Aim: To investigate the effects of exercise on salivary concentrations of inflammatory markers by analyzing a panel of 25 inflammatory markers in subjects who had participated in bicycle ergometer tests varying in workload and hydration status. Methods: Fifteen healthy young men (20-35 years) had performed 4 different exercise protocols of 1 hour duration in a randomly assigned cross-over design, preceded by a rest protocol. Individual workloads depended on participant's pre-assessed individual maximum workload (Wmax): rest (protocol 1), 70% Wmax in hydrated (protocol 2) and dehydrated (protocol 3) state, 50% Wmax (protocol 4) and intermittent 85%/55% Wmax in 2 min blocks (protocol 5). Saliva samples were collected before (T0) and immediately after exercise (T1), and at several time points after exercise (2 hours (T3), 3 hours (T4), 6 hours (T5) and 24 hours (T6)). Secretory Leukocyte Protease Inhibitor (SLPI), Matrix Metallopeptidase-9 (MMP-9) and lactoferrin was analyzed using a commercial ELISA kit, a panel of 22 cytokines and chemokines were analyzed using a commercial multiplex immunoassay. Data was analyzed using a multilevel mixed linear model, with multiple test correction. Results: Among a panel of 25 inflammatory markers, SLPI concentrations were significantly elevated immediately after exercise in all protocols compared to rest and higher concentrations reflected the intensity of exercise and hydration status. MMP-9 showed a significant increase in the 70% Wmax dehydrated, 50% Wmax and intermittent protocols. Conclusions: Salivary concentrations of SLPI and MMP-9 seem associated with exercise intensity and hydration status and may offer non-invasive biomarkers to study (local) inflammatory responses to different exercise intensities in human studies. sa
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Introduction: Patients with cancer receiving radio- or chemotherapy undergo many immunological stressors. Chronic regular exercise has been shown to positively influence the immune system in several populations, while exercise overload may have negative effects. Exercise is currently recommended for all patients with cancer. However, knowledge regarding the effects of exercise on immune markers in patients undergoing chemo- or radiotherapy is limited. The aim of this study is to systematically review the effects of moderate- and high-intensity exercise interventions in patients with cancer during chemotherapy or radiotherapy on immune markers. Methods: For this review, a search was performed in PubMed and EMBASE, until March 2023. Methodological quality was assessed with the PEDro tool and best-evidence syntheses were performed both per immune marker and for the inflammatory profile. Results: Methodological quality of the 15 included articles was rated fair to good. The majority of markers were unaltered, but observed effects included a suppressive effect of exercise during radiotherapy on some proinflammatory markers, a preserving effect of exercise during chemotherapy on NK cell degranulation and cytotoxicity, a protective effect on the decrease in thrombocytes during chemotherapy, and a positive effect of exercise during chemotherapy on IgA. Conclusion: Although exercise only influenced a few markers, the results are promising. Exercise did not negatively influence immune markers, and some were positively affected since suppressed inflammation might have positive clinical implications. For future research, consensus is needed regarding a set of markers that are most responsive to exercise. Next, differential effects of training types and intensities on these markers should be further investigated, as well as their clinical implications.
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The metabolic syndrome (MetS) comprises cardiometabolic risk factors frequently found in individuals with obesity. Guidelines to prevent or reverse MetS suggest limiting fat intake, however, lowering carbohydrate intake has gained attention too. The aim for this review was to determine to what extent either weight loss, reduction in caloric intake, or changes in macronutrient intake contribute to improvement in markers of MetS in persons with obesity without cardiometabolic disease. A meta-analysis was performed across a spectrum of studies applying low-carbohydrate (LC) and low-fat (LF) diets. PubMed searches yielded 17 articles describing 12 separate intervention studies assessing changes in MetS markers of persons with obesity assigned to LC (<40% energy from carbohydrates) or LF (<30% energy from fat) diets. Both diets could lead to weight loss and improve markers of MetS. Meta-regression revealed that weight loss most efficaciously reduced fasting glucose levels independent of macronutrient intake at the end of the study. Actual carbohydrate intake and actual fat intake at the end of the study, but not the percent changes in intake of these macronutrients, improved diastolic blood pressure and circulating triglyceride levels, without an effect of weight loss. The homeostatic model assessment of insulin resistance improved with both diets, whereas high-density lipoprotein cholesterol only improved in the LC diet, both irrespective of aforementioned factors. Remarkably, changes in caloric intake did not play a primary role in altering MetS markers. Taken together, these data suggest that, beyond the general effects of the LC and LF diet categories to improve MetS markers, there are also specific roles for weight loss, LC and HF intake, but not reduced caloric intake, that improve markers of MetS irrespective of diet categorization. On the basis of the results from this meta-analysis, guidelines to prevent MetS may need to be re-evaluated.
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Background and aims: Observational data indicate that diets rich in fruits and vegetables have a positive effect on inflammatory status, improve metabolic resilience and may protect against the development of non-communicable diseases. Nevertheless, experimental evidence demonstrating a causal relationship between nutrient intake (especially whole foods) and changes in metabolic health is scarce. This study investigated the pleiotropic effects of sulforaphane from broccoli sprouts, compared to pea sprouts, on biomarkers of endothelial function, inflammation and metabolic stress in healthy participants subjected to a standardized caloric challenge.Methods: In this double-blind, crossover, randomized, placebo-controlled trial 12 healthy participants were administered 16 g broccoli sprouts, or pea sprouts (placebo) followed by the standardized high-caloric drink PhenFlex given to disturb healthy homeostasis. Levels of inflammatory biomarkers and metabolic parameters were measured in plasma before and 2 h after the caloric overload.Results: Administration of broccoli sprouts promoted an increase in levels of CCL-2 induced by caloric load (p = 0.017). Other biomarkers (sICAM-1, sVCAM-1, hs-CRP, and IL-10) individually showed insignificant tendencies toward increase with administration of sulforaphane. Combining all studied biomarkers into the systemic low-grade inflammation score further confirmed upregulation of the inflammatory activity (p = 0.087) after sulforaphane. No significant effects on biomarkers of metabolic stress were detected.Conclusion: This study has demonstrated that sulforaphane facilitated development of a mild pro-inflammatory state during the caloric challenge, which could be suggestive of the onset of the hormetic response induced by this phytonutrient. The use of integrative outcomes measures such as the systemic low-grade inflammation score can be viewed as a more robust approach to study the subtle and pleiotropic effects of phytonutrients.Clinical trial registration:www.clinicaltrials.gov, identifier NCT05146804.Keywords: biomarkers; diet; glucoraphanin; hormesis; inflammation; nutrients; phenotypic flexibility; sulforaphane.
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Exercise is one of the external factors associated with impairment of intestinal integrity, possibly leading to increased permeability and altered absorption. Here, we aimed to examine to what extent endurance exercise in the glycogen‐depleted state can affect intestinal permeability toward small molecules and protein‐derived peptides in relation to markers of intestinal function. Eleven well‐trained male volunteers (27 ± 4 years) ingested 40 g of casein protein and a lactulose/rhamnose (L/R) solution after an overnight fast in resting conditions (control) and after completing a dual – glycogen depletion and endurance – exercise protocol (first protocol execution). The entire procedure was repeated 1 week later (second protocol execution). Intestinal permeability was measured as L/R ratio in 5 h urine and 1 h plasma. Five‐hour urine excretion of betacasomorphin‐7 (BCM7), postprandial plasma amino acid levels, plasma fatty acid binding protein 2 (FABP‐2), serum pre‐haptoglobin 2 (preHP2), plasma glucagon‐like peptide 2 (GLP2), serum calprotectin, and dipeptidylpeptidase‐4 (DPP4) activity were studied as markers for excretion, intestinal functioning and recovery, inflammation, and BCM7 breakdown activity, respectively. BCM7 levels in urine were increased following the dual exercise protocol, in the first as well as the second protocol execution, whereas 1 h‐plasma L/R ratio was increased only following the first exercise protocol execution. FABP2, preHP2, and GLP2 were not changed after exercise, whereas calprotectin increased. Plasma citrulline levels following casein ingestion (iAUC) did not increase after exercise, as opposed to resting conditions. Endurance exercise in the glycogen depleted state resulted in a clear increase of BCM7 accumulation in urine, independent of DPP4 activity and intestinal permeability. Therefore, strenuous exercise could have an effect on the amount of food‐derived bioactive peptides crossing the epithelial barrier. The health consequence of increased passage needs more in depth studies.
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Acne vulgaris is considered one of the most common medical skin conditions globally, affecting approximately 85% of individuals worldwide. While acne is most prevalent among adolescents between 15 to 24 years old, it is not uncommon in adults either. Acne addresses a number of different challenges, causing a multidimensional disease burden. These challenges include clinical sequelae, such as post inflammatory hyperpigmentation (PIH) and the chance of developing lifelong disfiguring scars, psychological aspects such as deficits in health related quality of life, chronicity of acne, economic factors, and treatment-related issues, such as antimicrobial resistance. The multidimensionality of the disease burden stipulates the importance of an effective and timely treatment in a well organised care system. Within the Netherlands, acne care provision is managed by several types of professional care givers, each approaching acne care from different angles: (I) general practitioners (GPs) who serve as ‘gatekeepers’ of healthcare within primary care; (II) dermatologists providing specialist medical care within secondary care; (III) dermal therapists, a non-physician medical professional with a bachelor’s degree, exclusively operating within the Australian and Dutch primary and secondary health care; and (IV) beauticians, mainly working within the cosmetology or wellness domain. However, despite the large variety in acne care services, many patients experience a delay between the onset of acne and receiving an effective treatment, or a prolonged use of care, which raises the question whether acne related care resources are being used in the most effective and (cost)efficient way. It is therefore necessary to gain insights into the organization and quality of Dutch acne health care beyond conventional guidelines and protocols. Exploring areas of care that may need improvement allow Dutch acne healthcare services to develop and improve the quality of acne care services in harmony with patient needs.
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Background: Glucocorticoids are potent anti-inflammatory agents used for the treatment of diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease and psoriasis. Unfortunately, usage is limited because of metabolic side-effects, e.g. insulin resistance, glucose intolerance and diabetes. To gain more insight into the mechanisms behind glucocorticoid induced insulin resistance, it is important to understand which genes play a role in the development of insulin resistance and which genes are affected by glucocorticoids. Medline abstracts contain many studies about insulin resistance and the molecular effects of glucocorticoids and thus are a good resource to study these effects. Results: We developed CoPubGene a method to automatically identify gene-disease associations in Medline abstracts. We used this method to create a literature network of genes related to insulin resistance and to evaluate the importance of the genes in this network for glucocorticoid induced metabolic side effects and anti-inflammatory processes. With this approach we found several genes that already are considered markers of GC induced IR, such as phosphoenolpyruvate carboxykinase (PCK) and glucose-6-phosphatase, catalytic subunit (G6PC). In addition, we found genes involved in steroid synthesis that have not yet been recognized as mediators of GC induced IR. Conclusions: With this approach we are able to construct a robust informative literature network of insulin resistance related genes that gave new insights to better understand the mechanisms behind GC induced IR. The method has been set up in a generic way so it can be applied to a wide variety of disease networks. © 2013 Fleuren et al.; licensee BioMed Central Ltd.
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Introduction: Strenuous physical stress induces a range of physiological responses, the extent depending, among others, on the nature and severity of the exercise, a person’s training level and overall physical resilience. This principle can also be used in an experimental set-up by measuring time-dependent changes in biomarkers for physiological processes. In a previous report, we described the effects of workload delivered on a bicycle ergometer on intestinal functionality. As a follow-up, we here describe an analysis of the kinetics of various other biomarkers. Aim: To analyse the time-dependent changes of 34 markers for different metabolic and immunological processes, comparing four different exercise protocols and a rest protocol. Methods: After determining individual maximum workloads, 15 healthy male participants (20–35 years) started with a rest protocol and subsequently performed (in a cross-over design with 1-week wash-out) four exercise protocols of 1-h duration at different intensities: 70% Wmax in a hydrated and a mildly dehydrated state, 50% Wmax and intermittent 85/55% Wmax in blocks of 2 min. Perceived exertion was monitored using the Borg’ Rating of Perceived Exertion scale. Blood samples were collected both before and during exercise, and at various timepoints up to 24 h afterward. Data was analyzed using a multilevel mixed linear model with multiple test correction. Results: Kinetic changes of various biomarkers were exercise-intensity-dependent. Biomarkers included parameters indicative of metabolic activity (e.g., creatinine, bicarbonate), immunological and hematological functionality (e.g., leukocytes, hemoglobin) and intestinal physiology (citrulline, intestinal fatty acid-binding protein, and zonulin). In general, responses to high intensity exercise of 70% Wmax and intermittent exercise i.e., 55/85% Wmax were more pronounced compared to exercise at 50% Wmax. Conclusion: High (70 and 55/85% Wmax) and moderate (50% Wmax) intensity exercise in a bicycle ergometer test produce different time-dependent changes in a broad range of parameters indicative of metabolic activity, immunological and hematological functionality and intestinal physiology. These parameters may be considered biomarkers of homeostatic resilience. Mild dehydration intensifies these time-related changes. Moderate intensity exercise of 50% Wmax shows sufficient physiological and immunological responses and can be employed to test the health condition of less fit individuals.
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Lichamelijke zwakte is een belangrijk onderdeel van kwetsbaarheid en komt veel voor bij oudere volwassenen. Terwijl vrouwen een hogere prevalentie en een eerder begin van kwetsbaarheid kennen zijn sekseverschillen in de ontwikkeling van lichamelijke zwakte nauwelijks bestudeerd. Daarom hebben we in spieren de veranderingen onderzocht die onderscheid maken tussen fitte en zwakke ouderen voor elk geslacht afzonderlijk. Mannen (n = 28) en vrouwen (n = 26) van 75 jaar en ouder werden gegroepeerd op basis van hun fysieke prestatiecriteria. Er werd gebruik gemaakt van spierbiopten genomen uit de vastus lateralis-spier voor genexpressie- en histologisch onderzoek. Er werden paarsgewijze vergelijkingen gemaakt tussen de sterkste en de zwakste groepen voor elk geslacht afzonderlijk, en potentiële geslachts-specifieke effecten werden beoordeeld. Zwakke vrouwen toonden een hogere expressie van ontstekingsroutes, infiltratie van NOX2-immuuncellen, samen met een hogere VCAM1-expressie. Zwakke mannen werden gekenmerkt door een kleinere diameter van type 2 (snelle) spiervezels en lagere expressie van PRKN. Zwakte-geassocieerde genexpressie-veranderingen in de spieren waren verschillend van veroudering-geassocieerde genexpressie-veranderingen, wat erop wijst dat de pathofysiologie van fysieke zwakte niet noodzakelijkerwijs afhankelijk is van veroudering. We concluderen dat zwakte-geassocieerde veranderingen in de spieren sekse-specifiek zijn. Aanbevolen wordt om bij onderzoek naar kwetsbaarheid rekening te houden met sekseverschillen, omdat deze verschillen een grote impact kunnen hebben over de ontwikkeling van (farmaceutische) interventies tegen kwetsbaarheid.
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In patients with cancer, weight loss can be related to simple starvation, disturbedmetabolism, or both. In patients with head and neck cancer (HNC), weight loss often is attributed to simple starvation because the obvious oral symptoms are known to hinder dietary intake. In this population, cachexia remains a relatively unexplored phenomenon. The aim of this study was to explore the prevalence of cachexia and precachexia in patients with newly diagnosed HNC.Methods: Fifty-nine patients with newly diagnosed HNC were asked to participate in the prospective cohort study, from which only baseline data were used in the analyses. Measurements were performed 1 wk before cancer treatment, that is, cachexia status by Fearon’s cancer-specific framework,dietary intake, muscle mass, muscle strength, and biochemical markers (C-reactive protein, albumin, hemoglobin, interleukin-1b, interleukin-6, and tumor necrosis factor-a) were assessed.Results: Data of 26 patients were included in the analyses (59% participation rate). Forty-two percent of the patients (n ¼ 12) were classified as cachectic and 15% (n ¼ 4) as precachectic. Muscle mass depletion was significantly more frequent in cachectic patients (67%) than in noncachectic patients (14%; P ¼ 0.014). No differences in inflammatory markers were observed betweencachectic and noncachectic patients.Conclusion: This exploratory study suggested a high prevalence of cachexia (42%) in patients with newly diagnosed HNC. Although a large study is needed to further elucidate the role of cachexia in patients with HNC, the data presented here suggest that cachexia is a common problem in this patient population, which has therapeutic and prognostic implications.
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