RESUMO
Metabolic effects of high diet acid load (DAL) have been studied for years in adults, although only recently in children. Contemporary diets, especially those of Western societies, owe their acidogenic effect to high animal-origin protein content and low contribution of base-forming elements, such as fruits and vegetables. This imbalance, where dietary acid precursors exceed the body's buffering capacity, results in an acid-retaining state known by terms such as "eubicarbonatemic metabolic acidosis," "low-grade metabolic acidosis," "subclinical acidosis," or "acid stress". Its consequences have been linked to chronic systemic inflammation, contributing to various noncommunicable diseases traditionally considered more common in adulthood, but now have been recognized to originate at much earlier ages. In children, effects of high DAL are not limited to growth impairment caused by alterations of bone and muscle metabolism, but also represent a risk factor for conditions such as obesity, insulin resistance, diabetes, hypertension, urolithiasis, and chronic kidney disease (CKD). The possibility that high DAL may be a cause of chronic acid-retaining states in children with growth impairment should alert pediatricians and pediatric nephrologists, since its causes have been attributed traditionally to inborn errors of metabolism and renal pathologies such as CKD and renal tubular acidosis. The interplay between DAL, overall diet quality, and its cascading effects on children's health necessitates comprehensive nutritional assessments and interventions. This narrative review explores the clinical relevance of diet-induced acid retention in children and highlights the potential for prevention through dietary modifications, particularly by increasing fruit and vegetable intake alongside appropriate protein consumption.
RESUMO
INTRODUCTION: Aging is accompanied by changes in body composition, such as an increase in fat mass (FM), a decrease in skeletal muscle mass index (SMMI) and muscle strength, combined with a chronic inflammatory process (CI). OBJECTIVE: Determine the relationship between age and excess body fat with markers of chronic inflammation, skeletal muscle mass and strength. METHODS: A cross-sectional alitical study was carried out in a convenience sample of adults 45 to 59 years old (n = 100) and older adults 60 to 74 years old (n = 133). All participants had their body composition measured with an impedance meter. They were subsequently divided into two groups: (i) with excess fat (WEF), (ii) without excess fat (NEF), in order to relate excess fat and age with inflammation, muscle mass and strength. RESULTS: NEF adults and older adults had similar values of SMMI (9.1 ± 1.5 vs. 8.8 ± 1.3, p > 0.05) and strength (28 ± 8 vs. 27 ± 8.6, p > 0.05). Likewise, WEF adults showed significantly lower values than NEF adults in the SMMI (7.9 ± 0.8 vs. 9.1 ± 1.5, p < 0.05) and strength (28 ± 8 vs. 22 ± 5, p < 0.001). Also, WEF older adults presented significantly lower values in the SMMI (15.9 ± 1.8 vs. 22.8 ± 5.1, p < 0.05) and strength (17.9 ± 4.8 vs. 27 ± 8.6, p < 0.001). CONCLUSIONS: Our findings suggest that excess fat mass is a risk factor that has a significantly greater influence than aging per se on the index of skeletal muscle mass and strength.
RESUMO
BACKGROUND & AIMS: We examined the dietary inflammatory potential in patients who underwent liver transplantation (LTx), associated factors and its relationship with clinical outcomes ten years after the initial evaluation. METHODS: Dietary Inflammatory Index (DII®) scores were generated from data derived from the 24-h recall in 108 patients. RESULTS: Patients with higher DII scores (highest tertile), indicating a pro-inflammatory diet, had significantly higher serum LDL cholesterol (108.0 vs 78.2 mg/dL, p = <0.01) at the initial evaluation. However, DII scores did not significantly predict the occurrence of clinical outcomes after ten years of follow-up. Patient age was predictive of neoplasia (OR:1.05 95% CI:1.00-1.11; p = 0.03). Higher BMI at the initial evaluation was associated with steatosis (OR:1.51; 95% CI:1.29-1.77; p < 0.01), and smoking history was associated with the occurrence of cardiovascular events (OR:7.71; 95% CI:1.53-38.79; p = 0.01). CONCLUSIONS: A pro-inflammatory diet was associated with higher serum LDL cholesterol in the initial evaluation but may not be strongly related to clinical outcomes during long-term follow-up.
Assuntos
Índice de Massa Corporal , LDL-Colesterol , Dieta , Inflamação , Transplante de Fígado , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , LDL-Colesterol/sangue , Seguimentos , Fatores de Risco , Adulto , Resultado do Tratamento , Doenças Cardiovasculares , Fígado Gorduroso , IdosoRESUMO
Chronic inflammation plays a crucial role in the onset and progression of pathologies like neurodegenerative and cardiovascular diseases, diabetes, and cancer, since tumor development and chronic inflammation are linked, sharing common signaling pathways. At least 20% of breast and colorectal cancers are associated with chronic inflammation triggered by infections, irritants, or autoimmune diseases. Obesity, chronic inflammation, and cancer interconnection underscore the importance of population-based interventions in maintaining healthy body weight, to disrupt this axis. Given that the dietary inflammatory index is correlated with an increased risk of cancer, adopting an anti-inflammatory diet supplemented with nutraceuticals may be useful for cancer prevention. Natural products and their derivatives offer promising antitumor activity with favorable adverse effect profiles; however, the development of natural bioactive drugs is challenging due to their variability and complexity, requiring rigorous research processes. It has been shown that combining anti-inflammatory products, such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and statins, with plant-derived products demonstrate clinical utility as accessible adjuvants to traditional therapeutic approaches, with known safety profiles. Pharmacological approaches targeting multiple proteins involved in inflammation and cancer pathogenesis emerge as a particularly promising option. Given the systemic and multifactorial nature of inflammation, comprehensive strategies are essential for long term success in cancer therapy. To gain insights into carcinogenic phenomena and discover diagnostic or clinically relevant biomarkers, is pivotal to understand genetic variability, environmental exposure, dietary habits, and TME composition, to establish therapeutic approaches based on molecular and genetic analysis. Furthermore, the use of endocannabinoid, cannabinoid, and prostamide-type compounds as potential therapeutic targets or biomarkers requires further investigation. This review aims to elucidate the role of specific etiological agents and mediators contributing to persistent inflammatory reactions in tumor development. It explores potential therapeutic strategies for cancer treatment, emphasizing the urgent need for cost-effective approaches to address cancer-associated inflammation.
RESUMO
OBJECTIVE: Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator. It is not known whether the pro-resolving effects of Ang-(1-7) are sustained and protect the lung from a subsequent inflammatory challenge. This study sought to investigate the impact of treatment in face of a second allergic or lipopolysaccharide (LPS) challenge. METHODS: Mice, sensitized and challenged with ovalbumin (OVA), received a single Ang-(1-7) dose at the peak of eosinophilic inflammation, 24 h after the final OVA challenge. Subsequently, mice were euthanized at 48, 72, 96, and 120 h following the OVA challenge, and cellular infiltrate, inflammatory mediators, lung histopathology, and macrophage-mediated efferocytic activity were evaluated. The secondary inflammatory stimulus (OVA or LPS) was administered 120 h after the last OVA challenge, and subsequent inflammatory analyses were performed. RESULTS: Treatment with Ang-(1-7) resulted in elevated levels of IL-10, CD4+Foxp3+, Mres in the lungs and enhanced macrophage-mediated efferocytic capacity. Moreover, in allergic mice treated with Ang-(1-7) and then subjected to a secondary OVA challenge, inflammation was also reduced. Similarly, in mice exposed to LPS, Ang-(1-7) effectively prevented the lung inflammation. CONCLUSION: A single dose of Ang-(1-7) resolves lung inflammation and protect the lung from a subsequent inflammatory challenge highlighting its potential therapeutic for individuals with asthma.
Assuntos
Angiotensina I , Lipopolissacarídeos , Pulmão , Ovalbumina , Fragmentos de Peptídeos , Animais , Angiotensina I/uso terapêutico , Angiotensina I/farmacologia , Angiotensina I/administração & dosagem , Fragmentos de Peptídeos/farmacologia , Fragmentos de Peptídeos/uso terapêutico , Fragmentos de Peptídeos/administração & dosagem , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/imunologia , Ovalbumina/imunologia , Camundongos , Masculino , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Camundongos Endogâmicos BALB C , Inflamação/tratamento farmacológico , Eosinofilia/tratamento farmacológico , Eosinofilia/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/citologiaRESUMO
In 1992, a transcendental report suggested that the receptor of advanced glycation end-products (RAGE) functions as a cell surface receptor for a wide and diverse group of compounds, commonly referred to as advanced glycation end-products (AGEs), resulting from the non-enzymatic glycation of lipids and proteins in response to hyperglycemia. The interaction of these compounds with RAGE represents an essential element in triggering the cellular response to proteins or lipids that become glycated. Although initially demonstrated for diabetes complications, a growing body of evidence clearly supports RAGE's role in human diseases. Moreover, the recognizing capacities of this receptor have been extended to a plethora of structurally diverse ligands. As a result, it has been acknowledged as a pattern recognition receptor (PRR) and functionally categorized as the RAGE axis. The ligation to RAGE leads the initiation of a complex signaling cascade and thus triggering crucial cellular events in the pathophysiology of many human diseases. In the present review, we intend to summarize basic features of the RAGE axis biology as well as its contribution to some relevant human diseases such as metabolic diseases, neurodegenerative, cardiovascular, autoimmune, and chronic airways diseases, and cancer as a result of exposure to AGEs, as well as many other ligands.
Assuntos
Produtos Finais de Glicação Avançada , Inflamação , Receptor para Produtos Finais de Glicação Avançada , Humanos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Inflamação/metabolismo , Transdução de Sinais , Neoplasias/metabolismo , Animais , Doenças Cardiovasculares/metabolismo , Doenças Neurodegenerativas/metabolismo , Doenças Metabólicas/metabolismo , Doenças Autoimunes/metabolismoRESUMO
OBJECTIVE AND DESIGN: Our aim was to determine an age-dependent role of Nav1.8 and ASIC3 in dorsal root ganglion (DRG) neurons in a rat pre-clinical model of long-term inflammatory pain. METHODS: We compared 6 and 24 months-old female Wistar rats after cutaneous inflammation. We used behavioral pain assessments over time, qPCR, quantitative immunohistochemistry, selective pharmacological manipulation, ELISA and in vitro treatment with cytokines. RESULTS: Older rats exhibited delayed recovery from mechanical allodynia and earlier onset of spontaneous pain than younger rats after inflammation. Moreover, the expression patterns of Nav1.8 and ASIC3 were time and age-dependent and ASIC3 levels remained elevated only in aged rats. In vivo, selective blockade of Nav1.8 with A803467 or of ASIC3 with APETx2 alleviated mechanical and cold allodynia and also spontaneous pain in both age groups with slightly different potency. Furthermore, in vitro IL-1ß up-regulated Nav1.8 expression in DRG neurons cultured from young but not old rats. We also found that while TNF-α up-regulated ASIC3 expression in both age groups, IL-6 and IL-1ß had this effect only on young and aged neurons, respectively. CONCLUSION: Inflammation-associated mechanical allodynia and spontaneous pain in the elderly can be more effectively treated by inhibiting ASIC3 than Nav1.8.
Assuntos
Canais Iônicos Sensíveis a Ácido , Hiperalgesia , Canal de Sódio Disparado por Voltagem NAV1.8 , Dor , Animais , Feminino , Ratos , Canais Iônicos Sensíveis a Ácido/genética , Canais Iônicos Sensíveis a Ácido/metabolismo , Canais Iônicos Sensíveis a Ácido/farmacologia , Analgésicos/uso terapêutico , Gânglios Espinais , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Inflamação/metabolismo , Dor/tratamento farmacológico , Dor/metabolismo , Ratos Sprague-Dawley , Ratos Wistar , Células Receptoras Sensoriais/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.8/metabolismoRESUMO
Idiopathic inflammatory myopathies (IIMs) are chronic, autoimmune connective tissue diseases associated with significant morbidity and disability. Nutrients can activate the immune system and contribute to chronic low-grade inflammation (LGI). Chronic muscle inflammation leads to imbalanced pro-inflammatory and anti-inflammatory cytokines, causing inadequate nutrition, weight loss and muscle weakness during a negative cycle. Owing to its potential to modulate LGI in various diseases, the Mediterranean diet (Med Diet) has been extensively studied. This scoping review explores the nutritional implications and recommendations of the Med Diet as a treatment for immune-mediated diseases, focusing on the gaps in IIM nutritional interventions. A comprehensive literature search of the MEDLINE and EBSCO databases between September 2018 and December 2022 was performed. We identified that the Med Diet and its specific components, such as omega-3 (nω3) fatty acids, vitamin D and antioxidants, play a role in the dietary treatment of connective tissue-related autoimmune diseases. Nutritional interventions have demonstrated potential for modulating disease activity and warrant further exploration of IIMs through experimental studies. This review introduces a dietary therapeutic approach using the Med Diet and related compounds to regulate chronic inflammatory processes in IIMs. However, further clinical studies are required to evaluate the efficacy of the Med Diet in patients with IIMs. Emphasising a clinical-nutritional approach, this study encourages future research on the anti-inflammatory effects of the Med Diet on IIMs. This review highlights potential insights for managing and treating these conditions using a holistic approach.
Assuntos
Dieta Mediterrânea , Miosite , Humanos , Miosite/dietoterapia , Ácidos Graxos Ômega-3/administração & dosagem , Antioxidantes/administração & dosagem , Vitamina D/administração & dosagem , Masculino , FemininoRESUMO
Multiple sclerosis (MS) is an autoimmune debilitating disease of the central nervous system caused by a mosaic of interactions between genetic predisposition and environmental factors. The pathological hallmarks of MS are chronic inflammation, demyelination, and neurodegeneration. Oxidative stress, a state of imbalance between the production of reactive species and antioxidant defense mechanisms, is considered one of the key contributors in the pathophysiology of MS. This review is a comprehensive overview of the cellular and molecular mechanisms by which oxidant species contribute to the initiation and progression of MS including mitochondrial dysfunction, disruption of various signaling pathways, and autoimmune response activation. The detrimental effects of oxidative stress on neurons, oligodendrocytes, and astrocytes, as well as the role of oxidants in promoting and perpetuating inflammation, demyelination, and axonal damage, are discussed. Finally, this review also points out the therapeutic potential of various synthetic antioxidants that must be evaluated in clinical trials in patients with MS.
Assuntos
Esclerose Múltipla , Humanos , Esclerose Múltipla/genética , Esclerose Múltipla/tratamento farmacológico , Estresse Oxidativo/fisiologia , Antioxidantes/uso terapêutico , Sistema Nervoso Central/metabolismo , Inflamação/metabolismoRESUMO
BACKGROUND: Most anaemia studies focus on children and women of childbearing age. We assessed the frequency and main aetiologies of anaemia according to sociodemographic characteristics at the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a cohort of middle-aged adults. METHODS: The primary analyses included 15,051 participants aged 35-74 years with a valid blood cell count. We built logistic models to analyse the association between socioeconomic characteristics and anaemia diagnosis. We also described the main aetiologies in a subset (n = 209) of participants with anaemia. RESULTS: Anaemia was present in 3.0% (95% confidence interval [95%CI]: 2.6-3.4%) of men and 7.4% (95%CI: 6.9-8.0%) of women. The frequency of anaemia diagnosis was higher in women in all subgroups except for the oldest age stratum (65-74 years). The frequency of anaemia was particularly high in Blacks (6.0% and 15.5% in men and women, respectively). The most common causes of anaemia were iron deficiency (in women), chronic kidney disease, and chronic inflammation (in men). The frequency of unexplained anaemia was respectively 33.3% and 34.2% for men and women, and this condition was more frequent among participants of Black or Mixed races. CONCLUSIONS: Anaemia was associated with age, female sex, Black race, and low socioeconomic status. Unexplained anaemia was common and more frequent in individuals of Black and Mixed races. ELSA-Brasil follow-up data may provide further insight into the relevance of unexplained anaemia in this setting.
This study aims to assess the frequency, associated factors, and (in a subsample) the leading causes of anaemia in a large epidemiological study in 6 Brazilian state capitals. Our primary analyses included 15,051 participants aged 3574 years. Anaemia was present in 3.0% of men and 7.4% of women. The frequency of anaemia diagnosis was higher in women in all subgroups except for the oldest age stratum (6574 years). The frequency of anaemia was particularly high in Blacks (6.0% and 15.5% in men and women, respectively). The most common causes of anaemia were iron deficiency (in women), chronic kidney disease, and chronic inflammation (in men). Despite an extensive workout to determine the causes of anaemia, this condition remained unexplained in approximately one-third of cases. Unexplained anaemia was more frequent among participants of Black or Mixed races. Besides providing a clear epidemiological description of anaemia in this setting, our work also provides insight into the interpretation of current cutoffs for anaemia diagnosis.