Human milk (HM) is recognized as an ideal nutritional source to meet the developmental needs of babies. However, a significant portion does not meet quality standards for immediate consumption, rendering it an interesting raw material for the production of by-products. This study aimed to evaluate the lipid composition and cytokines interleukin-10 (IL-10) and transforming growth factor-beta 1 (TGF-β1) in ice cream containing HM. Three formulations were developed: F1 with 93.46% HM, F2 with 46.73% cows’ milk and 46.73% HM, and F3 with 46.73% infant formula and 46.73% HM. Fatty acids (FA) and their nutritional quality, the triacylglycerol (TAG) profile, and the concentrations of cytokines IL-10 and TGF-β1 were analyzed. F1 and F3 exhibited the highest concentrations of essential FAs (18:2n-6 and 18:3n-3) compared to F2. This trend extended to eicosapentaenoic acid + docosahexaenoic acid, with higher values in F1 (10.62 ± 0.26) and F3 (11.16 ± 0.28) versus F2 (3.67 ± 0.18). Both cytokines IL-10 and TGF-β1, present in the ice creams, experienced a decrease in concentration due to the processing of the raw materials. Therefore, ice creams produced with HM have promising potential, making them recommended for use, providing a new destination for waste, and creating a novel product that can be used as a complementary food.

Abstract Submandibular salivary gland inflammation has been suggested as one of the mechanisms underlying impaired salivary secretion associated with sleep deprivation (SD). However, whether the salivary inflammatory response occurs to the same extent in paradoxical sleep deprivation with or without sleep recovery remains unknown. Objective: This study evaluated the extent to which inflammation influences salivary impairments associated with paradoxical sleep deprivation with or without sleep recovery. Methodology: Male Wistar rats were randomly assigned into three groups as control, partial SD (PSD) with sleep recovery for four hours a day and total SD (TSD). Paradoxical SD was carried out for seven days in the SD groups, after which saliva, blood, and submandibular gland samples were taken. Levels of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and nitrite were determined in saliva, serum, and the submandibular salivary gland. Leucocyte count and neutrophil-lymphocyte ratio were determined in all groups. One-way ANOVA and the Tukey's post hoc tests were used for data analysis. P-values < 0.05 were considered statistically significant. Results: Levels of TNF-α, IL-6, and nitrite in the submandibular salivary glands were significantly higher in the TSD groups (p=0.04,p<0.001, p=0.03, respectively) than in the control. Saliva level of TNF-α was higher in the PSD and TSD groups (p=0.003 and p=0.01 respectively) than in the control. Neutrophil-lymphocyte ratio was significantly higher in both PSD and TSD groups than in the control (p<0.01 for both). Conclusion: While total SD produced higher inflammatory response in the submandibular salivary gland, four-hour sleep recovery ameliorated this impact. This finding suggests that sleep recovery is crucial to improve inflammatory salivary gland dysfunction induced by sleep deprivation.

Abstract Introduction: Cervical Human Papillomavirus (HPV) infection, a common sexually transmitted infection, can lead to cervical cancer. This study investigates the impact of Photodynamic Therapy (PDT) on cellular immune function in cervical HPV-infected patients. Methods: From October 2022 to February 2023, 60 patients with cervical HPV infection were randomly assigned to a control group (conventional treatment) or a PDT group (PDT treatment), each with 30 patients. Peripheral blood samples and cervical tissue were collected before treatment, at 3 months, and at 6 months post-treatment. Flow cytometry assessed T-cell subsets (CD4+, CD8+, CD3+), and ELISA measured cytokine levels (TNF-α, IL-6, IL-8). Results: Baseline characteristics were similar between the PDT and control groups. The PDT group showed significantly higher HPV clearance rates at 3-months (70.00 %) and 6 months (100.00 %) compared to the control group 43.33 % and 80.00 %, respectively (p < 0.05). PDT significantly increased CD3+ and CD4+ cell levels at 3- and 6-months post-treatment compared to controls (p < 0.05). CD8+ levels and the CD4+/CD8+ ratio also significantly increased in the PDT group at 6 months. Additionally, PDT significantly reduced IL-6, IL-8, and TNF-α levels at 3- and 6-months post-treatment (p < 0.05). Conclusion: PDT enhances cellular immune function in cervical HPV-infected patients by increasing CD4+ and CD8+ T-cells and reducing pro-inflammatory cytokines. These findings highlight the potential of PDT in modulating immune responses and improving therapeutic strategies for cervical HPV infection.

Abstract Viral hepatitis is a public health problem, about 1 million people die due to complications of this viral disease, the etiological agents responsible for inducing cirrhosis and cellular hepatocarcinoma are HBV and HCV, both hepatotropic viruses that cause asymptomatic infection in most cases. The regulation of the microbiota performs many physiological functions, which can induce normal intestinal function and produce essential nutrients for the human body. Metabolites derived from gut microbiota or direct regulation of host immunity and metabolism have been reported to profoundly affect tumorigenesis in liver disease. If the microbiota is unbalanced, both exogenous and symbiotic microorganisms can affect a pathological process. It is well understood that the microbiota plays a role in viral diseases and infections, specifically the hepatic portal pathway has been linked to the gut-liver axis. In HBV and HCV infections, the altered bacterial representatives undergo a state of dysbiosis, with subsequent establishment of the pathobiome with overexpression of taxons such as Bacteroides, Clostridium, Lactobacillus, Enterobacter, and Enterococcus. This dysregulated microbiome induces a microenvironment conducive to the development of hepatic complications in patients with acute and chronic HBV and HCV infection, with subsequent dysregulation of cytokines IFN-α/β, TNF-α, IL-1β, TGF-β, IL-6 and IL-10, which alter the dysfunction and damage of the hepatic portal system. In view of the above, this review aimed to correlate the pathophysiological mechanisms in HBV and HCV infection, the dysregulation of the microbiome in patients infected with HBV and HCV, the most altered cytokines in the microbiome, and the most altered bacterial representatives in the pathobiome of infection.

ABSTRACT Purpose: To establish a profile of the inflammatory response in the preoperative and postoperative period of pulmonary resection of patients without postoperative complications, in order to trace the inflammatory profile of lung resection surgery. Methods: Six collections of arterial and venous blood were performed for data analysis, one sample in the preoperative, immediate postoperative, 4, 8, 24, and 48 hours after surgery. Twenty-seven patients with a median age of 63 years old, ranging from 29 to 80 years old, were included. Results: The leukocyte count showed a significant increase in the times: immediate postoperative and 4 hours after surgery, in relation to the preoperative period. Concomitantly, there was an increase in lactate, heart rate, interleukin (IL)-6 and IL-8 after 4 hours of surgery. The platelet count showed a significant decrease in 48 h, associated with an increase in IL-1β and tumor necrosis factor-α. A significant increase in IL-10 was observed in the immediate postoperative. Conclusion: The study may contribute to the search for more specific and adequate alternatives for controlling the inflammatory response. In this way, the intervention would be specific to that cytokine that causes the greatest harm to the patient, as well as to the moment of the intervention.

RESUMO: Echinacea angustifolia é uma planta perene que vem sendo utilizada para tratar diversas enfermidades de origem microbiana. Neste estudo foram avaliadas propriedades antivirais, in vitro, de um extrato etanólico de E. angustifolia frente ao alphaherpesvírus bovino 1 (BoHV-1). BoHV-1 causa enfermidades que afetam principalmente o trato respiratório e genital de bovinos, e que resultam em grandes perdas econômicas. Quando células foram tratadas com o extrato de E. angustifolia em concentração não citotóxica em diferentes tempos (3, 6, ou 24h) antes da inoculação do BoHV-1, não foi possível detectar o vírus por até 72 horas após, enquanto que nas células não tratadas o vírus alcançou o título de 105.5TCID50/25µl (média). A incubação do extrato com BoHV-1 24 horas antes da inoculação celular não resultou em inativação da infectividade viral. Células infectadas com 103 TCID50 de BoHV-1 não tratadas com E. angustifolia apresentaram em média 45,8% de viabilidade após 48 horas da infecção, enquanto que 91,1% permaneceram viáveis quando tratadas após 6 horas ou 84,1% após 24 horas da infecção, demonstrando uma significativa redução no desenvolvimento de efeito citopático. Além disso, E. angustifolia reduziu significativamente a expressão relativa de mRNA das citocinas antivirais IFNα e IFNβ nas células tratadas, sugerindo que a atividade antiviral não ocorre devido a imunomodulação. E. angustifolia reduziu significativamente a expressão relativa de mRNA das citocinas antivirais IFNα e IFNβ nas células tratadas, indicando que a atividade antiviral não ocorre devido a imunomodulação. Os dados obtidos indicam que o extrato etanólico da E. angustifolia pode interferir com a adsorção, penetração e/ou o egresso viral das células infectadas. Tomados em conjunto, os dados apresentados enfatizam uma promissora atividade antiviral da E. angustifolia contra o BoHV-1. RESUMO microbiana vitro E BoHV1. BoHV1 BoHV . (BoHV-1) BoHV- bovinos econômicas 3, 3 (3 24h h BoHV1, 1, 7 1055TCID5025µl TCIDµl 105 5TCID50 25µl TCID µl média. (média) 2 10 TCID5 458 45 8 45,8 4 infecção 911 91 91,1 841 84 84,1 citopático disso imunomodulação adsorção eou conjunto 1. (BoHV-1 ( 5TCID5 (média 45, 9 91, 84, (BoHV- 5TCID (BoHV

ABSTRACT: Echinacea angustifolia is a perennial plant that has been traditionally used to treat various microbial diseases. This study evaluated the in vitro antiviral properties of an ethanolic extract of E. angustifolia against bovine alphaherpesvirus 1 (BoHV-1). BoHV-1 infection is associated with respiratory, reproductive and neurological disease in cattle, resulting in major economic losses. When cells were treated with E. angustifolia extract at a non-cytotoxic concentration at different times (3, 6 or 24 hours) before BoHV-1 inoculation, no viral detection was possible after 72h, while in untreated cells the virus reached a titer of 105.5TCID50 /25µl (median). Incubating the extract with BoHV-1 24 hours before cell inoculation did not result in loss of viral infectivity. Cells infected with 103 TCID50 of BoHV-1 and not treated with E. angustifolia showed an average of 45.8% viability after 48 hours of infection, while 91.1% remained viable when treated 6 hours after or 84.1% 24 hours after infection, demonstrating a significant reduction in the cytopathic effect. In addition, E. angustifolia significantly reduced the relative mRNA expression of the antiviral cytokines IFNα and IFNβ in the treated cells, suggesting that the antiviral activity is not due to immunomodulation. The obtained data indicated that the ethanolic extract of E. angustifolia may directly interfere with virus attachment, entry, and/or egress from infected cells. Taken together, the presented data emphasized the promising antiviral activity of E. angustifolia against BoHV-1. ABSTRACT diseases E BoHV1. BoHV1 BoHV . (BoHV-1) BoHV- respiratory cattle losses noncytotoxic non cytotoxic 3, 3 (3 2 72h h 1055TCID50 TCID 105 5TCID50 105.5TCID5 25µl µl median. median (median) infectivity 10 TCID5 458 45 8 45.8 4 911 91 91.1 841 84 84.1 effect addition immunomodulation attachment entry andor together 1. (BoHV-1 ( 1055TCID5 5TCID5 105.5TCID (median 45. 9 91. 84. (BoHV- 1055TCID 5TCID (BoHV

The poultry gastrointestinal microbiome consists of more than 900 bacterial species and their metabolites; it serves as an indicator of bird health and is influenced by nutrition, medication, and other factors. Dysbiosis is a form of reduced microbial diversity, characterised by the loss of beneficial microbes, the expansion of opportunistic microbes, and the disruption of tight junctions, as well as raised pro-inflammatory cytokines (interleukin-6 and interleukin-17), tumour necrosis factor-α, and Enterobacteriaceae, and decreased short-chain fatty acids. Dysbiosis leads to various disorders, including liver disorders, metabolic disease, cardiovascular disease, and neurological problems. It also impacts several bodily systems, such as the gastrointestinal tract, kidneys, the gut-liver axis (liver disease, hepatocellular carcinoma, autoimmune liver disease, and metabolic-associated fatty liver disease), the gut-lung axis (pneumonia and chronic obstructive pulmonary disease), the gut-microbiota axis (irritable bowel syndrome, inflammatory bowel disease, and constipation or stool hardness), and the gut-islet axis (hypertension, hyperglycaemia, diabetes, and hypercreatinaemia syndrome). Many factors, including medications (antibiotics, anti-tumour, and immunosuppressants), environmental pollutants (heavy metals, pesticides, microplastics, and atmospheric particulates), high levels of nutrients (protein, fat, salt, and sugar), and others (age, disease, habits, and genes), cause and enable gastrointestinal dysbiosis to develop. Nutritional strategies such as the administration of probiotics, prebiotics, antibiotics, or phytogenic feed additives, and the consumption of a high-quality, balanced diet, as well as early detection of gut health malfunction and an emphasis on increasing bird resilience, can reduce the risk of dysbiosis, modify the gut microbial balance, and make microbial eubiosis possible.

SUMMARY: Cerebral ischemic stroke -reperfusion (CIS/R) injury poses a significant threat to cognitive function. In this study, we explored the effects of Vaccinium arctostaphylos L. seeds oil (VASO) on a CIS/R model in Wistar rats and investigated its underlying mechanisms. Fifty Wistar rats were randomly divided into five groups: a normal group, a VASO-supplemented group (receiving 400 mg/kg VASO), an ischemic stroke-reperfusion (IS/R) group, and two IS/R groups treated with 200 mg/kg and 400 mg/ kg VASO, each comprising 10 rats. Cognitive performance was assessed using the Y-electric maze test. Additionally, we employed enzyme-linked immunosorbent assay (ELISA) and real-time PCR to examine the expression of proteins and genes associated with neurotrophic growth, inflammation, and apoptosis in the brain. Compared to the normal group, rats subjected to IS/R exhibited a significant delay in meeting the maze criteria. The IS/R group also demonstrated markedly elevated levels of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), alongside reduced levels of anti-inflammatory cytokines (IL-4 and IL-10) and neurotrophic growth factors [brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF)]. The group treated with 400 mg/kg VASO after IS/R displayed improvements, with increased levels of neurotrophic growth factors, and a favorable shift in the protein and gene expression profiles of inflammatory and apoptotic markers (including glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF-6), Bcl-2, Bax, and p53) compared to the IS/ R group. These results suggest that VASO extract may mitigate cognitive impairments following IS/R in rats, potentially through its modulation of microglia-secreted inflammatory factors.

RESUMEN: La lesión cerebral por ataque cerebrovascular isquémico-reperfusión (CIS/R) plantea una amenaza significativa para la función cognitiva. En este estudio, exploramos los efectos del aceite de semillas de Vaccinium arctostaphylos L. (VASO) en un modelo CIS/R en ratas Wistar e investigamos sus mecanismos subyacentes. Cincuenta ratas Wistar se dividieron aleatoriamente en cinco grupos: un grupo normal, un grupo suplementado con VASO (que recibió 400 mg/kg de VASO), un grupo de ataque cerebrovascular isquémico-reperfusión (IS/R) y dos grupos IS/R tratados con 200 mg/kg y 400 mg/kg de VASO, cada uno compuesto por 10 ratas. El rendimiento cognitivo se evaluó mediante la prueba del laberinto eléctrico Y. Además, empleamos un ensayo inmunoabsorbente ligado a enzimas (ELISA) y PCR en tiempo real para examinar la expresión de proteínas y genes asociados con el crecimiento neurotrófico, la inflamación y la apoptosis en el cerebro. En comparación con el grupo normal, las ratas sometidas a IS/R exhibieron un retraso significativo en el cumplimiento de los criterios del laberinto. El grupo IS/R también demostró niveles marcadamente elevados de citocinas proinflamatorias, incluidas la interleucina-1β (IL-1β), IL-6 y el factor de necrosis tumoral-α (TNF-α), junto con niveles reducidos de citocinas antiinflamatorias (IL-4 e IL-10) y factores de crecimiento neurotrófico [factor neurotrófico derivado del cerebro (BDNF) y factor neurotrófico derivado de la línea celular glial (GDNF)]. El grupo tratado con 400 mg/kg de VASO después de la IS/R mostró mejoras, con mayores niveles de factores de crecimiento neurotrófico y un cambio favorable en los perfiles de expresión de proteínas y genes de marcadores inflamatorios y apoptóticos (incluyendo la proteína regulada por glucosa 78 (GRP78), el factor de transcripción activador 6 (ATF-6), Bcl-2, Bax y p53) en comparación con el grupo IS/R. Estos resultados sugieren que el extracto de VASO puede mitigar los deterioros cognitivos posteriores a la IS/R en ratas, potencialmente a través de su modulación de los factores inflamatorios secretados por la microglia.

Abstract Atopic dermatitis is a chronic, recurrent, and multifactorial skin-mucosal manifestation resulting from the interaction between elements mainly associated with the skin barrier deficit, the homeostasis of the immune response, neurological aspects, and patterns of reactivity to environmental antigens, which are established in genetically predisposed individuals. In addition to the skin, atopic diathesis involves other organs such as the airways (upper and lower), eyes, digestive tract, and neuropsychiatric aspects, which inflict additional morbidity on the dermatological patient. The different phenotypes of the disease fundamentally depend on the participation of each of these factors, in different life circumstances, such as age groups, occupational exposure patterns, physical activity, pollution, genetic load, and climatic factors. A better understanding of the complexity of its pathogenesis allows not only the understanding of therapeutic targets but also how to identify preponderant elements that mediate disease activity in each circumstance, for selecting the best treatment strategies and mitigation of triggering factors. This narrative review presents an update on the pathogenesis of atopic dermatitis, especially aimed at understanding the clinical manifestations, the main disease phenotypes and the context of available therapeutic strategies. chronic recurrent skinmucosal mucosal deficit response aspects antigens individuals upper lower, lower , lower) eyes tract patient factors circumstances groups pollution load circumstance manifestations

SUMMARY: This study aimed to explore the potential of Nasturtium officinale L. leaves extract (NOLE) in safeguarding hepatocytes against N-diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) by investigating its effects on biochemical, molecular, and antioxidant pathways. The study also delved into NOLE's role in modulating the HOTAIR/miR-124/Notch1 axis pathway. In this study, 50 Wistar rats were divided into five groups (n=10/group): normal, HCC-induced (100 mg/kg DEN), HCC rats treated with 100 and 200 mg/kg DEN + NOLE, and normal rats treated with 200 mg/kg NOLE. At the study's conclusion, serum levels of liver function markers (such as albumin, total protein, bilirubin, C-reactive protein, ALT, AST, and ALP), inflammatory cytokines (IL-6, IL- 1b, IL-10, and TNF-a), and oxidative parameters [including glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) enzyme activity, and nitric oxide (NO) levels] were assessed. The levels of HOTAIR, miR-124, Notch1, and Jagged1 genes and proteins in liver tissue were measured. Immunohistochemical analysis was used to evaluate P53-positive cells in liver hepatocytes. DEN administration led to significant alterations in body and liver weight, serum liver enzymes, antioxidant levels, inflammatory markers, and expression of genes/proteins related to the HOTAIR/miR-124/Notch1 axis in liver pathways. NOLE exhibited dose-dependent effects in mitigating these changes, notably enhancing weight, liver health, antioxidant capacity, and inflammatory responses, especially at the 200 mg/kg dosage. Histopathological assessments revealed structural improvements in liver tissue with NOLE treatment. In conclusion, our study highlights the potential of NOLE in exerting anti-cancer effects against DEN-induced HCC.

RESUMEN: Este estudio tuvo como objetivo explorar el potencial del extracto de hojas de Nasturtium officinale L. (NOLE) para proteger los hepatocitos contra el carcinoma hepatocelular (HCC) inducido por N-dietilnitrosamina (DEN) mediante la investigación de sus efectos sobre las vías bioquímicas, moleculares y antioxidantes. El estudio también profundizó en el papel de NOLE en la modulación de la vía del eje HOTAIR/miR-124/Notch1. En este estudio, 50 ratas Wistar se dividieron en cinco grupos (n=10/ grupo): ratas normales, inducidas por HCC (100 mg/kg de DEN), ratas con HCC tratadas con 100 y 200 mg/kg de DEN + NOLE y ratas normales tratadas con 200 mg/kg de NOLE. Al concluir el estudio, se midieron los niveles séricos de marcadores de función hepática (como albúmina, proteína total, bilirrubina, proteína C reactiva, ALT, AST y ALP), citoquinas inflamatorias (IL-6, IL-1β, IL-10 y TNF-α) y parámetros oxidativos [incluidos los niveles de glutatión peroxidasa (GPx), superóxido dismutasa (SOD), catalasa (CAT) y óxido nítrico (NO)]. Se midieron los niveles de los genes y proteínas HOTAIR, miR-124, Notch1 y Jagged1 en el tejido hepático. Se utilizó análisis inmunohistoquímico para evaluar las células P53 positivas en los hepatocitos del hígado. La administración de DEN provocó alteraciones significativas en el peso corporal y hepático, las enzimas hepáticas séricas, los niveles de antioxidantes, los marcadores inflamatorios y la expresión de genes/proteínas relacionadas con el eje HOTAIR/miR-124/Notch1 en las vías hepáticas. NOLE exhibió efectos dependientes de la dosis para mitigar estos cambios, en particular mejorando el peso, la salud del hígado, la capacidad antioxidante y las respuestas inflamatorias, especialmente en la dosis de 200 mg/kg. Las evaluaciones histopatológicas revelaron mejoras estructurales en el tejido hepático con el tratamiento NOLE. En conclusión, nuestro estudio destaca el potencial de NOLE para ejercer efectos anticancerígenos contra el CHC inducido por DEN.

SUMMARY: Cerebral hemorrhage (CH) presents a significant risk for cognitive decline. Our research aimed to assess the impact of Apricot Kernel Oil (AKO) on cognitive function and inflammatory response in a hemorrhagic stroke model using Wistar rats, and to examine their correlation. Fifty Wistar rats were randomly assigned to five groups: a control group, an AKO supplemented group (receiving 400 mg/kg AKO), a CH group (with induced CH), and CH groups supplemented with 200 and 400 mg/kg AKO, each containing 10 rats. Cognitive function was evaluated using the Y-electric maze test across these groups. Additionally, enzyme-linked immunosorbent assay and real-time PCR were utilized to analyze the protein and gene expression profiles of inflammatory and apoptotic factors in the brain. Compared to the control group, rats in the CH group took longer to master the maze criteria (P<0.05). Moreover, the CH group exhibited significantly increased levels of pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α, and decreased levels of anti-inflammatory cytokines IL-4 and IL-10 compared to the control group (P<0.05). Conversely, rats in the CH+400 mg/kg AKO group showed opposite trends in electrical simulation time, inflammatory factor protein, and gene expression profile (Bcl- 2, BAX, Caspase-3, and p53) compared to the CH group (P<0.05). Our findings suggest that AKO extract may ameliorate cognitive dysfunction following CH in rats, potentially through modulation of inflammatory factors secreted by microglia.

RESUMEN: La hemorragia cerebral (HC) presenta un riesgo significativo de deterioro cognitivo. Nuestra investigación tuvo como objetivo evaluar el impacto del aceite de semilla de albaricoque (ASA) en la función cognitiva y la respuesta inflamatoria en un modelo de accidente cerebrovascular hemorrágico utilizando ratas Wistar, y examinar su correlación. Se asignaron aleatoriamente cincuenta ratas Wistar a cinco grupos: un grupo control, un grupo suplementado con ASA (que recibió 400 mg/kg de ASA), un grupo HC (con HC inducido) y grupos HC suplementados con 200 y 400 mg/kg de ASA, cada uno. La función cognitiva se evaluó mediante la prueba del laberinto eléctrico Y en estos grupos. Además, se utilizaron un ensayo inmunoabsorbente ligado a enzimas y una PCR en tiempo real para analizar los perfiles de expresión de proteínas y genes de factores inflamatorios y apoptóticos en el cerebro. En comparación con el grupo de control, las ratas del grupo HC tardaron más en dominar los criterios del laberinto (P<0,05). Además, el grupo HC exhibió niveles significativamente mayores de citocinas proinflamatorias interleucina-1β (IL-1β), IL-6 y factor de necrosis tumoral- α, y niveles reducidos de citocinas antiinflamatorias IL-4 e IL-10 en comparación al grupo control (P<0,05). Por el contrario, las ratas del grupo HC+400 mg/kg ASA mostraron tendencias opuestas en el tiempo de simulación eléctrica, la proteína del factor inflamatorio y el perfil de expresión génica (Bcl-2, BAX, Caspasa-3 y p53) en comparación con el grupo HC (P <0,05). Nuestros hallazgos sugieren que el extracto de ASA puede mejorar la disfunción cognitiva después de la HC en ratas, potencialmente mediante la modulación de factores inflamatorios secretados por la microglia.

ABSTRACT Introduction: The experience of using therapeutic plasmapheresis in autoimmune and inflammatory diseases allowed us to propose and indicate this therapy in combination with Cuban biotechnological drugs in patients with COVID-19; a disease characterized by the uncontrolled release of cytokines that activate the proinflammatory response, acute respiratory failure syndrome, thrombotic events and multiorgan failure. Objective: To describe the results of the use of therapeutic plasmapheresis combined with Cuban biotechnological drugs in patients with worsening of COVID-19 disease. Methodology: The research was carried out during the second wave of the COVID-19 pandemic at the "Manuel Fajardo Rivero" Army Military Hospital in Villa Clara, during the months of March and April 2021. Case study involving 16 patients over 18 years of age with positive PCR-RT for SARS-CoV-2, with deterioration in their clinical and laboratory condition who underwent plasmapheresis treatment and Cuban biotechnological drugs: Itolizumab, Jusvinza, HeberFERON® e Intacglobin®. Results: 75% of the patients were classified as potentially serious. Half of the patients received Itolizumab and at least one therapeutic plasmapheresis session. The response was favorable, 100% had negative PCR-RT, and D-dimer normalized more quickly, followed by C - reactive protein. Fewer plasmapheresis sessions were needed to achieve recovery. Conclusions: Therapeutic plasmapheresis in patients with COVID-19 was a complementary and promising treatment; combined with biopharmaceuticals, innovative and necessary to reduce the inflammatory and viral load and achieve the recovery of the patient with clinical worsening of his condition.

RESUMEN Introducción: la experiencia del uso de la plasmaféresis terapéutica en enfermedades autoinmunes e inflamatorias permitió proponerla e indicarla en combinación con fármacos biotecnológicos en el paciente con COVID-19; enfermedad caracterizada por la liberación de citocinas no controlada que activa la respuesta proinflamatoria, síndrome de insuficiencia respiratoria aguda, eventos trombóticos y fallo multiorgánico. Objetivo: describir los resultados del empleo de la plasmaféresis terapéutica combinado con los fármacos biotecnológicos cubanos en pacientes con empeoramiento de la enfermedad por COVID-19. Metodología: se realizó la investigación durante la segunda oleada de pandemia de COVID-19 en el Hospital Militar “Manuel Fajardo Rivero” durante los meses marzo y abril del año 2021. El estudio de caso involucró a 16 pacientes mayores de 18 años de edad con reacción en cadena de la polimerasa con transcriptasa inversa positivo al coronavirus 2 del síndrome respiratorio agudo severo, con deterioro de su estado clínico y de laboratorio que fueron sometidos a tratamiento de plasmaféresis y fármacos biotecnológicos cubanos: Itolizumab, Jusvinza, HeberFERON® e Intacglobin®. Resultados: el 75% de los pacientes fueron clasificados potencialmente graves. La mitad de los enfermos recibió Itolizumab y al menos una sesión de plasmaféresis terapéutica. La respuesta fue favorable, el 100% negativizó la reacción en cadena de la polimerasa con transcriptasa inversa y el dímero D se normalizó con mayor rapidez, seguido de la proteína C reactiva. Se necesitaron menos sesiones de plasmaféresis para lograr la recuperación. Conclusiones: la plasmaféresis terapéutica en pacientes con COVID-19 fue un tratamiento complementario y prometedor; combinado con los biofármacos cubanos fue innovador y necesario para reducir la carga inflamatoria-viral y lograr la recuperación del paciente con agravamiento clínico de su estado.

Resumen Este estudio tuvo como objetivo determinar las concentraciones salivales de interleucina (IL)-1β, IL-2, IL-10, IL-23, factor de crecimiento transformante (TGF)-β y factor de necrosis tumoral (TNF)-α, nitrato (subproducto de la oxidación del óxido nítrico) y cortisol en pacientes con liquen plano oral (OLP). En este estudio transversal se incluyeron veinte pacientes diagnosticados con OLP y 20 voluntarios sanos (HV) del mismo sexo. Saliva entera no estimulada Se recolectó por la mañana, se determinaron las concentraciones de citocinas y cortisol en saliva mediante ensayo inmunoabsorbente ligado a enzimas (ELISA), se determinó nitrato mediante un analizador de óxido nítrico, se encontraron concentraciones salivales mayores de IL-2 (p<0,003), IL- 23 (p<0,04) y TGF-β (p=0,05) en pacientes con OLP en comparación con HV. No se encontraron diferencias significativas en los niveles salivales de TNF-α, IL-1β e IL-10. Las concentraciones de nitrato fueron marcadamente aumentó en pacientes con OLP (1227,0 ± 738,8 µM/mg de proteína total), en comparación con HV (261,6 ± 166,8 µM/mg; p<0,0001). Los niveles de cortisol salival también fueron más altos en los pacientes con OLP que en los controles (2,79 ± 1,39 vs. 1,94 ±1,21 ng/mg; p<0,048). Los niveles de óxido nítrico en saliva aumentaron notablemente en pacientes con OLP, lo que sugiere una relación de esta molécula con la muerte celular y el daño tisular observado en las lesiones de OLP.

Abstract This study aimed to determine salivary concentrations of interleukin (IL)-1β, IL-2, IL-10, IL- 23, transforming growth factor (TGF)-β, tumor necrosis factor (TNF)-α, nitrate (a by-product of nitric oxide oxidation), and cortisol in patients with oral lichen planus (OLP). Twenty patients diagnosed with OLP and 20 sex-matched healthy volunteers (HV) were included in this cross-sectional study. Unstimulated whole saliva was collected in the morning. Salivary cytokine and cortisol concentrations were determined by enzyme-linked immunosorbent assays (ELISA). Nitrate was measured in a nitric oxide analyzer. We found higher salivary concentrations of IL-2 (p<0.003), IL-23 ( p<0.04), and TGF-β (p=0.05) in patients with OLP compared to HV. No significant differences were found in salivary levels of TNF-α, IL-1β, or IL-10. Nitrate concentrations were markedly increased in OLP patients (1,227.0 ± 738.8 µM/mg total protein) when compared to HV (261.6 ± 166.8 µM/mg; p<0.0001). Salivary cortisol levels were also higher in OLP patients (2.79 ± 1.39 vs. 1.94 ±1.21 ng/mg; p<0.048). The markedly increased salivary levels of nitric oxide in patients with OLP suggest a relationship of this molecule with the cell death and tissue damage observed in these lesions.

RESUMEN La pandemia de la COVID-19 ha dejado como consecuencia una alta mortalidad, así como una disminución de la respuesta de los servicios de salud a nivel mundial. Muchas personas modificaron sus estilos de vida debido al deterioro de su salud tanto durante el proceso agudo de la enfermedad como en la etapa posterior. La depresión y, especialmente, los trastornos del sueño merecen atención debido a su alta prevalencia dentro del denominado síndrome pos-COVID-19 por estar relacionados con un deterioro de la calidad de vida de los afectados. Conocer su prevalencia y entender su fisiopatología, espectro clínico y forma de tratamiento aún son motivo de investigación. El objetivo de la presente revisión narrativa es mostrar los últimos alcances acerca de los trastornos del sueño como manifestación del síndrome pos-COVID-19; para ello, se consultó literatura científica utilizando tres bases de datos, PubMed, Scopus y SciELO, obteniendo un total de 867 artículos, los cuales fueron sometidos a revisión por título y resumen. Esta búsqueda se actualizó en dos oportunidades, y de esta evaluación resultaron 61 artículos que fueron incluidos para esta revisión narrativa. Se destaca una prevalencia de los trastornos del sueño en el síndrome pos-COVID-19 de 9,7 % hasta 50 %; en la determinación de la causa se identifica que es de origen multifactorial, donde la respuesta inflamatoria sistémica podría jugar un papel fundamental por la acción tóxica de las citoquinas y la respuesta neuronal deficiente para revertir el proceso inflamatorio. El insomnio es el síntoma más frecuente; el sexo femenino y los trastornos depresivos concomitantes representan los factores de riesgo prevalentes. Existe un posible efecto benéfico de los fármacos antidepresivos para el control de los síntomas, así como de medidas no farmacológicas como la terapia física individualizada y un régimen nutricional antioxidante. Se concluye que aún existen muchos vacíos respecto a la comprensión de esta patología y que dilucidarlos amerita mayor investigación.

ABSTRACT The COVID-19 pandemic has resulted in both high mortality rates and a decrease in the response of health services worldwide. Many people changed their lifestyles due to the deterioration of their health both during the acute and post-illness stages. Depression, and especially sleep disorders, deserve attention due to their high prevalence within the so-called post-COVID-19 syndrome because they are associated with a deterioration in the quality of life of those affected. Knowing its prevalence and understanding its pathophysiology, clinical spectrum and treatment methods remain matters of research. The objective of this narrative review is to present the latest findings on sleep disorders as manifestations of post-COVID-19 syndrome. For this purpose, scientific literature was consulted using three databases-PubMed, Scopus and SciELO-resulting in a total of 867 articles, which were reviewed by title and abstract. This search was updated twice, resulting in 61 articles, which were included in this narrative review. A prevalence of sleep disorders in post-COVID-19 syndrome ranging from 9.7 % to 50 % is noted; its cause is identified as multifactorial, and the systemic inflammatory response may play a fundamental role due to the toxic action of cytokines and the poor neuronal response to revert the inflammatory process. Insomnia is the most frequent symptom; being female and suffering from concomitant depressive disorders are prevalent risk factors. There is a possible beneficial effect on symptom control resulting from antidepressants as well as non-pharmacological treatments such as individualized physical therapy and an antioxidant nutritional regimen. It is concluded that many gaps remain in the understanding of this pathology and further research is needed to elucidate them.

RESUMEN En la COVID-19, la inmunidad es fundamental. Poco se sabe de los mecanismos del factor de necrosis tumoral (TNF-α) y su capacidad de estimular la producción de anticuerpos anti-SARS-CoV-2. Asimismo, sobre la respuesta y agotamiento celular de los linfocitos T (LT). Evaluar el comportamiento, antes y después de la tercera dosis de vacunación, de los niveles de IgG (anti-spike), TNF-α y poblaciones linfocitarias incluyendo su agotamiento celular. Se utilizó suero y células mononucleares de sangre periférica de sujetos con infección (G1, n=07) y asintomáticos (G2, n= 08 y G3, n=10) vacunados con la tercera dosis de la vacuna BNT162b2 (G1 y G2) o de ChAdOx1-S (G3). Se usó ELISA para determinar los niveles de IgG y TNF-α y citometría de flujo para determinar los niveles y el agotamiento celular de LT. La IgG (anti-spike) antes y después de la tercera dosis no cambió. Se observó en G1 un aumento significativo de TNF-α después de recibir la tercera dosis. Los linfocitos totales (T, B y NK) mostraron una disminución significativa en G2 y, aunque los LT(CD3+) no variaron, en G3 sí hubo una disminución de LTCD4+ con aumento de PD-1+ y un aumento de LTCD8+ y PD-1+ antes y después de la tercera dosis, respectivamente. Se encontró una correlación positiva después de la tercera dosis en G3 entre IgG y CD4+PD-1+(p=0,034) y CD8+PD-1+(p=0,028), respectivamente. La respuesta humoral (IgG) e inflamatoria (TNF-α) no se modificó significativamente; la vacunación heteróloga (G3) incrementó los niveles de LT CD4+, una subpoblación que sostiene la inmunidad adaptativa antiviral. Adicionalmente, evito el agotamiento celular de LT.

SUMMARY Immunity against COVID-19 is crucial. Little is known about the mechanisms involved in stimulating antibody production against SARS-CoV-2 by the tumor necrosis factor alpha (TNF-α) and the exhaustion of T-cells. To evaluate the IgG (anti-spike) response, TNF-α, T-cell subsets, and their exhaustion. Serum samples and peripheral mononuclear cells of subjects with infection (G1, n=07), asymptomatic (G2, n=08 y G3, n=10) vaccinated with three doses of the BNT162b2 (G1 and G2) or the ChAdOx1-S (G3) vaccines. ELISA determined the level of IgG and TNF-α, and flow cytometry determined the T-cell subsets and exhaustion. No change was observed in the levels of IgG before and after vaccination. G1 significantly increased TNF-α levels after receiving the third vaccine dose. Total lymphocytes significantly decreased in G2, but CD3+ did not change. G3 had a reduction in LTCD4+ and an increase in PD-1+, LTCD8+, and PD-1+ before and after the third vaccine dose. A positive correlation was observed after the third vaccine dose in G3 among IgG and CD4+PD-1+(p=0.034) and CD8+PD-1+(p=0.028), respectively. Humoral (IgG) and inflammatory (TNF-α) responses were not modified significantly; the heterologous vaccine (G3) increased levels of CD4+ cells, a subset that sustains antiviral adaptative immunity, and avoids T-cell exhaustion.