Biomimetic Platelet-Cloaked Nanoparticles for the Delivery of Anti-Inflammatory Curcumin in the Treatment of Atherosclerosis.

Atherosclerosis still represents a major driver of cardiovascular diseases worldwide. Together with accumulation of lipids in the plaque, inflammation is recognized as one of the key players in the formation and development of atherosclerotic plaque. Systemic anti-inflammatory treatments are successful in reducing the disease burden, but are correlated with severe side effects, underlining the need for targeted formulations. In this work, curcumin is chosen as the anti-inflammatory payload model and further loaded in lignin-based nanoparticles (NPs). The NPs are then coated with a tannic acid (TA)- Fe (III) complex and further cloaked with fragments derived from platelet cell membrane, yielding NPs with homogenous size. The two coatings increase the interaction between the NPs and cells, both endothelial and macrophages, in steady state or inflamed status. Furthermore, NPs are cytocompatible toward endothelial, smooth muscle and immune cells, while not inducing immune activation. The anti-inflammatory efficacy is demonstrated in endothelial cells by real-time quantitative polymerase chain reaction and ELISA assay where curcumin-loaded NPs decrease the expression of Nf-κb, TGF-ß1, IL-6, and IL-1ß in lipopolysaccharide-inflamed cells. Overall, due to the increase in the cell-NP interactions and the anti-inflammatory efficacy, these NPs represent potential candidates for the targeted anti-inflammatory treatment of atherosclerosis.

Embryonic NIPP1 Depletion in Keratinocytes Triggers a Cell Cycle Arrest and Premature Senescence in Adult Mice.

NIPP1 is a ubiquitously expressed regulatory subunit of PP1. Its embryonic deletion in keratinocytes causes chronic sterile skin inflammation, epidermal hyperproliferation, and resistance to mutagens in adult mice. To explore the primary effects of NIPP1 deletion, we first examined hair cycle progression of NIPP1 skin knockouts (SKOs). The entry of the first hair cycle in the SKOs was delayed owing to prolonged quiescence of hair follicle stem cells. In contrast, the entry of the second hair cycle in the SKOs was advanced as a result of precocious activation of hair follicle stem cells. The epidermis of SKOs progressively accumulated senescent cells, and this cell-fate switch was accelerated by DNA damage. Primary keratinocytes from SKO neonates and human NIPP1-depleted HaCaT keratinocytes failed to proliferate and showed an increase in the expression of cell cycle inhibitors (p21, p16/Ink4a, and/or p19/Arf) and senescence-associated-secretory-phenotype factors as well as in DNA damage (γH2AX and 53BP1). Our data demonstrate that the primary effect of NIPP1 deletion in keratinocytes is a cell cycle arrest and premature senescence that gradually progresse to chronic senescence and likely contribute to the decreased sensitivity of SKOs to mutagens.

Cerebellar Volumetry in Ataxias: Relation to Ataxia Severity and Duration.

Cerebellar atrophy is the neuropathological hallmark of most ataxias. Hence, quantifying the volume of the cerebellar grey and white matter is of great interest. In this study, we aim to identify volume differences in the cerebellum between spinocerebellar ataxia type 1 (SCA1), SCA3 and SCA6 as well as multiple system atrophy of cerebellar type (MSA-C). Our cross-sectional data set comprised mutation carriers of SCA1 (N=12), SCA3 (N=62), SCA6 (N=14), as well as MSA-C patients (N=16). Cerebellar volumes were obtained from T1-weighted magnetic resonance images. To compare the different atrophy patterns, we performed a z-transformation and plotted the intercept of each patient group's model at the mean of 7 years of ataxia duration as well as at the mean ataxia severity of 14 points in the SARA sum score. In addition, we plotted the extrapolation at ataxia duration of 0 years as well as 0 points in the SARA sum score. Patients with MSA-C demonstrated the most pronounced volume loss, particularly in the cerebellar white matter, at the late time intercept. Patients with SCA6 showed a pronounced volume loss in cerebellar grey matter with increasing ataxia severity compared to all other patient groups. MSA-C, SCA1 and SCA3 showed a prominent atrophy of the cerebellar white matter. Our results (i) confirmed SCA6 being considered as a pure cerebellar grey matter disease, (ii) emphasise the involvement of cerebellar white matter in the neuropathology of SCA1, SCA3 and MSA-C, and (iii) reflect the rapid clinical progression in MSA-C.

Fatores associados às atitudes dos enfermeiros quanto à importância da família nos cuidados de enfermagem / Factors associated with nurses' attitudes toward the family involvement in nursing care / Factores asociados a las actitudes de los enfermeros respecto a la importancia de la familia en los cuidados de enfermería

Resumo Enquadramento: A participação da família nos cuidados potencia ganhos em saúde, sendo a atitude dos enfermeiros, influenciada por múltiplos fatores. Objetivo: Conhecer as atitudes dos enfermeiros quanto à importância atribuida à integração das famílias nos cuidados e determinar a relação entre essas atitudes e a idade, habilitações académicas, tempo na carreira, categoria profissional, sentido de vida e sintomatologia depressiva/ansiosa dos enfermeiros. Metodologia: Estudo transversal, descritivo-correlacional, realizado com 317 enfermeiros de um Centro Hospitalar da Região Centro de Portugal. Aplicou-se um questionário sociodemográfico, a escala Importância das Famílias nos Cuidados de Enfermagem-Atitudes dos Enfermeiros, o Inventário da Saúde Mental e a Escala dos Objetivos de Vida. Resultados: A maioria dos participantes documenta atitudes integrativas, sendo as correlações da variável em estudo com os fatores associados, coerentes com o esperado. Conclusão: Apesar da maioria dos enfermeiros documentar atitudes inclusivas da família, são os mais velhos, com mais habilitações e tempo na carreira, detentores de categoria profissional mais elevada, com maior extensão de sentido de vida e menor sintomatologia depressiva/ansiosa que mais priorizam o envolvimento da família nos cuidados.

Abstract Background: Family involvement in care increases health gains, and multiple factors influence nurses' attitudes toward family involvement. Objective: To identify nurses' attitudes toward family involvement in care and determine the association between nurses' attitudes and their age, education level, years in the profession, professional category, purpose in life, and symptoms of depression/anxiety. Methodology: Cross-sectional, descriptive-correlational study, carried out 317 nurses from a hospital center in the central region of Portugal. Nurses answered a sociodemographic questionnaire and completed the Families' Importance in Nursing Care-Nurses' Attitudes scale, the Mental Health Inventory, and the Purpose in Life Test. Results: Most participants reported supportive attitudes toward family involvement in care. The correlations between the variable under study and the associated factors were consistent with the expected. Conclusion: Most participants have supportive attitudes toward family involvement in care. Older nurses, with higher education levels, more years in the profession, higher professional category, a higher sense of purpose in life, and fewer symptoms of depression/anxiety attach more importance to family involvement in nursing care.

Resumen Marco contextual: La participación de la familia en los cuidados optimiza los beneficios para la salud y la actitud de los enfermeros hacia esta participación se ve influida por múltiples factores Objetivo: Identificar las actitudes de los enfermeros con respecto a la importancia que conceden a la integración de las familias en los cuidados y determinar la relación entre las actitudes de los enfermeros y su edad, titulación académica, tiempo en la profesión, categoría profesional, sentido de la vida y sintomatología depresiva/ansiedad. Metodología: Estudio transversal, descriptivo-correlacional, que se realizó con 317 enfermeros de un centro hospitalario de la Región Centro de Portugal. Los participantes respondieron a un cuestionario sociodemográfico, a la escala "La Importancia de la Familia en los Cuidados de Enfermería-Actitudes de los Enfermeros", al "Inventario de Salud Mental" y a la "Escala de los Objetivos de Vida". Resultados: La mayoría de los participantes documentan actitudes integradoras de la familia hacia el cuidado y el resultado de las correlaciones de la variable objeto de estudio con los factores asociados es coherente con lo esperado. Conclusión: La mayoría de los participantes mostraron actitudes integradoras hacia la familia en los cuidados de enfermería, y fueron los enfermeros de mayor edad, con más titulación y tiempo en la profesión, mayor categoría profesional, mayores extensiones del sentido de vida y menores índices de sintomatología depresiva/ansiedad los que atribuyeron más importancia a la familia en los cuidados de enfermería.

Antinociceptive effect of Nephelium lappaceum L. fruit peel and the participation of nitric oxide, opioid receptors, and ATP-sensitive potassium channels.

Introduction: Nephelium lappaceum L. (Sapindaceae) is a plant known as rambutan. It is used for various purposes in traditional medicine. Objective: We aimed to evaluate the antinociceptive effects of the ethanol extract of the fruit peel of N. lappaceum (EENL), the mechanisms involved in these effects, and the acute toxicity in zebrafish. Methods: We performed chromatography coupled to mass spectrometry, acute toxicity assay in zebrafish, and evaluation in mice submitted to models of nociception and locomotor activity. Results: We identified (epi)-catechin, procyanidin B, and ellagic acid and its derivatives in EENL. We did not find any toxicity in zebrafish embryos incubated with EENL. The locomotor activity of mice submitted to oral pretreatment with EENL was not changed, but it reduced the abdominal constrictions induced by acetic acid, the licking/biting time in both the first and second phase of formalin testing and capsaicin testing, and carrageenan-induced paw mechanical allodynia. Oral pretreatment with EENL increased latency time in the hot plate test. This antinociceptive effect was significantly reversed by naloxone, L-arginine, and glibenclamide respectively showing the participation of opioid receptors, nitric oxide, and KATP channels as mediators of EENL-induced antinociception. Conclusion: EENL causes antinociception with the participation of opioid receptors, nitric oxide, and KATP channels, and is not toxic to zebrafish.

Cerebellar volumetry in ataxias: Relation to ataxia severity and duration.

Background: Cerebellar atrophy is the neuropathological hallmark of most ataxias. Hence, quantifying the volume of the cerebellar grey and white matter is of great interest. In this study, we aim to identify volume differences in the cerebellum between spinocerebellar ataxia type 1 (SCA1), SCA3 and SCA6 as well as multiple system atrophy of cerebellar type (MSA-C). Methods: Our cross-sectional data set comprised mutation carriers of SCA1 (N=12), SCA3 (N=62), SCA6 (N=14), as well as MSA-C patients (N=16). Cerebellar volumes were obtained from T1-weighted magnetic resonance images. To compare the different atrophy patterns, we performed a z-transformation and plotted the intercept of each patient group's model at the mean of 7 years of ataxia duration as well as at the mean ataxia severity of 14 points in the SARA sum score. In addition, we plotted the extrapolation at ataxia duration of 0 years as well as 0 points in the SARA sum score. Results: Patients with MSA-C demonstrated the most pronounced volume loss, particularly in the cerebellar white matter, at the late time intercept. Patients with SCA6 showed a pronounced volume loss in cerebellar grey matter with increasing ataxia severity compared to all other patient groups. MSA-C, SCA1 and SCA3 showed a prominent atrophy of the cerebellar white matter. Conclusion: Our results (i) confirmed SCA6 being considered as a pure cerebellar gray matter disease, (ii) emphasise the involvement of cerebellar white matter in the neurophatology of SCA1, SCA3 and MSA-C, and (iii) reflect the rapid clinical progression in MSA-C.

Pesticide-Induced Inflammation at a Glance.

The increasing number of studies reporting the risks of the exposure to pesticides aligned with the intensified use of such hazardous chemicals has emerged as a pressing contemporary issue, notably due to the potential effects to both the environment and human health. Pesticides, while broadly applied in modern agriculture for pest control and crop protection, have raised concerns due to their unintended effects on non-target organisms. The immune system exerts a key role in the protection against the exposome, which could result in cellular imbalances and tissue damage through the inflammatory response. Pesticides, which encompass a diverse array of chemicals, have been linked to inflammation in experimental models. Therefore, the aim of this review is to discuss the increasing concern over the risks of pesticide exposure focusing on the effects of various chemical classes on inflammation by covering, as broadly as possible, different experimental approaches as well as the multiple or co-exposure of pesticides. Overall, pesticides potentially induce inflammation in different experimental models, manifested through skin irritation, respiratory impairment, or systemic effects. The connection between pesticides and inflammation highlights the importance of proper handling and regulation of these substances and underscores the need for research into safer and sustainable practices to reduce our reliance on synthetic pesticides and fertilizers.

Prevalência da disfagia na pessoa com acidente vascular cerebral na fase aguda / Prevalence of dysphagia in people with stroke in the acute phase

Foi desenvolvido este trabalho no âmbito do mestrado em enfermagem de Reabilitação, sendo que a primeira parte do mesmo diz respeito ao relatório de estágio onde são elencadas as competências obtidas e as experiências vividas. A capacidade de deglutição, enquanto processo fisiológico fundamental da alimentação, irá interferir com todos os aspetos da vida social e de lazer, com grande impacto na qualidade de vida da pessoa que sofreu um acidente vascular cerebral (AVC). Assim, torna-se imperativo perceber se o impacto da disfagia é considerável e deve ser visto como uma questão de grande preocupação por todos os elementos envolvidos na equipa multidisciplinar e, neste caso específico, pelo EEER. Objetivo: Descrever as experiências vividas e as competências obtidas em contexto de estágio e avaliar a prevalência da disfagia em doentes pós acidente vascular cerebral na fase aguda. Métodos: Estudo de coorte retrospetivo utilizando uma base de dados, criada para este efeito, que inclui informação de todos doentes admitidos numa unidade de AVC entre janeiro e março de 2023. Resultados: 64 doentes com diagnóstico de AVC, maioritariamente mulheres, com uma idade média de 71,3 anos, prevalece o AVC isquémico com lesão predominante do hemisfério direito. Na admissão há um maior número de doentes que revelaram deglutição comprometida (53,1%), sendo que destes 12,5% apresentaram disfagia ligeira, 14,1% disfagia moderada e 23,4% disfagia grave. Na alta não houve uma alteração significativa destes valores. No entanto, houve um doente que alterou o grau de disfagia ligeira para sem disfagia e outro que, pelo contrário, de sem disfagia passou para disfagia ligeira. A disfagia grave manteve os mesmos valores (23,4%). A disfagia moderada aumentou os valores (17,2%), uma vez que houve dois doentes que agravaram o status de disfagia ligeira para moderada. Conclusão: Entre o momento da admissão e a alta, nesta amostra, não de verificaram grandes alterações no que diz respeito à gravidade e ao número de doentes com disfagia. Esta monitorização é importante para que se possa trabalhar preventivamente, minimizando as complicações que a disfagia pode espoletar.

This work was developed as part of the Master's program in Rehabilitation Nursing, with the first part of it relating to the internship report, listing the acquired skills and lived experiences. Wallowing capacity, as a fundamental physiological process in feeding, affects all aspects of social and leisure life, significantly impacting the quality of life for individuals who have experienced a stroke. Therefore, it is imperative to understand whether the impact of dysphagia is considerable and should be a matter of great concern for all members of the multidisciplinary team involved, particularly the EEER Aim: To evaluate the prevalence of dysphagia in patients during the acute phase following a stroke. Methods: We conducted a retrospective cohort study utilizing a hospital database specifically created for this purpose, which includes information on all patients admitted to a stroke unit between January and March 2023. Results: The study comprised 64 patients diagnosed with stroke, predominantly females, with an average age of 71,3 years. Ischemic stroke with predominant right hemisphere lesions was the most prevalent type. Upon admission, a higher number of patients (53,1%) exhibited compromised swallowing function, with 12,5% showing mild dysphagia, 14,1% moderate dysphagia, and 23,4% severe dysphagia. There were no significant changes in these values at the time of discharge. However, one patient transitioned from mild dysphagia to no dysphagia, while another patient changed from no dysphagia to mild dysphagia. Severe dysphagia remained constant at 23,4%. Moderate dysphagia increased in prevalence (17,2%) due to two patients whose status worsened from mild to moderate dysphagia Conclusion: In this sample, no significant changes were observed in the severity and number of patients with dysphagia between admission and discharge. Regular monitoring is essential to work preventively and minimize the complications that dysphagia may trigger.

Distinct anti-NP, anti-RBD and anti-Spike antibody profiles discriminate death from survival in COVID-19.

Introduction: Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces rapid production of IgM, IgA, and IgG antibodies directed to multiple viral antigens that may have impact diverse clinical outcomes. Methods: We evaluated IgM, IgA, and IgG antibodies directed to the nucleocapsid (NP), IgA and IgG to the Spike protein and to the receptor-binding domain (RBD), and the presence of neutralizing antibodies (nAb), in a cohort of unvaccinated SARS-CoV-2 infected individuals, in the first 30 days of post-symptom onset (PSO) (T1). Results: This study included 193 coronavirus disease 2019 (COVID-19) participants classified as mild, moderate, severe, critical, and fatal and 27 uninfected controls. In T1, we identified differential antibody profiles associated with distinct clinical presentation. The mild group presented lower levels of anti-NP IgG, and IgA (vs moderate and severe), anti-NP IgM (vs severe, critical and fatal), anti-Spike IgA (vs severe and fatal), and anti-RBD IgG (vs severe). The moderate group presented higher levels of anti-RBD IgA, comparing with severe group. The severe group presented higher levels of anti-NP IgA (vs mild and fatal) and anti-RBD IgG (vs mild and moderate). The fatal group presented higher levels of anti-NP IgM and anti-Spike IgA (vs mild), but lower levels of anti-NP IgA (vs severe). The levels of nAb was lower just in mild group compared to severe, critical, and fatal groups, moreover, no difference was observed among the more severe groups. In addition, we studied 82 convalescent individuals, between 31 days to 6 months (T2) or more than 6 months (T3), PSO, those: 12 mild, 26 moderate, and 46 severe plus critical. The longitudinal analyzes, for the severe plus critical group showed lower levels of anti-NP IgG, IgA and IgM, anti-Spike IgA in relation T3. The follow-up in the fatal group, reveals that the levels of anti-spike IgG increased, while anti-NP IgM levels was decreased along the time in severe/critical and fatal as well as anti-NP IgG and IgA in several/critical groups. Discussion: In summary, the anti-NP IgA and IgG lower levels and the higher levels of anti-RBD and anti-Spike IgA in fatal compared to survival group of individuals admitted to the intensive care unit (ICU). Collectively, our data discriminate death from survival, suggesting that anti-RBD IgA and anti-Spike IgA may play some deleterious effect, in contrast with the potentially protective effect of anti-NP IgA and IgG in the survival group.

Revisiting Retinal Degeneration Hallmarks: Insights from Molecular Markers and Therapy Perspectives.

Visual impairment and blindness are a growing public health problem as they reduce the life quality of millions of people. The management and treatment of these diseases represent scientific and therapeutic challenges because different cellular and molecular actors involved in the pathophysiology are still being identified. Visual system components, particularly retinal cells, are extremely sensitive to genetic or metabolic alterations, and immune responses activated by local insults contribute to biological events, culminating in vision loss and irreversible blindness. Several ocular diseases are linked to retinal cell loss, and some of them, such as retinitis pigmentosa, age-related macular degeneration, glaucoma, and diabetic retinopathy, are characterized by pathophysiological hallmarks that represent possibilities to study and develop novel treatments for retinal cell degeneration. Here, we present a compilation of revisited information on retinal degeneration, including pathophysiological and molecular features and biochemical hallmarks, and possible research directions for novel treatments to assist as a guide for innovative research. The knowledge expansion upon the mechanistic bases of the pathobiology of eye diseases, including information on complex interactions of genetic predisposition, chronic inflammation, and environmental and aging-related factors, will prompt the identification of new therapeutic strategies.

Orthostatic Stress and Baroreflex Sensitivity: A Window into Autonomic Dysfunction in Lone Paroxysmal Atrial Fibrillation.

The abnormal neural control of atria has been considered one of the mechanisms of paroxysmal atrial fibrillation (PAF) pathogenesis. The baroreceptor reflex has an important role in cardiovascular regulation and may serve as an index of autonomic function. This study aimed to analyze the baroreceptor reflex's role in heart rate regulation during upright tilt (HUT) in patients with lone PAF. The study included 68 patients with lone PAF and 34 healthy individuals who underwent baroreflex assessment. Parameters such as baroreflex sensitivity (BRS), number of systolic blood pressure (BP) ramps, and the baroreflex effectiveness index (BEI) were evaluated. The study found that PAF patients had comparable resting BPs and heart rates (HRs) to healthy individuals. However, unlike healthy individuals, PAF patients showed a sustained increase in BP with an upright posture followed by the delayed activation of the baroreceptor function with a blunted HR response and lower BEI values. This indicates a pronounced baroreflex impairment in PAF patients, even at rest. Our data suggest that together with BRS, BEI could be used as a marker of autonomic dysfunction in PAF patients, making it important to further investigate its relationship with AF recurrence after ablation and its involvement in cardiovascular autonomic remodeling.

Envenomations caused by fish in Brazil: an evolutionary, morphological, and clinical vision of a neglected problem.

Venomous fish are commonly found in Brazilian waters. The most important marine venomous fish species are stingrays (Dasyatidae, Gimnuridae, Myliobatidae, and Rhinopteridae families), catfish (Ariidae family), scorpionfish and lionfish (both Scorpaenidae family), and toadfish (Batrachoididae family). Meanwhile, Potamotrygonidae stingrays and Pimelodidae catfish are the most important venomous freshwater fish. The mechanisms of envenomation vary and involve various venomous apparatuses and glands. Despite not being highly developed, these venomous apparatuses in fish appear rudimentary, using structures such as fins and rays to inoculate toxins and rarely presenting with specialized structures. Toxins are produced by glandular tissue made up of proteinaceous cells, lacking true glands, and are positioned along the inoculation structures. However, systemic manifestations are rare. No antivenom serum has been developed for any species of American venomous fish. Brazilian venomous fish and their venoms have only recently attracted attention, leading to new studies not only addressing clinical issues in humans, but also exploring the discovery of new active substances with immense pharmacological potential.

Effective Pre-Clinical Treatment of Fish Envenoming with Polyclonal Antiserum.

Envenomation by venomous fish, although not always fatal, is capable of causing damage to homeostasis by activating the inflammatory process, with the formation of edema, excruciating pain, necrosis that is difficult to heal, as well as hemodynamic and cardiorespiratory changes. Despite the wide variety of pharmacological treatments used to manage acute symptoms, none are effective in controlling envenomation. Knowing the essential role of neutralizing polyclonal antibodies in the treatment of envenoming for other species, such as snakes, this work aimed to produce a polyclonal antiserum in mice and test its ability to neutralize the main toxic effects induced by the venoms of the main venomous Brazilian fish. We found that the antiserum recognizes the main toxins present in the different venoms of Thalassophryne nattereri, Scorpaena plumieri, Potamotrygon gr. Orbignyi, and Cathorops spixii and was effective in pre-incubation trials. In an independent test, the antiserum applied immediately to the topical application of T. nattereri, P. gr orbygnyi, and C. spixii venoms completely abolished the toxic effects on the microcirculation, preventing alterations such as arteriolar contraction, slowing of blood flow in postcapillary venules, venular stasis, myofibrillar hypercontraction, and increased leukocyte rolling and adherence. The edematogenic and nociceptive activities induced by these venoms were also neutralized by the immediate application of the antiserum. Importantly, the antiserum prevented the acute inflammatory response in the lungs induced by the S. plumieri venom. The success of antiserum containing neutralizing polyclonal antibodies in controlling the toxic effects induced by different venoms offers a new strategy for the treatment of fish envenomation in Brazil.

Inflammasome Coordinates Senescent Chronic Wound Induced by Thalassophryne nattereri Venom.

Thalassophryne nattereri toadfish (niquim) envenomation, common in the hands and feet of bathers and fishermen in the north and northeast regions of Brazil, is characterized by local symptoms such as immediate edema and intense pain. These symptoms progress to necrosis that lasts for an extended period of time, with delayed healing. Wound healing is a complex process characterized by the interdependent role of keratinocytes, fibroblasts, and endothelial and innate cells such as neutrophils and macrophages. Macrophages and neutrophils are actively recruited to clear debris during the inflammatory phase of wound repair, promoting the production of pro-inflammatory mediators, and in the late stage, macrophages promote tissue repair. Our hypothesis is that injury caused by T. nattereri venom (VTn) leads to senescent wounds. In this study, we provide valuable information about the mechanism(s) behind the dysregulated inflammation in wound healing induced by VTn. We demonstrate in mouse paws injected with the venom the installation of γH2AX/p16Ink4a-dependent senescence with persistent neutrophilic inflammation in the proliferation and remodeling phases. VTn induced an imbalance of M1/M2 macrophages by maintaining a high number of TNF-α-producing M1 macrophages in the wound but without the ability to eliminate the persistent neutrophils. Chronic neutrophilic inflammation and senescence were mediated by cytokines such as IL-1α and IL-1ß in a caspase-1- and caspase-11-dependent manner. In addition, previous blocking with anti-IL-1α and anti-IL-ß neutralizing antibodies and caspase-1 (Ac YVAD-CMK) and caspase-11 (Wedelolactone) inhibitors was essential to control the pro-inflammatory activity of M1 macrophages induced by VTn injection, skewing towards an anti-inflammatory state, and was sufficient to block neutrophil recruitment and senescence.

An Overview towards Zebrafish Larvae as a Model for Ocular Diseases.

Despite the obvious morphological differences in the visual system, zebrafish share a similar architecture and components of the same embryonic origin as humans. The zebrafish retina has the same layered structure and cell types with similar metabolic and phototransduction support as humans, and is functional 72 h after fertilization, allowing tests of visual function to be performed. The zebrafish genomic database supports genetic mapping studies as well as gene editing, both of which are useful in the ophthalmological field. It is possible to model ocular disorders in zebrafish, as well as inherited retinal diseases or congenital or acquired malformations. Several approaches allow the evaluation of local pathological processes derived from systemic disorders, such as chemical exposure to produce retinal hypoxia or glucose exposure to produce hyperglycemia, mimicking retinopathy of prematurity or diabetic retinopathy, respectively. The pathogenesis of ocular infections, autoimmune diseases, or aging can also be assessed in zebrafish larvae, and the preserved cellular and molecular immune mechanisms can be assessed. Finally, the zebrafish model for the study of the pathologies of the visual system complements certain deficiencies in experimental models of mammals since the regeneration of the zebrafish retina is a valuable tool for the study of degenerative processes and the discovery of new drugs and therapies.

The Anti-Inflammatory Peptide TnP Is a Candidate Molecule for Asthma Treatment.

Asthma is the most common chronic lung disease, with increasing morbidity and mortality worldwide. Accumulation of peribronchial leukocytes is the hallmark of asthma, in particular, eosinophils, which have been reported as the primary cell associated with the induction of airway hyperresponsiveness. Continued exacerbation and accumulation of other leukocytes, such as neutrophils, Th1, and Th17 cells correlate with many of the long-term effects of asthma, such as airway remodeling. We have patented the TnP family of synthetic cyclic peptides, which is in the preclinical phase of developmental studies for chronic inflammatory diseases. The aim of this work was to investigate whether TnP could show anti-inflammatory activity in a murine model of asthma that includes a mixed phenotype of eosinophilic and neutrophilic inflammation. For this, Balb/c mice, sensitized with OVA and exposed to 1% challenge with OVA aerosol, were submitted to prophylactic treatment, receiving TnP at 0.3 mg/kg orally, 1 h before each challenge. We found that sensitized mice challenged with OVA and treated with TnP showed no airway hyperreactivity or lung remodeling. TnP acts systemically in secondary lymphoid organs and locally in the lung, inhibiting the production of Th2/Th17 cytokines. Furthermore, TnP prevented the infiltration of eosinophils and neutrophils in the BAL and lung tissue, inhibited the production of IgE/IgG1, prevented hyperplasia of mucus-producing cells, and decreased the thickening and deposition of sub-epithelial collagen. Our results showed TnP as a candidate molecule for the treatment of airway remodeling associated with inflammatory diseases, such as asthma.

Integrated Metabolic and Inflammatory Signatures Associated with Severity of, Fatality of, and Recovery from COVID-19.

Severe manifestations of coronavirus disease 2019 (COVID-19) and mortality have been associated with physiological alterations that provide insights into the pathogenesis of the disease. Moreover, factors that drive recovery from COVID-19 can be explored to identify correlates of protection. The cellular metabolism represents a potential target to improve survival upon severe disease, but the associations between the metabolism and the inflammatory response during COVID-19 are not well defined. We analyzed blood laboratorial parameters, cytokines, and metabolomes of 150 individuals with mild to severe disease, of which 33 progressed to a fatal outcome. A subset of 20 individuals was followed up after hospital discharge and recovery from acute disease. We used hierarchical community networks to integrate metabolomics profiles with cytokines and markers of inflammation, coagulation, and tissue damage. Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes significant alterations in the plasma metabolome, whose activity varies according to disease severity and correlates with oxygen saturation. Differential metabolism underlying death was marked by amino acids and related metabolites, such as glutamate, glutamyl-glutamate, and oxoproline, and lipids, including progesterone, phosphocholine, and lysophosphatidylcholines (lysoPCs). Individuals who recovered from severe disease displayed persistent alterations enriched for metabolism of purines and phosphatidylinositol phosphate and glycolysis. Recovery of mild disease was associated with vitamin E metabolism. Data integration shows that the metabolic response is a hub connecting other biological features during disease and recovery. Infection by SARS-CoV-2 induces concerted activity of metabolic and inflammatory responses that depend on disease severity and collectively predict clinical outcomes of COVID-19. IMPORTANCE COVID-19 is characterized by diverse clinical outcomes that include asymptomatic to mild manifestations or severe disease and death. Infection by SARS-CoV-2 activates inflammatory and metabolic responses that drive protection or pathology. How inflammation and metabolism communicate during COVID-19 is not well defined. We used high-resolution mass spectrometry to investigate small biochemical compounds (<1,500 Da) in plasma of individuals with COVID-19 and controls. Age, sex, and comorbidities have a profound effect on the plasma metabolites of individuals with COVID-19, but we identified significant activity of pathways and metabolites related to amino acids, lipids, nucleotides, and vitamins determined by disease severity, survival outcome, and recovery. Furthermore, we identified metabolites associated with acute-phase proteins and coagulation factors, which collectively identify individuals with severe disease or individuals who died of severe COVID-19. Our study suggests that manipulating specific metabolic pathways can be explored to prevent hyperinflammation, organ dysfunction, and death.

Telomere length dynamics measured by flow-FISH in patients with obesity undergoing bariatric surgery.

Obesity has negative effects on comorbidities, health-related quality of life and survival. Telomere length (TL) changes after bariatric surgery have been reported, but the studies are contradictory, and analyses using state-of-the art techniques for TL measurement, such as flow-FISH, are sparse. We measured TL dynamics via flow-FISH in patients undergoing bariatric surgery and compared their TL with 105 healthy individuals. Patients with obesity who underwent bariatric surgery were included. Lymphocyte and granulocyte absolute and age-adjusted (aa) TL were analyzed by flow-FISH before (preoperative cohort, n = 45) and after surgery (follow-up cohort, n = 35) at month 5.5 ± 3.9 (mean ± standard deviation [SD]). The initial lymphocyte aaTL was significantly shorter (-0.37 kb ± 0.18 kb, P = 0.045) in patients with obesity, while the granulocyte aaTL was not different from that in the healthy comparison population (0.28 kb ± 0.17 kb, P = 0.11). The telomere dynamics after surgery showed an increase in mean TL in both lymphocytes and granulocytes of patients with a pronounced BMI loss of ≥ 10 kg/m2. We did not find any association between TL increase after surgery and age, sex or the type of procedure selected for bariatric surgery. We confirmed that patients suffering from obesity have significantly shorter lymphocyte TL using flow-FISH. Along with and dependent on the degree of weight reduction after bariatric surgery, TL significantly increased in both lymphocytes and granulocytes after a mean of 5.5 months. Our results show that bariatric surgery affects not only body weight but also biomarkers of aging, such as TL.

Envenomations caused by fish in Brazil: an evolutionary, morphological, and clinical vision of a neglected problem

ABSTRACT Venomous fish are commonly found in Brazilian waters. The most important marine venomous fish species are stingrays (Dasyatidae, Gimnuridae, Myliobatidae, and Rhinopteridae families), catfish (Ariidae family), scorpionfish and lionfish (both Scorpaenidae family), and toadfish (Batrachoididae family). Meanwhile, Potamotrygonidae stingrays and Pimelodidae catfish are the most important venomous freshwater fish. The mechanisms of envenomation vary and involve various venomous apparatuses and glands. Despite not being highly developed, these venomous apparatuses in fish appear rudimentary, using structures such as fins and rays to inoculate toxins and rarely presenting with specialized structures. Toxins are produced by glandular tissue made up of proteinaceous cells, lacking true glands, and are positioned along the inoculation structures. However, systemic manifestations are rare. No antivenom serum has been developed for any species of American venomous fish. Brazilian venomous fish and their venoms have only recently attracted attention, leading to new studies not only addressing clinical issues in humans, but also exploring the discovery of new active substances with immense pharmacological potential.