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1.
Int J Mol Sci ; 22(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200792

RESUMO

Hyperhomocysteinemia (HHcy) is remarkably common among the aging population. The relation between HHcy and the development of neurodegenerative diseases, such as Alzheimer's disease (AD) and eye diseases, and age-related macular degeneration (AMD) and diabetic retinopathy (DR) in elderly people, has been established. Disruption of the blood barrier function of the brain and retina is one of the most important underlying mechanisms associated with HHcy-induced neurodegenerative and retinal disorders. Impairment of the barrier function triggers inflammatory events that worsen disease pathology. Studies have shown that AD patients also suffer from visual impairments. As an extension of the central nervous system, the retina has been suggested as a prominent site of AD pathology. This review highlights inflammation as a possible underlying mechanism of HHcy-induced barrier dysfunction and neurovascular injury in aging diseases accompanied by HHcy, focusing on AD.


Assuntos
Doenças do Sistema Nervoso Central/patologia , Homocisteína/metabolismo , Hiper-Homocisteinemia/patologia , Inflamação/fisiopatologia , Fatores Etários , Animais , Doenças do Sistema Nervoso Central/etiologia , Doenças do Sistema Nervoso Central/metabolismo , Humanos , Hiper-Homocisteinemia/etiologia , Hiper-Homocisteinemia/metabolismo
2.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203944

RESUMO

Uterine inflammation is a very common and serious pathology in domestic animals, the development and progression of which often result from disturbed myometrial contractility. We investigated the effect of inflammation on the protein expression of galanin (GAL) receptor subtypes (GALR)1 and GALR2 in myometrium and their role in the contractile amplitude and frequency of an inflamed gilt uterus. The gilts of the E. coli and SAL groups received E. coli suspension or saline in their uteri, respectively, and only laparotomy was performed (CON group). Eight days later, the E. coli group developed severe acute endometritis and lowered GALR1 protein expression in the myometrium. Compared to the pretreatment period, GAL (10-7 M) reduced the amplitude and frequency in myometrium and endometrium/myometrium of the CON and SAL groups, the amplitude in both stripes and frequency in endometrium/myometrium of the E. coli group. In this group, myometrial frequency after using GAL increased, and it was higher than in other groups. GALR2 antagonist diminished the decrease in amplitude in myometrium and the frequency in endometrium/myometrium (SAL, E. coli groups) induced by GAL (10-7 M). GALR1/GALR2 antagonist and GAL (10-7 M) reversed the decrease in amplitude and diminished the decrease in frequency in both examined stripes (CON, SAL groups), and diminished the drop in amplitude and abolished the rise in the frequency in the myometrium (E. coli group). In summary, the inflammation reduced GALR1 protein expression in pig myometrium, and GALR1 and GALR2 participated in the contractile regulation of an inflamed uterus.


Assuntos
Galanina/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Receptor Tipo 1 de Galanina/metabolismo , Receptor Tipo 2 de Galanina/metabolismo , Contração Uterina/fisiologia , Útero/fisiopatologia , Animais , Endométrio/fisiopatologia , Feminino , Miométrio/fisiopatologia , Receptor Tipo 2 de Galanina/antagonistas & inibidores , Suínos
3.
Molecules ; 26(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206441

RESUMO

DJ-1 was originally identified as an oncogene product while mutations of the gene encoding DJ-1/PARK7 were later associated with a recessive form of Parkinson's disease. Its ubiquitous expression and diversity of function suggest that DJ-1 is also involved in mechanisms outside the central nervous system. In the last decade, the contribution of DJ-1 to the protection from ischemia-reperfusion injury has been recognized and its involvement in the pathophysiology of cardiovascular disease is attracting increasing attention. This review describes the current and gaps in our knowledge of DJ-1, focusing on its role in regulating cardiovascular function. In parallel, we present original data showing an association between increased DJ-1 expression and antiapoptotic and anti-inflammatory markers following cardiac and vascular surgical procedures. Future studies should address DJ-1's role as a plausible novel therapeutic target for cardiovascular disease.


Assuntos
Coração/fisiopatologia , Traumatismo por Reperfusão Miocárdica , Miocárdio , Proteína Desglicase DJ-1/metabolismo , Animais , Biomarcadores/metabolismo , Humanos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia
4.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206170

RESUMO

Pleiotrophin (PTN) is a neurotrophic factor that regulates glial responses in animal models of different types of central nervous system (CNS) injuries. PTN is upregulated in the brain in different pathologies characterized by exacerbated neuroinflammation, including Parkinson's disease. PTN is an endogenous inhibitor of Receptor Protein Tyrosine Phosphatase (RPTP) ß/ζ, which is abundantly expressed in the CNS. Using a specific inhibitor of RPTPß/ζ (MY10), we aimed to assess whether the PTN/RPTPß/ζ axis is involved in neuronal and glial injury induced by the toxin MPP+. Treatment with the RPTPß/ζ inhibitor MY10 alone decreased the viability of both SH-SY5Y neuroblastoma cells and BV2 microglial cultures, suggesting that normal RPTPß/ζ function is involved in neuronal and microglial viability. We observed that PTN partially decreased the cytotoxicity induced by MPP+ in SH-SY5Y cells underpinning the neuroprotective function of PTN. However, MY10 did not seem to modulate the SH-SY5Y cell loss induced by MPP+. Interestingly, we observed that media from SH-SY5Y cells treated with MPP+ and MY10 decreases microglial viability but may elicit a neuroprotective response of microglia by upregulating Ptn expression. The data suggest a neurotrophic role of microglia in response to neuronal injury through upregulation of Ptn levels.


Assuntos
Proteínas de Transporte/metabolismo , Comunicação Celular , Citocinas/metabolismo , Microglia/metabolismo , Neurônios/metabolismo , Doença de Parkinson/metabolismo , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/metabolismo , Animais , Humanos , Inflamação/metabolismo , Inflamação/fisiopatologia , Camundongos , Microglia/fisiologia , Modelos Biológicos , Neurônios/fisiologia , Doença de Parkinson/fisiopatologia , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/fisiologia , Transdução de Sinais
5.
FASEB J ; 35(7): e21747, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34151467

RESUMO

We tested the hypothesis that the cognitive impairment associated with inflammatory pain may result from dysregulation of the top-down control of locus ceruleus's (LC) activity by the medial prefrontal cortex (mPFC). Injection of complete Freund's adjuvant (CFA) served as a model for inflammatory pain. The CFA injection decreased the thermal thresholds in both sexes but only the male mice showed increased anxiety-like behavior and diminished cognition, while the females were not affected. Increased calcium fluorescence, a marker for neuronal activity, was detected by photometry in the mPFC of males but not in females with CFA. Next, while chemogenetic inhibition of the projections from the mPFC to the LC improved the object recognition memory of males with pain, the inhibition of the mPFC to LC pathway in female mice produced anxiolysis and spatial memory deficits. The behavior results prompted us to compare the reciprocal innervation of mPFC and LC between the sexes. We used an anterograde transsynaptic tagging technique, which relies on postsynaptic cre transfer, to assess the innervation of LC by mPFC efferents. The males showed a higher rate of postsynaptic cre transfer into LC neurons from mPFC efferents than the females. And vice versa, a retrograde tracing experiment demonstrated that LC to mPFC projection neurons were more numerous in females when compared to males. In conclusion, we provide evidence that subtle differences in the reciprocal neuronal circuit between the LC and mPFC may contribute to sex differences associated with the adverse cognitive effects of inflammatory pain.


Assuntos
Inflamação/fisiopatologia , Locus Cerúleo/fisiopatologia , Dor/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Animais , Feminino , Masculino , Transtornos da Memória/fisiopatologia , Camundongos , Neurônios/fisiologia , Caracteres Sexuais , Memória Espacial/fisiologia
6.
Int J Mol Sci ; 22(10)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069553

RESUMO

Orofacial pain is a universal predicament, afflicting millions of individuals worldwide. Research on the molecular mechanisms of orofacial pain has predominately focused on the role of neurons underlying nociception. However, aside from neural mechanisms, non-neuronal cells, such as Schwann cells and satellite ganglion cells in the peripheral nervous system, and microglia and astrocytes in the central nervous system, are important players in both peripheral and central processing of pain in the orofacial region. This review highlights recent molecular and cellular findings of the glia involvement and glia-neuron interactions in four common orofacial pain conditions such as headache, dental pulp injury, temporomandibular joint dysfunction/inflammation, and head and neck cancer. We will discuss the remaining questions and future directions on glial involvement in these four orofacial pain conditions.


Assuntos
Dor Facial/metabolismo , Dor Facial/fisiopatologia , Neuroglia/fisiologia , Animais , Dor Facial/terapia , Neoplasias de Cabeça e Pescoço/fisiopatologia , Cefaleia/fisiopatologia , Humanos , Inflamação/fisiopatologia , Microglia/fisiologia , Neurônios/fisiologia , Nociceptividade/fisiologia , Gânglio Trigeminal/fisiologia
7.
Int J Mol Sci ; 22(10)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34068881

RESUMO

Neuroinflammation is a major component of central nervous system (CNS) injuries and neurological diseases, including Alzheimer's disease, multiple sclerosis, neuropathic pain, and brain trauma. The activation of innate immune cells at the damage site causes the release of pro-inflammatory cytokines and chemokines, which alter the functionality of nearby tissues and might mediate the recruitment of leukocytes to the injury site. If this process persists or is exacerbated, it prevents the adequate resolution of the inflammation, and ultimately enhances secondary damage. Adenosine 5' triphosphate (ATP) is among the molecules released that trigger an inflammatory response, and it serves as a chemotactic and endogenous danger signal. Extracellular ATP activates multiple purinergic receptors (P2X and P2Y) that have been shown to promote neuroinflammation in a variety of CNS diseases. Recent studies have shown that Pannexin-1 (Panx1) channels are the principal conduits of ATP release from dying cells and innate immune cells in the brain. Herein, we review the emerging evidence that directly implicates Panx-1 channels in the neuroinflammatory response in the CNS.


Assuntos
Conexinas/metabolismo , Inflamação/fisiopatologia , Proteínas do Tecido Nervoso/metabolismo , Doenças do Sistema Nervoso/fisiopatologia , Animais , Humanos , Inflamação/metabolismo , Doenças do Sistema Nervoso/metabolismo
8.
Clin Interv Aging ; 16: 1057-1070, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135578

RESUMO

Introduction: The prevalence of metabolic syndrome among the elderly population is growing. The elements of metabolic syndrome in an aging society are currently being researched. Atherosclerosis is a slow process in which the first symptoms may be observed after many years. The mechanisms underlying the progression of atherosclerosis are oxidative stress and inflammation. Inflammation and oxidative stress are associated with the increased incidence of metabolic syndrome. Taking the above into consideration, metabolic syndrome is thought to be a clinical equivalent of atherosclerosis. Aim: The aim of this paper is to review the impact of the interplay of oxidant-antioxidant and inflammation markers in metabolic syndrome in general as well as its components in the pathophysiology which underlies development of atherosclerosis in elderly individuals. Methods: A systematic scan of online resources designed for elderly (≥65 years) published from 2005 to the end of 2020 were reviewed. This was supplemented with grey literature and then all resources were narratively analyzed. The analysis included the following terms: "atherosclerosis or metabolic syndrome" and "oxidative stress or inflammation" and "elderly" to find reports of atherosclerotic disease from asymptomatic to life-threatening among the elderly population with metabolic syndrome . Results: The work summarizes articles that were applicable to this study, including systematic reviews, qualitative studies and opinion pieces. Current knowledge focuses on monitoring the inflammation and oxidant-antioxidant imbalance in disentangling atherosclerosis in patients diagnosed with metabolic syndrome. The population-based studies described inflammation, increased oxidative stress and weak antioxidant defense systems as the mechanisms underlying atherosclerosis development. Moreover, there are discussions that these targets could potentially be a point of intervention to reduce the development of atherosclerosis in the elderly, especially those with altered glucose and lipid metabolism. Specific markers may be used as an approach for the prevention and lifestyle modification of atherosclerotic disease in such population. Conclusion: Metabolic syndrome and its components are important contributors in the progression of atherosclerotic disease in the elderly population but constant efforts should be made to broaden our knowledge of elderly groups who are the most susceptible for the development of atherosclerosis complications.


Assuntos
Antioxidantes/metabolismo , Aterosclerose/metabolismo , Inflamação/metabolismo , Síndrome Metabólica/metabolismo , Oxidantes/metabolismo , Idoso , Envelhecimento/fisiologia , Aterosclerose/fisiopatologia , Biomarcadores/metabolismo , Humanos , Inflamação/fisiopatologia , Metabolismo dos Lipídeos , Masculino , Síndrome Metabólica/fisiopatologia , Obesidade/metabolismo , Estresse Oxidativo/fisiologia
9.
Cell Mol Life Sci ; 78(14): 5469-5488, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34100980

RESUMO

Within an articulately characterized family of ion channels, the voltage-gated sodium channels, exists a black sheep, SCN7A (Nax). Nax, in contrast to members of its molecular family, has lost its voltage-gated character and instead rapidly evolved a new function as a concentration-dependent sensor of extracellular sodium ions and subsequent signal transducer. As it deviates fundamentally in function from the rest of its family, and since the bulk of the impressive body of literature elucidating the pathology and biochemistry of voltage-gated sodium channels has been performed in nervous tissue, reports of Nax expression and function have been sparse. Here, we investigate available reports surrounding expression and potential roles for Nax activity outside of nervous tissue. With these studies as justification, we propose that Nax likely acts as an early sensor that detects loss of tissue homeostasis through the pathological accumulation of extracellular sodium and/or through endothelin signaling. Sensation of homeostatic aberration via Nax then proceeds to induce pathological tissue phenotypes via promotion of pro-inflammatory and pro-fibrotic responses, induced through direct regulation of gene expression or through the generation of secondary signaling molecules, such as lactate, that can operate in an autocrine or paracrine fashion. We hope that our synthesis of much of the literature investigating this understudied protein will inspire more research into Nax not simply as a biochemical oddity, but also as a potential pathophysiological regulator and therapeutic target.


Assuntos
Fibrose/fisiopatologia , Homeostase , Inflamação/fisiopatologia , Sódio/metabolismo , Canais de Sódio Disparados por Voltagem/metabolismo , Animais , Humanos , Transdução de Sinais , Canais de Sódio Disparados por Voltagem/genética
10.
Int J Mol Sci ; 22(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064558

RESUMO

The discovery and characterization of sirtuins as NAD+-dependent deacylases have transformed our understanding of post-translational protein regulation [...].


Assuntos
Inflamação/fisiopatologia , Nefropatias/fisiopatologia , Neoplasias/fisiopatologia , Sirtuínas/metabolismo , Animais , Humanos , Inflamação/metabolismo , Nefropatias/metabolismo , Neoplasias/metabolismo
11.
Int J Mol Sci ; 22(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067872

RESUMO

Inflammation is a key mechanism for the clearance of infective agents and other inflammatory triggers and is pivotal for the repairing processes of the affected tissues. Inflammation is a multistep process driven by a great number of mediators which regulate specific aspects of the inflammatory response, in agreement with a well-defined chronobiological program. A great number of inflammation-related diseases show a deeply altered immune chronobiology (e.g., COVID-19-related cytokines storm). This aspect highlights the need for a deeper understanding of the inflammatory phenomenon. It is fundamental to study inflammation as a multilevel phenomenon. Of particular interest is the low-grade chronic inflammation, which is an etiological factor of many chronic diseases. Nowadays, the therapeutic approach to low grade chronic inflammation is one of the great challenges of traditional pharmacology. Currently, no drugs specifically designed for the treatment of chronic inflammatory forms are available. Today, bioregulatory systems medicine (BrSM) and low dose medicine (LDM), two pharmacological paradigms grounded in systems medicine, potentially represent new tools for the treatment of inflammation-related diseases. Scientific research has assessed the effectiveness and safety of both these therapeutic approaches, in particular for the management of chronic inflammatory conditions and chronic immunological dysregulations.


Assuntos
Anti-Inflamatórios/farmacologia , COVID-19/metabolismo , Síndrome da Liberação de Citocina/metabolismo , Citocinas/metabolismo , Inflamação/metabolismo , Análise de Sistemas , Doença Aguda , Anti-Inflamatórios/uso terapêutico , COVID-19/imunologia , COVID-19/fisiopatologia , Doença Crônica/tratamento farmacológico , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/fisiopatologia
12.
Int J Mol Sci ; 22(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065385

RESUMO

In retinitis pigmentosa (RP), one of many possible genetic mutations causes rod degeneration, followed by cone secondary death leading to blindness. Accumulating evidence indicates that rod death triggers multiple, non-cell-autonomous processes, which include oxidative stress and inflammation/immune responses, all contributing to cone demise. Inflammation relies on local microglia and recruitment of immune cells, reaching the retina through breakdowns of the inner blood retinal barrier (iBRB). Leakage in the inner retina vasculature suggests similarly altered outer BRB, formed by junctions between retinal pigment epithelium (RPE) cells, which are crucial for retinal homeostasis, immune response, and privilege. We investigated the RPE structural integrity in three models of RP (rd9, rd10, and Tvrm4 mice) by immunostaining for zonula occludens-1 (ZO-1), an essential regulatory component of tight junctions. Quantitative image analysis demonstrated discontinuities in ZO-1 profiles in all mutants, despite different degrees of photoreceptor loss. ZO-1 interruption zones corresponded to leakage of in vivo administered, fluorescent dextran through the choroid-RPE interface, demonstrating barrier dysfunction. Dexamethasone, administered to rd10 mice for rescuing cones, also rescued RPE structure. Thus, previously undetected, stereotyped abnormalities occur in the RPE of RP mice; pharmacological targeting of inflammation supports a feedback loop leading to simultaneous protection of cones and the RPE.


Assuntos
Retina/fisiopatologia , Epitélio Pigmentado da Retina/fisiopatologia , Retinite Pigmentosa/fisiopatologia , Animais , Dexametasona/farmacologia , Modelos Animais de Doenças , Estudos de Avaliação como Assunto , Inflamação/metabolismo , Inflamação/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Retina/efeitos dos fármacos , Retina/metabolismo , Células Fotorreceptoras Retinianas Cones/efeitos dos fármacos , Células Fotorreceptoras Retinianas Cones/metabolismo , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/efeitos dos fármacos , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Vasos Retinianos/efeitos dos fármacos , Vasos Retinianos/metabolismo , Retinite Pigmentosa/metabolismo , Rodopsina/metabolismo , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
13.
Life Sci ; 278: 119635, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34015285

RESUMO

Diabetic nephropathy (DN), a persistent microvascular problem of diabetes mellitus is described as an elevated level of albumin excretion in urine and impaired renal activity. The morbidity and mortality of type-1 diabetics and type-2 diabetics due to end stage renal disease is also a result of the increased prevalence of DN. DN typically occurs as a consequence of an association among metabolic and hemodynamic variables, activating specific pathways leading to renal injury. According to current interventions, intensive glucose regulation decreases the threat of DN incidence and growth, and also suppressing the renin-angiotensin system (RAS) is a significant goal for hemodynamic and metabolism-related deformities in DN. However, the pathogenesis of DN is multifactorial so novel approaches other than glucose and blood pressure control are required for treatment. This review briefly summarizes the reported pathogenesis of DN, current interventions for its treatment, and possible novel interventions to unweave the thread of DN.


Assuntos
Nefropatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/terapia , Animais , Anti-Hipertensivos/uso terapêutico , Nefropatias Diabéticas/metabolismo , Dietoterapia , Estilo de Vida Saudável , Humanos , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Inflamação/metabolismo , Inflamação/fisiopatologia , Inflamação/terapia , Redes e Vias Metabólicas/efeitos dos fármacos , Terapia de Alvo Molecular , Abandono do Hábito de Fumar
14.
Nutr Res ; 90: 1-12, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34049184

RESUMO

Since the ongoing coronavirus disease 2019 (COVID-19) pandemic is linked to chronic inflammation, people with initial lower inflammatory status could have better outcomes from exposure to this disease. Because dietary habits are one of the most important modifiable risk factors for inflammation, identification of dietary components associated with inflammation could play a significant role in controlling or reducing the risk of COVID-19. We investigated the inflammatory potential of diets consumed by African American (AA) and Caucasian American (CA) women of childbearing age (n = 509) who are at high risk for exposure to COVID-19 by being residents of Birmingham, Alabama, a city severely affected by this pandemic. The overall pro- and anti- inflammatory scores were calculated using dietary intake data gathered using Block food frequency questionnaire. The proinflammatory potential of diets consumed by AAs was significantly higher compared to CAs. Several anti- and proinflammatory nutrients and food groups consumed differed by race. With consumption of a greater number of antioxidants and B-vitamins, CAs switched toward an anti-inflammatory score more effectively than AAs while AAs performed better than CAs in improving the anti-inflammatory score with the consumption of a greater number of minerals and vitamin D. Effective race-specific dietary modifications or supplementation with nutrients identified will be useful to improve proinflammatory diets toward anti-inflammatory. This approach could aid in controlling the current COVID-19 pandemic and future pandemics of a similar nature in women at risk for exposure.


Assuntos
Afro-Americanos/estatística & dados numéricos , COVID-19/prevenção & controle , Dieta/métodos , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Inflamação/fisiopatologia , Adulto , Alabama , Dieta/efeitos adversos , Dieta/estatística & dados numéricos , Feminino , Humanos , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Inquéritos e Questionários , Adulto Jovem
15.
Pain Res Manag ; 2021: 6662651, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34055120

RESUMO

Background: MicroRNAs play an essential role in regulating pain processing within a wide range of clinical pain disorders. Objectives: The present study aimed to evaluate the role of circulating miRNAs as biomarkers of lower back pain in older adults. In addition, the correlation between miRNAs and other related cofounders such as muscle function, adiposity, malnutrition, and Ca and vitamin D intake was assessed. Methods: A total of 110 older subjects with an age range of 40-60 years were included in this study. The participants were classified according to a modified Oswestry lower back pain disability questionnaire (OSW) into subjects with minimal LBP (n = 40; LBP score: 0-20%), moderate LBP (n = 35; LBP score: 20-40%), and severe LBP (n = 35; LBP score: 41-60%). RT-PCR and immunoassays were used to study the circulating miRNA profile, vitamin D status, and CRP, IL-6, TNF-α, s-Ca, s-BAP, s-OC, and s-NTX levels. In addition, malnutrition and muscle performance were estimated in all subjects as other factors related to LBP. Results: In this study, normal LBP-OSW cutoff values (8.96 ± 3.6) were reported in 36.4% of the total population, whereas 63.6% of the population had higher LBP-OSW scores, classified as follows: 31.8% with moderate LBP (LBP-OSW score: 31.4 ± 9.1) and 31.8% with severe LBP (LBP-OSW score: 54.9 ± 14.6). Four circulating miRNAs, namely, miR-146a, miR-558, miR-155, and miR-124a, as biomarkers of the intensity of back pain were identified in all participants. In subjects with moderate to severe LBP, the expression levels of miR-146a and miR-558 were significantly reduced and those of miR-155 and miR-124a were significantly increased compared to subjects with minimal LBP scores. Subjects with moderate to severe LBP showed a significant increase in adiposity markers, lower PA, muscle performance, malnutrition, and lower Ca and vitamin D intake compared to normal controls. In addition, serum levels of vitamin D and circulated plasma markers of inflammation and bone metabolism such as CRP, IL-6, TNF-α, s-Ca, s-BAP, s-OC, and s-NTX were significantly reduced in severe LBP cases compared to those with minimal LBP scores. The expressed circulating miRNAs were significantly associated with the measured muscle performance, adiposity, PA score, inflammation, and bone metabolism cofounders in subjects with higher LBP-OSW scores. The expressed miRNAs, along with other LBP cofounders, were significantly associated with ∼63.9-86.4% of the incidence of LBP in older adults. Conclusions: In older adults with vitamin D deficiency, the severity of LBP was significantly associated with the expression of circulating miRNAs, adiposity, bone metabolism, inflammation, and muscle performance. In addition, the expressed miRNAs, along with other LBP cofounders, were significantly associated with ∼63.9-86.4% of the incidence of LBP in older adults. These results suggest the possibility of using microRNAs as therapeutics to alleviate established pain and as biomarkers in old adults with painful conditions.


Assuntos
Biomarcadores/sangue , Osso e Ossos/metabolismo , Cálcio/sangue , MicroRNA Circulante/sangue , Inflamação/fisiopatologia , Dor Lombar/diagnóstico , Deficiência de Vitamina D/sangue , Adulto , Feminino , Humanos , Dor Lombar/fisiopatologia , Masculino , Pessoa de Meia-Idade
16.
Am J Physiol Heart Circ Physiol ; 320(6): H2371-H2384, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33961505

RESUMO

Both aberrant vascular reactivity to acute cardiovascular stress and epigenetic mechanisms such as microRNA (miR) may underlie the increased propensity for African Americans (AA) to develop cardiovascular disease. This study assessed racial differences in acute induced endothelial inflammation and related miRs. Cultured human umbilical vein endothelial cells (HUVECs) derived from AA and Caucasian Americans (CA) were exposed to influenza vaccine to determine changes in inflammatory markers, endothelial nitric oxide synthase (eNOS), and miR expression/release. Endothelial function [flow-mediated dilation (FMD)], circulating IL-6, and circulating miR were also measured in young, healthy AA and CA individuals before and after receiving the influenza vaccine. There were no significant racial differences in any parameters at baseline. The vaccine induced increases in IL-6 release (24%, P = 0.02) and ICAM-1 mRNA (40%, P = 0.03), as well as reduced eNOS mRNA (24%, P = 0.04) in AA HUVECs, but not in CA HUVECs (all P > 0.05). Intracellular levels of anti-inflammatory miR-221-3p and miR-222-3p increased specifically in CA HUVECs (72% and 53%, P = 0.04 and P = 0.06), whereas others did not change in either race. HUVEC secretion of several miRs decreased in both races, whereas the release of anti-inflammatory miR-150-5p was decreased only by AA cells (-30%, P = 0.03). In individuals of both races, circulating IL-6 increased approximately twofold 24 h after vaccination (both P < 0.01) and returned to baseline levels by 48 h, whereas FMD remained unchanged. Although macrovascular function was unaffected by acute inflammation in AA and CA individuals, AA endothelial cells exhibited increased susceptibility to acute inflammation and unique changes in related miR.NEW & NOTEWORTHY Used as an acute inflammatory stimulus, the influenza vaccine induced an inflammatory response and decreased eNOS gene expression in endothelial cells derived from African Americans, but not Caucasian Americans. Race-specific changes in intracellular expression and release of specific microRNAs also occurred and may contribute to an exaggerated inflammatory response in African Americans. In vivo, the vaccine caused similar systemic inflammation but had no effect on endothelial function or circulating microRNAs in individuals of either race.


Assuntos
Afro-Americanos , Endotélio/efeitos dos fármacos , Grupo com Ancestrais do Continente Europeu , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Inflamação/metabolismo , Vacinas contra Influenza/farmacologia , MicroRNAs/efeitos dos fármacos , Adulto , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio/metabolismo , Endotélio/fisiopatologia , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/fisiopatologia , Molécula 1 de Adesão Intercelular/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/genética , Interleucina-6/metabolismo , Masculino , MicroRNAs/metabolismo , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/genética , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Vasodilatação/fisiologia , Adulto Jovem
17.
J Int Soc Sports Nutr ; 18(1): 36, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001168

RESUMO

BACKGROUND: Elite athletes may suffer from impaired immune function and gastro-intestinal (GI) symptoms, which may affect their health and may impede their performance. These symptoms may be reduced by multi-strain probiotic supplementation. Therefore, the aim of the current study is to examine the effects of probiotic supplementation on aerobic fitness characteristics, inflammatory markers and incidence and severity of GI symptoms in elite cyclists. METHODS: Twenty-seven male cyclists, ranked elite or category 1 level competitions, were randomly assigned to a multi-strain probiotic-supplemented group (E, n = 11) or placebo group (C, n = 16). All participants visited the laboratory at the beginning of the study and following 90 d of supplementation/placebo. Prior to testing, all participants completed a GI symptoms questionnaire and underwent physical and medical examination, and anthropometric measurements. Venous blood was drawn for inflammatory markers analysis. The cyclists then underwent maximal oxygen consumption (VO2max) test and time-to-fatigue (TTF) test at 85 % of maximal power, 3 h following the VO2max test. All testing procedures were repeated after 90 d of probiotic / placebo treatment (double blind design). RESULTS: Lower incidence of nausea, belching, and vomiting (P < 0.05) at rest, and decreased incidence of GI symptoms during training were found in E group vs. C Group, respectively (∆GI -0.27 ± 0.47 % vs. 0.08 ± 0.29 %, P = 0.03), no significant changes were observed in the incidence of total overall GI symptoms (∆GI -5.6 ± 14.7 % vs. 2.6 ± 11.6 %, P = 0.602) Mean rate of perceived exertion (RPE) values during the TTF were lower in E group (∆RPE: -0.3 ± 0.9 vs. 0.8 ± 1.5, P = 0.04). No significant changes were measured between and within groups in VO2max and TTF values, mean levels of C-reactive protein (CRP), IL-6-and tumor necrosis factor alpha (TNFα) values following treatment. CONCLUSIONS: Probiotics supplementation may have beneficial effects on GI symptoms in elite cyclists. Future studies, using higher doses and during different training seasons, might help understanding the effects of probiotic supplementation on elite athletes' health and performance. TRIAL REGISTRATION: NIH clinicaltrial.gov #NCT02756221 Registered 25 April 2016.


Assuntos
Desempenho Atlético/fisiologia , Ciclismo/fisiologia , Suplementos Nutricionais , Gastroenteropatias/prevenção & controle , Inflamação/prevenção & controle , Probióticos/administração & dosagem , Adulto , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Método Duplo-Cego , Gastroenteropatias/fisiopatologia , Humanos , Inflamação/fisiopatologia , Interleucina-6/sangue , Masculino , Fadiga Muscular , Consumo de Oxigênio , Condicionamento Físico Humano/fisiologia , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
18.
Cell Prolif ; 54(6): e13050, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33960559

RESUMO

OBJECTIVES: In this study, we study the transplantation of tauroursodeoxycholic acid (TUDCA)-induced M2-phenotype (M2) macrophages and their ability to promote anti-neuroinflammatory effects and functional recovery in a spinal cord injury (SCI) model. METHODS: To this end, compared to the granulocyte-macrophage colony-stimulating factor (GM-CSF), we evaluated whether TUDCA effectively differentiates bone marrow-derived macrophages (BMDMs) into M2 macrophages. RESULTS: The M2 expression markers in the TUDCA-treated BMDM group were increased more than those in the GM-CSF-treated BMDM group. After the SCI and transplantation steps, pro-inflammatory cytokine levels and the mitogen-activated protein kinase (MAPK) pathway were significantly decreased in the TUDCA-induced M2 group more than they were in the GM-CSF-induced M1 group and in the TUDCA group. Moreover, the TUDCA-induced M2 group showed significantly enhanced tissue volumes and improved motor functions compared to the GM-CSF-induced M1 group and the TUDCA group. In addition, biotinylated dextran amine (BDA)-labelled corticospinal tract (CST) axons and neuronal nuclei marker (NeuN) levels were increased in the TUDCA-induced M2 group more than those in the GM-CSF-induced M1 group and the TUDCA group. CONCLUSIONS: This study demonstrates that the transplantation of TUDCA-induced M2 macrophages promotes an anti-neuroinflammatory effect and motor function recovery in SCI. Therefore, we suggest that the transplantation of TUDCA-induced M2 macrophages represents a possible alternative cell therapy for SCI.


Assuntos
Macrófagos/transplante , Traumatismos da Medula Espinal/terapia , Ácido Tauroquenodesoxicólico/metabolismo , Animais , Células Cultivadas , Feminino , Inflamação/metabolismo , Inflamação/fisiopatologia , Inflamação/terapia , Macrófagos/metabolismo , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia
19.
Life Sci ; 278: 119617, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34004250

RESUMO

Intracranial aneurysm (IA) is one of the most challenging vascular lesions in the brain for clinicians. It was reported that 1%-6% of the world's population is affected by IAs. Owing to serious complications arising from these lesions, much attention has been paid to better understand their pathophysiology. Non-coding RNAs including short non-coding RNAs and long non-coding RNAs, have critical roles in modulating physiologic and pathological processes. These RNAs are emerging as new fundamental regulators of gene expression, are related with the progression of IA. Non-coding RNAs act via multiple mechanisms and be involved in vascular development, growth and remodeling. Furthermore, these molecules are involved in the regulation of inflammation, a key process in the formation and rupture of IA. Studying non-coding RNAs can yield a hypothetical mechanism for better understanding IA. The present study aims to focus on the role of these non-coding RNAs in the pathogenesis of IA.


Assuntos
Inflamação/fisiopatologia , Aneurisma Intracraniano/patologia , RNA Longo não Codificante/genética , Animais , Humanos , Aneurisma Intracraniano/etiologia , Aneurisma Intracraniano/metabolismo
20.
Biomed Pharmacother ; 139: 111558, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33894624

RESUMO

Erythropoietin (EPO) is a hypoxia-induced hormone produced in adult kidneys with erythropoietic and non-erythropoietic effects. In vivo studies represent an important role to comprehend the efficacy and safety in the early phase of repurposing drugs. The aim is to evaluate the potential anti-inflammatory effect of EPO observed in animal models of disease. Following PRISMA statements, electronic database Medline via PubMed platform was used to search articles with the research expression ((erythropoietin [MeSH Terms]) AND (inflammation [MeSH Terms]) AND (disease models, animal [MeSH Terms])). The inclusion criteria were original articles, studies where EPO was administered, studies where inflammation was studied and/or evaluated, non-clinical studies in vivo with rodents, and articles published in English. Thirty-six articles met the criteria for qualitative analysis. Exogenous EPO was used in models of sepsis, traumatic brain injury, and autoimmune neuritis, with an average of 3000 IU/Kg for single and multiple doses, using mice and rats. Biomarkers such as immune-related effectors, cytokines, reactive oxygen species, prostaglandins, and other biomarkers were assessed. EPO has been recognized as a multifunctional cytokine with anti-inflammatory properties, showing its significant effect both in acute and chronic models of inflammation. Further non-clinical studies are suggested for the enlightenment of anti-inflammatory mechanisms of EPO in lower doses, allowing us to understand the translational data for humans.


Assuntos
Anti-Inflamatórios/farmacologia , Eritropoetina/farmacologia , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Animais , Biomarcadores , Avaliação Pré-Clínica de Medicamentos , Humanos , Roedores
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