Trained immunity-based vaccines for infections and allergic diseases.

Trained immunity has emerged as a new concept in immunology associated with the memory of innate immune cells and linked to specific metabolic and epigenetic reprogramming of these cells. Trained immunity may confer nonspecific and sustained protection against a broad range of pathogens, and recent findings show that it might also be involved in allergy mechanisms. Some conventional vaccines have demonstrated trained immunity induction as the mechanism underlying their heterologous protection. The development of novel vaccines especially designed for this purpose (trained immunity-based vaccines) might be useful in the absence of conventional vaccines or in specific clinical settings. Under certain circumstances, trained immunity could lead to persistent inflammatory innate immune cell responses in allergic subjects, which could be associated with the development and worsening of allergy by promoting and amplifying aberrant type 2 immune responses. In other cases, trained immunity may help promote healthy immune responses to allergens, such as type 1 responses that counterbalance type 2 inflammation or regulatory T cells that induce tolerance. Trained immunity-based allergen vaccines could become the next generation of allergen-specific immunotherapy vaccines, harnessing the potential of trained immunity to induce allergen tolerance. The identification and characterization of proper training inducers might well pave the way for the development of novel immunotherapies.

Blue maize with pigmented germ: Phytochemical compounds and tortilla color.

Blue maize is used in the production of various traditional foods, and its phytochemical composition has been claimed to possess health benefits. In this study, two blue maize hybrids with pigmented germ grown in five environments were studied under the hypothesis that the germ could have a different anthocyanin profile from that of anthocyanins synthesized in the aleurone layer, and that those in the germ could increase the total anthocyanin content in the whole grain. The percentage of pigmented germ, total anthocyanin content (TA) and total soluble phenols in the germ, whole grain and tortilla were evaluated to determine how tortilla color is modified. For the first time, the anthocyanin and fatty acid profiles of pigmented germ were determined. In the anthocyanin profile, anthocyanins derived from peonidin stood out, making 50.7 %. The most abundant fatty acid was linoleic acid (40.6 %). Whole kernel TA content increased when the maize had a higher percentage of pigmented germ, with minimal changes when grain was transformed to tortilla, resulting in darker tortillas. The large variation in TA among environments highlights the importance of identifying the environments that most favor anthocyanin synthesis.

Influence of Cesarean Section Scar on the Mean Pulsatility Index of the Uterine Artery Doppler between 20 and 34 Weeks of Gestation.

Objective: The aim of this study was to assess the influence of the cesarean section scars on the mean pulsatility index (PI) of the uterine artery Doppler between 20 and 34 weeks of gestation. A secondary objective was to assess the association between previous cesarean section and adverse maternal/perinatal outcomes. Methods: A retrospective cohort study was conducted with pregnant women who had their deliveries between March 2014 and February 2023. PI of the uterine arteries Doppler was performed transvaginally between 20-24 weeks and transabdominally between 28-34 weeks. The following variables were considered adverse perinatal outcomes: birth weight < 10th percentile for gestational age, preeclampsia, premature birth, placental abruption, perinatal death, postpartum hemorrhage, neonatal intensive care unit (NICU) admission. Results: A total of 479 pregnant women were included in the final statistical analysis, being that 70.6% (338/479) had no (Group I) and 29.4% (141/479) had at least one previous cesarean section (Group II). Pregnant women with a previous cesarean had higher median of mean PI (1.06 vs. 0.97, p = 0.044) and median MoM of mean PI uterine arteries Doppler (1.06 vs. 0.98, p = 0.037) than pregnant women without previous cesarean section at ultrasound 20-24 weeks. Pregnant women with a previous cesarean section had higher median of mean PI (0.77 vs. 0.70, p < 0.001) and mean MoM PI uterine arteries Doppler (1.08 vs. 0.99, p < 0.001) than pregnant women without previous cesarean section at ultrasound 28-34 weeks. Pregnant women with ≥ 2 previous cesarean sections had a higher median of mean PI uterine arteries Doppler than those with no previous cesarean sections (1.19 vs. 0.97, p = 0.036). Group II had a lower risk of postpartum hemorrhage (aPR 0.31, 95% CI 0.13-0.75, p = 0.009) and composite neonatal outcome (aPR 0.66, 95% CI 0.49-0.88, p = 0.006). Group II had a higher risk of APGAR score at the 5th minute < 7 (aPR 0.75, 95% CI 1.49-51.29, p = 0.016). Conclusion: The number of previous cesarean sections had a significant influence on the mean PI uterine arteries Doppler between 20-24 and 28-34 weeks of gestation. Previous cesarean section was an independent predictor of postpartum hemorrhage and APGAR score at the 5th minute < 7. Pregnancy-associated arterial hypertension and number of previous deliveries influenced the risk of composite neonatal outcome, but not the presence of previous cesarean section alone.

Indole-3-carbinol loaded-nanocapsules modulated inflammatory and oxidative damages and increase skin wound healing in rats.

This study evaluated the effects of topically applied hydrogels (HG) containing nanoencapsulated indol-3-carbinol (I3C) and its free form in a rat model of skin wounds. Formulations were topically applied twice a day for five days to the wounds. On days 1, 3, and 6, the wound area was measured to verify the % of regression. On the sixth day, the animals were euthanized for the analysis of the inflammatory and oxidative profile in wounds. The nanocapsules (NC) exhibited physicochemical characteristics compatible with this kind of suspension. After five hours of exposure to ultraviolet C, more than 78% of I3C content in the suspensions was still observed. The NC-I3C did not modify the physicochemical characteristics of HG when compared to the HG base. In the in vivo study, an increase in the size of the wound was observed on the 3rd experimental day, which was lower in the treated groups (mainly in HG-NC-I3C) compared to the control. On the 6th day, HG-I3C, HG-NC-B, and HG-NC-I3C showed lower regression of the wound compared to the control. Additionally, HG-NC-I3C exhibited an anti-inflammatory effect (as observed by decreased levels of interleukin-1B and myeloperoxidase), reduced oxidative damage (by decreased reactive species, lipid peroxidation, and protein carbonylation levels), and increased antioxidant defense (by improved catalase activity and vitamin C levels) compared to the control. The current study showed more satisfactory results in the HG-NC-I3C group than in the free form of I3C in decreasing acute inflammation and oxidative damage in wounds.

I3C nanocapsules exhibited characteristics compatible with this kind of suspension;On 3rd day, I3C nanocapsules prevented the increase of wound area;I3C nanocapsules decreased oxidative damage in wound tissue;Inflammatory proteins were decreased in I3C nanocapsules treated group.

Carrageenan-xanthan nanocomposite film with improved bioadhesion and permeation profile in human skin: A cutaneous-friendly platform for ketoprofen local delivery.

Ketoprofen (KET), commonly used for inflammation in clinical settings, leads to systemic adverse effects with prolonged use, mitigated by topical administration. Nanotechnology-based cutaneous forms, like films, may enhance KET efficacy. Therefore, this study aimed to prepare and characterize films containing KET nanoemulsions (F-NK) regarding mechanical properties, chemical composition and interactions, occlusive potential, bioadhesion, drug permeation in human skin, and safety. The films were prepared using a κ-carrageenan and xanthan gum blend (2 % w/w, ratio 3: 1) plasticized with glycerol through the solvent casting method. Non-nanoemulsioned KET films (F-K) were prepared for comparative purposes. F-NK was flexible and hydrophilic, exhibited higher drug content and better uniformity (94.40 ± 3.61 %), maintained the NK droplet size (157 ± 12 nm), and was thinner and lighter than the F-K. This film also showed increased tensile strength and Young's modulus values, enhanced bioadhesion and occlusive potential, and resulted in more of the drug in the human skin layers. Data also suggested that nano-based formulations are homogeneous and more stable than F-KET. Hemolysis and chorioallantoic membrane tests suggested the formulations' safety. Thus, the nano-based film is suitable for cutaneous KET delivery, which may improve the drug's efficacy in managing inflammatory conditions.

The Role of Regulatory T Cells in Allergic Diseases: Collegium Internationale Allergologicum (CIA) Update 2024.

BACKGROUND: Allergy represents a major health problem of increasing prevalence worldwide with a high socioeconomic impact. Our knowledge on the molecular mechanisms underlying allergic diseases and their treatments has significantly improved over the last years. The generation of allergen-specific regulatory T cells (Tregs) is crucial in the induction of healthy immune responses to allergens, preventing the development and worsening of allergic diseases. SUMMARY: In the last decades, intensive research has focused on the study of the molecular mechanisms involved in Treg development and Treg-mediated suppression. These mechanisms are essential for the induction of sustained tolerance by allergen-specific immunotherapy (AIT) after treatment discontinuation. Compelling experimental evidence demonstrated altered suppressive capacity of Tregs in patients suffering from allergic rhinitis, allergic asthma, food allergy, or atopic dermatitis, as well as the restoration of their numbers and functionality after successful AIT. KEY MESSAGE: The better understanding of the molecular mechanisms involved in Treg generation during allergen tolerance induction might well contribute to the development of novel strategies for the prevention and treatment of allergic diseases.

The Association of Oleic Acid and Dexamethasone Acetate into Nanocapsules Enables a Reduction in the Effective Corticosteroid Dose in a UVB Radiation-Induced Sunburn Model in Mice.

Dexamethasone has a high anti-inflammatory efficacy in treating skin inflammation. However, its use is related to the rebound effect, rosacea, purple, and increased blood glucose levels. Nanotechnology approaches have emerged as strategies for drug delivery due to their advantages in improving therapeutic effects. To reduce dexamethasone-related adverse effects and improve the anti-inflammatory efficacy of treatments, we developed nanocarriers containing this corticosteroid and oleic acid. Nanocapsules and nanoemulsion presented dexamethasone content close to the theoretical value and controlled dexamethasone release in an in vitro assay. Gellan gum-based hydrogels were successfully prepared to employ the nanostructured systems. A permeation study employing porcine skin showed that hydrogels containing non-nanoencapsulated dexamethasone (0.025%) plus oleic acid (3%) or oleic acid (3%) plus dexamethasone (0.025%)-loaded nanocapsules provided a higher amount of dexamethasone in the epidermis compared to non-nanoencapsulated dexamethasone (0.5%). Hydrogels containing oleic acid plus dexamethasone-loaded nanocapsules effectively inhibited mice ear edema (with inhibitions of 89.26 ± 3.77% and 85.11 ± 2.88%, respectively) and inflammatory cell infiltration (with inhibitions of 49.58 ± 4.29% and 27.60 ± 11.70%, respectively). Importantly, the dexamethasone dose employed in hydrogels containing the nanocapsules that effectively inhibited ear edema and cell infiltration was 20-fold lower (0.025%) than that of non-nanoencapsulated dexamethasone (0.5%). Additionally, no adverse effects were observed in preliminary toxicity tests. Our study suggests that nanostructured hydrogel containing a reduced effective dose of dexamethasone could be a promising therapeutic alternative to treat inflammatory disorders with reduced or absent adverse effects. Additionally, testing our formulation in a clinical study on patients with skin inflammatory diseases would be very important to validate our study.

4-(Phenylselanyl)-2H-chromen-2-one-Loaded Nanocapsule Suspension-A Promising Breakthrough in Pain Management: Comprehensive Molecular Docking, Formulation Design, and Toxicological and Pharmacological Assessments in Mice.

Therapies for the treatment of pain and inflammation continue to pose a global challenge, emphasizing the significant impact of pain on patients' quality of life. Therefore, this study aimed to investigate the effects of 4-(Phenylselanyl)-2H-chromen-2-one (4-PSCO) on pain-associated proteins through computational molecular docking tests. A new pharmaceutical formulation based on polymeric nanocapsules was developed and characterized. The potential toxicity of 4-PSCO was assessed using Caenorhabditis elegans and Swiss mice, and its pharmacological actions through acute nociception and inflammation tests were also assessed. Our results demonstrated that 4-PSCO, in its free form, exhibited high affinity for the selected receptors, including p38 MAP kinase, peptidyl arginine deiminase type 4, phosphoinositide 3-kinase, Janus kinase 2, toll-like receptor 4, and nuclear factor-kappa ß. Both free and nanoencapsulated 4-PSCO showed no toxicity in nematodes and mice. Parameters related to oxidative stress and plasma markers showed no significant change. Both treatments demonstrated antinociceptive and anti-edematogenic effects in the glutamate and hot plate tests. The nanoencapsulated form exhibited a more prolonged effect, reducing mechanical hypersensitivity in an inflammatory pain model. These findings underscore the promising potential of 4-PSCO as an alternative for the development of more effective and safer drugs for the treatment of pain and inflammation.

Xanthan-carrageenan film containing sesame seed oil: A nanocomposite pharmaceutical platform for trichomoniasis treatment.

Trichomoniasis is a common sexually transmitted infection that poses significant complications for women. Challenges in treatment include adverse effects and resistance to standard antimicrobial agents. Given this context, a sesame seed oil nanoemulsion (SONE) was developed and showed anti-Trichomonas vaginalis activity. To facilitate the local application of SONE, a polysaccharide film was developed using xanthan gum (XG) and κ-carrageenan gum (CG). A blend of XG and CG (at 2 %, ratio 1:3) plasticized with glycerol produced a more promising film (XCF) than using the gums individually. The film containing SONE (SONE-XCF) was successfully obtained by replacing the aqueous solvent with SONE via solvent evaporation technique. The hydrophilic SONE-XCF exhibited homogeneity and suitable mechanical properties for vaginal application. Furthermore, SONE-XCF demonstrated mucoadhesive properties and high absorption capacity for excessive vaginal fluids produced in vaginitis. It also had a disintegration time of over 8 h, indicating long retention at the intended site of action. Hemolysis and chorioallantoic membrane tests confirmed the safety of the film. Therefore, SONE-XCF is a biocompatible film with a natural composition and inherent activity against T. vaginalis, possessing exceptional characteristics that make it appropriate for vaginal application, offering an interesting alternative for trichomoniasis treatment.

Sociodemographic, socioeconomic and motivational profile of brazilian triathletes / Perfil sociodemográfico, socioeconómico y motivacional de los triatletas brasileños / Perfil sociodemográfico, socioeconômico e motivacional de triatletas brasileiros

ABSTRACT Introduction: Triathlon can be considered one of the most successful endurance sports worldwide due to the wide dissemination of information, expansion of the offer of competitions, and greater popularity. Objective: To analyze Brazilian triathletes' sociodemographic, socioeconomic, and motivational profiles. Methods: 411 triathletes participated in the study, 127 women [37.87 ± 9.34 years] and 284 men [36.02 ± 9.23 years]. Three questionnaires were sent electronically to assess sociodemographic, socioeconomic, and motivational data. In addition, descriptive analyses and statistical tests were performed to compare motivation between age, sex, and technical level groups. Results: It was found that there is a prevalence of male triathletes, amateurs, aged between 30-40 years, employed and economically favored. Amateur athletes have running as a base sport for Triathlon, and professionals start their sports career through swimming. Among the most practiced distances are the sprint Triathlon and half Ironman. Regarding motivation, women differ in the dimensions of group activity (p=0.020), emotion (p=0.002), and technical competence (p=0.007). Professional triathletes had higher scores in the dimensions of social recognition (p=0.001) and competition (p=0.001) and lower scores in the physical fitness dimension (p=0.005). Triathletes aged between 35 and 49 years had lower averages in the social recognition dimension (p=0.007), (p=0.012) and (p=0.004) and competition (p=0.028), (p=0.008) and (p=0.044) when compared to athletes aged 20 to 29 years. Conclusion: the profile of Brazilian triathletes is diverse, and differences in sex, age, and technical level impacted the motivation of the evaluated triathletes. Level of Evidence III; Diagnostic studies - Investigation of a diagnosis test; Study of non-consecutive patients, with no uniformly applied "gold standard".

RESUMEN Introducción: El triatlón puede considerarse uno de los deportes de resistencia de mayor éxito a nivel mundial debido a la gran difusión de información, ampliación de la oferta de competiciones y mayor popularidad. Objetivo: Analizar el perfil sociodemográfico, socioeconómico y motivacional de los triatletas brasileños. Métodos: Participaron en el estudio 411 triatletas, 127 mujeres [37,87 ± 9,34 años] y 284 hombres [36,02 ± 9,23 años]. Se enviaron electrónicamente tres cuestionarios para evaluar datos sociodemográficos, socioeconómicos y de motivación. Se realizaron análisis descriptivos y pruebas estadísticas para comparar la motivación entre grupos de edad, sexo y nivel técnico. Resultados: Se encontró que existe un predominio de triatletas masculinos, amateurs, con edades entre 30-40 años, empleados y económicamente favorecidos. Los deportistas aficionados tienen la carrera como deporte base para el Triatlón y los profesionales inician su carrera deportiva a través de la natación. Entre las distancias más practicadas se encuentran el Triatlón sprint y el medio Ironman. Respecto a la motivación, las mujeres difieren en las dimensiones actividad grupal (p=0,020), emoción (p=0,002) y competencia técnica (p=0,007). Los triatletas profesionales obtuvieron puntuaciones más altas en las dimensiones de reconocimiento social (p=0,001) y competición (p=0,001) y puntuaciones más bajas en la dimensión de condición física (p=0,005). Los triatletas con edades comprendidas entre 35 y 49 años tuvieron medias más bajas en la dimensión reconocimiento social (p=0,007), (p=0,012) y (p=0,004) y competición (p=0,028), (p=0,008) y (p=0,044) en comparación con atletas de 20 a 29 años. Conclusión: el perfil de los triatletas brasileños es diverso y las diferencias de sexo, edad y nivel técnico impactaron en la motivación de los triatletas evaluados. Nivel de Evidencia III; Estudios diagnósticos - Investigación de un diagnóstico prueba; Estudio de pacientes no consecutivos, sin un "patrón oro" aplicado uniformemente.

RESUMO Introdução: O Triathlon pode ser considerado um dos esportes endurance de maior sucesso mundialmente devido à grande disseminação de informações, ampliação da oferta de competições e maior popularidade. Objetivo: Analisar o perfil sociodemográfico, socioeconômico e motivacional de triatletas brasileiros. Métodos: Participaram da pesquisa 411 triatletas, sendo 127 mulheres [37,87 ± 9,34 anos] e 284 homens [36,02 ± 9,23 anos]. Foram enviados eletronicamente três questionários que avaliam dados sociodemográficos, socioeconômicos e a motivação. Foram realizadas análises descritivas e testes estatísticos para comparar a motivação entre grupos de idade, sexo e nível técnico. Resultados: Verificou-se que há prevalência de triatletas homens, amadores, com faixa etária entre 30-40 anos, empregados e economicamente favorecidos. Atletas amadores possuem a corrida como esporte de base para o Triathlon e profissionais iniciam sua carreira esportiva pela natação. Entre as distâncias mais praticadas estão o Triathlon sprint e meio Ironman. Sobre a motivação, mulheres diferem nas dimensões de atividade de grupo (p=0,020), emoção (p=0,002) e competência técnica (p=0,007). Triatletas profissionais apresentaram maiores pontuações nas dimensões de reconhecimento social (p=0,001) e competição (p=0,001) e menores pontuações na dimensão aptidão física (p=0,005). Triatletas com idades entre 35 a 49 anos obtiveram menores médias na dimensão reconhecimento social (p=0,007), (p=0,012) e (p=0,004) e competição (p=0,028), (p=0,008) e (p=0,044) quando comparados com atletas de 20 a 29 anos. Conclusão: o perfil de triatletas brasileiros é diverso e as diferenças de sexo, idade e nível técnico impactaram na motivação dos triatletas avaliados. Nível de Evidência III; Estudos diagnósticos - Investigação de um diagnóstico este; Estudo de pacientes não consecutivos, sem "padrão ouro" aplicado de maneira uniforme.

Atención a la paciente obstétrica en el contexto de la pandemia de COVID-19 / Obstetric patient care in the context of COVID-19 pandemic

La infección causada por el SARS-CoV-2, tuvo una repercusión negativa en la evolución clínica de un número importante de gestantes y puérperas en todo el mundo. Este trabajo tiene como objetivo, exponer los principales resultados de la organización del proceso de atención a la paciente obstétrica en el contexto de la pandemia por la COVID-19. Está basado en la organización y elementos fundamentales seguidos con las pacientes que ingresaron, por afecciones relacionadas con el aborto, embarazo o puerperio, con sospecha de COVID-19 o con RT-PCR para SARS-CoV-2 positivo, en el año 2020, y las positivas al SARS-CoV-2 en 2021, de las provincias La Habana, Mayabeque y Artemisa, que fueron atendidas en el Hospital Militar Central Dr. Luis Díaz Soto. Se tuvo en cuenta el total de casos ingresados, pacientes confirmadas, ingresos en unidad de cuidados intensivos obstétricos, en servicio de vigilancia intensiva obstétrica, y la evolución clínica Con la organización de la atención médica a las pacientes obstétricas con la COVID-19, se logró el cumplimiento de los protocolos establecidos y la integración multidisciplinaria en el seguimiento de los casos, lo cual contribuyó a la evolución favorable de la mayoría de las pacientes(AU)

The infection caused by SARS-CoV-2 had a negative impact on the clinical evolution of a significant number of pregnant and puerperal women worldwide. The aim of this work is to present the main results of the organization of the obstetric patient care process in the context of the COVID-19 pandemic. It is based on the organization and fundamental elements followed with the patients who were admitted, for conditions related to abortion, pregnancy or puerperium, with suspicion of COVID-19 or with positive RT-PCR for SARS-CoV-2, in the year 2020, and those positive to SARS-CoV-2 in 2021, from Havana, Mayabeque and Artemisa provinces, who were attended at the Central Military Hospital Dr. Luis Díaz Soto. The total number of cases admitted, confirmed patients, admissions to the obstetric intensive care unit, obstetric intensive surveillance service, and clinical evolution were taken into account. With the organization of medical care for obstetric patients with COVID-19, compliance with established protocols and multidisciplinary integration in the follow-up of cases was achieved, which contributed to the favorable evolution of most patients(AU)

A tumor-associated heparan sulfate-related glycosaminoglycan promotes the generation of functional regulatory T cells.

Functional Tregs play a key role in tumor development and progression, representing a major barrier to anticancer immunity. The mechanisms by which Tregs are generated in cancer and the influence of the tumor microenvironment on these processes remain incompletely understood. Herein, by using NMR, chemoenzymatic structural assays and a plethora of in vitro and in vivo functional analyses, we demonstrate that the tumoral carbohydrate A10 (Ca10), a cell-surface carbohydrate derived from Ehrlich's tumor (ET) cells, is a heparan sulfate-related proteoglycan that enhances glycolysis and promotes the development of tolerogenic features in human DCs. Ca10-stimulated human DCs generate highly suppressive Tregs by mechanisms partially dependent on metabolic reprogramming, PD-L1, IL-10, and IDO. Ca10 also reprograms the differentiation of human monocytes into DCs with tolerogenic features. In solid ET-bearing mice, we found positive correlations between Ca10 serum levels, tumor size and splenic Treg numbers. Administration of isolated Ca10 also increases the proportion of splenic Tregs in tumor-free mice. Remarkably, we provide evidence supporting the presence of a circulating human Ca10 counterpart (Ca10H) and show, for the first time, that serum levels of Ca10H are increased in patients suffering from different cancer types compared to healthy individuals. Of note, these levels are higher in prostate cancer patients with bone metastases than in prostate cancer patients without metastases. Collectively, we reveal novel molecular mechanisms by which heparan sulfate-related structures associated with tumor cells promote the generation of functional Tregs in cancer. The discovery of this novel structural-functional relationship may open new avenues of research with important clinical implications in cancer treatment.

Karaya/Gellan-Gum-Based Bilayer Films Containing 3,3'-Diindolylmethane-Loaded Nanocapsules: A Promising Alternative to Melanoma Topical Treatment.

This study aimed to incorporate nanocapsules containing 3,3'-diindolylmethane (DIM) with antitumor activity into a bilayer film of karaya and gellan gums for use in topical melanoma therapy. Nanocarriers and films were prepared by interfacial deposition of the preformed polymer and solvent casting methods, respectively. Incorporating DIM into nanocapsules increased its antitumor potential against human melanoma cells (A-375) (IC50 > 24.00 µg/mL free DIM × 2.89 µg/mL nanocapsules). The films were transparent, hydrophilic (θ < 90°), had homogeneous thickness and weight, and had a DIM content of 106 µg/cm2. Radical ABTS+ scavenger assay showed that the DIM films presented promising antioxidant action. Remarkably, the films showed selective bioadhesive potential on the karaya gum side. Considering the mechanical analyses, the nanotechnology-based films presented appropriate behavior for cutaneous application and controlled DIM release profile, which could increase the residence time on the application site. Furthermore, the nanofilms were found to increase the permeation of DIM into the epidermis, where melanoma develops. Lastly, the films were non-hemolytic (hemolysis test) and non-irritant (HET-CAM assay). In summary, the combination of karaya and gellan gum in bilayer films that contain nanoencapsulated DIM has demonstrated potential in the topical treatment of melanoma and could serve as a viable option for administering DIM for cutaneous melanoma therapy.

Ética y derechos humanos en el servicio hospitalario por COVID-19 / Ethics and human rights in the hospital service by COVID-19

Resumen Objetivo: Analizar las experiencias de los organismos internacionales y el Gobierno de México en el establecimiento de recomendaciones para proteger los derechos humanos de los usuarios, de los servicios hospitalarios a causa de la COVID-19, tomando en cuenta la ética médica. Materiales y métodos: La presente investigación se centró en un enfoque cualitativo, donde se analizaron las experiencias, perspectivas y enfoques en materia de ética y derechos humanos durante la pandemia COVID-19. Con ello, se estudiaron libros, artículos científicos, informes y documentos oficiales de los organismos y dependencias involucradas. Resultados: En la pandemia por el coronavirus, los sistemas de salud se vieron obligados a buscar apoyo de la sociedad civil para contrarrestar sus efectos negativos en la economía y la protección de los derechos humanos. No obstante, hoy en día, la tarea del sector salud continua, ya que se siguen suscitando casos de COVID-19, además, existen pacientes que aún tienen secuelas y que deben ser atendidos sin exclusión. De modo que se continue privilegiando la accesibilidad oportuna, aceptable y asequible a los servicios de salud con la calidad suficiente. Conclusiones: La pandemia COVID-19 modificó el goce de los derechos humanos, incluyendo el derecho a la salud, por lo que la labor médica se modificó a partir de las recomendaciones de organismos internacionales y los gobiernos de los tres niveles. En la atención de la emergencia sanitaria fue fundamental proteger la integridad humana; actuar con respeto, solidaridad, empatía y reciprocidad; y entendiendo que todos debían ser atendidos sin discriminación, es decir, con inclusión y considerando la existencia de grupos vulnerables, basando la atención en la ética médica y los valores.

Abstract Objective: To analyze the experiences of international organizations and the Government of Mexico in establishing recommendations to protect the human rights of users of hospital services due to COVID-19, taking into account medical ethics. Materials and methods: This research focused on a qualitative approach, where experiences, perspectives, and approaches to ethics and human rights during the COVID-19 pandemic were analyzed. With this, books, scientific articles, reports and official documents of the organizations and dependencies involved were studied. Results: In the coronavirus pandemic, health systems were forced to seek support from civil society to counter its negative effects on the economy and the protection of human rights. However, today, the task of the health sector continues, since cases of COVID-19 continue to arise, in addition, there are patients who still have sequelae and who must be treated without exclusion. So that timely, acceptable and affordable access to health services with sufficient quality continues to be privileged. Conclusions: The COVID-19 pandemic modified the enjoyment of human rights, including the right to health, for which reason medical work was modified based on the recommendations of international organizations and governments of the three levels. In the care of the health emergency, it was essential to protect human integrity; act with respect, solidarity, empathy and reciprocity; and understanding that everyone should be cared for without discrimination, that is, with inclusion and considering the existence of vulnerable groups, basing care on medical ethics and values.

Flowered Grain Quality and Phytochemical Content of Non-Conventional Maize Hybrids from the Mexican Subtropics across Three Growing Cycles.

Development of non-conventional hybrids responds to the demand for the Elotes Occidentales land-race for production of pozole. The effect of growing cycle (2019, 2020, and 2021) on physical characteristics, flowered grain quality, and phytochemical content of two non-conventional hybrids of pozolero maize, as well as the effect of the presence or absence of pedicel, type of pollination (open and controlled, 2019), and parents (female and male, 2020) on flowered grain quality and content of phytochemical compounds, were evaluated. Size, hardness, color, total phenols, and anthocyanins in unprocessed grain were determined. Yield, volume, and puncture force were measured in flowered grain. Results were analyzed with a factorial arrangement in a completely randomized design. There were significant differences (p ≤ 0.05) in most of the variables studied by effect of crop cycle and hybrid. Non-conventional hybrids had large grains (40 g 100 grains-1), soft endosperm (flotation index > 60), pink-purple color, and phenol and anthocyanin contents similar to those reported for the Elotes Occidentales land-race. The presence or absence of the pedicel did not affect flowered grain quality. Controlled pollination favored anthocyanin synthesis. The female parent determined the anthocyanin content of non-conventional hybrids. Thermal processing reduced anthocyanins by 60%; however, they leached into the flowering broth, so that the pozole made from non-conventional hybrids can have improved nutraceutical value, relative to that of pozole made with Cacahuacintle land-race.

Hydrogel Containing Silibinin-Loaded Pomegranate Oil-Based Nanocapsules for Cutaneous Application: In Vitro Safety Investigation and Human Skin Biometry and Permeation Studies.

In previous studies, we developed a hydrogel formulation containing silibinin-loaded pomegranate oil nanocapsules (HG-NCSB) that had improved in vivo anti-inflammatory action in comparison to non-encapsulated silibinin. To determine skin safety and whether the nanoencapsulation influences silibinin skin permeation, NCSB skin cytotoxicity, HG-NCSB permeation in human skin, and a biometric study with healthy volunteers were conducted. The formulation of nanocapsules was prepared by the preformed polymer method while the HG-NCSB was obtained by thickening the suspension of nanocarriers with gellan gum. The cytotoxicity and phototoxicity of nanocapsules were assessed in Keratinocytes (HaCaT) and fibroblast (HFF-1) using the MTT assay. The hydrogels were characterized regarding the rheological, occlusive, and bioadhesive properties, and silibinin permeation profile in human skin. The clinical safety of HG-NCSB was determined by cutaneous biometry in healthy human volunteers. NCSB yielded better cytotoxicity results than the blank nanocapsules (NCPO). NCSB did not cause photocytotoxicity, while NCPO and the non-encapsulated substances (SB and pomegranate oil) were phototoxic. The semisolids presented non-Newtonian pseudoplastic flow, adequate bioadhesiveness, and low occlusive potential. The skin permeation demonstrated that HG-NCSB retained a higher SB amount in the outermost layers than HG-SB. In addition, HG-SB reached the receptor medium and had a superior concentration of SB in the dermis layer. In the biometry assay, there was no significant cutaneous alteration after the administration of any of the HGs. Nanoencapsulation promoted greater SB retention in the skin, averted percutaneous absorption, and made the topical use of SB and pomegranate oil safer.

Ultrasound-Guided Electroacupuncture for Thoracic Myofascial Pain Syndrome: A Case Report.

Myofascial pain syndrome is a painful condition characterized by trigger points in muscles that can be treated effectively with acupuncture. While cross-fiber palpation can help localize trigger points, needle accuracy may be limited and accidental puncture of delicate structures, such as the lung, is a risk, as evidenced by reports of pneumothorax after acupuncture. Ultrasound imaging can help in reducing the risk of iatrogenic pneumothorax from needling, but there is a paucity of papers describing the use of ultrasound imaging during acupuncture. We present a report on electroacupuncture treatment for myofascial pain syndrome using real-time ultrasound guidance, aimed at avoiding accidental puncture of the pleura when targeting deep muscle layers in the thoracic region.

Cannabinoid WIN55,212-2 reprograms monocytes and macrophages to inhibit LPS-induced inflammation.

Introduction: Chronic or uncontrolled activation of myeloid cells including monocytes, macrophages and dendritic cells (DCs) is a hallmark of immune-mediated inflammatory disorders. There is an urgent need for the development of novel drugs with the capacity to impair innate immune cell overactivation under inflammatory conditions. Compelling evidence pointed out cannabinoids as potential therapeutic tools with anti-inflammatory and immunomodulatory capacity. WIN55,212-2, a non-selective synthetic cannabinoid agonist, displays protective effects in several inflammatory conditions by mechanisms partially depending on the generation of tolerogenic DCs able to induce functional regulatory T cells (Tregs). However, its immunomodulatory capacity on other myeloid cells such as monocytes and macrophages remains incompletely understood. Methods: Human monocyte-derived DCs (hmoDCs) were differentiated in the absence (conventional hmoDCs) or presence of WIN55,212-2 (WIN-hmoDCs). Cells were stimulated with LPS, cocultured with naive T lymphocytes and their cytokine production and ability to induce T cell responses were analysed by ELISA or flow cytometry. To evaluate the effect of WIN55,212-2 in macrophage polarization, human and murine macrophages were activated with LPS or LPS/IFNγ, in the presence or absence of the cannabinoid. Cytokine, costimulatory molecules and inflammasome markers were assayed. Metabolic and chromatin immunoprecipitation assays were also performed. Finally, the protective capacity of WIN55,212-2 was studied in vivo in BALB/c mice after intraperitoneal injection with LPS. Results: We show for the first time that the differentiation of hmoDCs in the presence of WIN55,212-2 generates tolerogenic WIN-hmoDCs that are less responsive to LPS stimulation and able to prime Tregs. WIN55,212-2 also impairs the pro-inflammatory polarization of human macrophages by inhibiting cytokine production, inflammasome activation and rescuing macrophages from pyroptotic cell death. Mechanistically, WIN55,212-2 induced a metabolic and epigenetic shift in macrophages by decreasing LPS-induced mTORC1 signaling, commitment to glycolysis and active histone marks in pro-inflammatory cytokine promoters. We confirmed these data in ex vivo LPS-stimulated peritoneal macrophages (PMΦs), which were also supported by the in vivo anti-inflammatory capacity of WIN55,212-2 in a LPS-induced sepsis mouse model. Conclusion: Overall, we shed light into the molecular mechanisms by which cannabinoids exert anti-inflammatory properties in myeloid cells, which might well contribute to the future rational design of novel therapeutic strategies for inflammatory disorders.

Cationic nanocapsule suspension as an alternative to the sublingual delivery of nifedipine.

Nifedipine (NIFE) is a calcium channel blocker drug used to treat cardiovascular diseases, angina, and hypertension. However, NIFE is photolabile, has a short biological half-life, low aqueous solubility, and undergoes an intense first-pass effect, compromising its oral bioavailability. Thus, this study aimed to develop NIFE-loaded nanocapsules for sublingual administration. Nanocapsule suspensions of Eudragit® RS100 and medium chain triglycerides containing NIFE were prepared by the interfacial deposition of preformed polymer technique. The developed formulations showed particle size around 170 nm, polydispersity index below 0.2, positive zeta potential, and acid pH. The NIFE content was 0.98 ± 0.03 mg/mL, and the encapsulation efficiency was 99.9%. The natural light photodegradation experiment showed that the nanocapsules were able to provide NIFE photoprotection. The nanocapsules reduced the cytotoxicity of NIFE and showed no genotoxic effects in the Allium cepa model. Through the HET-CAM test, the formulations were classified as non-irritating. The developed nanocapsule suspension demonstrated a controlled release of NIFE and mucoadhesive potential. The in vitro permeation assay showed that the nanocapsules favored the NIFE permeation to the receptor compartment. In addition, the nanocapsules provided greater drug retention in the mucosa. Thus, the development of polymeric nanocapsule suspensions showed that this system could be a promising platform for NIFE sublingual administration.