bone mineral density. Anticonvulsant use, joint contractures, immobilization, low physical activity, poor nutrition, the genotype, and lower calcium and vitamin D intakes all significantly impair skeletal maturation and bone mass accrual in Rett syndrome patients, making them more susceptible to fragility fractures. This review summarizes the knowledge on risk factors for fragility fracture in patients with Rett syndrome and suggests a possible diagnostic and therapeutic care pathway for improving low bone mineral density and reducing the risk of fragility fractures. The optimization of physical activity, along with adequate nutrition and the intake of calcium and vitamin D supplements, should be recommended. In addition, subjects with Rett syndrome and a history of fracture should consider using bisphosphonates.

Bilosomes and Biloparticles for the Delivery of Lipophilic Drugs: A Preliminary Study.

In this study, bile acid-based vesicles and nanoparticles (i.e., bilosomes and biloparticles) are studied to improve the water solubility of lipophilic drugs. Ursodeoxycholic acid, sodium cholate, sodium taurocholate and budesonide were used as bile acids and model drugs, respectively. Bilosomes and biloparticles were prepared following standard protocols with minor changes, after a preformulation study. The obtained systems showed good encapsulation efficiency and dimensional stability. Particularly, for biloparticles, the increase in encapsulation efficiency followed the order ursodeoxycholic acid < sodium cholate < sodium taurocholate. The in vitro release of budesonide from both bilosytems was performed by means of dialysis using either a nylon membrane or a portion of Wistar rat small intestine and two receiving solutions (i.e., simulated gastric and intestinal fluids). Both in gastric and intestinal fluid, budesonide was released from bilosystems more slowly than the reference solution, while biloparticles showed a significant improvement in the passage of budesonide into aqueous solution. Immunofluorescence experiments indicated that ursodeoxycholic acid bilosomes containing budesonide are effective in reducing the inflammatory response induced by glucose oxidase stimuli and counteract ox-inflammatory damage within intestinal cells.

A Plant-Based Dietary Supplement Improves Measures of Metabolic Detoxification and the Quality of Life: A Phase II Multicenter Randomized, Blinded, Placebo-Controlled Clinical Trial.

Background: Persistent accumulation and hindered clearance of toxins from tissues over time may promote the development and exacerbation of several diseases. Hepatic metabolic detoxification is a key physiological process responsible for the clearance of toxic substances from the body. A healthy diet with nutritional dietary supplementation may support metabolic detoxification and help mitigate the negative effects of toxin burden. Methods: A multicenter, randomized, single-blind, controlled trial was conducted to test the effects of a dietary detoxification product (detox; n = 20) versus an active dietary control product (active control; n = 20) on selected biomarkers of metabolic detoxification, general health, and well-being following 28 days of dietary supplementation. Study participants displayed multiple symptoms commonly associated with elevated toxin burden, but otherwise healthy. Results: The detox group displayed significantly decreased levels of red blood cell total toxic metals, decreased urine total porphyrins, and decreased urine mutagenicity potency compared with baseline. Both the detox and active control groups showed improvements in the symptoms attributed to elevated toxin burden. Fatigue and sleep disruption scores were significantly reduced in the detox group compared with baseline. No significant differences in anthropometric measures and vital signs, and no adverse events or side effects were detected in either group over the study period. Conclusions: This study demonstrates the benefit of nutritional intervention for supporting metabolic detoxification, evidenced by significant changes in multiple detoxification biomarkers and improvement in questionnaire scores related to quality of life, general health, and well-being.

Tension as a key factor in skin responses to pollution.

Being the more apparent organ exposed to the outdoor stressors, the effect of pollution on the skin has been widely studied in the last few decades. Although UV light is known as the most aggressive stressor to which our cutaneous tissue is daily exposed, other components of the tropospheric pollution have also shown to affect skin health and functionality. Among them, ozone has been proven to be one of the most toxic due to its high reactivity with the epidermal lipids. Studying the cutaneous effect of pollution in a laboratory setting presents challenges, therefore it becomes critical to employ appropriate and tailored models that aim to answer specific questions. Several skin models are available nowadays: in vitro models (2D cell lines and 3D cutaneous tissues), ex vivo skin explants and in vivo approaches (animals and humans). Although in the last 20 years researchers developed skin models that closely resemble human skin (3D cutaneous tissues), ex vivo skin explants still remain one of the best models to study cutaneous responses. Unfortunately, one important cutaneous property that is not present in the traditional ex vivo human skin explants is the physiological tension, which has been shown to be a cardinal player in skin structure, homeostasis, functional properties and responses to external stimuli. For this reason, in this study, to confirm and further comprehend the harmful mechanism of ozone exposure on the integumentary system, we have performed experiments using the state of art in cutaneous models: the innovative TenSkin™ model in which ex vivo human skin explants are cultured under physiologically relevant tension during the whole experimental procedure. Specifically, we were interested in corroborating previous findings showing that ozone exposure modulates the expression of cutaneous antimicrobial peptides (AMPs). The present work demonstrates that cutaneous exposure to ozone induces AMPs gene and protein levels (CAMP/LL-37, hBD2, hBD3) and that the presence of tension can further modulate their expression. In addition, different responses between tension and non-tension cultured skin were also observed during the evaluation of OxInflammatory markers [cyclooxygenase-2 (COX2), aryl hydrocarbon receptor (AhR), matrix-metallo-proteinase 9 (MMP9) and 4-hydroxy-nonenal (4HNE)]. This current study supports our previous findings confirming the ability of pollution to induce the cutaneous expression of AMPs via redox signaling and corroborates the principle that skin explants are a good and reliable model to study skin responses even though it underlines the need to holistically consider the role of skin tension before extrapolating the data to real life.

Moderate red wine intake and cardiovascular health protection: a literature review.

Wine is a complex matrix consisting primarily of water (86%) and ethyl alcohol (12%), as well as other different molecules, such as polyphenols, organic acids, tannins, compound minerals, vitamins and biologically active compounds which play an important role in the specific characteristics of each wine. According to the Dietary Guidelines for Americans 2015-2020, moderate red wine consumption-defined as up to two units of alcohol per day for men and up to one unit of alcohol per day for women-significantly reduces the risk of cardiovascular disease which represents the major causes of mortality, and disability, in developed countries. We reviewed the available literature concerning the potential relationship between moderate red wine consumption and cardiovascular health. We searched Medline, Scopus and Web of Science (WOS) for randomized controlled studies and case-control studies published from 2002 to 2022. A total of 27 articles were selected for the review. According to epidemiological evidence, drinking red wine in moderation lowers the risk of developing cardiovascular disease and diabetes. Red wine contains both alcoholic and non-alcoholic ingredients; however, it is yet unclear which is to blame for these effects. Combining wine with the diet of healthy individuals may add additional benefits. New studies should focus more on the characterization of the individual components of wine, to allow the analysis and study of the impact of each of them on the prevention and treatment of certain diseases.

Redox Regulation of Nucleotide-Binding and Oligomerization Domain-Like Receptors Inflammasome.

Significance: Inflammasomes are multimeric complexes that, as part of the innate immune response, sense a wide range of pathogenic and sterile stimuli. They consist of three components, namely a sensor protein, an adaptor, and procaspase-1, which once activated result in secretion of proinflammatory interleukin (IL)-1ß and IL-18 and, eventually, in a gasdermin D-dependent lytic cell death called pyroptosis. Recent Advances: Since their discovery 20 years ago, the molecular mechanisms underlying the regulation of inflammasomes have been extensively studied. Oxidative stress appears as a major contributor to modulate inflammasomes, especially NLRP3 as well as NLRP1, NLRP6, and NLRC4. Growing evidence supports the idea that the positive feedback between redox imbalance and inflammasome-driven inflammation fuels an OxInflammatory state in a variety of human pathologies. Critical Issues: The current knowledge about the redox signaling pathways involved in inflammasomes activation and functions are here highlighted. In addition, we discuss the role of this complex molecular network interaction in the onset and progression of pathological conditions including neurological and metabolic diseases as well as skin disorders, also with an insight on COVID-19-related pathology. Finally, the therapeutic strategies able to mitigate the redox-mediated inflammasome activation with synthetic and natural compounds as well as by acting on inflammasome-related post-translational modifications and microRNAs are also addressed. Future Directions: Further investigations leading to a deeper understanding of the reciprocal interaction between inflammasomes and reactive oxygen species will help identify other molecular targets for modulating their hyperactivated state, and to design novel therapeutics for chronic OxInflammatory conditions. Antioxid. Redox Signal. 39, 744-770.

Lipid-Based Nanosystems for the Topical Application of Ferulic Acid: A Comparative Study.

In this study, we examined and compared two different lipid-based nanosystems (LBNs), namely Transferosomes (TFs) and Monoolein Aqueous Dispersions (MADs), as delivery systems for the topical application of Ferulic Acid (FA), an antioxidant molecule derived from natural sources. Our results, as demonstrated through Franz-cell experiments, indicate that the LBNs produced with poloxamer 188 in their composition create a multilamellar system. This system effectively controls the release of the drug. Nonetheless, we found that the type of non-ionic surfactant can impact the drug release rate. Regarding FA diffusion from the MAD, this showed a lower diffusion rate compared with the TF. In terms of an in vivo application, patch tests revealed that all LBN formulations tested were safe when applied under occlusive conditions for 48 h. Additionally, human skin biopsies were used to determine whether FA-containing formulations could influence skin tissue morphology or provide protection against O3 exposure. Analyses suggest that treatment with TFs composed of poloxamer 188 and MAD formulations might protect against structural skin damage (as observed in hematoxylin/eosin staining) and the development of an oxidative environment (as indicated by 4-hyroxinonenal (4HNE) expression levels) induced by O3 exposure. In contrast, formulations without the active ingredient did not offer protection against the detrimental effects of O3 exposure.Inizio modulo.

Development of Spray Dried Spirulina Protein-Berry Pomace Polyphenol Particles to Attenuate Pollution-Induced Skin Damage: A Convergent Food-Beauty Approach.

Spray drying (SD) microencapsulation of phytochemicals from berry pomaces with Spirulina protein (SP) was incorporated into a cosmeceutical topical formulation to mitigate pollution skin damage. Initially, microparticles produced with SP and polyphenols recovered from fruit pomaces (elderberry SP-EB and muscadine grape SP-MG) were characterized regarding physicochemical and phytochemical content (polyphenol load, carotenoid and phycocyanin contents and antioxidant activity). SP had low total phenolic content (7.43 ± 0.23 mg GAE/g DW), but complexation with elderberry or muscadine grape pomaces polyphenols led to a substantial increase (27.63 ± 1.15 SP-EB and 111.0 ± 2.6 mg GAE/g DW SP-MG). SP-MG particles had higher anthocyanin (26.87 ± 1.25 mg/g) and proanthocyanidin (9.02 ± 0.74 mg/g) contents compared to SP-EB particles. SP-MG were prioritized to prepare a topical gel to attenuate skin oxinflammatory markers and prevent skin barrier disruption using ex vivo human biopsies exposed to diesel engine exhaust (DEE). The immunofluorescence results showed increased oxidative protein damage and inflammation associated with impaired skin barrier function after DEE exposure while topical application of gel formulated with SP-MG mitigated these effects. Overall, this study demonstrated that protein-polyphenol complexation is a synergistic strategy to stabilize and deliver residual fruit/algae phytoactives into cosmeceutical products for skin health applications.

Ox-inflammasome involvement in neuroinflammation.

Neuroinflammation plays a crucial role in the onset and the progression of several neuropathologies, from neurodegenerative disorders to migraine, from Rett syndrome to post-COVID 19 neurological manifestations. Inflammasomes are cytosolic multiprotein complexes of the innate immune system that fuel inflammation. They have been under study for the last twenty years and more recently their involvement in neuro-related conditions has been of great interest as possible therapeutic target. The role of oxidative stress in inflammasome activation has been described, however the exact way of action of specific endogenous and exogenous oxidants needs to be better clarified. In this review, we provide the current knowledge on the involvement of inflammasome in the main neuropathologies, emphasizing the importance to further clarify the role of oxidative stress in its activation including the role of mitochondria in inflammasome-induced neuroinflammation.

Identification of bromelain subfamily proteases encoded in the pineapple genome.

Papain (aka C1A) family proteases, including bromelain enzymes, are widespread across the plant kingdom and play critical regulatory functions in protein turnover during development. The proteolytic activity exhibited by papain family proteases has led to their increased usage for a wide range of cosmetic, therapeutic, and medicinal purposes. Bromelain enzymes, or bromelains in short, are members of the papain family that are specific to the bromeliad plant family. The only major commercial extraction source of bromelain is pineapple. The importance of C1A family and bromelain subfamily proteases in pineapple development and their increasing economic importance led several researchers to utilize available genomic resources to identify protease-encoding genes in the pineapple genome. To date, studies are lacking in screening bromelain genes for targeted use in applied science studies. In addition, the bromelain genes coding for the enzymes present in commercially available bromelain products have not been identified and their evolutionary origin has remained unclear. Here, using the newly developed MD2 v2 pineapple genome, we aimed to identify bromelain-encoding genes and elucidate their evolutionary origin. Orthologous and phylogenetic analyses of all papain-family proteases encoded in the pineapple genome revealed a single orthogroup (189) and phylogenetic clade (XIII) containing the bromelain subfamily. Duplication mode and synteny analyses provided insight into the origin and expansion of the bromelain subfamily in pineapple. Proteomic analysis identified four bromelain enzymes present in two commercially available bromelain products derived from pineapple stem, corresponding to products of four putative bromelain genes. Gene expression analysis using publicly available transcriptome data showed that 31 papain-family genes identified in this study were up-regulated in specific tissues, including stem, fruit, and floral tissues. Some of these genes had higher expression in earlier developmental stages of different tissues. Similar expression patterns were identified by RT-qPCR analysis with leaf, stem, and fruit. Our results provide a strong foundation for future applicable studies on bromelain, such as transgenic approaches to increase bromelain content in pineapple, development of bromelain-producing bioreactors, and studies that aim to determine the medicinal and/or therapeutic viability of individual bromelain enzymes.

Blueberry Supplementation and Skin Health.

Environmental stressors such as air pollutants, ozone, and UV radiation are among the most noxious outdoor stressors affecting human skin and leading to premature skin aging. To prevent the extrinsic aging, the skin is equipped with an effective defensive system. However, cutaneous defense mechanisms can be overwhelmed through chronic exposure to environmental pollutants. Recent studies have suggested that the topical usage of natural compounds, such as blueberries, could be a good strategy to prevent skin damage from the environment. Indeed, blueberries contain bioactive compounds found to induce an active skin response against the environmental noxious effects. In this review, results from recent studies on this topic are discussed in order to build the argument for blueberries to possibly be an effective agent for skin health. In addition, we hope to highlight the need for further research to elucidate the mechanisms behind the use of both topical application and dietary supplementation with blueberries to bolster cutaneous systems and defensive mechanisms.