Move Your Body toward Healthy Aging: Potential Neuroprotective Mechanisms of Irisin in Alzheimer's Disease.

Alzheimer's disease (AD) is the leading cause of dementia in older adults, having a significant global burden and increasing prevalence. Current treatments for AD only provide symptomatic relief and do not cure the disease. Physical activity has been extensively studied as a potential preventive measure against cognitive decline and AD. Recent research has identified a hormone called irisin, which is produced during exercise, that has shown promising effects on cognitive function. Irisin acts on the brain by promoting neuroprotection by enhancing the growth and survival of neurons. It also plays a role in metabolism, energy regulation, and glucose homeostasis. Furthermore, irisin has been found to modulate autophagy, which is a cellular process involved in the clearance of protein aggregates, which are a hallmark of AD. Additionally, irisin has been shown to protect against cell death, apoptosis, oxidative stress, and neuroinflammation, all of which are implicated in AD pathogenesis. However, further research is needed to fully understand the mechanisms and therapeutic potential of irisin in AD. Despite the current gaps in knowledge, irisin holds promise as a potential therapeutic target for slowing cognitive decline and improving quality of life in AD patients.

Advances in Alzheimer's disease's pharmacological treatment.

Alzheimer's disease (AD) is the most common type of dementia in the elderly. Several hypotheses emerged from AD pathophysiological mechanisms. However, no neuronal protective or regenerative drug is available nowadays. Researchers still work in drug development and are finding new molecular targets to treat AD. Therefore, this study aimed to summarize main advances in AD pharmacological therapy. Clinical trials registered in the National Library of Medicine database were selected and analyzed accordingly to molecular targets, therapeutic effects, and safety profile. The most common outcome was the lack of efficacy. Only seven trials concluded that tested drugs were safe and induced any kind of therapeutic improvement. Three works showed therapeutic effects followed by toxicity. In addition to aducanumab recent FDA approval, antibodies against amyloid-ß (Aß) showed no noteworthy results. 5-HT6 antagonists, tau inhibitors and nicotinic agonists' data were discouraging. However, anti-Aß vaccine, BACE inhibitor and anti-neuroinflammation drugs showed promising results.

Inflammatory stimulus worsens the effects of UV-A exposure on J774 cells.

UV-A radiation affects skin homeostasis by promoting oxidative distress. Endogenous photosensitizers in the dermis and epidermis of human skin absorb UV-A radiation forming excited states (singlet and triplet) and reactive oxygen species (ROS) producing oxidized compounds that trigger biological responses. The activation of NF-kB induces the expression of pro-inflammatory cytokines and can intensify the generation of ROS. However, there is no studies evaluating the cross talks between inflammatory stimulus and UV-A exposure on the levels of redox misbalance and inflammation. In here, we evaluated the effects of UV-A exposure on J774 macrophage cells previously challenged with LPS in terms of oxidative distress, release of pro-inflammatory cytokines, and activation of regulated cell death pathways. Our results showed that LPS potentiates the dose-dependent UV-A-induced oxidative distress and cytokine release, in addition to amplifying the regulated (autophagy and apoptosis) and non-regulated (necrosis) mechanisms of cell death, indicating that a previous inflammatory stimulus potentiates UV-A-induced cell damage. We discuss these results in terms of the current-available skin care strategies.

Mixed-Cell Type Choroidal Melanoma in a Middle-Aged Woman / Melanoma de Coroide do Tipo Misto em uma Mulher de Meia-Idade / Melanoma Coroideo de Tipo Mixto en una Mujer de Mediana Edad

Introduction: Melanomas are malignant neoplasms that occur in various anatomical sites, including the eye. Ocular melanomas account for 5% of all melanomas and are mainly described in Caucasian and older individuals. This study describes the clinical and pathological characteristics of uveal (choroid) melanoma in a Caucasian patient. Case report: A 41-year-old Caucasian female patient, brown eyes, without history of ophthalmological diseases or family history of cancer experienced pain and loss of visual acuity in the left eye. On clinical examination, an increase of ocular pressure was detected. Ultrasound showed a mushroom-like neoformation. Moreover, magnetic resonance imaging showed a mass with spontaneous hypersignal on T1-weighted images, intense gadolinium enhancement, and marked hyposignal on T2-weighted images. The patient was referred to the Oncology Ophthalmology department for enucleation due to suspected uveal melanoma. Anatomopathological analysis revealed a blackened mass in the eyeball. Histologically, the mass comprised spindle cells (50%) and epithelioid cells (50%). A diagnosis of choroidal melanoma was established based on the identification of ophthalmoscopic, imaging, and histological characteristics of the tumor. Conclusion: Choroidal melanomas usually occur in males, clear-eyed, and older individuals. A wide variety of ocular lesions may mimic choroidal melanoma, which should be included in the differential diagnosis of choroidal nevus and peripheral hemorrhages

Introdução: Melanomas são neoplasias malignas que ocorrem em vários sítios anatômicos, incluindo o olho. Os melanomas oculares correspondem a 5% de todos os melanomas e são descritos principalmente em indivíduos caucasianos e idosos. Este estudo descreve as características clinicopatológicas de um caso de melanoma uveal (coroide) em um paciente caucasiano. Relato do caso: Paciente, sexo feminino, 41 anos, caucasiana, olhos castanhos, sem antecedentes de doenças oftalmológicas e sem história familiar de câncer, com queixa de dor e perda da acuidade visual no olho esquerdo. No exame clínico, observou-se aumento da pressão ocular. O ultrassom revelou neoformação com aspecto de cogumelo, e a ressonância magnética, massa com hipersinal espontâneo em T1, intenso realce pelo gadolínio e marcado hipossinal em T2. A paciente foi encaminhada para cirurgia de enucleação em razão da suspeita de melanoma uveal. Foi realizada análise anatomopatológica que evidenciou massa enegrecida no interior do globo ocular. Histologicamente, a massa era constituída por 50% de células fusiformes e 50% de células epitelioides. O diagnóstico de melanoma de coroide baseou-se nas características oftalmoscópicas, imaginológicas e histológicas do tumor. Conclusão: Melanomas de coroide geralmente ocorrem em pacientes do sexo masculino, de olhos claros e idosos. Alerta-se que uma grande variedade de lesões oculares pode se assemelhar ao melanoma de coroide e este deve ser considerado no diagnóstico diferencial de nevo de coroide e hemorragias periféricas

Introducción: Los melanomas son neoplasias malignas que se presentan en varios sitios anatómicos, incluido el ojo. Los melanomas oculares representan el 5% de todos los melanomas y se describen principalmente en individuos caucásicos y de mayor edad. Este estudio describe las características clínicas y patológicas del melanoma uveal (coroides) en un paciente caucásico. Informe del caso: Paciente femenino de 41 años, caucásica, ojos marrones, sin antecedentes de enfermedades oftalmológicas y sin antecedentes familiares de cáncer, que consulta por dolor y pérdida de agudeza visual en el ojo izquierdo. En el examen clínico se observó aumento de la presión ocular. La ecografía mostró una neoformación con aspecto de hongo y la resonancia magnética mostró una masa con hiperseñal espontánea en T1, realce intenso de gadolinio y marcada hiposeñal en T2. La paciente fue remitida para cirugía de enucleación por sospecha de melanoma uveal. Se realizó análisis anatomopatológico, el cual mostró una masa ennegrecida en el interior del globo ocular. Histológicamente, la masa constaba de un 50 % de células fusiformes y un 50 % de células epitelioides. El diagnóstico de melanoma de coroides se basó en las características oftalmoscópicas, imagenológicas e histológicas del tumor. Conclusión: Los melanomas coroideos generalmente ocurren en pacientes masculinos, de ojos claros y de edad avanzada. Se advierte que una amplia variedad de lesiones oculares puede asemejarse al melanoma coroideo, y esto debe incluirse en el diagnóstico diferencial de nevus coroideo y hemorragias periféricas

Neurobiological mechanisms of mood disorders: Stress vulnerability and resilience.

Stress is an important factor in the development of several human pathologies. The response of rodents and humans to stress depends on many factors; some people and rodents develop stress-related mood disorders, such as depression and anxiety in humans, depression-like and anxiety-like behavior in mice and rats, while others report no new psychological symptoms in response to chronic or acute stress, and are considered susceptible and resilient to stress, respectively. Resilience is defined as the ability to thrive in the face of adversity and is a learned process that can help protect against occupational stressors and mental illnesses. There is growing interest in the underlying mechanisms involved in resilience and vulnerability to depression caused by stress, and some studies have demonstrated that individual variability in the way animals and humans respond to stress depends on several mechanisms, such as oxidative stress, neuronal plasticity, immunology and genetic factors, among others not discussed in this review, this review provides a general overview about this mechanism.

Infecção do trato urinário: estudo de sensibilidade e resistência bacteriana em pacientes internados / Urinary tract infection: study of bacterial sensitivity and resistance in hospitalized patients

Infecção do Trato Urinário (ITU) é uma doença bacteriana que acomete principalmente o sexo feminino com maior prevalência em crianças e idosos. Os antibióticos possuem uma capacidade de inibir o crescimento bem como destruir as bactérias que causam a ITU. O uso de antibióticos sem condução do antibiograma tem aumentado o número de isolados resistentes. O foco deste estudo foi investigar a incidência e a resistência aos antibióticos das bactérias causadoras da ITU em hospitais de Colatina. Laudos da urocultura dos pacientes hospitalizados no período de 2015 a 2019 foram investigados. Faixa etária, sexo, agentes etiológicos mais freqüentes e resistência aos antibióticos foram analisados. A avaliação estatística foi realizada pelo programa Origin 8,0 a p<0,05. Os resultados mostraram maior incidência de ITU em crianças e idosos com acometimento maior em pacientes do sexo feminino (56%). Klebsiella pneumoniae (31%), Escherichia coli (29%), Enterococcus sp (20%), Pseudomonas aeruginosa (7%), Proteus (7%) e Stapylococcus coagulase negativa (6%) foram as bactérias mais prevalentes. Klebsiella pneumoniae mostrou-se resistente em 41% dos antibióticos administrados, Stapylococcus coagulase negativa 38%, Pseudomonas aeruginosa 30%, Proteus 29%, Escherichia coli 21% e Enterococcus sp 19%. Amicacina, gentamicina, imipenem e vancomicina foram os antibióticos mais eficazes para o tratamento da ITU. Pacientes internados em hospitais de Colatina com ITU apresentaram resistência bacteriana em torno de 40% para a maioria dos antibióticos administrados. Portanto faz-se necessário o uso do antibiograma para evitar o aumento da resistência bacteriana nos ambientes hospitalares de Colatina ­ ES (AU).

Urinary Tract Infection (UTI) is a bacterial disease that mainly affects females with a higher prevalence in children and the elderly. Antibiotics have an ability to inhibit growth as well as destroy the bacteria that cause UTI. The use of antibiotics without conducting the antibiogram has increased the number of resistant isolates. The focus of this study was to investigate the incidence and antibiotic resistance of bacteria that cause UTI in the Colatina hostitals. Uroculture reports of hospitalized patients from 2015 to 2019 were investigated. The statistical evaluation was performed using the Origin 8.0 program at p <0.05. The results showed a higher incidence of UTI in children and the elderly with greater number of female patients (56%). Klebsiella pneumoniae (31%), Escherichia coli (29%), Enterococcus sp (20%), Pseudomonas aeruginosa (7%), Proteus (7%) and Staphylococcus sp (6%) were the most prevalent. Klebsiella pneumoniae was resistant to 41% of antibiotics administered. The other bacteria showed 38% resistance to Stapylococcus sp, 30% Pseudomonas aeruginosa, 29% Proteus, 21% Escherichia coli and 19% Enterococcus sp. Amikacin, gentamicin, imipenem and vancomycin were the most effective antibiotics for the treatment of UTI. Patients admitted to Colatina hospitals with UTI showed bacterial resistance around 40% for most antibiotics administered. Therefore, it is necessary to use the antibiogram to avoid increasing bacterial resistance in hospital environments in Colatina - ES (AU)

Melanin photosensitization and the effect of visible light on epithelial cells.

Protecting human skin from sun exposure is a complex issue that involves unclear aspects of the interaction between light and tissue. A persistent misconception is that visible light is safe for the skin, although several lines of evidence suggest otherwise. Here, we show that visible light can damage melanocytes through melanin photosensitization and singlet oxygen (1O2) generation, thus decreasing cell viability, increasing membrane permeability, and causing both DNA photo-oxidation and necro-apoptotic cell death. UVA (355 nm) and visible (532 nm) light photosensitize 1O2 with similar yields, and pheomelanin is more efficient than eumelanin at generating 1O2 and resisting photobleaching. Although melanin can protect against the cellular damage induced by UVB, exposure to visible light leads to pre-mutagenic DNA lesions (i.e., Fpg- and Endo III-sensitive modifications); these DNA lesions may be mutagenic and may cause photoaging, as well as other health problems, such as skin cancer.

Efeitos da luz UV-A e visível em células da pele e no cabelo / Effects UV-A and visible light on skin cells and hair

A luz solar apresenta ondas eletromagnéticas em ampla faixa espectral, incluindo as regiões do ultravioleta (UV-C, UV-B, UV-A), visível e infravermelho. Cada região interage com a pele de forma dependente da fotofísica e da fotoquímica dos seus respectivos compostos absorvedores. A luz UV-A causa a geração de espécies reativas de oxigênio e de nitrogênio (EROs e ERNs) através da fotossensibilização de moléculas endógenas (co-enzimas de flavina, porfirinas, melaninas). Quando fotossensibilizadores produzem quantidades de EROs e ERNs maiores do que a capacidade celular de supressão destas espécies, caracteriza-se um quadro de desbalanço redox, que causa lesão em biomoléculas como os ácidos nucleicos, lipídeos e as proteínas. Essas lesões podem levar à morte celular ou a outras transformações fenotípicas e genotípicas e também estimulam a liberação de citocinas pró-inflamatórias. Com a finalidade de melhor compreender a dinâmica dos mecanismos de resposta celular após exposição ao UV-A e ao visível, nós caracterizamos inicialmente as propriedades fotofísicas da melanina e detectamos a produção de oxigênio singlete (1O2) pela fotossensibilização no visível e a supressão desta espécie excitada pela reação do oxigênio singlete com a dupla ligação reativa dos grupos indóis presentes na melanina. Estes processos também foram observados no cabelo e levaram-nos a propor um modelo que explica o efeito da luz visível na estrutura e cor dos cabelos. Demonstramos também que a feomelanina produz mais (30%) 1O2 do que a eumelanina, que sofre maior modificação na sua estrutura por fotodegradação. O efeito destes processos na pele foi estudado a nível celular. Demonstramos que células epiteliais com maior teor de melanina apresentaram maior geração de 1O2 que causa lesão no DNA e morte necro-apoptótica após irradiação com luz visível. A foto-oxidação da melanina pela luz visível nos motivou a estudar um pigmento que fosse foto-protetor não somente contra luz UV-B mas também contra luz visível. A pigmentação com Acetil-Tirosina se mostrou atóxica e protetora contra luz UV-B e visível ao contrário do pigmento com tirosina, que se mostrou protetor do UV-B mas tóxico no visível. Este efeito foi relacionado com a localização celular do polímero e não com a estrutura do mesmo. A luz UV-A, por sua vez, promove o acúmulo de lipofuscina dentro dos vacúolos autofágicos de queratinócitos da pele e que também ativa a fototoxicidade pela luz visível. A lipofuscina dentro dos vacúolos autofágicos é foto-oxidada pela luz visível, causando lesão no DNA e morte celular programada tipo II. Doses UV-A que desencadeiam a liberação de citocinas também foram caracterizados

Sunlight presents electromagnetic radiation over a wide spectral range, including the regions of ultraviolet (UV-C, UV-B, UV-A), visible and infrared. Each region interacts with skin dependending on the photophysics and photochemistry of the respective absorbing compounds. UV-A light causes the generation of reactive oxygen and nitrogen species (ROS and RNS) by photosensitization of endogenous molecules (flavin coenzymes, porphyrins, melanins). When photosensitizers produce amounts of ROS and RNS larger than the cell capacity to suppress these species, a set of redox imbalance, which damages biomolecules such as nucleic acids, lipids and proteins. This damage cause cell death and to other phenotypic and genotypic changes and also stimulates the release of proinflammatory cytokines. In order to better understand the dynamics of the mechanisms of cellular responses after exposure to UV-A and visible light, we initially characterized the photophysical properties of melanin and detected the production of singlet oxygen (1O2) by photosensitization in the visible, as well as the suppression of these excited species by reaction of singlet oxygen with the double bonds of the reactive groups presented in the melanin indols. These processes were also observed in hair and led us to propose a model that explains the effects of visible light on the structure and color of hair. We also demonstrated that pheomelanin produces more (30%) 1O2 than eumelanin, which undergoes a quick change on its structure by photodegradation. The effect of these processes in the skin was studied at the cellular level. We demonstrated that epithelial cells with larger melanin content have stronger generation of 1O2, which causes DNA damage and necro-apoptotic death after irradiation with visible light. The photo-oxidation of melanin by visible light has motivated us to study a pigment that was not only able to protect against UV-B but also against visible. Pigmentation with Acetyl-Tyrosine proved nontoxic and protective against UV-B and visible light instead of pigmentation with Tyrosine, which shielded against UV-B but showed toxicity in the visible. This effect was associated with the polymer, cell location and not with its structure. UV-A light, in turn, promotes the accumulation of lipofuscin, within autophagic vacuoles of keratinocytes also enabling phototoxicity in the visible light. The lipofuscin within the autophagic vacuoles is fotooxidized by visible light, causing DNA damage and programmed cell death type II. Linear dose of UV-A that trigger the release of cytokines were also characterized

Quercetin as a shuttle for labile iron.

The antioxidant activity of flavonoids may involve their ability to complex body iron in non-redox-active forms. In this study, it was found that the catechol flavonoids rutin and quercetin are able to suppress redox-active labile plasma iron (LPI) in both buffered solution and in iron-overloaded sera. Both flavonoids are effective in loading the metal into the iron-transport protein transferrin. Iron derivatives of quercetin and rutin are able to permeate cell membranes, however, only free quercetin is able to gain access to the cytosol and decrease intracellular labile iron pools. These results suggest that the antioxidant activity of quercetin may be dependent on its ability to shuttle labile iron from cell compartments followed by its transfer to transferrin.

Retrospective study on Porcine circovirus-2 by nested pcr and real time pcr in archived tissues from 1978 in Brazil

Porcine circovirus-2 (PCV-2) infection is currently considered an important disease of swine. The pathogenic agent was first described in Brazil in 2000. This study detected the PCV-2 DNA in four Brazilian pig tissues collected between 1978 and 1979. This observation is the oldest description of this virus in Brazil.

Generation and suppression of singlet oxygen in hair by photosensitization of melanin.

We have studied the spectroscopic properties of hair (white, blond, red, brown, and black) under illumination with visible light, giving special emphasis to the photoinduced generation of singlet oxygen ((1)O(2)). Irradiation of hair shafts (λ(ex)>400 nm) changed their properties by degrading the melanin. Formation of C3 hydroperoxides in the melanin indol groups was proven by (1)H NMR. After 532-nm excitation, all hair shafts presented the characteristic (1)O(2) emission (λ(em)=1270 nm), whose intensity varied inversely with the melanin content. (1)O(2) lifetime was also shown to vary with hair type, being five times shorter in black hair than in blond hair, indicating the role of melanin as a (1)O(2) suppressor. Lifetime ranged from tenths of a nanosecond to a few microseconds, which is much shorter than the lifetime expected for (1)O(2) in the solvents in which the hair shafts were suspended, indicating that (1)O(2) is generated and suppressed inside the hair structure. Both eumelanin and pheomelanin were shown to produce and to suppress (1)O(2), with similar efficiencies. The higher amount of (1)O(2) generated in blond hair and its longer lifetime is compatible with the stronger damage that light exposure causes in blond hair. We propose a model to explain the formation and suppression of (1)O(2) in hair by photosensitization of melanin with visible light and the deleterious effects that an excess of visible light may cause in hair and skin.

Development and evaluation of a recombinant DNA vaccine candidate expressing porcine circovirus 2 structural protein: [revision] / Desenvolvimento e avaliação de um candidato à vacina de DNA recombinante expressando a proteína estrutural do circovírus suíno: [revisão]

Porcine circovirus 2 (PCV2) is generally associated with the porcine circovirosis syndrome, which is considered an important disease of swine and has potentially serious economic impact on the swine industry worldwide. This article describes the construction of a recombinant plasmid expressing the PCV2 structural protein and the evaluation of cellular and humoral immune responses produced by this recombinant vaccine in BALB/c mice. The vaccine candidate was obtained and analyzed in vivo, in an effort to determine the ability to induce a specific immune response in mice. DNA was extracted from a Brazilian PCV2 isolate and the gene coding for Cap protein was amplified by PCR and inserted into an expression plasmid. Groups of BALB/c mice were inoculated intra-muscularly and intradermally in a 15-day interval, with 100 µg and 50 µg of the vaccine construct, respectively. Another group was inoculated intramuscularly with 100 µg of empty plasmid, corresponding to the control group. Seroconversion and cellular response in BALB/c mice were compared and used for vaccine evaluation. Seroconversion was analyzed by ELISA. After a series of 3 immunizations the spleen cells of the immunized animals were used to perform lymphocyte proliferation assays. Seroconversion to PCV2 was detected by ELISA in the animals inoculated with the vaccine construct when compared with control groups. Lymphocyte proliferation assays showed a stronger cell proliferation in the inoculated animals compared with the control group. Thus, the vaccine candidate construct demonstrated to be able to induce both humoral and cellular responses in inoculated mice.

O circovírus suíno 2 (PCV2) é geralmente associado à síndrome da circovirose suína, que é considerada uma importante doença de suínos e possui um sério impacto econômico na suinocultura mundial. Este trabalho descreve a construção de um plasmídeo recombinante que expressa a proteína estrutural do PCV2 e a avaliação das respostas imune humoral e celular por meio de vacinação em camundongos BALB/c. O candidato vacinal foi submetido a análises in vivo, determinando a capacidade de induzir resposta imune específica em camundongos. O DNA de um isolado brasileiro de PCV2 foi extraído e o gene que codifica para a proteína do capsídeo foi amplificado por PCR e inserido num plasmídeo de expressão. Grupos de camundongos BALB/c foram inoculados por via intramuscular e intradérmica a cada 15 dias, com 100µg e 50µg da construção vacinal, respectivamente. Outro grupo foi inoculado com 100µg do plasmídeo original, correspondente ao grupo controle. A soroconversão e a resposta celular dos grupos de camundongos BALB/c vacinados foram comparados como parâmetros de avaliação vacinal. A soroconversão foi avaliada por um teste de ELISA. Após 3 imunizações, as células esplênicas dos animais imunizados foram utilizadas nos ensaios de linfoproliferação. A soroconversão para o PCV2 foi detectada por ELISA nos animais inoculados com a construção vacinal quando comparados com o grupo controle. Nos ensaios de linfoproliferação foi observada uma grande proliferação celular nos animais inoculados comparados ao grupo controle. Portanto, o candidato vacinal demonstrou ser capaz de induzir tanto uma resposta humoral e celular nos camundongos inoculados.