Colorectal cancer affects the large intestine, leading to loss of white adipose tissue (WAT) and alterations in adipokine secretion. Lower incidence of colorectal cancer is associated with increased fibre intake. Fructooligosaccharides (FOS) are fibres that increase production of butyrate by the intestinal microbiota. Tributyrin, a prodrug of butyric acid, exerts beneficial anti-inflammatory effects on colorectal cancer. Our aim was to characterise the effects of diets rich in FOS and tributyrin within the context of a colon carcinogenesis model, and characterise possible support of tumorigenesis by WAT. C57/BL6 male mice were divided into four groups: a control group (CT) fed with chow diet and three colon carcinogenesis-induced groups fed either with chow diet (CA), tributyrin-supplemented diet (BUT), or with FOS-supplemented diet. Colon carcinogenesis decreased adipose mass in subcutaneous, epididymal, and retroperitoneal tissues, while also reducing serum glucose and leptin concentrations. However, it did not alter the concentrations of adiponectin, interleukin (IL)-6, IL-10, and tumour necrosis factor alpha (TNF)-α in WAT. Additionally, the supplements did not revert the colon cancer affected parameters. The BUT group exhibited even higher glucose tolerance and levels of IL-6, VEGF, and TNF-α in WAT. To conclude our study, FOS and butyrate supplements were not beneficial. In addition, butyrate worsened adipose tissue inflammation.
Aim This study aimed to evaluate if physical activity is associated with systemic and cellular immunometabolic responses, in young adults after mild-to-moderate COVID-19 infection. Methods Mild- to- moderate post-COVID-19 patients (70.50 ± 43.10 days of diagnosis; age: 29.4 (21.9– 34.9) years; BMI: 25.5 ± 4.3 kg m 2 n = 20) and healthy age-matched controls (age: 29.3 (21.2 – 32.6) years; BMI: 25.4 ± 4.7 kg m 2 ; n = 20) were evaluated. Physical activity levels (PAL), body composition, dietary habits, muscular and pulmonary function, mental health, sleep quality, metabolic parameters, immune phenotypic characterization, stimulated whole blood and PBMC culture (cytokine production), mRNA, and mitochondrial respiration in PBMCs were evaluated. Results The post-COVID-19 group exhibited lower levels of moderate to vigorous physical activity (MVPA) (p = 0.038); therefore, all study comparisons were performed with adjustment for MVPA. Post-COVID-19 impacted the pulmonary function (FEV1, FEV1%pred, FVC, and FVC %pred) compared with the control (p adjusted by MVPA (p adj) <0.05). Post-COVID-19 exhibited lower levels of serum IL-6 (p adj <0.01), whereas it showed higher serum IL-10, triglyceride, leptin, IgG, ACE activity, TNFRSF1A, and PGE 2 (p adj <0.05) levels compared with controls. Post-COVID-19 presented a lower percentage of Treg cells (p adj = 0.03) and altered markers of lymphocyte activation and exhaustion (lower CD28 expression in CD8 + T cells (p adj = 0.014), whereas CD4 + T cells showed higher PD1 expression (p adj = 0.037)) compared with the control group. Finally, post- COVID-19 presented an increased LPS-stimulated whole- blood IL-10 concentration (p adj <0.01). When exploring mitochondrial respiration and gene expression in PBMCs, we observed a higher LEAK state value (p adj <0.01), lower OXPHOS activity (complex I) (p adj = 0.04), and expression of the Rev-Erb-α clock mRNA after LPS stimulation in the post-COVID-19 patients than in the control (p adj <0.01). Mainly, PAL was associated with changes in IL-10, triglyceride, and leptin levels in the plasma of post-COVID-19 patients. PAL was also associated with modulation of the peripheral frequency of Treg cells and the expression of PD-1 in CD8+ T cells, although it abrogated the statistical effect in the analysis of TNF-α and IL-6 production by LPS- and PMA-stimulated PBMC of post-COVID-19 patients. Conclusion Young adults after mild-to-moderate SARS-CoV-2 infection appeared to have lower physical activity levels, which can be associated with clinical and immunometabolic responses in a complex manner.
Background Doxorubicin is an antibiotic largely used in clinical practice for the treatment of several types of tumors. However, its application may be limited by triggering some host’s deleterious effects, such as extreme fatigue, anorexia, sarcopenia, cardiovascular diseases, among others [1]. The role of skeletal muscle in this process should be further elucidated as this tissue is still important for glucose homeostasis [2] and becomes impaired by doxorubicin treatment. Knowledge of doxorubicin’s effect in the skeletal muscle and in the mechanism of action involved on the systemic insulin sensitivity is still incipient. The aim of this study is to evaluate the mechanism of insulin resistance after doxorubicin treatment.
Introduction Post-COVID-19 condition (PCC) is characterised by a plethora of symptoms, with fatigue appearing as the most frequently reported. The alterations that drive both the persistent and post-acute disease newly acquired symptoms are not yet fully described. Given the lack of robust knowledge regarding the mechanisms of PCC we have examined the impact of inflammation in PCC, by evaluating serum cytokine profile and its potential involvement in inducing the different symptoms reported. Methods In this cross-sectional study, we recruited 227 participants who were hospitalised with acute COVID-19 in 2020 and came back for a follow-up assessment 6–12 months after hospital discharge. The participants were enrolled in two symptomatic groups: Self-Reported Symptoms group (SR, n = 96), who did not present major organ lesions, yet reported several debilitating symptoms such as fatigue, muscle weakness, and persistent loss of sense of smell and taste; and the Self-Reported Symptoms and decreased Pulmonary Function group (SRPF, n = 54), composed by individuals with the same symptoms described by SR, plus diagnosed pulmonary lesions. A Control group ( n = 77), with participants with minor complaints following acute COVID-19, was also included in the study. Serum cytokine levels, symptom questionnaires, physical performance tests and general clinical data were obtained in the follow-up assessment. Results SRPF presented lower IL-4 concentration compared with Control ( q = 0.0018) and with SR ( q = 0.030), and lower IFN-α2 serum content compared with Control ( q = 0.007). In addition, SRPF presented higher MIP-1β serum concentration compared with SR ( q = 0.029). SR presented lower CCL11 ( q = 0.012 and q = 0.001, respectively) and MCP-1 levels ( q = 0.052 for both) compared with Control and SRPF. SRPF presented lower G-CSF compared to Control ( q = 0.014). Female participants in SR showed lower handgrip strength in relation to SRPF ( q = 0.0082). Male participants in SR and SRPF needed more time to complete the timed up-and-go test, as compared with men in the Control group ( q = 0.0302 and q = 0.0078, respectively). Our results indicate that different PCC symptom profiles are accompanied by distinct inflammatory markers in the circulation. Of particular concern are the lower muscle function findings, with likely long-lasting consequences for health and quality of life, found for both PCC phenotypes.
Objective Nicotine dependence is a worldwide health problem and the second cause of death worldwide. This article aims to present the improvement in the technique used by us. The results of the implementation of the treatment program with the use of varenicline as a specific medicine for nicotine dependence during admission to a clinic for chemical dependency treatment. We also demonstrate that this treatment is possible and safe for patients with comorbid psychiatric disorders and drug use disorders. Methods Between August 2012 and August 2013, 98 patients were evaluated in a clinic for psychiatric and drug use treatment in Rio de Janeiro, Brazil. The treatment consisted of a smoking cessation therapy concurrently with the psychiatric treatment. These patients had used pharmacological therapy associated with intensive cognitive behavioral therapy, occupational therapy and moderate physical activity. In addition to the associated therapy, smoking was limited to three cigarettes daily beginning the first day of hospitalization. The drug use disorders and psychiatric illnesses were treated as usual. Results The patients adhered to the treatment. Hundred percent of the treatment group were discharged from the clinic such as tobacco abstainers. The percentage of abstinence in patients after discharge according to previous assessments (2008–2009) with follow-up of 18 months was 51%. Results of the current study are still under evaluation. Conclusions Behavioral group therapy and physical activities can be important allies for varenicline. Behavioral changes also exert great influence in the maintenance of abstinence.
Chronic diseases, such as obesity and cancer, have high prevalence rates. Both diseases have hyperinsulinemia, hyperglycemia, high levels of IGF-1 and inflammatory cytokines in common. Therefore, these can be considered triggers for cancer development and growth. In addition, low-grade inflammation that modulates the activation of immune cells, cellular metabolism, and production of cytokines and chemokines are common in obesity, cancer, and insulin resistance. Pharmacological strategies are necessary when a change in lifestyle does not improve glycemic homeostasis. In this regard, thiazolidinediones (TZD) possess multiple molecular targets and regulate PPARγ in obesity and cancer related to insulin resistance, while metformin acts through the AMPK pathway.The aim of this study was to review TZD and metformin as pharmacological treatments for insulin resistance associated with obesity and cancer.Thiazolidinediones restored adiponectin secretion and leptin sensitivity, reduced lipid droplets in hepatocytes and orexigen peptides in the hypothalamus. In cancer cells, TZD reduced proliferation, production of reactive oxygen species, and inflammation by acting through the mTOR and NFκB pathways. Metformin has similar effects, though these are AMPK-dependent. In addition, both drugs can be efficient against certain side effects caused by chemotherapy.
Abstract Aging is one of the risk factors for the development of low‐grade inflammation morbidities, such as several types of cancer and neurodegenerative diseases, due to changes in the metabolism, hormonal secretion, and immunosenescence. The senescence of the immune system leads to improper control of infections and tissue damage increasing age‐related diseases. One of the mechanisms that maintain cellular homeostasis is autophagy, a cell‐survival mechanism, and it has been proposed as one of the most powerful antiaging therapies. Regular exercise can reestablish autophagy, probably through AMP‐activated protein kinase activation, and help in reducing the age‐related senescence diseases. Therefore, in this study, we discuss the effects of exercise training in immunosenescence and autophagy, preventing the two main age‐related disease, cancer and neurodegeneration.
West Nile Virus (WNV) is a mosquito-borne flavivirus, which has been known to cause human infection in Africa, the Middle East, and southwestern Asia. It has also been isolated in Australia and sporadically in Europe but never in the Americas. Clinical features include acute fever, severe myalgias, headache, conjunctivitis, lymphadenopathy, and a roseolar rash. Rarely is encephalitis or meningitis seen. During the month of August 1999, a cluster of 5 patients with fever, confusion, and weakness were admitted to the intensive care unit of the same hospital in New York City. Ultimately 4 of the 5 developed flaccid paralysis and required ventilatory support. Three patients with less-severe cases presented shortly thereafter. With the assistance of the New York City and New York State health departments and the Centers for Disease Control and Prevention, these were documented as the first cases of WNV infection on this continent.
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