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Introduction: Cape gooseberry (Physalis peruviana L.) is a wellconsumed crop in Ecuador, whose fruits are abundant in bioactive molecules. Its rapid post-harvest deterioration and safety limit its market potential. Methodology: To gather baseline data on the prevalence of bacterial taxa among groups, we employed 16S ribosomal RNA (16S rRNA) amplicon gene sequencing to detect changes in the bacterial community structure in cape gooseberry fruits harvested from an organic farm production system (# 270 samples x two ripeness stages), and fruits obtained from an open-air market (#270). Results: This is the first report of bacterial taxa inhabiting cape gooseberry fruits. Shannon's diversity index revealed that the fruits purchased from the market and the unripe stage had the highest level of bacterial diversity (average Shannon indices of 3.3 and 3.1) followed by those collected from the field at the mature ripe stage (2.07). Alpha diversity analysis indicated that there were no significant differences in the number of taxa or evenness within the sample, whereas there was a significant difference in beta diversity between the groups. Rhizobiaceae was the most abundant family in fruits originating from the field regardless of the ripe stage, while Acetobacteraceae, Pseudomonadaceae, Fusobacteriaceae, Bacteroidaceae, and Erwiniaceae were the most abundant families in the market group. At the genus level, Liberibacter was the most abundant phytopathogen in fruits originating from the field, while Gluconobacter was the most abundant in samples collected from the market. The phytopathogen Candidatus_Liberibacter was the most abundant in samples collected from the field, while the fruits purchased from the market stands contained opportunistic enteric pathogens such as Escherichia vulneris, Klebsiella pneumoniae, and K. variicola, their relative abundance varied with the sample. In addition, potential pathogens of animal origin such as Fusobacterium necrophorum, Porphyromonas levii, Helcococcus ovis, and Trueperella pyogenes were found in almost all samples at varying relative abundance. Conclusion: Our study provides basic information on the microbiome of cape gooseberries from agriculture fields to the table along with the detection of several pathogenic microorganisms with possible impact on food safety and public health therefore, strategies for reducing bacterial contamination in both farm and retail markets are compulsory.

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Introduction: Foodborne infections, which are frequently linked to bacterial contamination, are a serious concern to public health on a global scale. Whether agricultural farming practices help spread genes linked to antibiotic resistance in bacteria associated with humans or animals is a controversial question. Methods: This study applied a long-read Oxford Nanopore MinION-based sequencing to obtain the complete genome sequence of a multi-drug resistant Escherichia coli strain (L1PEag1), isolated from commercial cape gooseberry fruits (Physalis peruviana L.) in Ecuador. Using different genome analysis tools, the serotype, Multi Locus Sequence Typing (MLST), virulence genes, and antimicrobial resistance (AMR) genes of the L1PEag1 isolate were determined. Additionally, in vitro assays were performed to demonstrate functional genes. Results: The complete genome sequence of the L1PEag1 isolate was assembled into a circular chromosome of 4825.722 Kbp and one plasmid of 3.561 Kbp. The L1PEag1 isolate belongs to the B2 phylogroup, sequence type ST1170, and O1:H4 serotype based on in silico genome analysis. The genome contains 4,473 genes, 88 tRNA, 8 5S rRNA, 7 16S rRNA, and 7 23S rRNA. The average GC content is 50.58%. The specific annotation consisted of 4,439 and 3,723 genes annotated with KEEG and COG respectively, 3 intact prophage regions, 23 genomic islands (GIs), and 4 insertion sequences (ISs) of the ISAs1 and IS630 families. The L1PEag1 isolate carries 25 virulence genes, and 4 perfect and 51 strict antibiotic resistant gene (ARG) regions based on VirulenceFinder and RGI annotation. Besides, the in vitro antibiotic profile indicated resistance to kanamycin (K30), azithromycin (AZM15), clindamycin (DA2), novobiocin (NV30), amikacin (AMK30), and other antibiotics. The L1PEag1 isolate was predicted as a human pathogen, matching 464 protein families (0.934 likelihood). Conclusion: Our work emphasizes the necessity of monitoring environmental antibiotic resistance, particularly in commercial settings to contribute to develop early mitigation techniques for dealing with resistance diffusion.

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The focus of this study was on the development, physicochemical characterisation and evaluation of the antioxidant activity of cape gooseberry calyx extract loaded into nanoliposomal systems. Various nanoliposomes were prepared and optimised using the ethanol injection method and characterised based on particle size, polydispersity and zeta potential measurements. Subsequently, the encapsulation efficiency and in vitro release profile of the natural antioxidant extract (NAE) were evaluated, and its antioxidant activity was assessed using the oxygen radical absorbance capacity assay. The results revealed that NAE-loaded nanoliposomes described desired quality features (e.g., particle size of < 200 nm, polydispersity index of < 0.3, zeta potential of > -40 mV and encapsulation efficiency of ∼70%). Furthermore, it was found that NAE release is controlled by various stages, and its antioxidant activity improves by around 30% when loaded into the nanoliposomes, suggesting that it could be a promising antioxidant functional raw material.

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Introducción: CAPE-V es ampliamente utilizado para evaluación perceptual vocal y ha sido adaptado y validado en múltiples idiomas. A través de un análisis exhaustivo, este estudio buscó avanzar en establecer un estándar en el método utilizado para su adaptación y validación. Objetivo: Revisar los artículos publicados entre 2002 y 2022 que han adaptado y validado CAPE-V a distintos idiomas, para evaluar exhaustivamente la adaptación, metodología y estadísticas utilizadas. Métodos: Se realizó una revisión sistemática utilizando Scopus, Google Scholar y PubMed para identificar artículos que adaptaran y/o validaran CAPE-V entre 2002 y 2022. Se analizó el título y resumen para preseleccionar la muestra. Para evaluar el riesgo de sesgo de los estudios incluidos se analizó de forma crítica el texto completo. Resultados: La búsqueda inicial identificó 568 artículos. Al eliminar duplicados se revisaron 559 y 23 fueron preseleccionados. 12 se incluyeron finalmente y fueron analizados, considerando adaptación, metodología y análisis estadístico. Los resultados revelan que la adaptación y validación de CAPE-V a diversos idiomas es fundamental para garantizar mediciones precisas y confiables en diferentes poblaciones. Análisis y discusión: Existe heterogeneidad en la forma de realizar la adaptación y validación de CAPE-V. No obstante, todos los estudios tuvieron éxito en producir resultados válidos, subrayando la importancia de estos procesos para la práctica clínica. Conclusiones: Las adaptaciones y validaciones de CAPE-V se realizaron heterogéneamente por ausencia de un protocolo estándar. Es necesario generar orientaciones para realizar estos procesos por el aporte de esta escala a la clínica, asegurando calidad y confiabilidad de los resultados.

Introduction: CAPE-V is widely used for vocal perceptual evaluation and has been adapted and validated in multiple languages. Through an exhaustive analysis, this study sought to advance in establishing a standard in the method used in its adaptation and validation. Objective: To review articles published between 2002 and 2022 that have adapted and validated CAPE-V in different languages, to thoroughly evaluate the adaptation, methodology, and statistics used. Methods: A systematic review was conducted using Scopus, Google Scholar and PubMed to identify articles that adapted and/or validated CAPE-V between 2002 and 2022. The title and summary were analyzed to pre-select the sample. To evaluate the risk of bias of the included studies, the full text was critically analyzed. Results: The initial search identified 568 items. When duplicates were removed, 559 were reviewed and 23 were pre-selected. 12 were finally included and analyzed considering adaptation, methodology, and statistical analysis. The results show that the adaptation and validation of CAPE-V to different languages is essential to ensure accurate and reliable measurements in different populations. Analysis and discussion: There is heterogeneity in how CAPE-V is adapted and validated. However, all studies were successful in producing valid results, underlining the importance of these processes for clinical practice. Conclusions: Adaptations and validations of CAPE-V were performed heterogeneously due to the absence of a standard protocol. It is necessary to generate guidelines to perform these processes by providing this scale to the clinic, ensuring quality and reliability of results.

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Neurodegenerative disorders are characterized by a progressive process of degeneration and neuronal death, where oxidative stress and neuroinflammation are key factors that contribute to the progression of these diseases. Therefore, two major pathways involved in these pathologies have been proposed as relevant therapeutic targets: The nuclear transcription factor erythroid 2 (Nrf2), which responds to oxidative stress with cytoprotecting activity; and the nuclear factor NF-κB pathway, which is highly related to the neuroinflammatory process by promoting cytokine expression. Caffeic acid phenethyl ester (CAPE) is a phenylpropanoid naturally found in propolis that shows important biological activities, including neuroprotective activity by modulating the Nrf2 and NF-κB pathways, promoting antioxidant enzyme expression and inhibition of proinflammatory cytokine expression. Its simple chemical structure has inspired the synthesis of many derivatives, with aliphatic and/or aromatic moieties, some of which have improved the biological properties. Moreover, new drug delivery systems increase the bioavailability of these compounds in vivo, allowing its transcytosis through the blood-brain barrier, thus protecting brain cells from the increased inflammatory status associated to neurodegenerative and psychiatric disorders. This review summarizes the biosynthesis and chemical synthesis of CAPE derivatives, their miscellaneous activities, and relevant studies (from 2010 to 2023), addressing their neuroprotective activity in vitro and in vivo.

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AIM: Using in vitro assay and eukaryotic cell model of Saccharomyces cerevisiae, we investigated the impact of microbial fermentation on the antioxidant activity of phenolic substances. METHODS AND RESULTS: Caffeic acid phenethyl ester (CAPE) and mangiferin were fermented by lactic acid bacteria (LAB), and the antioxidant activity of the fermented products was compared to that of the pure substances. This comparison was assessed using high-performance liquid chromatography (HPLC), in vitro by 2,2-Diphenyl-1-picrylhydrazyl (DPPH), and in vivo in yeast cells. The wild-type strain (BY4741) and its isogenic mutants in glutathione (Δgsh1), catalase (Δctt1), and superoxide dismutase (Δsod1) were treated with CAPE and mangiferin, fermented or not, and exposed to hydrogen peroxide (H2O2)-induced stress. The antioxidant activity was evaluated by cellular viability, intracellular oxidation, and lipid peroxidation. We expected that fermentation would change the antioxidant activity of phenolic substances. While HPLC analysis revealed changes in the composition of fermented products, significant alterations in antioxidant activity were only observed when using mutant strains. The fermentation of mangiferin increased dependency on GSH compared to the respective pure phenolic substance to resolve H2O2-induced stress. Additionally, CAPE appeared to act as a preconditioning agent, enhancing antioxidant responses, and promoting increased tolerance to H2O2 stress, and this mechanism was maintained after fermentation. CONCLUSIONS: This study highlights that fermentation impacts the enzymatic mechanism of oxidative stress resolution, even though differences could not be observed in in vitro assays or in the wild-type strain.

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The use of microbial consortia has become a promising alternative for the management of various diseases. In this study, 18 artificial consortia were designed, consisting of five bacteria, five fungi, and a mixture of five fungi and five bacteria; from a collection of microorganisms isolated from the rhizosphere of cape gooseberry plants grown in two soils potentially suppressive against Fusarium oxysporum. When evaluated under greenhouse conditions for their biocontrol activity on cape gooseberry plants, one consortium was selected for their high efficacy (over 90%) in the control of vascular wilt caused by F. oxysporum f. sp. physali. This was constituted by 10 microorganisms, the bacteria Paenibacillus peoriae, Bacillus subtilis, Lysinibacillus sp., B. simplex, and Pseudomonas chlororaphis; and the fungi Beauveria bassiana, Scopulariopsis brevicaulis, Trichoderma gamsii, T. ghanense, and T. lignicola. On the other hand, four of the consortia evaluated in the presence of the pathogen mitigated the deleterious effect produced by the pathogen on plant growth, expressing higher dry weights, both in the aerial and root parts. This work represents the first report on using these mixtures of microorganisms to control vascular wilt produced by F. oxysporum. However, further studies are needed to determine their activity in cape gooseberry fields.

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Background: The CAPE Vulnerability Index serves as a worldwide foreign policy indicator that implies which countries should get assistance first. It provides an evidence-based, well-structured, and well-reasoned strategy for employing aid in bilateral arrangements with mental health as a basis. Objective: The second edition of the CAPE VI has been developed to identify which nations should get priority foreign aid. Materials and Methods: We considered various indices or measures at the country level reflecting the average national health status or factors influencing public health. To make our choice, we used 26 internationally accessible and verified indicators. For the study, we have scored the countries according to these indices and prioritized those with the worst scores. Results: The CAPE Vulnerability Index is based on the number of times a country is ranked among the low-scoring nations. It is based on nine parameters and is an independent measure even though there may be a correlation with similar indices such as life expectancy, disability-adjusted life years(DALYs), physician numbers, and gross domestic product(GDP). Conclusion: We concluded that low-scoring countries were fragile or failed states, such as nations where governments lack complete oversight or power, are often oppressive and corrupt, have allegations of violations of human rights, or are marked by political turmoil in different forms, drawbacks from severe environmental damage, severe impoverishment, inequalities, cultural and racial divisions, cannot supply fundamental amenities, are victims of terrorism, and so on. To address these essential problems impacting fragile nations, administrations, aid donors, local organizations, mental health specialists, and associations should collaborate.

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Despite the Naegleria genus being isolated from different natural environments such as water, soil, and air, not all Naegleria species are capable of causing infections in humans, and they are capable of completing their life cycle in environmental niches. However, the presence of this genus may suggest the existence of one of the highly pathogenic free-living amoeba (FLA) species: Naegleria fowleri or the brain-eating amoeba. This facultative parasitic protozoon represents a risk to public health, mainly related to domestic and agricultural waters. In this research, our main objective was to determine the existence of pathogenic protozoa in the Santa Cruz wastewater treatment plant, Santiago Island. Using 5 L of water we confirmed the presence of potentially pathogenic Naegleria australiensis, being the first report on Naegleria species in Cape Verde. This fact demonstrates the low efficiency in the treatment of wastewater and, consequently, a potential threat to public health. Nevertheless, more studies will be needed for the prevention and control of possible infections in this Macaronesian country.

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Golden berry (Physalis peruviana) is a tropical fruit rich in antioxidants that has been proposed to be able to control the lipid profile in hypercholesterolemic patients. Dyslipidemia is an independent risk factor for cardiometabolic diseases. The gut microbiota is strongly associated with cardiometabolic risk and is involved in redox balance, intestinal permeability, and inflammation. However, the impacts of golden berry on some of these factors, including the human gut microbiota, have never been tested, and there are no tools for compliance monitoring or dietary intake assessment regarding nutritional interventions with this fruit. In the pre-post quasi-experimental nutritional intervention presented here, 18 adult men (27-49 years old) consumed golden berries (Dorada variety) for three weeks. We evaluated putative biomarkers of exposure through an untargeted metabolomics approach (liquid chromatography-mass spectrometry LC-MS), quantified the biomarkers of oxidative stress, gut permeability, and inflammation in plasma, and assessed the effects of fruit intake on the gut microbiota through 16S rRNA gene sequencing of feces (Illumina MiSeq V2). First, syringic acid and kaempferol were identified as putative biomarkers of golden berry consumption. Intervention with this fruit promoted physiological changes in the participants after three weeks, reducing the level of the oxidative stress marker 8-isoprostane (-148 pg/ml; 36.1 %; p = 0.057) and slightly altering gut permeability by increasing the plasma levels of LBP (2.91 µg/ml; 54.6 %; p = 0.0005) and I-FABP (0.15, 14.7 %, p = 0.04) without inducing significant inflammation; i.e., the levels of IL-1ß, TNF-α and IL-8 changed by 0.7 (2.0 %), -4.0 (-9.6 %) and -0.4 (-1.8 %) pg/ml, respectively. Notably, the consumption of golden berries did not affect the gut microbiota of the individuals consistently but instead shifted it in a personalized manner. The compositions of the gut microbiota of a given individual at the end of intervention and one month after the end of intervention were statistically more similar to their own baseline than to a corresponding sample from a different individual. This intervention identified putative biomarkers of golden berry intake along with potential benefits of its consumption relevant to cardiometabolic disease risk reduction. Golden berries are likely to positively modulate redox balance, although this effect must be proven in a future controlled clinical trial.

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Propolis has gained wide popularity over the last decades in several parts of the world. In parallel, the literature about propolis composition and biological properties increased markedly. A great number of papers have demonstrated that propolis from different parts of the world is composed mainly of phenolic substances, frequently flavonoids, derived from plant resins. Propolis has a relevant role in increasing the social immunity of bee hives. Experimental evidence indicates that propolis and its components have activity against bacteria, fungi, and viruses. Mechanisms of action on bacteria, fungi, and viruses are known for several propolis components. Experiments have shown that propolis may act synergistically with antibiotics, antifungals, and antivirus drugs, permitting the administration of lower doses of drugs and higher antimicrobial effects. The current trend of growing resistance of microbial pathogens to the available drugs has encouraged the introduction of propolis in therapy against infectious diseases. Because propolis composition is widely variable, standardized propolis extracts have been produced. Successful clinical trials have included propolis extracts as medicine in dentistry and as an adjuvant in the treatment of patients against COVID-19. Present world health conditions encourage initiatives toward the spread of the niche of propolis, not only as traditional and alternative medicine but also as a relevant protagonist in anti-infectious therapy. Production of propolis and other apiary products is environmentally friendly and may contribute to alleviating the current crisis of the decline of bee populations. Propolis production has had social-economic relevance in Brazil, providing benefits to underprivileged people.

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Social exclusion and poverty are associated with increased mental health issues. In addition, the current political and civil conflicts worldwide are also considered as leading factors to mental disorders and substance use disorders. The Compassion, Assertive action, Pragmatism and Evidence (CAPE) index comprises nine country-level measures and highlights the need for assistance in countries with a high degree of vulnerability. Several findings from previous studies reported a broad relationship between CAPE indices and increased levels of mental disorders and substance use. In this paper, we identified the prevalence of mental disorders and substance use disorders among those countries reporting higher (i.e., highest CAPE Index scores) as well as lower (i.e., highest Quality of Life Index scores) vulnerability. We extracted prevalence data from the Institute for Health Metrics and Evaluation global database in 2019. There was a lower prevalence of mental (12.5%) and substance use (1.7%) disorders in highly vulnerable countries than less vulnerable ones (15.1% and 3.5%, respectively). These findings suggest an urgent need for early detection of mental and substance use disorders in vulnerable countries: increasing mental health literacy among non-specialized health professionals in these regions may greatly improve the level of detection and treatment.

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The broadnose sevengill shark, Notorynchus cepedianus (Péron, 1807), is a large marine top predator in temperate coastal ecosystems. Some aspects of its life history have been determined, but its growth pattern is yet to be fully understood. The authors used a multi-modelling approach and a sensitivity test to estimate growth parameters from young-of-year (YOY) length data collected off San Antonio Cape (SAC), Argentina, a critical habitat in the Southwest Atlantic Coastal Zone (SACZ). The best selected model, a sex-combined logistic growth model, estimated an asymptotic length (L∞ ) of 92.58 cm TL (95% C.I.: 86.48-105.89 cm), a growth coefficient (K) of 0.006818 days -1 (95% C.I.: 0.004948-0.008777) and a size at birth (L0 ) of 40.73 cm. The predicted annual growth (i.e., L1 - L0 ) was 43.2 cm TL. Males had smaller L0 , higher K and achieved larger sizes after 1 year. The YOY in SAC attained a larger L1 and grew faster than their Australian and South African wild counterparts. The consistent year-round presence of YOY in the SAC highlights the importance of this area as a pupping ground and potential nursery for N. cepedianus; this has direct implications for the allocation of research and management effort for the conservation of this species in the Southwest Atlantic.

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INTRODUCTION: The Consensus Auditory Perceptual Evaluation of Voice (CAPE-V) scale is a modern, clinical-scientific approach to voice analysis. It has been translated and culturally adapted to Brazilian Portuguese, but it still lacks validation. OBJECTIVE: To validate the Brazilian Portuguese version of the CAPE-V scale using the previously translated and culturally adapted version. METHOD: Forty voice samples were selected (30 dysphonic, 10 nondysphonic), and the degree of vocal deviation was evaluated by a committee of three voice specialists. Nine voice specialists judged the 40 voice samples plus 20% repetition (total of 48 samples) using the CAPE-V. To ensure construct validity of the CAPE-V, its analysis was compared to the Grade-Roughness-Breathiness-Asthenia-Strain (GRBAS) scale that was performed 48-72 hours later. Finally, the intra- and inter-rater reliability values were verified and the correlation between the nine judges and the previously defined evaluation was analyzed. RESULTS: The Brazilian CAPE-V presented significant intra (0.860-0.997) and inter-rater reliability values (0.707-0.964) for the overall degree and strong correlation with GRBAS (above 0.828). Deviant voice quality had greater consensus among raters than normal voices. A strong correlation was observed between the analysis of the nine raters and that of the committee. CONCLUSION: CAPE-V is an important diagnostic instrument that contributes to the standardization of vocal quality evaluation in several languages, including Brazilian Portuguese. Thus, its usefulness is neither related to a single language nor to a single set of raters.

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ABSTRACT The Neuropteran fauna on the most meridional part of South America is relatively scarce. Two families, Hemerobiidae and Coniopterigydae, have been recorded so far. Accordingly, only a few species have reached the south of Tierra del Fuego. Currently, the southernmost records of these species, Hemerobius chilensis Nakahara, 1965 and Megalomus flinti (Nakahara, 1965), are from Puerto Williams, Navarino Island (54°56′S 67°37′W), which makes them the southernmost distributed neuropterans in the continent. Here we provide the first records for two Neuroptera species, Hemerobius nekoi Monserrat, 1996 and Megalomus flinti; from Deceit Island, a remote subantarctic island within the Cape Horn archipelago (55°51′41″S 67°08′31″W). The records provided makes these species the southernmost recorded lacewings in the continent; extending the known distribution of neuropterans in South America nearly 110km towards the south.

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Physalis is an herbaceous species native to the Andes region. Currently, it is cultivated in various Brazilian states due to the economic interest of growers for this new fruit. Physalis plants grown in the field showed symptoms of shoot proliferation, leaf malformation, and chlorosis. Since these symptoms are commonly induced by phytoplasmas, this study investigated to confirm the presence of these prokaryotes in symptomatic plants. After DNA extraction from symptomatic and asymptomatic plants, phytoplasmas were found in all affected plants through the nested PCR. Examination by transmission electron microscopy (TEM) using appropriately prepared segments of leaf veins allowed the visualization of typical pleomorphic cells of phytoplasmas in the phloem of symptomatic plants. The computer-simulated RFLP patterns and the phylogenetic analysis allowed identifying the detected phytoplasmas as a 'Candidatus Phytoplasma fraxini'-related strain belonging to the 16SrVII-B subgroup. Moreover, physalis was identified as an additional host species for phytoplasmas in the 16SrVII group, expanding the current knowledge on the host range of phytoplasmas in this group.

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Physalis peruviana L. belongs to the Solanaceae family and produces a spherical fruit used to treat various diseases. However, the chemical composition, nutritional characterization, and bioactive properties of the P. peruviana growing in the Andean region of the Atacama Desert have not been conducted so far. The results showed clear differences in the nutritional and bioactive characteristics of the fruits grown in arid environmental conditions, which were comparable to those from countries with a production tradition. The fruits studied showed a higher Ca, Cu, Mn, P, and Zn content and bioactive compounds such as flavonoids and tannins than those reported in the literature. UHPLC was performed to determine the main phenols. Gallic acid was identified as the predominant phenolic compound in this species (303.63 mg/100 g FW), of which to our knowledge no previous study has reported similar concentrations in this species. Moreover, Cape gooseberry extract has antioxidant and antimicrobial activity against Gram-positive and Gram-negative bacteria. Pseudomonas syringae (MIC 0.313 mg/mL and MBC 1.25 mg/mL) was the most susceptible bacterium. Meanwhile, Erwinia rhapontici was the most resistant bacterium (MIC and MIB 5.00 mg/mL). Furthermore, it was found to inhibit α-amylase activity with an IC50 value (39.28 µg/mL) similar to that of acarbose (35.74 µg/mL). These results expand the knowledge of the species cultivated in arid environmental conditions and suggest an alternative for the potential use of this fruit to manage chronic diseases such as diabetes.

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Candida auris is an emerging healthcare-associated fungal pathogen that has become a serious global health threat. Current treatment options are limited due to drug resistance. New therapeutic strategies are required to target this organism and its pathogenicity. Plant polyphenols are structurally diverse compounds that present a vast range of biological properties. In the present study, plant-derived molecules ellagic acid (EA) and caffeic acid phenethyl ester (CAPE) were investigated for their antifungal and antivirulence activities against Candida auris. We also tested against C. albicans. The minimum inhibitory concentration (MIC) for EA ranged from 0.125 to 0.25 µg/mL and for CAPE ranged from 1 to 64 µg/mL against drug-resistant C. auris strains. Killing kinetics determined that after 4 h treatment with CAPE, there was a complete reduction of viable C. auris cells compared to fluconazole. Both compounds might act by modifying the fungal cell wall. CAPE significantly reduced the biomass and the metabolic activity of C. auris biofilm and impaired C. auris adhesion to cultured human epithelial cells. Furthermore, both compounds prolonged the survival rate of Galleria mellonella infected by C. auris (p = 0.0088 for EA at 32 mg/kg and p = 0.0028 for CAPE at 4 mg/kg). In addition, EA at 4 µg/mL prolonged the survival of C. albicans-infected Caenorhabditis elegans (p < 0.0001). CAPE was not able to prolong the survival of C. albicans-infected C. elegans. These findings highlight the antifungal and antivirulence effects of EA and CAPE against C. auris, and warrant further investigation as novel antifungal agents against drug-resistant infections.

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Candida albicans is the main fungal species associated with the development of oral candidiasis. Currently, therapeutic options for these infections are limited by the adverse effects of antifungal drugs and by the emergence of drug resistant strains. Thus, the development of new antifungal agents is needed for the prevention and treatment of oral Candida infections. Caffeic acid phenethyl ester (CAPE) is a natural compound from propolis polyphenolic groups that exhibits many pharmacological properties. In this study, we investigated whether CAPE can have antifungal and immunomodulatory effects on oral candidiasis. Preliminary tests to assess the antifungal activity of CAPE were performed using the Minimum Inhibitory Concentration (MIC) assay that demonstrated inhibition in a range from 16 to 32 µg/mL, confirming its antifungal activity on several C. albicans strains isolated from the oral cavity. Subsequently, we analyzed Candida spp biofilms formed in vitro, in which CAPE treatment at 5 x MIC caused a reduction of 68.5% in the total biomass and ~2.60 Log in the viable cell count (CFU/mL) in relation to the untreated biofilm (p<0.0001). Next, RNA was extracted from untreated and CAPE-treated biofilms and analyzed by real-time qPCR. A series of genes analyzed (ALS1, ECE1, EPA1, HWP1, YWP1, BCR1, BGR1, CPH1, EFG1, NDT80, ROB1, TEC1, UME6, SAP2, SAP5, PBL2, and LIP9) were downregulated by CAPE compared to the untreated control group (p<0.0001). In in vivo studies using Galleria mellonella, the treatment with CAPE prolonged survival of larvae infected by C. albicans by 44.5% (p < 0.05) and accompanied by a 2.07-fold increase in the number of hemocytes. Flow cytometry revealed the most prominent increases were in types P2 and P3 hemocytes, granular cells, which phagocytize pathogens. In addition, CAPE treatment decreased the fungal load in the hemolymph and stimulated the expression of antifungal peptide genes such as galiomicin and gallerimycin. The antifungal and immunomodulatory activities observed in G. mellonella were extended to a murine model of oral candidiasis, in which CAPE decreased the levels of C. albicans colonization (~2 log CFU/mL) in relation to the untreated control group. In addition, CAPE treatment significantly reduced pseudomembranous lesions, invasion of hyphae on epithelium surfaces, tissue damage and inflammatory infiltrate (p < 0.05). CAPE was also able to increase the expression of ß-defensin 3 compared to the infected and untreated group by 3.91-fold (p < 0.0001). Taken together, these results show that CAPE has both antifungal and immunomodulatory effects, making it a promising natural antifungal agent for the treatment and prevention of candidiasis and shows impact to oral candidiasis.

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Propolis is produced by honeybees from materials collected from plants they visit. It is a resinous material having mixtures of wax and bee enzymes. Propolis is also known as bee glue and used by bees as a building material in their hives, for blocking holes and cracks, repairing the combs and strengthening their thin borders. It has been extensively used since ancient times for different purposes in traditional human healthcare practices. The quality and composition of propolis depend on its geographic location, climatic zone and local flora. The New Zealand and Brazilian green propolis are the two main kinds that have been extensively studied in recent years. Their bioactive components have been found to possess a variety of therapeutic potentials. It was found that Brazilian green propolis improves the cognitive functions of mild cognitive impairments in patients living at high altitude and protects them from neurodegenerative damage through its antioxidant properties. It possesses artepillin C (ARC) as the key component, also known to possess anticancer potential. The New Zealand propolis contains caffeic acid phenethyl ester (CAPE) as the main bioactive with multiple therapeutic potentials. Our lab performed in vitro and in vivo assays on the extracts prepared from New Zealand and Brazilian propolis and their active ingredients. We provided experimental evidence that these extracts possess anticancer, antistress and hypoxia-modulating activities. Furthermore, their conjugation with γCD proved to be more effective. In the present review, we portray the experimental evidence showing that propolis has the potential to be a candidate drug for different ailments and improve the quality of life.

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