Melatonin as a natural anti-inflammatory and anti-oxidant therapy in the testis: a focus on infertility and aging†.

Melatonin is a pineal hormone that regulates testicular activity (i.e., steroidogenesis and spermatogenesis) through two complementary mechanisms, indirect effects exerted via the hypothalamic-adenohypophyseal axis and direct actions that take place on the different cell populations of the male gonad. The effects of increased age on the testis and the general mechanisms involved in testicular pathology leading to infertility are still only poorly understood. However, there is growing evidence that link testicular aging and idiopathic male infertility to local inflammatory and oxidative stress events. Because literature data strongly indicate that melatonin exhibits anti-inflammatory and anti-oxidant properties, this review focuses on the potential benefits exerted by this indoleamine at testicular level in male reproductive fertility and aging. Taking into account that the effects of melatonin supplementation on testicular function are currently being investigated, the overview covers not only promising prospects but also many questions concerning the future therapeutic value of this indoleamine as an anti-aging drug as well as in the management of cases of male infertility for which there are no medical treatments currently available.

Glioprotective Effects of Sulforaphane in Hypothalamus: Focus on Aging Brain.

Sulforaphane is a natural compound with neuroprotective activity, but its effects on hypothalamus remain unknown. In line with this, astrocytes are critical cells to maintain brain homeostasis, and hypothalamic astrocytes are fundamental for sensing and responding to environmental changes involved in a variety of homeostatic functions. Changes in brain functionality, particularly associated with hypothalamic astrocytes, can contribute to age-related neurochemical alterations and, consequently, neurodegenerative diseases. Thus, here, we investigated the glioprotective effects of sulforaphane on hypothalamic astrocyte cultures and hypothalamic cell suspension obtained from aged Wistar rats (24 months old). Sulforaphane showed anti-inflammatory and antioxidant properties, as well as modulated the mRNA expression of astroglial markers, such as aldehyde dehydrogenase 1 family member L1, aquaporin 4, and vascular endothelial growth factor. In addition, it increased the expression and extracellular levels of trophic factors, such as glia-derived neurotrophic factor and nerve growth factor, as well as the release of brain-derived neurotrophic factor and the mRNA of TrkA, which is a receptor associated with trophic factors. Sulforaphane also modulated the expression of classical pathways associated with glioprotection, including nuclear factor erythroid-derived 2-like 2, heme oxygenase-1, nuclear factor kappa B p65 subunit, and AMP-activated protein kinase. Finally, a cell suspension with neurons and glial cells was used to confirm the predominant effect of sulforaphane in glial cells. In summary, this study indicated the anti-aging and glioprotective activities of sulforaphane in aged astrocytes.

Renin-angiotensin system inhibitors positively impact on multiple aging regulatory pathways: Could they be used to protect against human aging?

The renin-angiotensin system (RAS)-a classical blood pressure regulator-largely contributes to healthy organ development and function. Besides, RAS activation promotes age-related changes and age-associated diseases, which are attenuated/abolished by RAS-blockade in several mammalian species. RAS-blockers also increase rodent lifespan. In previous work, we discussed how RAS-blockade downregulates mTOR and growth hormone/IGF-1 signaling, and stimulates AMPK activity (together with klotho, sirtuin, and vitamin D-receptor upregulation), and proposed that at least some of RAS-blockade's aging benefits are mediated through regulation of these intermediaries and their signaling to mitochondria. Here, we included RAS-blockade's impact on other aging regulatory pathways, that is, TGF-ß, NF-kB, PI3K, MAPK, PKC, Notch, and Wnt, all of which affect mitochondria. No direct evidence is available on RAS/RAS-blockade-aging regulatory pathway-mitochondria interactions. However, existing results allow to conjecture that RAS-blockers neutralize mitochondrial dysfunction by acting on the discussed pathways. The reviewed evidence led us to propose that the foundation is laid for conducting clinical trials aimed at testing whether angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB)-even at subclinical doses-offer the possibility to live longer and in better health. As ACEi and ARB are low cost and well-tolerated anti-hypertension therapies in use for over 35 years, investigating their administration to attenuate/prevent aging effects seems simple to implement.

Histological investigation in aging male and female gerbil prostates after prenatal exposure to pequi (Caryocar brasiliense Cambess) oil and 17α-ethinylestradiol.

The female prostate, also known as Skene's gland, is present in both humans and rodents. Prenatal exposure to ethinylestradiol (EE2), a synthetic estrogen found in oral contraceptives, induces pormotes neoplasic prostate lesions in gerbils (Meriones unguiculatus). Conversely, pequi oil (Pe), extracted from the Brazilian Cerrado fruit, has antioxidant, anti-inflammatory, and anticancer properties, mitigates risks associated with chronic diseases related to lifestyle and aging. This study evaluates the impact of prenatal exposure to Pe (300 mg/kg) on senile gerbil offspring's male and female prostates under normal conditions and EE2 exposure (15 µg/kg/day). Histological and morphometric analyses revealed that Pe reduced male body weight and prostate epithelial height, along with a thinner muscle layer. In females, EE2 exposure reduced prostatic weight, while Pe exposure lowered epithelial height and the relative stromal compartment volume, increasing the muscle layer. Pequi oil holds potential in mitigating alterations induced by exposure to the endocrine disruptor EE2.

The anti-aging, anti-tuberculosis and antioxidant potential benefits of Saudi Arabia Olea-Europaea Leaves extracts / Potenciais benefícios antienvelhecimento, antituberculose e antioxidantes dos extratos de folhas de Olea-Europaea da Arábia Saudita

The olive leaf extract and olive leaf indicated a high potential for application in food additives and foodstuffs. It could be these bio-products useful and important in condition therapy related with oxidative stress and can use it to develop functional foods and to improve the food's shelf life. The olive leaf chemical composition of Oleaeuropaea L. grown from eljouf in Saudi Arabia, using solvents of increasing polarity cyclohexane, dichloromethane, chloroform, ethyl acetate, methanol and ethanol was determined using by GC/MS. Furthermore, the antioxidant activity (diphenylpicrylhydrazyl (DPPH), anti-aging, and anti-tuberculosis of olive leaf extracts were evaluated. The results indicated that extract of Oleaeuropaea L. has a considerable contains in polyphenols (hydroxytyrosol, oleuropein and their derivatives) regarding its antioxidant effects, the major components were detected by GC/MS in Olea dichloromethane extract are Hexadecanoic acid (15.82%), 7(4Dimethylaminophenyl)3,3,12trimethyl3,12dihydro6 Hpyrano[2,3c]acridin 6 one (11.21%), and in Olea chloroform extract are Hexatriacontane (12.68%), nTetratr iacontane (10.95%). The results concluded that the plant extract of chloroform showed no anti-aging activities and the lower anti-aging activities for cyclohexane extract, while, the Olea dichloromethane extract was the most active extract. The obtained data confirmed that the most active extract of anti-tubercolisis was for chloroform and ethyl acetate extract, while, anti-tubercolisis activity of ethanolic extract was the lower. The extract amount as well as the solvent polarity influence the inhibitory activity. A favorable connection was demonstrated inter alia the leaf extracts antioxidant activity and the content of total phenol.

O extrato de folha de oliveira e a folha de oliveira indicaram alto potencial para aplicação em aditivos alimentares e alimentos. Esses bioprodutos podem ser úteis e importantes na terapia de condições relacionadas ao estresse oxidativo e podem ser utilizados para desenvolver alimentos funcionais e melhorar a vida útil dos alimentos. A composição química da folha de oliveira de Olea europaea L. cultivada em Eljouf na Arábia Saudita, usando solventes de polaridade crescente ciclohexano, diclorometano, acetato de etil clorofórmio, metanol e etanol foi determinada usando GC/MS. Além disso, foi avaliada a atividade antioxidante (difenilpicrilhidrazil - DPPH) antienvelhecimento e antituberculose de extratos de folha de oliveira. Os resultados indicaram que o extrato de Olea europaea L. que consideravelmente possui polifenois (hidroxitirosol, oleuropeína e seus derivados) quanto aos seus efeitos antioxidantes, os componentes majoritários detectados por GC/MS no extrato diclorometânico de Olea são o ácido hexadecanoico (15,82%), 7-(4-Dimetilaminofenil)-3,3,12-trimetil-3,12-dihidro-6H-pirano[2,3c]acridin-6-ona (11,21%) e no extrato de clorofórmio de Olea são Hexatriacontane (12,68%), nTetratr iacontane (10,95%). Os resultados concluíram que o extrato vegetal de clorofórmio não apresentou atividades antienvelhecimento e as atividades antienvelhecimento mais baixas para o extrato de cicloexanona, enquanto o extrato de Olea diclorometano foi o extrato mais ativo. Os dados obtidos confirmaram que o extrato mais ativo de antituberculose foi para clorofórmio e extrato de acetato de etila, enquanto a atividade antituberculose de extrato etanoico foi menor. A quantidade de extrato, bem como a polaridade do solvente influenciam a atividade inibitória, atividade e o teor de fenol total.

Uso de hidroxiapatita de cálcio no tratamento da dermatoporose / Use of calcium hydroxyapatite in the treatment of dermatoporosis

A dermatoporose é a síndrome de fragilidade cutânea. Acomete principalmente indivíduos acima de 60 anos, com maior prevalência no sexo feminino. Os principais fatores de risco são: envelhecimento, exposição solar intensa e uso de corticoterapia tópica e sistêmica. Se manifesta clinicamente por atrofia cutânea, púrpuras senis, pseudo cicatrizes estrelares e lacerações, podendo evoluir com hematomas dissecantes e infecções graves. Trata-se de uma doença com grande impacto na qualidade de vida dos pacientes e, até o presente momento, não há terapias com resultados satisfatórios. Hidratação, vitamina C tópica e oral, luz intensa pulsada foram algumas das terapêuticas estudadas. A hidroxiapatita de cálcio é um bioestimulador de colágeno composto por microesferas em um veículo de carboximetilcelulose (Radiesse®). Tem sido usada para estimular a produção endógena de colágeno e consequentemente melhorar a qualidade e espessura da pele. Este efeito do produto poderia melhorar o quadro clínico da dermatoporose. O estudo teve como objetivo avaliar a melhora das lesões purpúricas e da atrofia da pele após aplicação de Radiesse® no antebraço de 5 pacientes portadores de dermatoporose no setor de Dermatologia do Hospital do Servidor Público Municipal de São Paulo. Os 5 pacientes foram submetidos a aplicação de Radiesse® nos antebraços e foram avaliadas 45 e 90 dias após o procedimento, o número de lesões purpúricas, grau de atrofia da pele através do teste de pinçamento e realizado comparação fotográfica. Após o tratamento, observou-se melhora do número das lesões purpúricas, melhora da atrofia da pele e melhora da qualidade de pele quando comparada fotograficamente. Dessa forma, o tratamento com Radiesse® mostrou-se promissor, com resultados satisfatórios e com um bom perfil de segurança. Palavras-chave: Dermatoporose. Púrpura senil. Radiesse. Bioestimulador. Tratamento.

Estratégias anti-aging baseadas em moléculas químicas naturais como potentes ativadores de telomerase / Anti-aging strategies based on natural chemical molecules as potent telomerase activators / Estrategias antienvejecimiento basadas en moléculas químicas naturales como potentes activadores de la telomerasa

Mesmo em tempos modernos, os grandes avanços tecnológicos não permitem de forma comprovada retardar o envelhecimento nos seres humanos. Neste sentido, uma das estratégias é o uso moléculas químicas naturais que possuem a ação de ativadores de telomerase, uma vez de que a telomerase é uma ribonucleoproteína transcriptase reversa que possui a função de alongar os telômeros e neutralizar a erosão normal dos telômeros. Neste contexto, este estudo de revisão dedicou-se a aprofundar o conhecimento sobre o uso de moléculas químicas naturais derivadas de plantas que possuem função de ativadores de telomerase para atividade anti-aging. Inúmeras moléculas têm sido propostas e, estudas os seus mecanismos com o intuito de desenvolver novas ferramentas para prevenir/retardar e tratar doenças relacionadas a idade e o envelhecimento. Adicionalmente, o uso de moléculas como ativadores da telomerase têm sido um meio de prolongar o encurtamento dos temoleros, como no caso, de moléculas isolada da erva Astragalus membranaceus (TA-65), curcumina, silbinina e alicina; ademais, outras moléculas de origem natural possuem atividade anti-aging comprovadas, conforme reportadas nesta revisão. Sendo assim, a procura por biomarcadores à base de compostos químicos naturais que estimulem a telomerase, a fim de prolongar a vida dos telômero e assim, retardar o processo de envelhecimento do organismo têm despertado o interesse de diversos pesquisadores ao redor do mundo.

Even in modern times, the great technological advances do not allow in a proven way to delay aging in humans. In this sense, one of the strategies is the use of natural chemical molecules that have telomerase activators, since telomerase is a ribonucleoprotein reverse transcriptase that has the function of lengthening telomeres and neutralizing the normal erosion of telomeres. In this context, this review study was dedicated to deepening the knowledge about the use of natural chemical molecules derived from plants that have telomerase activator function for anti-aging activity. Numerous molecules have been proposed and their mechanisms studied in order to develop new tools to prevent/delay and treat aging-related diseases. Additionally, the use of molecules as telomerase activators has been a means of prolonging the shortening of temolers, as in the case of molecules isolated from the herb Astragalus membranaceus (TA-65), curcumin, silbinin and allicin; in addition, other molecules of natural origin have proven anti-aging activity, as reported in this review. Therefore, the search for biomarkers based on natural chemical compounds that stimulate telomerase in order to prolong the life of telomeres and, thus delay the aging process of the organism has aroused the interest of several researchers around the world.

Aún en los tiempos modernos, los grandes avances tecnológicos no permiten de manera comprobada retrasar el envejecimiento en los humanos. En este sentido, una de las estrategias es el uso de moléculas químicas naturales que tengan activadores de la telomerasa, ya que la telomerasa es una ribonucleoproteína transcriptasa inversa que tiene la función de alargar los telómeros y neutralizar la erosión normal de los telómeros. En este contexto, este estudio de revisión se dedicó a profundizar en el conocimiento sobre el uso de moléculas químicas naturales derivadas de plantas que tienen función activadora de la telomerasa para la actividad antienvejecimiento. Se han propuesto numerosas moléculas y se han estudiado sus mecanismos para desarrollar nuevas herramientas para prevenir/retrasar y tratar enfermedades relacionadas con el envejecimiento. Adicionalmente, el uso de moléculas como activadores de la telomerasa ha sido un medio para prolongar el acortamiento de temolers, como es el caso de moléculas aisladas de la hierba Astragalus membranaceus (TA-65), curcumina, silbinina y alicina; además, otras moléculas de origen natural han demostrado actividad antienvejecimiento, como se reporta en esta revisión. Por ello, la búsqueda de biomarcadores basados en compuestos químicos naturales que estimulen la telomerasa para prolongar la vida de los telómeros y así retrasar el proceso de envejecimiento del organismo ha despertado el interés de varios investigadores a nivel mundial.

Skincare application of medicinal plant polysaccharides - A review.

Polysaccharides are macromolecules with important inherent properties and potential biotechnological applications. These complex carbohydrates exist throughout nature, especially in plants, from which they can be obtained with high yields. Different extraction and purification methods may affect the structure of polysaccharides and, due to the close relationship between structure and function, modify their biological activities. One of the possible applications of these polysaccharides is acting on the skin, which is the largest organ in the human body and can be aged by intrinsic and extrinsic processes. Skincare has been gaining worldwide attention not only to prevent diseases but also to promote rejuvenation in aesthetic treatments. In this review, we discussed the polysaccharides obtained from plants and their innovative potential for skin applications, for example as wound-healing, antimicrobial, antioxidant and anti-inflammatory, antitumoral, and anti-aging compounds.

Graptopetalum paraguayense Extract Ameliorates Proteotoxicity in Aging and Age-Related Diseases in Model Systems.

Declines in physiological functions are the predominant risk factors for age-related diseases, such as cancers and neurodegenerative diseases. Therefore, delaying the aging process is believed to be beneficial in preventing the onset of age-related diseases. Previous studies have demonstrated that Graptopetalum paraguayense (GP) extract inhibits liver cancer cell growth and reduces the pathological phenotypes of Alzheimer's disease (AD) in patient IPS-derived neurons. Here, we show that GP extract suppresses ß-amyloid pathology in SH-SYS5Y-APP695 cells and APP/PS1 mice. Moreover, AMP-activated protein kinase (AMPK) activity is enhanced by GP extract in U87 cells and APP/PS1 mice. Intriguingly, GP extract enhances autophagy in SH-SYS5Y-APP695 cells, U87 cells, and the nematode Caenorhabditis elegans, suggesting a conserved molecular mechanism by which GP extract might regulate autophagy. In agreement with its role as an autophagy activator, GP extract markedly diminishes mobility decline in polyglutamine Q35 mutants and aged wild-type N2 animals in C. elegans. Furthermore, GP extract significantly extends lifespan in C. elegans.

Black Bean (Phaseolus vulgaris L.) Polyphenolic Extract Exerts Antioxidant and Antiaging Potential.

Phenolic compounds present in common beans (Phaseolus vulgaris L.) have been reported to possess antimicrobial, anti-inflammatory and ultraviolet radiation (UVR) protective properties. UVR from sunlight, which consists of UV-B and UV-A radiations, induces reactive oxygen species (ROS) and free radical formation, consequently activating proteinases and enzymes such as elastase and tyrosinase, leading to premature skin aging. The objective of this work was to extract, characterize and evaluate the antioxidant and antiaging potential of polyphenols from a black bean endemic variety. The polyphenolic extract was obtained from black beans by supercritical fluid extraction (SFE) using CO2 with a mixture of water-ethanol as a cosolvent and conventional leaching with a mixture of water-ethanol as solvent. The polyphenolic extracts were purified and characterized, and antioxidant potential, tyrosinase and elastase inhibitory potentials were measured. The extract obtained using the SFE method using CO2 and H2O-Ethanol (50:50 v/v) as a cosolvent showed the highest total phenolic compounds yield, with 66.60 ± 7.41 mg GAE/g coat (p > 0.05) and 7.30 ± 0.64 mg C3GE/g coat (p < 0.05) of anthocyanins compared to conventional leaching. Nineteen tentative phenolic compounds were identified in leaching crude extract using ESI-QTOF. Quercetin-3-D-galactoside was identified in crude and purified extracts. The purified SFC extract showed IC50 0.05 ± 0.002 and IC50 0.21 ± 0.008 mg/mL for DPPH and ABTS, respectively. The lowest IC50 value of tyrosinase inhibition was 0.143 ± 0.02 mg/mL and 0.005 ± 0.003 mg/mL of elastase inhibition for leaching purified extract. Phenolic compounds presented theoretical free energy values ranging from -5.3 to -7.8 kcal/mol for tyrosinase and -2.5 to -6.8 kcal/mol for elastase in molecular docking (in silico) studies. The results suggest that the purified extracts obtained by SFE or conventional leaching extraction could act as antioxidant and antiaging ingredients for cosmeceutical applications.

Characterization of the onset of leptin effects on the regulation of energy balance.

Leptin is a hormone required for the regulation of body weight in adult animals. However, during the postnatal period, leptin is mostly involved in developmental processes. Because the precise moment at which leptin starts to exert its metabolic effects is not well characterized, our objective was to identify the approximate onset of leptin effects on the regulation of energy balance. We observed that male Lepob/ob mice started to exhibit increased body fat mass from postnatal day 13 (P13), whereas in females, the increase in adiposity began on P20. Daily leptin injections from P10 to P22 did not reduce the weight gain of WT mice. However, an acute leptin injection induced an anorexigenic response in 10-day-old C57BL/6 mice but not in 7-day-old mice. An age-dependent increase in the number of leptin receptor-expressing neurons and leptin-induced pSTAT3 cells was observed in the hypothalamus of P7, P10 and P16 mice. Leptin deficiency started to modulate the hypothalamic expression of transcripts involved in the regulation of metabolism between P7 and P12. Additionally, fasting-induced hypothalamic responses were prevented by leptin replacement in 10-day-old mice. Finally, 12-day-old males and females showed similar developmental timing of axonal projections of arcuate nucleus neurons in both WT and Lepob/ob mice. In summary, we provided a detailed characterization of the onset of leptin's effects on the regulation of energy balance. These findings contribute to the understanding of leptin functions during development.

D-(+)-Galactose-induced aging: A novel experimental model of erectile dysfunction.

Erectile dysfunction (ED) is defined as the inability to achieve and/or maintain penile erection sufficient for satisfactory sexual relations, and aging is one of the main risk factors involved. The D-(+)-Galactose aging model is a consolidated methodology for studies of cardiovascular aging; however, its potential for use with ED remain unexplored. The present study proposed to characterize a new experimental model for ED, using the D-(+)-Galactose aging model. For the experiments, the animals were randomly divided into three groups receiving: vehicle (CTL), D-galactose 150 mg/kg (DGAL), and D-(+)-galactose 150 mg/Kg + sildenafil 1.5 mg/Kg (DGAL+SD1.5) being administered daily for a period of eight weeks. All of the experimental protocols were previously approved by the Ethics Committee on the Use of Animals at the Federal University of Paraíba n° 9706070319. During the treatment, we analyzed physical, molecular, and physiological aspects related to the aging process and implicated in the development of ED. Our findings demonstrate for the first time that D-(+)-Galactose-induced aging represents a suitable experimental model for ED assessment. This was evidenced by an observed hyper-contractility in corpora cavernosa, significant endothelial dysfunction, increased ROS levels, an increase in cavernous tissue senescence, and the loss of essential penile erectile components.

Docosahexaenoic and Arachidonic Acids as Neuroprotective Nutrients throughout the Life Cycle.

The role of docosahexaenoic acid (DHA) and arachidonic acid (AA) in neurogenesis and brain development throughout the life cycle is fundamental. DHA and AA are long-chain polyunsaturated fatty acids (LCPUFA) vital for many human physiological processes, such as signaling pathways, gene expression, structure and function of membranes, among others. DHA and AA are deposited into the lipids of cell membranes that form the gray matter representing approximately 25% of the total content of brain fatty acids. Both fatty acids have effects on neuronal growth and differentiation through the modulation of the physical properties of neuronal membranes, signal transduction associated with G proteins, and gene expression. DHA and AA have a relevant role in neuroprotection against neurodegenerative pathologies such as Alzheimer's disease and Parkinson's disease, which are associated with characteristic pathological expressions as mitochondrial dysfunction, neuroinflammation, and oxidative stress. The present review analyzes the neuroprotective role of DHA and AA in the extreme stages of life, emphasizing the importance of these LCPUFA during the first year of life and in the developing/prevention of neurodegenerative diseases associated with aging.

Folic Acid Supplementation in the Gestational Phase of Female Rats Improves Age-Related Memory Impairment and Neuroinflammation in Their Adult and Aged Offspring.

Folic acid (FA) supplementation is important during pregnancy to avoid malformations in the offspring. However, it is unknown if it can affect the offspring throughout their lives. To evaluate the offspring, female mother rats (dams) were separated into 5 groups: Four groups received the AIN-93 diet, divided into control and FA (5, 10, and 50 mg/kg), and an additional group received a FA-deficient diet, and the diet was performed during pregnancy and lactation. We evaluated the female offspring of these dams (at 2 and 18 months old). The aged offspring fed with FA-deficient diet presented habituation, spatial and aversive memory impairment and the FA maternal supplementation prevented this. The natural aging caused an increase in the TNF-α and IL-1ß levels in the hippocampus from 18-month-old offspring. FA maternal supplementation was able to prevent the increase of these cytokines. IL-4 levels decreased in the prefrontal cortex from aged control rats and FA prevented it. FA deficiency decreased the levels of IL-4 in the hippocampus of the young offspring. In addition, natural aging and FA deficiency decreased brain-derived neurotrophic factor levels in the hippocampus and nerve growth factor levels in the prefrontal cortex and FA supplementation prevented it. Thus, the present study shows for the first time the effect of FA maternal supplementation on memory, cytokines, and neurotrophins in the aged offspring.

Efeito do polimento superficial a seco ou úmido sobre o brilho, rugosidade e desgaste de resina composta nanoparticulada antes e após envelhecimento artificial / Effect of dry or wet surface polishing on the gloss, roughness and wear of nanoparticulate composite resin before and after artificial aging

Este trabalho teve como objetivo investigar a rugosidade, o desgaste e o brilho superficial de uma resina composta nanoparticulada (Filtek Z350 XT - 3M ESPE), com diferentes sistemas de polimento a seco e lubrificado antes e após envelhecimento artificial. Foram confeccionados 100 espécimes de resina composta em forma de disco, divididos em: grupo controle (sem polimento) e em três sistemas de polimento (pontas de diamante de etapa única Dimanto - VOCO, discos de lixa Sof-Lex Pop-On - 3M ESPE - e escova de polimento com carbeto de silício nas cerdas Astrobrush - IVOCLAR VIVADENT). Os sistemas polidores foram empregados sem lubrificação, com água e com vaselina. Após a fase de envelhecimento por escovação, foi realizado o repolimento das amostras, exceto no grupo controle. Ao final de cada tempo do estudo (inicial, polimento, envelhecimento e repolimento), os grupos foram submetidos as leituras de rugosidade, desgaste e brilho, verificando assim a efetividade de cada sistema de polimento. Os dados referentes a cada avaliação quantitativa foram submetidos à análise estatística de variância de medidas repetidas. As comparações múltiplas foram realizadas por teste Pos-hoc de Tukey. Diferenças significantes foram determinadas por p < 0,05. Para as análises de brilho e rugosidade póspolimento o Dimanto não foi influenciado pelo uso ou não de lubrificantes. O Sof-Lex Pop-On obteve melhor desempenho sem utilização de lubrificante, enquanto a escova Astrobrush apresentou maiores valores de brilho e menor rugosidade quando lubrificada por água ou vaselina. Em relação ao desgaste superficial, o Dimanto foi melhor, quando associado a vaselina. O Sof-Lex PopOn apresentou menor desgaste, quando utilizado com água. A escova Astrobrush obteve o pior resultado quando lubrificada com vaselina. Portanto, o brilho, a rugosidade e o desgaste superficial dependem do polidor e da combinação com ou sem lubrificação(AU)

The aim of this study was to investigate the roughness, wear and surface gloss of a nanoparticulated resin composite (Filtek Z350 XT - 3M ESPE), with dry and lubricated polishing systems before and after artificial aging. One hundred resin composite specimens were fabricated in cylindrical shape, which was further divided into: control group (no polishing) and three polishing systems (One step diamond tips Dimanto -VOCO, Sof-Lex Pop-On -3M ESPE, and a silicon carbide polishing brush - Astrobrush -IVOCLAR VIVADENT). Polishing systems was used dry, with water or petroleum jelly. After aging by simulated tooth brushing, the samples' repolishing was carried out, except in the control group. After each study period (initial, polishing, aging and repolishing), the groups were subjected to roughness, wear and gloss, thus verifying the effectiveness of each polishing system. The data for each quantitative evaluation was submitted to repeated-measures analysis of variance. Multiple comparisons were performed by Tukey post-hoc test. Significant differences were determined by p <0.05. For post-polishing gloss and roughness analyzes, Dimanto was not influenced by the use or not of lubricants. Sof-Lex Pop-On achieved better performance without using lubricant, while the Astrobrush brush showed higher values of gloss and less roughness when lubricated by water or petroleum jelly. Regarding surface wear, Dimanto was better when associated with petroleum jelly. Sof-Lex Pop-On showed less wear when used with water. The Astrobrush brush obtained the worst result when lubricated with petroleum jelly. The brightness, roughness and surface wear depend on the polisher and the combination with or without lubrication(AU).

Rapamycin Eyedrops Increased CD4+Foxp3+ Cells and Prevented Goblet Cell Loss in the Aged Ocular Surface.

Dry eye disease (DED), one of the most prevalent conditions among the elderly, is a chronic inflammatory disorder that disrupts tear film stability and causes ocular surface damage. Aged C57BL/6J mice spontaneously develop DED. Rapamycin is a potent immunosuppressant that prolongs the lifespan of several species. Here, we compared the effects of daily instillation of eyedrops containing rapamycin or empty micelles for three months on the aged mice. Tear cytokine/chemokine profile showed a pronounced increase in vascular endothelial cell growth factor-A (VEGF-A) and a trend towards decreased concentration of Interferon gamma (IFN)-γ in rapamycin-treated groups. A significant decrease in inflammatory markers in the lacrimal gland was also evident (IFN-γ, IL-12, CIITA and Ctss); this was accompanied by slightly diminished Unc-51 Like Autophagy Activating Kinase 1 (ULK1) transcripts. In the lacrimal gland and draining lymph nodes, we also observed a significant increase in the CD45+CD4+Foxp3+ cells in the rapamycin-treated mice. More importantly, rapamycin eyedrops increased conjunctival goblet cell density and area compared to the empty micelles. Taken together, evidence from these studies indicates that topical rapamycin has therapeutic efficacy for age-associated ocular surface inflammation and goblet cell loss and opens the venue for new investigations on its role in the aging process of the eye.

Effects of (-)-epicatechin on neuroinflammation and hyperphosphorylation of tau in the hippocampus of aged mice.

Evidence has implicated oxidative stress (OS) and inflammation as drivers of neurodegenerative pathologies. We previously reported on the beneficial effects of (-)-epicatechin (Epi) treatment on aging-induced OS and its capacity to restore modulators of mitochondrial biogenesis in the prefrontal cortex of 26-month-old male mice. In the present study using the same mouse model of aging, we examined the capacity of Epi to mitigate hippocampus OS, inflammation, hyperphosphorylation of tau protein, soluble ß-amyloid protein levels, cell survival, memory, anxiety-like behavior levels and systemic inflammation. Mice were subjected to 4 weeks of Epi treatment (1 mg kg-1 day-1) and samples of the hippocampus were obtained. Assessments of the OS markers, protein carbonyls, and malondialdehyde levels demonstrated their significant increase (∼3 fold) with aging that were partially suppressed by Epi. The protein levels of the glial fibrillary acidic protein, inflammatory factor 1 (Iba1), pro-inflammatory cytokines, interleukins (IL-1ß, IL-3, 5, 6 and 15), cyclooxygenase 2, tumor necrosis factor α, nuclear factor-activated B cells and interferon γ increase with aging and were also significantly decreased with Epi treatment. However, anti-inflammatory cytokines, IL-1ra, IL-10 and 11 decrease with aging and were restored with Epi. Epi also reversed the aging effects on the hyperphosphorylation of tau, increased soluble ß-amyloid levels (∼2 fold), cellular death (as per caspase 3 and 9 activity), and reduced nerve growth factor and triggering receptor expressed on myeloid cells 2 levels. Measures of anxiety like-behavior and memory demonstrated improvements with Epi treatment. Indicators of systemic inflammation increase with aging and Epi was capable of decreasing blood inflammatory markers. Altogether, the results show a significant capacity of Epi to mitigate hippocampus OS and inflammation leading to improved brain function.

Calcium Bioavailability in the Soluble and Insoluble Fibers Extracted from Opuntia ficus indica at Different Maturity Stages in Growing Rats.

Childhood and adolescence are crucial stages of life for bone health. Therefore, an adequate calcium intake and a healthy life style constitute the main strategies to prevent the risk of osteoporosis-related fractures during adulthood. It has been demonstrated that inclusion of indigestible carbohydrates in foods can help improve calcium absorption in growing stages. The objective of this study was to evaluate the effect of supplementation of soluble and insoluble fibers extracted from O. ficus indica cladodes on calcium bioavailability. Male Wistar rats 4-week old were fed diets added with soluble and insoluble fibers extracted from O. ficus indica cladodes at early and late maturity stages, as the only source of calcium. The mineral content, bone mineral density (BMD), physical, microstructural, and biomechanical properties of rat femurs were determined. The bones of rats fed with diets containing a soluble fiber extracted from O. ficus indica at early and late maturity stages exhibited better bone properties (resistance to fracture, microarchitecture, and calcium content) than control rats and rats fed with an insoluble fiber from O. ficusindica cladodes at both maturity stages. As expected, based on these results, the BMD values were higher in adolescent and pubertal rats fed with a diet containing the O. ficus indica soluble fiber. These results demonstrate that the soluble fiber from O. ficus indica cladodes is indeed a valuable source of bioavailable calcium, which contributes to improve physical, densitometric, biomechanical, and microstructural properties of bone in growing rats.

New Sustainable Process for Hesperidin Isolation and Anti-Ageing Effects of Hesperidin Nanocrystals.

Hesperidin, a secondary orange (Citrus sinensis) metabolite, was extracted from orange bagasse. No organic solvents or additional energy consumption were used in the clean and sustainable process. Hesperidin purity was approximately 98% and had a yield of 1%. Hesperidin is a known supplement due to antioxidant, chelating, and anti-ageing properties. Herein, hesperidin application to eliminate dark eye circles, which are sensitive and thin skin regions, was studied. In addition, the proposed method for its aqueous extraction was especially important for human consumption. Further, the most effective methods for hesperidin nanonization were explored, after which the nanoemulsions were incorporated into a cream formulation that was formulated for a tropical climate. Silky cream formulations (oil in water) were tested in vitro on artificial 3D skin from cultured cells extracted from skin residues after plastic surgery. The proposed in vitro assay avoided tests of the different formulations in human volunteers and animals. It was shown that one of the nanonized hesperidin formulations was the most skin-friendly and might be used in cosmetics.

Hippocampal Impairment Triggered by Long-Term Lead Exposure from Adolescence to Adulthood in Rats: Insights from Molecular to Functional Levels.

Lead (Pb) is an environmental and occupational neurotoxicant after long-term exposure. This study aimed to investigate the effects of systemic Pb exposure in rats from adolescence to adulthood, evaluating molecular, morphologic and functional aspects of hippocampus. For this, male Wistar rats were exposed to 50 mg/kg of Pb acetate or distilled water for 55 days by intragastric gavage. For the evaluation of short-term and long-term memories, object recognition and step-down inhibitory avoidance tests were performed. At the end of the behavioral tests, the animals were euthanized and the hippocampus dissected and processed to the evaluation of: Pb content levels in hippocampal parenchyma; Trolox equivalent antioxidant capacity (TEAC), glutathione (GSH) and malondialdehyde (MDA) levels as parameters of oxidative stress and antioxidant status; global proteomic profile and neuronal degeneration by anti-NeuN immunohistochemistry analysis. Our results show the increase of Pb levels in the hippocampus of adult rats exposed from adolescence, increased MDA and GSH levels, modulation of proteins related to neural structure and physiology and reduced density of neurons, hence a poor cognitive performance on short and long-term memories. Then, the long-term exposure to Pb in this period of life may impair several biologic organizational levels of the hippocampal structure associated with functional damages.