Allergen content of popular chemical hair relaxers: A product analysis.

BACKGROUND: Chemical hair relaxers are widely utilized by black women, yet little research exists on the allergens present in these products. OBJECTIVE: This study aims to investigate allergen prevalence in the most popular chemical hair relaxers. METHODS: We analysed 41 products from five major retailers, identifying allergens through ingredient lists and comparing them to the 2020 American Contact Dermatitis Group Core allergen series. RESULTS: The most common contact allergens in chemical relaxers include propylene glycol, cetyl steryl alcohol, fragrance, D/L-a-tocopherol, tea tree oil and cocamidopropyl betaine. CONCLUSION: Understanding allergen exposure in products used by individuals with textured hair is needed for managing contact dermatitis in diverse populations. This analysis underscores the presence of potential allergens in hair relaxers, emphasizing the importance of dermatologists' awareness and patient scrutiny of ingredient lists.

Flood risk behaviors of United States riverine metropolitan areas are driven by local hydrology and shaped by race.

Flooding risk results from complex interactions between hydrological hazards (e.g., riverine inundation during periods of heavy rainfall), exposure, vulnerability (e.g., the potential for structural damage or loss of life), and resilience (how well we recover, learn from, and adapt to past floods). Building on recent coupled conceptualizations of these complex interactions, we characterize human-flood interactions (collective memory and risk-enduring attitude) at a more comprehensive scale than has been attempted to date across 50 US metropolitan statistical areas with a sociohydrologic (SH) model calibrated with accessible local data (historical records of annual peak streamflow, flood insurance loss claims, active insurance policy records, and population density). A cluster analysis on calibrated SH model parameter sets for metropolitan areas identified two dominant behaviors: 1) "risk-enduring" cities with lower flooding defenses and longer memory of past flood loss events and 2) "risk-averse" cities with higher flooding defenses and reduced memory of past flooding. These divergent behaviors correlated with differences in local stream flashiness indices (i.e., the frequency and rapidity of daily changes in streamflow), maximum dam heights, and the proportion of White to non-White residents in US metropolitan areas. Risk-averse cities tended to exist within regions characterized by flashier streamflow conditions, larger dams, and larger proportions of White residents. Our research supports the development of SH models in urban metropolitan areas and the design of risk management strategies that consider both demographically heterogeneous populations, changing flood defenses, and temporal changes in community risk perceptions and tolerance.

The Role of ZO-2 in Modulating JAM-A and γ-Actin Junctional Recruitment, Apical Membrane and Tight Junction Tension, and Cell Response to Substrate Stiffness and Topography.

This work analyzes the role of the tight junction (TJ) protein ZO-2 on mechanosensation. We found that the lack of ZO-2 reduced apical membrane rigidity measured with atomic force microscopy, inhibited the association of γ-actin and JAM-A to the cell border, and instead facilitated p114RhoGEF and afadin accumulation at the junction, leading to an enhanced mechanical tension at the TJ measured by FRET, with a ZO-1 tension probe, and increased tricellular TJ tension. Simultaneously, adherens junction tension measured with an E-cadherin probe was unaltered. The stability of JAM-A and ZO-2 binding was assessed by a collaborative in silico study. The absence of ZO-2 also impacted the cell response to the substrate, as monolayers plated in 20 kPa hydrogels developed holes not seen in parental cultures and displayed a retarded elongation and formation of cell aggregates. The absence of ZO-2 was sufficient to induce YAP and Snail nuclear accumulation in cells cultured over glass, but when ZO-2 KD cells were plated in nanostructured ridge arrays, they displayed an increased abundance of nuclear Snail and conspicuous internalization of claudin-4. These results indicate that the absence of ZO-2 also impairs the response of cells to substrate stiffness and exacerbates transformation triggered by substrate topography.

Regulation of the Nfkbiz Gene and Its Protein Product IkBζ in Animal Models of Sepsis and Endotoxic Shock.

Sepsis is a life-threatening condition that arises from a poorly regulated inflammatory response to pathogenic organisms. Current treatments are limited to antibiotics, fluid resuscitation, and other supportive therapies. New targets for monitoring disease progression and therapeutic interventions are therefore critically needed. We previously reported that lipocalin-2 (Lcn2), a bacteriostatic mediator with potent proapoptotic activities, was robustly induced in sepsis. Other studies showed that Lcn2 was a predictor of mortality in septic patients. However, how Lcn2 is regulated during sepsis is poorly understood. We evaluated how IkBζ, an inducer of Lcn2, was regulated in sepsis using both the cecal ligation and puncture (CLP) and endotoxemia (lipopolysaccharide [LPS]) animal models. We show that Nfkbiz, the gene encoding IkBζ, was rapidly stimulated but, unlike Lcn2, whose expression persists during sepsis, mRNA levels of Nfkbiz decline to near basal levels several hours after its induction. In contrast, we observed that IkBζ expression remained highly elevated in septic animals following CLP but not LPS, indicating the occurrence of a CLP-specific mechanism that extends IkBζ half-life. By using an inhibitor of IkBζ, we determined that the expression of Lcn2 was largely controlled by IkBζ. Altogether, these data indicate that the high IkBζ expression in tissues likely contributes to the elevated expression of Lcn2 in sepsis. Since IkBζ is also capable of promoting or repressing other inflammatory genes, it might exert a central role in sepsis.

Whole-cell bioconversion of naringenin to high added value hydroxylated compounds using Yarrowia lipolytica 2.2ab in surface and liquid cultures.

The bioconversion process of bioactive naringenin by whole-cells of Yarrowia lipolytica 2.2ab for the production of increased value-added compounds is successfully achieved in surface and liquid cultures. This approach is an alternative to the commercial production of these bioactive compounds from vegetable sources, which are limited due to their low concentrations and the complexity of the purification processes. The experimentation rendered seven value-added compounds in both surface and liquid bioconversion cultures. Some of the compounds produced have not been previously reported as products from the bioconversion processes, such as the case of ampelopsin. Biosynthetic pathways were suggested for the naringenin bioconversion using whole-cells of Y. lipolytica 2.2ab. Finally, the extracts obtained from the naringenin bioconversion in liquid cultures showed higher percentage of inhibition of DPPH· and ABTS· radicals up to 32.88 and 2.08 times, respectively, compared to commercial naringenin.

Predicting flood insurance claims with hydrologic and socioeconomic demographics via machine learning: Exploring the roles of topography, minority populations, and political dissimilarity.

Current research on flooding risk often focuses on understanding hazards, de-emphasizing the complex pathways of exposure and vulnerability. We investigated the use of both hydrologic and social demographic data for flood exposure mapping with Random Forest (RF) regression and classification algorithms trained to predict both parcel- and tract-level flood insurance claims within New York State, US. Topographic characteristics best described flood claim frequency, but RF prediction skill was improved at both spatial scales when socioeconomic data was incorporated. Substantial improvements occurred at the tract-level when the percentage of minority residents, housing stock value and age, and the political dissimilarity index of voting precincts were used to predict insurance claims. Census tracts with higher numbers of claims and greater densities of low-lying tax parcels tended to have low proportions of minority residents, newer houses, and less political similarity to state level government. We compared this data-driven approach and a physically-based pluvial flood routing model for prediction of the spatial extents of flooding claims in two nearby catchments of differing land use. The floodplain we defined with physically based modeling agreed well with existing federal flood insurance rate maps, but underestimated the spatial extents of historical claim generating areas. In contrast, RF classification incorporating hydrologic and socioeconomic demographic data likely overestimated the flood-exposed areas. Our research indicates that quantitative incorporation of social data can improve flooding exposure estimates.

A nine-year study on the benefits and risks of soil and water conservation practices in the humid highlands of Ethiopia: The Debre Mawi watershed.

A nine-year (2010-2018) field study in the Debre Mawi watershed was conducted to understand the effect of governmentally-imposed and farmer-initiated conservation practices. The watershed is in the sub-humid Ethiopian Highlands which experience high and increasing erosion rates despite years of conservation efforts. Consequently, reservoirs are filling up with sediment and soil degradation is enhanced, calling for the evaluation of conservation practices currently in use. The few past long-term experimental studies on structural practices are inconclusive. In addition, only anecdotal information is available for streamflow and sediment loss. Precipitation, stream discharge, and suspended sediment concentrations were recorded manually in the Debre Mawi watershed during the nine-year period. Groundwater depth and total saturated area measurements were taken for selected periods. From 2012 to 2014, government-mandated conservation practices were constructed, which consisted of 50-cm-deep infiltration furrows with bunds downslope. These furrows were filled in with sediment by 2018. At the same time, the acreage of eucalyptus trees planted by farmers on the most vulnerable lands tripled to 5% of the total area with most trees fully grown in 2018. Runoff coefficients and sediment concentrations decreased steadily throughout the nine years. In the saturated bottomlands, the observations suggested that government-sponsored infiltration furrows in the saturated bottomlands were ineffective and may concentrate flows and enhance gully erosion, while eucalyptus trees appear effective. The results of this observational study point to both the potential benefits of conservation practices in this sub-humid tropical highland region and to emerging long-term risks. If structural conservation is to be pursued in watersheds like Debre Mawi, due attention must be given to the safe removal of excess water from the valley bottoms. The vegetative farmer-initiated practice of planting eucalyptus trees effectively reduced streamflow and erosion, but at the same time, might dry up wells during the dry monsoon phase which should be investigated further.

ZO-2 Is a Master Regulator of Gene Expression, Cell Proliferation, Cytoarchitecture, and Cell Size.

ZO-2 is a cytoplasmic protein of tight junctions (TJs). Here, we describe ZO-2 involvement in the formation of the apical junctional complex during early development and in TJ biogenesis in epithelial cultured cells. ZO-2 acts as a scaffold for the polymerization of claudins at TJs and plays a unique role in the blood-testis barrier, as well as at TJs of the human liver and the inner ear. ZO-2 movement between the cytoplasm and nucleus is regulated by nuclear localization and exportation signals and post-translation modifications, while ZO-2 arrival at the cell border is triggered by activation of calcium sensing receptors and corresponding downstream signaling. Depending on its location, ZO-2 associates with junctional proteins and the actomyosin cytoskeleton or a variety of nuclear proteins, playing a role as a transcriptional repressor that leads to inhibition of cell proliferation and transformation. ZO-2 regulates cell architecture through modulation of Rho proteins and its absence induces hypertrophy due to inactivation of the Hippo pathway and activation of mTOR and S6K. The interaction of ZO-2 with viral oncoproteins and kinases and its silencing in diverse carcinomas reinforce the view of ZO-2 as a tumor regulator protein.

Influence of Medical Interpreters on the Healthcare Experiences of Hospitalized Spanish-Speaking Patients.

Introduction: The perspective of hospitalized patients with limited English proficiency (LEP) in US hospitals interacting with language-discordant healthcare providers remains understudied. Our goal is to examine the inpatient experiences of Spanish-speaking patients and offer suggestions to improve patient satisfaction. Methods: A survey was administered to Spanish-speaking patients using interpreters during their admission to medicine at an urban, academic hospital. Qualitative thematic analysis of responses was conducted. Results: Thirty-six patients completed the survey. Despite limited use of interpreters, the majority of patients rated interpretation services as excellent, reported high level of involvement in care and respect of their opinions, and preferred video remote interpreting and in-person interpreters. Language barrier and cost affected patients' comfort level requesting health care services. The mean patient satisfaction score was 9.64. Patients suggested an increase in bilingual personnel, improved access to interpreters, specifically in-person. Conclusion: Although highly satisfied, patients reported inconsistent use of interpretation services in the inpatient setting and suboptimal access. Hospitals should strive to provide language-concordant care and patient-centered interpretation. Patients' understanding of their health care rights needs better assessment to ease the inpatient experience. Further research is needed to estimate the regard for autonomy by Spanish-speaking patients in their own care.

Impact of storm events on disinfection byproduct precursors in a drinking water source in the Northeastern United States.

Storm events play a crucial role in organic matter transport within watersheds and can increase the concentration and alter the composition of NOMs and DBP formation potential. To assess the impact that storm events can have on drinking water quality, samples were collected and analyzed across four storm events in the Neversink River, Catskill region, New York in 2019 and 2022. Source water natural organic matter (NOM) was characterized, and the change of NOM quality was evaluated due to storm impacts. During storm events, a high level of NOM mobilization is initiated by heavy precipitation causing overland flow and a rise in the water table. In this way, storms result in increased access to stored NOM pools that are generated during inter-storm periods. A significant correlation was observed between several organic water quality parameters such as UV absorbance (UV254), dissolved organic carbon (DOC) and chlorine demand. Precursors for the total trihalomethanes (TTHM), dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) exhibited comparable patterns with UV254, DOC, and chlorine demand for four storms. Despite the potential for increased dilution resulting from higher discharges, all organic water quality parameters, including yields of disinfection byproducts (i.e., DBP precursors), exhibited elevated concentrations during periods of higher flows. Three of the four storms showed hysteresis patterns with higher observed concentrations of organic constituents in the falling limb of the hydrographs. Precursors for the nitrogenous DBPs (N-DBPs) were proportional to the DOC for all four storms. The coefficient of determination (R2) for TTHM, DCAA, TCAA with UV254 is higher (R2 0.92-0.98) than corresponding correlations with DOC (R2 0.89-0.92). The R2 for UV254 showed the following hierarchy: DCAA≈TCAA>TTHM. Additionally, the R2 for DOC and specific ultraviolet absorbance (SUVA) had the following hierarchy: DCAA>TCAA>TTHM and TCAA>DCAA>TTHM respectively. A significant correlation between UV254 and DOC (R = 0.99) for all storms was observed. Chlorine demand also yielded a strong correlation (R = 0.91∼0.98) with UV254 and DOC. This research indicates that a significant and disproportionate export of NOM to source waters occurs during storm events compared to baseflow conditions. Consequently, it is recommended for drinking water treatment facilities to reassess chlorine dosages during these events. Treatment plants can employ UV254 as a tool to determine appropriate chlorine dosages, aiming to mitigate DBP formation in treated waters.

Enhanced Antioxidant, Antifungal, and Herbicidal Activities through Bioconversion of Diosgenin by Yarrowia lipolytica P01a.

This study explores the bioconversion of diosgenin by Yarrowia lipolytica P01a, focusing on enhancing the antioxidant, antifungal, and herbicidal activities of the resulting extracts. The bioconversion process, involving glycosylation and hydroxylation, produced significant amounts of protodioscin and soyasaponin I. The extracts showed superior antioxidant activity, with up to 97.02% inhibition of ABTS· radicals and 33.30% inhibition of DPPH· radicals at 1000 mg L-1 of diosgenin. Antifungal assays revealed strong inhibitory effects against Botrytis cinerea, Alternaria sp., and Aspergillus niger, with maximum inhibition rates of 67.34%, 35.63%, and 65.53%, respectively. Additionally, the herbicidal activity of the bioconverted extracts was comparable to commercial herbicides, achieving 100% inhibition of seed germination in both monocotyledonous and dicotyledonous plants. These findings suggest that the Y. lipolytica P01a-mediated bioconversion of diosgenin could provide a sustainable and eco-friendly alternative for developing natural biofungicides and bioherbicides.

Identification of candidate genes in rice for resistance to sheath blight disease by whole genome sequencing.

Recent advances in whole genome sequencing (WGS) have allowed identification of genes for disease susceptibility in humans. The objective of our research was to exploit whole genome sequences of 13 rice (Oryza sativa L.) inbred lines to identify non-synonymous SNPs (nsSNPs) and candidate genes for resistance to sheath blight, a disease of worldwide significance. WGS by the Illumina GA IIx platform produced an average 5× coverage with ~700 K variants detected per line when compared to the Nipponbare reference genome. Two filtering strategies were developed to identify nsSNPs between two groups of known resistant and susceptible lines. A total of 333 nsSNPs detected in the resistant lines were absent in the susceptible group. Selected variants associated with resistance were found in 11 of 12 chromosomes. More than 200 genes with selected nsSNPs were assigned to 42 categories based on gene family/gene ontology. Several candidate genes belonged to families reported in previous studies, and three new regions with novel candidates were also identified. A subset of 24 nsSNPs detected in 23 genes was selected for further study. Individual alleles of the 24 nsSNPs were evaluated by PCR whose presence or absence corresponded to known resistant or susceptible phenotypes of nine additional lines. Sanger sequencing confirmed presence of 12 selected nsSNPs in two lines. "Resistant" nsSNP alleles were detected in two accessions of O. nivara that suggests sources for resistance occur in additional Oryza sp. Results from this study provide a foundation for future basic research and marker-assisted breeding of rice for sheath blight resistance.

Case report: Long-term follow-up of a large full-thickness skin defect treated with a photosynthetic scaffold for dermal regeneration.

It is broadly described that almost every step of the regeneration process requires proper levels of oxygen supply; however, due to the vascular disruption in wounds, oxygen availability is reduced, being detrimental to the regeneration process. Therefore, the development of novel biomaterials combined with improved clinical procedures to promote wound oxygenation is an active field of research in regenerative medicine. This case report derives from a cohort of patients enrolled in a previously published ongoing phase I clinical trial (NCT03960164), to assess safety of photosynthetic scaffolds for the treatment of full skin defects. Here, we present a 56 year old patient, with a scar contracture in the cubital fossa, which impaired the elbow extension significantly affecting her quality of life. As part of the treatment, the scar contracture was removed, and the full-thickness wound generated was surgically covered with a photosynthetic scaffold for dermal regeneration, which was illuminated to promote local oxygen production. Then, in a second procedure, an autograft was implanted on top of the scaffold and the patient's progress was followed for up to 17 months. Successful outcome of the whole procedure was measured as improvement in functionality, clinical appearance, and self-perception of the treated area. This case report underscores the long-term safety and applicability of photosynthetic scaffolds for dermal regeneration and their stable compatibility with other surgical procedures such as autograft application. Moreover, this report also shows the ability to further improve the clinical outcome of this procedure by means of dermal vacuum massage therapy and, more importantly, shows an overall long-term improvement in patient´s quality of life, supporting the translation of photosynthetic therapies into human patients.

ZO-2 favors Hippo signaling, and its re-expression in the steatotic liver by AMPK restores junctional sealing.

ZO-2 is a peripheral tight junction (TJ) protein whose silencing in renal epithelia induces cell hypertrophy. Here, we found that in ZO-2 KD MDCK cells, in compensatory renal hypertrophy triggered in rats by a unilateral nephrectomy and in liver steatosis of obese Zucker (OZ) rats, ZO-2 silencing is accompanied by the diminished activity of LATS, a kinase of the Hippo pathway, and the nuclear concentration of YAP, the final effector of this signaling route. ZO-2 appears to function as a scaffold for the Hippo pathway as it associates to LATS1. ZO-2 silencing in hypertrophic tissue is due to a diminished abundance of ZO-2 mRNA, and the Sp1 transcription factor is critical for ZO-2 transcription in renal cells. Treatment of OZ rats with metformin, an activator of AMPK that blocks JNK activity, augments ZO-2 and claudin-1 expression in the liver, reduces the paracellular permeability of hepatocytes, and serum bile acid content. Our results suggest that ZO-2 silencing is a common feature of hypertrophy, and that ZO-2 is a positive regulator of the Hippo pathway that regulates cell size. Moreover, our observations highlight the importance of AMPK, JNK, and ZO-2 as therapeutic targets for blood-bile barrier dysfunction.

Impact of human immunodeficiency virus on pulmonary vascular disease.

With the advent of anti-retroviral therapy, non-AIDS-related comorbidities have increased in people living with HIV. Among these comorbidities, pulmonary hypertension (PH) is one of the most common causes of morbidity and mortality. Although chronic HIV-1 infection is independently associated with the development of pulmonary arterial hypertension, PH in people living with HIV may also be the outcome of various co-morbidities commonly observed in these individuals including chronic obstructive pulmonary disease, left heart disease and co-infections. In addition, the association of these co-morbidities and other risk factors, such as illicit drug use, can exacerbate the development of pulmonary vascular disease. This review will focus on these complex interactions contributing to PH development and exacerbation in HIV patients. We also examine the interactions of HIV proteins, including Nef, Tat, and gp120 in the pulmonary vasculature and how these proteins alter the endothelial and smooth muscle function by transforming them into susceptible PH phenotype. The review also discusses the available infectious and non-infectious animal models to study HIV-associated PAH, highlighting the advantages and disadvantages of each model, along with their ability to mimic the clinical manifestations of HIV-PAH.

Zonula occludens 2 and Cell-Cell Contacts Are Required for Normal Nuclear Shape in Epithelia.

MAGUK protein ZO-2 is present at tight junctions (TJs) and nuclei. In MDCK ZO-2 knockdown (KD) cells, nuclei exhibit an irregular shape with lobules and indentations. This condition correlates with an increase in DNA double strand breaks, however cells are not senescent and instead become resistant to UV-induced senescence. The irregular nuclear shape is also observed in isolated cells and in those without TJs, due to the lack of extracellular calcium. The aberrant nuclear shape of ZO-2 KD cells is not accompanied by a reduced expression of lamins A/C and B and lamin B receptors. Instead, it involves a decrease in constitutive and facultative heterochromatin, and microtubule instability that is restored with docetaxel. ZO-2 KD cells over-express SUN-1 that crosses the inner nuclear membrane and connects the nucleoskeleton of lamin A to nesprins, which traverse the outer nuclear membrane. Nesprins-3 and -4 that indirectly bind on their cytoplasmic face to vimentin and microtubules, respectively, are also over-expressed in ZO-2 KD cells, whereas vimentin is depleted. SUN-1 and lamin B1 co-immunoprecipitate with ZO-2, and SUN-1 associates to ZO-2 in a pull-down assay. Our results suggest that ZO-2 forms a complex with SUN-1 and lamin B1 at the inner nuclear membrane, and that ZO-2 and cell-cell contacts are required for a normal nuclear shape.

Development of a Novel Perfusable Solution for ex vivo Preservation: Towards Photosynthetic Oxygenation for Organ Transplantation.

Oxygen is the key molecule for aerobic metabolism, but no animal cells can produce it, creating an extreme dependency on external supply. In contrast, microalgae are photosynthetic microorganisms, therefore, they are able to produce oxygen as plant cells do. As hypoxia is one of the main issues in organ transplantation, especially during preservation, the main goal of this work was to develop the first generation of perfusable photosynthetic solutions, exploring its feasibility for ex vivo organ preservation. Here, the microalgae Chlamydomonas reinhardtii was incorporated in a standard preservation solution, and key aspects such as alterations in cell size, oxygen production and survival were studied. Osmolarity and rheological features of the photosynthetic solution were comparable to human blood. In terms of functionality, the photosynthetic solution proved to be not harmful and to provide sufficient oxygen to support the metabolic requirement of zebrafish larvae and rat kidney slices. Thereafter, isolated porcine kidneys were perfused, and microalgae reached all renal vasculature, without inducing damage. After perfusion and flushing, no signs of tissue damage were detected, and recovered microalgae survived the process. Altogether, this work proposes the use of photosynthetic microorganisms as vascular oxygen factories to generate and deliver oxygen in isolated organs, representing a novel and promising strategy for organ preservation.

Antibacterial fatty acids: An update of possible mechanisms of action and implications in the development of the next-generation of antibacterial agents.

The antibacterial activity of fatty acids (FA) is well known in the literature and represents a promising option for developing the next-generation of antibacterial agents to treat a broad spectrum of bacterial infections. FA are highly involved in living organisms' defense system against numerous pathogens, including multidrug-resistant bacteria. When combined with other antibacterial agents, the remarkable ability of FA to enhance their bactericidal properties is a critical feature that is not commonly observed in other naturally-occurring compounds. More reviews focusing on FA antibacterial activity, traditional and non-traditional mechanisms and biomedical applications are needed. This review is intended to update the reader on the antibacterial properties of recent FA and how their chemical structures influence their antibacterial activity. This review also aims to better understand both traditional and non-traditional mechanisms involved in these recently explored FA antibacterial activities.

A First in Human Trial Implanting Microalgae Shows Safety of Photosynthetic Therapy for the Effective Treatment of Full Thickness Skin Wounds.

Insufficient oxygen supply represents a relevant issue in several fields of human physiology and medicine. It has been suggested that the implantation of photosynthetic cells can provide oxygen to tissues in the absence of a vascular supply. This approach has been demonstrated to be successful in several in vitro and in vivo models; however, no data is available about their safety in human patients. Here, an early phase-1 clinical trial (ClinicalTrials.gov identifier: NCT03960164, https://clinicaltrials.gov/ct2/show/NCT03960164) is presented to evaluate the safety and feasibility of implanting photosynthetic scaffolds for dermal regeneration in eight patients with full-thickness skin wounds. Overall, this trial shows that the presence of the photosynthetic microalgae Chlamydomonas reinhardtii in the implanted scaffolds did not trigger any deleterious local or systemic immune responses in a 90 days follow-up, allowing full tissue regeneration in humans. The results presented here represent the first attempt to treat patients with photosynthetic cells, supporting the translation of photosynthetic therapies into clinics. Clinical Trial Registration: www.clinicaltrials.gov/ct2/show/NCT03960164, identifier: NCT03960164.

Endothelial TRP channels and cannabinoid receptors are involved in affinin-induced vasodilation.

Affinin is mainly recognized by its antinociceptive effect. Recently, our research group demonstrated that this compound produces vasodilation via activation of the gasotransmitters signaling pathways. However, the molecular targets of affinin were not identified. Considering the structural similarity of this alkamide with anandamide, we hypothesized that affinin-induced vasodilation could involve participation of TRP channels and cannabinoid receptors. In this work, by using the isolated rat aorta assay, we assessed involvement of TRP channels, the cannabinoid system, and the HNO-CGRP-TRPA1 pathway on the mechanism of action of affinin. Additionally, we measured NO and H2S levels elicited by affinin on rat aorta homogenates and carried out computer simulations of molecular interactions between affinin and the TRPA1 and TRPV1 channels and the CB1 receptor. Our results indicated that affinin induces an increase in aortic NO and H2S levels. We found evidence that the vasodilator effect induced by affinin involves activation of TRPA1 and TRPV1 channels and the CB1 and eCB receptors. In silico analyses showed that affinin is able to bind with high affinity to these molecular targets. Moreover, we also proved that affinin-induced vasodilation is partly mediated via activation of the HNO-TRPA1-CGRP pathway. Based on these results we propose a novel mechanism of action to explain the vasodilatory effect of affinin, which could be developed as an alternative drug to treat cardiovascular diseases.